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Sample records for high-dose 3d-crt results

  1. Out-of-field doses from pediatric craniospinal irradiations using 3D-CRT, IMRT, helical tomotherapy and electron-based therapy

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    De Saint-Hubert, Marijke; Verellen, Dirk; Poels, Kenneth; Crijns, Wouter; Magliona, Federica; Depuydt, Tom; Vanhavere, Filip; Struelens, Lara

    2017-07-01

    Medulloblastoma treatment involves irradiation of the entire central nervous system, i.e. craniospinal irradiation (CSI). This is associated with the significant exposure of large volumes of healthy tissue and there is growing concern regarding treatment-associated side effects. The current study compares out-of-field organ doses in children receiving CSI through 3D-conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT) and an electron-based technique, and includes radiation doses resulting from imaging performed during treatment. An extensive phantom study is performed, using an anthropomorphic phantom corresponding to a five year old child, in which organ absorbed doses are measured using thermoluminescent detectors. Additionally, the study evaluates and explores tools for calculating out-of-field patient doses using the treatment planning system (TPS) and analytical models. In our study, 3D-CRT resulted in very high doses to a limited number of organs, while it was able to spare organs such as the lungs and breast when compared to IMRT and HT. Both IMRT and HT spread the dose over more organs and were able to spare the heart, thyroid, bladder, uterus and testes when compared to 3D-CRT. The electron-based technique considerably decreased the out-of-field doses in deep-seated organs but could not avoid nearby out-of-field organs such as the lungs, ribs, adrenals, kidneys and uterus. The daily imaging dose is small compared to the treatment dose burden. The TPS error for out-of-field doses was most pronounced for organs further away from the target; nevertheless, no systematic underestimation was observed for any of the studied TPS systems. Finally, analytical modeling was most optimal for 3D-CRT although the number of organs that could be modeled was limited. To conclude, none of the techniques studied was capable of sparing all organs from out-of-field doses. Nevertheless, the electron-based technique showed the most

  2. Simulation of 3D-CRT treatment for lung cancer

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    Thalhofer, Jardel L.; Silva, Ademir X. da; Junior, Juraci R.P., E-mail: jardellt@yahoo.com.br [Coordenacao dos Programas de Pos-Graduacao de Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil); Rebello, Wilson F., E-mail: rebello@ime.eb.br [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Secao de Engenharia Nuclear; Correa, Samanda C.A., E-mail: samandacristine@uezo.rj.gov.br [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil); Souza, Edmilson M., E-mail: emonteiro@nuclear.ufrj.br [Centro Universitario da Zona Oeste (UEZO), Rio de Janeiro, RJ (Brazil). Colegiado de Comutacao e Matematica; Batista, Delano V.S., E-mail: delano@inca.gov.br [Instituto Nacional de Cancer (INCA), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    In radiotherapy treatment for lung cancer, occurs doses deposition in healthy organs. During the treatment planning are calculated some doses due to photons. This dose deposition in healthy organs could induce to the appearance of new cancers foci. The aim of this study was to analyze the equivalent doses in healthy organs of a patient treated by radiotherapy for lung cancer. In order to calculate the doses, was done a computer simulation of radiotherapy treatment for lung cancer, adopting database of the treatment performed by INCA. To perform the simulation was used several tools, among them, the radiation transport code MCNPX, in which was shaped the radiotherapy room and the head from the linear accelerator Varian 2300 C / D, the patient was simulated by Voxel male phantom in Rex,and the treatment protocol adopted considers a beam with energy of 6 MV focusing on three gantry tilt angles (0 deg, 180 deg and 45 deg). In addition, there was variation in the opening of the radiation field according to the angle of inclination. The results of this study point to the organs close to the irradiated area are predominantly affected by the dose due to photons, affecting organs from different body systems, such as esophagus, heart, thymus, spine and lymph nodes. The calculated values demonstrating that the angle of 0 deg was the most responsible for the deposit of unwanted dose. The results showed that the simulations in this paper is developed in accordance with the planning data described in different studies and literature. (author)

  3. Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

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    Ling, Ted C.; Slater, Jerry M.; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M.; Patyal, Baldev; Slater, Jerry D.; Yang, Gary Y., E-mail: gyang@llu.edu [Department of Radiation Medicine, Loma Linda University Medical Center, 11234 Anderson Street, A875, Loma Linda, CA 92354 (United States)

    2014-12-05

    Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

  4. Analysis of Intensity-Modulated Radiation Therapy (IMRT, Proton and 3D Conformal Radiotherapy (3D-CRT for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

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    Ted C. Ling

    2014-12-01

    Full Text Available Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT, proton and 3D conformal radiotherapy (3D-CRT with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

  5. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

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    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Fusella, Marco; Giglioli, Francesca Romana [Medical Physics, AOU Città della Salute e della Scienza Hospital, Torino (Italy); Lohr, Frank [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by

  6. Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement: a comparison of second cancers and heart disease risk.

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    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an

  7. Postoperative Radiotherapy for Prostate Cancer: A Comparison of Four Consensus Guidelines and Dosimetric Evaluation of 3D-CRT Versus Tomotherapy IMRT

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    Malone, Shawn, E-mail: smalone@ottawahospital.on.ca [Division of Radiation Oncology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Croke, Jennifer [Division of Radiation Oncology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Roustan-Delatour, Nicolas; Belanger, Eric [Department of Pathology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Avruch, Leonard [Department of Radiology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Malone, Colin [Division of Radiation Oncology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Morash, Christopher [Division of Urology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Kayser, Cathleen; Underhill, Kathryn; Li Yan; Malone, Kyle [Division of Radiation Oncology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Nyiri, Balazs [Department of Medical Physics, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada); Spaans, Johanna [Division of Radiation Oncology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario (Canada)

    2012-11-01

    Purpose: Despite the benefits of adjuvant radiotherapy after radical prostatectomy, approximately one-half of patients relapse. Four consensus guidelines have been published (European Organization for Research and Treatment of Cancer, Faculty of Radiation Oncology Genito-Urinary Group, Princess Margaret Hospital, Radiation Therapy Oncology Group) with the aim of standardizing the clinical target volume (CTV) delineation and improve outcomes. To date, no attempt has been made to compare these guidelines in terms of treatment volumes or organ at risk (OAR) irradiation. The extent to which the guideline-derived plans meet the dosimetric constraints of present trials or of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) trial is also unknown. Our study also explored the dosimetric benefits of intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 20 patients treated with postoperative RT were included. The three-dimensional conformal radiotherapy (3D-CRT) plans were applied to cover the guideline-generated planning target volumes (66 Gy in 33 fractions). Dose-volume histograms (DVHs) were analyzed for CTV/planning target volume coverage and to evaluate OAR irradiation. The OAR DVHs were compared with the constraints proposed in the QUANTEC and Radiotherapy and Androgen Deprivation In Combination After Local Surgery (RADICALS) trials. 3D-CRT plans were compared with the tomotherapy plans for the Radiation Therapy Oncology Group planning target volume to evaluate the advantages of IMRT. Results: The CTV differed significantly between guidelines (p < 0.001). The European Organization for Research and Treatment of Cancer-CTVs were significantly smaller than the other CTVs (p < 0.001). Differences in prostate bed coverage superiorly accounted for the major volumetric differences between the guidelines. Using 3D-CRT, the DVHs rarely met the QUANTEC or RADICALS rectal constraints, independent of the guideline used. The RADICALS

  8. Comparison and Limitations of DVH-Based NTCP Models Derived From 3D-CRT and IMRT Data for Prediction of Gastrointestinal Toxicities in Prostate Cancer Patients by Using Propensity Score Matched Pair Analysis

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    Troeller, Almut [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich (Germany); Yan, Di, E-mail: dyan@beaumont.edu [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Marina, Ovidiu; Schulze, Derek [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Alber, Markus [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Parodi, Katia [Department of Medical Physics, Ludwig-Maximilians-Universität, Munich (Germany); Belka, Claus; Söhn, Matthias [Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich (Germany)

    2015-02-01

    Purpose: This study compared normal tissue complication probability (NTCP) modeling of chronic gastrointestinal toxicities following prostate cancer treatment for 2 treatment modalities. Possible factors causing discrepancies in optimal NTCP model parameters between 3-dimensional conformal radiation therapy (3D-CRT) and intensity modulated RT (IMRT) were analyzed and discussed, including the impact of patient characteristics, image guidance, toxicity scoring bias, and NTCP model limitations. Methods and Materials: Rectal wall dose-volume histograms of 1115 patients treated for prostate cancer under an adaptive radiation therapy protocol were used to model gastrointestinal toxicity grade ≥2 (according to Common Terminology Criteria for Adverse Events). A total of 457 patients were treated with 3D-CRT and 658 with IMRT. 3D-CRT patients were matched to IMRT patients based on various patient characteristics, using a propensity score–based algorithm. Parameters of the Lyman equivalent uniform dose and cut-off dose logistic regression NTCP models were estimated for the 2 matched treatment modalities and the combined group. Results: After they were matched, the 3D-CRT and IMRT groups contained 275 and 550 patients with a large discrepancy of 28.7% versus 7.8% toxicities, respectively (P<.001). For both NTCP models, optimal parameters found for the 3D-CRT groups did not fit the IMRT patients well and vice versa. Models developed for the combined data overestimated NTCP for the IMRT patients and underestimated NTCP for the 3D-CRT group. Conclusions: Our analysis did not reveal a single definitive cause for discrepancies of model parameters between 3D-CRT and IMRT. Patient characteristics and bias in toxicity scoring, as well as image guidance alone, are unlikely causes of the large discrepancy of toxicities. Whether the cause was inherent to the specific NTCP models used in this study needs to be verified by future investigations. Because IMRT is increasingly used

  9. RAPIDARC (RA) in the uterine cervical cancer; dosimetric gain vs 3D-Crt; RAPIDARC (RA) en el cancer de cervix uterino; ganancia dosimetrica vs 3D-CRT

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    Ramirez, J.; Garcia, B.; Quispe, K.; Gonzales, A.; Marquina, J., E-mail: jose.ramirez@aliada.com.pe [Clinica Aliada, Oncologia Integral, Av. Jose Galvez Barrenechea 1044, San Isidro, Lima (Peru)

    2014-08-15

    This work aims to quantitatively assess RAPIDARC (RA) treatments versus three dimensional-Conformal Radiation Therapy with field to field technique (3D-Crt-Fin F). 11 patients with cervical cancer treated at our institution radically or adjuvant clinical stages I-III B were evaluated. The prescribed dose was 50 Gy (2 Gy / Fr). The RA plans consisted of two isocentric complete arcs and conformational plans of 4 isocentric fields (previous, subsequent, right side and left side) with 3D-Crt-Fin F technique; both cases carried out ??in the Eclipse version 10 planner with calculation algorithm analytical anisotropic algorithm (AAA) and volumetric optimization software (for VMAT plans). Homogeneity indices (Hi), conformity indices (CI) Sigma indices (S-Index), monitor units (MU) and the time required for each treatment were compared. The mean age was 52 years (32-65) of the 11 patients 9 were clinical stages I-II B. The Hi varied from 0.052 for RA to 0.163 for 3D-Crt-Fin F (p = 0.009), and the CI between 1.005 and 1.35 (p = 0.26), the S-index from 1.2 to 3.7 (p = 0.001) and the H-index of 1.08 to 1.15 (p = 0.24). All dose limits in risk organs were met with a significant difference in the RA plans versus 3D-Crt-Fin F. In patients with cervical cancer the treatment plans quality with the indices aforementioned seems to be better with the RA technique, being observed a significant reduction of radiation to surrounding organs. (author)

  10. Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases.

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    Peyraga, Guillaume; Caron, Delphine; Lizee, Thibaut; Metayer, Yann; Septans, Anne-Lise; Pointreau, Yoann; Denis, Fabrice; Ganem, Gerard; Lafond, Cedrik; Roche, Sophie; Dupuis, Olivier

    2017-12-23

    The palliative treatment for cervico-thoracic spinal metastases is based on a three-dimensional conformal radiation therapy (3D-CRT). Digestive toxicities are common and cause a clinical impact frequently underestimated in patients. We performed a retrospective study of digestive side effects occurring after palliative 3D-CRT for cervico-thoracic spinal metastases. All patients receiving palliative 3D-CRT at Jean Bernard Center from January 2013 to December 2014 for spinal metastases between the 5th cervical vertebra (C5) and the 12th thoracic vertebra (T12) were eligible. Three-dimensional conformal RT was delivered by a linear accelerator (CLINAC, Varian). Premedication to prevent digestive toxicities was not used. Adverse events ("esophagitis" and "nausea and/or vomiting") were evaluated according to the NCI-CTCae (version 4). From January 2013 to December 2014, 128 patients met the study criteria. The median age was 68.6 years [31.8; 88.6]. Most patients (84.4%) received 30 Gy in 10 fractions. The median overall time of treatment was 13 days [3-33]. Forty patients (31.3%) suffered from grade ≥ 2 of "esophagitis" (35 grade 2 (27.4%) and 5 grade 3 (3.9%)). Eight patients (6.3%) suffered from grade ≥ 2 of "nausea and/or vomiting" (6 grade 2 (4.7%), 1 grade 3 (0.8%), and 1 grade 4 (0.8%)). The high incidence of moderate to severe digestive toxicities after palliative 3D-CRT for cervico-thoracic spinal metastases led to consider static or dynamic intensity-modulated radiation therapy (IMRT) to reduce the dose to organ at risk (the esophagus and stomach). Dosimetric studies and implementation in the clinic should be the next steps.

  11. A retrospective study of californium-252 neutron brachytherapy combined with EBRT versus 3D-CRT in the treatment of esophageal squamous cell cancer.

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    Wang, Qifeng; Li, Tao; Lang, Jinyi; Wang, Jie; Wang, Jian; Liu, Huiming; Jia, Xitang; Liu, Bo; Wang, C-K Chris

    2015-10-24

    We conducted a retrospective analysis on 884 patients who were diagnosed with esophageal squamous cell carcinoma (ESCC) and treated with either the neutron brachytherapy in combination with external beam radiotherapy (NBT + EBRT) or 3-dimensional conformal radiation therapy (3D-CRT) to determine the differences in efficacy and morbidity between the two treatment groups. The 884 ESCC patients treated with either NBT + EBRT or 3D-CRT between 2002 and 2012 were retrospectively reviewed and analyzed. Multivariable Cox regression was used to compare oncologic outcomes of the two groups of patients in the context of other clinically relevant variables. The acute and chronic toxicities associated with the two groups were compared using Fisher exact and log-rank tests, respectively. Among the 884 patients, 545 received NBT + EBRT and 339 received 3D-CRT (i.e. EBRT-only). The age range is 39-95 years (median 66). The follow-up time range is 3-145 months (median 32). The analysis shows that the NBT + EBRT group has higher overall survival rate and local control rate than that of the 3D-CRT group. The acute toxicity effects were acceptable for both groups of patients with the NBT + EBRT group showing higher rates of leukopenia and thrombocytopenia and the 3D-CRT group showing higher rates on fistula and massive bleeding. The patients treated with NBT + EBRT showed better oncologic outcomes than those treated with 3D-CRT. The toxicity effects were acceptable for both groups with the NBT + EBRT group showing higher rates on the acute effects and the 3D-CRT group showing higher rates on the late effects.

  12. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

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    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  13. Class solution to decrease rectal dose in prostate radiotherapy treatments 3D-CRT; Solucion de clase para disminuir dosis en recto en tratamientos de prostata con radioterapia 3D-CRT

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    Andres Rodriguez, C.; Tortosa Oliver, R.; Alonso Hernandez, D.; Mari Palacios, A.; Castillo Belmonte, A. del

    2011-07-01

    This paper contains a method developed in our center with conventional 3D radiotherapy techniques to increase the dose conformation around the target volume in prostate cancer treatments significantly reduced the doses to the rectum. To evaluate the goodness of the method, the results are compared with two classical techniques of treatment.

  14. Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

    Science.gov (United States)

    Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

    2015-01-01

    This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients

  15. Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model

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    Tomatis, S.; Rancati, T.; Fiorino, C.; Vavassori, V.; Fellin, G.; Cagna, E.; Mauro, F. A.; Girelli, G.; Monti, A.; Baccolini, M.; Naldi, G.; Bianchi, C.; Menegotti, L.; Pasquino, M.; Stasi, M.; Valdagni, R.

    2012-03-01

    The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with

  16. SU-E-T-632: A Dosimetric Comparison of the 3D-CRT Planning of Chest Wall in Post-Mastectomy Breast Cancer Patients, with and Without Breast Board Setup

    Energy Technology Data Exchange (ETDEWEB)

    Muzaffar, Ambreen; Masood, Asif; Ullah, Haseeb; Mehmood, Kashif; Qasim, Uzma; Afridi, M. Ali; Khan, Salim; Hameed, Abdul [Radiation Oncology Department, Shifa International Hospitals Ltd. Sector H-8/4 Islamabad (Pakistan)

    2014-06-15

    Purpose: Breast boards are used in breast radiation which increases normal lung and heart doses, when supraclavicular field is included. Therefore, in this study through dose volume histogram (DVHs), lung and heart doses comparison was done between two different setups i.e. with and without breast board, for the treatment of left chest wall and supraclavicular fossa in postmastectomy left breast cancer. Methods: In this study, CT-Simulation scans of ten breast cancer patients were done with and without breast board, at Shifa International Hospitals Islamabad, to investigate the differences between the two different setups of the irradiation of left chest wall in terms of lung and heart doses. For immobilization, support under the neck, shoulders and arms was used. Precise PLAN 2.15 treatment planning system (TPS) was used for 3D-CRT planning. The total prescribed dose for both the plans was 5000 cGy/25 fractions. The chest wall was treated with a pair of tangential photon fields and the upper supraclavicular nodal regions were treated with an anterior photon field. A mono-isocentric technique was used to match the tangential fields with the anterior field at the isocentre. The dose volume histogram was used to compare the doses of heart and ipsilateral lung. Results: Both the plans of each patient were generated and compared. DVH results showed that for the same PTV dose coverage, plans without breast board resulted in a reduction of lung and heart doses compared with the plans with breast board. There was significant reductions in V20, V<25 and mean doses for lung and V<9 and mean doses for heart. Conclusion: In comparison of both the plans, setup without breast board significantly reduced the dose-volume of the ipsilateral lung and heart in left chest wall patients. Waived registration request has been submitted.

  17. Design and implementation of a rotational radiotherapy technique for breast cancer treatment and their comparison with 3-D-Crt irradiation technique; Diseno e implementacion de una tecnica de radioterapia rotacional para tratamiento de cancer de mama y su comparacion contra la tecnica 3D-CRT de irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez M, J. G.; Lopez V, A.; Rivera M, T. [IPN, Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada, Av. Legaria 694, Col. Irrigacion, 11500 Mexico D. F. (Mexico); Velazquez T, J. J.; Adame G, C. S. [Centro Medico Nacional Siglo XXI, Hospital de Oncologia, Departamento de Fisica Medica, Av. Cuauhtemoc No. 330, Col. Doctores, 06720 Mexico D. F. (Mexico); Rubio N, O.; Chagoya G, A.; Hernandez G, J. C., E-mail: jggm25@yahoo.com.mx [Centro Medico Nacional Siglo XXI, Hospital de Oncologia, Departamento de Radioterapia, Av. Cuauhtemoc No. 330, Col. Doctores, 06720 Mexico D. F. (Mexico)

    2015-10-15

    Breast cancer is one of oncological diseases worldwide, as well in Mexico, which causes even more deaths than cervical cancer; this condition is the second death cause in women aged 30-54 years and threatens all socio-economic groups. The treatment is highly dependent on the stage which is detected and based on protocols that include a combination of surgery, chemotherapy and radiotherapy. This paper studies the main irradiation technique for patients with mastectomy, breast full cycle (irradiation of the chest well and supraclavicular nodes) in their mode Three Dimensional - Conformal Radiation Therapy (3-D-Crt), and compared with the Volumetric Modulated Arc Therapy (VMAT) technique proposed in this paper. In both techniques the prescription was 50 Gy divided into 25 fractions. The techniques were applied in three female patients (being an initial study) with disease of the left side, the target volume and organs at risk were delineated by the medical treating radiation oncologist, the planning system used was Eclipse version 10; for quantitative comparison of both plans indexes of homogeneity were used, con formality, the target volume coverage and normal tissue, sub factors and overdosing, the conformation number and coverage quality. They were evaluated and compared the media, maximum and minimum dose of the organs at risk, based on the fact that the coverage of the target volume, dose gradient and dose at risk organs are acceptable (prescription dose greater that 90% coverage, gradient less that 20% and organs at risk in accordance with the Quantec limitations for both versions). (Author)

  18. Risk of isolated nodal failure for non-small cell lung cancer (NSCLC) treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) techniques--a retrospective analysis.

    Science.gov (United States)

    Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka

    2008-01-01

    To estimate retrospectively the rate of isolated nodal failures (INF) in NSCLC patients treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT). One hundred and eighty-five patients with I-IIIB stage treated with 3D-CRT in consecutive clinical trials differing in an extent of the ENI were analyzed. According to the extent of the ENI, two groups were distinguished: extended (n = 124) and limited (n = 61) ENI. INF was defined as regional nodal failure occurring without local progression. Cumulative Incidence of INF (CIINF) was evaluated by univariate and multivariate analysis with regard to prognostic factors. With a median follow up of 30 months, the two-year actuarial overall survival was 35%. The two-year CIINF rate was 12%. There were 16 (9%) INF, eight (6%) for extended and eight (13%) for limited ENI. In the univariate analysis bulky mediastinal disease (BMD), left side, higher N stage, and partial response to RT had a significant negative impact on the CIINF. BMD was the only independent predictor of the risk of incidence of the INF (p = 0.001). INF is more likely to occur in case of more advanced nodal status.

  19. High-dose-rate brachytherapy for uterine cervical cancer: the results of different fractionation regimen

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Won Sup; Kim, Tae Hyun; Yang, Dae Sik; Choi, Myung Sun; Kim, Chul Yong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    2002-09-15

    Although high-dose-rate (HDR) brachytherapy regimens have been practiced with a variety of modalities and various degrees of success, few studies on the subject have been conducted. The purpose of this study was to compare the results of local control and late complication rate according to different HDR brachytherapy fractionation regimens in uterine cervical cancer patients. From November 1992 to March 1998, 224 patients with uterine cervical cancer were treated with external beam irradiation and HDR brachytherapy. In external pelvic radiation therapy, the radiation dose was 45 {approx} 54 Gy (median dose 54 Gy) with daily fraction size 1.8 Gy, five times per week. In HDR brachytherapy, 122 patients (Group A) were treated with three times weekly with 3 Gy to line-A (isodose line of 2 cm radius from source) and 102 patients (Group B) underwent the HDR brachytherapy twice weekly with 4 or 4.5 Gy to line-A after external beam irradiation. Iridium-192 was used as the source of HDR brachytherapy. Late complication was assessed from grade 1 to 5 using the RTOG morbidity grading system. The local control rate (LCR) at 5 years was 80% in group A and 84% in group B ({rho} = 0.4523). In the patients treated with radiation therapy alone, LCR at 5 years was 60.9% in group A and 76.9% in group B ({rho} = 0.2557). In post-operative radiation therapy patients, LCR at 5 years was 92.6% in group A and 91.6% in group B ({rho} 0.8867). The incidence of late complication was 18% (22 patients) and 29.4% (30 patients), of bladder complication was 9.8% (12 patients) and 14.7% (15 patients), and of rectal complication was 9.8% (12 patients) and 21.6% (22 patients), in group A and B, respectively. Lower fraction sized HDR brachytherapy was associated with decrease in late complication ({rho} =0.0405) (rectal complication, {rho} = 0.0147; bladder complication, {rho} =0.115). The same result was observed in postoperative radiation therapy patients ({rho} = 0.0860) and radiation only

  20. High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

    Energy Technology Data Exchange (ETDEWEB)

    Hauswald, Henrik; Kamrava, Mitchell R.; Fallon, Julia M.; Wang, Pin-Chieh; Park, Sang-June; Van, Thanh; Borja, Lalaine; Steinberg, Michael L.; Demanes, D. Jeffrey, E-mail: JDemanes@mednet.ucla.edu

    2016-03-15

    Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

  1. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome.

    Science.gov (United States)

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-10-01

    The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy.

  2. Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

    Science.gov (United States)

    Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

    2014-01-01

    The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, pbone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, pmarrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, pbone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover. PMID:23954507

  3. Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma--a retrospective analysis.

    Science.gov (United States)

    Yamashita, Hideomi; Okuma, Kae; Wakui, Reiko; Kobayashi-Shibata, Shino; Ohtomo, Kuni; Nakagawa, Keiichi

    2011-02-01

    To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy. One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume. All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local=20 and distant=20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids: Feasibility and Early Results

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Ping, E-mail: ping.jiang@uksh.de [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Baumann, René [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Dunst, Juergen [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Department of Radiation Oncology, University of Copenhagen, Copenhagen (Denmark); Geenen, Matthias [Department of Reconstructive Surgery, Lubinus Clinic Kiel, Kiel (Germany); Siebert, Frank-André [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Niehoff, Peter [Department of Radiation Oncology, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany); Department of Radiation Oncology, Community Clinic Köln, Köln (Germany); Department of Radiation Oncology, University Witten/Herdecke, Witten (Germany); Bertolini, Julia; Druecke, Daniel [Department of Reconstructive Surgery, University Clinic Schleswig-Holstein, Campus Kiel, Kiel (Germany)

    2016-03-01

    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 immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission. After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours after surgery, the other 2 fractions on the first postoperative day. Thus, a total dose of 18 Gy in 3 fractions was administered within 36 hours after the resection. Results: The treatment was feasible in all patients. No procedure-related complications (eg, secondary infections) occurred. Nineteen patients had keloid-related symptoms before treatment like pain and pruritus; disappearance of symptoms was noticed in all patients after treatment. After a median follow-up of 29.4 months (range, 7.9-72.4 months), 2 keloid recurrences and 2 mildly hypertrophied scars were observed. The local control rate was 94%. Pigmentary abnormalities were detected in 3 patients, and an additional 6 patients had a mild delay in the wound-healing process. Conclusions: The early results of this study prove the feasibility and the efficacy of brachytherapy for the prevention of keloids. The results also suggest that brachytherapy may be advantageous in the management of high-risk keloids or as salvage treatment for failure after external beam therapy.

  5. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    Energy Technology Data Exchange (ETDEWEB)

    Renis, M.; Malfa, G.; Tomasello, B. [Drug Sciences Department, University of Catania, Catania (Italy); Borghesi, M.; Schettino, G. [Queen' s University Belfast, Northern Ireland (United Kingdom); Favetta, M.; Romano, F.; Cirrone, G. A. P. [National Institute for Nuclear Physics (INFN-LNS), Catania (Italy); Manti, L. [Physics Science Department, University of Naples Federico II, Naples, and National Institute for Nuclear Physics (INFN), Naples (Italy)

    2013-07-26

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

  6. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    Science.gov (United States)

    Renis, M.; Borghesi, M.; Favetta, M.; Malfa, G.; Manti, L.; Romano, F.; Schettino, G.; Tomasello, B.; Cirrone, G. A. P.

    2013-07-01

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

  7. 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%.

  8. High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, Nikolaos [Department of Radiation Oncology, Klinikum Offenbach, Offenbach (Germany); Tselis, Nikolaos, E-mail: ntselis@hotmail.com [Department of Radiation Oncology, Klinikum Offenbach, Offenbach (Germany); Baltas, Dimos [Department of Medical Physics and Engineering, Klinikum Offenbach, Offenbach (Germany); Buhleier, Thomas [Department of Radiation Oncology, Klinikum Offenbach, Offenbach (Germany); Martin, Thomas [Department of Radiation Oncology, Klinikum Bremen-Mitte, Bremen (Germany); Milickovic, Natasa; Papaioannou, Sokratis [Department of Medical Physics and Engineering, Klinikum Offenbach, Offenbach (Germany); Ackermann, Hanns [Institute of Biostatistics, J.W. Goethe University of Frankfurt, Frankfurt (Germany); Tunn, Ulf W. [Department of Urology, Klinikum Offenbach, Offenbach (Germany)

    2013-03-01

    Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

  9. High-dose-rate interstitial brachytherapy for T1-T2-stage penile carcinoma: short-term results.

    Science.gov (United States)

    Sharma, Daya Nand; Joshi, Nikhil P; Gandhi, Ajeet Kumar; Haresh, Kunhi P; Gupta, Subhash; Julka, Pramod Kumar; Rath, Goura Kisor

    2014-01-01

    Interstitial brachytherapy (IBT) is a preferred treatment option over partial penectomy in selected patients with T1-T2-stage penile carcinoma because of its organ preservation ability. Literature is mostly based on the use of low-dose-rate IBT, and experience with high-dose-rate (HDR) IBT is extremely limited. We studied the role of HDR-IBT alone in patients with T1-T2-stage penile carcinoma. Between April 2010 and July 2013, 14 patients with T1-T2-stage penile carcinoma were treated with HDR-IBT at our center. Size of the primary lesion ranged from 1.5 to 4.0cm. A two-to-four-plane free-hand implant was performed using plastic catheters. The prescribed dose of HDR-IBT was 42-51Gy in 14-17 fractions using twice-a-day fractionation schedule. Patients were followed up regularly for assessment of local control, survival, toxicity, and sexual function. At a median followup of 22 months, 2 patients developed recurrent disease at locoregional site. The 3-year overall survival was 83% with penis preservation rate of 93%. All patients developed acute Grade III skin toxicity that healed during 6-8-weeks time. Urethral stenosis and soft tissue necrosis was not seen in any of the patients. A total of 4 patients experienced mild asymptomatic fibrosis in the implanted area. Around 10 patients had satisfactory sexual function status at the last followup visit. Although it was a small sample size, our results have demonstrated excellent local control rate and acceptable toxicity with HDR-IBT in patients with T1-T2-stage penile carcinoma. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  10. High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Viani, Gustavo Arruda, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil)

    2012-08-01

    Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

  11. High-dose-rate Three-dimensional Conformal Radiotherapy Combined with Active Breathing Control for Stereotactic Body Radiotherapy of Early-stage Non-small-cell Lung Cancer.

    Science.gov (United States)

    Wang, Ruozheng; Yin, Yong; Qin, Yonghui; Yu, Jinming

    2015-12-01

    The purpose of this study was to evaluate the feasibility and benefits of using high-dose-rate three-dimensional conformal radiotherapy (3D-CRT) combined with active breathing control (ABC) for stereotactic body radiotherapy (SBRT) of patients with early-stage non-small-cell lung cancer (NSCLC). Eight patients with early-stage NSCLC underwent CT scans under standard free-breathing (FB) and moderately deep inspiration breath-hold (mDIBH) with ABC. Two high-dose-rate 3D-CRT plans (1000 Mu/min) were designed based on the CT scans with FB and mDIBH. The maximal dose (D1%), minimal dose (D99%), conformity index (CI), and homogeneity index (HI) of the planning target volume (PTV), and dose-volume indices of the organs at risk between each plan were compared. The mean PTV volume decreased from 158.04 cm(3) with FB to 76.90 cm(3) with mDIBH (p < 0.05). When mDIBH was used, increases in the affected lung volume (by 47%), contralateral lung volume (by 55%), and total lung volume (by 50%) were observed compared to FB (p < 0.05). The V5-V40 of the affected lung (Vx represented the percentage volume of organs receiving at least the x Gy), V5-V40 and the mean dose for the total lung, V5-V40 and mean dose of the chest wall, and the maximum dose of the spinal cord were less for mDIBH than FB (p < 0.05). There were no significant differences in CI, HI, D1%, or D99% for the PTV between the plans. In conclusion, high-dose-rate 3D-CRT combined with ABC reduced the radiation dose to the lungs and chest wall without affecting the dose distribution in SBRT of early-stage NSCLC patients. © The Author(s) 2014.

  12. High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma - Results of a comprehensive meta-analysis

    NARCIS (Netherlands)

    Greb, Alexander; Bohlius, Julia; Trelle, Sven; Schiefer, Daniel; De Souza, Carmino A.; Gisselbrecht, Christian; Lntragumtornchai, Tanin; Kaiser, Ulrich; Kluin-Nelemans, Hanneke C.; Martelli, Maurizio; Milpied, Noel Jean; Santini, Gino; Verdonck, Leo F.; Vitolo, Umberto; Schwarzer, Guido; Engert, Andreas

    Background: Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-tine treatment of patients with aggressive non-Hodgkin lymphoma (NHL). Methods: We performed a systematic meta-analysis to

  13. High-dose etanercept in ankylosing spondylitis: results of a 12-week randomized, double blind, controlled multicentre study (LOADET study).

    Science.gov (United States)

    Navarro-Sarabia, Federico; Fernández-Sueiro, José L; Torre-Alonso, Juan C; Gratacos, Jordi; Queiro, Rubén; Gonzalez, Carlos; Loza, Eduardo; Linares, Luis; Zarco, Pedro; Juanola, Xavier; Román-Ivorra, José; Martín-Mola, Emilio; Sanmartí, Raimon; Mulero, Juan; Diaz, Gema; Armendáriz, Yolanda; Collantes, Eduardo

    2011-10-01

    Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS. Adult patients with AS were randomized to receive etanercept 50 mg twice a week (biw), or etanercept 50 mg once a week (qw) for 12 weeks. The primary efficacy endpoint was Ankylosing Spondylitis Assessment Study (ASAS20) response at Week 12; secondary endpoints included ASAS40, ASAS50, ASAS70 and ASAS5/6 responses, partial remission and quality of life. Safety was assessed until 15 days after the last visit. A total of 108 patients were randomly selected and treated, 54 in each arm. At 12 weeks, ASAS20 response was achieved by 34 (71%) out of 48 patients of the etanercept 50 mg biw group and by 37 (76%) out of 49 patients of the etanercept 50 mg qw group (not statistically significant differences). Other efficacy variables improved significantly over time, but not between treatment groups. Fifty-six patients experienced at least one adverse event (generally, infections and infestations, gastrointestinal disorders and injection site reactions), most of them mild or moderate. High-dose (100 mg/week) etanercept in the treatment of AS for 12 weeks is as safe as the standard dose (50 mg/week). However, it does not significantly increase its efficacy. Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, NCT00873730.

  14. High-dose-rate brachytherapy as a monotherapy for prostate cancer--Single-institution results of the extreme fractionation regimen.

    Science.gov (United States)

    Kukiełka, Andrzej Marek; Dąbrowski, Tomasz; Walasek, Tomasz; Olchawa, Agnieszka; Kudzia, Roksana; Dybek, Dorota

    2015-01-01

    We report a single-institution retrospective analysis of the outcomes, disease control, and toxicity of high-dose-rate (HDR) brachytherapy used as the only treatment modality (monotherapy) for localized prostate cancer. Between 2006 and 2012, 77 patients with diagnosed prostate cancer were treated with HDR brachytherapy as a monotherapy. The prescribed dose was 45 Gy in three separate implants 21 days apart, with single fraction per implant. Of the 77 patients, 67 (87%) received hormonal therapy. Prostate-specific antigen failure was defined according to Phoenix consensus, as nadir + 2 ng/mL. Toxicity was scored according to Common Terminology Criteria for Adverse Events, version 4.03. The median followup time was 57 months (4.75 years). The 5-year actuarial overall survival was 98.7%, biochemical control 96.7%, local control 96.9%, and metastasis-free survival 98.4%. Younger age at the beginning of brachytherapy predicted the onset of bounce phenomenon. There were no Grade 3 or higher acute toxicities detected, and Grade 2 genitourinary acute toxicity developed in 19 patients (24.6%). There were no Grade 2 gastrointestinal complications. No Grade 4 or 5 late toxicity was detected. There were also no Grade 3 gastrointestinal toxicities detected. One patient (1.3%) underwent transurethral resection of the prostate because of Grade 3 urethral stenosis and urinary retention. A total of 26 patients (33.8%) developed Grade 2 late toxicity. HDR brachytherapy as monotherapy for localized prostate cancer was feasible, effective, and had acceptable toxicity profile. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  15. Low-dose and high-dose acetylsalicylic acid, with and without dipyridamole: a review of clinical trial results

    NARCIS (Netherlands)

    Tijssen, J. G.

    1998-01-01

    Publication of the results of the second European Stroke Prevention Study (ESPS-2) provided the incentive for an update of the meta-analyses of aspirin and dipyridamole in the secondary prevention of stroke. After review of published randomized trials of prolonged treatment with aspirin,

  16. High-dose-rate interstitial brachytherapy for accelerated partial breast irradiation – trial results of Azerbaijan National Center of Oncology

    Directory of Open Access Journals (Sweden)

    Jamil A. Aliyev

    2017-04-01

    Full Text Available Purpose : To describe early results of two cohorts of patients with low and intermediate risk of early breast cancer treated with accelerated partial breast irradiation (APBI using different schedules of multicatheter brachytherapy. Material and methods: Patients with early stage breast cancer after breast conserving surgery were enrolled for a prospective analysis. The APBI, using multicatheter brachytherapy, was delivered either eight times 4 Gy in five days with a planned total dose of 32 Gy, or seven times 5 Gy in four days with a planned total dose of 35 Gy. Primary endpoints were side effects. Results : Forty-eight patients were enrolled between 2012 and 2014. Patients characteristics were as follow: median age of patients was 55 years, early breast cancer was defined according GEC-ESTRO recommendations. With a median follow-up period of 37 months, no significant differences regarding late side effects and cosmesis between two cohorts of patients were documented. In total, cosmesis was excellent in 13/48 (27.1% patients, good in 34/48 (70.8% patients, and moderate in 1/48 patient (2.1%. Conclusions : Accelerated partial breast irradiation using multicatheter brachytherapy with 32 Gy/8 fractions and 35 Gy/7 fractions for early breast cancer seems to be similar in terms of late side effects. According to our findings, APBI was also feasible for intermediate-risk of early breast cancer patients.

  17. Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors: results of a randomized crossover trial.

    Science.gov (United States)

    Pantin, Jeremy; Purev, Enkhtsetseg; Tian, Xin; Cook, Lisa; Donohue-Jerussi, Theresa; Cho, Elena; Reger, Robert; Hsieh, Matthew; Khuu, Hanh; Calandra, Gary; Geller, Nancy L; Childs, Richard W

    2017-03-01

    Hematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 μg/kg) plerixafor in CD34+ cell mobilization in healthy donors. Subjects were randomly assigned to receive either a high dose or a conventional dose (240 μg/kg) of plerixafor, given as a single subcutaneous injection, in a two-sequence, two-period, crossover design. Each treatment period was separated by a 2-week minimum washout period. The primary endpoint was the peak CD34+ count in the blood, with secondary endpoints of CD34+ cell area under the curve (AUC), CD34+ count at 24 hours, and time to peak CD34+ following the administration of plerixafor. We randomized 23 subjects to the two treatment sequences and 20 subjects received both doses of plerixafor. Peak CD34+ count in the blood was significantly increased (mean 32.2 versus 27.8 cells/μL, P=0.0009) and CD34+ cell AUC over 24 hours was significantly increased (mean 553 versus 446 h cells/μL, Phealthy donors and mobilizes greater numbers of CD34+ cells than conventional-dose plerixafor, which may improve CD34+ graft yields and reduce the number of apheresis procedures needed to collect sufficient stem cells for allogeneic transplantation. (ClinicalTrials.gov, identifier: NCT00322127). Copyright© Ferrata Storti Foundation.

  18. Chemoradiation in cervical cancer with cisplatin and high-dose rate brachytherapy combined with external beam radiotherapy. Results of a phase-II study

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, H.G.; Laban, C.; Puschmann, D.; Koelbl, H. [Dept. of Gynecology, Martin-Luther Univ. Halle-Wittenberg (Germany); Kuhnt, T.; Pigorsch, S.; Dunst, J.; Haensgen, G. [Dept. of Radiotherapy, Martin-Luther Univ. Halle-Wittenberg (Germany)

    2002-07-01

    Background: In 1999, five randomized studies demonstrated that chemoradiation with cisplatin and low-dose rate (LDR) brachytherapy has a benefit in locally advanced cervical cancer and for surgically treated patients in high-risk situations. We evaluated the safety and efficacy of concomitant chemoradiation with cisplatin and high-dose rate (HDR) brachytherapy in patients with cervical cancer. Patients and Method: 27 patients were included in our phase-II trial: 13 locally advanced cases (group A) and 14 adjuvant-therapy patients in high-risk situations (group B). A definitive radiotherapy was performed with 25 fractions of external beam therapy (1.8 Gy per fraction/middle shielded after eleven fractions). Brachytherapy was delivered at HDR schedules with 7 Gy in point A per fraction (total dose 35 Gy) in FIGO Stages IIB-IIIB. The total dose of external and brachytherapy was 70 Gy in point A and 52-54 Gy in point B. All patients in stage IVA were treated without brachytherapy. Adjuvant radiotherapy was performed with external beam radiotherapy of the pelvis with 1.8 Gy single-dose up to 50.4 Gy. Brachytherapy was delivered at HDR schedules with two fractions of 5 Gy only in patients with tumor-positive margins or tumor involvement of the upper vagina. The chemotherapeutic treatment schedule provided six courses of cisplatin 40 mg/m{sup 2} weekly recommended in the randomized studies GOG-120 and -123. Results: A total of 18/27 patients (66.7%) completed all six courses of chemotherapy. Discontinuation of radiotherapy due to therapy-related morbidity was not necessary in the whole study group. G3 leukopenia (29.6%) was the only relevant acute toxicity. There were no differences in toxicity between group A and B. Serious late morbidity occurred in 2/27 patients (7.4%). 12/13 patients (92.3%) with IIB-IVA cervical cancer showed a complete response (CR). 13/14 adjuvant cases (92.8%) are free of recurrence (median follow up: 19.1 months). Conclusion: Concomitant

  19. Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment of intermediate-risk prostate cancer - long term results.

    Science.gov (United States)

    Cury, Fabio L; Duclos, Marie; Aprikian, Armen; Patrocinio, Horacio; Kassouf, Wassim; Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis

    2012-03-15

    We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. High-dose therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group.

    Science.gov (United States)

    Caballero, M D; Pérez-Simón, J A; Iriondo, A; Lahuerta, J J; Sierra, J; Marín, J; Gandarillas, M; Arranz, R; Zuazu, J; Rubio, V; Fernández de Sevilla, A; Carreras, E; García-Conde, J; García-Laraña, J; Grande, C; Sureda, A; Vidal, M J; Rifón, J; Pérez-Equiza, C; Varela, R; Moraleda, J M; García Ruíz, J C; Albó, C; Cabrera, R; San Miguel, J F; Conde, E

    2003-01-01

    The purpose of this study was to analyse the results and prognostic factors influencing overall survival (OS) and disease-free survival (DFS) in 452 patients diagnosed with diffuse large cell lymphomas (DLCL) treated with high-dose therapy (HDT) included in the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) Spanish registry. At transplantation, median age was 42 years (range 15-73), 146 patients (32%) were transplanted in first complete remission (1st CR), 19% in second CR (2nd CR) and 47% had active disease: sensitive disease in 157 (35%) patients [95 were in first partial remission (1st PR) and 62 in second PR (2nd PR)] and refractory disease in 55 (12%) patients. Age-adjusted International Prognostic Index (IPI) was 2 or 3 in 51 patients (12%). Conditioning regimen consisted of BEAM (carmustine, etoposide, cytarabine and melphalan) in 39% of patients, BEAC (carmustine, etoposide, cytarabine and cyclophosphamide) in 33%, CBV (carmustine, etoposide and cyclophosphamide) in 10% and cyclophosphamide plus total body irradiation (TBI) in 12%. Estimated overall survival (OS) and disease-free survival (DFS) at 5 years were 53% and 43%, respectively. The transplant-related mortality was 11% (53 cases). By multivariate analysis three variables significantly influenced OS and DFS: number of protocols to reach 1st CR, disease status at transplant and TBI in the conditioning regimen. Age-adjusted IPI at transplantation also influenced OS. Prolonged OS and DFS can be achieved in patients with DLCL after HDT and our results suggest that the best line of chemotherapy should be used up-front in patients considered as candidates for HDT in order to obtain an early CR. Resistant patients are not good candidates for HDT and they should be offered newer strategies. Finally, polichemotherapy conditioning regimens offer better results compared with TBI.

  1. High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

    Science.gov (United States)

    Burdach, S; Meyer-Bahlburg, A; Laws, H J; Haase, R; van Kaik, B; Metzner, B; Wawer, A; Finke, R; Göbel, U; Haerting, J; Pape, H; Gadner, H; Dunst, J; Juergens, H

    2003-08-15

    Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

  2. Phase II Trial of Combined High Dose Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

    Science.gov (United States)

    Hsu, I-Chow; Bae, Kyounghwa; Shinohara, Katsuto; Pouliot, Jean; Purdy, James; Ibbott, Geoffrey; Speight, Joycelyn; Vigneault, Eric; Ivker, Robert; Sandler, Howard

    2010-01-01

    Purpose To estimate the rate of late grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) following treatment with external beam radiation therapy and prostate high dose rate (HDR) brachytherapy. Methods and Materials Each participating institution submitted CT based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined T1c-T3b prostate cancer were eligible for this study. All patients were treated with 45 Gy in 25 fractions from external beam radiotherapy and one HDR implant delivering 19 Gy in 2 fractions. All AEs were graded according to CTCAEv3.0. Late GU/ GI AEs were defined as those occurring more than nine months from the start of the protocol treatment, in patients with at least 18 months of potential follow-up. Results A total of 129 patients from 14 institutions were enrolled in this study. 125 patients were eligible and AE data was available for 112 patients. The pretreatment characteristics of the patients were as follows: T1c-T2c 91%, T3a-T3b 9%, PSA ≤ 10 70%, PSA >10-≤20 30%, GS 2-6 10%, GS 7 72%, and GS 8-10 18%. At a median follow-up time of 29.6 months, 3 acute and 4 late grade 3 GU/GI AEs were reported. The estimated rate of late grade 3-5 GU and GI AE at 18 months was 2.56%. Conclusion This is the first prospective, multi-institutional trial of CT based HDR brachytherapy and external beam radiotherapy. The technique and doses used in this study resulted in acceptable levels of adverse events. PMID:20207506

  3. A prospective cohort study to compare treatment results between 2 fractionation schedules of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer.

    Science.gov (United States)

    Huang, Eng-Yen; Sun, Li-Min; Lin, Hao; Lan, Jen-Hong; Chanchien, Chan-Chao; Huang, Yu-Jie; Wang, Chang-Yu; Wang, Chong-Jong

    2013-01-01

    To compare the treatment results of 2 fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy×4 (HDR-4) (n=144) or 4.5 Gy×6 (HDR-6) (n=123) to point A of ICBT using 192Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6. There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5-year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged≥62 years old (P=.012) but not in patients agedschedules. The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Updated results of high-dose rate brachytherapy and external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO phoenix definition

    Directory of Open Access Journals (Sweden)

    Antonio C. Pellizzon

    2008-06-01

    Full Text Available PURPOSE: To evaluate the prognostic factors for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (RT and high dose rate brachytherapy (HDR according to the RTOG-ASTRO Phoenix Consensus Conference. MATERIALS AND METHODS: The charts of 209 patients treated between 1997 and 2005 with localized RT and HDR as a boost at the Department of Radiation Oncology, AC Camargo Hospital, Sao Paulo, Brazil were reviewed. Clinical and treatment parameters i.e.: patient's age, Gleason score, clinical stage, initial PSA (iPSA, risk group (RG for biochemical failure, doses of RT and HDR were evaluated. Median age and median follow-up time were 68 and 5.3 years, respectively. Median RT and HDR doses were 45 Gy and 20 Gy. RESULTS: Disease specific survival (DSS at 3.3 year was 94.2%. Regarding RG, for the LR (low risk, IR (intermediate risk and HR (high risk, the DSS rates at 3.3 years were 91.5%, 90.2% and 88.5%, respectively. On univariate analysis prognostic factors related to DSS were RG (p = 0.040, Gleason score ≤ 6 ng/mL (p = 0.002, total dose of HDR ≥ 20 Gy (p < 0.001 On multivariate analysis the only statistical significant predictive factor for biochemical control (bNED was the RG, p < 0.001 (CI - 1.147-3.561. CONCLUSIONS: Although the radiation dose administered to the prostate is an important factor related to bNED, this could not be established with statistical significance in this group of patients. To date , in our own experience, HDR associated to RT could be considered a successful approach in the treatment of prostate cancer.

  5. Electron and high-dose-rate brachytherapy boost in the conservative treatment of stage I-II breast cancer. First results of the randomized Budapest boost trial

    Energy Technology Data Exchange (ETDEWEB)

    Polgar, C.; Fodor, J. [National Institute of Oncology, Department of Radiotherapy, Budapest (Hungary); Orosz, Z. [National Institute of Oncology, Center of Experimental and Human Tumor Pathology Budapest (HU)] [and others

    2002-11-01

    Background and Aims: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. Patients and Methods: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n=104) or no further radiotherapy (n=103). Boost treatments consisted of either 16 Gy electron irradiation (n=52) or 12-14.25 Gy HDR BT (n=52). Breast cancer-related events, side effects, and cosmetic results were assessed. Results: At a median follow-up of 5.3 years, the crude rate of local recurrence was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs 84.9% (p=0.049), 76.6% vs 66.2% (p=0.044), and 90.4% vs. 82.1% (p=0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs 91.4%; p=0.74). On multivariate analysis, patient age <40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs 7.8%; p=0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p=0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p=0.29). Conclusions: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age

  6. A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Shayna L., E-mail: snl2t@virginia.edu [Division of Surgical Oncology, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Petroni, Gina [Division of Translation Research and Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Trifiletti, Daniel M.; Libby, Bruce [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Schroen, Anneke T.; Brenin, David R. [Division of Surgical Oncology, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Dalal, Parchayi [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Smolkin, Mark [Division of Translation Research and Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Reardon, Kelli A.; Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States)

    2016-09-01

    Purpose: Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT. Methods and Materials: A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size <3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity. Results: Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit. Conclusions: CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.

  7. High dose irradiation with hyperfractionation

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Hideo; Kurashima, Shoji; Hasegawa, Maki; Akiyama, Kazuo (Sagamihara National Hospital, Kanagawa (Japan))

    1990-10-01

    From March 1988 to January 1990, 12 patients including 7 primary lung cancers, 2 lung metastases of colorectal cancer, and each 1 gall bladder cancer, ovarian cancer, and spinal cord metastasis of prostatic cancer, received {sup 60}Co-irradiation with high dose by hyperfractionation. This hyperfractionation consisted of 1.2 Gy per fraction, twice a day with 6 hour interval, and 5 days (10 fractions) a week. The total dose administered was 81.6{approx}100 Gy. The acute reaction of skin, lung, and intestines was tolerable, and it seemed that the late damage of normal tissues was slighter and the treatment result was favorable in comparison with the conventional fractionation, but this estimation was not definite because of short observation period. It was discussed that further reduction of dose per fraction (1 Gy or below) and more increased total dose (100 Gy or more) would be promising in hyperfractionation. (author).

  8. Feasibility of high-dose dobutamine stress SSFP Cine MRI at 3 Tesla with patient adaptive local RF Shimming using dual-source RF transmission: initial results.

    Science.gov (United States)

    Strach, K; Clauberg, R; Müller, A; Wonneberger, U; Naehle, C P; Kouwenhoven, M; Gieseke, J; Schild, H H; Thomas, D

    2013-01-01

    To investigate the feasibility of high-dose dobutamine stress (HDDS) imaging using SSFP sequences at 3 T employing patient-adaptive local RF-shimming using a dual-source RF transmission system. 13 Patients underwent a HDDS protocol on a 3 T MRI scanner (Achieva 3.0T-TX, Philips Healthcare), equipped with a dual-source RF transmission system. SSFP cine sequences using patient-adaptive local RF-shimming (RF-S) were compared to cine images acquired without additional shimming. Image quality was evaluated on a 4-point grading scale and number of non-diagnostic segments assessed. Contrast (CN) between myocardium (SIM) and blood pool (SIB) was calculated [(SIB-SIM)/(SIB+SIM)]. Image quality both at rest and maximum stress was significantly improved with RF-S (ED:3.56±0.5 vs. 3.23±0.63; ES:3.4±0.5 vs. 3.1±0.7) compared to no RF-S (ED:2.9±0.72 vs. 2.15±0.78; ES:2.64±0.74 vs. 1.95±0.76; pstress (3 vs. 39; 19 vs. 78, psource RF transmission system allows for reliable SSFP imaging in a clinical high-dose dobutamine stress protocol at 3 T. RF-S significantly improves image quality and reduces the number of non-diagnostic myocardial segments. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Lengthening of insect development on Bt zone results in adult emergence asynchrony: does it influence the effectiveness of the high dose/refuge zone strategy?

    Science.gov (United States)

    Gryspeirt, Aiko; Grégoire, Jean-Claude

    2012-11-15

    The “High Dose/Refuge” strategy (HD/R) is the currently recommended Insect Resistance Management strategy (IRM) to limit resistance development to Bacillus thuringiensis (Bt) plants. This strategy requires planting a “refuge zone” composed of non-Bt plants suitable for the target insect and in close proximity to a “Bt zone” expressing a high toxin concentration. One of the main assumptions is that enough susceptible adults mate with resistant insects. However, previous studies have suggested that the high toxin concentration produced by Bt plants induces slower insect development, creating an asynchrony in emergence between the refuge and the Bt zone and leading to assortative mating between adults inside each zone. Here, we develop a deterministic model to estimate the impact of toxin concentration, emergence asynchrony and refuge zone size on the effectiveness of the HD/R strategy. We conclude that emergence asynchrony only affects resistance when toxin concentration is high and resistance is recessive. Resistance develops more rapidly and survival of susceptible insects is higher at lower toxin concentration, but in such situations, resistance is insensitive to emergence asynchrony.

  10. Complete response of endemic Kaposi sarcoma lesions with high-dose-rate brachytherapy: treatment method, results, and toxicity using skin surface applicators.

    Science.gov (United States)

    Kasper, Michael E; Richter, Sam; Warren, Nicholas; Benda, Rashmi; Shang, Charles; Ouhib, Zoubir

    2013-01-01

    To analyze the clinical outcome of Kaposi sarcoma skin lesions treated with high-dose-rate (HDR) brachytherapy in patients with a minimum of 2 years of followup. Between February 2006 and July 2008, all patients with Kaposi sarcoma who received (192)Ir HDR brachytherapy using a skin surface applicator were evaluated for clinical response. Responses to treatment and toxicity were scored using standard criteria. Sixteen cases were collected. Treatment was delivered in four to six fractions, over a period of approximately 12 days. The specified dose ranged from 24 to 35Gy. Median followup the lesion was 41.4 months. No lesion was greater than 2cm. All patients had a complete response to treatment, with no evidence of local recurrence or tumor progression. Thirteen lesions developed Grade 1 and two lesions had Grade 2 acute skin reactions. One patient developed late skin changes with telangiectasias and hypopigmentation. HDR brachytherapy treatment seems to be an effective noninvasive option for patients with small cutaneous Kaposi sarcoma lesions, delivering excellent cosmesis and local control in our small series. Fewer fractions over a shorter period used in our group offer patients more convenience compared with other common regimens. Although HDR is being used more frequently for many surface applications, additional clinical studies with larger numbers of patients and longer followup are needed to confirm the general impression that it is an excellent option for many patients. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  11. Image-guided high-dose-rate brachytherapy boost to the dominant intraprostatic lesion using multiparametric magnetic resonance imaging including spectroscopy: Results of a prospective study.

    Science.gov (United States)

    Vigneault, Eric; Mbodji, Khaly; Racine, Louis-Gabriel; Chevrette, Eric; Lavallée, Marie-Claude; Martin, André-Guy; Després, Philippe; Beaulieu, Luc

    To evaluate the long-term outcomes of image-guided high-dose-rate (HDR) brachytherapy boost to the dominant intraprostatic lesion (DIL) using multiparametric magnetic resonance imaging (MRI), including spectroscopy (MRI/magnetic resonance spectroscopy [MRS]). Between December 2009 and March 2011, 20 patients with intermediate-risk prostate cancer underwent multiparametric MRI/MRS protocol before treatment. All patients were treated with an external beam radiotherapy dose of 40 Gy, combined with an HDR brachytherapy boost of 15 Gy. Concurrently, the DIL received a boost of 18 Gy. Missing data during followup were handled with multiple imputations. The median followup was 62 months (range, 23-71 months). Six patients (31%) were classified as favorable intermediate risk and 13 patients (69%) as unfavorable intermediate risk. One patient experienced a prostate-specific antigen biochemical failure, and the 5-year biochemical failure-free survival rate was of 94.7%. The mean International Prostate Symptom Score rose from 7, with respect to baseline, to 10.42 1 month after treatment, and rapidly decreased to 6.97 after 3 months. Grade 1, 2, and 3 acute genitourinary toxicities were reported in 13 (68%), 3 (16%), and 1 (5%) patients, respectively. Grade 1 and 2 late genitourinary toxicities were reported in 9 (53%) and 3 (18%) patients, respectively. Only grade 1 acute and late gastrointestinal toxicities were reported in 4 (21%) and 3 (18%) patients, respectively. Delivering an HDR brachytherapy boost to the DIL using image-guided multiparametric MRI/MRS is feasible with good outcomes for biochemical control, acute and late toxicities, and dosimetric constraints for critical organs. Copyright © 2016 American Brachytherapy Society. All rights reserved.

  12. Salvage High-Dose Chemotherapy for Relapsed Pure Seminoma in the Last 10 Years: Results From the European Society for Blood and Marrow Transplantation Series 2002-2012.

    Science.gov (United States)

    Necchi, Andrea; Lo Vullo, Salvatore; Bregni, Marco; Rosti, Giovanni; Mariani, Luigi; Raggi, Daniele; Giannatempo, Patrizia; Secondino, Simona; Schumacher, Kathrin; Massard, Christophe; Kanfer, Edward; Oechsle, Karin; Laszlo, Daniele; Michieli, Mariagrazia; Ifrah, Norbert; Mercier, Melanie; Crysandt, Martina; Wuchter, Patrick; Nagler, Arnon; Wahlin, Anders; Martino, Massimo; Badoglio, Manuela; Pedrazzoli, Paolo; Lanza, Francesco

    2017-02-01

    The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT). Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic. From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations. Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Routine High Dose Excretory Urography

    Science.gov (United States)

    Gronner, Arthur T.; Arkoff, Robert S.; Burhenne, H. Joachim

    1967-01-01

    Radiologic evaluation of 316 excretory urograms utilizing a single 50 ml injection of a 50 to 60 per cent tri-iodinated contrast medium indicated that these studies are of better quality than those previously obtained with the injection of 30 ml. The low incidence of side effects coincides with recent reports in the literature that this dosage level is safe. High dose intravenous drip infusion pyelography was necessary only in selected cases. High dose excretory urography is recommended for routine use. ImagesFigure 1A, 1BFigure 2. PMID:6045483

  14. High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults.

    Science.gov (United States)

    Louis-Auguste, John; Greenwald, Stephen; Simuyandi, Michelo; Soko, Rose; Banda, Rose; Kelly, Paul

    2014-01-15

    Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection. In a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 μm muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 μm muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat. 18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 μm; 95% CI of difference 17.7-95.9 μm; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 μm2/100 μm; 95% CI of difference 818-11130 μm2/100 μm; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 μm/100 μm; 95% CI of difference 16.3-146.2 μm/100 μm; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM. MM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional intervention may therefore selectively influence

  15. Fluzone High-Dose Seasonal Influenza Vaccine

    Science.gov (United States)

    ... Variant Pandemic Other Fluzone High-Dose Seasonal Influenza Vaccine Questions & Answers Language: English (US) Español Recommend on ... flu season. What is Fluzone High-Dose influenza vaccine? Fluzone High-Dose is an influenza vaccine, manufactured ...

  16. High Dose Atorvastatin Decreases Cellular Markers of Immune Activation Without Affecting HIV-1 RNA Levels: Results of a Double-Blind Randomized Placebo Controlled Clinical Trial

    Science.gov (United States)

    2011-02-15

    test to assess drug carryover revealed no differential effect by period. Overall, atorvastatin use did not result in a statistically signifi- cant... Proteinuria , creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. J Infect Dis 2009; 200:614–8. 31. Crowe SM

  17. Intensive induction chemotherapy followed by early high-dose therapy and hematopoietic stem cell transplantation results in improved outcome for patients with hepatosplenic T-cell lymphoma: a single institution experience.

    Science.gov (United States)

    Voss, Martin H; Lunning, Matthew A; Maragulia, Jocelyn C; Papadopoulos, Esperanza B; Goldberg, Jenna; Zelenetz, Andrew D; Horwitz, Steven M

    2013-02-01

    Hepatosplenic T-cell lymphoma is a rare form of extranodal non-Hodgkin lymphoma, first recognized as a distinct entity in the Revised European-American Lymphoma classification. Typical presentation includes lymphomatous infiltration of spleen and liver, and peripheral lymphadenopathy is rarely seen. The prognosis is almost uniformly poor, and there are no prospective studies of treatment of HSTCL. For this report, we conducted a retrospective review of all pts who underwent treatment for HSTCL at our institution. Individual chart review was performed to report clinical presentation, management, and outcome. We identified 14 pts with HSTCL managed at our center, 7 of which remain alive with median follow-up of 65.6 months. Six of 7 received alternative induction chemotherapy regimens such as ICE (ifosfamide, carboplatin, etoposide) or IVAC (ifosfamide, etoposide, high-dose cytarabine) as opposed to CHOP and all surviving pts had proceeded to undergo either autologous or allogeneic SCT. Our results suggest that use of non-CHOP induction regimen and early use of high dose therapy and SCT consolidation may translate to improved survival for pts with HSTCL. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. A randomised phase II trial of weekly high-dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial.

    NARCIS (Netherlands)

    Ducreux, M.; Cutsem, E. van; Laethem, J. van; Gress, T.M.; Jeziorski, K.; Rougier, P.; Wagener, T.; Anak, O.; Baron, B.; Nordlinger, B.

    2005-01-01

    Previous small phase II trials have demonstrated that the combination of 5-fluorouracil (5FU) and cisplatin(CDDP) could have clinical activity in metastatic biliary tract cancer. This randomised phase II trial was designed to assess the activity and safety of a high-dose infusional weekly 5FU alone

  19. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

    Energy Technology Data Exchange (ETDEWEB)

    Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk [Institute of Cancer Research, Royal Marsden NHSFT (National Health Service Foundation Trust) (United Kingdom); Hall, Emma [Institute of Cancer Research (United Kingdom); Hussain, Syed A. [University of Liverpool (United Kingdom); Jenkins, Peter [Gloucestershire Hospitals NHSFT (United Kingdom); Rawlings, Christine [South Devon Healthcare NHSFT (United Kingdom); Tremlett, Jean [Brighton and Sussex University Hospitals (United Kingdom); Crundwell, Malcolm [Royal Devon and Exeter NHSFT (United Kingdom); Adab, Fawzi A. [University Hospital of North Staffordshire NHS Trust (United Kingdom); Sheehan, Denise [Royal Devon and Exeter NHSFT (United Kingdom); Syndikus, Isabel [Clatterbridge Cancer Centre NHSFT (United Kingdom); Hendron, Carey [University of Birmingham (United Kingdom); Lewis, Rebecca; Waters, Rachel [Institute of Cancer Research (United Kingdom); James, Nicholas D. [University of Birmingham (United Kingdom)

    2013-10-01

    Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.

  20. Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results

    Directory of Open Access Journals (Sweden)

    Olivier Lauche

    2016-04-01

    Full Text Available Purpose : To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT boost for prostate cancer using real-time transrectal ultrasound (TRUS based planning. Material and methods : From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions was performed before (31% or after (69% HDRBT boost. Genito-urinary (GU and gastro-intestinal (GI toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS and the common terminology criteria for adverse events (CTCAE v3.0. Results : All dose-planning objectives were achieved in 90% of patients. Prostate D 90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V 150 ≤ 40% in 99%, prostate V 200 < 11% in 96%, urethra D 10 < 120% for 99%, urethra V 125 = 0% in 100%, and rectal V 75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn’t receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. Conclusions : Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

  1. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org [Hospital Universitario de la Princesa, Madrid (Spain); Guerrero, Araceli [Hospital Son Espases, Palma de Mallorca (Spain); Maldonado, Xavier [Hospital Universitari Vall d' Hebron, Barcelona (Spain); Álvarez, Ana; González-San Segundo, Carmen [Hospital General Universitario Gregorio Marañón, Madrid (Spain); Cabeza Rodriguez, Maria Angeles [Hospital Universitario 12 de Octubre, Madrid (Spain); Macías, Victor [Hospital General de Catalunya, Sant Cugat del Vallès and Hospital Universitario de Salamanca, Salamanca (Spain); Pedro Olive, Agustí [Hospital Plató, Barcelona (Spain); Casas, Francesc [Hospital Clinic, Barcelona (Spain); Boladeras, Ana [Institut Català d' Oncologia, Barcelona (Spain); Martín de Vidales, Carmen [Hospital Universitario de la Princesa, Madrid (Spain); Vázquez de la Torre, Maria Luisa [Hospital Do Meixoeiro, Vigo (Spain); Calvo, Felipe A. [Hospital General Universitario Gregorio Marañón, Madrid (Spain)

    2016-10-01

    Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of

  2. Concomitant chemoradiotherapy with high dose rate brachytherapy ...

    African Journals Online (AJOL)

    Purpose: This study aims to report the incidence of treatment-induced acute toxicities, local control and survival of patients with cervix cancer treated by external beam radiotherapy (EBR) and high-dose-rate (HDR) brachytherapy concomitant with weekly Cisplatin chemotherapy. Methods: Forty patients with FIGO Stages IB2 ...

  3. 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.

  4. Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Ikuo, E-mail: isekine@ncc.go.jp [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako; Ito, Yoshinori [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Kubota, Kaoru; Tamura, Tomohide [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2012-02-01

    Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

  5. High dose rate brachytherapy for oral cancer

    Science.gov (United States)

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

    2013-01-01

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

  6. High-dose cytarabine (24 g/m2) in combination with idarubicin (HiDAC-3) results in high first-cycle response with limited gastrointestinal toxicity in adult acute myeloid leukaemia.

    Science.gov (United States)

    Low, M; Lee, D; Coutsouvelis, J; Patil, S; Opat, S; Walker, P; Schwarer, A; Salem, H; Avery, S; Spencer, A; Wei, A

    2013-03-01

    Although induction chemotherapy comprising high-dose cytarabine (HiDAC) in combination with idarubicin and etoposide or 'ICE' for adult acute myeloid leukaemia (AML) produces a complete remission rate of nearly 80%, gastrointestinal toxicity is significant. Omission of etoposide may produce similar clinical outcomes with potentially less gastrointestinal toxicity. Fifty-three consecutive patients aged 15-60 with newly diagnosed AML, receiving high-dose cytarabine induction at the Alfred Hospital, Melbourne, were retrospectively analysed. Regimens included HiDAC-3 (idarubicin 12 mg/m(2) day 1-3, cytarabine 3 gm/m(2) bd day 1,3,5,7) or ICE (idarubicin 9 mg/m(2) day 1-3, cytarabine 3 g/m(2) bd day 1,3,5,7, etoposide 75 mg/m(2) day 1-7). Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.03. Thirty-one patients received HIDAC-3 and 22 patients received ICE induction. HiDAC-3 was better tolerated than ICE in terms of lower frequency of grade 3-4 nausea (0% vs 41%; P ICE. Eighty-four per cent of HiDAC-3-treated patients achieved complete remission after the first cycle of therapy, compared with 77% with ICE. No differences in survival were evident between the two regimens. HiDAC-3 is a clinically effective induction regimen for adult AML, producing a high rate of first-cycle complete remission with less treatment-related gastrointestinal toxicity than ICE. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

  7. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  8. 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.

  9. Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation.

    Science.gov (United States)

    Jensen, Gitte S; Drapeau, Cassandra; Lenninger, Miki; Benson, Kathleen F

    2016-07-01

    The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ∼1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism.

  10. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial.

    Science.gov (United States)

    Willemze, Roelof; Suciu, Stefan; Meloni, Giovanna; Labar, Boris; Marie, Jean-Pierre; Halkes, Constantijn J M; Muus, Petra; Mistrik, Martin; Amadori, Sergio; Specchia, Giorgina; Fabbiano, Francesco; Nobile, Francesco; Sborgia, Marco; Camera, Andrea; Selleslag, Dominik L D; Lefrère, Francois; Magro, Domenico; Sica, Simona; Cantore, Nicola; Beksac, Meral; Berneman, Zwi; Thomas, Xavier; Melillo, Lorella; Guimaraes, Jose E; Leoni, Pietro; Luppi, Mario; Mitra, Maria E; Bron, Dominique; Fillet, Georges; Marijt, Erik W A; Venditti, Adriano; Hagemeijer, Anne; Mancini, Marco; Jansen, Joop; Cilloni, Daniela; Meert, Liv; Fazi, Paola; Vignetti, Marco; Trisolini, Silvia M; Mandelli, Franco; de Witte, Theo

    2014-01-20

    Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD

  11. Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

    Energy Technology Data Exchange (ETDEWEB)

    Wortel, Ruud C.; Incrocci, Luca [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Pos, Floris J.; Heide, Uulke A. van der; Lebesque, Joos V. [Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Aluwini, Shafak [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Witte, Marnix G. [Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Heemsbergen, Wilma D., E-mail: w.heemsbergen@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2016-06-01

    Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-02-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  14. 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)

  15. 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.

  16. Dose determination in high dose-rate brachytherapy.

    Science.gov (United States)

    Houdek, P V; Schwade, J G; Wu, X; Pisciotta, V; Fiedler, J A; Serago, C F; Markoe, A M; Abitbol, A A; Lewin, A A; Braunschweiger, P G

    1992-01-01

    Although high dose-rate brachytherapy with a single, rapidly moving radiation source is becoming a common treatment modality, a suitable formalism for determination of the dose delivered by a moving radiation source has not yet been developed. At present, brachytherapy software simulates high dose-rate treatments using only a series of stationary sources, and consequently fails to account for the dose component delivered while the source is in motion. We now describe a practical model for determination of the true, total dose administered. The algorithm calculates both the dose delivered while the source is in motion within and outside of the implanted volume (dynamic component), and the dose delivered while the source is stationary at a series of fixed dwell points. It is shown that the dynamic dose element cannot be ignored because it always increases the dose at the prescription points and, in addition, distorts the dose distribution within and outside of the irradiated volume. Failure to account for the dynamic dose component results in dosimetric errors that range from significant (> 10%) to negligible (source activity, and source speed as defined by the implant geometry.

  17. Cone damage in patients receiving high-dose irofulven treatment.

    Science.gov (United States)

    Lee, Michael S; Gupta, Nisha; Penson, Richard T; Loewenstein, John; Wepner, Meredith S; Seiden, Michael V; Milam, Ann H

    2005-01-01

    To describe the clinical, perimetric, and electroretinographic (ERG) results of 4 patients with cone dysfunction following irofulven treatment including the histopathologic and immunocytochemical features of one patient's retinas. Observational case series. The patients were examined clinically, including perimetric and ERG evaluations. Eyes from patient 1 and healthy postmortem eyes were processed for histopathologic and immunocytochemistry studies with antibodies specific for cones, rods, and reactive Müller cells. Clinical signs and symptoms, perimetry, ERG, retinal histopathologic and immunocytochemistry study results. All 4 patients had ERG changes consistent with abnormal cone responses and relatively normal rod responses. Compared with control eyes, the retina of patient 1 had approximately half the normal numbers of macular cones and fewer peripheral cones. The number of rods were normal but all rod and cone outer segments were shortened. High-dose irofulven treatment causes cone-specific damage with relative sparing of rods.

  18. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

    Frenkel, J.; Kool, G.; de Kraker, J.

    1995-01-01

    Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

  19. 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.

  20. Prediction of the cumulated dose for external beam irradiation of prostate cancer patients with 3D-CRT technique

    Directory of Open Access Journals (Sweden)

    Giżyńska Marta

    2016-03-01

    Full Text Available Nowadays in radiotherapy, much effort is taken to minimize the irradiated volume and consequently minimize doses to healthy tissues. In our work, we tested the hypothesis that the mean dose distribution calculated from a few first fractions can serve as prediction of the cumulated dose distribution, representing the whole treatment. We made our tests for 25 prostate cancer patients treated with three orthogonal fields technique. We did a comparison of dose distribution calculated as a sum of dose distribution from each fraction with a dose distribution calculated with isocenter shifted for a mean setup error from a few first fractions. The cumulative dose distribution and predicted dose distributions are similar in terms of gamma (3 mm 3% analysis, under condition that we know setup error from seven first fractions. We showed that the dose distribution calculated for the original plan with the isocenter shifted to the point, defined as the original isocenter corrected of the mean setup error estimated from the first seven fractions supports our hypothesis, i.e. can serve as a prediction for cumulative dose distribution.

  1. 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

    Science.gov (United States)

    2017-12-29

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

  2. 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.

  3. Irreversible encephalopathy after treatment with high-dose intravenous metronidazole.

    NARCIS (Netherlands)

    Groothoff, M.V.R.; Hofmeijer, J.; Sikma, M.A.; Meulenbelt, J.

    2010-01-01

    BACKGROUND: Encephalopathy associated with metronidazole is rare and, in most cases, reversible following discontinuation. OBJECTIVE: We describe a case of fatal encephalopathy after treatment with high-dose intravenous metronidazole and the potential causes of the irreversibility. CASE SUMMARY: A

  4. Irreversible Encephalopathy After Treatment With High-Dose Intravenous Metronidazole

    NARCIS (Netherlands)

    Groothoff, Miriam V. R.; Hofmeijer, Jannette; Sikma, Maaike A.; Meulenbelt, Jan

    Background: Encephalopathy associated with metronidazole is rare and, in most cases, reversible following discontinuation. Objective: We describe a case of fatal encephalopathy after treatment with high-dose intravenous metronidazole and the potential causes of the irreversibility. Case summary: A

  5. 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)

  6. 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

  7. 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

  8. Trends in high-dose opioid prescribing in Canada.

    Science.gov (United States)

    Gomes, Tara; Mamdani, Muhammad M; Paterson, J Michael; Dhalla, Irfan A; Juurlink, David N

    2014-09-01

    To describe trends in rates of prescribing of high-dose opioid formulations and variations in opioid product selection across Canada. Population-based, cross-sectional study. Canada. Retail pharmacies dispensing opioids between January 1, 2006, and December 31, 2011. Opioid dispensing rates, reported as the number of units dispensed per 1000 population, stratified by province and opioid type. The rate of dispensing high-dose opioid formulations increased 23.0%, from 781 units per 1000 population in 2006 to 961 units per 1000 population in 2011. Although these rates remained relatively stable in Alberta (6.3% increase) and British Columbia (8.4% increase), rates in Newfoundland and Labrador (84.7% increase) and Saskatchewan (54.0% increase) rose substantially. Ontario exhibited the highest annual rate of high-dose oxycodone and fentanyl dispensing (756 tablets and 112 patches per 1000 population, respectively), while Alberta's rate of high-dose morphine dispensing was the highest in Canada (347 units per 1000 population). Two of the highest rates of high-dose hydromorphone dispensing were found in Saskatchewan and Nova Scotia (258 and 369 units per 1000 population, respectively). Conversely, Quebec had the lowest rate of high-dose oxycodone and morphine dispensing (98 and 53 units per 1000 population, respectively). We found marked interprovincial variation in the dispensing of high-dose opioid formulations in Canada, emphasizing the need to understand the reasons for these differences, and to consider developing a national strategy to address opioid prescribing. Copyright© the College of Family Physicians of Canada.

  9. Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors

    Directory of Open Access Journals (Sweden)

    Inrig Jula K

    2011-12-01

    Full Text Available Abstract Background High-dose erythropoiesis-stimulating agents (ESA for anemia of chronic kidney disease (CKD have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR. Methods A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α ( Results Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week vs usual-dose (0.5 μg/kg/week ESA. In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p s = 0.39, p = 0.03. In adjusted analyses, higher ESA dose (per μcg/kg/week was associated with a 53% greater odds of sEpoR being above the median (p Conclusion High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted. Trial registration Clinicaltrials.gov NCT00526747

  10. High dose vitamin D may improve lower urinary tract symptoms in postmenopausal women.

    Science.gov (United States)

    Oberg, Johanna; Verelst, Margareta; Jorde, Rolf; Cashman, Kevin; Grimnes, Guri

    2017-10-01

    Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000IU of vitamin D 3 twice a week (high dose group) or similar looking placebo (standard dose group). In addition, all the participants received 1g of calcium and 800IU of vitamin D daily. A validated questionnaire regarding LUTS was filled in at baseline and after 12 months. At baseline, 76 women in the high dose group and 82 in the standard dose group reported any LUTS. Levels of serum 25(OH)D increased significantly more in the high dose group (from 64.7 to 164.1nmol/l compared to from 64.1 to 81.8nmol/l, p<0.01). No differences between the groups were seen regarding change in LUTS except for a statistically significant reduction in the reported severity of urine incontinence in the high dose group as compared to the standard dose group after one year (p<0.05). The results need confirmation in a study specifically designed for this purpose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  12. High-dose N-acetylcysteine for the prevention of contrast-induced nephropathy.

    Science.gov (United States)

    Trivedi, Hariprasad; Daram, Sumanth; Szabo, Aniko; Bartorelli, Antonio L; Marenzi, Giancarlo

    2009-09-01

    Whether N-acetylcysteine is beneficial for the prevention of contrast-induced nephropathy is uncertain. We conducted a meta-analysis to evaluate the efficacy of high-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Our prespecified inclusion criteria were as follows: adult subjects; English language literature; administration of high-dose N-acetylcysteine a priori defined as a daily dose greater than 1200 mg or a single periprocedural dose (within 4 hours of contrast exposure) greater than 600 mg; prospective trials of individuals randomized to N-acetylcysteine, administered orally or intravenously, versus a control group; and trials that included the end point of the incidence of contrast-induced nephropathy. Trials that compared N-acetylcysteine with another active treatment were excluded. Sixteen comparisons of patients randomized to high-dose N-acetylcysteine versus controls met our prespecified inclusion criteria with a total sample size of 1677 subjects (842 assigned to high-dose N-acetylcysteine and 835 assigned to the control arm). The average population age was 68 years, 38.7% were diabetic, and the majority was male (67.8% of reported instances). The weighted mean baseline creatinine of the overall population was 1.58 mg/dL. No significant heterogeneity was detected (P = .09; I(2) = 34%). The overall effect size assuming a common odds ratio revealed an odds ratio of 0.46 (95% confidence interval [CI], 0.33-0.63) for the occurrence of contrast-induced nephropathy with the use of high-dose N-acetylcysteine. The results of the more conservative random effects approach were similar (odds ratio = 0.52; 95% CI, 0.34-0.78). There was no evidence of publication bias (P = .34). Our results suggest that high-dose N-acetylcysteine decreases the incidence of contrast-induced nephropathy.

  13. High-Dose Intravenous Ribavirin Therapy for Subacute Sclerosing Panencephalitis

    Science.gov (United States)

    Hosoya, Mitsuaki; Shigeta, Shiro; Mori, Shuichi; Tomoda, Akemi; Shiraishi, Seiji; Miike, Teruhisa; Suzuki, Hitoshi

    2001-01-01

    Two patients with subacute sclerosing panencephalitis (SSPE) were treated safely and effectively with high doses of intravenous ribavirin combined with intraventricular alpha interferon. The ribavirin concentrations maintained in the serum and cerebrospinal fluid were higher than those which inhibit SSPE virus replication in vitro and in vivo. PMID:11181386

  14. High-dose chemotherapy regimens for solid tumors

    NARCIS (Netherlands)

    Wall, E. van der; Beijnen, J.H.; Rodenhuis, S.

    1995-01-01

    High-dose chemotherapy with blood progenitor cell transplantation is increasingly recognized as a potentially valuable treatment for breast cancer, germ cell cancer, ovarian cancer and other solid tumors. A variety of cytotoxic drugs, particularly alkylating agents, have been investigated either

  15. 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, 6...

  16. Transit dose calculation in high dose rate brachytherapy (HDR ...

    African Journals Online (AJOL)

    Transit doses around a high dose rate 192Ir brachytherapy source were calculated using Sievert Integral at positions where the moving source was located exactly between two adjacent dwell positions. The correspond-ing transit dose rates were obtained by using energy absorption coefficients. Discrete step sizes of 0.25 ...

  17. Effect of high dose thiamine therapy on activity and molecular ...

    African Journals Online (AJOL)

    ajl yemi

    2011-11-28

    Nov 28, 2011 ... This study was therefore designed to investigate the effect of high dose thiamine therapy on the activity and molecular aspects of transketolase in Type 2 diabetic patients. Over 100 Type 2 microalbuminuric diabetics were enrolled in a randomized, double blind placebo controlled clinical trial for 6 months.

  18. Unusual complication and successful high-dose chemotherapy ...

    African Journals Online (AJOL)

    Adult Burkitt's lymphoma emerged as an AIDS-defining condition in the 1980s. We describe a case of HIV-associated adult Burkitt's lymphoma diagnosed and treated with high-dose chemotherapy in our institution, complicated by unusual bilateral renal vein tumour thrombi and tumour lysis syndrome. We believe this ...

  19. 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)

    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

  20. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

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

    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

  1. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; 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. Six patients responded. Side effects

  2. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.; Mikaeilian, Argin G.; Hsu, Sophia; Cao, Minsong

    2017-05-01

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

  4. 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

  5. High-dose midazolam infusion for refractory status epilepticus.

    Science.gov (United States)

    Fernandez, Andres; Lantigua, Hector; Lesch, Christine; Shao, Belinda; Foreman, Brandon; Schmidt, J Michael; Hirsch, Lawrence J; Mayer, Stephan A; Claassen, Jan

    2014-01-28

    This study compares 2 treatment protocols allowing low vs high continuous IV midazolam (cIV-MDZ) doses. We compared adults with refractory status epilepticus treated with a protocol allowing for high-dose cIV-MDZ (n = 100; 2002-2011) with those treated with the previous lower-dose cIV-MDZ (n = 29; 1996-2000). We collected data on baseline characteristics, cIV-MDZ doses, seizure control, hospital course, and outcome. Median maximum cIV-MDZ dose was 0.4 mg/kg/h (interquartile range [IQR] 0.2, 1.0) for the high-dose group and 0.2 mg/kg/h (IQR 0.1, 0.3) for the low-dose group (p cIV-MDZ start was 1 day (IQR 1, 3) for the high-dose group and 2 days (IQR 1, 5) for the low-dose group (p = 0.016). "Withdrawal seizures" (occurring within 48 hours of discontinuation of cIV-MDZ) were less frequent in the high-dose group (15% vs 64%, odds ratio 0.10, 95% confidence interval 0.03-0.27). "Ultimate cIV-MDZ failure" (patients requiring change to a different cIV antiepileptic medication) and hospital complications were not different between groups. Hypotension was more frequent with higher cIV-MDZ doses but was not associated with worse outcome. Discharge mortality was lower in the high-dose group (40% vs 62%, odds ratio 0.34, 95% confidence interval 0.13-0.92 in multivariate analysis). High-dose cIV-MDZ treatment of refractory status epilepticus can be performed safely, is associated with a lower seizure rate after cIV-MDZ discontinuation, and may be associated with lower mortality than traditional lower-dose protocols. This study provides Class III evidence that midazolam at higher infusion rates is associated with a reduction in seizure recurrence within 48 hours after discontinuation and may be associated with lower mortality.

  6. 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.

  7. Severe beta blocker and calcium channel blocker overdose: Role of high dose insulin.

    Science.gov (United States)

    Seegobin, Karan; Maharaj, Satish; Deosaran, Ansuya; Reddy, Pramod

    2018-01-10

    A 54-year-old female presented after taking an overdose of an unknown amount of hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially refractory to treatment with conventional therapy (intravenous fluids, activated charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and atropine). Furthermore, insulin at 4 U/kg was not effective in improving her hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there was dramatic improvement in hemodynamics resulting in three of five vasopressors being weaned off in 8 h. She was subsequently off all vasopressors after six additional hours. The role of high dose insulin has been documented in prior cases, however it is generally recommended after other conventional therapies have failed. However, there are other reports that suggest it as initial therapy. Our patient failed conventional therapies and responded well only with maximum dose of insulin. Physicians should consider high dose insulin early in severe beta blocker or calcium channel blocker overdose for improvement in hemodynamics. This leads to early discontinuation of vasopressors. It is important that emergency physicians be aware of the beneficial effects of high dose insulin when initiated early as opposed to waiting for conventional therapy to fail; as these patients often present first to the emergency department. Early initiation in the emergency department can be beneficial in these patients. Copyright © 2018. Published by Elsevier Inc.

  8. Preliminary evidence that high-dose vitamin C has a vascular disrupting action in mice

    Directory of Open Access Journals (Sweden)

    Bruce Charles Baguley

    2014-11-01

    Full Text Available High intravenous doses of vitamin C (ascorbic acid have been reported to benefit cancer patients but the data are controversial and there is incomplete knowledge of what physiological mechanisms might be involved in any response. Vitamin C is taken up efficiently by cells expressing SVCT2 transporters and since vascular endothelial cells express SVCT2, we explored the hypothesis that administration of high dose vitamin C (up to 5 g/kg to mice might affect vascular endothelial function. A single administration of vitamin C to mice induced time- and dose-dependent increases in plasma concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA, a marker for vascular disrupting effects. Responses were comparable to those for the tumor vascular disrupting agents vadimezan and fosbretabulin. High-dose vitamin C administration decreased tumor serotonin concentrations, consistent with the release of serotonin from platelets and its metabolism to 5-HIAA. High-dose vitamin C also significantly increased the degree of hemorrhagic necrosis in tumors removed after 24 hours, and significantly decreased tumor volume after 2 days. However, the effect on tumor growth was temporary. The results support the concept that vitamin C at high dose increases endothelial permeability, allowing platelets to escape and release serotonin. Plasma 5-HIAA concentrations could provide a pharmacodynamic biomarker for vitamin C effects in clinical studies.

  9. 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.

  10. 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.

  11. 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.

  12. Risk of atrial fibrillation with high-dose corticosteroids.

    Science.gov (United States)

    Chiappini, Bruno; El Khoury, Gebrine

    2006-11-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia observed in clinical practice. Some drugs have been associated with the onset of AF, but knowledge about the role of drugs in the development of AF is scarce. High-dose corticosteroid therapy has been associated with the development of AF, but this is mainly based on case reports. Therefore, the authors review the available data in the international literature about the cause-effect relationship between corticosteroid therapy and the onset of AF.

  13. 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

  14. Assessment of renal function after conformal radiotherapy and intensity-modulated radiotherapy by functional {sup 1}H-MRI and {sup 23}Na-MRI

    Energy Technology Data Exchange (ETDEWEB)

    Haneder, S.; Michaely, H.J.; Schoenberg, S.O. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Inst. of Clinical Radiology and Nuclear Medicine; Konstandin, S.; Schad, L.R. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Computer-Assisted Clinical Medicine; Siebenlist, K.; Wertz, H.; Wenz, F.; Lohr, F.; Boda-Heggemann, J. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology

    2012-12-15

    the 3D-CRT group was significantly reduced, while the expected corticomedullary {sup 23}Na-concentration gradient was partially conserved. Conclusions: Functional MRI can assess postradiotherapeutic renal changes. As expected, marked morphological/functional effects were observed in high-dose areas (3D-CRT), while, unexpectedly, no alteration in kidney function was observed in IG-IMRT patients, supporting the hypothesis that reducing total/fractional dose to the renal parenchyma by IMRT is clinically beneficial. (orig.)

  15. Pelvic Ewing sarcomas. Three-dimensional conformal vs. intensity-modulated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mounessi, F.S.; Lehrich, P.; Haverkamp, U.; Eich, H.T. [Muenster Univ. (Germany). Dept. of Radiation Oncology; Willich, N. [Muenster Univ. (Germany). Dept. of Radiation Oncology; Universitaetsklinikum Muenster (Germany). RiSK - Registry for the Evaluation of Late Side Effects after Radiotherapy in Childhood and Adolescence; Boelling, T. [Center for Radiation Oncology, Osnabrueck (Germany)

    2013-04-15

    The goal of the present work was to assess the potential advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3D-CRT) planning in pelvic Ewing's sarcoma. A total of 8 patients with Ewing sarcoma of the pelvis undergoing radiotherapy were analyzed. Plans for 3D-CRT and IMRT were calculated for each patient. Dose coverage of the planning target volume (PTV), conformity and homogeneity indices, as well as further parameters were evaluated. Results The average dose coverage values for PTV were comparable in 3D-CRT and IMRT plans. Both techniques had a PTV coverage of V{sub 95} > 98 % in all patients. Whereas the IMRT plans achieved a higher conformity index compared to the 3D-CRT plans (conformity index 0.79 {+-} 0.12 vs. 0.54 {+-} 0.19, p = 0.012), the dose distribution across the target volumes was less homogeneous with IMRT planning than with 3D-CRT planning. This difference was statistically significant (homogeneity index 0.11 {+-} 0.03 vs. 0.07 {+-} 0.0, p = 0.035). For the bowel, D{sub mean} and D{sub 1%}, as well as V{sub 2} to V{sub 60} were reduced in IMRT plans. For the bladder and the rectum, there was no significant difference in D{sub mean}. However, the percentages of volumes receiving at least doses of 30, 40, 45, and 50 Gy (V{sub 30} to V{sub 50}) were lower for the rectum in IMRT plans. The volume of normal tissue receiving at least 2 Gy (V{sub 2}) was significantly higher in IMRT plans compared with 3D-CRT, whereas at high dose levels (V{sub 30}) it was significantly lower. Compared to 3D-CRT, IMRT showed significantly better results regarding dose conformity (p = 0.012) and bowel sparing at dose levels above 30 Gy (p = 0.012). Thus, dose escalation in the radiotherapy of pelvic Ewing's sarcoma can be more easily achieved using IMRT. (orig.)

  16. High-dose irradiated food: Current progress, applications, and prospects

    Science.gov (United States)

    Feliciano, Chitho P.

    2018-03-01

    Food irradiation as an established and mature technology has gained more attention in the food industry for ensuring food safety and quality. Primarily used for phytosanitary applications, its use has been expanded for developing various food products for varied purposes (e.g. ready-to-eat & ready-to-cook foods, hospital diets, etc.). This paper summarized and analyzed the recent progress and application of high-dose irradiation and discussed its prospects in the field of food product development, its safety and quality.

  17. 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.

  18. 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.

  19. [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.

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

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    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 immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission....... After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours...

  1. 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.

  2. A hypothesis on the mechanism of action of high-dose thyroid in refractory mood disorders.

    Science.gov (United States)

    Kelly, Tammas

    2016-12-01

    Multiple lines of evidence suggest the hypothesis that high dose thyroid therapy corrects for cellular hypothyroidism found in bipolar disorders. Evidence indicates that bipolar disorders are associated with mitochondrial dysfunction which results in low cellular adenosine 5'-triphosphate (ATP) levels. Transport of thyroid hormones into cells is energy intensive and dependent on ATP except in the pituitary gland. Inadequate ATP levels makes it difficult to get thyroid hormone into cells leading to cellular hypothyroidism. This creates a condition where the blood and pituitary levels of thyroid hormone are normal but low in other tissues. High dose thyroid therapy produces a gradient that is sufficient for thyroid hormone to diffuse into cells correcting cellular hypothyroidism. If this hypothesis is correct there are number of implications. The two most important are: On average patients suffering from a bipolar disorder die 10-20years earlier than the general population. The medical sequelae associated with bipolar disorders cause far more deaths than suicide. If high dose thyroid corrects for cellular hypothyroidism it could well decrease the medical morbidity and mortality associated with bipolar disorders that are the result of cellular hypothyroidism. Thus high dose thyroid would be a first treatment that decreases the considerable medical morbidity and mortality associated with the bipolar disorders. This would stand in stark contrast to most psychiatric medications that can that increase morbidity and mortality. It would also reinforce the safety of HDT. The second implication is thyroid hormone blood levels in patients suffering from a bipolar disorder do not accurately reflect the true thyroid status. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Charge collection efficiency in ionization chambers exposed to electron beams with high dose per pulse.

    Science.gov (United States)

    Laitano, R F; Guerra, A S; Pimpinella, M; Caporali, C; Petrucci, A

    2006-12-21

    The correction for charge recombination was determined for different plane-parallel ionization chambers exposed to clinical electron beams with low and high dose per pulse, respectively. The electron energy was nearly the same (about 7 and 9 MeV) for any of the beams used. Boag's two-voltage analysis (TVA) was used to determine the correction for ion losses, k(s), relevant to each chamber considered. The presence of free electrons in the air of the chamber cavity was accounted for in determining k(s) by TVA. The determination of k(s) was made on the basis of the models for ion recombination proposed in past years by Boag, Hochhäuser and Balk to account for the presence of free electrons. The absorbed dose measurements in both low-dose-per-pulse (less than 0.3 mGy per pulse) and high-dose-per-pulse (20-120 mGy per pulse range) electron beams were compared with ferrous sulphate chemical dosimetry, a method independent of the dose per pulse. The results of the comparison support the conclusion that one of the models is more adequate to correct for ion recombination, even in high-dose-per-pulse conditions, provided that the fraction of free electrons is properly assessed. In this respect the drift velocity and the time constant for attachment of electrons in the air of the chamber cavity are rather critical parameters because of their dependence on chamber dimensions and operational conditions. Finally, a determination of the factor k(s) was also made by zero extrapolation of the 1/Q versus 1/V saturation curves, leading to the conclusion that this method does not provide consistent results in high-dose-per-pulse beams.

  4. High-dose hook effect in six automated human chorionic gonadotrophin assays.

    Science.gov (United States)

    Al-Mahdili, Huda A; Jones, Graham R D

    2010-07-01

    The high-dose hook effect is a well-known phenomenon of two-site immunoassays including those for human chorionic gonadotrophin (hCG). We investigated the occurrence of a high-dose hook effect in six routinely available hCG assays using a sample with a total hCG concentration of approximately 3,600,000 IU/L. Dilutions of a sample with high hCG concentration were analysed using six common methods: Advia Centaur, Immulite 2000, Dimension RxL, Unicel DxI 800, Roche E170 and Abbott Architect. The measured concentrations and corresponding assay signals were obtained for each method. Performance was compared with manufacturer claims. Four of the tested platforms demonstrated a clear high-dose hook effect, while the other methods showed no hook effect at the highest level tested. Our results indicate that the hook effect may occur in some hCG assays, although the risk of reporting falsely low results was in most cases at higher concentrations than those indicated in manufacturers' product information. Assay design plays a major role in its occurrence. Laboratories should be aware of the assay limitations in this regard.

  5. High dose antithrombin supplementation in early preeclampsia: A randomized, double blind, placebo-controlled study.

    Science.gov (United States)

    D'Angelo, Armando; Valsecchi, Luca

    2016-04-01

    Antithrombin levels are often reduced in preeclampsia and infusion of antithrombin concentrates has been reported to prolong gestation in severe preeclampsia. We aimed to evaluate efficacy and safety of high-dose antithrombin (ATIII) supplementation in patients with single pregnancies and preeclampsia occurring before 30 weeks of gestation. In November 2004 a double-blind, placebo-controlled trial (code KB033) was started in 13 Italian centers. The planned sample size was of 240 patients (intention-to-treat, ITT population) to detect a 30% relative risk reduction of the primary endpoint, composite perinatal morbidity. Eligible patients were randomized to high dose AT (3000 IU/daily, ATIII Kedrion S.p.A., Italy), or placebo (1% glycine) for 7 days or less until delivery, whichever came first. The per-protocol (PP) population was restricted to patients receiving at least two days of treatment. The study was terminated by the sponsor in October 2007 after the enrolment of 38 evaluable patients - 20 randomized to high dose AT and 18 to placebo, 27 treated for 2 days or more - out of 164 screened patients. Enrolment failures were mainly represented by requirement for immediate delivery and consent refusal (91 patients). The primary endpoint occurred in 15 of 38 patients (39.5%), with a relative risk in the AT arm of 0.85 (95% CI 0.42-1.75) and 0.79 (95% CI 0.30-2.11) in the ITT and PP populations, respectively. Living neonates in the two arms had similar weight at birth, Apgar scores, and duration of hospitalization in neonatal ICU. In mothers, AT supplementation was associated with reduced blood loss at delivery and with surrogate laboratory markers (LDH, d-dimer). The results of this markedly underpowered trial, albeit suggestive of a potential maternal benefit, cannot support high-dose AT supplementation to improve fetal/neonatal outcomes in early preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Efficacy of High-Dose Vitamin D Supplements for Elite Athletes.

    Science.gov (United States)

    Owens, Daniel J; Tang, Jonathan C Y; Bradley, Warren J; Sparks, Andy S; Fraser, William D; Morton, James P; Close, Graeme L

    2017-02-01

    Supplementation with dietary forms of vitamin D is commonplace in clinical medicine, elite athletic cohorts, and the general population, yet the response of all major vitamin D metabolites to high doses of vitamin D is poorly characterized. We aimed to identify the responses of all major vitamin D metabolites to moderate- and high-dose supplemental vitamin D3. A repeated-measures design was implemented in which 46 elite professional European athletes were block randomized based on their basal 25[OH]D concentration into two treatment groups. Athletes received either 35,000 or 70,000 IU·wk vitamin D3 for 12 wk, and 42 athletes completed the trial. Blood samples were collected for 18 wk to monitor the response to supplementation and withdrawal from supplementation. Both doses led to significant increases in serum 25[OH]D, and 1,25[OH]2D3. 70,000 IU·wk also resulted in a significant increase of the metabolite 24,25[OH]2D at weeks 6 and 12 that persisted after supplementation withdrawal at week 18, despite a marked decrease in 1,25[OH]2D3. Intact parathyroid hormone was decreased in both groups by week 6 and remained suppressed throughout the trial. High-dose vitamin D3 supplementation (70,000 IU·wk) may be detrimental for its intended purposes because of increased 24,25[OH]2D production. Rapid withdrawal from high-dose supplementation may inhibit the bioactivity of 1,25[OH]2D3 as a consequence of sustained increases in 24,25[OH]2D that persist as 25[OH]D and 1,25[OH]2D concentrations decrease. These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable.

  7. Autologous bone marrow infusion following high dose chemotherapy of the canine transmissible venereal tumor (TVT).

    Science.gov (United States)

    Epstein, R B; Sarpel, S C

    1980-07-01

    The present study was undertaken to evaluate infusion of cryopreserved autologous bone marrow following supralethal chemotherapy in canines bearing a solid tumor thought to be moderately sensitive to cytotoxic agents. Initial studies in 5 dogs established a combination of busulfan (Bu) 3 mg/kg X 2 days and cyclophosphamide (Cy) 50 mg/kg on day 3 to produce bone marrow lethality within 14 days (high dose regime). Bu 1 mg/kg, Cy 20 mg/kg produced tolerable toxicity (low dose regime). Eight pairs of dogs were challenged with 3 X 10(8) transmissible venereal tumor cells. Measurable progressive tumor growth occurred in all instances. Marrow aspirated from the femoral shafts of the animals was cryopreserved in 10% DMSO. One dog of each pair received the high dose Bu + Cy regime followed in 30 h by marrow infusion and his partner received the low dose regime without marrow. Tumors were measured serially for at least 2 months. Infusion of marrow resulted in evidence of hematologic recovery within 2 weeks following the high dose regime. Tumor responses occurred in both groups when compared to 8 untreated tumor challenged controls. High dose animals had greater initial responses than low dosed dogs but long term responses were not significantly different. Eight dogs rechallenged with tumor cells after initial successful therapy failed to develop tumors. It was concluded that: a) cryopreserved autologous bone marrow infusion was effective in protecting tumor bearing canines from otherwise lethal chemotherapy; b) the transmissible venereal tumor of canines responded to both high and low dose regimes; c) the rescue of dogs by stored autologous marrow did not offer additional benefits in tumor control over a standard regime; d) chemotherapy treated dogs resisted tumor rechallenge. This model may offer a large animal system to study the autologous marrow rescue concept during controlled periods of tumor evolution.

  8. Multifocal cognitive dysfunction in high-dose benzodiazepine users: a cross-sectional study.

    Science.gov (United States)

    Federico, Angela; Tamburin, Stefano; Maier, Alice; Faccini, Marco; Casari, Rebecca; Morbioli, Laura; Lugoboni, Fabio

    2017-01-01

    Benzodiazepines (BZDs) are the most widely prescribed drug class in developed countries, but they have high potential for tolerance, dependence and abuse. Cognitive deficits in long-term BZD users have long been known, but previous results might have been biased by patients' old age, coexisting neurological or psychiatric conditions or concurrent alcohol or psychotropic drug dependence. The study was aimed to explore the neuropsychological effect of high-dose BZD dependence, which represents an emerging addiction phenomenon. We recruited a group of high-dose BZD users with neither neurological or psychiatric comorbidity except anxiety or depression nor concurrent alcohol or psychotropic drug dependence. They underwent a battery of cognitive tests to explore verbal, visuospatial memory, working memory, attention, and executive functions. All the neuropsychological measures were significantly worse in patients than controls, and some of them were influenced by the BZD cumulative dose. The severity of depression and anxiety had a minimal influence on cognitive tests. Patients with high-dose BZD intake show profound changes in cognitive function. The impact of cognition should be considered in this population of patients, who may be involved in risky activities or have high work responsibilities.

  9. High-dose Vitamin D supplementation precipitating hypercalcemic crisis in granulomatous disorders

    Directory of Open Access Journals (Sweden)

    Vijaya Sarathi

    2017-01-01

    Full Text Available Background: Vitamin D supplementation precipitating hypercalcemic crisis is often the first manifestation in patients with granulomatous disorders. Methods: We report our experience on patients presenting with hypercalcemic crisis due to granulomatous disorder and the role of Vitamin D supplementation in the precipitation of hypercalcemic crisis in them. Results: The study included five patients with granulomatous disorders who presented with hypercalcemic crisis. All patients initially presented with nonspecific constitutional symptoms to other health-care centers to receive high-dose Vitamin D supplementation (60,000 U/week or 600,000 U intramuscular single dose. All of these patients presented with hypercalcemic crisis (serum calcium: 16.04 ± 0.3 mg/dl to our centers after a period of 32.8 ± 9.62 days. Three patients were diagnosed to have sarcoidosis, and two were diagnosed to have tuberculosis. All five patients had parathyroid hormone-independent hypercalcemia with elevated serum 1,25-dihydroxy Vitamin D. Serum angiotensin-converting enzyme level was elevated in all the three patients with sarcoidosis. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography was performed in two patients with sarcoidosis which demonstrated diffusely increased tracer uptake in liver. In these two patients, liver biopsy confirmed the diagnosis. Conclusions: High-dose Vitamin D supplementation is most often the underlying cause of hypercalcemic crisis in patients with granulomatous disorders. Hence, high-dose Vitamin D supplementation should be used judiciously.

  10. 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. © 2015 Wiley Publishing Asia Pty Ltd.

  11. 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)

  12. The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients

    Directory of Open Access Journals (Sweden)

    Cui Lihong

    2015-07-01

    Full Text Available Purpose: To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. Methods: A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups: 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole sodium once every 12 h for 72 h. Results: Compared with the conventional dose group, the total efficiency of the high-dose group and conventional dose group was 98.08% and 86.00%, respectively (p < 0.05, the hemostatic time was 22.10 h ± 5.18 h and 28.27 h ± 5.96 h, respectively (p < 0.05. Conclusion: Both doses of intravenous esomeprazole have good hemostatic effects on stress ulcer bleeding in trauma patients. The high-dose esomeprazole is better for hemostasis.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease.

    Science.gov (United States)

    Bradstock, Kenneth F; Bilmon, Ian; Kwan, John; Micklethwaite, Kenneth; Blyth, Emily; Deren, Stephanie; Bayley, Angela; Gebski, Val; Gottlieb, David

    2015-05-01

    High-dose cyclophosphamide given early after allogeneic hemopoietic cell transplantation has been shown to be effective prophylaxis against graft-versus-host disease (GVHD) in the setting of HLA-matched myeloablative bone marrow grafts, allowing avoidance of long-term immunosuppression with calcineurin inhibitors in some patients. Whether this approach is feasible using granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell grafts is unknown. We conducted an exploratory phase 2 trial of cyclophosphamide given at 50 mg/kg i.v. on days 3 and 4 after transplantation as sole GVHD prophylaxis in recipients of G-CSF-mobilized peripheral blood stem cell grafts from HLA-matched related or unrelated donors after reduced-intensity conditioning therapy with fludarabine, carmustine, and melphalan. Five patients, ages 52 to 67 years, with high-risk hematologic malignancies were enrolled. Four of the 5 developed severe acute GVHD of grades 3 to 4, requiring treatment with methylprednisolone and cyclosporine; 3 were steroid refractory and were given salvage therapy. One of these 4 patients died of hepatic GVHD, one died of sepsis, and 2 survived. We conclude that post-transplantation cyclophosphamide is inadequate as sole GVHD prophylaxis in the context of peripheral blood reduced-intensity conditioning transplantations from HLA-matched donors. This trial is registered at ACTRN12613001154796. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  16. 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, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S; Chalfant, Charles E; Brophy, Donald F; Fowler Iii, Alpha A; Natarajan, Ramesh

    2017-02-04

    To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). 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). VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P 0.05). 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 and prostaglandin E2, as well as products of

  17. Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine and Langone Medical Center, New York, New York (United States); Hsu, Howard; Fenton-Kerimian, Maria [Department of Radiation Oncology, New York University School of Medicine and Langone Medical Center, New York, New York (United States); Roses, Daniel; Guth, Amber [Department of Surgery, New York University School of Medicine and Langone Medical Center, New York, New York (United States); Jozsef, Gabor [Department of Radiation Oncology, New York University School of Medicine and Langone Medical Center, New York, New York (United States); Goldberg, Judith D. [Division of Biostastistics, Department of Environmental Medicine, New York University School of Medicine and Langone Medical Center, New York, New York (United States); DeWyngaert, J. Keith [Department of Radiation Oncology, New York University School of Medicine and Langone Medical Center, New York, New York (United States)

    2012-11-01

    Purpose: To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. Methods and Materials: Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone setup. 3D-CRT was delivered at a dose of 30 Gy in five 6-Gy/day fractions over 10 days with port film verification at each treatment. Rates of ipsilateral breast failure, ipsilateral nodal failure, contralateral breast failure, and distant failure were estimated using the cumulative incidence method. Rates of disease-free, overall, and cancer-specific survival were recorded. Results: One hundred patients were enrolled in this institutional review board-approved prospective trial, one with bilateral breast cancer. One patient withdrew consent after simulation, and another patient elected to interrupt radiotherapy after receiving two treatments. Ninety-eight patients were evaluable for toxicity, and, in 1 case, both breasts were treated with partial breast irradiation. Median patient age was 68 years (range, 53-88 years); in 55% of patients the tumor size was <1 cm. All patients had hormone receptor-positive cancers: 87% of patients underwent adjuvant antihormone therapy. At a median follow-up of 64 months (range, 2-125 months), there was one local recurrence (1% ipsilateral breast failure) and one contralateral breast cancer (1% contralateral breast failure). There were no deaths due to breast cancer by 5 years. Grade 3 late toxicities occurred in 2 patients (one breast edema, one transient breast pain). Cosmesis was rated good/excellent in 89% of patients with at least 36

  18. 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 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-dose-requiring women. Nine nonsynonymous variants were unique to the high-dose-requiring group. These included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V, R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173

  19. High-dose radiation sensor with wireless optical detection

    Science.gov (United States)

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

    2017-05-01

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

  20. 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.

  1. 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.

  2. High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

    Science.gov (United States)

    Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

    2017-08-01

    Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Transient tetraparesis after intrathecal and high-dose systemic methotrexate.

    Science.gov (United States)

    Massenkeil, G; Späth-Schwalbe, E; Flath, B; Gottschalk, S; Lehmann, R; Arnold, R

    1998-11-01

    Aggressive polychemotherapy, intrathecal cytostatic prophylaxis and cranial irradiation have contributed to the remarkable improvement in the prognosis of acute lymphoblastic leukemia (ALL) and subtypes of high-grade non-Hodgkin's lymphoma (NHL) and the reduction of central nervous system (CNS) relapses. Early and late neurologic changes have been observed after different CNS-directed therapies. We report on the rare event of an acute tetraparesis after methotrexate (MTX) without other CNS-directed therapy. A young female with a diffuse large B-cell lymphoma developed signs of meningeal irritation a few hours after intrathecal prophylaxis with MTX, cytosine-arabinoside and dexamethasone. She recovered quickly. Ten days after her last course of systemic chemotherapy including high dose MTX she was admitted with a tetraparesis and motoric aphasia. A computer assisted tomography (CT) scan was normal. On magnetic resonance imaging (MRI) hyperintense white matter lesions were visible in the periventricular white matter. Initially, the radiologic signs were progressive while the patient's clinical condition improved. MRI controls after complete neurologic normalization revealed delayed partial regression of the white matter abnormalities. The patient has now been free of neurologic symptoms for 16 months. This case report demonstrates acute and subacute neurotoxic effects of MTX in the same patient and illustrates that radiologic CNS changes can persist irrespective of the disappearance of clinical symptoms.

  4. 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

  5. Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy.

    Science.gov (United States)

    McMasters, Kelly M; Egger, Michael E; Edwards, Michael J; Ross, Merrick I; Reintgen, Douglas S; Noyes, R Dirk; Martin, Robert C G; Goydos, James S; Beitsch, Peter D; Urist, Marshall M; Ariyan, Stephan; Sussman, Jeffrey J; Davidson, B Scott; Gershenwald, Jeffrey E; Hagendoorn, Lee J; Stromberg, Arnold J; Scoggins, Charles R

    2016-04-01

    The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI. © 2016 by American Society of Clinical Oncology.

  6. High dose proton implantations into silicon: a combined EBIC, SRP and TEM study

    Energy Technology Data Exchange (ETDEWEB)

    Kirnstoetter, Stefan [Institute of Solid State Physics, Graz University of Technology, Graz (Austria); Infineon Technologies Austria AG, Villach (Austria); Faccinelli, Martin; Hadley, Peter [Institute of Solid State Physics, Graz University of Technology, Graz (Austria); Gspan, Christian; Grogger, Werner [Institute for Electron Microscopy and Nanoanalysis (FELMI), Graz University of Technology, Graz (Austria); Jelinek, Moriz; Schustereder, Werner [Infineon Technologies Austria AG, Villach (Austria); Laven, Johannes G.; Schulze, Hans-Joachim [Infineon Technologies AG, Munich (Germany)

    2014-11-15

    Proton (H{sup +}) implantations are used in power semiconductor devices to introduce recombination centers (Hazdra et al., Microelectron. J. 32(5), 449-456 (2001)) or to form hydrogen related donor complexes (Zohta et al., Jpn. J. Appl. Phys. 10, 532-533 (1991)). Proton implantations are also used in the 'smart cut' process to generate defects that can be used to cleave thin wafers (Romani and Evans, Nucl. Instrum. Methods Phys. Res. B 44, 313-317 (1990)). However, the implantation damage resulting from H{sup +}implantations is not completely understood. In this study, protons with energies from 400 keV up to 4 MeV and doses up to 10{sup 16} H{sup +}/cm{sup 2} were implanted into highly ohmic boron doped m:Cz silicon (100). Electron Beam Induced Current (EBIC) measurements were performed to locally determine the minority charge carrier diffusion length. The diffusion length decreases with increasing implantation dose and incorporated damage. Spreading Resistance Profiling (SRP) measurements were performed to analyze the charge carrier concentration profiles for different annealing procedures. The electrical activation and growth of the defect complexes varies strongly with the annealing parameters. Transmission Electron Microscopy measurements were made to investigate the microscopic structures formed by the high dose implantation processes. Due to the high local damage density resulting from low energy and high dose H{sup +} implants, platelet structures are formed. During high-energy high-dose H{sup +}implantations, the implanted hydrogen generates strain in the crystal lattice resulting in changes in the distances between atomic planes. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. High-dose hemodialysis versus conventional in-center hemodialysis: a cost-utility analysis from a UK payer perspective.

    Science.gov (United States)

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

    2015-01-01

    To investigate the cost-effectiveness of high-dose hemodialysis (HD) versus conventional in-center HD (ICHD), over a lifetime time horizon from the UK payer's perspective. We used a Markov modeling approach to compare high-dose HD (in-center or at home) with conventional ICHD using current and hypothetical home HD reimbursement tariffs in England. Sensitivity analyses tested the robustness of the results. The main outcome measure was the incremental cost-effectiveness ratio (ICER) expressed as a cost per quality-adjusted life-year (QALY). Over a lifetime, high-dose HD in-center (5 sessions/wk) is associated with higher per-patient costs and QALYs (increases of £108,713 and 0.862, respectively) versus conventional ICHD. The corresponding ICER (£126,106/QALY) indicates that high-dose HD in-center is not cost-effective versus conventional ICHD at a UK willingness-to-pay threshold of £20,000 to £30,000. High-dose HD at home is associated with lower total costs (£522 less per patient) and a per-patient QALY increase of 1.273 compared with ICHD under the current Payment-by Results reimbursement tariff (£456/wk). At an increased home HD tariff (£575/wk), the ICER for high-dose HD at home versus conventional ICHD is £17,404/QALY. High-dose HD at home had a 62% to 84% probability of being cost-effective at a willingness-to-pay threshold of £20,000 to £30,000/QALY. Although high-dose HD has the potential to offer improved clinical and quality-of-life outcomes over conventional ICHD, under the current UK Payment-by Results reimbursement scheme, it would be considered cost-effective from a UK payer perspective only if conducted at home. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  8. 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

    .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...... in the methylene tetrahydrofolate reductase (MTHFR) gene and coadministration of antimetabolites on post-HDMTX toxicity. METHODS: Toxicity was retrospectively analysed after 656 HDMTX courses administered to 88 paediatric ALL patients at a single treatment centre. RESULTS: High-dose methotrexate with high...

  9. Advantages of high-dose rate (HDR) brachytherapy in treatment of prostate cancer

    Science.gov (United States)

    Molokov, A. A.; Vanina, E. A.; Tseluyko, S. S.

    2017-09-01

    One of the modern methods of preserving organs radiation treatment is brachytherapy. This article analyzes the results of prostate brachytherapy. These studies of the advantages of high dose brachytherapy lead to the conclusion that this method of radiation treatment for prostate cancer has a favorable advantage in comparison with remote sensing methods, and is competitive, preserving organs in comparison to surgical methods of treatment. The use of the method of polyfocal transperineal biopsy during the brachytherapy session provides information on the volumetric spread of prostate cancer and adjust the dosimetry plan taking into account the obtained data.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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

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

    Science.gov (United States)

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

    2017-05-01

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

  14. Interstitial high-dose-rate brachytherapy in eyelid cancer.

    Science.gov (United States)

    Mareco, Virgínia; Bujor, Laurentiu; Abrunhosa-Branquinho, André N; Ferreira, Miguel Reis; Ribeiro, Tiago; Vasconcelos, Ana Luisa; Ferreira, Cidalina Reis; Jorge, Marília

    2015-01-01

    To report the experience and the outcomes of interstitial high-dose-rate (HDR) brachytherapy (BT) of eyelid skin cancer at the Department of Radiotherapy of Hospital de Santa Maria in Lisbon. Seventeen patients (pts; mean age, 73.75 years) who underwent eyelid interstitial HDR BT with an (192)Ir source between January 2011 and February 2013 were analyzed. Lesions were basal (94%) and squamous (6%) cell carcinomas, on lower (88%) or upper (6%) eyelids, and on inner canthus (6%). T-stage was Tis (6%), T1 (46%), T2 (36%), and T3a (12%). The purpose of BT was radical (12%), adjuvant to surgery (71%), or salvage after surgery (18%). The BT implant and treatment planning were based on the Stepping Source Dosimetry System. The median total dose was 42.75 Gy (range, 32-50 Gy), with a median of 10 fractions (range, 9-11 fractions), twice daily, 6 h apart. The median V100 was 2.38 cm(3) (range, 0.83-5.59 cm(3)), and the median V150 was 1.05 cm(3) (range, 0.24-3.12 cm(3)). At a median followup of 40 months (range, 7-43 months), the local control was 94.1%. There was one local recurrence and one non-related death. The BT was well tolerated. Madarosis was the most common late effect (65% of pts) and was related with higher values of V100 (p = 0.027). Cosmetic outcomes were good and excellent in 70% of pts. Interstitial HDR BT is a feasible and safe technique for eyelid skin cancers, with good local control. Recurrent lesions and higher volumes receiving the prescribed dose were associated with worse outcomes. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

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    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.

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

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    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

  17. The effect of high dose radioiodine therapy on formation of radiation retinopathy during thyroid cancer treatment.

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

    2014-10-05

    Non-thyroidspan>al 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. 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. 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. 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.

  18. High dose compressive loads attenuate bone mineral loss in humans with spinal cord injury

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    Dudley-Javoroski, S.; Saha, P. K.; Liang, G.; Li, C.; Gao, Z.

    2012-01-01

    Summary People with spinal cord injury (SCI) lose bone and muscle integrity after their injury. Early doses of stress, applied through electrically induced muscle contractions, preserved bone density at high-risk sites. Appropriately prescribed stress early after the injury may be an important consideration to prevent bone loss after SCI. Introduction Skeletal muscle force can deliver high compressive loads to bones of people with spinal cord injury (SCI). The effective osteogenic dose of load for the distal femur, a chief site of fracture, is unknown. The purpose of this study is to compare three doses of bone compressive loads at the distal femur in individuals with complete SCI who receive a novel stand training intervention. Methods Seven participants performed unilateral quadriceps stimulation in supported stance [150% body weight (BW) compressive load—“High Dose” while opposite leg received 40% BW—“Low Dose”]. Five participants stood passively without applying quadriceps electrical stimulation to either leg (40% BW load—“Low Dose”). Fifteen participants performed no standing (0% BW load—“Untrained”) and 14 individuals without SCI provided normative data. Participants underwent bone mineral density (BMD) assessment between one and six times over a 3-year training protocol. Results BMD for the High Dose group significantly exceeded BMD for both the Low Dose and the Untrained groups (p0.05), indicating that BMD for participants performing passive stance did not differ from individuals who performed no standing. High-resolution CT imaging of one High Dose participant revealed 86% higher BMD and 67% higher trabecular width in the High Dose limb. Conclusion Over 3 years of training, 150% BW compressive load in upright stance significantly attenuated BMD decline when compared to passive standing or to no standing. High-resolution CT indicated that trabecular architecture was preserved by the 150% BW dose of load. PMID:22187008

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

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

    2015-01-01

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

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

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    Ray Monika

    2012-05-01

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

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

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    Shabani Ramin

    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.

  2. Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder.

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    Qi, Wei; Gevonden, Martin; Shalev, Arieh

    2017-02-01

    Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.

  3. High doses of methylprednisolone in the management of caustic esophageal burns.

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    Usta, Merve; Erkan, Tülay; Cokugras, Fugen Cullu; Urganci, Nafiye; Onal, Zerrin; Gulcan, Mahir; Kutlu, Tufan

    2014-06-01

    Caustic substance ingestion in childhood is a public health issue in developing countries, and several management protocols have been proposed to prevent the resulting esophageal strictures. The role of corticosteroids in preventing corrosive-induced strictures is controversial. Our aim was to study the influence of high doses of corticosteroids in preventing esophageal strictures. Eighty-three children with a mean age of 4.10 6 2.63 years and with grade IIb esophageal burns (an esophagogastroscopy was performed within 24–48 hours of injury) due to corrosive substance ingestion were enrolled in our study between 2005 and 2008. Forty-two children (study group) received methylprednisolone (1 g/1.73 m2 per day for 3 days), ranitidine, ceftriaxone, and total parenteral nutrition. Forty-one children (control group) were administered the same regimen excluding methylprednisolone. Stricture development was compared between groups based on endoscopic and radiologic findings. During the endoscopic examination, stricture development was observed in 4 patients (10.8%) in the study group and in 12 patients (30%) in the control group. The difference was statistically significant (P = .038). The stricture development rate in the upper gastrointestinal system with barium meal was 14.3% and 45.0% in the study and control groups, respectively. The difference was statistically significant (P = .004). The duration of total parenteral nutrition was shorter in the study group compared with the control group (P = .001). High doses of methylprednisolone were well tolerated in the study group without any side effects. High doses of methylprednisolone used for the management of grade IIb esophageal burns may reduce stricture development.

  4. Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults.

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    Pettersen, Jacqueline A

    2017-04-01

    Insufficiency of 25-hydroxyvitamin D [25(OH)D] has been associated with dementia and cognitive decline. However, the effects of vitamin D supplementation on cognition are unclear. It was hypothesized that high dose vitamin D3 supplementation would result in enhanced cognitive functioning, particularly among adults whose 25(OH)D levels were insufficient (cognitive performance were assessed and the latter consisted of: Symbol Digit Modalities Test, verbal (phonemic) fluency, digit span, and the CANTAB® computerized battery. There were no significant baseline differences between Low (n=40) and High (n=42) dose groups. Serum 25(OH)D increased significantly more in the High Dose (from 67.2±20 to 130.6±26nmol/L) than the Low Dose group (60.5±22 to 85.9±16nmol/L), p=0.0001. Performance improved in the High Dose group on nonverbal (visual) memory, as assessed by the Pattern Recognition Memory task (PRM), from 84.1±14.9 to 88.3±13.2, p=0.043 (d=0.3) and Paired Associates Learning Task, (PAL) number of stages completed, from 4.86±0.35 to 4.95±0.22, p=0.044 (d=0.5), but not in the Low Dose Group. Mixed effects modeling controlling for age, education, sex and baseline performance revealed that the degree of improvement was comparatively greater in the High Dose Group for these tasks, approaching significance: PRM, p=0.11 (d=0.4), PAL, p=0.058 (d=0.4). Among those who had insufficient 25(OH)D (memory seems to benefit from higher doses of vitamin D supplementation, particularly among those who are insufficient (memory and other cognitive domains do not. These findings are consistent with recent cross-sectional and longitudinal studies, which have demonstrated significant positive associations between 25(OH)D levels and nonverbal, but not verbal, memory. While our findings require confirmation, they suggest that higher 25(OH)D is particularly important for higher level cognitive functioning, specifically nonverbal (visual) memory, which also utilizes executive

  5. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis.

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

    2014-10-23

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

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

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    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)

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

    Science.gov (United States)

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

    2010-04-01

    We propose that elevation of mitochondrial enzyme cofactors may prevent or ameliorate neurodegenerative diseases by improving mitochondrial function. In the present study, we investigated the effects of high doses of B vitamins, the precursors of mitochondrial enzyme cofactors, on mitochondrial dysfunction, oxidative stress, and Parkinsonism in a 4-week long rotenone treatment-induced cellular model of Parkinson's disease (PD). Pretreatment with B vitamins (also 4 weeks) prevented rotenone-induced: (1) mitochondrial dysfunction, including reduced mitochondrial membrane potential and activities of complex I; (2) oxidative stress, including increase in reactive oxygen species, oxidative DNA damage and protein oxidation, and (3) Parkinsonism parameters, including accumulation of alpha-synuclein and poly-ubiquitin. The optimum doses were found around 2.5- and 5-fold of that in normal MEM medium. The 4-week pretreatment was chosen based on time-dependent experiments that pretreatments longer than 2 weeks resulted in a decrease in oxidants, an increase in oxygen consumption, and up-regulation of complex I activity and PGC-1alpha expression. Individual B vitamins at the same doses did not show a similar effect suggesting that these B vitamins work synergistically. These results suggest that administration of high doses of B vitamins sufficient to elevate mitochondrial enzyme cofactors may be effective in preventing PD by reducing oxidative stress and improving mitochondrial function. Copyright (c) 2008 Elsevier Inc. All rights reserved.

  8. Evaluation of a high-dose extended multipass gray writing system for 130-nm pattern generation

    Science.gov (United States)

    Chabala, Jan M.; Weaver, Suzanne; Alexander, David W.; Pearce-Percy, Henry T.; Lu, Maiying; Cole, Damon M.; Abboud, Frank E.

    2000-07-01

    Recent developments in electron-beam (e-beam) systems and mask-writing strategies facilitate pattern generation for the 130-nm IC generation. The MEBESR 5500 pattern generation system incorporates a high-dose electron optical system and a high-throughput writing strategy, Multipass Gray-II (MPG-II). We evaluate the effectiveness of these innovations by three criteria: improved resolution, improved critical dimension (CD) control, and increased throughput. The conclusions of this paper are based on results from extensive modeling, test masks, and factory acceptance masks. Mask resist choice and processing have been optimized for the MEBES 5500 system. A consequence of these improvements is greater productivity for 150 nm devices and early development of 130 nm devices. The MEBES 5500 system uses a high-dose gun and electron optical system. The maximum current density that can be delivered to the mask is 800 A/cm2, twice the value of previous MEBES systems. Without loss of throughput, it is possible to increase the dose deposited in the resist, while using smaller e-beam sizes. These capabilities are exploited to improve printing of submicrometer features, including 200 nm-scale optical proximity correction (OPC) patterns. At small data addresses (MEBES 4500 system. The fundamentals of the MPG-II strategy are described, as well as throughput and lithographic results.

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

    Science.gov (United States)

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

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

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

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    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.

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

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    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.

  12. Effects of High Dose and Long Term Montelukast Treatment on Skin:An Experimental Rat Study

    Directory of Open Access Journals (Sweden)

    Aysel Kükner

    2008-12-01

    Full Text Available Background and Design: The aim of this study was to assess the effects of long term, high dose montelukast administration on normal rat skin by histological examination.Material and Method: Sixteen rats were randomly divided into 2 groups-the control and the montelukast treated (study group (n=8. In the control group 0.2ml of 0.9% NaCl was administered intraperitonealy (i.p. daily for 6 weeks. In the study group the same amount of solution containing 1 mg/kg montelukast was administered i.p. daily for six weeks. At the end of the 6 weeks skin biopsies were taken and histologically examined.Results: There was no significant difference between two groups regarding the dermal and epidermal thickness. Histologic examination of collagen fiber structure did not show difference between two groups. Toluidin blue stained specimens showed that the number of mast cells in dermis significantly decreased in montelukast treated group (p=0.001. Conclusion: Montelukast treatment has significantly decreased the number of mast cells in dermis without any effect on the dermal or epidermal thickness and collagen fiber structure. We think that with the support of further studies, high dose montelukast may have an effective role on the treatment of inflammatory skin disease. (Turkderm 2008; 42: 118-21

  13. High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep.

    Science.gov (United States)

    Murakami, Kazunori; Enkhbaatar, Perenlei; Shimoda, Katsumi; Mizutani, Akio; Cox, Robert A; Schmalstieg, Frank C; Jodoin, Jeffrey M; Hawkins, Hal K; Traber, Lillian D; Traber, Daniel L

    2003-04-01

    Thrombin is involved in various inflammatory responses. In sepsis, coagulation abnormalities are major complications. Acute lung injury is one of the most life-threatening problems that can result from sepsis. We hypothesized that high-dose heparin might be effective in attenuating acute lung injury in our sepsis model. Female sheep ( n =16) were surgically prepared for the study. After a tracheotomy, 48 breaths of cotton smoke (heparin infusion group ( n =6), a Ringer's lactate infusion group ( n =6), and a sham-injury group ( n =4; surgically prepared in the same fashion but receiving no inhalation injury or bacteria). The treatment was started 1 h after the insult, and was continued thereafter for 24 h. The dose of heparin was adjusted by monitoring to target an activated clotting time of between 300 and 400 s (baseline=approx. 150 s). Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes, including an increased cardiac output and a fall in systemic vascular resistance. There was a decrease in the arterial partial pressure of O(2). In conclusion, high-dose heparin did not prevent lung dysfunction in this model, in which acute lung injury was induced by combined smoke and septic challenge.

  14. Comparison of Short and Continuous Hydration Regimen in Chemotherapy Containing Intermediate- to High-Dose Cisplatin

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    Akira Ouchi

    2014-01-01

    Full Text Available Aim. The efficacy of the short hydration regimen was reported in chemotherapy containing intermediate- to high-dose cisplatin, and the use of outpatient chemotherapy containing cisplatin with short hydration has been widespread in recent years. Methods. We compared patients with gastric cancer, lung cancer, and urothelial cancer who received outpatient chemotherapy containing cisplatin (≥60 mg/m2/cycle with the short hydration regimen since April 2012 (n=13 with those who received hospital chemotherapy with continuous hydration between April 2011 and March 2013 (n=17 in our hospital. Results. Grade 2 or higher acute kidney injury occurred in 2 patients in the continuous hydration group and in no patient in the short hydration group; 1 patient discontinued treatment on account of nephrotoxicity. There was no difference between the 2 groups in maximum creatinine increment and maximum clearance decrement. Relative dose intensity in the short hydration group was higher than that in the continuous hydration group (89.5% versus 80.3%; P<0.01. Conclusions. The short hydration regimen in outpatient chemotherapy containing intermediate- to high-dose cisplatin is as safe as the continuous hydration regimen and increased the efficacy of chemotherapy.

  15. Perioperative high-dose-rate interstitial brachytherapy boost for patients with early breast cancer.

    Science.gov (United States)

    Sharma, Daya Nand; Deo, S V S; Rath, Goura Kisor; Shukla, Nootan Kumar; Thulkar, Sanjay; Madan, Renu; Julka, Pramod Kumar

    2013-01-01

    To evaluate the clinical results of perioperative high-dose-rate interstitial brachytherapy boost treatment preceding whole breast external beam radiation therapy in patients with early breast cancer. From 2005-2010, 100 patients with early breast cancer who met the eligibility criteria were enrolled in the study. Brachytherapy implant was performed during the breast-conserving surgery procedure. The boost treatment was started on the 3rd postoperative day to deliver a dose of 15 Gy in 6 fractions over 3 days. Three weeks later, external beam radiation therapy to the whole breast was started for a prescription dose of 50 Gy. The study end points were local recurrence, acute toxicity and cosmetic outcome. Median age of the patients was 46 years, and median follow-up was 52 months. No patient developed a local recurrence but 5 patients developed distant metastases. The 5-year overall survival and disease-free survival were 86% and 77%, respectively. Eleven patients had acute toxicity; 4 wound complications and 7 grade III skin toxicity. Nine of the 11 patients had breast size of more than 1500 cc. Except for the breast volume (>1500 cc), there was no statistically significant correlation between any of the patient or dosimetry-related factors and acute toxicity. Good-excellent cosmesis was observed in 87% of patients. Perioperative high-dose-rate interstitial brachytherapy boost followed by whole breast external beam radiation therapy provides excellent local control, acceptable acute toxicity and good-excellent breast cosmesis in patients with early breast cancer.

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

    Science.gov (United States)

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

    2011-08-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

  17. Age and Sex Interact to Mediate the Effects of Intermittent, High-Dose Ethanol Exposure on Behavioral Flexibility

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Barker

    2017-07-01

    Full Text Available Human alcoholics have been shown to have impaired cognitive control over actions and increased reliance on habitual response strategies. While it is unclear in humans whether these differences predate ethanol exposure or result from chronic drinking, data from animal studies suggest that ethanol acts to promote the development of inflexible behaviors. Here, we investigated how intermittent exposure to high doses of ethanol impacts the ability to flexibly regulate behavior in a habit model. As adolescence, may represent a period of increased drug taking and developmental vulnerability that may impact adult behavior, we compared the effects of high-dose ethanol exposure during adolescence to exposure during adulthood in male and female rats. Our findings indicated that the effects of intermittent, high-dose ethanol exposure on habitual behavior is mediated by age and sex such that ethanol exposure during adolescence promoted the use of habitual response strategies in adult females, but not males, and that the opposite pattern emerged following intermittent, high-dose ethanol exposure in adult rats.

  18. Cost-Effectiveness of High Dose Hemodialysis in Comparison to Conventional In-Center Hemodialysis in the Netherlands.

    Science.gov (United States)

    Beby, Anna Trisia; Cornelis, Tom; Zinck, Raymund; Liu, Frank Xiaoqing

    2016-11-01

    In the Netherlands, the current standard of care for treating patients with end-stage renal disease is three sessions of in-center hemodialysis (conventional ICHD). However, the literature indicates that high dose hemodialysis (high dose HD) may provide better health outcome such as survival and quality of life. The objective of this study was to determine the cost-effectiveness of high dose HD, both in-center and at home, in comparison to conventional ICHD from a Dutch payer's perspective over a 5 year period. Additionally, the cost-effectiveness of conventional HD at home in comparison to conventional ICHD will be analysed. A Markov model was developed assuming 28-day treatment cycles and was populated with data from Dutch and international renal registries, official tariffs and medical literature. Univariable and probabilistic sensitivity analyses were performed to test the robustness of the results. Using publicly available tariffs from the Dutch Healthcare Authority (Nederlandse Zorgautoriteit) of 2015, doing high dose ICHD instead of conventional ICHD shows an incremental cost-effectiveness ratio (ICER) of €275,747 per quality-adjusted life year (QALY) gained. In contrast, the ICER of high dose HD at home in comparison to conventional ICHD is €3248 per gained QALY. The final analysis shows that conventional HD at home is less costly per patient (-€3063) than conventional ICHD and results in health benefit improvement (+0.249 QALYs), and is therefore regarded as cost saving. Treating dialysis patients with conventional HD at home shows to be cost saving in comparison to conventional ICHD. However, the magnitude of clinical benefit of high dose HD at home is over two times greater than the clinical benefit of conventional HD at home. According to our analysis, from a payer's perspective, high dose HD should be offered as a home therapy to obtain its clinical benefits in a cost-effective manner. Future research should consider our findings alongside

  19. Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas

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    Bruno Kosa Lino Duarte

    2011-12-01

    Full Text Available OBJECTIVE: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. METHODS: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m² and granulocyte-colony stimulating factor (300 µg/day, followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m² and methotrexate (8 g/m² only for Hodgkin's lymphoma and autologous hematopoietic stem cell transplantation. RESULTS: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65 years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68 years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13% and 10 (9% non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. CONCLUSIONS: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality.

  20. Nasopharyngeal Carcinoma Treated with Precision-Oriented Radiation Therapy Techniques Including Intensity-Modulated Radiotherapy: Preliminary Results

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    Wen-Shan Liu

    2004-02-01

    Full Text Available This paper reports preliminary results with intensity-modulated radiotherapy (IMRT in nasopharyngeal carcinoma (NPC. Between August 2000 and May 2001, we treated 19 patients with NPC using IMRT. Twelve patients had stage I-II disease and seven had stage III-IV disease. Six patients received 9.0-19.8 Gy three-dimensional conformal radiotherapy (3D-CRT before IMRT and 18 patients received a brachytherapy boost after IMRT. The mean follow-up time was 13.0 months. All patients with stage II-IV disease except one received two cycles of chemoradiotherapy with cisplatin and 5-fluorouracil (5-FU during radiotherapy, followed by two to four cycles of chemotherapy after radiotherapy. Tumor response was assessed using clinical examination and computerized tomography or magnetic resonance imaging. The mean doses administered to the gross tumor volume and clinical tumor volume were 70.9 Gy and 63.2 Gy, respectively. The mean doses administered to the right and left parotid glands were 38.1 Gy and 38.6 Gy, respectively. All 19 patients had a complete response of primary and lymph node disease. Grade III mucositis developed during chemoradiotherapy in 15 patients (79%. In addition, clinical grade I xerostomia was recorded in nine patients, grade II in nine, and grade III in one. This study demonstrated that 3D-CRT, IMRT, intracavitary brachytherapy, and chemotherapy are effective and safe methods to treat NPC. Although IMRT treatment spared parotid gland function, its efficacy may be significantly influenced by disease stage and location of the neck lymph nodes. More cases and a longer follow-up to assess survival and complications are planned.

  1. High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels

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    Ichinomiya Taiga

    2012-03-01

    Full Text Available Abstract Background The current study was carried out to determine whether fasudil hydrochloride (fasudil, a Rho-kinase inhibitor, has myocardial postconditioning (PostC activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP channels. Methods Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg or high-dose (0.5 mg/kg fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD, an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR. Results Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively compared with that in the control (42 ± 7%. Under hyperglycemia, low-dose fasudil (40 ± 11% and diazoxide (44 ± 14% could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%. 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%. Conclusion Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.

  2. Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature

    Directory of Open Access Journals (Sweden)

    Durim Delishaj

    2016-12-01

    Full Text Available Purpose: The incidence of non-melanoma skin cancer (NMSC has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT. Material and methods: In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of “skin cancer”, “high dose rate brachytherapy”, “squamous cell carcinoma”, “basal cell carcinoma”, and “non melanoma skin cancer“ was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Results: Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%. Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Conclusions : Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy.

  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. Palliative chemotherapy after failure of high-dose chemotherapy in breast cancer--toxicity and efficacy

    NARCIS (Netherlands)

    Schrama, J. G.; de Boer, M. M.; Baars, J. W.; Schornagel, J. H.; Rodenhuis, S.

    2003-01-01

    We evaluated the toxicity and efficacy of the first palliative chemotherapy regimen after failure of high-dose chemotherapy in 148 patients with primary or metastatic breast cancer treated with high-dose chemotherapy (one full dose CTC, (cyclophosphamide 6000 mg/m2, thiotepa 480 mg/m2, carboplatin

  5. Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature.

    Science.gov (United States)

    Delishaj, Durim; Rembielak, Agata; Manfredi, Bruno; Ursino, Stefano; Pasqualetti, Francesco; Laliscia, Concetta; Orlandi, Francesca; Morganti, Riccardo; Fabrini, Maria Grazia; Paiar, Fabiola

    2016-12-01

    The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT). In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of "skin cancer", "high dose rate brachytherapy", "squamous cell carcinoma", "basal cell carcinoma", and "non melanoma skin cancer" was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy.

  6. The cost-effectiveness of high-dose oral proton pump inhibition after endoscopy in the acute treatment of peptic ulcer bleeding.

    Science.gov (United States)

    Barkun, A N; Herba, K; Adam, V; Kennedy, W; Fallone, C A; Bardou, M

    2004-07-15

    Recent data suggest a role for high-dose oral proton pump inhibition in ulcer bleeding. To compare the cost-effectiveness of oral high-dose proton pump inhibition to both high-dose intravenous proton pump inhibition and placebo administration. The model adopted a 30-day time horizon, and focused on patients with ulcer haemorrhage initially treated endoscopically for high-risk stigmata. Re-bleeding rates were set a priori based on non-head-to-head data from the literature, and charges and lengths of stay from a national American database. Sensitivity analyses were carried across a broad range of clinically relevant assumptions. Re-bleeding rates for patients receiving intravenous, oral, or placebo therapies were 5.9%, 11.8%, and 27%, respectively. The mean lengths of stay and costs for admitted patients with and without re-bleeding were 4.7 and 3 days; $11,802, and $7993, respectively. High-dose intravenous proton pump inhibition was more effective and less costly (dominant) than high-dose oral proton pump inhibition with incremental savings of $136.40 per patient treated. The oral high-dose strategy in turn dominated placebo administration. Results remained robust according to one- and two-way sensitivity analyses. In patients undergoing endoscopic haemostasis, subsequent high-dose intravenous proton pump inhibition is more cost-effective than high-dose oral proton pump inhibition, which in turn dominates placebo. The results from this exploratory-type cost analysis require confirmation by head-to-head prospective trials performed in Western populations.

  7. Preliminary results of accelerated partial breast irradiation in the combination organ-saving treatment of patients with early-stage breast cancer

    Directory of Open Access Journals (Sweden)

    O. P. Trofimova

    2013-01-01

    Full Text Available Objective: to develop and introduce an accelerated partial breast irradiation procedure in patients with early-stage breast cancer after organ-saving operations using three-dimensional conformal teleradiotherapy (3D CRT and to assess the preliminary results of treat- ment.Subjects and methods: the trial enrolled 48 patients with verified T1-2N0-1micM0 stage breast cancer who received organ-saving treatment in the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, in 2008–2012. The median age of the patients was 63 years. All the patients underwent organ-saving operations with subsequent 3D CRT applied to the resected tumor bed with margins. Radiotherapy with a dose of 2.5 Gy was performed twice daily; the daily dose was 5 Gy; the course dose was 40 Gy. Indications for accelerated partial irradiation of the tumor bed were listed; the data of randomized trials were given.Results. The median follow-up was 27 months; locoregional recurrences or distant metastases were found in no patients. Late radia- tion skin and soft tissue injuries were seen in no cases. All the patients were ascertained to have early-stage grade I radiation cutane- ous injuries according to the RTOG-EORTC classification. Excellent, good, fair, and poor cosmetic results were obtained in 12 (25 %, 34 (71 %, 2 (4 %, and 0 patients, respectively.Conclusion. The developed accelerated partial breast irradiation procedure in patients with early-stage breast cancer after organ- saving operations at the median follow-up of 27 months showed good results, such as no local recurrences or distant metastases. Excel- lent and good cosmetic results were noted in 96 % of the patients.

  8. Accelerated partial breast irradiation with external beam three-dimensional conformal radiotherapy. Five-year results of a prospective phase II clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Mozsa, Emoeke [National Institute of Oncology, Centre of Radiotherapy, Budapest (Hungary); Landesklinikum Wiener Neustadt, Department of Radiooncology and Radiotherapy, Wiener Neustadt (Austria); Meszaros, Norbert; Major, Tibor; Froehlich, Georgina; Stelczer, Gabor; Fodor, Janos; Polgar, Csaba [National Institute of Oncology, Centre of Radiotherapy, Budapest (Hungary); Sulyok, Zoltan [National Institute of Oncology, Centre of Surgery, Budapest (Hungary)

    2014-05-15

    The aim of this study was to report the 5-year results of accelerated partial breast irradiation (APBI) using external beam three-dimensional conformal radiotherapy (3D-CRT). Between 2006 and 2011, 44 patients with low-risk, stage I-II breast cancer underwent breast-conserving surgery. Postoperative APBI was given by means of 3D-CRT using three to five non-coplanar fields. The total dose of APBI was 36.9 Gy (nine fractions of 4.1 Gy b.i.d.). The mean follow-up time was 58.2 months for surviving patients. Survival results, side effects, and cosmetic results were assessed. One (2.3 %) local recurrence was observed, for a 5-year actuarial rate of 3.7 %. Neither regional nor distant failure was observed. Two patients died of internal disease. The 5-year disease-free, cancer-specific, and overall survival rates were 96.3, 100, and 95.1 %, respectively. Acute side effects included grade 1 (G1) erythema in 75 %, G1 parenchymal induration in 46 %, and G1 pain in 46 % of patients. No G2 or higher acute side effect occurred. Late side effects included G1, G2, and G3 fibrosis in 44, 7, and 2 % of patients, respectively, G1 skin pigmentation in 12 %, and G1 pain in 2 %. Asymptomatic fat necrosis occurred in 14 %. Cosmetic results were rated excellent or good in 86 % of cases by the patients themselves and 84 % by the physicians. The 5-year local tumor control, toxicity profile, and cosmetic results of APBI delivered with external beam 3D-CRT are encouraging and comparable to other APBI series. (orig.) [German] Evaluation der 5-Jahres-Ergebnisse bezueglich Ueberleben, Tumorkontrolle, Nebenwirkungen und Kosmetik nach Teilbrustbestrahlung (APBI) mittels 3-D-konformaler, akzelerierter Radiotherapie (3D-CRT). Zwischen 2006 und 2011 wurden 44 Patienten mit Brustkrebs im Stadium I-II und niedrigem Risikoprofil brusterhaltend operiert. Die adjuvante, 3-D-konformale APBI wurde mittels 3-5 nonkoplanarer Feldern durchgefuehrt. Die Gesamtdosis betrug 36,9 Gy bei 9 -mal 4,1 Gy b.i.d.. Nach

  9. Clinical characteristics of veterans prescribed high doses of opioid medications for chronic non-cancer pain.

    Science.gov (United States)

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

    2010-12-01

    Little is known about patients prescribed high doses of opioids to treat chronic non-cancer pain, though these patients may be at higher risk for medication-related complications. We describe the prevalence of high-dose opioid use and associated demographic and clinical characteristics among veterans treated in a VA regional healthcare network. Veterans with chronic non-cancer pain prescribed high doses of opioids (≥ 180 mg/day morphine equivalent; n=478) for 90+ consecutive days were compared to two groups with chronic pain: Traditional-dose (5-179 mg/day; n=500) or no opioid (n=500). High-dose opioid use occurred in 2.4% of all chronic pain patients and in 8.2% of all chronic pain patients prescribed opioids long-term. The average dose in the high-dose group was 324.9 (SD=285.1)mg/day. The only significant demographic difference among groups was race (p=0.03) with black veterans less likely to receive high doses. High-dose patients were more likely to have four or more pain diagnoses and the highest rates of medical, psychiatric, and substance use disorders. After controlling for demographic factors and VA facility, neuropathy, low back pain, and nicotine dependence diagnoses were associated with increased likelihood of high-dose prescriptions. High-dose patients frequently did not receive care consistent with treatment guidelines: there was frequent use of short-acting opioids, urine drug screens were administered to only 25.7% of patients in the prior year, and 32.0% received concurrent benzodiazepine prescriptions, which may increase risk for overdose and death. Further study is needed to identify better predictors of high-dose usage, as well as the efficacy and safety of such dosing. Published by Elsevier B.V.

  10. A safety trial of high dose glyceryl triacetate for Canavan disease.

    Science.gov (United States)

    Segel, Reeval; Anikster, Yair; Zevin, Shoshana; Steinberg, Avraham; Gahl, William A; Fisher, Drora; Staretz-Chacham, Orna; Zimran, Ari; Altarescu, Gheona

    2011-07-01

    Canavan disease (CD MIM#271900) is a rare autosomal recessive neurodegenerative disorder presenting in early infancy. The course of the disease is variable, but it is always fatal. CD is caused by mutations in the ASPA gene, which codes for the enzyme aspartoacylase (ASPA), which breaks down N-acetylaspartate (NAA) to acetate and aspartic acid. The lack of NAA-degrading enzyme activity leads to excess accumulation of NAA in the brain and deficiency of acetate, which is necessary for myelin lipid synthesis. Glyceryltriacetate (GTA) is a short-chain triglyceride with three acetate moieties on a glycerol backbone and has proven an effective acetate precursor. Intragastric administration of GTA to tremor mice results in greatly increased brain acetate levels, and improved motor functions. GTA given to infants with CD at a low dose (up to 0.25 g/kg/d) resulted in no improvement in their clinical status, but also no detectable toxicity. We present for the first time the safety profile of high dose GTA (4.5 g/kg/d) in 2 patients with CD. We treated 2 infants with CD at ages 8 months and 1 year with high dose GTA, for 4.5 and 6 months respectively. No significant side effects and no toxicity were observed. Although the treatment resulted in no motor improvement, it was well tolerated. The lack of clinical improvement might be explained mainly by the late onset of treatment, when significant brain damage was already present. Further larger studies of CD patients below age 3 months are required in order to test the long-term efficacy of this drug. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  14. 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

  15. 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).

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

    Science.gov (United States)

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

    2017-10-01

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

  17. 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.

  18. Adjuvant high dose rate brachytherapy for soft tissue sarcomas: initial experience report

    Directory of Open Access Journals (Sweden)

    Robert Whitfield

    2011-03-01

    Full Text Available Purpose: Adjuvant high-dose-rate brachytherapy (HDRBT offers advantages over low dose rate brachytherapy (LDRBT, although there are little data on local tumor control and treatment related toxicity. We report outcome in patients with primary, recurrent, and metastatic extremity and superficial trunk soft tissue sarcoma. Material and methods: Eleven patients (12 sites with intermediate or high grade sarcoma were treated with adjuvant HDRBT following surgical resection. Patients were treated at 3.4 Gy fractions delivered twice daily to a total dose of 34 Gy (1 patient received 9 fractions. Results: With median follow-up of 20.8 months, 1 patient developed a local recurrence. 2-year local control and overall survival are 89% and 71%, respectively. Wound complications occurred in 3 sites. Two of the wound complications developed in the area of previous external beam radiotherapy (EBRT. Conclusion: Surgical resection followed by HDRBT is associated with excellent early local tumor control and acceptable wound complication.

  19. Study of the response reduction of LiF:Mg, Ti dosimeter for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Torkzadeh, Falamarz [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School; AEOI, Tehran (Iran, Islamic Republic of); Faripour, Heidar [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Laser and Optics Research School; AEOI, Tehran (Iran, Islamic Republic of); Mardashti, Forough; Manouchehri, Farhad [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School

    2017-07-15

    A single crystal and 5 polycrystalline samples of LiF:Mg, Ti and their pellets were prepared and investigated so as to apply thermoluminescence high gamma dose dosimetry. Three zones of single crystal with dopant concentrations of 200 ppm of Mg and 20 ppm of Ti were also used to prepare the single crystal samples. For polycrystalline samples, dopant concentrations of 0.062 mol% Mg and Ti concentrations in the range of 0.016 and 0.046 mol% were used. All the samples were exposed to gamma doses of 1 kGy to 700 kGy and their response changes were determined by a gamma dose test of about 60 mGy. According to the results obtained, the use of response reduction by curve-fitting up to about 300 kGy can be performed reliably for high dose gamma dosimetry.

  20. The Effects of High Doses of Nandrolone Decanoate on Cardiac Muscle Tissue

    Directory of Open Access Journals (Sweden)

    Sretenovic Jasmina

    2016-12-01

    Full Text Available In recent decades, steroid abuse has become very popular and widespread among professional and recreational athletes. The aim of this study was to examine the chronic effects of training combined with high doses of nandrolone decanoate on cardiac muscle tissue. The study included 32 Wistar albino rats divided into 4 groups: control (T-N-, steroid (T-N+, exercisetraining (T+N- and exercise plus steroid (T+N+ groups. The T+N- and T+N+ group swam for 4 weeks, 1 hour per day, 5 days per week. The N+ (nandrolone positive groups received nandrolone decanoate (20 mg/kg once per week, subcutaneously. After 4 weeks of training, the rats were sacrificed. Heart biopsy specimens were routinely fixed and embedded in paraffin. Fivemicrometre thick sections were stained with haematoxylin and eosin (H/E and Masson-Trichrome dyes. Captured microscopic images were processed by special software for image analysis to quantify results. Our results showed that the combination of nandrolone and training causes left ventricular wall thickening of 30%. Average cardiac muscle cell longitudinal diameter was increased by 6% in the T-N+ group, by 16% in the T+N- group and by 25% in the T+N+ group. The cross sectional muscle cell area was increased in the T+N+ group by 33%. Heart collagen content was increased in the nandrolone group compared to the control group by 261%. Collagen content was decreased in the T+N+ group by 34%. High doses of AAS induced left ventricle hypertrophy and excessive heart collagen deposition.

  1. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats

    Science.gov (United States)

    2013-01-01

    Background High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased mortality in the chronic kidney disease (CKD) population. CKD patients are often treated with iv iron therapy in order to maintain iron stores and erythropoietin responsiveness, also in the case of not being iron depleted. Therefore, the effect of a single high iv dose of two different iron preparations, iron isomaltoside 1000 (IIM) and ferric carboxymaltose (FCM), on plasma levels of FGF23 and phosphate was examined in normal and uremic iron repleted rats. Methods Iron was administered iv as a single high dose of 80 mg/kg bodyweight and the effects on plasma levels of iFGF23, phosphate, Ca2+, PTH, transferrin, ferritin and iron were examined in short and long term experiments (n = 99). Blood samples were obtained at time 0, 30, 60, 180 minutes, 24 and 48 hours and in a separate study after 1 week. Uremia was induced by 5/6-nephrectomy. Results Nephrectomized rats had significant uremia, hyperparathyroidism and elevated FGF23. Iron administration resulted in significant increases in plasma ferritin levels. No significant differences were seen in plasma levels of iFGF23, phosphate and PTH between the experimental groups at any time point within 48 hours or at 1 week after infusion of the iron compounds compared to vehicle. Conclusions In non-iron depleted normal and uremic rats a single high dose of either of two intravenous iron preparations, iron isomaltoside 1000, and ferric carboxymaltose, had no effect on plasma levels of iFGF23 and phosphate for up to seven days. PMID:24373521

  2. Regression of atherosclerosis in apolipoprotein E-deficient mice is feasible using high-dose angiotensin receptor blocker, candesartan.

    Science.gov (United States)

    Hayashi, Kaori; Sasamura, Hiroyuki; Azegami, Tatsuhiko; Itoh, Hiroshi

    2012-01-01

    Clinical studies have suggested that renin-angiotensin inhibitors are effective for the prevention of atherosclerosis progression, but the results for the regression of established lesions are equivocal. The aim of this study was to examine the effects of different doses of the angiotensin receptor blocker (ARB) candesartan on the regression of atherosclerosis and lipid-induced nephropathy in apolipoprotein E (apoE)-deficient spontaneously hyperlipidemic (SHL) mice. Male SHL were given an atherogenic diet together with salt loading to induce atherosclerosis. The mice were then treated with various doses of candesartan (0-50 mg/kg/d) for 12 weeks. Treatment with high-dose candesartan caused clear regression of atherosclerotic plaques in the aorta, which was not observed with normal-dose candesartan. Biglycan and ACAT1 expression were significantly decreased, and aortic free cholesterol: cholesterol ester ratios were increased in these mice. Treatment of cultured THP-1 macrophages in vitro with candesartan resulted in a similar decrease in ACAT1 expression. In the kidney, glomerular lipid accumulation, mesangial expansion, and albuminuria were significantly regressed after treatment with high-dose candesartan, while biglycan and ACAT1 expressions were decreased. These results suggest that regression of established atherosclerosis lesions in ApoE-deficient mice is feasible using high-dose candesartan, by mechanisms involving (i) a decrease in the lipid-retaining proteoglycan biglycan, and (ii) suppression of ACAT1 expression resulting in increased free cholesterol for lipid release.

  3. 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.

  4. 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

    2017-01-04

    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.

  5. A comparison of high dose Ga-67 SPECT and FDG PET imaging in malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kaliff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)

    1998-06-01

    Full text: Ga-67 imaging for tumour localisation lost favour in the 1970`s. With improvement in technology and use of higher doses, it has now found an important role in lymphoma. A similar phenomenon may be possible in the staging of melanoma. This study therefore compares high dose (370 MBq) Ga-67 imaging using a day 5 and 7 whole-body and comprehensive SPECT protocol, with (100 MBq) F-18 fluorodeoxyglucose (FDG) imaging using positron emission tomography (PET): a technique recently shown to be highly accurate in this condition. 85 patients; 46 males, mean age 52+17 yrs: range 22-83 yrs, underwent both studies within 9{+-}16 days (max-91 days). Scans were judged as positive (+ve), negative (-ve) or equivocal (EQ) for local, regional and distant disease. Clinical follow-up resolved discordant scan findings. PET and Ga-67 results were concordant in 61 (70%) patients (19 with +ve, 37 -ve and 5 EQ scans). None of the 9 ps with one EQ and one eye scan had disease on follow-up. Follow-up was available in 4/5 patients with discordantly +ve (3 patients) or more extensive Ga-67 abnormality: 3 patients had disease confirmed, 1 patient false +ve (asymmetric lung hilum). Follow-up was available in 9/10 patients with discordantly +ve (3 patients) or more extensive PET abnormality: 4 patients had confirmed disease, l pt false +ve (bladder diverticulum). A further 4 patients had second primaries (2 rectal carcinomas, 1 plasmacytoma, 1 basal cell carcinoma). High dose Ga-67 scanning incorporating SPECT appears to be a reasonable alternative to FDG PET for screening patients with melanoma. In this series PET`s main advantages were in the detection of other occult tumours, greater patient convenience and lower radiation dosimetry.

  6. 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

  7. High-dose extended-release lansoprazole (dexlansoprazole) and amoxicillin dual therapy for Helicobacter pylori infections.

    Science.gov (United States)

    Attumi, Taraq A; Graham, David Y

    2014-08-01

    Helicobacter pylori infections have become increasingly difficult to treat. To examine whether amoxicillin and high-dose dexlansoprazole would reliably achieve an H. pylori eradication rate of ≥90%. An open-label prospective pilot study of H. pylori eradication in treatment-naïve subjects with active H. pylori infection (positive by two tests). amoxicillin 1 g and dexlansoprazole 120 mg each twice a day at approximately 12-hour intervals for 14 days. Success was accessed by urea breath test. An effective therapy was defined as a per-protocol treatment success of 90% or greater; treatment success of 80% or less was prespecified as an unacceptable result. After 13 subjects were entered (12 men, one woman; average age of 54 years), the prespecified stopping rule of six treatment failures was achieved (i.e., the 95% confidence interval excluded achieving the required 90% success rate even if the proposed study of 50 completed patients were entered) and enrollment was stopped. Per-protocol and intention-to-treat treatment success were both 53.8%; (7/13); 95% CI = 25-80%. Compliance was 100%. Three patients (23%) reported side effects, all of which were mild and none interrupted therapy. Theoretically, dual PPI plus amoxicillin should reliably eradicate H. pylori provided nearly neutral intragastric pH can be maintained. Clearly, dexlansoprazole, despite being administered at high dose and twice a day (i.e., total daily dose 240 mg), failed to achieve an intragastric milieu consistent with dual PPI plus amoxicillin therapy being an effective anti-H. pylori regimen. © 2014 John Wiley & Sons Ltd.

  8. 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.

  9. Bladder wall recurrence of prostate cancer after high-dose-rate brachytherapy.

    Science.gov (United States)

    Raleigh, David R; Hsu, I-Chow; Braunstein, Steve; Chang, Albert J; Simko, Jeffry P; Roach, Mack

    2015-01-01

    Prostate cancer seeding after needle biopsy has been reported in the perineum, rectal wall, and periprostatic soft tissue. In this article, we report the results of a localized prostate cancer recurrence in the bladder following protrusion of a single high-dose-rate brachytherapy catheter through the bladder wall at the ultimate site of failure. A 62-year-old man with high-risk prostate adenocarcinoma was treated with long-term androgen deprivation therapy, intensity-modulated radiation, and high-dose-rate brachytherapy boost. He developed biochemical recurrence 4 years after treatment, and a CT scan of the pelvis revealed a nodule in the posterior, inferior bladder wall. Surgical pathology following transurethral resection of tumor within the bladder was consistent with high-grade prostate adenocarcinoma. The patient's prostate-specific antigen level fell to the range of normal postoperatively, and whole body imaging, including a multi-parametric MRI of the prostate with diffusion and spectroscopy, failed to reveal any other sites of disease. Review of the CT scan obtained for dosimetry at the time of brachytherapy demonstrated a lone catheter protruding through the bladder wall at the site of eventual recurrence. The tumor recurred in the bladder 12 months later, once more without evidence of disease within the prostate itself or distantly, and the patient was started on salvage androgen deprivation therapy. This case is the first report of prostate cancer recurrence in the bladder wall after brachytherapy and raises questions about prostate cancer biology, brachytherapy technique, and the timing of brachytherapy boost relative to whole pelvic radiotherapy for prostate cancer. Published by Elsevier Inc.

  10. High-dose statin use does not impair aerobic capacity or skeletal muscle function in older adults

    OpenAIRE

    Traustadóttir, Tinna; Stock, Anthoney A.; Harman, S. Mitchell

    2008-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are lipid-lowering agents widely employed for atherosclerosis prevention. HMG-CoA reductase blockade reduces skeletal muscle coenzyme Q10 (CoQ10) levels and mitochondrial respiratory chain activities and may produce mild to severe skeletal muscle myopathy. This study investigated whether high-dose statin treatment would result in measurably decreased exercise capacity in older men and women. Maximal oxygen consumpt...

  11. Thermally stimulated processes in Li and Cu doped alkali fluorides irradiated with electron beams of ultra-high dose

    Science.gov (United States)

    Mamytbekov, Zh K.; Tcherepanov, A. N.; Slesarev, A. I.; Kidibaev, M. M.; Shi, Q.; Ivanovskikh, K. V.; Ivanov, V. Yu; Egamberdieva, A. A.; Shulgin, B. V.

    2017-05-01

    The thermally stimulated luminescence (TSL) and exoemission (TSE) in Li and Cu doped NaF and LiF single crystals irradiated with electron high energy electron beams of (10 MeV, doses 0.75 and 2 MGy) have been investigated. The results obtained reveal important properties that suggest that the crystals have a sufficient radiation stability and sensitivity for high energy electron beams and are promising for application as high-dose detectors of electron radiation.

  12. Thoracic radiotherapy and breath control: current prospects; Radiotherapie thoracique et controle de la respiration: perspectives actuelles

    Energy Technology Data Exchange (ETDEWEB)

    Reboul, F.; Mineur, L.; Paoli, J.B.; Bodez, V.; Oozeer, R.; Garcia, R. [Institut Sainte-Catherine, 84 - Avignon (France)

    2002-11-01

    Three-dimensional conformal radiotherapy (3D CRT) is adversely affected by setup error and organ motion. In thoracic 3D CRT, breathing accounts for most of intra-fraction movements, thus impairing treatment quality. Breath control clearly exhibits dosimetric improvement compared to free breathing, leading to various techniques for gated treatments. We review benefits of different breath control methods -i.e. breath-holding or beam gating, with spirometric, isometric or X-ray respiration sensor- and argument the choice of expiration versus inspiration, with consideration to dosimetric concerns. All steps of 3D-CRT can be improved with breath control. Contouring of organs at risk (OAR) and target are easier and more accurate on breath controlled CT-scans. Inter- and intra-fraction target immobilisation allows smaller margins with better coverage. Lung outcome predictors (NTCP, Mean Dose, LV20, LV30) are improved with breath-control. In addition, inspiration breath control facilitates beam arrangement since it widens the distance between OAR and target, and leaves less lung normal tissue within the high dose region. Last, lung density, as of CT scan, is more accurate, improving dosimetry. Our institutions choice is to use spirometry driven, patient controlled high-inspiration breath-hold; this technique gives excellent immobilization results, with high reproducibility, yet it is easy to implement and costs little extra treatment time. Breath control, whatever technique is employed, proves superior to free breathing treatment when using 3D-CRT. Breath control should then be used whenever possible, and is probably mandatory for IMRT. (authors)

  13. Postoperative radiotherapy for prostate cancer. Evaluation of target motion and treatment techniques (intensity-modulated versus conformal radiotherapy)

    Energy Technology Data Exchange (ETDEWEB)

    Pinkawa, M.; Siluschek, J.; Gagel, B.; Piroth, M.D.; Demirel, C.; Asadpour, B.; Eble, M.J. [Dept. of Radiotherapy, RWTH Aachen (Germany)

    2007-01-15

    Purpose: to determine the extent of target motion in postprostatectomy radiotherapy (RT) and the value of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT). Patients and methods: 20 patients underwent CT scans in supine position with both a full bladder (FB) and an empty bladder (EB) before RT and at three dates during the RT series. Displacements of the CTV (clinical target volume) center of mass and the posterior border were determined. 3D-CRT and IMRT treatment plans were compared regarding homogeneity, conformity, and dose to organs at risk. Results: in the superior-inferior direction, larger displacements were found for EB compared to FB scans; anterior-posterior and right-left displacements were similar. With an initial rectum volume of < 115 cm{sup 3}, 90% of displacements at the posterior border were within a margin of 6 mm. The non-target volume irradiated in the high-dose area doubled in 3D-CRT versus IMRT plans (80 cm{sup 3} vs. 38 cm{sup 3} encompassed by the 95% isodose). Bladder dose was significantly lower with IMRT, but no advantage was found for the integral rectal dose. An adequate bladder filling was paramount to reduce the dose to the bladder. Conclusion: postprostatectomy RT can be recommended with FB due to an improved CTV position consistency and a lower dose to the bladder. With improved non-target tissue and bladder volume sparing, IMRT is an option for dose escalation. However, this analysis did not find an advantage concerning the integral rectal dose with IMRT versus 3D-CRT. (orig.)

  14. Predictors of High-grade Esophagitis After Definitive Three-dimensional Conformal Therapy, Intensity-modulated Radiation Therapy, or Proton Beam Therapy for Non-small cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martel, Mary K.; Mohan, Radhe; Balter, Peter A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Hospitales Universitarios Virgen del Rocio, Seville (Spain); Liu Hongmei; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-11-15

    Introduction: We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Methods and Materials: Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade {>=}3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Results: Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade {>=}3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Conclusions: Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT.

  15. High-dose versus low-dose oxytocin infusion regimens for induction of labour at term.

    Science.gov (United States)

    Budden, Aaron; Chen, Lily J Y; Henry, Amanda

    2014-10-09

    When women require induction of labour, oxytocin is the most common agent used, delivered by an intravenous infusion titrated to uterine contraction strength and frequency. There is debate over the optimum dose regimen and how it impacts on maternal and fetal outcomes, particularly induction to birth interval, mode of birth, and rates of hyperstimulation. Current induction of labour regimens include both high- and low-dose regimens and are delivered by either continuous or pulsed infusions, with both linear and non-linear incremental increases in oxytocin dose. Whilst low-dose protocols bring on contractions safely, their potentially slow induction to birth interval may increase the chance of fetal infection and chorioamnionitis. Conversely, high-dose protocols may cause undue uterine hyperstimulation and fetal distress. To determine the effectiveness and safety of high- versus low-dose oxytocin for induction of labour at term We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014) and the reference lists of relevant papers. Randomised controlled trials and quasi-randomised controlled trials that compared oxytocin protocol for induction of labour for women at term, where high-dose oxytocin is at least 100 mU oxytocin in the first 40 minutes, with increments delivering at least 600 mU in the first two hours, compared with low-dose oxytocin, defined as less than 100 mU oxytocin in the first 40 minutes, and increments delivering less than 600 mU total in the first two hours. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We have included nine trials, involving 2391 women and their babies in this review. Trials were at a moderate to high risk of bias overall.Results of primary outcomes revealed no significant differences in rates of vaginal delivery not achieved within 24 hours (risk ratio (RR) 0.94, 95% confidence interval

  16. Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rheumatoid arthritis.

    Science.gov (United States)

    Rasch, Linda A; van Tuyl, Lilian H D; Lems, Willem F; Boers, Maarten

    2015-01-01

    Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low. © 2014 S. Karger AG, Basel.

  17. Effect of high dose natural ionizing radiation on the immune system of the exposed residents of Ramsar Town, Iran.

    Science.gov (United States)

    Attar, Massoud; Molaie Kondolousy, Yaghob; Khansari, Nemat

    2007-06-01

    Iran is one of several countries that has regions of high dose natural ionizing radiation. Two well-known villages in the suburb of Ramsar Town in the Caspian Sea strip, Taleshmahaleh and Chaparsar, have background radiation that is 13 times higher than normal. This radiation is the result of Radium 226 and Radon gas both of which are highly water soluble. While people living in these regions do not suffer from any major health problems, we decided to study the their immune responses to infection and inflammation in order to determine if their habitat affects their immune defense mechanisms as a way of compensating for their exposure to high dose environmental ionizing radiation. Our results showed that the total serum antioxidant level in the exposed people was significantly lower than the individuals not exposed to high dose natural ionizing radiation. The exposed individuals also had higher lymphocyte-induced IL-4 and IL-10 production, and lower IL-2 and IFN-gamma production. In addition, neutrophil NBT, phagocytosis, and locomotion were higher in the exposed group. In contrast, lymphocyte proliferation in response to PHA was unaffected. We conclude that the immune system of individuals exposed to high dose ionizing radiation has adapted to its environment by shifting from a Type 1 to a Type 2 response to promote anti-inflammation. This may be because inflammatory Type 1 responses generate more free radicals than Type 2 responses, in addition to the free radicals generated as a result of high environmental radiation. Thus, the serum total antioxidant level in the exposed residents was lower than the unexposed group.

  18. Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma.

    Science.gov (United States)

    Werthmann, Paul Georg; Helling, Dieter; Heusser, Peter; Kienle, Gunver Sophia

    2014-07-31

    Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically originates in the salivary glands. Surgical removal can lead to functional loss and psychological distress. Viscum album extract (VAE) is a herbal remedy with dose-dependent cytotoxic, apoptogenic and immunological effects. In some case reports, tumour regression has been observed following high-dose local applications of VAE. An active 88-year-old man with fast-growing ACC of the hard palate refused surgical removal and received high-dose intratumoural injections of VAE (alone) over a 10-month period. The tumour decreased in size, softened and loosened from its surroundings. A biopsy during the course showed inflammation. The patient remained well and without functional limitations during the therapy and follow-up period (5 months). VAE produced no reported side effects. This aged patient exemplifies a satisfying course of ACC under VAE resulting in good quality of life and partial tumour regression. 2014 BMJ Publishing Group Ltd.

  19. Effect of high dose thiamine therapy on activity and molecular ...

    African Journals Online (AJOL)

    Also q-polymerase chain reaction (PCR) was used to determine expression levels of transketolase gene in mononuclear cells. All enrolled Type 2 diabetics had > 40% lower mononuclear transketolase activity as compared to healthy individuals. Thiamine therapy for three months resulted in a 65% significant increase in ...

  20. MR imaging in recurrent pain after back surgery. A comparative study using standard and high doses of gadolinium contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Aakeson, P. [Univ. Hospital, Lund (Sweden). Dept. of Radiology; Annertz, M. [Univ. Hospital, Lund (Sweden). Dept. of Radiology; Kristoffersen, D.T. [Nycomed Imaging AS, Oslo (Norway); Jonsson, E. [Nycomed AB, Stockholm (Sweden); Holtaas, S. [Univ. Hospital, Lund (Sweden). Dept. of Radiology

    1996-11-01

    Purpose: To compare the diagnostic results following injection of (a) a high dose (0.3 mmol/kg b.w.) of gadodiamide injection and (b) the standard dose (0.1 mmol/kg b.w.) of Gd-DTPA, in patients with recurrent symptoms after surgery for lumbar disc herniation. Material and Methods: Twenty patients with recurrent or sustained symptoms after surgery for lumbar disc herniations were examined. MR imaging (0.3 T) was first performed before and after Gd-DTPA at 0.1 mmol/kg b.w., and then within one month (17 patients) or within 3 months (3 patients) before and after gadodiamide injection at 0.3 mmol/kg b.w. The examinations were first evaluated by 2 neuroradiologists blinded to dose but not to patient as the images were presented in pairs. Six months later the same investigators evaluated the examinations again, this time blinded to both dose and patient. Results: At the evaluation in pairs (with the investigators blinded to dose only) the high-dose examinations were considered the most informative (p=0.05). However, at the later evaluation (with the investigators blinded both to dose and patient) no significant difference between high and standard dose was found regarding diagnosis or diagnostic certainty. Conclusion: In this study the high-dose contrast enhancement of MR imaging at 0.3 T did not increase the diagnostic information for differentiating between scar and recurrent hernia. The high-dose images were considered more informative when evaluated in pairs, but gave no additional or different information when evaluated separately. The study also indicated that comparisons in pairs should be interpreted with caution. (orig.).

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Medication error - Inadvertent high dose intradermal cloxacillin induced skin necrosis.

    Science.gov (United States)

    Surendiran, Adithan; Kaku, Mayur V; Adithan, Chandrasekaran

    2012-01-01

    Medication error is one of the important causes of preventable adverse drug reactions. It can occur in the form of administration of a wrong drug, in the wrong dose, to the wrong patient, in an unsuitable dosage form, for the wrong duration or by using an inappropriate route of administration. Intradermal skin testing for cloxacillin hypersensitivity is done at low doses to check for drug allergy. In this report, three patients were given 50 times higher dose of cloxacillin than recommended for skin testing, resulting in pain and necrosis at the site of injection. The error occurred due to wrong dilution of the drug as done by a nursing intern. Some reasons for this could be overtime working, under trained staff, unsupervised nursing interns, complicated and unclear protocols, interpersonal communication gap between health care professionals and also poor availability of ideal resources. Pharmacovigilance centers must alert health care professionals about the significance of reporting medication errors through bulletins and journals.

  3. High-Dose Benzodiazepine Users' Perceptions and Experiences of Anterograde Amnesia

    National Research Council Canada - National Science Library

    Liebrenz, Michael; Schneider, Marcel; Buadze, Anna; Gehring, Marie-Therese; Dube, Anish; Caflisch, Carlo

    2016-01-01

    .... This study was a qualitative exploration of high-dose benzodiazepine users' experiences of anterograde amnesia symptoms and their beliefs about their behavior during the phases of memory impairment...

  4. Provider Knowledge of Trivalent Inactivated and High-Dose Influenza Vaccines

    OpenAIRE

    Tewell, Chad; Wright, Patty W.; Talbot, H. Keipp

    2014-01-01

    The objective of this study was to assess provider knowledge about trivalent inactivated and high dose influenza vaccines. Hence, a 20 item survey was distributed to providers within the Internal Medicine department at an urban academic medical center.

  5. Acute effects of high-dose furosemide on residual renal function in CAPD patients

    NARCIS (Netherlands)

    van Olden, Rudolf W.; Guchelaar, Henk-Jan; Struijk, Dirk G.; Krediet, Raymond T.; Arisz, Lambertus

    2003-01-01

    BACKGROUND: High doses of furosemide can increase urine volume in chronic peritoneal dialysis (CAPD) patients. However, no information is available about effects on urinary solute excretion in relation to residual glomerular filtration rate (GFR), urinary furosemide excretion, and peritoneal solute

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    van den Berkmortel, F; Gidding, C; De Kanter, M; 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 patient was treated with high-dose chemotherapy and autologous stem cell transplantation. She developed a severe treatment-related encephalopathy which affected her quality of life and neurocognitive functioning for the rest of her life. Possible causative factors are discussed and central nervous system toxicity by high-dose chemotherapy in brain tumour patients is reviewed. Case reports on severe central nervous system toxicity have been reported, but data from prospective studies on neurocognitive functioning are not available. These data strongly support a systematic long-term follow-up of brain tumour patients treated with high-dose chemotherapy with emphasis on neurocognitive function tests.

  8. 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)

  9. Exploring the Antitumor Mechanism of High-Dose Cytarabine through the Metabolic Perturbations of Ribonucleotide and Deoxyribonucleotide in Human Promyelocytic Leukemia HL-60 Cells

    Directory of Open Access Journals (Sweden)

    Zheng Li

    2017-03-01

    Full Text Available Despite the apparent clinical benefits of high-dose cytarabine (Ara-C over lower dose Ara-C in acute myeloid leukemia (AML therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60 after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment. Combining metabolic perturbation and cell cycle analysis, we conjectured that, apart from the acknowledged mechanism of Ara-C on tumor inhibition, high-dose Ara-C could present a specific action pathway. It was suggested that the pronounced rise in AMP/ATP ratio induced by high-dose Ara-C can trigger AMP-activated protein kinase (AMPK and subsequently Forkhead Box, class O (FoxO, to promote cell cycle arrest. Moreover, the significant decrease in CDP pool induced by high-dose Ara-C might further accelerate the reduction of dCTP, which then aggravates DNA synthesis disturbance. As a result, all of these alterations led to heightened tumor inhibition. This study provides new insight in the investigation of potential mechanisms in the clinical benefits of high-dose Ara-C in therapy for AML.

  10. Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Shin Young; Lee, Jaetae [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2010-06-15

    Radioactive iodine ({sup 131}I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, {sup 131}I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the {sup 131}I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of {sup 131}I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of {sup 131}I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with {sup 131}I-induced sialadenitis that is unresponsive to medical treatment.

  11. Cation disorder in high dose neutron irradiated spinel

    Energy Technology Data Exchange (ETDEWEB)

    Sickafus, K.E.; Larson, A.C.; Yu, N.; Nastasi, M. [Los Alamos National Lab., NM (United States); Hollenberg, G.W.; Garner, F.A. [Pacific Northwest Lab., Richland, WA (United States); Bradt, R.C. [Univ. of Nevada, Reno, NV (United States)

    1994-06-01

    The crystal structures of MgAl{sub 2}O{sub 4} spinel single crystals irradiated to high neutron fluences (>5{center_dot}10{sup 26} n/m{sup 2} (E{sub n}>0.1 MeV)), were examined by neutron diffraction. Crystal structure refinement of the highest dose sample indicated that the average scattering strength of the tetrahedral crystal sites decreased by {approximately}20% while increasing by {approximately}8% on octahedral sites. Since the neutron scattering length for Mg is considerably larger than for Al, this result is consistent with site exchange between Mg{sup 2+} ions on tetrahedral sites and Al{sup 3+} ions on octahedral sites. Least squares refinements also indicated that in all irradiated samples, at least 35% of Mg{sup 2+} and Al{sup 3+} ions in the crystal experienced disordering replacements. This retained dpa on the cation sublattices is the largest retained damage ever measured in an irradiated spinel material.

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

    OpenAIRE

    Tülay Kaçar Güvel; Sezer Özkan; Müge Öner Tamam

    2014-01-01

    Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 fe...

  13. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement

    DEFF Research Database (Denmark)

    Jørgensen, C C; Pitter, F T; Kehlet, H

    2017-01-01

    Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation....... Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications....

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

    OpenAIRE

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

    2011-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered ...

  15. High-dose ambroxol reduces pulmonary complications in patients with acute cervical spinal cord injury after surgery.

    Science.gov (United States)

    Li, Qiang; Yao, Gaiqi; Zhu, Xi

    2012-04-01

    Ambroxol has a very high affinity for lung tissues; its concentration is approximately 20 times higher in the lung than in the serum. We aimed to evaluate the effectiveness of high-dose ambroxol (990 mg/day) in the improvement of oxygenation and prevention of postoperative respiratory complications in the patients with acute cervical spinal cord injury (CSCI). A total of 61 acute CSCI patients admitted to the Intensive Care Unit (ICU) of our hospital between January 2009 and June 2011 were included in the study. They were graded as ASIA A and ASIA B according to the classification of the American Spinal Injury Association (ASIA) and were randomly divided into two groups: one group received intravenous ambroxol at 990 mg/day for 5 consecutive days after operation; the other group treated without ambroxol served as control. The results of arterial blood gas analysis on postoperative day 3 and 5 and occurrence of pulmonary complications within 5 days after operation were evaluated. The group treated with high-dose ambroxol showed a lower rate of postoperative pneumonia and hypoxemia within 5 days after operation. On the 3rd and 5th days, the oxygenation index in the high-dose ambroxol group (291.02 ± 34.96 and 301.28 ± 37.69) was significantly higher than in the control group (230.08 ± 26.25 and 253.82 ± 26.26), with significant differences between the two groups (P = 0.045 and 0.041). Administration of high-dose ambroxol should be considered as an alternative and effective approach to reduce the postoperative respiratory complications and improve the oxygenation status in acute CSCI patients.

  16. Albuminuria Reduction after High Dose of Vitamin D in Patients with Type 1 Diabetes Mellitus: A Pilot Study

    Directory of Open Access Journals (Sweden)

    João Soares Felício

    2017-08-01

    Full Text Available BackgroundSome studies suggest an association between diabetic kidney disease (DKD and vitamin D (VD, but there is no data about the effect of high dose of VD on DKD in type 1 diabetes mellitus (T1DM. Our pilot study aims to evaluate albuminuria reduction in patients with T1DM supplemented with high dose of VD.Methods22 patients received doses of 4,000 and 10,000 IU/day of cholecalciferol for 12 weeks according to patient’s previous VD levels. They were submitted to continuous glucose monitoring system, 24 hours ambulatory blood pressure monitoring and urine albumin-to-creatinine ratio before and after VD supplementation.ResultsThere was a reduction of DKD prevalence at the end of the study (68 vs 32%; p = 0.05, with no changes on insulin doses, glycated hemoglobin, glycemic variability and blood pressure values. A correlation between percentage variation of VD levels (ΔVD and albuminuria at the end of the study was presented (r = −0.5; p < 0.05. Among T1DM patients with DKD at the beginning of the study, 8/13 (62% had their DKD stage improved, while the other five ones (38% showed no changes (p < 0.05.ConclusionOur pilot study suggests an association between VD high dose supplementation, lower prevalence and improvement in stages of DKD in T1DM.

  17. A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Mizumoto, Kazuhiro; Qian, Li-Wu; Zhang, Li.; Nagai, Eishi; Kura, Shinobu; Tanaka, Masao [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences

    2002-03-01

    The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gamma-ray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluorescence intensity of propidium iodide before and after a digitonin treatment. The sensitizing effect of PR-350 on cell killing by high-dose irradiation was confirmed by time-course, dose-dependency, and microscopic observations. In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry. The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer. (author)

  18. Numerical reconstruction of high dose rate zones due to the Fukushima Dai-ichi Nuclear Power Plant accident.

    Science.gov (United States)

    Katata, Genki; Terada, Hiroaki; Nagai, Haruyasu; Chino, Masamichi

    2012-09-01

    To understand how the high dose rate zones were created during the Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident on March 2011, the atmospheric dispersion of radionuclides during the period from 15 to 17 March was reproduced by using a computer-based nuclear emergency response system, WSPEEDI-II. With use of limited environmental monitoring data, prediction accuracy of meteorological and radiological fields by the system was improved to obtain best estimates of release rates, radiation dose maps, and plume movements. A large part of current high dose rate zones in Fukushima was explained by simulated surface deposition of radionuclides due to major releases of radionuclides on 15 March. In the simulation, the highest dose rate zones to the northwest of FNPP1 were created by a significant deposition of radionuclides discharged from FNPP1 during the afternoon. The results indicate that two environmental factors, i.e., rainfall and topography, strongly affected the spatial patterns of surface deposition of radionuclides. The wet deposition due to rainfall particularly played an important role in the formation of wide and heterogeneous distributions of high dose rate zones. The simulation also demonstrated that the radioactive plume flowed along the valleys to its leeward, which can expand the areas of a large amount of surface deposition in complex topography. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment.

    Science.gov (United States)

    Sassoon, Catherine Sh; Caiozzo, Vincent J

    2009-01-01

    Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible.

  20. Influence of long-term, high-dose dexamethasone administration on proliferation and apoptosis in porcine hepatocytes.

    Science.gov (United States)

    Mikiewicz, Mateusz; Otrocka-Domagała, Iwona; Paździor-Czapula, Katarzyna; Rotkiewicz, Tadeusz

    2017-06-01

    The aim of this study was to examine the influence of long-term, high-dose dexamethasone administration on the liver, with particular emphasis on hepatocyte proliferation and apoptosis, using a swine model. The study included 48 large, female Polish breed pigs aged 3months (weighing ca. 30kg) divided into groups I (control; n=24) and II (dexamethasone; n=24) that receiving intra-muscular injections of monosodium phosphate dexamethasone for 29days. The pigs were euthanized on days subsequent to the experiment. Immediately after the euthanasia, the pig livers were sampled, fixed, and processed routinely for histopathology, histochemistry, and immunohistochemistry (for proliferating cell nuclear antigen, Bcl-2, and caspase-3). Apoptosis was visualized by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL). Dexamethasone administration gradually caused hepatocyte glycogen degeneration and finally lipid degeneration, accompanied by sinusoid and central vein dilatation and nuclear chromatin condensation. The proliferating cell nuclear antigen index, mean number of argyrophilic nucleolar organizer regions and proliferation index of argyrophilic nucleolar organizer regions were lower, while Bcl-2 expression was higher in group II compared with group I. The results from this study suggest that safe high-dose dexamethasone administration time is difficult to establish. Long-term, high-dose dexamethasone administration can cause pronounced morphological changes in hepatocytes by diminishing their transcriptional and proliferation activity but also protects them from apoptosis by potentially affecting Bcl-2 expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Effects of High-Dose Capsaicin on TMD Subjects

    Science.gov (United States)

    Campbell, B.K.; Fillingim, R.B.; Lee, S.; Brao, R.; Price, D.D.; Neubert, J.K.

    2016-01-01

    relatively safe, simple, and effective treatment for patients with TMD. Knowledge Transfer Statement: This study evaluated a novel topical capsaicin therapy for reducing orofacial pain. The results of this study can be used to provide another treatment option for patients with TMD. PMID:28879245

  2. Radiochromic and radiofluorogenic 3D solid polymer dosimeter: initial results for high doses

    DEFF Research Database (Denmark)

    Bernal Zamorano, Maria del Rocio; Sanders, Nicolai Højer; Lindvold, Lars René

    2017-01-01

    The complexity of dose distributions has increased with the advent of intensity modulated radiation therapy (IMRT). For that reason, experimental measurements using 3D dosimeters with high spatial resolution are required to check the delivered dose. In this study a new 3D solid polymer dosimeter...... with absorbance and fluorescence responses to radiation is presented. Measuring fluorescence instead of absorbance improves the spatial resolution and eases the read out of the dosimeter. The proposed dosimeter is tissue-equivalent and can be moulded in any shape by a controllable and fast photopolymerization...

  3. [Buprenorphine abuse: high dose intravenous administration of buprenorphine].

    Science.gov (United States)

    Varescon, I; Vidal-Trécan, G; Nabet, N; Boissonnas, A

    2002-01-01

    Drogues et des Toxicomanies (OFDT). Of the 779 consecutive drug addicts interviewed, 770 completed the questionnaire. The study has shown that the majority of subjects were male (77.2%), mean age was 31.3 (SD: 5.98). Most of them were unmarried (67.5%). They had no real employment (56.5%). The mean age at the first use opiate was 19.5 (SD: 4.5). The mean age at the first heroin injection was 20.7 (SD: 4.6). At the time of interview, most of drugs addict used more than two types of drugs (42.6%). Many associations with buprenorphine are described particularly associations to alcohol (41.2%), benzodiazepines (40%), cocaine (12.4%), heroin (7.8%), crack (7.2%); most of these subjects getting buprenorphine without any medical prescription. Most drug addicts had asked themselves for using buprenorphine (61.0%). Near fifty per cent (49.5%) injected buprenorphine. Among them, 39.6% injected this substance the first time they used it. Curiosity (72.8%), need for injection (69.0%), sensation seeking (49.0%) were reasons given by drug addicts for buprenorphine injection. Others reasons were given: an inadequate dosage of sublingual buprenorphine, to find buprenorphine in black market. Buprenorphine injection took place in the secure environment (57.5%). Drug addicts were not alone when they injected (53.6%). The introducer was an buprenorphine user (57%). The first buprenorphine injection sensation was not pleasant (61%), although injection of buprenorphine is usually performed by 80% of them. However, 93% had been informed that buprenorphine injection was contra-indicated. Since six years, many French patients have received a treatment for opiate addiction. High dosage buprenorphine is actually the principal treatment for substitution medication in France. Some misappropriations and wrong uses have been seen, the most frequent and sever being using tablets for injections. The prevalence of buprenorphine injection is high among drug addicts. The results of the study show that the

  4. Very high frequency of fragility fractures associated with high-dose glucocorticoids in postmenopausal women: A retrospective study

    Directory of Open Access Journals (Sweden)

    Goichi Kageyama

    2017-06-01

    Fragility fractures associated with high-dose glucocorticoid therapy are common among postmenopausal women. Extreme care should be taken especially for postmenopausal women when high-dose glucocorticoid therapy is required.

  5. Monte Carlo dose calculations for high-dose-rate brachytherapy using GPU-accelerated processing.

    Science.gov (United States)

    Tian, Z; Zhang, M; Hrycushko, B; Albuquerque, K; Jiang, S B; Jia, X

    2016-01-01

    Current clinical brachytherapy dose calculations are typically based on the Association of American Physicists in Medicine Task Group report 43 (TG-43) guidelines, which approximate patient geometry as an infinitely large water phantom. This ignores patient and applicator geometries and heterogeneities, causing dosimetric errors. Although Monte Carlo (MC) dose calculation is commonly recognized as the most accurate method, its associated long computational time is a major bottleneck for routine clinical applications. This article presents our recent developments of a fast MC dose calculation package for high-dose-rate (HDR) brachytherapy, gBMC, built on a graphics processing unit (GPU) platform. gBMC-simulated photon transport in voxelized geometry with physics in (192)Ir HDR brachytherapy energy range considered. A phase-space file was used as a source model. GPU-based parallel computation was used to simultaneously transport multiple photons, one on a GPU thread. We validated gBMC by comparing the dose calculation results in water with that computed TG-43. We also studied heterogeneous phantom cases and a patient case and compared gBMC results with Acuros BV results. Radial dose function in water calculated by gBMC showed GPU-based MC dose calculation package, gBMC, for HDR brachytherapy make it attractive for clinical applications. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  6. A PROSPECTIVE RANDOMIZED TRIAL COMPARING SEQUENTIAL GANCICLOVIR-HIGH DOSE ACYCLOVIR TO HIGH DOSE ACYCLOVIR FOR PREVENTION OF CYTOMEGALOVIRUS DISEASE IN ADULT LIVER TRANSPLANT RECIPIENTS

    Science.gov (United States)

    Martin, Maureen; Mañez, Rafael; Linden, Peter; Estores, David; Torre-Cisneros, Julian; Kusne, Shimon; Ondick, Linnea; Ptachcinski, Richard; Irish, William; Kisor, David; Felser, Ilene; Rinaldo, Charles; Stieber, Andrei; Fung, John; Ho, Monto; Simmons, Richard; Starzl, Thomas

    2010-01-01

    Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07–6.56; Pganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05–12.75; P=0.000l). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P=0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P=0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population. PMID:7940710

  7. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Cox, Brett W., E-mail: coxb@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jackson, Andrew; Hunt, Margie [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark [Department of Surgery (Neurosurgical Division), Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2012-08-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade {>=}3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade {>=}3 toxicity at V12 = 3.78 cm{sup 3} (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm{sup 3} (RR 13, P=.0013), V20 = 0.11 cm{sup 3} (RR 6, P=0.01), and V22 = 0.0 cm{sup 3} (RR 13, P=.0013). The median split for D2.5 cm{sup 3} (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm{sup 3}. One hundred percent (n = 7) of grade {>=}4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade {>=}3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with

  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. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Stein, M S; Liu, Y; Gray, O M; Baker, J E; Kolbe, S C; Ditchfield, M R; Egan, G F; Mitchell, P J; Harrison, L C; Butzkueven, H; Kilpatrick, T J

    2011-10-25

    Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.

  10. High-Dose Aspirin is Associated with Anemia and Does Not Confer Benefit to Disease Outcomes in Kawasaki Disease.

    Directory of Open Access Journals (Sweden)

    Ho-Chang Kuo

    hepcidin and a delayed decrease in hepcidin level after receiving IVIG in group 1 (p = 0.04 and 0.02, respectively.These results provide evidence demonstrating that high-dose aspirin in the acute phase of KD does not confer any benefit with regards to inflammation and it does not appear to improve treatment outcomes. Therefore, high-dose aspirin is unnecessary in acute phase KD.

  11. Fabrication of a flexible polycarbonate/porphyrin film dosimeter for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Feizi, Shahzad [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of). Radiation Application Research School

    2017-10-01

    Dyed polycarbonate (PC) Radiochromic films with 20 μm thickness were prepared by casting of organic solution of PC containing 0.5 wt.% tetrakis (pentafluorophenyl) porphyrin (TPPF{sub 20}) on a glass petri dish. Characterization of the film as a routine dosimeter was studied. On subjecting PC/TPPF{sub 20} film dosimeter to gamma radiation, a gradual decrease in the color of films was observed. The sensitivity of these films and the linearity of dose-response curves were studied under {sup 60}Co γ-rays expose in dose range of 0-100 kGy. The results were compared with the commercial and non-commercial dosimeters. Experimental parameters including humidity, temperature and pre-irradiation (shelf-life) and post-irradiation storage in dark and in indirect sunlight were examined. The maximum absorbance of soret band of TPPF{sub 20} had a bathochromic shift and appeared at 414 nm which remained intact in the investigated dose range. The dyed films characteristics were found to be stable enough in media with high degrees of temperature and humidity. The results indicate that radiation induced decoloration of PC/TPPF{sub 20} films can be reliably used in high dose dosimetry.

  12. Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

    Science.gov (United States)

    O'Connell, Thomas F; Carpenter, Patrick S; Caballero, Nadia; Putnam, Andrew J; Steere, Joshua T; Matz, Gregory J; Foecking, Eileen M

    2014-01-01

    Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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. © The Author(s) 2016.

  16. Nonlinear dynamic characteristics of electroencephalography in a high-dose pilocarpine-induced status epilepticus model.

    Science.gov (United States)

    Jung, Ki-Young; Kim, Jae-Moon; Kim, Dong Wook

    2003-05-01

    We applied nonlinear analysis to the results of electroencephalography (EEG) in a pilocarpine-induced status epilepticus (SE) model to characterize nonlinear dynamics according to SE phase. Nine male Sprague-Dawley rats weighing 150-250 g were used. EEG was classified into four phases in addition to baseline EEG (phase 0) as follows: phase 1, discrete seizures; phase 2, continuous ictal discharges; phase 3, early periodic epileptiform discharges (PEDs); and phase 4, late PEDs. High-dose diazepam was administered at phase 4 to terminate SE. Diazepam controlled SE in five rats (group 1), while it failed to stop SE in the rest (group 2). The presence of nonlinearity was determined by time reversal asymmetry statistics using a surrogate data set. The correlation dimension (D(2)) was calculated to characterize the dimensional complexity of each phase of SE. EEG of later phases of SE showed strong nonlinearity, whereas no or only weak nonlinearity was noted at phases 0 and 1. D(2) showed the highest value at phase 0 and decreased progressively. Considering therapeutic responsiveness, D(2) showed significant differences between the two groups at phases 2 and 4. These results suggest that nonlinear dynamic changes in the later SE phases reflect underlying pathophysiological changes that contribute to determining therapeutic responsiveness in the pilocarpine-induced SE model.

  17. Verification of SuperMC for simulation of a high-dose-rate brachytherapy source

    Science.gov (United States)

    Naeem, Hamza; Wasaye, Muhammad Abdul; Chen, Chaobin; Zheng, Huaqing; Hao, Lijuan

    2017-06-01

    In this study, SuperMC (Super Monte Carlo simulation program for nuclear and radiation simulation) was tested and verified for simulation of a high-dose-rate brachytherapy source. The Monte Carlo simulation includes calculations of the air kerma strength, dose rate constant, radial dose function and anisotropy function as recommended by the American Association of Physicists in Medicine (AAPM) in Task Group reports 43 and 43U1 (TG-43, TG-43U1). The air kerma strength, dose rate constant, radial dose function and anisotropy function were compared with previously published Monte Carlo simulation results and experimental data. The calculated parameters were found to be in good agreement with published Monte Carlo and measured data. The value obtained from the SuperMC simulation for the air kerma strength was 9.779 × 10-8 U·Bq-1 and the dose rate constant was 1.1092 ± 0.02% cGy·h-1·U-1. The time to transport 5 × 107 photons showed SuperMC to be relatively faster than MCNP. The results show that SuperMC can be used for fast and accurate simulations and dosimetric calculations of HDR brachytherapy sources.

  18. 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)

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

    Science.gov (United States)

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

    2017-01-01

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

  20. Single high dose gentamicin for perioperative prophylaxis in orthopedic surgery: Evaluation of nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Yanina Dubrovskaya

    2015-10-01

    Full Text Available Background: Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group to those where it was not included (Control Group for perioperative prophylaxis and evaluated risk factors for nephrotoxicity. Methods: Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE criteria. Results: Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in Control Group: hip = 980, spine = 902, knee = 705, patients’ body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and Control Group. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in Control Group, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in Control Group, p = 0.49. In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25–28.97, p = 0.001, knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9–9.48, p = 0.0005 and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13–3.35, p = 0.016. Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97–2.35, p = 0.07. Conclusion: In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control

  1. In vivo measurements for high dose rate brachytherapy with optically stimulated luminescent dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Renu; Jursinic, Paul A. [Department of Radiation Oncology, West Michigan Cancer Center, 200 North Park Street, Kalamazoo, Michigan 49007 (United States)

    2013-07-15

    Purpose: To show the feasibility of clinical implementation of OSLDs for high dose-rate (HDR) in vivo dosimetry for gynecological and breast patients. To discuss how the OSLDs were characterized for an Ir-192 source, taking into account low gamma energy and high dose gradients. To describe differences caused by the dose calculation formalism of treatment planning systems.Methods: OSLD irradiations were made using the GammaMedplus iX Ir-192 HDR, Varian Medical Systems, Milpitas, CA. BrachyVision versions 8.9 and 10.0, Varian Medical Systems, Milpitas, CA, were used for calculations. Version 8.9 used the TG-43 algorithm and version 10.0 used the Acuros algorithm. The OSLDs (InLight Nanodots) were characterized for Ir-192. Various phantoms were created to assess calculated and measured doses and the angular dependence and self-absorption of the Nanodots. Following successful phantom measurements, patient measurements for gynecological patients and breast cancer patients were made and compared to calculated doses.Results: The OSLD sensitivity to Ir-192 compared to 6 MV is between 1.10 and 1.25, is unique to each detector, and changes with accumulated dose. The measured doses were compared to those predicted by the treatment planning system and found to be in agreement for the gynecological patients to within measurement uncertainty. The range of differences between the measured and Acuros calculated doses was -10%-14%. For the breast patients, there was a discrepancy of -4.4% to +6.5% between the measured and calculated doses at the skin surface when the Acuros algorithm was used. These differences were within experimental uncertainty due to (random) error in the location of the detector with respect to the treatment catheter.Conclusions: OSLDs can be successfully used for HDR in vivo dosimetry. However, for the measurements to be meaningful one must account for the angular dependence, volume-averaging, and the greater sensitivity to Ir-192 gamma rays than to 6 MV x

  2. High-dose tranexamic acid reduces intraoperative and postoperative blood loss in posterior lumbar interbody fusion.

    Science.gov (United States)

    Kushioka, Junichi; Yamashita, Tomoya; Okuda, Shinya; Maeno, Takafumi; Matsumoto, Tomiya; Yamasaki, Ryoji; Iwasaki, Motoki

    2017-03-01

    OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. Previous studies included limitations in terms of different TXA dose regimens, different levels and numbers of fused segments, and different surgical techniques. Therefore, the authors decided to strictly limit TXA dose regimens, surgical techniques, and fused segments in this study. There have been no reports of using TXA for prevention of intraoperative and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The purpose of the study was to evaluate the efficacy of high-dose TXA in reducing blood loss and its safety during single-level PLIF. METHODS The study was a nonrandomized, case-controlled trial. Sixty consecutive patients underwent single-level PLIF at a single institution. The first 30 patients did not receive TXA. The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the skin incision was performed and received the same dose again 16 hours after the surgery. Intra- and postoperative blood loss was compared between the groups. RESULTS There were no statistically significant differences in preoperative parameters of age, sex, body mass index, preoperative diagnosis, or operating time. The TXA group experienced significantly less intraoperative blood loss (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA group also had significantly less postoperative blood loss over 40 hours (mean 321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss in the TXA group (mean 574 ml) was significantly lower than in the control group (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in the TXA group was consistently significantly lower. There were no perioperative complications, including thromboembolic events. CONCLUSIONS High-dose TXA significantly reduced both intra

  3. Use of high-dose nandrolone aggravates septic shock in a mouse model

    Directory of Open Access Journals (Sweden)

    Che Lin

    2011-06-01

    Full Text Available Nandrolone, an anabolic-androgenic steroid, is widely misused by athletes who wish to rapidly increase muscle mass and performance. An increasing number of reports have indicated that nandrolone may affect and modulate the immune system. This study aimed to investigate the effects of nandrolone on septic shock-caused immune responses and the cellular mechanism of action using a sepsis murine model. Before septic shock induction, BALB/c mice were given a high dose of nandrolone or peanut oil only. After septic shock induction, mice were sacrificed at different time points. Their blood and tissue specimens were analyzed. It was found that the high-dose nandrolone group had significantly increased mortality compared with the control group (p<0.001. The serum malondialdehyde level was significantly increased in the high-dose group compared with the control group. Animals administered a high dose of nandrolone had significantly increased hepatic tumor necrosis factor-α or splenic interferon-γ at 0 and 6 hours. In lung tissue, insulin-like growth factor-1, insulin-like growth factor binding proteins (IGFBPs and insulin-like growth factor-1 receptor, and IGFBP1 and IGFBP2 mRNA expression were increased in the high-dose nandrolone group at 6 hours. Nandrolone abuse may hasten the death of patients with septic shock and may aggravate septic shock in mice.

  4. 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.

  5. Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection.

    Science.gov (United States)

    Zhou, Kai; Wang, Jing; Li, An; Zhao, Wenming; Wang, Dongfang; Zhang, Wei; Yan, Jinghua; Gao, George Fu; Liu, Wenjun; Fang, Min

    2016-02-15

    It is generally unclear what roles NK cells play during influenza virus infection with regard to different host genetic backgrounds. In this study, we show that in six inbred mouse strains, NK cells play an important protective role only in 129 mice during high-dose influenza A H1N1 virus infection. Swift and strong NK cell responses efficiently control early pulmonary viral replication in 129 mice, providing survival privilege. In addition, we identified that early activation of TLRs and RIG-I signaling in 129 mice resulted in quick production of type 1 IFNs and inflammatory cytokines, which are important reasons for the swift kinetics of NK cell responses post influenza virus infection. Thus, under different microenvironments, NK cells play differential roles against viral infections. The kinetics and magnitude of NK cell responses correlate with the distinct roles that NK cells play against influenza virus infections. Thus, our works further our understandings about the complex role of NK cells during influenza virus infection. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. High-Dose Fluoride Induces Apoptosis and Inhibits Ameloblastin Secretion in Primary Rat Ameloblast.

    Science.gov (United States)

    Wang, Lin; Zhu, Yong; Wang, Danyang

    2016-12-01

    The objectives of this study are to establish the in vitro culture system for rat primary ameloblast and to investigate the effects of fluoride on cell viability, apoptosis, and ameloblastin (AMBN) secretion of primary rat ameloblast in vitro. Ameloblast was isolated from the tooth germ of the maxillomandibular molar and cultured in vitro. Cells were treated with NaF at 0.4, 0.8, 1.6, 3.2, and 6.4 mM for 24, 48, and 72 h, respectively. Cell viability was measured by MTT assay and apoptosis was tested by flow cytometry. The activation of Fas ligand (FasL)/Fas pathway was detected using immunoblotting for FasL, Fas, cleaved caspase-8, cleaved caspase-3, and cleaved PARP. Secretion of AMBN in culture medium was measured using ELISA. Primary rat ameloblast was successfully isolated and cultured. The effects of low-dose fluoride on cell viability were bi-phasic, while high-dose fluoride resulted in decreased cell viability uniformly. Fluoride induced ameloblast apoptosis via activation of FasL/Fas signaling pathway and diminished secretion of AMBN by ameloblast. Fluoride could decrease ameloblast viability, induce ameloblast apoptosis via activating FasL/Fas signaling pathway, and reduce AMBN secretion.

  7. 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.

  8. Solid ferrous ammonium sulfate as a dosimeter at low temperatures and high doses

    Energy Technology Data Exchange (ETDEWEB)

    Juarez-calderon, J.M.; Ramos B, S.; Negron M, A. [Mexico Univ. Nacional Autonoma, Instituto de Ciencias Nucleares (Mexico)

    2006-07-01

    This paper presents the results obtained from a study of the radiation induced oxidation of crystalline ferrous ammonium sulfate with gamma rays at 295 K, 263 K and 77 K and doses from 0 to 300 kGy. The radiation induced decomposition of ferrous ammonium sulfate has been studied by the dissolution of the irradiated salt in 0,8 N sulfuric acid. The main product is ferric ion (Fe{sup 3+}) and its molar concentration was determined spectrophotometrically in the UV region at 304 nm. The optical density values showed a linear dependence with dose, indicating that the data obtained might be used to create a calibrating curve. Color in irradiated salt changes from blue to green, yellow and orange according to the absorbed dose. The accuracy and the reproducibility of the system were tested. In addition, some other characteristics make possible the use of this system as a dosimeter, similar to Fricke chemical dosimeter, for studies and works at low temperatures and high doses. (authors)

  9. Fractionated high-dose-rate brachytherapy in the management of uterine cervical cancer.

    Science.gov (United States)

    Park, Hee-Chul; Suh, Chang Ok; Kim, Gwi Eon

    2002-12-01

    It is well known that intracavitary radiotherapy (ICR), either alone or in combination with external-beam radiotherapy (EBRT) is an essential component of the radiation treatment of uterine cervical cancer. Although low-dose-rate (LDR) brachytherapy has been successfully applied to the management of such patients, several radiation oncologists have experience of using high-dose-rate (HDR) brachytherapy with promising clinical results over the past 4 decades. However, there has been a considerable reluctance by radiation oncologists and gynecologists in North America to employ the HDR remote afterloading technique instead of the more firmly established LDR treatment modality. In contrast, the HDR-ICR system is rapidly gaining acceptance in Korea since the introduction of the Ralstron, remotely controlled afterloading system using HDR Co-60 sources, at the Yonsei Cancer Center in 1979. According to brachytherapy statistics reported by the Korean Society of Therapeutic Radiology and Oncology, in 1997, brachytherapy was performed upon 1,758 Korean patients with uterine cervical cancer, of whom approximately 83% received HDR brachytherapy. In this review, we present our experiences of HDR-ICR for the treatment of uterine cervical cancer. In addition, we discuss the controversial points, which are raised by those considering the use of HDR-ICR for uterine cervical cancer; these issues include physical and radiobiological considerations, and the prospect of future technical improvements.

  10. Prognostic factors in squamous cell lip carcinoma treated with high-dose-rate brachytherapy.

    Science.gov (United States)

    Guinot, Jose-Luis; Arribas, Leoncio; Vendrell, Juan B; Santos, Miguel; Tortajada, Maria I; Mut, Alejandro; Cruz, Julia; Mengual, Jose L; Chust, Maria L

    2014-12-01

    The purpose of this study was for us to present our analysis of the results and prognostic factors in squamous lip carcinoma treated with high-dose-rate (HDR) brachytherapy. From 1999 to 2010, 102 patients were treated with HDR-brachytherapy, 54 with T1, 33 with T2, and 15 with T4. Eight cases were N+. Twenty-one patients were treated with surgery plus brachytherapy because of close/positive margins. Nine fractions of 5 Gy were given over 5 days in 67% of the patients. Elective neck treatment was performed in 23 cases. The 10-year actuarial local control was 94.6%, nodal regional control was 88.6%, disease-free survival was 84.6%, and cause-specific survival was 93.2%. In the univariate analysis, T4 tumors had higher risk of local failure and T2 of regional relapse. In the multivariate analysis, skin involvement was the only significant factor for tumor progression. HDR-brachytherapy yields excellent local control rates. Skin involvement increases the risk of local and cervical recurrence. Elective neck treatment should be done in T2 to T4 tumors or with skin or commissure involvement. © 2014 Wiley Periodicals, Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  12. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial.

    Science.gov (United States)

    Wu, Yvonne W; Mathur, Amit M; Chang, Taeun; McKinstry, Robert C; Mulkey, Sarah B; Mayock, Dennis E; Van Meurs, Krisa P; Rogers, Elizabeth E; Gonzalez, Fernando F; Comstock, Bryan A; Juul, Sandra E; Msall, Michael E; Bonifacio, Sonia L; Glass, Hannah C; Massaro, An N; Dong, Lawrence; Tan, Katherine W; Heagerty, Patrick J; Ballard, Roberta A

    2016-06-01

    To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy. In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epo-treated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05). High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function. Copyright © 2016 by the American Academy of Pediatrics.

  13. c-Fos immunoreactivity of neural cells in intoxication due to high-dose methamphetamine.

    Science.gov (United States)

    Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Shibaike, Yoshinori; Yoshinari, Haruhiko; Tee, Jia Wei; Iwachidou, Nobuhisa; Miyamoto, Osamu

    2013-01-01

    Methamphetamine (METH) is a powerful and toxic psychostimulant that is abused worldwide. Although many studies of its toxic functions have been done on animals and humans, the mechanism is still poorly understood. In addition, the doses of METH examined have often been low. Here, we investigated the effects of intoxication due to administration of 20 mg/kg METH on neuronal activity. The mice showed hyperthermia and stereotyped behavior during 60 min after injection. We examined plasma stress hormone levels, which indicated that exposure to METH stimulated the hypothalamic-pituitary-adrenal (HPA) axis and caused release of stress hormones soon after injection. The maximum levels of adrenocorticotropic hormone and corticosterone occurred 10 and 60 min, respectively, after injection. We examined c-Fos protein in 16 different brain regions at 60 min post injection to identify potential brain regions subject to the stimulant effect. Nine regions, including the anterior hypothalamic area, medial preoptic area, lateral hypothalamic area, paraventricular thalamic nucleus, lateral anterior hypothalamic nucleus, lateral septum, striatum, nucleus accumbens, and amygdala, showed a significant increase in c-Fos expression, while the other seven regions did not. These results indicate that responsive neurons in the regions containing c-Fos immunoreactivity (Fos-IR) may undergo cellular reaction to high-dose METH administration. The present study provides support for a relationship among hyperthermia, the HPA axis and neuronal activities in limited brain regions on exposure to 20 mg/kg METH.

  14. [AIDS-related eosinophilic folliculitis. Efficacy of high dose topical corticotherapy].

    Science.gov (United States)

    Grange, F; Schoenlaub, P; Tortel, M C; Peter, B; Audhuy, B; Guillaume, J C

    1996-01-01

    A chronic pruriginous eruption of eosinophil-rich follicular papules and pustules is observed in AIDS patients. The pathogenesis of this disease, termed eosinophil folliculitis, is poorly understood and treatment is debated. A 30-year-old woman with AIDS developed highly pruriginous lesions of 5 month duration localized on the face, the trunk and upper limbs. There were papulo-pustules and excoriated papules. The elementary lesion was a follicular pustula. The eosinophil count was normal. The pathology examination revealed a rich eosinophil infiltration around the hair follicles and sebaceous glands as well as follicular spongiosis. Search for demodex, pityrosporons and a large number of infectious agents was negative. Oral minocyclin was uneffective. Local high-dose corticosteroids produced a remarkable effect and led to complete remission in 9 months. Most cases of eosinophil folliculitis associated with AIDS have been reported in men, but rarely in Europe. The remarkable efficacy of the local corticosteroid in this case was exceptional. This condition could result from inappropriate inflammatory reaction in AIDS induced by various factors including demodex and pityrosporon. Several therapeutic approaches have been proposed to eradicate the triggering factors and others to modify the immune response. The exceptional response to the short local treatment with corticosteroids would suggest that this approach could be proposed as first intention treatment in eosinophil folliculitis associated with AIDS.

  15. 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. © 2014 Japanese Teratology Society.

  16. Preoperative high dose rate brachytherapy for clinical stage II endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Alexander Olawaiye

    2011-07-01

    Full Text Available Purpose: We sought to evaluate pathological response, tolerance, and outcome after preoperative (neoadjuvant high dose rate brachytherapy in a small series of patients with clinical stage II endometrial carcinoma, and to evaluate a dose and fractionation protocol for this treatment. Material and methods: Twelve women diagnosed with clinical stage II endometrial carcinoma from 1999-2010 were treated with preoperative radiation therapy. Their medical charts were retrospectively analyzed for HDR treatment regimen, pathological response, and longitudinal outcomes. Radiation doses were normalized to a biologically equi­valent dose of 2 Gy per fraction (EQD2. Results: Two patients had complete pathological response to neoadjuvant therapy; five more had only microscopic residual disease at the time of surgery. At a median follow up of 37 months (1-91 months, one patient has developed recurrence at the vaginal apex six months after completing initial therapy, while another developed a lung recurrence at 28 months. Two-year disease-free and cause-specific survivals were 88% and 100%, respectively. Conclusions: Our small study shows that the HDR fractionation schedule, as done in our series for preoperative radiation therapy for clinical stage II endometrial cancer, is well tolerated and would be an option for patients treated with neoadjuvant radiation therapy.

  17. Characteristics of LiF:Mg,Cu,P thermoluminescence at ultra-high dose range

    Energy Technology Data Exchange (ETDEWEB)

    Bilski, P. [Institute of Nuclear Physics (IFJ), Krakow (Poland)], E-mail: pawel.bilski@ifj.edu.pl; Obryk, B.; Olko, P. [Institute of Nuclear Physics (IFJ), Krakow (Poland); Mandowska, E.; Mandowski, A. [Institute of Physcis, Jan Dlugosz University (AJD), Czestochowa (Poland); Kim, J.L. [Korean Atomic Energy Research Institute (KAERI), Dejoan (Korea, Republic of)

    2008-02-15

    The behaviour of LiF:Mg,Cu,P (MCP-N) detectors at ultra-high doses up to 500 kGy has been investigated. Some very significant changes of the glow-curve shape have been revealed. The most important finding is the appearance of a new peak at exposures above 50 kGy, the position of which shifts toward higher temperatures with increasing dose (from 405 to 470 deg. C at 500 kGy), in contradiction to standard TL models. The E and s trapping parameters also increase with increasing dose. This new peak appears to have potential application for ultra-high-dose measurements. The TL emission spectrum also changes at such high doses with the appearance of several new bands of wavelengths up to 800 nm.

  18. The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients.

    Science.gov (United States)

    Cui, Li-Hong; Li, Chao; Wang, Xiao-Hui; Yan, Zhi-Hui; He, Xing; Gong, San-Dong

    2015-01-01

    To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups: 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole sodium once every 12 h for 72 h. Compared with the conventional dose group, the total efficiency of the high-dose group and conventional dose group was 98.08% and 86.00%, respectively (p esomeprazole have good hemostatic effects on stress ulcer bleeding in trauma patients. The high-dose esomeprazole is better for hemostasis.

  19. Custom-made micro applicators for high-dose-rate brachytherapy treatment of chronic psoriasis

    Directory of Open Access Journals (Sweden)

    Ivan M. Buzurovic

    2017-06-01

    Full Text Available Purpose: In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR brachytherapy. The custom-made micro applicators (CMMA were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. Material and methods: The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands. The clinical target was defined as the length from the fingertip to the distal interphalangeal joint. For the accurate and reproducible setup in the multi-fractional treatment delivery, the CMMAs were designed. Five needles were embedded into the dense plastic mesh and covered with 5 mm bolus material for each micro applicator. Five CMMAs were designed, resulting in the usage of 25 catheters in total. Results: The prescription dose was planned to the depth of the anterior surface of the distal phalanx, allowing for the sparing of the surrounding tissue. The total number of the active dwell positions was 145 with step size of 5 mm. The total treatment time was 115 seconds with a 7.36 Ci activity of the 192Ir source. The treatment resulted in good pain control. The patient did not require further injections to the nail bed. After this initial treatment, additional two patients with similar symptoms received HDR brachytherapy. The treatment outcome was favorable in all cases. Conclusions : The first HDR brachytherapy treatment of psoriasis of the nail bed is presented. The initial experience revealed that brachytherapy treatment was well-tolerated and resulted in adequate control of the disease. A larger cohort of patients will be required for additional conclusions related to the long-term clinical benefits.

  20. 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

  1. Comparison of porous and nano zinc oxide for replacing high-dose dietary regular zinc oxide in weaning piglets.

    Science.gov (United States)

    Long, Lina; Chen, Jiashun; Zhang, Yonggang; Liang, Xiao; Ni, Hengjia; Zhang, Bin; Yin, Yulong

    2017-01-01

    The aim of this study was to compare the effect of dietary supplementation with low dose of porous and nano zinc oxide (ZnO) on weaning piglets, and to evaluate the possibility of using them as an alternative to high dose of regular ZnO. Piglets were randomly allocated into four treatment groups fed with four diets: (1) basal diet (NC), (2) NC+ 3000 mg/kg ZnO (PC), (3) NC + 500 mg/kg porous ZnO (HiZ) and (4) NC + 500 mg/kg nano ZnO (ZNP). The result showed that piglets in HiZ group had less diarrhea than ZNP group (P 0.05). Analysis of trace metal elements revealed that piglets fed with high dose of regular ZnO had the highest Zn level in kidney (P < 0.05), which may induce kidney stone formation. Additionally, a decrease in ileal crypt depth was observed in PC, HiZ and ZNP group, suggesting an effective protection against intestinal injury. Results of mRNA analysis in intestine showed that ZNP supplementation had better effects on up-regulated trefoil factor 3 (TFF3) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels in duodenum and jejunum than HiZ did (P < 0.05), implying that nano ZnO may possess higher anti-inflammatory capacity than porous ZnO. In conclusion, dietary supplementation with low dose of porous and nano ZnO had similar (even better) effect on improving growth performance and intestinal morphology, reducing diarrhea and intestinal inflammatory as high dose of regular ZnO in weaning piglets. Compared with nano ZnO, porous ZnO had better performance on reducing diarrhea but less effect on up-regulation of intestinal TFF3 and Nrf2.

  2. Assessment of The Dose-Response Relationship of Radiation-Induced Bystander Effect in Two Cell Lines Exposed to High Doses of Ionizing Radiation (6 and 8 Gy).

    Science.gov (United States)

    Bahreyni Toossi, Mohammad Taghi; Khademi, Sara; Azimian, Hosein; Mohebbi, Shokoufeh; Soleymanifard, Shokouhozaman

    2017-10-01

    The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints. This experimental study used the medium transfer technique to induce RIBE. The cells were divided into two main groups: QU-DB cells which received medium from autologous irradiated cells and MRC5 cells which received medium from irradiated QU-DB cells. Colony, MTT, and micronucleus assays were performed to quantify bystander responses. The medium was diluted and transferred to bystander cells to investigate whether medium dilution could revive the RIBE response that disappeared at a high dose. The RIBE level in QU-DB bystander cells increased in the dose range of 0.5 to 4 Gy, but decreased at 6 and 8 Gy. The Micronucleated cells per 1000 binucleated cells (MNBN) frequency of QU-DB bystander cells which received the most diluted medium from 6 and 8 Gy QU-DB irradiated cells reached the maximum level compared to the MNBN frequency of the cells that received complete medium (PMRC5 cells which received the most diluted medium from 4 Gy QU-DB irradiated cells reached the maximum level compared to MNBN frequency of cells that received complete medium (P<0.0001). Our results showed that RIBE levels decreased at doses above 4 Gy; however, RIBE increased when diluted conditioned medium was transferred to bystander cells. This finding confirmed that a negative feedback mechanism was responsible for the decrease in RIBE response at high doses. Decrease of RIBE at high doses might be used to predict that in radiosurgery, brachytherapy and grid therapy, in which high dose per fraction is applied, normal tissue damage owing to RIBE may decrease.

  3. 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.

  4. Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide.

    Science.gov (United States)

    Papaccio, G; Pisanti, F A; Latronico, M V; Ammendola, E; Galdieri, M

    2000-02-01

    Streptozotocin (STZ) is a widely used diabetogenic agent that damages pancreatic islet beta cells by activating immune mechanisms, when given in multiple low doses, and by alkylating DNA, when given at a single high dose. Actually, STZ contains a nitroso moiety. Incubation of rat islets with this compound has been found to generate nitrite; moreover, photoinduced NO production from STZ has been demonstrated. These reports have suggested that direct NO generation may be a mechanism for STZ toxicity in diabetogenesis. Several other studies have denied such a mechanism of action. This study has shown that (1) the multiple low-dose (MLDS) treatment does not stimulate NO production at the islet level; in fact, nitrite + nitrate levels and aconitase activity (also in the presence of an NO-synthase inhibitor, namely NAME) remain unmodified; RT-PCR analysis demonstrates that this treatment does not stimulate iNOS activity; (2) the high-dose (HDS) treatment does not stimulate NO production; in fact nitrite + nitrate levels remain unmodified and iNOS mRNA levels are not altered, although aconitase activity is significantly decreased. Moreover, we have confirmed that the MLDS treatment is able to decrease SOD activity by day 11 and that STZ, given in a single high dose, transiently increases superoxide dismutase (SOD) values (24 h from the administration), then dramatically lowers SOD levels. On the basis of our results, we conclude that STZ, "in vivo" is unable to generate NO, both as a MLDS or HDS treatment, thus excluding that NO exerts a role in streptozotocin-dependent diabetes mellitus. Copyright 2000 Wiley-Liss, Inc.

  5. The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial.

    Science.gov (United States)

    Lane, W; Weinrib, S; Rappaport, J; Hale, C

    2014-09-01

    Patients with type 2 diabetes and insulin resistance may require high insulin doses to control hyperglycaemia. The addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin therapy has been shown to reduce insulin requirement while reducing insulin-associated weight gain [1,2]. The effect of GLP-1 RA therapy added to intensive (basal/bolus) insulin therapy has not been studied in a prospective trial. This trial evaluated the effect of the addition of liraglutide to high-dose intensive insulin therapy compared with standard insulin up-titration in obese insulin-resistant patients with type 2 diabetes requiring high-dose insulin therapy. Thirty-seven subjects with type 2 diabetes requiring >100 units of insulin daily administered either by continuous subcutaneous insulin infusion (CSII) or by multiple daily injections (MDIs) with or without metformin were randomized to receive either liraglutide plus insulin (LIRA) or intensive insulin only (controls). Liraglutide was initiated at 0.6 mg subcutaneously (sq) per day and increased to either 1.2 or 1.8 mg daily in combination with intensive insulin therapy. Controls received intensive insulin up-titration only. At 6 months, subjects receiving liraglutide plus insulin experienced statistically significant reductions in HbA1c, weight, insulin dose and glycaemic variability (GV) by continuous glucose monitor (CGM) compared with the control group receiving insulin only. Adding liraglutide to intensive high-dose (basal/bolus) insulin therapy results in greater improvement in glycaemic control than insulin therapy alone, with additional benefits of weight loss and reduced GV. © 2014 John Wiley & Sons Ltd.

  6. Effects of high-dose fenfluramine treatment on monoamine uptake sites in rat brain: Assessment using quantitative autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Appel, N.M.; Mitchell, W.M.; Contrera, J.F.; De Souza, E.B. (NIDA Addiction Research Center, Baltimore, MD (USA))

    1990-01-01

    Fenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high-dose d,l-fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long-lasting decreases in brain serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid, and high-affinity 5HT uptake sites. Moreover, this high-dose treatment regimen causes both selective long-lasting decreases in fine-caliber 5HT-immunoreactive axons and appearance of other 5HT-immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and that it relies on presence of the antigen (in this case 5HT), and the 5HT-depleting effects of fenfluramine are well known. In the present study, we used quantitative in vitro autoradiography to assess, in detail, the density and regional distribution of (3H)paroxetine-labeled 5HT and (3H)mazindol-labeled catecholamine uptake sites in response to the high-dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine-containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine treatment regimen. Marked decreases in densities of (3H)paroxetine-labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT-like immunostaining when compared to saline-treated control rats. These included cerebral cortex, caudate putamen, hippocampus, thalamus, and medial hypothalamus.

  7. Fertility of tall girls treated with high-dose estrogen, a dose-response relationship

    NARCIS (Netherlands)

    A.E.J. Hendriks (Emile); S.L.S. Drop (Stenvert); J.S.E. Laven (Joop); A.M. Boot (Annemieke)

    2012-01-01

    textabstractContext: 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

  8. Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin

    NARCIS (Netherlands)

    de Jonge, Milly E.; Mathôt, Ron A. A.; van Dam, Selma M.; Beijnen, Jos H.; Rodenhuis, Sjoerd

    2002-01-01

    An obese 53-year-old woman (height 167 cm, weight 130 kg) with metastatic breast cancer received high-dose chemotherapy comprising cyclophosphamide, thiotepa and carboplatin (CTC). The cyclophosphamide (1 g/m(2) per day) and thiotepa (80 mg/m(2) per day) doses were based on body surface area (BSA)

  9. Postoperative high-dose-rate brachytherapy in the prevention of keloids

    NARCIS (Netherlands)

    Veen, Ronald E.; Kal, Henk B.

    2007-01-01

    Background: The aim of this study is to show the efficiency of keloidectomy and postoperative interstitial high-dose-rate (HDR) brachytherapy in the prevention of keloids. Methods and Materials: Between 1998 and 2004, 35 patients with 54 keloids were treated postoperatively with HDR brachytherapy.

  10. The Value Of High Dose Frusemide In The Management Of 350 ...

    African Journals Online (AJOL)

    Objective: To report our experience in the use of high dose infusion of frusemide in the postoperative management of 350 open prostatectomy and discuss its benefits. Patient and Methods: The study ... Fluid intake, urine output, sodium and potassium losses in urine were studied in both group of patients. Frusemide infusion ...

  11. Treatment of electrical status epilepticus during slow-wave sleep with high-dose corticosteroid.

    Science.gov (United States)

    Okuyaz, Cetin; Aydin, Kürşad; Gücüyener, Kivilcim; Serdaroğlu, Ayşe

    2005-01-01

    A 4-year-old female patient with epilepsy with continuous spike-and-waves during slow-wave sleep not classified as Landau-Klefner syndrome, refractory to antiepileptic drugs including valproate, benzodiazepines, and lamotrigine, was treated successfully with high-dose intravenous methylprednisolone therapy. Valproate, clobazam, and lamotrigine were continued at the same dose during and after high-dose intravenous corticosteroid therapy. During corticosteroid therapy, awake and sleep electroencephalogram was recorded every day. On day 7, a dramatic clinical and electroencephalographic response was observed. After high-dose intravenous methylprednisolone, prednisolone was administered orally (2 mg/kg daily) for 2 months, then gradually withdrawn. After the withdrawal of corticosteroid therapy, the patient maintained the clinical improvement in behavior, and no continuous spike-and-wave electrical status epilepticus during slow-wave sleep occurred on routine monthly sleep electroencephalogram performed for the last 6 months. In the present case, an add-on high-dose intravenous corticosteroid seems to be effective in the treatment of patients with electrical status epilepticus during slow-wave sleep syndrome, especially when antiepileptic drugs fail.

  12. High-dose intravenous vancomycin therapy and the risk of nephrotoxicity.

    Science.gov (United States)

    Rostas, Sara E; Kubiak, David W; Calderwood, Michael S

    2014-07-01

    National guidelines recommend higher serum trough concentrations when using vancomycin to treat certain clinical conditions, but there is concern that higher-dose vancomycin therapy causes nephrotoxicity. We evaluated risk factors associated with nephrotoxicity in patients receiving high-dose intravenous vancomycin. This retrospective cohort study evaluated the clinical outcome of 80 hospitalized adult patients with normal baseline renal function who received ≥4 g/d of intravenous vancomycin for ≥48 hours between January 1, 2011, and December 31, 2011. After abstracting clinical risk factors, we used an analysis by methods of best clinical subsets to develop a multivariable model predicting nephrotoxicity in patients receiving high-dose vancomycin. The overall rate of nephrotoxicity in the study population was 6%. Trough concentrations >20 mg/L were identified in a similar proportion of patients who did and did not develop nephrotoxicity. Patients who developed nephrotoxicity trended toward having a lower body mass index, higher daily dose, longer duration of therapy, and greater exposure to intravenous contrast and nephrotoxic medications. In a multivariable model, the combination of intravenous contrast and nephrotoxic medications was a significant predictor of nephrotoxicity, and duration of high-dose vancomycin was a significant confounder. Administration of high-dose intravenous vancomycin may have less associated nephrotoxicity than previously reported, although duration of vancomycin therapy may play a role. Concomitant exposure to intravenous contrast and other nephrotoxic medications is a more significant predictor of developing nephrotoxicity than vancomycin dose or trough. Published by EM Inc USA.

  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

    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

  14. Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms

    DEFF Research Database (Denmark)

    Lindell, G; Bukhave, Klaus; Lilja, I

    1997-01-01

    Peptic ulcer disease is overrepresented among smokers; they also heal slowly and relapse frequently. Data are accumulating that smoking is detrimental to gastroduodenal mucosal cytoprotection. This study was designed to assess acute effects of high-dose intragastric nicotine, as it has been shown...

  15. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S; Bontenbal, M; Beex, LVAM; Wagstaff, J; Richel, DJ; Nooij, MA; Voest, EE; Hupperets, P; van Tinteren, H; Peterse, HL; TenVergert, EM; de Vries, EGE

    2003-01-01

    BACKGROUND: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes. METHODS: Patients younger than 56 years of age who had undergone surgery for breast cancer

  16. 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.

    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

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

    Science.gov (United States)

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

    2014-12-01

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

  18. Learning curve of MRI-based planning for high-dose-rate brachytherapy for prostate cancer

    DEFF Research Database (Denmark)

    Buus, Simon; Rylander, Susanne; Hokland, Steffen

    2016-01-01

    Purpose To evaluate introduction of MRI-based high-dose-rate brachytherapy (HDRBT), including procedure times, dose-volume parameters, and perioperative morbidity. Methods and Materials Study included 42 high-risk prostate cancer patients enrolled in a clinical protocol, offering external beam...

  19. 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.

  20. High-dose chemotherapy : studies on supportive care, quality of life and late effects of treatment

    NARCIS (Netherlands)

    Nieboer, Peter

    2008-01-01

    Drug resistance is a major problem in the treatment of malignancies. Based on steep dose-response relationship for certain chemotherapeutic drugs in vitro on tumor cell survival, high-dose chemotherapy was considered of interest for the treatment of malignancies. Introduction of autologous

  1. High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

    1996-01-01

    Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

  2. Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support

    NARCIS (Netherlands)

    van der Lelie, H.; Baars, J. W.; Rodenhuis, S.; Van Dijk, M. A.; de Glas-Vos, C. W.; Thomas, B. L.; van Oers, R. H.; von dem Borne, A. E.

    1995-01-01

    BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is

  3. 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

  4. Absorption of high-dose enteral vitamin A in low- birth-weight ...

    African Journals Online (AJOL)

    A randomised, double-blind placebo-controlled trial was designed to detennine whether high-dose (25 000 IU) enteral vitamin A. to correct deficiency, would be absorbed and well tolerated in low-birth-weight (LBW) neonates. Thirty-five LBW infants (950 - 1 700 g; gestational age. 27 - 36 weeks) were allocated to receive ...

  5. Absorption of high-dose enteral vitamin A in lowbirth- weight neonates

    African Journals Online (AJOL)

    A randomised, double-blind placebo-controlled trial was designed to detennine whether high-dose (25 000 IU) enteral vitamin A. to correct deficiency, would be absorbed and well tolerated in low-birth-weight (LBW) neonates. Thirty-five LBW infants (950 - 1 700 g; gestational age 27 - 36 weeks) were allocated to receive ...

  6. New applications for the twincer disposable high dose dry powder inhaler

    NARCIS (Netherlands)

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

    Purpose: The Twincer disposable dry powder inhaler was developed for the administration of high drug doses in cystic fibrosis and tuberculosis therapy. Its excellent performance on several antibiotics has challenged testing of other high dose drugs for pulmonary administration with the Twincer. The

  7. 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...... to the AB0 blood type system....

  8. the non-genomic effects of high doses of rosiglitazone on cell growth

    African Journals Online (AJOL)

    DR. AMINU

    Received: April, 2009. Accepted: July, 2009. THE NON-GENOMIC EFFECTS OF HIGH DOSES OF ROSIGLITAZONE ON. CELL GROWTH AND APOPTOSIS IN CULTURED MONOCYTIC CELLS. *S.A. Isa, L.S. Mainwaring, R. Webb, and A.W. Thomas. Centre for Biomedical Sciences, University of Wales Institute, Cardiff CF5 ...

  9. 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.

  10. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

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    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.

  11. Dosimetric impact of interfraction catheter movement in high-dose rate prostate brachytherapy.

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    Foster, William; Cunha, J Adam M; Hsu, I-Chow; Weinberg, Vivan; Krishnamurthy, Devan; Pouliot, Jean

    2011-05-01

    To evaluate the impact of interfraction catheter movement on dosimetry in prostate high-dose-rate (HDR) brachytherapy. Fifteen patients were treated with fractionated HDR brachytherapy. Implants were performed on day 1 under transrectal ultrasound guidance. A computed tomography (CT) scan was performed. Inverse planning simulated annealing was used for treatment planning. The first fraction was delivered on day 1. A cone beam CT (CBCT) was performed on day 2 before the second fraction was given. A fusion of the CBCT and CT was performed using intraprostatic gold markers as landmarks. Initial prostate and urethra contours were transferred to the CBCT images. Bladder and rectum contours were drawn, and catheters were digitized on the CBCT. The planned treatment was applied to the CBCT dataset, and dosimetry was analyzed and compared to the initial dose distribution. This process was repeated after a reoptimization was performed, using the same constraints used on day 1. Mean interfraction catheter displacement was 5.1 mm. When we used the initial plan on day 2, the mean prostate V100 (volume receiving 100 Gy or more) decreased from 93.8% to 76.2% (p < 0.01). Rectal V75 went from 0.75 cm(3) to 1.49 cm(3) (p < 0.01). A reoptimization resulted in a mean prostate V100 of 88.1%, closer to the initial plan (p = 0.05). Mean rectal V75 was also improved with a value of 0.59 cm(3). There was no significant change in bladder and urethra dose on day 2. A mean interfraction catheter displacement of 5.1 mm results in a significant decrease in prostate V100 and an increase in rectum dose. A reoptimization before the second treatment improves dose distribution. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. High-dose-rate interstitial brachytherapy for female peri-urethral cancer

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    Daya Nand Sharma

    2016-01-01

    Full Text Available Purpose: Peri-urethral cancer (PUC in females is a rare malignancy. Surgery is not usually contemplated due to associated morbidity. Radiation therapy (RT can be employed in the form of interstitial brachytherapy (IBT alone for early lesions, and external beam radiation therapy (EBRT with or without IBT for advanced lesions. We report our first experience in the literature to evaluate the role of high-dose-rate (HDR IBT in female PUC. Material and methods : Between 2008 and 2013, 10 female patients with PUC (5 primary and 5 recurrent were treated with HDR-IBT with or without EBRT at our center. Size of the lesion ranged from 1.5 cm to 5.0 cm. A 2-3 plane free-hand implant was performed using plastic catheters. The prescribed dose of HDR-IBT was 42 Gy in 14 fractions for brachytherapy alone (5 patients, and 18-21 Gy for the boost along with EBRT (5 patients. Patients were followed up regularly for assessment of disease control and toxicity. Results: At a median follow up of 25 months, six patients were disease free at their last follow up. Four patients developed recurrence: 2 at inguinal nodes, 1 at local site, and 1 at both local as well as inguinal nodes. Moist desquamation was the commonest acute toxicity observed in all 5 patients treated with IBT alone, which healed within 4 weeks’ time. Overall, grade II delayed complication rate was 30%. Conclusions : Though small sample size, the results of our study have shown that HDR-IBT provides good loco-regional control with acceptable toxicity for female PUC.

  13. Chronic High Doses of Nandrolone Decanoate on Blood Cell, Lipoprotein Profile, and Liver Enzymes in Male Rats

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    Mohammad Reza Shahraki

    2016-06-01

    Full Text Available Background Nandrolone decanoate (ND is a doping agent and it is used by athletes. Objectives This study was carried out to evaluate the chronic, high doses of ND administration on Blood cell, lipid profile, and Liver enzymes in male rats. Materials and Methods This experiment was executed on 30 wistar- Albino male rats divided, after weighing, in control, placebo, and test groups (n = 10. Test group received 15 mg/kg intramuscular (IM ND for duration of 8 weeks. Group placebo received the same volume of placebo although control group did not receive any agent during the trial period. At the end, animals were anesthetized by diethyl ether, scarified, and then blood samples were collected from cervical vessels immediately. Blood cell, lipoprotein profile, and liver enzymes were measured by ordinary methods. Obtained data were analyzed by SPSS V. 15, via ANOVA and Tukey test. Results were expressed as mean ± SD. Statistical difference was significantly recognized by P ≤ 0.05. Results Results showed that AST, ALT, cell blood count, hemoglobin, hematocrite, and cholesterol values in group test were increased significantly compared to those of other groups; however, HDL value in this group decreased noticeably compared to control and Placebo groups. Conclusions Present study revealed that chronic high doses of ND administration alter the liver enzymes, lipid profile, and blood parameter in male rats.

  14. Total skin electron irradiation therapy in mycosis fungoides using high-dose rate mode: a preliminary experience.

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    Parida, Dillip K; Verma, Kaushal K; Chander, Subhash; Joshi, R C; Rath, Goura K

    2005-10-01

    Total skin electron irradiation (TSEI) therapy is the treatment of choice for mycosis fungoides. However, conventional TSEI therapy is time consuming as well as patient unfriendly. Therefore we used high-dose rate (HDR) mode TSEI in these patients. High-dose rate mode of TSEI is a technological innovation attached to a Linear Accelerator (Philips, SL-20, Netherlands), which can deliver an electron beam of 30 Gy/min at the iso-center. The iso-center faces the patient, 100 cm away from the target of the linear accelerator. The patient is treated at a distance of 10 feet from the iso-center of the linear accelerator. The dose delivered to the skin was 1.13 Gy/min, making the treatment execution much easier and patient compliance much better. Seven male patients between 40 and 64 years in age having mycosis fungoides for 9-18 months were treated by TSEI using high-dose rate mode between 1998 and 2000. The TSEI was performed according to the Stanford technique, delivering a total dose of 36 Gy. Each patient received a dose of 1.2 Gy/field/day. There were six fields, i.e. anterior, posterior, left and right anterior obliques, and left and right posterior obliques in both the upper and lower parts of the body. The eyes and nails were shielded at each session of radiotherapy. The times taken at each session of the therapy and radiation-associated side-effects were determined in each patient. The patients were followed up to 26 months (median 9 months) to look for any relapse. Three patients had early stage disease (IB) whereas four patients had advanced disease (IIB). Six patients out of these had complete remission following TSEI while one patient died as a result of progression of the disease during treatment. The treatment time taken at each treatment session in each individual patient was approximately 15 min. Radiation-associated morbidity was seen in all patients. Cutaneous lesions relapsed in two patients after 4 and 10 months, respectively, while four patients were

  15. High-dose-rate brachytherapy as salvage modality for locally recurrent prostate cancer after definitive radiotherapy. A systematic review

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    Chatzikonstantinou, Georgios; Zamboglou, Nikolaos; Roedel, Claus; Tselis, Nikolaos [J.W. Goethe University of Frankfurt, Department of Radiotherapy and Oncology, Frankfurt am Main (Germany); Zoga, Eleni [Sana Klinikum Offenbach, Department of Radiotherapy and Oncology, Offenbach am Main (Germany); Strouthos, Iosif [Medical Center - University of Freiburg, Department of Radiotherapy and Oncology, University of Freiburg, Freiburg (Germany); Butt, Saeed Ahmed [Sana Klinikum Offenbach, Department of Medical Physics and Engineering, Offenbach am Main (Germany)

    2017-09-15

    To review the current status of interstitial high-dose-rate brachytherapy as a salvage modality (sHDR BRT) for locally recurrent prostate cancer after definitive radiotherapy (RT). A literature search was performed in PubMed using ''high-dose-rate, brachytherapy, prostate cancer, salvage'' as search terms. In all, 51 search results published between 2000 and 2016 were identified. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control (BC) and toxicity scores. Eleven publications reported clinical outcome and toxicity with follow-up ranging from 4-191 months. A variety of dose and fractionation schedules were described, including 19.0 Gy in 2 fractions up to 42.0 Gy in 6 fractions. The 5-year BC ranged from 18-77%. Late grade 3 genitourinary and gastrointestinal toxicity was 0-32% and 0-5.1%, respectively. sHDR BRT appears as safe and effective salvage modality for the reirradiation of locally recurrent prostate cancer after definitive RT. (orig.) [German] Zusammenfassende Darstellung relevanter Literatur zur interstitiellen High-Dose-Rate-Brachytherapie als Salvage-Modalitaet (sHDR-BRT) bei der Behandlung des lokal rezidivierten Prostatakarzinoms nach vorausgegangener definitiver Radiotherapie (RT). In der PubMed-Datenbank wurde eine Literaturrecherche mit den Suchbegriffen ''high-dose-rate, brachytherapy, prostate cancer, salvage'' durchgefuehrt. Zwischen den Jahren 2000 und 2016 wurden 51 Publikationen identifiziert. Die biochemische Kontrolle (BC) sowie das assoziierte Toxizitaetsprofil waren onkologische Hauptpunkte in der Analyse der beruecksichtigten Literatur. Von onkologischen Ergebnissen und Toxizitaeten berichteten 11 Publikationen bei einer medianen Nachbeobachtungszeit von 4-191 Monaten. Eine Variabilitaet von Dosis- und Fraktionierungsregimen wurde beschrieben mit totalen physikalischen Dosen von 19,0 Gy in 2 Fraktionen bis zu 42,0 Gy in 6 Fraktionen

  16. Polysubstance-induced relapse of schizoaffective disorder refractory to high-dose antipsychotic medications: a case report.

    Science.gov (United States)

    Tucker, Murray G; Kekulawala, Sebastian; Kent, Michelle; Mostafa, Sam; Harvey, Richard

    2016-09-06

    is resistant to medical management. High doses of multiple antipsychotic medications may be required to manage dangerous behaviors associated with these acute psychotic relapses. These patients require close monitoring for adverse effects with adjustment of dosing to ensure the optimal balance of risk versus benefit while the patient is acutely psychotic. The results are of relevance for the management of psychiatric emergencies in emergency departments and acute mental health settings.

  17. PHASE II STUDY OF HIGH DOSE PHOTON/PROTON RADIOTHERAPY IN THE MANAGEMENT OF SPINE SARCOMAS

    Science.gov (United States)

    DeLaney, Thomas F.; Liebsch, Norbert J.; Pedlow, Francis X.; Adams, Judith; Dean, Susan; Yeap, Beow Y.; McManus, Patricia; Rosenberg, Andrew E.; Nielsen, G. Petur; Harmon, David C.; Spiro, Ira J.; Raskin, Kevin A.; Suit, Herman D.; Yoon, Sam S.; Hornicek, Francis J.

    2009-01-01

    Purpose Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of ≥ 66 Gy are recommended. A Phase II clinical trial evaluated high dose photon/proton XRT for spine sarcomas. Materials/Methods Eligible patients had non-metastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or post-op photon/proton XRT +/- radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (GyRBE) to subclinical disease, 70.2 GyRBE to microscopic disease in the tumor bed, and 77.4 GyRBE to gross disease at 1.8 GyRBE q.d. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 GyRBE to surface/center. Intra-operative boost doses of 7.5-10 Gy could be given by dural plaque. Results 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n=25) or subtotal (n=12) resection or biopsy (n=13). With 48 month median follow-up, five-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence, p<0.001. Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared following 77.12-77.4 GyRBE. Conclusions Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 GyRBE are at risk for late toxicity. PMID:19095372

  18. Verification of High Dose Rate 192Ir Source Position During Brachytherapy Treatment Using Silicon Pixel Detectors

    Science.gov (United States)

    Batic, Matej; Burger, Janez; Cindro, Vladimir; Kramberger, Gregor; Mandic, Igor; Mikuz, Marko; Studen, Andrej; Zavrtanik, Marko

    2011-10-01

    A system for in-vivo tracking of 192Ir source during high dose rate or pulsed dose rate brachytherapy treatment was built using 1 mm thick silicon pad detectors as image sensors and knife-edge lead pinholes as collimators. With source self-images obtained from a dual-pinhole system, location of the source could be reconstructed in three dimensions in real time. The system was tested with 192Ir clinical source (kerma rate in air at 1 m 2.38 Gy/h) in air and plexi-glass phantom. The locations of the source were tracked from a distance of 40 cm in a field of view of 20 × 20 × 20 cm3. Reconstruction precision, defined as the average distance between true and reconstructed source positions, with data collected in less than 1 s with 22 GBq 192Ir source was about 5 mm. The reconstruction precision was in our case mainly limited by imperfect alignment of detectors and pinholes. With perfect alignment the statistical error would allow precision of about 1 mm which could further be improved with larger detector placed at larger distance from the pinhole. However already the modest precision of few millimeters is sufficient for in-vivo detection of larger deviations from planned treatment caused by various misadministrations or malfunctioning of the brachytherapy treatment apparatus. Usage of silicon detectors offers a possibility for building a compact device which could be used as an independent online quality assurance system. In this paper details about sensors, readout system and reconstruction algorithm are described. Results from measurements with clinical source are presented.

  19. False-negative urine human chorionic gonadotropin in molar pregnancy: " The high-dose hook effect" !

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    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.

  20. High-Dose Lanreotide in the Treatment of Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Case Report

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    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.

  1. Genetic compensation of high dose radiation-induced damage in an anhydrobiotic insect

    Science.gov (United States)

    Gusev, Oleg; Nakahara, Yuichi; Sakashita, Tetsuya; Kikawada, Takahiro; Okuda, Takashi

    Anhydrobiotic larvae of African chironomid Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. The tolerance against various extreme environments exhibited by that insect might be due to being almost completely desiccated replacing water with trehalose, a state where little or no chemical reactions occur. From 2005 dried larvae of this insect are being used in a number of space experiments, both inside and outside of ISS as a model organism for estimation the limits of higher organisms' resistance to space environment stresses and long-term storage of the alive anhydrobiotic organisms during continues spaceflight. We have shown previously that both hydrated and dried larvae of Polypedilum vanderplanki have very higher tolerance against both highand low-linear energy transfer (LET), surviving after 7000Gy irradiation. It was suggested that the larvae would have effective DNA-reparation system in addition to artificial protection provided by glass-stage without water. In the present study we conducted analysis of stress-related gene expression in the larvae after 70-2000 Gy irradiations. Both DNA damage level and activity of DNA-reparation, anti-apoptotic and protein-damage related genes were analyzed. Direct visualization of DNA damage in the larvae fat body cells using Comet Assay showed that fragmented by radiation DNA is re-arranged within 76-98 hours after exposure. We found that massive overexpression of hsp and anti-oxidant genes occur in larvae entering anhydrobiosis , and provides refolding of proteins after rehydration. In the irradiated larvae overexpression of DNA-reparation enzymes anti-apoptotic genes was confirmed, suggesting that survival after high-dose irradiation is a result of combination of highly effective blocking of entering the apoptosis after severe DNA damage and DNA reparation.

  2. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

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    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.

  3. Marital Relationship and Its Associated Factors in Veterans Exposed to High Dose Chemical Warfare Agents

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    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.

  4. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

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    Shim, Hee Jin; Lee, Eun-Mi; Nguyen, Long Duy; Shim, Jaekyung; Song, Young-Han

    2014-01-01

    Ionizing radiation (IR) treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs) generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis.

  5. Comparison of dose and catheter optimization algorithms in prostate high-dose-rate brachytherapy.

    Science.gov (United States)

    Poulin, Eric; Varfalvy, Nicolas; Aubin, Sylviane; Beaulieu, Luc

    2016-01-01

    The purpose of this work was to compare the hybrid inverse treatment planning optimization (HIPO), inverse dose-volume histogram-based optimization (DVHO), and fast simulated annealing stochastic algorithm (IPSA). The catheter optimization algorithm HIPO was also compared with the Centroidal Voronoi Tessellation (CVT) algorithm. In this study, eight high-dose-rate prostate cases were randomly selected from an anonymized bank of patients. Oncentra Prostate v4.1 was used to run DVHO and the HIPO catheter optimization (HIPO_cat), whereas Oncentra Brachy v4.3 was used for the remaining. For fixed catheter configurations, DVHO plans were compared with IPSA and HIPO. For catheter positions optimization, CVT and HIPO_cat algorithms were compared with standard clinical template plans. CVT catheters were further restrained to the template grid (CVT_grid) and compared with HIPO_cat. For dose optimization, IPSA and HIPO were not different from each other. The urethra D10 and the computation time were found significantly better with IPSA and HIPO compared with DVHO (p 0.05). For catheter placement, CVT plans were better, whereas HIPO_cat plans were significantly worse (p HIPO_cat plans do not for all catheter numbers. The CVT algorithm run time was significantly faster than HIPO_cat (p HIPO give similar dosimetric results. The CVT approach was found to be better than HIPO_cat and was able to reduce the number of catheters significantly. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  6. Pulsed laser annealing of high-dose Ag+-ion implanted Si layer

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    Batalov, R. I.; Nuzhdin, V. I.; Valeev, V. F.; Vorobev, V. V.; Osin, Yu N.; Ivlev, G. D.; Stepanov, A. L.

    2018-01-01

    The formation of a crystalline composite Ag:Si material with Ag nanoparticles by low-energy (E  =  30 keV) high-dose (D  =  1.5  ×  1017 ion cm‑2) Ag+ implantation into a monocrystalline c-Si substrate followed by nanosecond pulsed laser annealing (PLA) is demonstrated. Compared to traditional thermal annealing, PLA allows us to perform local heating of the sample both for its depth and area, and eliminate implantation-induced defects more efficiently, due to rapid liquid-phase recrystallization. Moreover, dopant diffusion during a nanosecond laser pulse is mainly limited by the molten region, where the dopant diffusion coefficient is several orders of magnitude higher than in the solid state. During PLA by a ruby laser (λ  =  0.694 µm), the optical probing of the irradiated zone at λ  =  1.064 µm with registration of time-dependent reflectivity R(t) was carried out. By scanning electron microscopy, it was established that Ag+ implantation leads to the creation of a thin amorphous Ag:Si layer of porous structure, containing Ag nanoparticles with sizes of 10–30 nm. PLA with energy density W  =  1.2–1.8 J cm‑2 results in the melting of the implanted layer (d ~ 60 nm) and the topmost layers of the c-Si substrate (d  x-ray (EDX) spectroscopy did not show a noticeable change of Ag atomic concentration in the implanted layer after PLA. Spectral dependence R(λ) of Ag:Si layers showed the partial recovery of c-Si bands with maxima at 275 and 365 nm with simultaneous weakening of plasmon band for Ag nanoparticles in Si at 835 nm.

  7. Intubation following high-dose rocuronium in a cat with protracted laryngospasm

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    Graeme M Doodnaught

    2017-10-01

    Full Text Available Case summary An 11-year-old spayed female domestic shorthair cat with a history of laryngospasm at induction of general anesthesia presented for dental evaluation and treatment. The cat was premedicated with hydromorphone (0.05 mg/kg and alfaxalone (0.5 mg/kg intravenously, pre-oxygenated for 5 mins (3 l/min, face mask and anesthesia was induced with alfaxalone (to effect intravenously. Lidocaine (0.1 ml, 2% was applied topically to the arytenoid cartilages following loss of jaw tone. Laryngospasm was not noted during or immediately following lidocaine application. However, after waiting 60 s for the onset of effect of the topical lidocaine, laryngospasm was apparent. Orotracheal intubation by direct visualization was unsuccessful after four attempts by three anesthetists (with increasing levels of experience. At this point, a failed intubation was declared and the non-depolarising neuromuscular blocking agent rocuronium (1 mg/kg IV given, resulting in arytenoid abduction and appropriate conditions for intubation. Successful intubation occurred 9 mins after induction of anesthesia. Oxygen was continuously supplemented throughout and arterial hemoglobin saturation with oxygen was never <94%. Relevance and novel information To the authors’ knowledge, this is the first report of the use of high-dose rocuronium to successfully resolve prolonged laryngospasm at induction of general anesthesia in a cat. Despite laryngospasm and a delay in achieving orotracheal intubation, low values for arterial hemoglobin saturation with oxygen (indicative of hypoxemia were not observed, highlighting the benefits of pre-oxygenation and apneic oxygenation. The principles of the Difficult Airway Society 2015 guidelines were followed in managing this difficult intubation.

  8. 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.

  9. 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.

  10. Individualized high-dose cabergoline therapy for hyperprolactinemic infertility in women with micro- and macroprolactinomas.

    Science.gov (United States)

    Ono, Masami; Miki, Nobuhiro; Amano, Kosaku; Kawamata, Takakazu; Seki, Toshiro; Makino, Rena; Takano, Kazue; Izumi, Shun-ichiro; Okada, Yoshikazu; Hori, Tomokatsu

    2010-06-01

    Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas. Eighty-five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week. Cabergoline normalized hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 microadenomas disappeared. Eighty patients (94%) conceived 95 pregnancies, two of which were cabergoline-free second pregnancies. The dose of cabergoline at the first pregnancy was 0.25-9 mg/wk overall and 2-9 mg/wk in the resistant patients. Of the 93 pregnancies achieved on cabergoline, 86 resulted in 83 single live births, one stillbirth, and two abortions; the remaining seven were ongoing. All babies were born healthy, without any malformations. No mothers experienced impaired vision or headache suggestive of abnormal tumor reexpansion throughout pregnancy. Cabergoline achieved a high pregnancy rate with uneventful outcomes in infertile women with prolactinoma, independent of tumor size and bromocriptine resistance or intolerance. Cabergoline monotherapy could substitute for the conventional combination therapy of pregestational surgery or irradiation plus bromocriptine in macroprolactinomas.

  11. Dosimetric verification of a high dose rate brachytherapy treatment planning system in homogeneous and heterogeneous media.

    Science.gov (United States)

    Uniyal, S C; Sharma, S D; Naithani, U C

    2013-03-01

    To verify the dosimetric accuracy of treatment plans in high dose rate (HDR) brachytherapy by using Gafchromic EBT2 film and to demonstrate the adequacy of dose calculations of a commercial treatment planning system (TPS) in a heterogeneous medium. Absorbed doses at chosen points in anatomically different tissue equivalent phantoms were measured using Gafchromic EBT2 film. In one case, tandem ovoid brachytherapy was performed in a homogeneous cervix phantom, whereas in the other, organ heterogeneities were introduced in a phantom to replicate the upper thorax for esophageal brachytherapy treatment. A commercially available TPS was used to perform treatment planning in each case and the EBT2 films were irradiated with the HDR Ir-192 brachytherapy source. Film measurements in the cervix phantom were found to agree with the TPS calculated values within 3% in the clinically relevant volume. In the thorax phantom, the presence of surrounding heterogeneities was not seen to affect the dose distribution in the volume being treated, whereas, a little dose perturbation was observed at the lung surface. Doses to the spinal cord and to the sternum bone were overestimated and underestimated by 14.6% and 16.5% respectively by the TPS relative to the film measurements. At the trachea wall facing the esophagus, a dose reduction of 10% was noticed in the measurements. The dose calculation accuracy of the TPS was confirmed in homogeneous medium, whereas, it was proved inadequate to produce correct dosimetric results in conditions of tissue heterogeneity. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  12. Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

    Directory of Open Access Journals (Sweden)

    Metha Maenhout

    2017-04-01

    Full Text Available Purpose : Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods : Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT. Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE version 4.0. Results : With a median follow-up of 12 months (range, 6-15, there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV was 4.8 cc (range, 1.9-6.6 cc. A median of 8 catheters (range, 6-9 were used, and the median dose to the treatment volume (GTV was a D95: 19.3 Gy (SD 15.5-19.4 Gy. Conclusions : Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

  13. Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gogna, Nirdosh Kumar, E-mail: kumar_gogna@health.qld.gov.au [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Burmeister, Elizabeth [Princess Alexandra Hospital, Brisbane, Queensland (Australia); Holt, Tanya [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia)

    2012-06-01

    Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

  14. A simple and safe method for 131I radiolabeling of rituximab for myeloablative high-dose radioimmunotherapy.

    Science.gov (United States)

    Tran, Ly; Baars, Joke W; Maessen, Harry J; Hoefnagel, Cornelis A; Beijnen, Jos H; Huitema, Alwin D R

    2009-02-01

    The aim of this study was to develop a safe and simple radiolabeling and purification procedure for high-dose (131)I-rituximab for treatment of patients with non-Hodgkin's lymphoma. As the starting point, the conventional Iodogen-coated vial method was applied. After the iodogen-coated monoclonal antibody (mAb) method, a labeling method involving much lower amounts of iodogen was assessed. Subsequently, (131)I-rituximab was purified with a tangential flow filtration system. Quality control of the final product was performed by using size-exclusion chromatography with ultraviolet detection and by instant high-performance thin-layer chromatography. Immunoreactivity was determined by using a cell-binding assay. During the labeling procedure, radiation exposure was monitored. The coated vial method resulted in a low radiation exposure, but immunoreactivity was highly compromised (37%). Also, formation of aggregates was observed. The maximal observed effective dose was 18 microSv, finger thermoluminescence dosemeters revealed a hand-dose measurement of 0.8 mSv. The second method resulted in an immunoreactivity of 70%. Radiochemical purity was >97% after purification. The maximal measured effective dose was 31 microSv, and detected exposure to the hands was 1.9 mSv. We have developed a simple labeling technique for the preparation of high-dose (131)I-rituximab. The method offers a high purity and retained immunoreactivity with minimal radiation exposure for involved personnel.

  15. High dose chemoradiation for unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy: a single tertiary care centre experience

    Science.gov (United States)

    Mehta, Shaesta; Kalyani, Nikhil; Chaudhari, Suresh; Dharia, Tejas; Shetty, Nitin; Chopra, Supriya; Goel, Mahesh; Kulkarni, Suyash; Shrivastava, Shyam Kishore

    2017-01-01

    Background We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. Methods From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. Results Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). Conclusions Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas. PMID:28280622

  16. Correlations between cytogenetic and molecular monitoring among patients with newly diagnosed chronic myeloid leukemia in chronic phase: post hoc analyses of the Rationale and Insight for Gleevec High-Dose Therapy study

    National Research Council Canada - National Science Library

    Akard, Luke P; Cortes, Jorge E; Albitar, Maher; Goldberg, Stuart L; Warsi, Ghulam; Wetzler, Meir; Ericson, Solveig G; Radich, Jerald P

    2014-01-01

    ...) monitoring methods may be more convenient. To conduct post hoc analyses of the Rationale and Insight for Gleevec High-Dose Therapy study to evaluate correlations between results of cytogenetic testing and molecular monitoring from BM and PB...

  17. 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

  18. High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series

    OpenAIRE

    von Schoen-Angerer, Tido; Wilkens, Johannes; Kienle, Gunver S; Kiene, Helmut; Vagedes, Jan

    2015-01-01

    Viscum album extract (European mistletoe), containing immune-active compounds with dose-dependent cytotoxic activity, is being used as an adjuvant cancer treatment in Europe. Few studies have been done with high-dose, fever-inducing Viscum album treatment. The authors retrospectively analyzed the case notes of patients with resectable bladder cancer who underwent initiation of high-dose Viscum album treatment at their clinic between January 2006 to December 2012. High-dose Viscum album showed...

  19. High dose rate endobronchial brachytherapy: a curative treatment; La curietherapie endobronchique de haut debit de dose: un traitement curatif

    Energy Technology Data Exchange (ETDEWEB)

    Peiffert, D.; Spaeth, D.; Winnefeld, J. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France); Menard, O. [Centre Hospitalier Universitaire Nancy-Brabois, 54 - Vandoeuvre-les-Nancy (France)

    2000-06-01

    New endobronchial techniques of treatment allow a good unblocking. Nevertheless, only high dose rate brachytherapy delivers a curative treatment for invasive carcinomas. This study analyses the results of the first 33 consecutive patients treated with curative intent by this technique from 1994 to 1997, and followed-up more than one year. Thirty-seven lesions were treated, with usual schedule delivering 30 Gy at 1 cm depth in six fractions and three to five weeks. All the patients were meticulously selected on the local involvement of the tumour and absolute contraindications to a surgical treatment. All of them have a pulmonary disease history or a general contraindication. With a 14-month follow-up, the local control at two months after the treatment was 95 % (endoscopic and histologic), and 90 % of the patients presented a prolonged local control. Four patients died of the treated cancer, another of a controlateral cancer. Ten patients died of another disease, five of them from a respiratory insufficiency. The overall survival rate at two years was 53 % and the specific survival rate 80 %. The acute tolerance was good, without incident. Asymptomatic bronchial stenoses, described by endoscopic follow-up, were described for seven patients. We conclude that, on the basis of a good selection of the patients, and a respect of the indications, high dose rate endobronchial brachytherapy is an effective curative treatment. It offers a new curative option and must be proposed for the small invasive carcinomas in non-operable patients. (author)

  20. The comparison between the efficacy of high dose acyclovir and erythromycin on the period and signs of pitiriasis rosea

    Directory of Open Access Journals (Sweden)

    Ehsani Amirhooshang

    2010-01-01

    Full Text Available Background: Pityriasis Rosea (PR is an acute inflammatory and self-limiting skin disorder, sometimes with troublesome symptoms. To date, there are few treatments available for this disorder. Aim: Compare the traditional treatment with erythromycin to a newly introduced antiviral treatment acyclovir for PR. Materials and Methods: Patients with clinically confirmed diagnosis of PR, matching our exclusion criteria, were enrolled. They were randomized in two groups that received high-dose oral acyclovir or erythromycin. The participants were evaluated two, four, and eight weeks after commencement of the study and followed for one year. Results: A total of 30 patients including 15 males and 15 females completed the study. After eight weeks, 13 patients in the acyclovir group experienced complete response, while in the erythromycin group only six patients had complete response (P < 0.05. Also, patients in the acyclovir group experienced faster resolution of pruritus in comparison with the erythromycin group (not significant. No adverse drug reaction was detected in both groups. Conclusion: It seemed that a high-dose of oral acyclovir was a safe and effective therapy for PR, although this remained to be confirmed in larger studies.

  1. High dose of aspirin moderates diabetes-induced changes of heart glycogen/glucose metabolism in rats.

    Science.gov (United States)

    Dervisevik, M; Dinevska-Kovkarovska, Suzana; Dimitrovska, M; Cipanovska, N; Miova, B

    2014-11-01

    Aspirin (ASA), as a multifunctional drug has been used as a hypoglycaemic agent in the treatment of diabetes and severe hyperglycaemia and has been established as a secondary strategy which may prevent many cardiovascular events. In this study we investigated high dose (100 mg/kg b.w./i.p) and time-dependent (2, 7 and 14 days) effects of ASA on the heart key enzymes and substrates from glycogen/glucose metabolism in control and diabetic rats. The results accomplished demonstrated that ASA significantly potentiates glycogen accumulation, as well as decreased blood glucose level and heart glycolytic potential in control rats. The treatment of diabetic rats with ASA caused moderation of the diabetic complication-significant inhibition of glycogen accumulation, lowering of blood glucose, as well as elevation of glycolytic potential. In conclusion, we propose that use of high-dose of ASA has anabolic effects in control rats and reduces heart glycogen glucose complications in diabetic rats. The moderation of diabetes-induced changes is time-dependent and involves reduction of glycogenogenesis and inhibited depression of glycolysis, with a tendency to maintenance control values.

  2. High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

    Science.gov (United States)

    Zheng, Jin-Ping; Wen, Fu-Qiang; Bai, Chun-Xue; Wan, Huan-Ying; Kang, Jian; Chen, Ping; Yao, Wan-Zhen; Ma, Li-Jun; Xia, Qi-Kui; Gao, Yi; Zhong, Nan-Shan

    2013-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

  3. High-dose inhaled salbutamol has no acute effects on aerobic capacity or oxygen uptake kinetics in healthy trained men

    DEFF Research Database (Denmark)

    Elers, J; Mørkeberg, Jakob; Jansen, T

    2012-01-01

    The prevalence of asthma is higher among elite athletes than in the general population. This has resulted in the frequent use of anti-asthmatic medication such as beta2-agonists among asthmatic athletes. Beta2-agonists are on the prohibited list of WADA. The use of the beta2-agonist salbutamol is......) deficit related to oxygen uptake kinetics. In conclusion, no ergogenic effect of a high dose of salbutamol on aerobic capacity was found....... is only permitted in therapeutic inhaled doses. Most studies have reported the lack of ergogenic effects of therapeutic doses of inhaled beta2-agonists measured in maximal oxygen uptake. No previous studies have examined any possible effects of high-dose inhaled salbutamol on oxygen uptake kinetics. We...... oxygen uptake kinetics. During the incremental test, there were no effects of inhaled salbutamol on VO(2max) in absolute or relative terms, and no effect on peak power and lactate threshold. During the submaximal test, we found no effects on the time constant, time delay, the mean response time or O(2...

  4. Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats.

    Science.gov (United States)

    Nakato, Yasuya; Abekawa, Tomohiro; Inoue, Takeshi; Ito, Koki; Koyama, Tsukasa

    2011-10-24

    We recently proposed a new psychostimulant animal model of the progressive pathophysiological changes of schizophrenia. Studies using that model produced a treatment strategy for preventing progression. Lamotrigine (LTG) blocks repeated high-dosage methamphetamine (METH)-induced initiation and expression of prepulse inhibition deficit and development of apoptosis in the medial prefrontal cortex (mPFC). Moreover, it inhibits METH-induced increases in extracellular glutamate levels in the mPFC (Nakato et al., 2011, Neurosci. Lett.). Abnormal behavior induced by METH or NMDA receptor antagonists is regarded as an animal model of schizophrenia. This study examined the effects of LTG on the development of behavioral sensitization to METH and cross-sensitization to dizocilpine (MK-801) by repeated administration of high-dose METH (2.5mg/kg, 10 times s.c.). Rats were injected repeatedly with LTG (30mg/kg) after 120min METH administration (2.5mg/kg). Repeated co-administration of LTG blocked the development of behavioral cross-sensitization to MK-801 (0.15mg/kg), but it did not prevent behavioral sensitization to METH (0.2mg/kg). The LTG-induced prevention of increased glutamate by high-dose METH might be related to the former finding. Combined results of our previous studies and this study suggest that LTG is useful to treat schizophrenia, especially at a critical point in its progression. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Early postnatal additional high-dose oral vitamin A supplementation versus placebo for 28 days for preventing bronchopulmonary dysplasia or death in extremely low birth weight infants.

    Science.gov (United States)

    Meyer, Sascha; Gortner, Ludwig

    2014-01-01

    Prematurity and the associated risk for bronchopulmonary dysplasia (BPD) remain a significant threat to extremely low birth weight (ELBW) infants. Vitamin A has been considered a therapeutic alternative in reducing the rate of BPD and mortality. To investigate whether early postnatal, additional high-dose oral vitamin A supplementation for 28 days is more efficient in reducing BPD or death in ELBW infants than placebo treatment. This is a multicenter, double-blind RCT comparing postnatal high-dose oral vitamin A supplementation (5,000 IU vitamin A/kg/day vs. placebo) for 28 days in ELBW neonates requiring mechanical ventilation, noninvasive ventilatory support or supplemental oxygen at 24 h of age. The primary end point is the proportion of children who died before 36 weeks' gestational age or developed moderate or severe BPD. BPD is defined as the need for supplemental oxygen to maintain SaO2 of ≥92% at rest at 36 weeks' postmenstrual age (PMA). Clinical secondary end points include the following: BPD (including mild form), intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, total number of days of mechanical ventilation and oxygen supplementation, and safety and tolerability of high-dose vitamin A supplementation. The results of the NeoVitaA trial will provide robust data with regard to the efficacy of high-dose oral vitamin A supplementation in reducing the incidence of BPD or death at 36 weeks' PMA in ELBW infants. © 2014 S. Karger AG, Basel.

  6. Finger Injection with High-Dose (1:1,000) Epinephrine: Does it Cause Finger Necrosis and Should it be Treated?

    Science.gov (United States)

    Fitzcharles-Bowe, Colleen; Denkler, Keith

    2006-01-01

    Objectives Accidental finger injections with high-dose (1:1,000) epinephrine is a new and increasing phenomenon. The purpose of this study is to document the incidence of finger necrosis and the treatment for this type of injury. The necessity or type of treatment required for this type of injury has not been established. Methods The literature was reviewed from 1900 to 2005 by hand and by Internet to document all cases of high-dose (1:1,000) finger epinephrine injection. In addition, the authors added five additional cases. Results There are a total of 59 reported cases of finger injections with high-dose epinephrine, of which, 32 cases were untreated. There were no instances of necrosis or skin loss, but neuropraxia lasting as long as 10 weeks and reperfusion pain were carefully documented. Treatment was not uniform for those who received it, but phentolamine was the most commonly used agent. Conclusions There is not one case of finger necrosis in all of the 59 reported cases of finger injections with 1:1,000 epinephrine in the world literature. The necessity or type of treatment of high-dose epinephrine injection injuries remains conjecture, but phentolamine is the most commonly used agent in the reported cases, and the rationale and evidence for its use are discussed PMID:18780041

  7. Successful management of a patient with toxic epidermal necrolysis by high dose intravenous immunoglobulin

    Directory of Open Access Journals (Sweden)

    Ali Güneş

    2013-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a disease that mostly caused by drug use and characterized by acute onset and rapidly progressive necrosis of the epidermis. In severe cases, mortality rate change between 20% and 60%. Although there is no definite treatment, some authors have reported the effectiveness of intravenous immunoglobulin (IVIG. Here, we presented a 9-year-old male patient with TEN. Skin rashes of patient began after three days of using ibuprofen, metronidazole, clarithromycin, and procaine penicillin. Skin lesions resembling second-degree burns covered 50% of the patient’s body surface area. After giving high-dose IVIG, the patient’s lesions improved. This case is an example of effect of high dose IVIG in the treatment of TEN. J Clin Exp Invest 2013; 4 (4: 503-505

  8. Remote afterloading high dose-rate intracavity radiotherapy for advanced maxillary cancer. Treatment with individual appliances

    Energy Technology Data Exchange (ETDEWEB)

    Horimoto, Susumu; Kakei, Masaki; Saito, Tomokatsu [Yokohama City Univ. (Japan). School of Medicine] [and others

    1998-08-01

    Seven advanced maxillary cancers, 5 squamous cell carcinomas, and 2 adenoid cystic carcinomas were treated with remote afterloading high dose-rate intracavity radiotherapy. For treatment, we fabricated individual dental acrylic appliances for the postoperative area of the oral cavity. Because the appliance was specially matched to the remaining maxillary structures, radiation doses to the treated area were easily reproduced without distress to the patient. However, minor or major complications (moderate or severe mucositis and osteoradionecrosis) were observed in all patients. In this study, the number of patients was too small to assess the significance of this treatment. Nevertheless, with improvements, we think that remote afterloading high dose-rate intracavity radiotherapy with a dental acrylic appliance will soon be used to treat advanced maxillary carcinoma. (author)

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Varney VA

    2011-09-01

    Full Text Available Veronica A Varney1, Jane Evans1, Amolak S Bansal2 1Department of Respiratory Medicine, 2Department of Immunology and Allergy, St. Helier Hospital, Carshalton, Surrey, UK Abstract: Reactive airways dysfunction syndrome is a controversial and poorly understood condition produced by inhalational injury from gas, vapors, or fumes. The symptoms mimic asthma, but appear unresponsive to asthma treatments. If symptoms persist for more than 6 months, there is a risk that they can become chronic. For these cases, effective treatments are lacking and quality of life is poor. We describe the first use of high-dose vitamin D in a patient with this condition, who fulfilled the 1995 American College of Chest Physicians criteria for this syndrome. The patient we describe presented an extremely difficult management problem and was refractory to conventional treatments, but responded to high-dose oral vitamin D supplements. Keywords: asthma, vitamin D, reactive airways dysfunction syndrome, cough, inhalational injury

  11. 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

    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....... 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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  14. 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)

  15. 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.

  16. Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

    Science.gov (United States)

    Akioka, K; Ishikawa, T; Osaka, M; Kadotani, Y; Okugawa, K; Nakano, K; Osaka, Y; Tsuchiya, K; Sako, H

    Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Faiz Anwer

    2015-01-01

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

  18. Inadvertent intramuscular administration of high dose bacillus Calmette Guerin vaccine in a pre-term infant

    Directory of Open Access Journals (Sweden)

    Asima Banu

    2013-01-01

    Full Text Available This case report examined the natural course of reaction after accidental intramuscular administration of high dose Bacille Calmette-Guιrin (BCG vaccine into the anterolateral aspect of thigh of a pre-term infant as a part of routine vaccination instead of intra-dermal injection into the arm. There is no consensus on the best management of this complication, although in this case healing was prolonged but was spontaneous without anti-tubercular chemotherapy.

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

    OpenAIRE

    Umesh, Shreekantiah; Sinha, Vinod Kumar

    2014-01-01

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

  20. 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

  1. Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl [Department of Brachytherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Gruszczynska, Ewelina; Bijok, Michal [Department of Medical Physics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Jonska-Gmyrek, Joanna [Department of Teleradiotherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Dabkowski, Mateusz [Department of Brachytherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Staniaszek, Jagna [Department of Teleradiotherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Michalski, Wojciech [Department of Clinical Trials and Biostatistics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Kowalczyk, Adam; Milanowska, Katarzyna [Department of Medical Physics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)

    2016-09-01

    Purpose: To evaluate the long-term results of computed tomography (CT)–planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. Methods and Materials: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. Results: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. Conclusions: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and

  2. 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

  3. 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.

  4. 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)

  5. Provider knowledge of trivalent inactivated and high-dose influenza vaccines.

    Science.gov (United States)

    Tewell, Chad; Wright, Patty W; Talbot, H Keipp

    2014-10-21

    The objective of this study was to assess provider knowledge about trivalent inactivated and high dose influenza vaccines. Hence, a 20-item survey was distributed to providers within the Internal Medicine department at an urban academic medical center. Two hundred and eighty-one (24.5%) providers responded. The correct response rate was 63.2%. The highest performing subspecialties were infectious diseases (80.5%), endocrinology (69.2%), and pulmonary (68%). Those who received an influenza vaccine during the most recent season scored significantly higher than those who did not (63.6% vs. 43.6%, p=.001). Areas where respondents did poorly included questions pertaining to contraindications to immunizations (27.4%), common adverse events after immunization (29.2%), target antigen (73.5%), number of strains in the trivalent inactivated vaccine (62.9%), and time to immunity (61.4%). High dose vaccine knowledge was poor, with 37% of providers unaware of its existence. Significant gaps in provider knowledge exist regarding both trivalent inactivated and high dose influenza vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. The Role of High Dose Intratympanic Dexamethasone as Salvage Therapy for Idiopathic Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Kordiš, Špela; Battelino, Saba

    2017-11-21

    The aim of this study was to assess the efficacy of a single high dose intratympanic (IT) dexamethasone (DEX) as salvage therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) after unsuccessful treatment with oral corticosteroid (CS). This was a prospective open-label study of 59 patients treated with IT DEX after systemic CS therapy has failed. All patients received high dose (24 mg/mL) IT DEX in a single injection through myringotomy. Of the 59 patients, 40.7% showed improvement in their mean pure tone average (PTA) with IT DEX (p=0.005). The difference in the mean PTA after oral CS treatment only from baseline was not statistically significant (p=0.074). The time from onset of hearing loss to the start of therapy was significantly associated with the outcome (p=0.03). We determined that high dose IT DEX as salvage therapy was beneficial when the primary treatment with oral CS had failed. An early start of the treatment significantly influenced the improvement of hearing.

  7. Applicator Attenuation Effect on Dose Calculations of Esophageal High-Dose Rate Brachytherapy Using EDR2 Film

    Directory of Open Access Journals (Sweden)

    Seyed Mohsen Hosseini Daghigh

    2012-03-01

    Full Text Available Introduction Interaluminal brachytherapy is one of the important methods of esophageal cancer treatment. The effect of applicator attenuation is not considered in dose calculation method released by AAPM-TG43. In this study, the effect of High-Dose Rate (HDR brachytherapy esophageal applicator on dose distribution was surveyed in HDR brachytherapy. Materials and Methods A cylindrical PMMA phantom was built in order to be inserted by various sizes of esophageal applicators. EDR2 films were placed at 33 mm from Ir-192 source and irradiated with 1.5 Gy after planning using treatment planning system for all applicators. Results The results of film dosimetry in reference point for 6, 8, 10, and 20 mm applicators were 1.54, 1.53, 1.48, and 1.50 Gy, respectively. The difference between practical and treatment planning system results was 0.023 Gy (

  8. 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

  9. Predictors of toxicity after image-guided high-dose-rate interstitial brachytherapy for gynecologic cancer.

    Science.gov (United States)

    Lee, Larissa J; Viswanathan, Akila N

    2012-12-01

    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. 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. 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). 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 adequate tumor coverage while minimizing the D2cc to the

  10. Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Yasuo, E-mail: yoshioka@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Kotsuma, Tadayuki [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Komiya, Akira [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Department of Urology, Chiba University Hospital, Chiba (Japan); Kariya, Shinji [Department of Radiology, Kochi Medical School, Kochi (Japan); Konishi, Koji [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nonomura, Norio [Department of Urology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Tanaka, Eiichi [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Nishimura, Kensaku [Department of Urology, Osaka National Hospital, Osaka (Japan); Fujiuchi, Yasuyoshi; Kitamura, Hiroshi [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Yamagami, Takuji [Department of Radiology, Kochi Medical School, Kochi (Japan); Yamasaki, Ichiro [Department of Urology, Kochi Medical School, Kochi (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Teshima, Teruki [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nakamura, Katsumasa [Department of Radiation Oncology, Hamamatsu University School of Medicine, Shizuoka (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2017-04-01

    Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

  11. High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference.

    Science.gov (United States)

    Piketty, Marie-Liesse; Prie, Dominique; Sedel, Frederic; Bernard, Delphine; Hercend, Claude; Chanson, Philippe; Souberbielle, Jean-Claude

    2017-05-01

    High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS) and is expected to be adopted by a large number of patients. Biotin therapy leads to analytical interference in many immunoassays that utilize streptavidin-biotin capture techniques, yielding skewed results that can mimic various endocrine disorders. We aimed at exploring this interference, to be able to remove biotin and avoid misleading results. We measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), parathyroid homrone (PTH), 25-hydroxyvitamin D (25OHD), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, C-peptide, cortisol (Roche Diagnostics assays), biotin and its main metabolites (liquid chromatography tandem mass spectrometry) in 23 plasmas from MS patients and healthy volunteers receiving high-dose biotin, and in 39 biotin-unsupplemented patients, before and after a simple procedure (designated N5) designed to remove biotin by means of streptavidin-coated microparticles. We also assayed fT4, TSH and PTH in the 23 high-biotin plasmas using assays not employing streptavidin-biotin binding. The biotin concentration ranged from 31.7 to 1160 µg/L in the 23 high-biotin plasmas samples. After the N5 protocol, the biotin concentration was below the detection limit in all but two samples (8.3 and 27.6 μg/L). Most hormones results were abnormal, but normalized after N5. All results with the alternative methods were normal except two slight PTH elevations. In the 39 biotin-unsupplemented patients, the N5 protocol did not affect the results for any of the hormones, apart from an 8.4% decrease in PTH. We confirm that most streptavidin-biotin hormone immunoassays are affected by high biotin concentrations, leading to a risk of misdiagnosis. Our simple neutralization method efficiently suppresses biotin interference.

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

    Science.gov (United States)

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

    2013-07-13

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

  13. Available evidence on re-irradiation with stereotactic ablative radiotherapy following high-dose previous thoracic radiotherapy for lung malignancies.

    Science.gov (United States)

    De Bari, Berardino; Filippi, Andrea Riccardo; Mazzola, Rosario; Bonomo, Pierluigi; Trovò, Marco; Livi, Lorenzo; Alongi, Filippo

    2015-06-01

    Patients affected with intra-thoracic recurrences of primary or secondary lung malignancies after a first course of definitive radiotherapy have limited therapeutic options, and they are often treated with a palliative intent. Re-irradiation with stereotactic ablative radiotherapy (SABR) represents an appealing approach, due to the optimized dose distribution that allows for high-dose delivery with better sparing of organs at risk. This strategy has the goal of long-term control and even cure. Aim of this review is to report and discuss published data on re-irradiation with SABR in terms of efficacy and toxicity. Results indicate that thoracic re-irradiation may offer satisfactory disease control, however the data on outcome and toxicity are derived from low quality retrospective studies, and results should be cautiously interpreted. As SABR may be associated with serious toxicity, attention should be paid for an accurate patients' selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. 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

  15. 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

  16. Learning curve of MRI-based planning for high-dose-rate brachytherapy for prostate cancer.

    Science.gov (United States)

    Buus, Simon; Rylander, Susanne; Hokland, Steffen; Søndergaard, Christian Skou; Pedersen, Erik Morre; Tanderup, Kari; Bentzen, Lise

    2016-01-01

    To evaluate introduction of MRI-based high-dose-rate brachytherapy (HDRBT), including procedure times, dose-volume parameters, and perioperative morbidity. Study included 42 high-risk prostate cancer patients enrolled in a clinical protocol, offering external beam radiotherapy + two HDRBT 8.5 Gy boosts. Time was recorded for initiation of anesthesia (A), fixation of needle implant (B), end of MR imaging (C), plan approval (D), and end of HDRBT delivery (E). We defined time A-E as total procedure time, A-B as operating room time, B-C as MRI procedure time, C-D as treatment planning time, and D to E as treatment delivery time. Dose-volume parameters were retrieved from the dose planning system. Results from the first 21 patients were compared with the last 21 patients. Total procedure time, operating room time, MRI procedure time, and treatment planning time decreased significantly from average 7.6 to 5.3 hours (p < 0.01), 3.6 to 2.4 hours (p < 0.01), 1.6 to 0.8 hours (p < 0.01), and 2.0 to 1.3 hours (p < 0.01), respectively. HDRBT delivery time remained unchanged at 0.5 hours. Clinical target volume prostate+3mmD90 fulfilled planning aim in 92% of procedures and increased significantly from average 8.3 to 9.0 Gy (p < 0.01). Urethral D0.1 cm(3) and rectal D2 cm(3) fulfilled planning aim in 78% and 95% of procedures, respectively, and did not change significantly. Hematuria occurred in (95%), hematoma (80%), moderate to strong pain (35%), and urinary retention (5%) of procedures. After introduction of MRI-based HDRBT, procedure times were significantly reduced. D90 Clinical target volumeprostate+3mm fulfilled constraints in most patients and improved over time, but not at expense of an increased urethral or rectal dose. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  17. Performance assessment of the BEBIG MultiSource® high dose rate brachytherapy treatment unit

    Science.gov (United States)

    Palmer, Antony; Mzenda, Bongile

    2009-12-01

    A comprehensive system characterisation was performed of the Eckert & Ziegler BEBIG GmbH MultiSource® High Dose Rate (HDR) brachytherapy treatment unit with an 192Ir 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

  18. Limitations of the TG-43 formalism for skin high-dose-rate brachytherapy dose calculations.

    Science.gov (United States)

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

    2014-02-01

    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. 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(60)Co and (192)Ir sources and a hypothetical (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. For a 5 cm × 5 cm(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 (60)Co and (192)Ir, yet -3% for (169)Yb. For the interstitial implant, dose differences at the skin surface were -7% for (60)Co, -0.6% for (192)Ir, and -2.5% for (169)Yb. 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 (60)Co and (192)Ir. For lower energy radionuclides like (169)Yb, bolus may be needed; and (iii) for the interstitial case, at

  19. 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

  20. 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.

  1. 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

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

    Science.gov (United States)

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

    2004-01-01

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

  3. The growth and physiological responses of tambaqui Colossoma macropomum fed on the high dose of clove oil-supplemented diet

    Directory of Open Access Journals (Sweden)

    Andi Tiara Eka Diana Puteri

    2016-02-01

    Full Text Available ABSTRACT In this study, tambaqui Colossoma macropomum juvenile were given feed supplemented with clove oil Syzygium aromaticum at a dose of 0 and 100 mg/100 g diet. This study purposed to assessment the effect of clove oil supplementation at high dose (100 mg/100 g diet on growth performance and health status of freshwater tambaqui. As many as 25 fishes with initial body weight 7.62±0.44 g maintained in 15 aquariums for 45 days. Each treatment consisted of three replications. Data were analyzed by t-test. The results showed that tambaqui growth performance on both treatments were not significantly different. However, supplementation of high doses 100 mg clove oil/100 g diet showed reduce on the blood parameters and declining the abundant of intestinal microflora in tambaqui gut, but the types seen more diverse. The observation of fish liver histology showed that hepatocyte cells in the treatment of 100 mg clove oil become smaller and dense compared with 0 mg clove oil treatment. The use of high doses of clove oil does not interfere with the tambaqui growth performance despite the downturn in the physiological responses were observed. Keywords: clove oil, Syzygium aromaticum, Colossoma macropomum, growth performance  ABSTRAK Di dalam penelitian ini, benih ikan bawal tawar Colossoma macropomum dipelihara dengan pemberian pakan yang ditambah minyak cengkeh Syzygium aromaticum pada kadar 0 dan 100 mg/100 g pakan. Tujuannya untuk melihat pengaruh penambahan minyak cengkeh di dalam pakan pada dosis tinggi (100 mg/100 g pakan terhadap performa pertumbuhan dan respons fisiologis ikan bawal. Sebanyak 25 ekor ikan bawal dengan bobot individu awal 7,62 ± 0,44 g dipelihara pada 15 akuarium selama 45 hari. Data yang diperoleh dianalisis dengan uji komparasi t-test antar dua perlakuan dengan tiga ulangan. Hasil penelitian menunjukkan bahwa tidak ada pengaruh dari kedua perlakuan terhadap parameter pertumbuhan. Namun, pemberian pakan yang mengandung

  4. On-Line High Dose-Rate Gamma Ray Irradiation Test of the CCD/CMOS Cameras

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jai Wan; Jeong, Kyung Min [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    In this paper, test results of gamma ray irradiation to CCD/CMOS cameras are described. From the CAMS (containment atmospheric monitoring system) data of Fukushima Dai-ichi nuclear power plant station, we found out that the gamma ray dose-rate when the hydrogen explosion occurred in nuclear reactors 1{approx}3 is about 160 Gy/h. If assumed that the emergency response robot for the management of severe accident of the nuclear power plant has been sent into the reactor area to grasp the inside situation of reactor building and to take precautionary measures against releasing radioactive materials, the CCD/CMOS cameras, which are loaded with the robot, serve as eye of the emergency response robot. In the case of the Japanese Quince robot system, which was sent to carry out investigating the unit 2 reactor building refueling floor situation, 7 CCD/CMOS cameras are used. 2 CCD cameras of Quince robot are used for the forward and backward monitoring of the surroundings during navigation. And 2 CCD (or CMOS) cameras are used for monitoring the status of front-end and back-end motion mechanics such as flippers and crawlers. A CCD camera with wide field of view optics is used for monitoring the status of the communication (VDSL) cable reel. And another 2 CCD cameras are assigned for reading the indication value of the radiation dosimeter and the instrument. In the preceding assumptions, a major problem which arises when dealing with CCD/CMOS cameras in the severe accident situations of the nuclear power plant is the presence of high dose-rate gamma irradiation fields. In the case of the DBA (design basis accident) situations of the nuclear power plant, in order to use a CCD/CMOS camera as an ad-hoc monitoring unit in the vicinity of high radioactivity structures and components of the nuclear reactor area, a robust survivability of this camera in such intense gamma-radiation fields therefore should be verified. The CCD/CMOS cameras of various types were gamma irradiated at a

  5. High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients’ Perceptions on Initiation, Reasons for Use, and Obtainment

    Science.gov (United States)

    Liebrenz, Michael; Schneider, Marcel; Buadze, Anna; Gehring, Marie-Therese; Dube, Anish; Caflisch, Carlo

    2015-01-01

    Background High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated. Methods We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group’s views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring’s qualitative content analysis was used to evaluate our data. Results In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination. Conclusions Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients

  6. Effect of high doses of L-ascorbic acid on the antioxidative/oxidative state in the rats

    DEFF Research Database (Denmark)

    Niemiec, T.; Sawosz, E.; Chwalibog, André

    2005-01-01

    The objective of this study was to determine the effects of mega-doses of vitamin C (0.3, 0.6 and 0.9% of diet) as a dietary supplement for rats on selected indices of the antioxidative/oxidative state in 40 growing Wistar rats (4x10). It was found that L-ascorbic acid and Total Antioxidative State...... (TAS) in plasma did not increase with increasing vitamin C supply. The results indicate that high doses of L-ascorbic acid (0.3 and 0.9 but not 0.6%) increased the concentration of this antioxidant in plasma. Supplementation of vitamin C above 0.3% to the diets had pro-oxidative effects on lipid...

  7. Pediatric peri-operative fractionated high-dose-rate brachytherapy for recurrent Wilms’ tumor using a reconstructed Freiburg flap

    Directory of Open Access Journals (Sweden)

    Emily Flower

    2016-10-01

    Full Text Available Purpose : To report peri-operative fractionated high-dose-rate (HDR brachytherapy with a 3D customized Freiburg flap applicator to treat locally recurrent Wilms’ tumor, followed by immediate hyperthermic intraperitoneal chemotherapy for a 16-year-old with a second recurrence of nephroblastoma (Wilms’ tumor. Material and methods: The tumor was excised and surgical bed was treated with fractionated HDR brachytherapy using a Freiburg flap applicator. Hyperthermic intraperitoneal chemotherapy was performed immediately after the removal of brachytherapy applicator. Results: The Freiburg flap was successfully reconstructed to enable delivery of conformable peri-operative HDR brachytherapy. The clinical target volume (CTV D90 was 26 Gy in 5 fractions. Conclusions : Peri-operative fractionated HDR brachytherapy with a customized Freiburg flap applicator was delivered successfully across a large multi-disciplinary team.

  8. Radiochromic film for dosimetric measurements in radiation shielding composites synthesized for applied in radiology procedures of high dose

    Energy Technology Data Exchange (ETDEWEB)

    Fontainha, C. C. P. [Universidade Federal de Minas Gerais, Departamento de Engenharia Nuclear, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil); Baptista N, A. T.; Faria, L. O., E-mail: crissia@gmail.com [Centro de Desenvolvimento da Tecnologia Nuclear / CNEN, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil)

    2015-10-15

    Full text: Medical radiology offers great benefit to patients. However, although specifics procedures of high dose, as fluoroscopy, Interventional Radiology, Computed Tomography (CT) make up a small percent of the imaging procedures, they contribute to significantly increase dose to population. The patients may suffer tissue damage. The probability of deterministic effects incidence depends on the type of procedure performed, exposure time, and the amount of applied dose at the irradiated area. Calibrated radiochromic films can identify size and distribution of the radiated fields and measure intensities of doses. Radiochromic films are sensitive for doses ranging from 0.1 to 20 c Gy and they have the same response for X-rays effective energies ranging from 20 to 100 keV. New radiation attenuators materials have been widely investigated resulting in dose reduction entrance skin dose. In this work, Bi{sub 2}O{sub 3} and ZrO{sub 2}:8 % Y{sub 2}O{sub 3} composites were obtained by mixing them with P(VDF-Tr Fe) copolymers matrix from casting method and then characterized by Ftir. Dosimetric measurements were obtained with Xr-Q A2 Gafchromic radiochromic films. In this setup, one radiochromic film is directly exposed to the X-rays beam and another one measures the attenuated beam were exposed to an absorbed dose of 10 mGy of RQR5 beam quality (70 kV X-ray beam). Under the same conditions, irradiated Xr-Q A2 films were stored and scanned measurement in order to obtain a more reliable result. The attenuation factors, evaluated by Xr-Q A2 radiochromic films, indicate that both composites are good candidates for use as patient radiation shielding in high dose medical procedures. (Author)

  9. A new model for volume recombination in plane-parallel chambers in pulsed fields of high dose-per-pulse

    Science.gov (United States)

    Gotz, M.; Karsch, L.; Pawelke, J.

    2017-11-01

    In order to describe the volume recombination in a pulsed radiation field of high dose-per-pulse this study presents a numerical solution of a 1D transport model of the liberated charges in a plane-parallel ionization chamber. In addition, measurements were performed on an Advanced Markus ionization chamber in a pulsed electron beam to obtain suitable data to test the calculation. The experiment used radiation pulses of 4 μs duration and variable dose-per-pulse values up to about 1 Gy, as well as pulses of variable duration up to 308 μs at constant dose-per-pulse values between 85 mGy and 400 mGy. Those experimental data were compared to the developed numerical model and existing descriptions of volume recombination. At low collection voltages the observed dose-per-pulse dependence of volume recombination can be approximated by the existing theory using effective parameters. However, at high collection voltages large discrepancies are observed. The developed numerical model shows much better agreement with the observations and is able to replicate the observed behavior over the entire range of dose-per-pulse values and collection voltages. Using the developed numerical model, the differences between observation and existing theory are shown to be the result of a large fraction of the charge being collected as free electrons and the resultant distortion of the electric field inside the chamber. Furthermore, the numerical solution is able to calculate recombination losses for arbitrary pulse durations in good agreement with the experimental data, an aspect not covered by current theory. Overall, the presented numerical solution of the charge transport model should provide a more flexible tool to describe volume recombination for high dose-per-pulse values as well as for arbitrary pulse durations and repetition rates.

  10. [Trimodal Therapy for Stage IIIA-B NSCLC Involving High Dose Neoadjuvant Chemoradiotherapy. Is Surgery a Rational Option?

    Science.gov (United States)

    Koryllos, Aris; Ludwig, Corinna; Engel-Riedel, Walburga; Hammer-Helmig, Michaela; Stoelben, Erich

    2017-09-01

    Introduction Stage III non-small cell lung cancer (NSCLC) and its possible multimodal therapy present a challenge to the responsible oncologist, chest surgeon and radiologist. The aim of the present retrospective study was to analyse and evaluate the treatment algorithm in our hospital for patients with stage III NSCLC (intention to treat). We compared an aggressive treatment regime with primary trimodal therapy (high dose radiochemotherapy and resection), independently of "multilevel" N2 or "single level" N3 status. These results were then compared with a historical group of our patients who solely received simultaneous radiochemotherapy (bimodal therapy). Materials and Methods Within the period of the study, 156 patients were diagnosed with stage III NSCLC and treated with trimodal therapy. The median age was 71 years. 103 patients (60%) were male, 53 (34%) female. In the group with bimodal therapy, 102 patients were evaluated. Results After radiological restaging and checking functional resectability, 90 patients (57.7%) in the trimodal therapy group received secondary resection, including 37 (41.1%) lobectomies/bilobectomies, 37 (41.1%) sleeve lobectomies, 13 (14.4%) pneumonectomies and 3 (3.3%) segmentectomies (for severely restricted pulmonary function). The median survival time in the trimodal therapy group was 535 days and in the bimodal group 388 days; this difference was not statistically significant (p = 0.1377). Finally the 5-year survival after actual therapy was performed ("as-treated trimodally" vs. "as-treated bimodally"). The median survival time was then 807 days for trimodal therapy and 427 days for bimodal therapy. Conclusion High dose neoadjuvant radiochemotherapy followed by secondary resection is still a valuable option for selected patients with stage III NSCLC. However, this retrospective analysis failed to find a statistically significant survival advantage for the "intention-to-treat" trimodal patients. Georg Thieme Verlag KG

  11. Therapeutic drug monitoring and use of an adjusted body weight strategy for high-dose voriconazole therapy.

    Science.gov (United States)

    Richards, Patrick G; Dang, Kimberlyn M; Kauffman, Carol A; Stalker, Kay Lyn; Sudekum, David; Kerr, Lisa; Brinker-Bodley, Michelle; Cheriyan, Beena; West, Nina; Collins, Curtis D; Polega, Shikha; Malani, Anurag N

    2017-04-01

    A high-dose 12 mg/kg/day (6 mg/kg twice daily) voriconazole regimen was recommended by the CDC to treat patients injected with contaminated methylprednisolone acetate that caused a multi-state fungal outbreak in 2012-13. Therapeutic drug monitoring results of this unique regimen are unknown, as is the most appropriate dosing weight for obese patients. We evaluated voriconazole trough measurements for this dosing scheme, as well as the use of adjusted body weight dosing for obese patients. Voriconazole trough levels were analysed in obese (BMI ≥35 kg/m 2 ) and non-obese (BMI voriconazole troughs were supratherapeutic (>5 mg/L) in 65 (47%) patients, therapeutic (2-5 mg/L) in 57 (41%) patients and subtherapeutic (Voriconazole doses >11 and >8 mg/kg/day produced mainly first steady-state supratherapeutic troughs in 44 obese and 94 non-obese patients, respectively. An initial 12 mg/kg/day was progressively lowered to a median maintenance dose of 8.5 mg/kg/day in the obese and 8.6 mg/kg/day in the non-obese. A high-dose voriconazole regimen produced initial supratherapeutic troughs that required dose adjustment downward by nearly 30%. Adjusted body weight dosing in obese patients resulted in a similar maintenance dose to total body weight dosing in the non-obese, and appears to be a sensible dosing strategy for these patients.

  12. Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Hebblewaite Diane

    2011-01-01

    Full Text Available Abstract Background In many preclinical AIDS research studies, antiretroviral therapy (ART is administered to experimentally simian immunodeficiency (SIV-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r-(phosphonomethoxy propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S-[2-(hydroxymethyl-1,3-oxathiolan-5-yl]cytosine; emtricitabine and stavudine (d4T. Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals. While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.

  13. [Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously].

    Science.gov (United States)

    Fievet, Patrick; Coppin, Mathilde; Brazier, François; Lefèvre, Magali; Stephan, Robin; Demontis, Renato

    2012-02-01

    Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self-limiting myalgia and arthralgia. No venous inflammatory reaction was noted. The administration of high doses of LMWID is effective in treating anemia of CKD in the predialysis stage with a satisfactory tolerance, without affecting kidney function and helps preserve the venous capital. It should be reserved for patients whose serum ferritin is less than or equal to 150 μg/L. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights

  14. 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.

  15. High doses of ethylene diurea (EDU) are not toxic to willow and act as nitrogen fertilizer.

    Science.gov (United States)

    Agathokleous, Evgenios; Paoletti, Elena; Saitanis, Costas J; Manning, William J; Shi, Cong; Koike, Takayoshi

    2016-10-01

    Ethylene diurea (EDU) is synthetic chemical which protects plants against damage caused by ground level O3 and is used experimentally as a biomonitoring tool at doses usually ranging from 200 to 400mgL(-1) a.i. Although several studies have investigated the protective action of EDU, this mechanism remains unclear. Important uncertainties in EDU action are whether EDU acts as a source of nitrogen (N) to plants and whether high doses are phytotoxic. In order to answer these questions, we conducted an open-field experiment where potted willow (Salix sachalinensis Fr. Schm) plants were exposed to ambient O3 conditions and treated with 0, 800 or 1600mgL(-1) EDU as a soil drench, every nine days, for about 2.5months. We examined approximately 50 response variables. Based on N content in different plant organs, we found that (a) all EDU was transferred to the leaves and (b) high doses of EDU increased the leaf N content. However, EDU did not affect the C content and distribution within the plant body. Still, even at the highest dose, EDU was not toxic to this fast-growing species (however such a high dose should not be applied in uncontrolled environments); and there was no EDU persistence in the soil, as indicated by soil N content. Notably, our soil was free from organic matter and N-poor. EDU per se does not cause toxicity to willow plants when applied as drench to a soil with no organic matter, rather, high EDU doses may act as nitrogen fertilizer in a nitrogen-poor soil. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-10-21

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

  17. High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

    Science.gov (United States)

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Hall, Kathi; Stein, C Michael

    2017-02-01

    Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects. The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point. We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline.

  18. Prior methamphetamine self-administration attenuates serotonergic deficits induced by subsequent high-dose methamphetamine administrations.

    Science.gov (United States)

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

    2012-11-01

    Pre-clinical studies indicate that high-dose, non-contingent methamphetamine (METH) administration both rapidly and persistently decreases serotonergic neuronal function. Despite research indicating the hippocampus plays an important role in METH abuse and is affected by METH use, effects of METH self-administration on hippocampal serotonergic neurons are not well understood, and were thus an important focus of the current study. Because humans often administer METH in a binge-like pattern, effects of prior METH self-administration on a subsequent "binge-like" METH treatment were also examined. Rats were treated as described above, and sacrificed 1 or 8d after self-administration or 1h or 7d after the final binge METH or saline exposure. Hippocampal serotonin (5-hydroxytryptamine; 5HT) content and transporter (SERT) function were assessed. METH self-administration per se had no persistent effect on hippocampal 5HT content or SERT function. However, this treatment attenuated the persistent, but not acute, hippocampal serotonergic deficits caused by a subsequent repeated, high-dose, non-continent METH treatment administered 1 d the last self-administration session. No attenuation in persistent deficits were seen when the high-dose administration of METH occurred 15d after the last self-administration session. The present findings demonstrate that METH self-administration alters serotonergic neurons so as to engender "tolerance" to the persistent serotonergic deficits caused by a subsequent METH exposure. However, this "tolerance" does not persist. These data provide a foundation to investigate complex questions including how the response of serotonergic neurons to METH may contribute to contingent-related disorders such as dependence and relapse. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Enhanced neurodegeneration after a high dose of methamphetamine in adenosine A3 receptor null mutant mice.

    Science.gov (United States)

    Shen, H; Luo, Y; Yu, S-J; Wang, Y

    2011-10-27

    Previous reports have indicated that adenosine A3 receptor (A3R) knockout mice are more sensitive to ischemic or hypoxic brain injury. The purpose of this study was to examine if suppression of A3R expression is associated with increase in sensitivity to injury induced by a high dose of methamphetamine (Meth). Adult male A3R null mutant (-/-) mice and their controls (+/+) were injected with four doses (2 h apart) of Meth (10 mg/kg) or saline. Animals were placed in a behavioral activity chamber, equipped with food and water, for 52 h starting from one day after injections. The first 4 h were used for studying exploratory behaviors, and the next 48 h were used to measure locomotor activity. High doses of Meth equally reduced the 4-h exploratory behavior in -/- and +/+ mice. Meth suppressed locomotor activity between 4 and 52 h in both groups, with a greater reduction being found in the -/- mice. Brain tissues were collected at 3 days after the Meth or saline injections. Meth treatment reduced striatal dopamine (DA) levels in both +/+ and -/- mice with an increase in 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio being found only in -/- animals. Meth also significantly increased ionized calcium-binding adaptor molecule 1 (Iba-1) and cleaved caspase-3 level in striatum, as well as Iba-1 and TNFα mRNA expression in nigra in -/-, compared to +/+, mice. Previous studies have shown that pharmacological suppression of vesicular monoamine transport 2 (VMAT2) by reserpine enhanced Meth toxicity by increasing cytosolic DA and inflammation. A significant reduction in striatal VMAT2 expression was found in -/- mice compared to +/+ mice, suggesting that increase in sensitivity to Meth injury in -/- mice may be related to a reduction in VMAT2 expression in these mice. In conclusion, our data suggest that A3R -/- mice are more sensitive to high doses of Meth. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  2. [Reversible lactic acidosis in a diabetic on high dose metformin (author's transl)].

    Science.gov (United States)

    Beaudot, C; Merceron, R E; Lavieuville, M; Noël, M; Brohon, J; Raymond, J P

    1980-09-01

    In a diabetic, who took a high dose of 5.85 g metformin daily for 75 days, urinary retention caused by a prostatic adenoma induced functional renal insufficiency and hyperlactacidemia, rapidly reversed with treatment. Plasma and urine levels of metformin were measured at the same time as lactate and pyruvate levels, until all returned to normal. Clinical and biological improvement occured at the same time. The case is discussed in the context of lactic acidosis in diabetics with functional or organic renal insufficiency, treated with metformin.

  3. Intermittent high-dose vitamin C therapy in patients with HTLV-I associated myelopathy.

    Science.gov (United States)

    Kataoka, A; Imai, H; Inayoshi, S; Tsuda, T

    1993-11-01

    The efficacy of intermittent high-dose vitamin C therapy was evaluated in seven patients with HTLV-I-associated myelopathy (HAM). All HAM patients responded well to this therapy without serious side effects. Grade of disability score improved at 9.7 (SD 5.8) months after the therapy from 7.1 (3.3) to 3.6 (2.0) (p < 0.01). Serum immunosuppressive acidic protein was elevated before and decreased after the therapy from 747 (316) to 398 (86) micrograms/ml (p < 0.05), suggesting favourable immunomodulatory action of vitamin C therapy in HAM patients.

  4. High-dose omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia.

    Science.gov (United States)

    Van Biervliet, S; Van Winckel, M; Robberecht, E; Kerremans, I

    2001-09-01

    The authors describe 4 children with recurrent stenosis and persistent esophagitis after secondary repair of a long gap esophageal atresia. They underwent an esophageal reconstruction by elongation of the lesser gastric curvature according to Schärli at the age of 11 to 14 months. All had esophagitis grade III to IV (Savary-Miller classification), esophageal stenosis, and failure to thrive. Effective treatment of the esophagitis and prevention of stenosis consisted in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment, the need for esophageal dilatation disappeared, and nutritional status normalized. Copyright 2001 by W.B. Saunders Company.

  5. A model for low dose effects of low-LET radiation delivered at high dose rates

    Science.gov (United States)

    Schöllnberger, H.; Stewart, R.D.; Mitchel, R.E.J.

    2011-01-01

    In vitro studies show that protective tumour-reducing effects occur for low dose rates (mGy per minute). To account for these phenomena, we have previously developed stochastic and deterministic multi-stage cancer models that include radiation-induced adaptations in DNA repair processes and radical scavenging. Here, these models are extended to account for the induction of radioprotective mechanisms for low doses of low LET radiation delivered at high dose rates. Cellular adaptations in DNA repair are related to temporal changes in the amount of DNA damage in a cell. The combined effects of endogenous DNA damage, background radiation and artificial irradiation are considered. PMID:22318364

  6. Chronical cervical infections and dysplasia (CIN I, CIN II): Vaginal vitamin D (high dose) treatment

    OpenAIRE

    Schulte-Uebbing, C; Schlett, S; Craiut, ID; Antal, L; Olah, H

    2014-01-01

    In a small praxis/ambulance study we evaluated data of 200 women with chronical recurrent cervical infections and with a cervix dysplasia (CIN 1, CIN 2). who got after the primary therapy a treatment with vitamin D vaginal suppositories (12.500 IU, 3 nights a week, for 6 weeks). We found that - when compared with the lactobacillus vaginal suppositories - the high dose vitamin D vaginal treatment might be more effective. Vitamin D showed very good anti-inflammatory effects. In the survey after...

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines [Instituto de Pesquisas Energeticas e Nucleares/Comissao Nacional de Energia Nuclear Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo (Brazil)], E-mail: miteixei@ipen.br; Melo, Adeilson P. [Instituto de Pesquisas Energeticas e Nucleares/Comissao Nacional de Energia Nuclear Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo (Brazil); Centro Federal de Educacao Tecnologica de Sergipe, Aracaju (Brazil)], E-mail: adeilson_pessoa_melo@yahoo.com.br; Ferraz, Gilberto M. [Depto. de Fisica Nuclear, Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil)], E-mail: gmarconf@if.usp.br; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares/Comissao Nacional de Energia Nuclear Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo (Brazil)], E-mail: lcaldas@ipen.br

    2010-04-15

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

  9. Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery

    Directory of Open Access Journals (Sweden)

    Satu Lakio

    2015-12-01

    Full Text Available In this study a carrier-free dry powder inhalation (DPI containing L-arginine (ARG was developed. As such, it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis. Various processing methods were used to manufacture high-dose formulation batches consisting various amounts of ARG and excipients. The formulations were evaluated using several analytical methods to assess suitability for further investigation. Several batches had enhanced in vitro aerolization properties. Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.

  10. Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain

    Directory of Open Access Journals (Sweden)

    Leppert W

    2015-12-01

    Full Text Available Wojciech Leppert, Grzegorz Kowalski Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Background: Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB] in cancer patients with severe neuropathic pain. However, high doses of TB of 140 µg/h are rarely used.Patients and methods: Three cancer patients with severe neuropathic Numeric Rating Scale (NRS pain scores of 8–10 who were successfully treated with high doses of TB up to 140 µg/h along with other opioids and adjuvant analgesics.Results: TB was administered for a long period of follow-up (9 months to 4 years, including 34–261 days of treatment with the dose of 140 µg/h, which allowed achievement of satisfactory analgesia (NRS 3–5 and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 µg/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment.Conclusion: TB at doses of up to 140 µg/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients’ quality of life. Clinical studies may explore higher than maximal 140 µg/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. Keywords: adverse effects, analgesia, cancer, neuropathic pain, transdermal buprenorphine, treatment

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

    Energy Technology Data Exchange (ETDEWEB)

    Fonteyne, Valerie, E-mail: valerie.fonteyne@uzgent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Ost, Piet [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Villeirs, Geert [Department of Radiology, Ghent University Hospital, Ghent (Belgium); Oosterlinck, Willem [Department of Urology, Ghent University Hospital, Ghent (Belgium); Impens, Aline; De Gersem, Werner; De Wagter, Carlos; De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-05-01

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

  12. Short-term assessment of BCR repertoires of SLE patients after high dose glucocorticoid therapy with high-throughput sequencing.

    Science.gov (United States)

    Shi, Bin; Yu, Jiang; Ma, Long; Ma, Qingqing; Liu, Chunmei; Sun, Suhong; Ma, Rui; Yao, Xinsheng

    2016-01-01

    We analyze and assess BCR repertoires of SLE patients before and after high dose glucocorticoid therapy to address two fundamental questions: (1) After the treatment, how the BCR repertoire of SLE patient change on the clone level? (2) How to screen putative autoantibody clone set from BCR repertoire of SLE patients? The PBMCs of two SLE patients (P1 and P2) at different time points were collected, and DNA of these samples were extracted. High-throughput sequencing technology was applied in detection of BCR repertoire. Finally, we used bioinformatic methodology to analyse sequence data. We found that these two patients lost some IGHV3 family genes usage after treatment compared with before treatment. For pairing of IGHV-IGHJ gene, no significant change was shown for each patient. In addition, analyses of the composition of H-CDR3 showed overall AA compositions of H-CDR3 at three time points in each SLE patients were very similar, and the results of H-CDR3 AA usage that had the same length (14 AA) and the same position were similar. Antinuclear antibody tests of SLE patients showed that level of some antinuclear antibodies reduced after treatment; however, there was no sign that the percentage of autoantibody clones in BCR repertoires would reduce. High dose glucocorticoid treatment in short term will have little impact on composition of BCR repertoire of SLE patient. Treatment can reduce the amount of autoantibody in the protein level, but may not reduce the percentage of autoantibody clones in BCR repertoire in the clonal level.

  13. High-dose, short-interval daptomycin regimen was safe and well tolerated in three patients with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Yabuno K

    2013-11-01

    Full Text Available Kaori Yabuno,1,2,* Masafumi Seki,1,* Koji Miyawaki,1,2 Yoshihiro Miwa,2 Kazunori Tomono11Division of Infection Control and Prevention, 2Department of Pharmacy, Osaka University Hospital, Osaka, Japan *These authors contributed equally to this workBackground: The recommended daptomycin dosage is 4 or 6 mg/kg/day for the treatment of complicated skin and soft tissue infections or for Staphylococcus aureus bacteremia, endocarditis, and osteomyelitis. Every other day administration is usually recommended for patients with mild to moderate renal impairment. Higher doses (>6 mg/kg/day have been explored as a possible alternative. Daptomycin is considered a safe anti-methicillin-resistant S. aureus (MRSA drug, although renal dysfunction may be worsened. In this paper we report on three patients with chronic renal failure who received a higher dose of daptomycin daily for successful treatment for MRSA bacteremia, MRSA osteomyelitis, and methicillin-resistant S. epidermidis (MRSE endocarditis.Results: Previous administration of other drugs, including vancomycin, teicoplanin, and linezolid, had failed. In spite of daily treatment with daptomycin instead of the recommended alternate day regimen, adverse effects, such as elevation of creatinine and creatine phosphokinase, did not occur.Conclusion: These experiences suggest that administration of high-dose/short-interval daptomycin can be efficient and safe even in the setting of renal dysfunction, and should be considered for the treatment of severe MRSA/MRSE infections in these patients.Keywords: daptomycin, high-dose, renal failure, methicillin-resistant Staphylococcus aureus, creatine phosphokinase

  14. Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

    Science.gov (United States)

    Armstrong, Eliana S; Mikulca, Janelle A; Cloutier, Daniel J; Bliss, Caleb A; Steenbergen, Judith N

    2016-11-25

    Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration. Patients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5-9 days after treatment) and late follow-up (21-42 days after treatment) visits in the microbiologically evaluable population (N = 327). Test-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ≤4 μg/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ≤0.06 μg/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit. Results from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ≥4 μg/mL. ClinicalTrials.gov, NCT01345929 and NCT01345955.

  15. Resorption and tolerance of the high doses of ferrous sulfate and ferrous gluconate in the patients on peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Laušević Mirjana

    2006-01-01

    Full Text Available Background/Aim. Iron supplementation plays a crucial role in peritoneal dialysis (PD patients. Oral iron substitution is more convenient than intravenous therapy in PD patients, but impaired absorption and adverse effects may be limiting factors for oral treatment. The aim of this study was to compare the absorption and side effects of high doses ferrous sulphate and ferrous gluconate in PD patients. Methods. Blood samples were taken from 29 PD patients at baseline, as well as 2, 4 and 8 hours after oral intake of 4 ferrous sulphate tablets (containing 105 mg elemental iron per tablet. The test was repeated using 8 ferrous gluconate drinkable ampoules (containing 50 mg elemental iron per ampoule. Results. The maximal increase in serum iron level during the test with iron sulphate was 113.51±103.37% versus the initial values of 183.87±37.38% during the ferrous gluconate test. The maximal values of serum iron after the intake of ferrous sulphate were 26.23±9.95 µmol/l versus 30.97±8.65 µmol/l after the intake of ferrous gluconate. There was a statistically significant difference between these two groups. Six patients showed an increase in serum iron of more than 300% after a high ferrous gluconate dose, while in 15 of the patients serum iron increased between 100% and 300%, and in 8 of the patients serum iron levels increased by less than 100%. Side effects occurred more frequently after the intake of ferrous sulphate than ferrous gluconate. Conclusion. High doses of oral iron were well absorbed and tolerated in PD patients. Ferrous gluconate was better absorbed and tolerated than ferrous sulphate, thus we recommend it for oral iron supplementation in PD patients.

  16. Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.

    OpenAIRE

    Schetelig, Johannes; Fetscher, Sebastian; Reichle, Albrecht; Berdel, Wolfgang E; Beguin, Yves; Brunet, Salut; Caballero, Dolores; Majolino, Ignazio; Hagberg, Hans; Johnsen, Hans E; Kimby, Eva; Montserrat, Emilio; Stewart, Douglas; Copplestone, Adrian; Rosler, Wolf

    2003-01-01

    BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the impact of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation in patients with AIL. Data on 29 patients, who were transplanted between 1992 and 1998 in 16 transplant centers, were collected on standardized documentation forms. RESULTS: The median age at transplant...

  17. Influence of high-dose intraoperative remifentanil with or without amantadine on postoperative pain intensity and morphine consumption in major abdominal surgery patients: a randomised trial.

    Science.gov (United States)

    Treskatsch, Sascha; Klambeck, Michael; Mousa, Shaaban A; Kopf, Andreas; Schäfer, Michael

    2014-01-01

    Human volunteer studies demonstrate ketamine-reversible opioid-induced hyperalgesia, consistent with reports of increased postoperative pain and analgesic consumption. However, recent clinical trials showed controversial results after intraoperative administration of high-dose remifentanil. To investigate in lower abdominal surgery patients whether postoperative pain intensity and analgesic consumption are increased following intraoperative high-dose vs. low-dose remifentanil, and whether this could be prevented by preoperative administration of the NMDA antagonist amantadine. Randomised, placebo-controlled, clinical study. University hospital. Sixty patients scheduled for elective major lower abdominal surgery. Patients were randomly assigned to one of three anaesthetic regimens. First, in the group 'low-dose remifentanil and preoperative isotonic saline' (n=15), a remifentanil infusion was maintained at a rate of 0.1 μg kg min throughout anaesthesia, and the end-tidal concentration of sevoflurane started at 0.5 minimum alveolar concentration (MAC) and was increased by 0.2% increments according to clinical demand. Preoperatively, 500 ml NaCl 0.9% were infused as study solution. Second, in the group 'high-dose remifentanil and preoperative saline' (n=17), the end-tidal concentration of sevoflurane was maintained at 0.5 MAC throughout anaesthesia. A remifentanil infusion was started at a rate of 0.2 μg kg min and subsequently increased by 0.05 μg kg min increments to clinical demand. Preoperatively, these patients also received a solution of 500 ml NaCl 0.9% as study solution. Third, the group 'high-dose remifentanil and preoperative amantadine' (n=16) received the same anaesthetic protocol as the second group, but the preoperative study solution was substituted by amantadine (200 mg/500 ml). Pain intensity measured by the numerical rating scale and cumulative morphine consumption. The remifentanil dose in both high-dose groups was significantly higher compared

  18. Adaptation of the CVT algorithm for catheter optimization in high dose rate brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Poulin, Eric; Fekete, Charles-Antoine Collins; Beaulieu, Luc [Département de Physique, de Génie Physique et d’Optique et Centre de recherche sur le cancer de l’Université Laval, Université Laval, Québec, Québec G1V 0A6, Canada and Département de Radio-Oncologie et Axe oncologie du Centre de Recherche du CHU de Québec, CHU de Québec, 11 Côte du Palais, Québec, Québec G1R 2J6 (Canada); Létourneau, Mélanie [Département de Radio-Oncologie, CHU de Québec, 11 Côte du Palais, Québec, Québec G1R 2J6 (Canada); Fenster, Aaron [Imaging Research Laboratories, Robarts Research Institute, 100 Perth Drive, London, Ontario N6A 5K8 (United Kingdom); Pouliot, Jean [Department of Radiation Oncology, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, San Francisco, California 94143-1708 (United States)

    2013-11-15

    Purpose: An innovative, simple, and fast method to optimize the number and position of catheters is presented for prostate and breast high dose rate (HDR) brachytherapy, both for arbitrary templates or template-free implants (such as robotic templates).Methods: Eight clinical cases were chosen randomly from a bank of patients, previously treated in our clinic to test our method. The 2D Centroidal Voronoi Tessellations (CVT) algorithm was adapted to distribute catheters uniformly in space, within the maximum external contour of the planning target volume. The catheters optimization procedure includes the inverse planning simulated annealing algorithm (IPSA). Complete treatment plans can then be generated from the algorithm for different number of catheters. The best plan is chosen from different dosimetry criteria and will automatically provide the number of catheters and their positions. After the CVT algorithm parameters were optimized for speed and dosimetric results, it was validated against prostate clinical cases, using clinically relevant dose parameters. The robustness to implantation error was also evaluated. Finally, the efficiency of the method was tested in breast interstitial HDR brachytherapy cases.Results: The effect of the number and locations of the catheters on prostate cancer patients was studied. Treatment plans with a better or equivalent dose distributions could be obtained with fewer catheters. A better or equal prostate V100 was obtained down to 12 catheters. Plans with nine or less catheters would not be clinically acceptable in terms of prostate V100 and D90. Implantation errors up to 3 mm were acceptable since no statistical difference was found when compared to 0 mm error (p > 0.05). No significant difference in dosimetric indices was observed for the different combination of parameters within the CVT algorithm. A linear relation was found between the number of random points and the optimization time of the CVT algorithm. Because the

  19. High-Dose Benzodiazepine Users' Perceptions and Experiences of Anterograde Amnesia.

    Science.gov (United States)

    Liebrenz, Michael; Schneider, Marcel; Buadze, Anna; Gehring, Marie-Therese; Dube, Anish; Caflisch, Carlo

    2016-09-01

    Associations between criminal activity and the use of psychotropic substances are well established. Flunitrazepam, specifically, has been suspected of triggering, per se, violent criminal behavior and severe memory disturbances in the form of anterograde amnesia. However, data from investigations of this relationship are scarce and have been primarily derived from forensic institutions, where there may be a reporting bias. This study was a qualitative exploration of high-dose benzodiazepine users' experiences of anterograde amnesia symptoms and their beliefs about their behavior during the phases of memory impairment in a nonforensic setting. Users subjectively reported experiencing symptoms of anterograde amnesia, especially after combining short-acting benzodiazepines with alcohol, but only rarely when using slow-onset, long-acting compounds. They perceived their experiences as unpleasurable, unpredictable, and embarrassing. Their awareness developed with time, triggered by descriptions of disinhibited and erratic behavior by others. Users described being victimized during phases of anterograde amnesia in addition to engaging in violent and criminal activities themselves. Although unable to recall, many participants believed that they had been able to make rational decisions while intoxicated with flunitrazepam, disregarding notions of diminished insight. In light of the varying terminology used for the phases of memory disturbance and these findings, we suggest that forensic experts additionally explore evaluees' beliefs about amnestic periods and their self-perceptions about their behaviors during these episodes, when evaluating high-dose benzodiazepine-dependent patients. © 2016 American Academy of Psychiatry and the Law.

  20. High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction.

    Science.gov (United States)

    Adamek, Anna; Hu, Kai; Bayer, Barbara; Wagner, Helga; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan

    2007-07-01

    Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.

  1. 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)

  2. Geriatric-oriented high dose nutraceutical ODTs: Formulation and Physicomechanical characterization.

    Science.gov (United States)

    Agiba, Ahmed M; Abdel-Hamid, Sameh; Nasr, Maha; Geneidi, Ahmed S

    2017-03-20

    Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance. Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment. Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburstTM C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems. Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. PharmaburstTM C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets. The improved disintegration and dissolution properties of our prepared ODTs is expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. [Optimal way of administration of high dose intravenous furosemide - continuous infusion or bolus?].

    Science.gov (United States)

    Gallusová, Jana; Halačová, Milada; Cerný, Dalibor

    2014-10-01

    Furosemide is a loop diuretic used in states of volume overload. The need for high doses is due to its reduced efficacy caused by lower concentration of furosemide achieved at the site of action in the renal tubule lumen and adaptation mechanisms. High doses have been associated with the development of ionic dysbalance, direct toxicity and intravascular volume fluctuations. The way of furosemide administration (intermitent versus continuously) to influence efficacy and safety is contradictory evaluated in EBM. The aim of this study is to analyze the available data for evaluation of the efficacy and safety of intermittent versus continuous dose regimens. A systematic search on PubMed from 1990 to 2013 using the keywords - furosemide, loop diuretic, bolus, continuous infusion, efficacy, safety, heart failure, ICU, critical care. The pharmacokinetic and pharmacodynamic knowledge of furosemide create a theoretical assumption for the preference of continuous infusions before intermittent boluses. Assessement of available studies, however, yet in clinical practice did not proof the advantage of one over the other route of administration.

  4. 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.

  5. Ureteral stent insertion for gynecologic interstitial high-dose-rate brachytherapy.

    Science.gov (United States)

    Demanes, D Jeffrey; Banerjee, Robyn; Cahan, Benjamin L; Lee, Steve P; Park, Sang-June; Fallon, Julia M; Reyes, Paula; Van, Thanh Q; Steinberg, Michael L; Kamrava, Mitchell R

    2015-01-01

    To determine the utility of ureteral stents in interstitial gynecological brachytherapy. We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined. There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D(0.1cc)) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan 3. Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk. Copyright © 2015. Published by Elsevier Inc.

  6. Quality of life in a cohort of high-dose benzodiazepine dependent patients.

    Science.gov (United States)

    Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

    2014-09-01

    Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Late Fecal Incontinence After High-Dose Radiotherapy for Prostate Cancer: Better Prediction Using Longitudinal Definitions

    Energy Technology Data Exchange (ETDEWEB)

    Fiorino, Claudio, E-mail: fiorino.claudio@hsr.it [Department of Medical Physics, San Raffaele Scientific Institute, Milano (Italy); Rancati, Tiziana [Prostate Program, Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Italy); Fellin, Gianni [Department of Radiotherapy, Ospedale Santa Chiara, Trento (Italy); Vavassori, Vittorio [Department of Radiotherapy, Cliniche Humanitas Gavazzeni, Bergamo (Italy); Cagna, Emanuela [Department of Radiotherapy, Ospedale Sant' Anna, Como (Italy); Casanova Borca, Valeria [Department of Medical Physics, Ospedale di Ivrea, Turin (Italy); Girelli, Giuseppe [Department of Radiotherapy, Ospedale di Ivrea, Turin (Italy); Menegotti, Loris [Department of Medical Physics, Ospedale Santa Chiara, Trento (Italy); Monti, Angelo Filippo [Department of Medical Physics, Ospedale Sant' Anna, Como (Italy); Tortoreto, Francesca [Department of Radiotherapy, Ospedale Fatebenefratelli, Roma (Italy); Delle Canne, Stefania [Department of Medical Physics, Ospedale Fatebenefratelli, Roma (Italy); Valdagni, Riccardo [Prostate Program, Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Italy)

    2012-05-01

    Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for {<=}3 years after RT) of 586 patients were available. The peak incontinence (P{sub I}NC) and two longitudinal definitions (chronic incontinence [C{sub I}NC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M{sub I}NC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P{sub I}NC (Grade 2 or greater), C{sub I}NC, and M{sub I}NC of {>=}1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models. Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M{sub I}NC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P{sub I}NC, M{sub I}NC {>=}1, and C{sub I}NC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P{sub I}NC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C{sub I}NC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of {>=}80% was predictive of a M{sub I}NC of {>=}1 (OR, 3.8; p = .008) and of C{sub I}NC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor

  8. Optimal bladder filling during high-dose-rate intracavitary brachytherapy for cervical cancer: a dosimetric study

    Directory of Open Access Journals (Sweden)

    Umesh Mahantshetty

    2017-04-01

    Full Text Available Purpose: The aim of this study is to compare 3D dose volume histogram (DVH parameters of bladder and other organs at risk with different bladder filling protocol during high-dose-rate intracavitary brachytherapy (HDR-ICBT in cervical cancer, and to find optimized bladder volume. Material and methods : This dosimetric study was completed with 21 patients who underwent HDR-ICBT with computed tomography/magnetic resonance compatible applicator as a routine treatment. Computed tomography planning was done for each patient with bladder emptied (series 1, after 50 ml (series 2, and 100 ml (series 3 bladder filling with a saline infusion through the bladder catheter. Contouring was done on the Eclipse Planning System. 7 Gy to point A was prescribed with the standard loading patterns. Various 3D DVH parameters including 0.1 cc, 1 cc, 2 cc doses and mean doses to the OAR’s were noted. Paired t-test was performed. Results : The mean (± SD bladder volume was 64.5 (± 25 cc, 116.2 (± 28 cc, and 172.9 (± 29 cc, for series 1, 2, and 3, respectively. The 0.1 cm 3 ,1 cm 3 , 2 cm 3 mean bladder doses for series 1, series 2, and series 3 were 9.28 ± 2.27 Gy, 7.38 ± 1.72 Gy, 6.58 ± 1.58 Gy; 9.39 ± 2.28 Gy, 7.85 ± 1.85 Gy, 7.05 ± 1.59 Gy, and 10.09 ± 2.46 Gy, 8.33 ± 1.75 Gy, 7.6 ± 1.55 Gy, respectively. However, there was a trend towards higher bladder doses in series 3. Similarly, for small bowel dose 0.1 cm 3 , 1 cm 3 , and 2 cm 3 in series 1, 2, and 3 were 5.44 ± 2.2 Gy, 4.41 ± 1.84 Gy, 4 ± 1.69 Gy; 4.57 ± 2.89 Gy, 3.78 ± 2.21 Gy, 3.35 ± 2.02 Gy, and 4.09 ± 2.38 Gy, 3.26 ± 1.8 Gy, 3.05 ± 1.58 Gy. Significant increase in small bowel dose in empty bladder (series 1 compared to full bladder (series 3 (p = 0.03 was noted. However, the rectal and sigmoid doses were not significantly affected with either series. Conclusions : Bladder filling protocol with 50 ml and 100 ml was well tolerated and achieved a reasonably reproducible bladder volume

  9. High-Dose Borna Disease Virus Infection Induces a Nucleoprotein-Specific Cytotoxic T-Lymphocyte Response and Prevention of Immunopathology†

    Science.gov (United States)

    Furrer, Esther; Bilzer, Thomas; Stitz, Lothar; Planz, Oliver

    2001-01-01

    Experimental Borna disease virus (BDV) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. The virus replicates slowly, and the cellular immune response results in immunopathology. CD8+ T cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J. M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 206:426–434, 1995) have reported protection against Borna disease after inoculation of high-dose cell-adapted BDV. Here we show that the outcome of the infection, i.e., immunopathology versus protection, is simply dependent on the amount of virus used for infection. High-dose BDV (106 FFU) triggers an early virus-specific reaction of the immune system, as demonstrated by strong cellular and humoral responses. In particular, the early presence and function of nucleoprotein-specific CD8+ T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and usually persistent virus infection, high-dose input virus mediates early control of the pathogen due to an efficient induction of an antiviral immune mechanism. From these data, we conclude that immune reactivity, in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention of the ensuing immunopathological disease or whether a persistent infection is established. PMID:11689651

  10. Initial High-Dose Prednisolone Combination Therapy Using COBRA and COBRA-Light in Early Rheumatoid Arthritis

    NARCIS (Netherlands)

    Rasch, L.A.; van Tuyl, L.H.D.; Lems, W.F.; Boers, M.

    2015-01-01

    Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very

  11. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy

    NARCIS (Netherlands)

    de Jonge, M. E.; Mathôt, R. A. A.; Dalesio, O.; Huitema, A. D. R.; Rodenhuis, S.; Beijnen, J. H.

    2002-01-01

    Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated

  12. Haloperidol Treatment after High-Dose Methamphetamine Administration Is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata

    National Research Council Canada - National Science Library

    Hatzipetros, Theo; Raudensky, Jamie G; Soghomonian, Jean-Jacques; Yamamoto, Bryan K

    2007-01-01

    .... We report here that subchronic haloperidol administration after a high-dose regimen of METH produces a heretofore unrecognized toxicity to GABAergic cells, as reflected by GAD67 mRNA expression...

  13. High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jenny E. Han

    2016-06-01

    Conclusions: In this pilot study, high-dose vitamin D3 safely increased plasma 25(OHD concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes.

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

    National Research Council Canada - National Science Library

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

    2011-01-01

    ... to evaluate its effect in the treatment of metastatic breast cancer. We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support...

  15. [Amniotic membrane transplantation and high-dose systemic cyclosporin A (Sandimmun optoral) for Mooren's ulcer].

    Science.gov (United States)

    Spelsberg, H; Sundmacher, R

    2007-02-01

    Mooren's ulcer is a rare, severe corneal autoimmune inflammation leading to blindness if treated insufficiently. High-dose systemic cyclosporin A (Sandimmun optoral) was shown to markedly reduce inflammation and stop corneal destruction. We report on three cases in which this immunosuppressive regimen required additional AM transplantation for complete healing. One 37-year-old male (M) and two 49- (F1) and 58-year-old females (F2) presented with unilateral Mooren's ulcer in different stages of the disease, which deteriorated despite high-dose systemic cyclosporin A (Sandimmun optoral M, F1) or treatment with topical cyclosporin A 2 % (F2). After surgical removal of all grossly affected corneal stroma, amniotic membrane was made to cover the entire cornea and fixed with episcleral sutures in two patients (M, F2). In one patient (F1) a deep marginal ulcer was covered with a fitted AM glap. All patients were treated postoperatively up to 6 months with high-dose systemic cyclosporin A (Sandimmun optoral). Blood trough levels aimed at 150 to 200 ng/mL. Topical cyclosporin A was administered in addition in two patients (M, F2) postoperatively for at least 6 months. Due to incompatibility, one patient (F1) was treated with topical steroids instead. Follow-up time was 42 months (M), 50 months (F1) and 54 months (F2). All three eyes exhibited clinical healing with stable corneal surfaces thereafter. Depending on the stage of Mooren's ulcer at the time of surgery, visual acuity remained at hand motions in one patient (M) and recovered to 1.0 and 0.6, respectively, in two patients (F1, F2). Due to its anti-inflammatory potential, coverage by AM seems to trigger a therapeutic turnaround in cases of Mooren's ulcer which do not heal with intensive immunosuppressive regimens alone. In order to maintain or restore as much visual function as possible, additional amniotic membrane surgery should be performed early enough in the course of the disease.