WorldWideScience

Sample records for chemotherapy including high-dose

  1. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

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

  2. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

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

    2005-01-01

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high

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

    Science.gov (United States)

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

    2016-10-01

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

  4. 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.

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  6. Relapsed Hodgkin lymphoma in adolescents: focus on current high-dose chemotherapy and autologous stem cell transplant

    Directory of Open Access Journals (Sweden)

    Guilcher GM

    2014-05-01

    Full Text Available Gregory MT Guilcher,1 Douglas A Stewart21University of Calgary, Section of Hematology/Oncology/Transplant, Alberta Children’s Hospital, Calgary, Canada; 2University of Calgary, Division of Medical Oncology, Tom Baker Cancer Centre, Calgary, CanadaAbstract: Hodgkin lymphoma is one of the most common cancers of adolescence and young adulthood. Most patients are cured of their disease, with very high cure rates in early stage disease and improving rates of cure even in those who present with advanced stage disease. Upfront therapy often involves chemotherapy and radiation therapy; with improving cure rates, acute and late effects of therapy are informing newer treatment protocols to avoid toxicities. Those children and adolescents with refractory or relapsed disease have lower rates of cure and generally warrant more intensive therapy. High-dose chemotherapy and autologous stem cell transplantation is often administered in such cases. This intensive intervention can be curative, but carries additional risks in the short and long term. This review includes a discussion of both transplant and non-transplant therapy for relapsed disease, commonly employed conditioning regimens, acute and late toxicities of therapy, as well as quality of life data. In addition, newer approaches to therapy for Hodgkin lymphoma are reviewed, with a focus on how such novel therapies might relate to high-dose chemotherapeutic approaches.Keywords: Hodgkin lymphoma, adolescents, high-dose chemotherapy, autologous stem cell transplant

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

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Testicular germ cell cancer (TGCC) is rare form ofmalignant disease that occurs mostly in young manbetween age 15 and 40. The worldwide incidence ofTGCC is 1.5 per 100000 man with the highest rates inNorth Europe. After discovery of cisplatin cure ratesof TGCC are very favorable between 90%-95% andunlike most solid tumors, cure rate for metastatic TGCCis around 80%. Metastatic TGCC is usually treatedwith 3-4 cycles of bleomycin, etoposide, cisplatinumchemotherapy with or without retroperitoneal surgeryand cure rates with this approach are between 41% inpoor risk group and 92% in good risk group of patients.Cure rates are lower in relapsed and refractory patientsand many of them will die from the disease if not curedwith first line chemotherapy. High dose chemotherapy(HDCT) approach was used for the first time during the1980s. Progress in hematology allowed the possibility tokeep autologous haematopoietic stem cells alive ex-vivoat very low temperatures and use them to repopulatethe bone marrow after sub-lethal dose of intesivemyeloablative chemotherapy. Despite the fact thatthere is no positive randomized study to prove HDCTconcept, cure rates in relapsed TGCC are higher afterhigh dose therapy then in historical controls in studieswith conventional treatment. Here we review clinicalstudies in HDCT for TGCC, possibilities of mobilisingsufficient number of stem cells and future directions inthe treatment of this disease.

  8. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G. [Duesseldorf Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Laws, H.J.; Kaik, B. van; Goebel, U. [Duesseldorf Univ. (Germany). Abt. Paediatrische Haematologie und Onkologie; Burdach, S. [Halle Univ. (Germany). Abt. Paediatrie; Juergens, H. [Muenster Univ. (Germany). Abt. Paediatrische Hematologie und Onkologie

    1999-10-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (<2 years after diagnosis) or multifocal relapse. Patients and Method: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Duesseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) oder Double-ME with whole lung irradiation up to 18 Gy (without TBI). Results: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. Conclusion: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion. (orig.) [German] Hintergrund: Ewing-Tumoren sind radio- und chemosensibel. Im metastasierten Stadium ist die Prognose schlecht. Patienten mit Knochen- oder Knochenmarkinfiltration haben nach drei Jahren eine

  9. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen).

    Science.gov (United States)

    Gianni, Alessandro M; Magni, Michele; Martelli, Maurizio; Di Nicola, Massimo; Carlo-Stella, Carmelo; Pilotti, Silvana; Rambaldi, Alessandro; Cortelazzo, Sergio; Patti, Caterina; Parvis, Guido; Benedetti, Fabio; Capria, Saveria; Corradini, Paolo; Tarella, Corrado; Barbui, Tiziano

    2003-07-15

    Mantle cell lymphoma (MCL) is rarely cured with standard-dose chemotherapy. From January 1997 to February 2000, 28 previously untreated advanced-stage MCL patients younger than 61 years of age were treated at 9 Italian hematologic departments with 3 cycles of standard-dose debulking chemotherapy followed by a high-dose rituximab-supplemented sequence (R-HDS) including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, high-dose melphalan, and high-dose mitoxantrone plus melphalan. Study end points included toxicity, clinical and molecular response rates, long-term event-free survival (EFS), and overall survival (OS) rates, as well as the ability to harvest tumor-free peripheral blood stem cells. Optimal amounts of polymerase chain reaction-negative (PCR-negative) CD34+ cells were collected from all 20 informative patients. One patient died of toxicity. All 27 patients assessable for response achieved a complete response (CR), of which 24 remain in continuous complete remission (CCR) after a median follow-up of 35 months. Three patients had transient evidence of PCR-detectable disease in the bone marrow. The OS and EFS rates at 54 months were 89% and 79%, respectively. These results compare with the 42% OS rate and the 18% EFS rate observed in 35 age-matched historic controls treated with standard-dose chemotherapy at the participating centers. The use of rituximab in combination with high-dose chemotherapy represents a very effective in vivo purging method. The R-HDS regimen can be safely applied in a multicenter hematology setting and leads to long-term EFS and OS in the majority of patients with an otherwise incurable disease.

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

    Directory of Open Access Journals (Sweden)

    Yang FY

    2012-02-01

    ratio (P < 0.001. Combining repeated pulsed HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has similar antitumor effects.Conclusion: This study demonstrates that targeted or untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a promising high-dose chemotherapy method that allows the desired brain tumor region to be targeted specifically.Keywords: repeated focused ultrasound, interleukin-4 receptor, blood-brain barrier, brain tumor, target drug delivery

  11. 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.

  12. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-04-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths.

  13. HIGH-DOSE CHEMOTHERAPY WITH STEM-CELL REINFUSION AND GROWTH-FACTOR SUPPORT FOR SOLID TUMORS

    NARCIS (Netherlands)

    DEVRIES, EGE; DEGRAAF, H; VANDERGRAAF, WTA; MULDER, NH; Boonstra, A.

    1995-01-01

    With the help of stem cell reinfusion and hematopoietic growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs, A number of reasons may have made high-dose chemotherapy less dangerous and the fore more acceptable in a more upfront treatment setting, O

  14. Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Hansen, Per Boye; Penkowa, Milena

    2016-01-01

    PURPOSE: High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey...... cytoprotection in non-malignant cells. METHODS: This trial was a prospective, randomised, double-blind, placebo-controlled pilot study of hematological inpatients (n = 50) receiving bismuth or placebo tablets, in order to identify any potential superiority of bismuth on toxicity from chemotherapy. RESULTS: We....... Also, lymphoma patients' adverse effects were linked to gender. For the first time, bismuth is demonstrated as a safe strategy against chemotherapy's toxicity without interfering with intentional anti-cancer efficiency. Also, we show how gender significantly influences various adverse effects...

  15. Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration.

    Science.gov (United States)

    Kerrigan, D P; Castillo, A; Foucar, K; Townsend, K; Neidhart, J

    1989-09-01

    The peripheral blood morphologic findings in 17 patients with cancer who had received high-dose cytotoxic chemotherapy followed by recombinant human-granulocyte colony-stimulating factor (rh-GCSF) were reviewed and compared with a control group of patients who received only high-dose chemotherapy. Both groups showed dysmyelopoiesis (abnormal granulation and nuclear lobulation) in the granulocytic series during the period of bone marrow recovery that followed the cytotoxic chemotherapy. Most of these morphologic abnormalities were more prominent in the rh-GCSF-treated group. Monocytic cells in both groups showed prominent vacuolation and immature nuclei. The percentages and absolute numbers of large granular lymphocytes were increased in the rh-GCSF group compared with the control group. No quantitative or qualitative abnormalities of eosinophilic or basophilic granulocytes were detected in either group. Both groups showed nonspecific red blood cell abnormalities, and large platelets were present in half of the control group smears. This report provides the first detailed peripheral blood morphologic description in patients treated with rh-GCSF and high-dose chemotherapy.

  16. Prospective study of long-term impact of adjuvant high-dose and conventional-dose chemotherapy on health-related quality of life

    NARCIS (Netherlands)

    Buijs, C.; Rodenhuis, S.; Seynaeve, C.M.; van Hoesel, Q.G.; van der Wall, E.; Smit, W.J.; Nooij, M.A.; Voest, E.; Hupperets, P.; TenVergert, E.M.; van Tinteren, H.; Willemse, P.H.; Mourits, M.J.; Aaronson, N.K.; Post, W.J.; de Vries, E.G.

    2007-01-01

    Purpose To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer. Patients and Methods Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were

  17. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    Science.gov (United States)

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas.

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

    Science.gov (United States)

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

    2014-08-01

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

  19. Risk Factors of anemia in head and neck cancer patients undergoing chemotherapy with high-dose cisplatin

    Directory of Open Access Journals (Sweden)

    Johan Kurnianda

    2008-12-01

    Full Text Available Cisplatin is well-known for its effectiveness against cancer, as well as its toxicity to human tissues. Of several documented side effects, anemia was reported to have significant association with decreased quality of life. This study was conducted to investigate development of cisplatin-induced anemia, and to identify independent factors contributing to anemia. Clinical data from head and neck cancer patients treated with high-dose cisplatin between December 2002 and December 2005 were obtained in this study. Incidence and risk factors of anemia were assessed in a model including age, sex, baseline hemoglobin level, baseline creatinine clearance, and occurrence of distant metastases. Multivariate logistic regression was used to define independent predictors of anemia. Among 86 eligible patients, 26 (30.2% developed anemia, defined as Hb level lower than 11 g/dL. Age > 55 years old (RR = 2.2, 95% CI, 1.2-4.0, female sex (RR = 2.0, 95% CI, 1.2-3.8, baseline Hb ≤ 13 g/dL (RR = 4.2, 95% CI, 1.9-9.4 and baseline CrCl < 50 mL/min (RR = 2.9, 95% CI, 1.7-5.1 were significantly correlated with incidence of anemia (P < 0.05. In multivariate analysis, baseline Hb and baseline CrCl were identified as independent risk factors for anemia. However, considerable confounding was observed in baseline CrCl after stratified by age (aRR = 2.2, 95% CI, 1.1-4.7. Thus, baseline Hb level was the strongest predictor of anemia. The findings suggested that baseline Hb and CrCl were useful to recognize cisplatin-treated patients at risk for anemia who might benefits from preventive measures. (Med J Indones 2008; 17: 248-54Keywords: anemia, cisplatin, chemotherapy, hemoglobin, creatinine clearance

  20. Chemotherapy of onchocerciasis with high doses of diethylcarbamazine or a single dose of ivermectin: microfilaria levels and side effects.

    Science.gov (United States)

    Albiez, E J; Newland, H S; White, A T; Kaiser, A; Greene, B M; Taylor, H R; Büttner, D W

    1988-03-01

    Fifty adult male subjects with moderate to heavy onchocerciasis from the Liberian rain forest were selected for a double-blind placebo-controlled chemotherapy study. The effects of high doses of diethylcarbamazine (DEC) - 30 mg/kg/d - over one week preceded by a one week initial treatment with normal oral doses of DEC or DEC lotion were compared with a single dose of ivermectin (150 micrograms/kg) and placebo. During the initial treatment DEC tablets or lotion caused distinctly more frequent and severe reactions than did invermectin. The reactions to ivermectin did not differ from those of the placebo patients. High doses of DEC caused, in about half of the patients, headache, dizziness, nausea or vomiting. DEC markedly increased the number of corneal microfilariae and of corneal opacities compared to ivermectin. All changes resolved with a return to pretreatment findings two months after treatment. The three treatment groups showed no differences at the ten months follow-up. In all treated patients skin microfilaria counts fell almost to zero by the end of the two week therapy. In the ivermectin group microfilaria counts remained significantly lower than in the DEC patients at the two and ten months examinations. In summary, ivermectin was much better tolerated than DEC and had a longer lasting effect on the microfilariae in the skin. Since high doses of DEC were less effective and caused more frequent and severe side effects, this approach cannot be recommended for treatment of onchocerciasis.

  1. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.

    Science.gov (United States)

    Ma, Yan; Chapman, Julia; Levine, Mark; Polireddy, Kishore; Drisko, Jeanne; Chen, Qi

    2014-02-05

    Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide rationale for reexamining ascorbate treatment. Because of marked pharmacokinetic differences, intravenous, but not oral, ascorbate produces millimolar concentrations both in blood and in tissues, killing cancer cells without harming normal tissues. In the interstitial fluid surrounding tumor cells, millimolar concentrations of ascorbate exert local pro-oxidant effects by mediating hydrogen peroxide (H(2)O(2)) formation, which kills cancer cells. We investigated downstream mechanisms of ascorbate-induced cell death. Data show that millimolar ascorbate, acting as a pro-oxidant, induced DNA damage and depleted cellular adenosine triphosphate (ATP), activated the ataxia telangiectasia mutated (ATM)/adenosine monophosphate-activated protein kinase (AMPK) pathway, and resulted in mammalian target of rapamycin (mTOR) inhibition and death in ovarian cancer cells. The combination of parenteral ascorbate with the conventional chemotherapeutic agents carboplatin and paclitaxel synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer. On the basis of its potential benefit and minimal toxicity, examination of intravenous ascorbate in combination with standard chemotherapy is justified in larger clinical trials.

  2. Circulating progenitors following high-dose sequential (HDS) chemotherapy with G-CSF: short intervals between drug courses severely impair progenitor mobilization.

    Science.gov (United States)

    Tarella, C; Caracciolo, D; Gavarotti, P; Bondesan, P; Cherasco, C; Omedè, P; Bregni, M; Siena, S; Gianni, A M; Pileri, A

    1995-08-01

    Sequential administration of high-dose chemotherapy courses possibly allows extensive in vivo purging before circulating progenitor collection for autograft. To evaluate whether progenitor cell mobilization was negatively affected by repeated high-dose chemotherapy courses, we studied 23 lymphoma patients undergoing the HDS regimen. The scheme includes the sequential administration of cyclophosphamide (CY) given at 7 g/m2 and etoposide (VP16) given at 2 g/m2, each followed by G-CSF (filgrastim) at 5 micrograms/kg/day. Eleven patients received the standard HDS sequence, with a short interval between first and second myelotoxic courses of less than 45 days (median: 30 days); the remaining 12 patients received a modified HDS where the interval between first and second high-dose course was protracted over 2 months (median: 70 days); in this latter group, 2 to 4 conventional debulking courses were delivered prior to HDS. In patients receiving the standard HDS, progenitor mobilization following the first course was consistently high (median circulating CFU-GM/ml peak value: 29,022); however, significantly lower values were observed at the second course (median CFU-GM/ml peak value 3757, P = 0.002). Circulating BFU-E and CD34+ cell values paralleled those of CFU-GM. No significant difference was observed in progenitor mobilization following either course in patients receiving HDS with extended interval (median circulating CFU-GM/ml peak value: 14,363 vs 9208, at first and second course respectively, P = 0.27). Eleven patients had their progenitor cells harvested following the second delayed course and 2-4 leucaphereses allowed very satisfactory harvests in all of them (CFU-GM/kg ranging from 39-340 x 10(4)).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Tolerability of piperacillin/tazobactam in children and adolescents after high dose radio-/chemotherapy and autologous stem cell transplantation.

    Science.gov (United States)

    Nürnberger, W; Bönig, H; Burdach, S; Göbel, U

    1998-01-01

    The combination of piperacillin with tazobactam (PIP/TAZ) extends the activity of piperacillin against gram-positive, gram-negative, and anaerobic bacteria. The broad-spectrum of this formulation, together with its low degree of organ toxicity observed in adults, makes PIP/TAZ a tempting choice for children with radio-/chemotherapy-induced neutropenia. However, the use of PIP/TAZ is not yet approved for children under 12 years of age. The tolerability of PIP/TAZ was assessed in 19 children and adolescents between 2 and 18 years of age who developed a fever during aplasia after high dose radio-/chemotherapy and autologous stem cell transplantation (HD-SCT) for primary multifocal or relapsed solid tumours. Treatment with PIP/TAZ was initiated on average 3 days after HD-SCT, and the treatment was continued for approximately 10 days. Both clinical observation and laboratory studies showed no relevant alterations that would have been attributable to PIP/TAZ treatment. These results indicate that PIP/TAZ appears to be well tolerated in children during the acute phase of HD-SCT.

  4. The toxicity of radiotherapy following high-dose chemotherapy with peripheral blood serum cell support in high-risk breast cancer: a preliminary analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wall, E. van der; Schaake-Koning, C.C.E.; Zandwijk, N. van [Nederlands Kanker Inst. `Antoni van Leeuwenhoekhuis`, Amsterdam (Netherlands)] [and others

    1996-08-01

    High-dose chemotherapy with autologous bone marrow and/or peripheral blood stem cell (PBSC) support is increasingly employed in the adjuvant treatment of high-risk breast cancer. Subsequent radiotherapy has been reported to be associated with morbidity and mortality resulting from pulmonary toxicity. In addition, the course of radiation therapy may be hampered by excess myelosuppression. The aim of this study was to investigate the contribution to radiation-induced toxicity of a high-dose chemotherapy regimen (CTC) that incorporates cyclophosphamide, thiotepa and carboplatin, in patients with high-risk breast cancer. (author).

  5. Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients

    NARCIS (Netherlands)

    Nieboer, P; de Vries, Elisabeth G. E.; Mulder, Nanno; Rodenhuis, S; Bontenbal, M; van der Wall, E; van Hoesel, Q G; Smit, W M; Hupperets, P; Voest, E E; Nooij, M A; Boezen, H M; van der Graaf, W T A

    2008-01-01

    Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and

  6. Pulmonary function after high-dose chemotherapy with autologous bone marrow transplantation and radiotherapy in patients with advanced loco-regional breast cancer

    NARCIS (Netherlands)

    Dolsma, WV; DeVries, EGE; VanderMark, TW; Sleijfer, DT; Willemse, PHB; VanderGraaf, WTA; Mulder, POM; Szabo, BG; Mulder, NH

    1997-01-01

    Our aim was to study the extent of pulmonary toxicity after high-dose chemotherapy and radiotherapy in breast cancer patients. In a retrospective study the pulmonary symptoms and chest X-rays were analysed before, during and after treatment in 17 patients, treated with loco-regional radiotherapy to

  7. Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients.

    NARCIS (Netherlands)

    Nieboer, P.; Vries, E.G. de; Mulder, N.H.; Rodenhuis, S.; Bontenbal, M.; Wall, E. van der; Hoesel, Q.G.C.M. van; Smit, W.M.; Hupperets, P.; Voest, E.E.; Nooij, M.A.; Boezen, H.M.; Graaf, W.T.A. van der

    2008-01-01

    Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and

  8. Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: no impact of chitotriosidase and mannose-binding lectin polymorphisms

    DEFF Research Database (Denmark)

    Klostergaard, Anja; Steffensen, Rudi; Møller, Jens K;

    2010-01-01

    in children with AML, and polymorphism in the MBL-coding gene (MBL2) seems to modify the risk of infections in several patient groups. The purpose of this study was to investigate the possible associations between polymorphisms in CHIT1, MBL2 and sepsis in adult patients treated with high-dose chemotherapy...

  9. Factors influencing haematological recovery following high-dose chemotherapy and peripheral stem-cell transplantation for haematological malignancies : 1-year analysis

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Vellenga, E; van der Graaf, WTA; Mulder, NH; Sluiter, WJ; de Wolf, JTM

    2004-01-01

    Peripheral blood Counts and factors influencing haematological recovery in 98 patients with a relapse-free survival of greater than or equal to 1 year treated with high-dose chemotherapy (HDC) and peripheral stem-cell transplantation (PSCT) for haematological malignancies were analysed. One year aft

  10. Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; Sleijfer, DT; Willemse, PHB; Hospers, GAP; Gietema, JA; Sluiter, WJ; van der Graaf, WTA

    2001-01-01

    Long-term peripheral blood counts and factors influencing long-term trilineage haematological recovery of consecutive patients in a single institution treated with high-dose chemotherapy (HDC) and ABMT or PSCT for solid tumours were examined. Patients with a relapse-free survival of >1 year were inc

  11. Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

    Science.gov (United States)

    Salazar, R; Solá, C; Maroto, P; Tabernero, J M; Brunet, J; Verger, G; Valentí, V; Cancelas, J A; Ojeda, B; Mendoza, L; Rodríguez, M; Montesinos, J; López-López, J J

    1999-01-01

    The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.

  12. High-dose chemotherapy as salvage treatment in germ-cell cancer: when, in whom and how.

    Science.gov (United States)

    Lorch, Anja; Beyer, Jörg

    2016-09-27

    Over the past two decades, the use of well-validated, guideline-based strategies resulted in high cure rates in patients with germ-cell cancer (GCC) often despite widespread metastatic disease at initial presentation. Yet, about 30 % of patients diagnosed with metastatic disease corresponding to about 5-10 % of GCC patients overall will experience disease progression or recurrence at some time point of their disease with the need for salvage treatment. Salvage treatment is more complex and less well validated than first-line treatment: Its rare patient cohorts are more heterogeneous and prognostic factors impact more compared to other treatment scenarios. In patients with metastatic GCC, there are several scenarios in which first-line treatment strategies can fail (Fig. 1). Prior to initiation of any salvage treatment, several considerations have to be made, which will be addressed in this review: verification that first-line treatment has indeed failed, estimation of the adequacy and the effectiveness of first-line treatment, search for metastatic sites and extent of disease recurrence, assessment of known prognostic factors and finally the choice of the optimal salvage strategy taking into account the aforementioned variables. High-dose chemotherapy will be a rational choice for many patients in need of salvage treatment, but careful patient selection will be required to avoid overtreatment and unnecessary long-term toxicity.

  13. Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Nirmalya Roy Moulik

    2016-01-01

    Full Text Available Purpose: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear. Methods: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined. Results: Twenty-one children were studied. Folate deficiency was associated with higher incidence of neutropenia (P = 0.03 and longer duration of chemotherapy interruption (P = 0.009. Children with MTHFR1298 mutations needed more red cell transfusion (P = 0.03. All 3 deaths encountered were seen in folate deficient children. Conclusions: Folate deficiency was associated with higher complications during high dose methotrexate therapy, the implications of which are important especially in resource poor settings with high prevalence of folate deficiency.

  14. A novel high-dose chemotherapy protocol with autologous hematopoietic rescue in patients with metastatic breast cancer or recurrent non-Hodgkin's lymphoma.

    Science.gov (United States)

    Fontelonga, A; Kelly, A J; MacKintosh, F R; Hall, S; Monroe, P; Wilson, G S; Shaft, D; Ruthven, A; Ascensao, J L

    1997-05-01

    In this phase II trial, we used a double dose-intensive chemotherapy and stem cell rescue protocol to treat breast cancer (BCA) patients or non-Hodgkin's lymphoma patients (NHL). The first cycle consisted of high-dose melphalan followed by ABMT. The second cycle used a novel chemotherapy combination; thiotepa, etoposide, carboplatin and cyclophosphamide (TECC) followed by ABMT. We treated 12 patients in total, nine with BCA, three with NHL. All nine BCA patients were treated with the two cycle protocol. The three NHL patients were treated with the second cycle only. Bone marrow (BM, 1 patient), peripheral blood stem cells (PBSC, 10 patients) or both (1 patient) were reinfused 60-72 h after completion of each cycle of chemotherapy. Recovery was rapid; the ANC rose to greater than 500/microl on day +11 (+8 to + 20) and the platelet count to greater than 20000/microl on day +12 (+6 to +20). The toxicities included the expected neutropenic fevers, severe mucositis, diarrhea, and a low incidence of mild renal insufficiency. No patients developed veno-occlusive disease, hemorrhagic cystitis or overt bleeding. With a mean follow-up of 37 months, 83.3% of the patients are alive. Six patients are in complete remission; one patient with BCA relapsed and expired; one patient with NHL is in CR now over 18 months after relapse and subsequent treatment with interferon; one patient is too early to evaluate. Progression-free survival overall is 75%, which is at least equivalent to many other recent studies using similar regimens. In addition, we have also found that delayed addition of G-CSF during the mobilization of PBSC was feasible and resulted in excellent CD34+ cell counts and engraftments, and reduced treatment costs. These results indicate that this chemotherapy is effective with good remission rates and high progression-free survival rates. It is also well tolerated with acceptable toxicities that are manageable. Long-term follow-up of a larger cohort of patients will be

  15. Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

    Science.gov (United States)

    Boudin, L; Gonçalves, A; Sabatier, R; Moretta, J; Sfumato, P; Asseeva, P; Livon, D; Bertucci, F; Extra, J-M; Tarpin, C; Houvenaegel, G; Lambaudie, E; Tallet, A; Resbeut, M; Sobol, H; Charafe-Jauffret, E; Calmels, B; Lemarie, C; Boher, J-M; Viens, P; Eisinger, F; Chabannon, C

    2016-08-01

    Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

  16. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

  17. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi [Keio Univ., Tokyo (Japan). School of Medicine

    1997-02-01

    The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

  18. [Role of high-dose BEAM-chemotherapy and autologous hemopoietic stem cell transplantation in the treatment of drug-resistant Hodgkin disease].

    Science.gov (United States)

    Uss, A L; Zmachinskiĭ, V A; Milanovich, N F; Skriagin, A E; Dziuba, E V; Vlasenkova, S V; Solov'eva, N S; Batan, Z E; Mitskevich, P B; Zavgorodniaia, I L; Aleĭnikova, O V; Zhavrid, E A

    2000-01-01

    In 1995-1999, 67 patients with relapsed Hodgkin's disease or refractory to chemotherapy (group A--first relapse, B--primary refractory disease, and C--repeated relapse) received cytoreductive (dexaBEAM, DHAP) therapy followed by high-dose BEAM chemotherapy and autologous bone marrow or blood cell transplantation. Early postoperative transplant-related mortality rate was 4.5%. At day 100, complete remission rates were: group A--95.6%; B--74.1%; and C--76.5%. Survival for all patients was: overall--61.9%; event-free--43.9%; disease-free--46%; and relapse-free survival--49.5%. Such factors as primary refractory disease, age over 30 years and response to cytoreductive therapy had significant influence on overall survival prognosis.

  19. Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation: A Randomized, Double Blinded Clinical Study

    Directory of Open Access Journals (Sweden)

    Jon-Magnus Tangen

    2015-01-01

    Full Text Available Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients or placebo (21 patients. Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.

  20. Combination chemotherapy with high-dose methotrexate and cytarabine with or without brain irradiation for primary central nervous system lymphomas.

    Science.gov (United States)

    Calderoni, Antonello; Aebi, Stefan

    2002-09-01

    Due to the limited clinical experience there is no standard treatment of primary CNS-lymphomas (PCNSL). Based on the actual data it seems that high-dose methotrexate (HTMRX) and high-dose cytarabine (ARA-C) qualify as treatments of choice for this disease. The role of radiation therapy is still unclear, due to the high long-term toxicity, especially in elderly patients. We treated 14 HIV negative patients with 4-5 cycles of methotrexate (MTX) at 3500 mg/m2 and MTX 15 mg intrathecal weekly or MTX 8000 mg/m2 weekly without intrathecal treatment. Younger patients (boost), older patientsts were not irradiated and continued CT. The following treatment consisted in ARA-C 3000 mg/m2 d1 + 2 every 3 weeks for two cycles. All patients received steroids for two months or until the end of radiotherapy. The overall response rate was 100%, 12/14 CR (86%). Two patients died still on treatment but not due to lymphoma (1 pulmonary embolism, 1 herpes encephalitis). Toxicity was very mild with no grade 3-4 non-haematological toxic events and almost 100% grade 3-4 leucopenia without episodes of neutropenic fever. After a median follow up of 39 months the PFS and OS are 65% (9/14) and 78% (11/14) respectively, and compare well with other trial results.

  1. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

    Science.gov (United States)

    Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

    2016-11-20

    Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

  2. Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Pieters Bradley R

    2007-07-01

    Full Text Available Abstract Background Results of high-dose chemo-radiotherapy (CRT, using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT alone were analyzed among all patients (pts with Non Small Cell Lung Cancer (NSCLC treated with curative intent in our department from 1995–2004. Material Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt. Treatment Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx/33 days combined with daily administration of cisplatin 6 mg/m2: 56 pts (standard. Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m2 d1, cisplatin 75 mg/m2 d2 followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts. Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts. Results The 1, 2, and 5 year actuarial overall survival (OS were 46%, 24%, and 15%, respectively. At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024 (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively. The incidence of local recurrence was 36%, the incidence of distant metastases 46%. Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal. For 32 patients insufficient data were available to assess late complications. Conclusion In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.

  3. The Prospective Oral Mucositis Audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT.

    NARCIS (Netherlands)

    McCann, S.; Schwenkglenks, M.; Bacon, P.; Einsele, H.; D'Addio, A.; Maertens, J.; Niederwieser, D.; Rabitsch, W.; Roosaar, A.; Ruutu, T.; Schouten, H.; Stone, R.; Vorkurka, S.; Quinn, B.; Blijlevens, N.M.A.

    2009-01-01

    The Prospective Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) undergoing, respectively, high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres. We evaluated the relationship between severe oral m

  4. A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

    Science.gov (United States)

    Grénman, Seija; Wiklund, Tom; Jalkanen, Jyrki; Kuoppala, Tapio; Mäenpää, Johanna; Kuronen, Arja; Leminen, Arto; Puistola, Ulla; Vuolo-Merilä, Päivi; Salmi, Tuula; Vuento, Maarit; Yliskoski, Merja; Itälä, Maija; Helenius, Hans; Joensuu, Heikki; Lehtovirta, Pentti

    2006-09-01

    Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

  5. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

    Science.gov (United States)

    Akhtar, Saad; Rauf, Shahzad M; Elhassan, Tusneem A M; Maghfoor, Irfan

    2016-09-01

    High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of young adults.

  6. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

    Science.gov (United States)

    Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

    2016-01-01

    We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

  7. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    Directory of Open Access Journals (Sweden)

    Eduard H. Panosyan

    2011-01-01

    Full Text Available Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR. Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009. Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma, 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n=16. Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs. Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P<.01. Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions.

  8. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  9. Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer.

    Science.gov (United States)

    Stiff, P; Chen, B; Franklin, W; Oldenberg, D; Hsi, E; Bayer, R; Shpall, E; Douville, J; Mandalam, R; Malhotra, D; Muller, T; Armstrong, R D; Smith, A

    2000-03-15

    The collection of small aliquots of bone marrow (BM), followed by ex vivo expansion for autologous transplantation may be less morbid, and more cost-effective, than typical BM or blood stem cell harvesting. Passive elimination of contaminating tumor cells during expansion could reduce reinoculation risks. Nineteen breast cancer patients underwent autotransplants exclusively using ex vivo expanded small aliquot BM cells (900-1200 x 10(6)). BM was expanded in media containing recombinant flt3 ligand, erythropoietin, and PIXY321, using stromal-based perfusion bioreactors for 12 days, and infused after high-dose chemotherapy. Correlations between cell dose and engraftment times were determined, and immunocytochemical tumor cell assays were performed before and after expansion. The median volume of BM expanded was 36.7 mL (range 15.8-87.0). Engraftment of neutrophils greater than 500/microL and platelets greater than 20,000/microL were 16 (13-24) and 24 (19-45) days, respectively; 1 patient had delayed platelet engraftment, even after infusion of back-up BM. Hematopoiesis is maintained at 24 months, despite posttransplant radiotherapy in 18 of the 19 patients. Transplanted CD34(+)/Lin(-) (lineage negative) cell dose correlated with neutrophil and platelet engraftment, with patients receiving greater than 2.0 x 10(5) CD34(+)/Lin(-) cells per kilogram, engrafting by day 28. Tumor cells were observed in 1 of the 19 patients before expansion, and in none of the 19 patients after expansion. It is feasible to perform autotransplants solely with BM cells grown ex vivo in perfusion bioreactors from a small aliquot. Engraftment times are similar to those of a typical 1000 to 1500 mL BM autotransplant. If verified, this procedure could reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which small stem cell doses are available, eg, cord blood transplants. (Blood. 2000;95:2169-2174)

  10. A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.; Olsen, Christine; Willers, Henning, E-mail: hwillers@mgh.harvard.edu

    2015-07-15

    Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.

  11. Long-Term Remission of Primary Bone Marrow Diffuse Large B-Cell Lymphoma Treated with High-Dose Chemotherapy Rescued by In Vivo Rituximab-Purged Autologous Stem Cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Kazama

    2012-01-01

    Full Text Available Primary bone marrow diffuse large B-cell lymphoma (DLBCL is a rare type of extranodal lymphoma with poor prognosis. Here, we report a case of primary bone marrow DLBCL successfully treated with high-dose chemotherapy and rescued by in vivo rituximab-purged autologous stem cells. A 39-year-old woman visited our hospital because of anemia. Bone marrow examination revealed a large B-cell lymphoma invasion. An 18F-fluorodeoxyglucose positron emission tomography scan revealed disseminated bone marrow uptake without evidence of dissemination at other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy and achieved complete remission. Subsequently, she received high-dose chemotherapy with an in vivo rituximab-purged autologous stem cell transplant. Seven years have passed since the transplantation, and she remains in remission. This suggests that transplantation of an in vivo rituximab-purged autograft is a promising strategy for primary bone marrow DLBCL.

  12. High-Dose Methotrexate and Cytarabine-Based Multi-Agent Chemotherapy (Modified Bonn Protocol) for Systemic Lymphoma with CNS Involvement.

    Science.gov (United States)

    Umino, Kento; Fujiwara, Shin-Ichiro; Sato, Kazuya; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2017-01-01

    The prognosis of patients with systemic lymphoma with central nervous system (CNS) involvement is very poor and there is no established standard therapy. We retrospectively analyzed 18 patients (4 untreated and 14 relapsed) with systemic lymphoma with CNS involvement who received methotrexate and cytarabine-based multiagent chemotherapy (modified Bonn protocol). Complete and partial responses were achieved in 56 and 22% of the patients, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) was 81.0 and 39.2%, respectively. Patients with parenchymal involvement showed a better 1-year PFS than those with either leptomeningeal involvement or both. In a multivariate analysis, poor performance status (PS) was the only independent prognostic factor for the 1-year OS and PFS (HR 10.8, 95% CI 1.09-108, p = 0.042; HR 20.8, 95% CI 2.39-181, p = 0.006, respectively). Grade 4 neutropenia and thrombocytopenia occurred in 17 patients each (94%), but there were no grade 4 nonhematopoietic adverse events. The modified Bonn protocol resulted in relatively favorable response and survival, and provided clinical benefits to patients with good PS, in particular. This study demonstrated that the modified Bonn protocol could be a feasible and encouraging treatment approach for lymphoma with CNS and systemic involvement.

  13. Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

    Science.gov (United States)

    Necchi, A; Miceli, R; Bregni, M; Bokemeyer, C; Berger, L A; Oechsle, K; Schumacher, K; Kanfer, E; Bourhis, J H; Massard, C; Laszlo, D; Montoro, J; Flechon, A; Arpaci, F; Secondino, S; Wuchter, P; Dreger, P; Crysandt, M; Worel, N; Kruger, W; Ringhoffer, M; Unal, A; Nagler, A; Campos, A; Wahlin, A; Michieli, M; Sucak, G; Donnini, I; Schots, R; Ifrah, N; Badoglio, M; Martino, M; Raggi, D; Giannatempo, P; Rosti, G; Pedrazzoli, P; Lanza, F

    2016-03-01

    Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.

  14. [Expression of adhesion molecules on CD34+ cells of BM and PB stem cell samples during high-dose chemotherapy combined with transplantation of autologous PB stem cells].

    Science.gov (United States)

    Liu, Peng; Han, Xiao-Hong; Shi, Yuan-Kai; He, Xiao-Hui; Yang, Cheng; Ai, Bin

    2004-12-01

    This study was aimed to investigate the expressions of adhesion molecules such as CD54, CD49d and CD62L by CD34(+) cells sampled from different stages of bone marrow (BM) and peripheral blood (PB) before/after G-CSF mobilization and after transplantation through the direct labeling with three colour-immunofluorescence and flow cytometry, and to explore the differences in expression of adhesion molecules on CD34(+) cells from different origins and their clinical significance. Mononuclear cells collected from BM and PB before mobilization, after collection of stem cells and hematopoietic recostruction of BM at the end of transplantation were marked with CD54-FITC, CD49d-FITC and CD62L-FITC separately, as well as CD34-PE and CD45PerCE. 3-color fluorescene analysis was carried out by FACS. The expression differences of CD34(+) and adhesion molecules between BM and APBSC were compared. The results showed that expression differences of CD54, CD49d and cd62Lon CD34(+) cells belore mobilization, after collection and reconstraction of transplantation were not statiscally significant, the difference of CD54, CD49d and CD62L on CD34(+) between 1st and 2nd collections of hematopoietic stem cells also were not statiscally significant. In the collected APBSC, the expression level of CD34(+) CD49d(+) was significantly lower than those in BM before mobilization (P = 0.001). It is concluded that the method of chemotherapy combined with G-CSF mobilization can down-regulate CD49d expression in BM CD34(+) cells, thus can mobilize and move theirs into peripheral blood. After the reconstitution by transplantation, the expression of CD49d on CD34(+) cells tends to normal, the clinical significance needs to be elucidated by accumulation of much more cases.

  15. γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Chiara Pratesi

    Full Text Available Autologous stem cell transplantation (ASCT is a feasible procedure for human immunodeficiency virus-1 (HIV-1 lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV- and Kaposi sarcoma-associated herpesvirus (KSHV-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs of 12 (median 12,135 copies/mL and 18 patients (median 417 copies/10(6 PBMCs, respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001. Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03 and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04. After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.

  16. [Preliminary clinical evaluation of low-dose cisplatin and continuous infusion of 5-FU (LFP) chemotherapy after weekly high-dose 5-FU therapy for the treatment of liver metastases from colorectal cancer].

    Science.gov (United States)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

    2002-07-01

    In this study, we evaluate the efficacy of low-dose cisplatin and continuous 5-FU infusion systemic chemotherapy (LFP therapy) for the treatment of unresectable and recurrent liver metastases from colorectal cancer after weekly high-dose 5-FU therapy via the hepatic artery (WHF therapy). At the start of chemotherapy, 12 patients with multiple extrahepatic lesions were treated with the LFP therapy (LFP group), and 18 patients with none or a few extrahepatic lesions were treated with the WHF therapy followed by the LFP therapy (LFP after WHF group). In the LFP group, the response rate was 50.0% (PR 6) and the one-year survival rate was 50.0%. On the contrary, in the LFP after WHF group, the response rate was 38.9% (CR 1, PR 6) and the one-year survival rate after LFP started was 46.0%. We conclude that the LFP therapy may be effective for the treatment of liver metastases from colorectal cancer even after the WHF therapy.

  17. Recombinant human thrombopoietin in combination with granulocyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy.

    Science.gov (United States)

    Somlo, G; Sniecinski, I; ter Veer, A; Longmate, J; Knutson, G; Vuk-Pavlovic, S; Bhatia, R; Chow, W; Leong, L; Morgan, R; Margolin, K; Raschko, J; Shibata, S; Tetef, M; Yen, Y; Forman, S; Jones, D; Ashby, M; Fyfe, G; Hellmann, S; Doroshow, J H

    1999-05-01

    Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 micrograms/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 micrograms/kg on days -3, -1, and 1, or 0.6 micrograms/kg on days -1 and 1. G-CSF, 5 micrograms/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34(+) cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 10(6)/kg (range, 1.3 to 17.6) versus 0.8 x 10(6)/ kg (range, 0.3 to 4.2), P =.0003. The targeted minimum yield of 3 x 10(6) CD34(+) cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P =.001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P =.0001) and platelet recovery (day 9 v 10, P =.07) were accelerated, and fewer erythrocyte (3 v 4, P =.02) and platelet (4 v 5, P =.02) transfusions were needed compared with G-CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P rhTPO at 0.6 microgram/kg. rhTPO is

  18. Design of the EXercise Intervention after Stem cell Transplantation (EXIST) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a individualized high intensity physical exercise program on fitness and fatigue in patients with multiple myeloma or (non-) Hodgkin's lymphoma treated with high dose chemotherapy and autologous stem cell transplantation

    NARCIS (Netherlands)

    S. Persoon; M.J. Kersten; M.J.M. Chinapaw; L.M. Buffart; H. Burghout; G. Schep; J. Brug; F. Nollet

    2010-01-01

    ABSTRACT: BACKGROUND: The use of high-dose chemotherapy combined with autologous stem cell transplantation has improved the outcome of hematologic malignancies. Nevertheless, this treatment can cause persistent fatigue and a reduced global quality of life, role and physical function. Physical exerci

  19. 胞苷脱氨酶基因对小鼠大剂量化疗的保护作用%Protection of a cytidine deaminase gene gainst toxicity of high dose chemotherapy in mice

    Institute of Scientific and Technical Information of China (English)

    Bo Chen; Caigang Liu; Yang Lu; Ping Lu; Feng Jin; Fan Yao; Ruishan Zhang; Jinlong Liu; Shicheng Zhao

    2008-01-01

    Objective:To explore the feasibility of transfecting cytidine deaminase(CD)gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppression following combination chemotherapy.Methods:Human cytidine deaminase gene was transfected into mice bone marrow cells by retroviral vector.Resistant colony-forming unit granulocyte-macrophage(CFU-GM)assay was performed after the transfected mice bone marrow cells treated by the Ara-C.DNA was extracted from mice bone marrow cells.The drug resistant gene in mice bone marrow cells after transfection was detected by PCR.Results:Bone marrow cells of lhe donor mice cultured with lhe retroviral producer cells showed the drug resistant colonies and resistance to Ara-C,so did accept mice transplanted with the CD gene(CFU-GM of donor mice was 52%,X2=124.62,P<0.01:accept mice was 54%,X2=126.26.P<0.01,both compared with the contrast group).The animal survival rate was significantly higher in gene transfected group than that of the control(X2=7.42.P<0.01).CD gene of transfected bone marrow cells was confirmed by PCR.Conclusion:CD gene can be transfected into bone marrow cells of mice efficiently and increase the drug resistance to Ara-C.

  20. Design of the EXercise Intervention after Stem cell Transplantation (EXIST study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of an individualized high intensity physical exercise program on fitness and fatigue in patients with multiple myeloma or (non- Hodgkin's lymphoma treated with high dose chemotherapy and autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Burghout Heleen

    2010-12-01

    Full Text Available Abstract Background The use of high-dose chemotherapy combined with autologous stem cell transplantation has improved the outcome of hematologic malignancies. Nevertheless, this treatment can cause persistent fatigue and a reduced global quality of life, role and physical function. Physical exercise interventions may be beneficial for physical fitness, fatigue and quality of life. However, the trials conducted so far to test the effects of physical exercise interventions in this group of patients were of poor to moderate methodological quality and economic evaluations are lacking. Hence there is need for a rigorous, appropriately controlled assessment of the effectiveness of exercise programs in these patients. The aims of the present study are (1 to determine the effectiveness of an individualized high intensity strength and interval training program with respect to physiological and psychological health status in patients with multiple myeloma or (non-Hodgkin's lymphoma who have recently undergone high dose chemotherapy followed by autologous stem cell transplantation; and (2 to evaluate the cost-effectiveness of this program. Methods A multicenter, prospective, single blind randomized controlled trial will be performed. We aim to recruit 120 patients within an inclusion period of 2 years at 7 hospitals in the Netherlands. The patients will be randomly assigned to one of two groups: (1 intervention plus usual care; or (2 usual care. The intervention consists of an 18-week individualized supervised high-intensity exercise program and counselling. The primary outcomes (cardiorespiratory fitness, muscle strength and fatigue and secondary outcomes are assessed at baseline, at completion of the intervention and at 12 months follow-up. Discussion The strengths of this study include the solid trial design with clearly defined research groups and standardized outcome measures, the inclusion of an economic evaluation and the inclusion of both

  1. High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

    Science.gov (United States)

    Martino, Massimo; Lanza, Francesco; Pavesi, Lorenzo; Öztürk, Mustafa; Blaise, Didier; Leno Núñez, Rubén; Schouten, Harry C; Bosi, Alberto; De Giorgi, Ugo; Generali, Daniele; Rosti, Giovanni; Necchi, Andrea; Ravelli, Andrea; Bengala, Carmelo; Badoglio, Manuela; Pedrazzoli, Paolo; Bregni, Marco

    2016-03-01

    The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials.

  2. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

    2008-12-15

    Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on anthracyclines. Overall survival and local control were assessed according to Kaplan-Meier methodology. Results: Local control and overall survival in five years were 90% and 73.5%, respectively. Conclusion: local control and overall survival were comparable to other forms of treatment. (author)

  4. High dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT) in the treatment of patients with small cell lung cancer%外周血干细胞移植(PBSCT)结合高剂量化疗治疗小细胞肺癌

    Institute of Scientific and Technical Information of China (English)

    鲍云华; 苏航; 申戈; 袁晓潮; 高红军; 杨武威

    2001-01-01

    Objective To investigate the therapeutic effect and safety of PBSCT combined with high dose chemotherapy in the treatment of small cell lung cancer(SCLC). Methods From March, 1994 to June, 1999, high dose chemotherapy combined with PBSCT was carried out in 20 patients with SCLC. Eight patients were in CR status while twelve patients were for salvaging therapy. Allo-PBSCT was performed in 1 patient and Auto-PBSCT in 19 patients. After mobilization of stem cell, mononeuclear cell (MNC) was collected for ≥3.0×108/kg, CD34+ cell≥2.0×106/kg. The high dose chemotherapy included carboplatin 350?mg/m2×3 days, VP-16 120?mg/m2×5 days, and E-ADM 40?mg/m2×2 days. Results Encouraging results were achieved in 8 patients who were in CR status. Seven of the eight patients survived after Auto-PBSCT. One patients survived more than 1 year, 4 cases over 2 years, and 3 cases over 3 years. Of the 3 patients, 2 survived more than 4 years. In the group of salvaging therapy, response was good, however there was no long-term survival and median remission time was only 3.5 months. Conclusion High dose chemotherapy combined with PBSCT in the treatment of SCLC with CR status is feasible and safe, although the side effects are severe too. It is worth further studying on clinical practice.%目的 研究外周血干细胞移植加高剂量化疗治疗小细胞肺癌的临床疗效和安全性。方法 从1994年3月至1999年6月,对20例小细胞肺癌患者应用高剂量化疗和外周血干细胞移植,8例处于完全缓解状态,12例属于挽救治疗。同种异体外周血造血干细胞移植(Allo-PBSCT)1例,自体外周血造血干细胞移植(Auto-PBSCT)19例。在干细胞动员后,采集单个核细胞数≥3.0×108/kg,CD34+细胞数≥2.0×106/kg。高剂量化疗采用卡铂350?mg/m2×3天,足叶乙甙120?mg/m2×5天,表阿霉素40?mg/m2×2天。结果 在完全缓解状态进行外周血造血干细胞移植的8

  5. 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.

  6. High Quality Nursing Service in Leukemia Bone Marrow Suppression After High-dose Chemotherapy Period of Intervention%优质护理服务在白血病大剂量化疗后骨髓抑制期的干预体现

    Institute of Scientific and Technical Information of China (English)

    侯玉洁; 钱昭丽; 王倩

    2016-01-01

    目的:探究白血病大剂量化疗后骨髓抑制期优质护理服务的优势。方法以2014年1月~2015年10月本科收治的采取大剂量化疗后出现骨髓抑制情况的白血病患者为研究对象,从中随机选取40例纳入本次研究,以随机数字表法进行分组,其中对照组采取基础护理,观察组在此基础上进行优质护理干预,两组均纳入20例。结果对比分析两组骨髓抑制期并发症发生几率、焦虑评分、生活质量评分,结果均显示观察组比对照组有明显优势(P<0.05)。结论对采取大剂量化疗后出现骨髓抑制情况的白血病患者,除做好基础护理工作外也应重视心理干预、饮食指导、环境干预等优质护理服务措施的应用,以便确保患者顺利度过骨髓抑制期,提高患者的生活质量。%Objective To explore the leukemia bone marrow suppression after high-dose chemotherapy period the advantages of high quality nursing service.Methods From January 2014 to October 2015, undergraduate bone marrow suppression after taking large doses of chemotherapy of leukemia patients were as the research object, from 40 patients were randomly selected in this study, with random number table method to group, the control group take the basic nursing, observation group on the basis of high quality nursing intervention, two groups are included in 20 cases.Results Analysis of two groups of bone marrow inhibitory stage complications rate, quality of life score, anxiety score, the result has obvious advantages according to observation group than the control group (P< 0.05).Conclusion To take high doses of bone marrow suppression after chemotherapy of leukemia patients, in addition to do a good job in basic nursing work also should pay attention to psychological intervention, diet instruction, application of high-quality care services such as environmental intervention measures, to ensure that patients through bone marrow inhibition

  7. Treatment response evaluation with {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Sachpekidis, Christos [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Bern, Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern (Switzerland); Hillengass, J.; Wagner, B. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); Goldschmidt, H. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

    2017-01-15

    The aim of this study was to assess the combined use of the radiotracers {sup 18}F-FDG and {sup 18}F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with {sup 18}F-FDG and {sup 18}F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, {sup 18}F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, {sup 18}F-FDG PET/CT-based treatment response revealed CR in 14 patients ({sup 18}F-FDG PET/CT CR), PR in 11 patients ({sup 18}F-FDG PET/CT PR) and progressive disease in four patients ({sup 18}F-FDG PET/CT PD). In terms of {sup 18}F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, {sup 18}F-NaF PET/CT depicted 56 of the 129 {sup 18}F-FDG positive lesions (43 %). Follow-up {sup 18}F-NaF PET/CT showed persistence of 81.5 % of the baseline {sup 18}F

  8. Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Eich, H.T.; Staar, S.; Mueller, R.P. [Dept. of Radiotherapy, Univ. of Cologne (Germany); Hero, B.; Berthold, F. [Dept. of Pediatric Oncology, Children' s Hospital, Univ. of Cologne (Germany); Micke, O. [Dept. of Radiotherapy, Univ. of Muenster (Germany); Seegenschmiedt, H. [Dept. of Radiotherapy, Alfried Krupp Hospital, Essen (Germany); Mattke, A. [Children' s Hospital, Olgaspital, Stuttgart (Germany)

    2003-04-01

    Background: To evaluate the efficacy of multimodality therapy in patients with esthesioneuroblastoma (ENB). Patients and Methods: From 01/1979 through 08/2001, 47 patients with ENB (20 men, 27 women, age 5-81 years), were registered from 18 oncologic centers. There were 14 tumors stage B and 33 stage C according to the Kadish classification. Initial treatment included surgery alone in seven patients, radiotherapy (RT) with or without chemotherapy (CTX) in twelve, surgery plus postoperative RT in 15, and multimodality therapy (surgery plus pre- or postoperative CTX plus postoperative RT) in 13. Results: The 5-year overall survival (OS) for the whole group was 64 {+-} 8% and the 5-year event-free survival (EFS) 50 {+-} 8%. Patients with multimodality treatment had a significantly better 5-year EFS (74 {+-} 13%) compared to the other patients (41 {+-} 9%; p = 0.05), while the 5-year OS was not significantly different between the treatment groups (p = 0.39). For patients with Kadish stage C, multimodality therapy (n = 11) resulted in superior 5-year EFS (72 {+-} 14% vs 17 {+-} 9%; p = 0.01). These patients tended to have an improved OS (69 {+-} 15% vs 47 {+-} 12%; p = 0.19) compared to the other treatment groups. None of the patients with multimodality treatment had a metastatic relapse. Conclusion: Multimodality treatment (surgery plus pre- or postoperative CTX plus postoperative RT) appears to be highly efficient in preventing local and systemic relapse in patients with advanced ENB. Timing and optimal agents of CTX need to be further evaluated. (orig.)

  9. 大剂量甲地孕酮防治食管癌化疗毒副反应的临床研究%Clinical study of high dose megestrol acetate in treatment of esophageal cancer chemotherapy toxicity

    Institute of Scientific and Technical Information of China (English)

    贾利; 贾霖; 韩建军; 王允; 高飞; 陈宓

    2013-01-01

      目的:观察预防性应用甲地孕酮减少食管癌化疗毒副反应的疗效。方法:将80例经病理学确诊、需行化疗治疗的食管癌患者随机分为2组,实验组(40例),对照组(40例)。实验组方案:在每个化疗周期开始的前一天,给予甲地孕酮分散片口服,2次/d ,每次160mg,直到化疗结束后3天。对照组方案:仅常规化疗。观察2组患者消化道反应和骨髓抑制情况,以及体重等变化。结果:实验组恶心呕吐症状明显减轻,白细胞下降发生率低,体重减轻发生率低,与对照组比较有显著性差异。结论:食管癌患者在全身化疗期间,预防性应用甲地孕酮可有效减轻化疗的毒副反应,改善患者营养状态,提高患者治疗耐受性和依从性。%Objective: To observe the preventive use of megestrol acetate effect of decreasing toxicity of chemotherapy of esophageal cancerMethods: 80 cases of esophageal cancer patients were randomly divided into pathological diagnosis, received chemotherapy treatment into 2 groups, experimental group (40 cases), control group (40 cases). The experimental group:the day before each chemotherapy cycle begins, giving megestrol tablets, 2 times /d, 160mg each time, until the end of 3 days after chemotherapy. Control group: routine chemotherapy scheme.2 groups were observed in patients with gastrointestinal reaction and bone marrow suppression, and body weight change.Results: the symptoms of nausea and vomiting was significantly reduced, the decrease of white blood cels occur rate is low, the weight loss rate was low, there is significant difference compared with the control group.Conclusion: Patients with esophageal cancer during the chemotherapy period, preventive application of megestrol acetate can effectively reduce the toxicity of chemotherapy, improve the nutritional status of patients, improve patient tolerance and compliance.

  10. Curability of cancer by radiotherapy and chemotherapy, including in neuraxial neoplasms

    Directory of Open Access Journals (Sweden)

    Jalali Rakesh

    2009-01-01

    Full Text Available In the October of 1996, Lance Armstrong, celebrated cyclist and one of the greatest athletes the world has ever seen, at the age of 24, was diagnosed with metastatic testicular cancer with disease having already spread to his abdomen, lungs and brain. Lance underwent four cycles of chemotherapy, actually the pretty standard one, pioneered at the Indiana University and not only did he get completely cured of his cancer, he remains extremely well till date, 12 years later. He sure did have a few adverse effects during those cycles of chemotherapy in the form of nausea, vomiting, weakness and fall in blood count but he knew and experienced them only for a short transient time and emerged triumphant and strong. In fact, he went on to win six awe-inspiring and incredible successive Tours de France victories from 1999-2005, one of the most grueling sporting events testing the endurance of the very fittest. After his retirement, he has been so inspired that he has completely devoted himself to educate people about the common myths about cancer, and promised to raise awareness and generate money for furthering research into surgery, radiation therapy and chemotherapy for cancer through his foundation. He says "I am indebted to the doctors, nurses and medicine and would want to pay them back for all their energy and caring." In his successful journey of overcoming cancer, he captures the essence of its treatment so well by declaring "Pain is temporary, it may last a minute, or an hour, or a day, or a year, but eventually, it will subside and something else will take its place. If I quit, however, it will last forever".

  11. 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.

  12. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy; Tratamento conservador dos carcinomas de mama localmente avancados T2 e T3, apos quimioterapia neoadjuvante, com quadrantectomia e braquiterapia de alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante

    Energy Technology Data Exchange (ETDEWEB)

    Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia]. E-mail: cefristachi@uol.com.br; Miziara Filho, Miguel Abrao; Soares, Celia Regina; Fogaroli, Ricardo Cesar; Pelosi, Edilson Lopes; Martins, Homero Lavieri Martins [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia; Baracat, Fausto Farah [Hospital do Servidor Publico Estadual de Sao Paulo (HSPE), SP (Brazil). Servico de Ginecologia e Mastologia; Piato, Sebastiao [Irmandade da Santa Casa de Misericordia de Sao Paulo, SP (Brazil). Dept. de Obstetricia e Ginecologia (DOGI)

    2005-07-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  13. [Chemotherapy-induced stomatitis and diarrhea].

    Science.gov (United States)

    Kadowaki, Shigenori; Yamaguchi, Kensei

    2011-11-01

    Chemotherapy-induced mucositis is a clinically important and sometimes dose-limiting toxicity of cancer treatment, including standard-dose chemotherapy, high-dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis.

  14. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  15. High-Dose Chemotherapy Assisted with Autologous Peripheral Blood Stem Cell Treatment for Small Cell Lung Cancer: A Meta-Analysis%自体外周血干细胞支持下大剂量化疗治疗小细胞肺癌疗效和安全性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    李秀; 何明生

    2012-01-01

    目的 系统评价外周血干细胞支持下大剂量化疗(APBSCT+HDC)治疗小细胞肺癌(SCLC)的疗效及安全性.方法 计算机检索MEDLINE (1970~2011.1)、Embase (1980~2011.1)、Science Direct( 1980~2011.1)、Cochrane图书馆(2010年第3期)、CNKI、CBM和WanFang Data(检索截至2010年12月),查找APBSCT+HDC治疗SCLC的随机对照试验(RCT).按纳入与排除标准选择试验、提取资料和评价方法学质量后,采用RevMan 5.0软件进行Meta分析.结果 共纳入6个RCT,737例患者,其方法学质量评级B级5篇,C级1篇.Meta分析结果显示:APBSCT+HDC治疗SCLC的总有效率和总生存率明显优于常规化疗,其差异有统计学意义[分别为RR=1.14,95%CI( 1.07,1.21),P<0.000 1;RR=3.74,95%CI (2.13,6.58),P<0.000 01].在Ⅲ/Ⅳ度红细胞及血小板降低的发生率方面,APBSCT+HDC治疗组高于常规化疗组,差异有统计学意义[分别为RR=1.97,95%CI( 1.15,3.38),P=0.01;RR=1.93,95%CI( 1.06,3.54),P=0.03];但在Ⅲ/Ⅳ度白细胞降低方面,两组差异无统计学意义.结论 与常规化疗相比,APBSCT+HDC治疗SCLC能提高总有效率及总生存率,但有增加重度血液学毒副反应发生率的风险.因本研究纳入样本量较少,方法学质量不够高,故所得结论尚需更多高质量多中心大样本RCT证实.%Objective To assess the effectiveness and safety of high-dose chemotherapy assisted with autologous peripheral blood stem cell treatment (APBSCT+HDC) for small cell lung cancer (SCLC). Methods The databases such as MEDLINE (1970 to January 2011), EMBASE (1980 to January 2011), Science Direct (1980 to January 2011), The Cochrane Library (Issue 3, 2010), CNKI (from the date of establishment to December 2010), CBM (from the date of establishment to December 2010) and Wanfang database (from the date of establishment to December 2010) were searched for collecting randomized controlled trials (RCTs) on APBSCT+HDC for SCLC. According to the inclusive and exclusive

  16. 米氮平预防大剂量顺铂化疗的恶心和呕吐的临床研究%A clinical study about Mirtazapine to prevent nausea and emesis caused by high-dose cisplatin-based chemotherapy

    Institute of Scientific and Technical Information of China (English)

    郑艳群; 李志勇; 张艳清; 祝毓琳; 朱步东

    2013-01-01

    的恶心、呕吐和食欲减退;而迟发性呕吐改善相对更明显。%Objective To observe the effects and safety of Mirtazapine in prevention of nausea and emesis caused by high-dose cisplatin-based chemotherapy. Methods This was a self-controlled crossover clinical trial. Sixty-three patients, treated by high-dose cisplatin(60 mg/m2 or 75 mg/m2) plus gemcitabine, were randomly assigned to either control (A) cycle or Mirtazapine (B) cycle with first course, with crossover to the opposite treatment with the second course. The identical chemotherapy regimen was used on cycle A and cycle B. The d1-d5 served as first day through fifth day of chemotherapy cycle. The significant protection from nausea, emesis and anorexia was denoted as control rates, the complete protection rate denoted by CR rates. The control rates of nausea, emesis and anorexia on d1-d5 were observed. Patients received ondansetron with dexamethasone on cycle A to prevent nausea, emesis and anorexia. The mirtazapine in combination with ondansetron and dexamethasone was used on cycle B. Drug methods was used as following:Ondansetron 8 mg (intravenous, iv), once daily on days 1 and 2 of chemotherapy, cisplatin 60 mg/m2 or 75 mg/m2, iv, used in two-day schedules, mirtazapine 15 mg orally once daily on days 1 through 5 of chemotherapy, dexamethasone 5 mg iv, once per day on days 1 and 2, and gemcitabine 1000 mg/m2 or 1250 mg/m2, iv, once daily on days 1 and days 8. Results The control rate of nausea, acute emesis, delayed emesis and anorexia on cycle B or A was 71.4%(45/63) or 65.1%(41 /63)(P0.05), 74.6%(47/63) or 60.3%(38/63)(P<0.01), 49.2%(31/63) or 22.2%(19/63)(P<0.01), and 47.6%(30/63) or 23.8%(15/63)(P<0.05) of patients, respectively. More protection from delayed emesis was observed than from acute emesis (27.0% vs. 11.1%, P<0.01). No serious adverse events were observed on cycle B or A. Conclusion Mirtazapine is effective in treatment of nausea, emesis and anorexia caused by high dose

  17. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-07-01

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

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

    Science.gov (United States)

    Sanchiz, F; Milla, A

    1990-01-01

    Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (including anthracyclines). They were included in a trial to receive 6 g/m3 ifosfamide, mixed with 6 g/m2 mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2-8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation.

  20. Clinical study on treatment of rectal carcinoma with Chinese herbal medicine and high dose fluorouracil emulsion via rectal infusion.

    Institute of Scientific and Technical Information of China (English)

    王晨光

    1999-01-01

    Objective: To study the clinical significance of rectal infusion of Chinese herbal medicine (CHM) plus high dose fluorouracil emulsion in treating rectal carcinoma. Methods: 86 patients of rectal carcinoma were randomly divided into CHM plus chemotherapy group and single chemotherapy group, and the

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

    Science.gov (United States)

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

    2014-12-01

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

  2. High-dose neutron detector project update

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-10

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

  3. 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.

  4. High-dose secondary calibration laboratory accreditation program

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-12-31

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

  5. 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...

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

    Directory of Open Access Journals (Sweden)

    D. A. Aliyev

    2011-01-01

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

  7. MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells

    Science.gov (United States)

    Jost, Edgar; Morin-Kensicki, Elizabeth; Goecke, Tamme W.; Bosio, Andreas; Rath, Björn; Brümmendorf, Tim H.; Bissels, Ute; Wagner, Wolfgang

    2015-01-01

    Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34+ hematopoietic stem and progenitor cells (HSPCs) – however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs) or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy – particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate) increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration. PMID:26024523

  8. MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Thomas Walenda

    Full Text Available Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+ hematopoietic stem and progenitor cells (HSPCs--however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34(+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy--particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration.

  9. CLINICAL-EXPERIENCE WITH HIGH-DOSE TUMOR-NECROSIS-FACTOR-ALPHA IN REGIONAL THERAPY OF ADVANCED MELANOMA

    NARCIS (Netherlands)

    LEJEUNE, F; LIENARD, D; EGGERMONT, A; KOOPS, HS; KROON, B; GERAIN, J; ROSENKAIMER, F; SCHMITZ, P

    1994-01-01

    Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-t

  10. Outcome of combined modality treatment including neoadjuvant chemotherapy of 128 cases of locally advanced breast cancer: Data from a tertiary cancer center in northern India

    Directory of Open Access Journals (Sweden)

    V Raina

    2011-01-01

    Full Text Available Background: Breast cancer is now the most common cancer in many parts of India and the incidence varies from 12 to 31/100000, and is rising. Locally advanced breast cancer (LABC accounts for 30 - 35% of all cases of breast cancers in India. LABC continues to present a challenge and imposes a major health impact in our country. Materials and Methods: We carried out a analysis of our LABC patients who received neoadjuvant chemotherapy (NACT at our hospital over a 10-year period, from January 1995 to December 2004. We analyzed the response to NACT, disease-free survival (DFS, and overall survival (OS. Results: Patients with stages IIIA, IIIB, and IIIC were included. LABC comprised of 26.24% (609 patients of new patients. One hundred and twenty-eight (31.1% patients received NACT. Median age was 48 years and estrogen receptor was positive in 64%. Chemotherapy protocol was an FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide regimen in the following doses: Cyclophosphamide 600 mg/m2, 5-FU 600 mg/m2, and Epirubicin 75 mg/m2 given every three weeks, six doses, followed by modified radical mastectomy (MRM and locoregional radiotherapy. The overall response rate (complete response (CR + partial response (PR was 84.4%, clinical CR (cCR was 13.3% and pathological CR (pCR was 7.8%. Median DFS and OS were 33 and 101 months, respectively. The disease-free survival (DFS and overall survival (OS at five years were 41 and 58%, respectively. Conclusions: This study analyzes the outcome in patients who received NACT, in the largest number of LABC patients from a single center in India, and our results are comparable to the results reported from other centers.

  11. Effects of high doses of diethylcarbamazine on adult Onchocerca volvulus examined by the collagenase technique and by histology.

    Science.gov (United States)

    Albiez, E J; Walter, G; Kaiser, A; Newland, H S; White, A T; Greene, B M; Taylor, H R; Büttner, D W

    1988-06-01

    Thirty adult male nodule carriers from a hyperendemic onchocerciasis area in the Liberian rain forest were treated with high doses of diethylcarbamazine (30 mg/kg/d) over one week. Another ten patients received placebo tablets and served as a control. All detectable nodules were removed from half of the patients at two months and from the remaining patients at ten months after chemotherapy. The adult worms in the nodules were examined for pathological alterations by the collagenase technique including embryogram, and by histology. No macrofilaricidal effect was observed at either time, and no significant reduction of microfilariae in the uteri of the female worms or in the tissue of the nodules was seen. Two months after the therapy there was a significant increase of degenerated stretched intrauterine microfilariae but this effect was no longer observed after ten months. No pathological effect was seen on the intrauterine coiled microfilariae. On the contrary, their number had significantly increased after ten months which could mean a stimulation of the embryogenesis. No effect on spermatogenesis was observed. Both techniques, the collagenase digestion and the histological examination of the nodules, provided similar results to demonstrate that there was no marked long lasting effect on O. volvulus after a treatment with high doses of diethylcarbamazine.

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

    Directory of Open Access Journals (Sweden)

    Ali Hosni

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rajeshwari S

    2007-01-01

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

  14. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    DEFF Research Database (Denmark)

    Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W;

    2015-01-01

    PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, can...

  15. Understanding Chemotherapy

    Science.gov (United States)

    N ational C ancer I nstitute Understanding Chemotherapy What is chemotherapy? Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. It is also called “chemo.” Today, there are ...

  16. Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

    Science.gov (United States)

    Bozec, Alexandre; Benezery, Karen; Chamorey, Emmanuel; Ettaiche, Marc; Vandersteen, Clair; Dassonville, Olivier; Poissonnet, Gilles; Riss, Jean-Christophe; Hannoun-Lévi, Jean-Michel; Chand, Marie-Eve; Leysalle, Axel; Saada, Esma; Sudaka, Anne; Haudebourg, Juliette; Hebert, Christophe; Falewee, Marie-Noelle; Demard, François; Santini, José; Peyrade, Frédéric

    2016-09-01

    The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

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

  19. Improved Pharmacy Department Workflow with New Method of Order Entry for Single-Agent, High-Dose Methotrexate

    Science.gov (United States)

    VanDyke, Thomas H.; Athmann, Paul W.; Mills, Lisa B.; Bonter, Michael P.; Bremer, Matthew W.; Dougherty, Mary L.; Foster, Ryan W.; Knight, Sandra K.; Slot, Martha G.; Steinmetz-Malato, Laura L.

    2014-01-01

    Purpose: To determine whether a process change impacted the proportion of orders for single-agent, high-dose methotrexate entered by chemotherapy pharmacists instead of general pharmacy staff. Coordination of antiemetic premedication and leucovorin rescue with the new method of order entry was evaluated. Methods: Adults treated with single-agent, high-dose methotrexate were identified retrospectively. Order entry of methotrexate and ancillary medications was examined to determine whether the old or new method was used and whether it was performed by a chemotherapy pharmacist. The fundamental difference between the old and new methods for order entry is use of the “unscheduled” frequency of medication administration to replace the administration frequency of “once” with a specified date and time. Timing of antiemetic premedication and leucovorin rescue relative to methotrexate administration were tallied for the new method. Chi-square analysis was performed for the primary objective. Observational statistics were performed otherwise. Results: The number of evaluable encounters identified was 158. A chemotherapy pharmacist entered a greater proportion of orders when the new method was utilized (P < .0001). The proportion of orders entered by a chemotherapy pharmacist increased during the hours of 0700 and 2259 with the new method. Appropriate coordination of antiemetic and leucovorin administration was documented for 96% and 100% of cases with the new method of order entry. Conclusion: The proportion of orders for single-agent, high-dose methotrexate entered by a chemotherapy pharmacist was significantly greater with the use of the new method. Administration of antiemetic premedication and leucovorin rescue were appropriately coordinated with the use of the new method for order entry of single-agent, high-dose methotrexate. PMID:25673893

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

    Science.gov (United States)

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

    2006-11-20

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

  1. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

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

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  2. 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.

  3. High-Dose Statins Boost Survival

    Science.gov (United States)

    ... atorvastatin (Lipitor) or 20 to 40 mg of rosuvastatin (Crestor) daily. Examples of moderate doses include 10 to ... of Lipitor and 5 to 10 mg of Crestor, the study reported. Unlike some previous studies, this ...

  4. HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era

    Directory of Open Access Journals (Sweden)

    J. A. Rodrigo

    2012-01-01

    Full Text Available Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL has improved substantially in the highly active antiretroviral therapy (HAART era. However, HIV-Burkitt lymphoma (BL, which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL 250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART.

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

    Directory of Open Access Journals (Sweden)

    Frank Van Fraeyenhove

    2014-03-01

    Full Text Available Pancreatic neuroendocrine tumors (NETs, including poorly differentiated carcinomas (NECs, are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel®. In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0. Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

  6. Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

    DEFF Research Database (Denmark)

    Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald;

    2012-01-01

    High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours a...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

  7. Cancer Chemotherapy

    Science.gov (United States)

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  8. 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

  9. 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)

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, J.F.

    1999-07-01

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

  12. Impact of high dose vitamin C on platelet function

    Science.gov (United States)

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

    2017-01-01

    AIM To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of VitC used here correspond to plasma VitC levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography (TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate (ATP) secretion in response to collagen or adenosine diphosphate (ADP); and flow cytometry, for changes in expression of CD-31, CD41a, CD62p and CD63. In addition, PLT intracellular VitC content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time (PT), partial thrombplastin time (PTT), functional fibrinogen] and Lipidomics analysis (UPLC ESI-MS/MS). RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P 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

  13. Phase II study of intensive chemotherapy with autologous bone marrow transplantation in patients in complete remission of disseminated breast cancer

    NARCIS (Netherlands)

    deVries, EGE; Rodenhuis, S; Hupperets, PSGJ; Dolsma, WV; Lebesque, JV; Blijham, GH; Bontenbal, M; Mulder, NH

    1996-01-01

    Background: This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer. Patients and methods: Thirty women, mean age 42.2 years (range 33-55) with metastatic breast cancer, received high-dose chemotherapy in a phase II stud

  14. Periodontal infection in cancer patients treated with high-dose chemotherapy

    NARCIS (Netherlands)

    Raber-Durlacher, JE; Epstein, JB; Raber, J; van Dissel, JT; van Winkelhoff, AJ; Guiot, HFL; van der Velden, U

    2002-01-01

    The infected and inflamed periodontium can act as a focus for systemic infection in neutropenic cancer patients. The incidence of these oral infections is unknown, but probably underestimated. Periodontal infections can easily be overlooked, primarily because symptoms of gingival inflammation may be

  15. Metastatic cervical lymphadenopathy from uterine leiomyosarcoma with good local response to radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Yoon Kyeong; Park, Hee Chul; Kee, Keun Hong; Jeon, Ho Jong; Park, You Hwan; Chung, Choon Hai [College of Medicine, Chosun Univ., Kwangju (Korea, Republic of)

    2000-12-01

    The metastasis of uterine leiomyosarcoma to the neck node has not been reported previously and the radiotherapy has been rarely used for the metastatic lesion of the other sites. We report a case of neck metastasis from a uterine leiomyosarcoma, which developed 10 months after surgery and postoperative pelvic radiotherapy. It also involved the parapharyngeal space, adjacent spine, and spinal canal. The metastatic neck mass was inoperable, and was treated by neck radiotherapy (6,000 cGy) and chemotherapy including taxol and carboplatin. The mass has regressed progressively to a nearly impalpable state. She has never developed spinal cord compression syndrome, and has maintained good swallowing for eight months since the neck radiotherapy and chemotherapy. Since the extensive metastatic neck mass showed good local response to high dose radiotherapy and chemotherapy, both treatments may be considered for an unresectable metastatic leiomyosarcoma.

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

    Directory of Open Access Journals (Sweden)

    Andry Juliansen

    2014-11-01

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

  17. p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Shien,Tadahiko

    2013-06-01

    Full Text Available While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB are needed to predict neoadjuvant chemotherapy (NAC response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane at the National Cancer Center Hospital (NCCH. We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD. In a comparison between the 9 (5% sensitive patients and 30 (16% insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p=0.045 and histological grade 3 (p=0.011 were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  19. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

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

    2000-01-01

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

  20. 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

  1. Oral lorazepam prevents seizure during high-dose busulfan in children undergoing hematopoietic stem cell transplantation: a prospective study.

    Science.gov (United States)

    Hamidieh, Amir Ali; Hamedani, Ravak; Hadjibabaie, Molouk; Amini, Mohsen; Sadrai, Sima; Ghavamzadeh, Ardeshir

    2010-10-01

    High-dose Busulfan in combination chemotherapy has been used commonly for hematopoietic stem cell transplantation. It crosses the blood-brain barrier and could cause seizure. Benzodiazepines have been used as anticonvulsant prophylaxis. This is a prospective study using oral lorazepam together with busulfan-based conditioning regimen in 30 children undergoing hematopoietic stem cell transplantation. The dose of lorazepam used ranged from 0.017 to 0.039 mg/kg (median = 0.026 mg/kg) per dose. None of the patients developed seizure while receiving oral lorazepam or within 72 hours of the last dose of Busulfan. Oral lorazepam was tolerated by the patients, but all patients needed dose reduction due to some adverse effects. In the authors' experience, oral lorazepam is a useful anticonvulsant prophylaxis for children receiving high-dose busulfan.

  2. Neurotoxicity of cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Miyoung Yang; Changjong Moon

    2013-01-01

    There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.

  3. High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Hannibal, J; Hallas, Jesper;

    1991-01-01

    In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low.......01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low...

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Science.gov (United States)

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

    2005-10-01

    Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of 1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

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

    Science.gov (United States)

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

    1980-05-01

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

  8. 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

  9. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-08-01

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

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

    Science.gov (United States)

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

    2002-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Kolar Vishwanath Vinod

    2014-01-01

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

  13. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , Sara ... cancer treatments. Breast cancer treatments include the following: Chemotherapy involves drugs that are intended to kill the ...

  14. Chemotherapy (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Chemotherapy KidsHealth > For Parents > Chemotherapy Print A A A ... have many questions and concerns about it. About Chemotherapy Chemotherapy (often just called "chemo") refers to medications ...

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo.

    Science.gov (United States)

    Hu, Yanmin; Liu, Alexander; Ortega-Muro, Fatima; Alameda-Martin, Laura; Mitchison, Denis; Coates, Anthony

    2015-01-01

    Although high-dose rifampicin holds promise for improving tuberculosis control by potentially shortening treatment duration, these effects attributed to eradication of persistent bacteria are unclear. The presence of persistent Mycobacterium tuberculosis was examined using resuscitation promoting factors (RPFs) in both in vitro hypoxia and in vivo murine tuberculosis models before and after treatment with incremental doses of rifampicin. Pharmacokinetic parameters and dose-dependent profile of rifampicin in the murine model were determined. The Cornell mouse model was used to test efficacy of high-dose rifampicin in combination with isoniazid and pyrazinamide and to measure relapse rate. There were large numbers of RPF-dependent persisters in vitro and in vivo. Stationary phase cultures were tolerant to rifampicin while higher concentrations of rifampicin eradicated plate count positive but not RPF-dependent persistent bacteria. In murine infection model, incremental doses of rifampicin exhibited a dose-dependent eradication of RPF-dependent persisters. Increasing the dose of rifampicin significantly reduced the risk of antibiotic resistance emergence. In Cornell model, mice treated with high-dose rifampicin regimen resulted in faster visceral clearance; organs were M. tuberculosis free 8 weeks post-treatment compared to 14 weeks with standard-dose rifampicin regimen. Organ sterility, plate count and RPF-dependent persister negative, was achieved. There was no disease relapse compared to the standard dose regimen (87.5%). High-dose rifampicin therapy results in eradication of RPF-dependent persisters, allowing shorter treatment duration without disease relapse. Optimizing rifampicin to its maximal efficacy with acceptable side-effect profiles will provide valuable information in human studies and can potentially improve current tuberculosis chemotherapy.

  20. High dose rifampicin kills persisters, shortens treatment duration and reduces relapse rate in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Yanmin eHu

    2015-06-01

    Full Text Available Although high-dose rifampicin holds promise for improving tuberculosis control by potentially shortening treatment duration, these effects attributed to eradication of persistent bacteria are unclear. The presence of persistent M. tuberculosis was examined using resuscitation promoting factors (RPF in both in vitro hypoxia and in vivo murine tuberculosis models before and after treatment with incremental doses of rifampicin. Pharmacokinetic parameters and dose-dependent profile of rifampicin in the murine model were determined. The Cornell mouse model was used to test efficacy of high-dose rifampicin in combination with isoniazid and pyrazinamide and to measure relapse rate. There were large numbers of RPF-dependent persisters in vitro and in vivo. Stationary phase cultures were tolerant to rifampicin while higher concentrations of rifampicin eradicated plate count positive but not RPF-dependent persistent bacteria. In murine infection model, incremental doses of rifampicin exhibited a dose-dependent eradication of RPF-dependent persisters. Increasing the dose of rifampicin significantly reduced the risk of antibiotic resistance emergence. In Cornell model, mice treated with high-dose rifampicin regimen resulted in faster visceral clearance; organs were M. tuberculosis free 8 weeks post-treatment compared to 14 weeks with standard-dose rifampicin regimen. Organ sterility, plate count and RPF-dependent persister negative, was achieved. There was no disease relapse compared to the standard dose regimen (87.5%. High-dose rifampicin therapy results in eradication of RPF-dependent persisters, allowing shorter treatment duration without disease relapse. Optimising rifampicin to its maximal efficacy with acceptable side-effect profiles will provide valuable information in human studies and can potentially improve current tuberculosis chemotherapy.

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

    Science.gov (United States)

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

    2013-05-22

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

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

    Science.gov (United States)

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

    2013-05-20

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-11

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

  4. 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.

  5. The effect of intraarterial high-dose cisplatin on lymph nodes in oral and oropharyngeal cancer

    Directory of Open Access Journals (Sweden)

    A F Kovács

    2012-01-01

    Full Text Available Aim of Study: To assess the effect of strictly local treatment [intraarterial chemotherapy (iaCHT with high-dose cisplatin and parallel neutralization] in the primary oral and oropharyngeal cancer (OOSCC on the dependent cervical lymph nodes. Patients and Methods: Seventeen consecutive patients with OOSCC and clinically positive necks underwent a prospective blinded comparison of two pre-surgical fluor18-deoxyglucose (FDG-positron emission tomography (PET examinations: baseline examination 1 week before and follow-up examination 3 weeks after iaCHT. Maximal standardized uptake (SUVmax values of lymph nodes were measured and compared with each other and histopathology. Results: The SUVmax value of the primary and all neck lymph nodes with uptake decreased significantly. Twelve/17 patients having metastases revealed significant decrease (P = 0.03, and benign lymph nodes showed non-significant decrease of the SUVmax. All neck lymph nodes with uptake and nodal metastases showed a significant reduction (P = 0.004 of standard uptake values (SUV. Conclusion: A regional effect of intraarterial cisplatin is proven. To date, it is not clear whether this is due to decreasing inflammatory reaction or a translymphatic anti-neoplastic effect.

  6. Arterial occlusion precipitated by cisplatinbased chemotherapy

    OpenAIRE

    2010-01-01

    Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

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

    Science.gov (United States)

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

  8. Outpatient chemotherapy, family-centered care, electronic information, and education in adolescents and young adults with osteosarcoma

    Directory of Open Access Journals (Sweden)

    Anderson P

    2013-01-01

    Full Text Available Pete Anderson, Patricia Wells, Theresa Lazarte, Laura Gore, Laura Salvador, Maritza Salazar-AbshireMD Anderson Cancer Center, Pediatrics, Houston TX, USAAbstract: Current osteosarcoma chemotherapy is “standard” (doxorubicin, cisplatin, high-dose methotrexate ± ifosfamide-mesna, and etoposide ± mifamurtide, but current regimens have many short-term, medium-term, and long-term side effects. Generally 12–15 cycles of chemotherapy are given in the hospital over 7–10 months. Even in the absence of new research protocols, improvement in quality of life is now possible, with all osteosarcoma chemotherapy agents now being able to be administered in the outpatient setting. Outpatient chemotherapy is not only less expensive, but in the adolescent and young adult population can result in better quality of life for some. In this paper, we share information to help reduce the frequency of hospitalization and review some tools and strategies to facilitate communication when providing outpatient chemotherapy, family-centered care, and information/education. These include antiemetics with both longer-acting 5HT antagonists and aprepitant, outpatient chemotherapy guidelines, and a 5-week editable calendar that is part of our electronic medical record. Sharing information on absolute lymphocyte count recovery is another means of maintaining hope and increasing understanding of the prognosis of osteosarcoma. Finally, this paper shares an advanced directive/palliative care “checklist” of issues for patients and caregivers to consider at end of life, ie, when “cure of cancer is not the answer”. In summary, better communication at all stages of osteosarcoma care can help reduce hospitalization, improve quality of life, and maintain hope in the adolescent and young adult population with osteosarcoma.Keywords: family-centered care, adolescent and young adult, flash drives, chemotherapy calendars, outpatient, osteosarcoma, chemotherapy

  9. A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma.

    Science.gov (United States)

    Dispenzieri, A; Wiseman, G A; Lacy, M Q; Litzow, M R; Anderson, P M; Gastineau, D A; Tefferi, A; Inwards, D J; Micallef, I N M; Ansell, S M; Porrata, L; Elliott, M A; Lust, J A; Greipp, P R; Rajkumar, S V; Fonseca, R; Witzig, T E; Erlichman, C; Sloan, J A; Gertz, M A

    2005-01-01

    Despite response rates of 30% after high-dose chemotherapy with autologous hematopoietic stem cell transplant, patients with multiple myeloma are not cured. 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet) is a short-range, beta-emitting therapeutic radiopharmaceutical with avid skeletal uptake. In total, 12 patients were treated with escalating doses of 153Sm-EDTMP (N=3/group; 6, 12, 19.8, and 30 mCi/kg) and a fixed dose of melphalan (200 mg/m(2)). No dose limiting toxicity was seen. To better standardize the marrow compartment radiation dose, the study was modified such that an additional six patients were treated at a targeted absorbed radiation dose to the red marrow of 40 Gy based on a trace labeled infusion 1 week prior to the therapy. Despite rapid elimination of unbound radiopharmaceutical via kidneys and bladder, no episodes of nephrotoxicity, hemorrhagic cystitis, or delayed radiation nephritis were observed with a median follow-up of 31 months (range 8.5-44). Median times to ANC>0.5 and platelet >20 x 10(6)/l were 12 and 11 days, respectively, with no graft failures. Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study.

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

    Science.gov (United States)

    Podgorsak, Matthew B.

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

  11. Image-guided high dose rate endorectal brachytherapy.

    Science.gov (United States)

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

    2007-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-21

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

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

    Science.gov (United States)

    McCarty, M F

    2000-05-01

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

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-07-01

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

  16. Remote Afterloading High Dose Rate Brachytherapy AMC EXPERIANCES

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-15

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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Ramin Shabani

    2016-08-01

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

  19. Types of chemotherapy

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  20. Chemotherapy for Thyroid Cancer

    Science.gov (United States)

    ... Type and Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  1. Chemotherapy for Testicular Cancer

    Science.gov (United States)

    ... Type and Stage Testicular Cancer Treating Testicular Cancer Chemotherapy for Testicular Cancer Chemotherapy (chemo) is the use of drugs to treat ... that is only in the testicle. Doctors give chemotherapy in cycles, with each period of treatment followed ...

  2. Side Effects of Chemotherapy

    Science.gov (United States)

    ... Jacket Fashion Show Contact Us Side Effects of Chemotherapy Each of the chemotherapy drugs available today works in a slightly different ... few rules of thumb when it comes to chemotherapy that should always be kept in mind. Ignore ...

  3. Chemotherapy and Your Mouth

    Science.gov (United States)

    ... Treatment and Oral Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being ... Problems Too? Remember Are You Being Treated With Chemotherapy for Cancer? If so, this booklet can help ...

  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. 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

  6. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  7. PROGNOSTIC FACTORS FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS TREATED WITH HIGH-DOSE METHOTREXATE-BASED CHEMO-RADIOTHERAPY

    Science.gov (United States)

    Nagane, Motoo; Lee, Jeunghun; Shishido-Hara, Yukiko; Suzuki, Kaori; Shimizu, Saki; Umino, Michiru; Kobayashi, Keiichi; Shiokawa, Yoshiaki

    2014-01-01

    BACKGROUND: Chemotherapy with high-dose methotrexate (HD-MTX) followed by whole brain radiotherapy (WBRT) is a conventional approach to treat primary central nervous system lymphomas (PCNSL), but some tumors relapse early leading to unfavorable outcome. Several biomarkers have been identified as prognostic factors in PCNSL, however, the correlation of both clinical factors including those related to MTX metabolism and B-cell differentiation and oncogenic biomarkers with response to and outcome by therapy is yet unclear. METHODS: We investigated 32 immunocompetent patients (19 males, 13 females) with PCNSL (all diffuse large B-cell type) treated with HD-MTX based therapy with or without WBRT since 2000 in our institution. Paraffin-embedded formalin-fixed tumor tissue sections were stained immunohistochemically with antibodies against following factors: B-cell differentiation markers (CD10, Bcl-6, Mum-1, CD138); MTX metabolism-related (MRP family, LRP, DHFR); cell cycle-related (p27KIP1, MIB-1); drug resistance-related (MGMT, MLH1, MSH2, MSH6, PMS2); and oncogenes (Myc, Bcl-2). Correlation between positivity of these factors and clinical outcomes were evaluated using logrank test and cox regression analysis. RESULTS: Among these factors, complete response to HD-MTX was significantly associated with longer progression-free survival (PFS)(P = 0.0012), while Bcl-6 expression as well as histological subtype (non-germinal center B-cell, non-GCB) was closely correlated with shorter PFS. Age (>60) (P = 0.006) and MSH2 expression (P = 0.017) were found to be better predictor for overall survival (OS), but in multivariate analysis, they were no longer significant. Other factors involved in MTX metabolism, DNA repair enzymes, and oncogenes did not affect outcome. CONCLUSIONS: Non-GCB subtype and Bcl-6 expression may be associated with worse outcome in patients with PCNSL treated with HD-MTX, while MTX-metabolism related factors did not influence prognosis. Further

  8. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  9. 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

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

    Science.gov (United States)

    Vuong, T; Devic, S; Podgorsak, E

    2007-11-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  12. Short-term response of sleep-potentiated spiking to high-dose diazepam in electric status epilepticus during sleep.

    Science.gov (United States)

    Sánchez Fernández, Iván; Hadjiloizou, Stavros; Eksioglu, Yaman; Peters, Jurriaan M; Takeoka, Masanori; Tas, Emir; Abdelmoumen, Imane; Rotenberg, Alexander; Kothare, Sanjeev V; Riviello, James J; Loddenkemper, Tobias

    2012-05-01

    We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by ≥50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = -4.287, P status epilepticus during sleep.

  13. High-dose corticosterone after fear conditioning selectively suppresses fear renewal by reducing anxiety-like response.

    Science.gov (United States)

    Wang, Hongbo; Xing, Xiaoli; Liang, Jing; Bai, Yunjing; Lui, Zhengkui; Zheng, Xigeng

    2014-09-01

    Exposure therapy is widely used to treat anxiety disorders, including posttraumatic stress disorder (PTSD). However, preventing the return of fear is still a major challenge after this behavioral treatment. An increasing number of studies suggest that high-dose glucocorticoid treatment immediately after trauma can alleviate the symptoms of PTSD in humans. Unknown is whether high-dose glucocorticoid treatment following fear conditioning suppresses the return of fear. In the present study, a typical fear renewal paradigm (AAB) was used, in which the fear response to an auditory cue can be restored in a novel context (context B) when both training and extinction occur in the same context (context A). We trained rats for auditory fear conditioning and administered corticosterone (CORT; 5 and 25mg/kg, i.p.) or vehicle with different delays (1 and 24h). Forty-eight hours after drug injection, extinction was conducted with no drug in the training context, followed by a test of tone-induced freezing behavior in the same (AAA) or a shifted (AAB) context. Both immediate and delayed administration of high-dose CORT after fear conditioning reduced fear renewal. To examine the anxiolytic effect of CORT, independent rats were trained for cued or contextual fear conditioning, followed by an injection of CORT (5 and 25mg/kg, i.p.) or vehicle at a 1 or 24h delay. One week later, anxiety-like behavior was assessed in the elevated plus maze (EPM) before and after fear expression. We found that high-dose CORT decreased anxiety-like behavior without changing tone- or context-induced freezing. These findings indicate that a single high-dose CORT administration given after fear conditioning may selectively suppress fear renewal by reducing anxiety-like behavior and not by altering the consolidation, retrieval, or extinction of fear memory.

  14. Early infections in patients undergoing high-dose treatment with stem cell support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma

    DEFF Research Database (Denmark)

    Gang, A O; Arpi, M.; Gang, U.J.O.;

    2010-01-01

    Background: Infections are life-threatening complications in patients undergoing high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious pathogens is essential to make a safe outpatient setting. Methods: We conducted a retrospective study of 208 patients treated with HDT...... related mortality was similar between the groups. Conclusion: The frequency of isolated pathogens, positive blood cultures, and the diversity of pathogens were higher in MM patients as compared to NHL patients. However, this did not translate into higher transplantation-related mortality, probably because...

  15. Optimized patient-trajectory for patients undergoing treatment with high-dose chemotherapy and autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Bartels, Frederik Reith; Smith, Nicholas Simon; Gørløv, Jette Sønderskov;

    2015-01-01

    to home exercises of 5.3 (± 2.8) days and a median weekly physical activity of 240 (± 153.8) minutes was found. During hospital stay the median attendance was 9 (± 3.9) days of 10 (± 6.9) possible. Two months after discharge the patients reported a median weekly physical activity of 360 (2745.5) minutes...... for use in the ambulatory setting and supervised exercise sessions Monday to Friday for 30-40 minutes during admission. Safety of the exercise program and physical tests were assessed by using a weekly questionnaire and report of inadvertent incidences. Adherence to the home-based exercise program...... to exercise program and assessments; performance of three days of physical exercises during ambulatory period and hospital stay and 150 minutes of weekly physical activity. RESULTS: Of the 25 patients who completed the exercise program during the ambulatory period prior to HD-ASCT a mean weekly attendance...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    BACKGROUND: /st>High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA). METHODS: /st>Forty-eight patients undergoing unilateral THA...... under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet...... well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length...

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

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-01-01

    Full Text Available Chronic phantom limb pain (PLP is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation. Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction.

  18. Addition of an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy improves survival in advanced malignancies.

    Science.gov (United States)

    Lasalvia-Prisco, Eduardo; Goldschmidt, Pablo; Galmarini, Felipe; Cucchi, Silvia; Vázquez, Jesús; Aghazarian, Martha; Lasalvia-Galante, Eduardo; Golomar, Wilson; Gordon, William

    2012-12-01

    Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.

  19. A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients

    Science.gov (United States)

    Jeong, Yusook; Han, Hye Sook; Lee, Hyo Duk; Yang, Jiyoul; Jeong, Jiwon; Choi, Moon Ki; Kwon, Jihyun; Jeon, Hyun-Jung; Oh, Tae-Keun; Lee, Ki Hyeong; Kim, Seung Taik

    2016-01-01

    Purpose Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. Materials and Methods Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. Results Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). Conclusion We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone. PMID:26987397

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

    Science.gov (United States)

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

    2012-09-07

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

  1. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-06-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. High-dose pelvic irradiation followed by ileal neobladder urinary diversion: complications and long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Gschwend, J.E.; May, F.; Paiss, T.; Gottfried, H.W.; Hautmann, R.E. [Ulm Univ. (Germany)

    1996-05-01

    The objective was to determine the risk of post-operative complications in patients receiving high-dose pelvic irradiation before radical cystectomy and urinary diversion. The post-operative course, including the duration of hospital stay, peri-operative complications and early functional results, did not differ from a control group of non-irradiated patients, and no patients died. The mean follow-up was 22 months (range 10-37) and revealed satisfactory results in seven of 11 patients. A neovesicoperitoneal fistula developed in one woman 10 months after surgery and was repaired by laparotomy. A neovesicovaginal fistula led to supravesical urinary diversion in the second woman. High-dose pelvic irradiation should not be a primary contra-indication for orthotopic urinary diversion using segments of small intestine. For patients who undergo combined external and after loading radiotherapy, the indication for orthotopic bladder replacement should be considered critically. (Author).

  5. A case of acute psychosis in a patient following exposure to a single high dose of styrene.

    Science.gov (United States)

    Moon, Eunsoo; Suh, Hwagyu; Lee, Byung Dae; Park, Je Min; Lee, Young Min; Jeong, Hee Jeong

    2015-09-01

    We report a case of acute psychotic symptoms following exposure to a single high dose of styrene monomer. The 24-year-old male patient showed psychotic and cognitive symptoms immediately after exposure. His psychotic symptoms included auditory hallucinations and delusions of reference. Brain magnetic resonance imaging, electroencephalography, and laboratory examinations were performed to evaluate any other causes. The clinical, neuroimaging, and laboratory review in this case suggested that the suddenly developed psychotic symptoms that led to chronic deterioration were caused by the single exposure to styrene monomer. This is the first recent report in which acute psychotic symptoms developed from a single high dose of styrene suffocation compared with previous findings showing symptoms because of long-term low-dose exposure.

  6. Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience

    Directory of Open Access Journals (Sweden)

    Knut Liseth

    2010-01-01

    Full Text Available In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.

  7. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    Directory of Open Access Journals (Sweden)

    De Souza C.A.

    2000-01-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  8. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  10. Chemotherapy | Smokefree.gov

    Science.gov (United States)

    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  11. Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy. Complications and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Mohnike, Konrad; Wolf, Steffen; Damm, Robert; Seidensticker, Max; Seidensticker, Ricarda; Fischbach, Frank; Pech, Maciej; Ricke, Jens [Otto-von-Guericke-Universitaet, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany); Peters, Nils; Hass, Peter; Gademann, Guenther [Otto-von-Guericke-Universitaet, Klinik fuer Strahlentherapie, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany)

    2016-05-15

    To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT). Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006-2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained. The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months. Image-guided iBT yields a low rate of major complications and is effective. (orig.) [German] Evaluierung der Komplikationsrate und Identifizierung von Risikofaktoren fuer Komplikationen und Nebenwirkungen bei Patienten mit Lebermalignomen, die mit der hochdosierten interstitiellen Brachytherapie (iBT) behandelt wurden. Von 2006 bis 2009 wurden 192 Patienten in 343 CT- oder MRT-gefuehrten Interventionen behandelt und deren Daten ausgewertet. Der groesste behandelte Tumor war in

  12. Uterine/Endometrial Cancer: Chemotherapy

    Science.gov (United States)

    ... Types of Gynecologic Cancers Uterine/Endometrial Cancer Chemotherapy Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected ...

  13. Dexamethasone Chemotherapy Does Not Disrupt Orexin Signaling

    Science.gov (United States)

    Kram, David E.; Krasnow, Stephanie M.; Levasseur, Peter R.; Zhu, Xinxia; Stork, Linda C.

    2016-01-01

    Background Steroid-induced sleep disturbance is a common and highly distressing morbidity for children receiving steroid chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL). Sleep disturbance can negatively impact overall quality of life, neurodevelopment, memory consolidation, and wound healing. Hypothalamic orexin neurons are influential wake-promoting neurons, and disturbances in orexin signaling leads to abnormal sleep behavior. A new class of drug, the orexin receptor antagonists, could be an intriguing option for sleep disorders caused by increased orexinergic output. Our aim was to examine the impact of ALL treatment doses of corticosteroids on the orexin system in rodents and in children undergoing treatment for childhood ALL. Methods We administered repeated injections of dexamethasone to rodents and measured responsive orexin neural activity compared to controls. In children with newly diagnosed standard risk B-cell ALL receiving dexamethasone therapy per Children’s Oncology Group (COG) induction therapy from 2014–2016, we collected pre- and during-steroids matched CSF samples and measured the impact of steroids on CSF orexin concentration. Results In both rodents, all markers orexin signaling, including orexin neural output and orexin receptor expression, were preserved in the setting of dexamethasone. Additionally, we did not detect a difference in pre- and during-dexamethasone CSF orexin concentrations in children receiving dexamethasone. Conclusions Our results demonstrate that rodent and human orexin physiology is largely preserved in the setting of high dose dexamethasone. The data obtained in our experimental model fail to demonstrate a causative role for disruption of the orexin pathway in steroid-induced sleep disturbance. PMID:27997622

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

    Science.gov (United States)

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

    2010-04-02

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

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

    Science.gov (United States)

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

    2012-09-01

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

  16. Whole-Body Radiation Therapy, Systemic Chemotherapy, and High-Dose Chemotherapy Followed By Stem Cell Rescue in Treating Patients With Poor-Risk Ewing Sarcoma

    Science.gov (United States)

    2015-01-07

    Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

  17. 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.

  18. Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus.

    Science.gov (United States)

    Juul, Sandra E; Beyer, Richard P; Bammler, Theo K; McPherson, Ronald J; Wilkerson, Jasmine; Farin, Federico M

    2009-05-01

    Recombinant human erythropoietin (rEpo) is neuroprotective in neonatal models of brain injury. Proposed mechanisms of neuroprotection include activation of gene pathways that decrease oxidative injury, inflammation, and apoptosis, while increasing vasculogenesis and neurogenesis. To determine the effects of rEpo on gene expression in 10-d-old BALB-c mice with unilateral brain injury, we compared microarrays from the hippocampi of brain-injured pups treated with saline or rEpo to similarly treated sham animals. Total RNA was extracted 24 h after brain injury and analyzed using Affymetrix GeneChip Mouse Exon 1.0 ST Arrays. We identified sex-specific differences in hippocampal gene expression after brain injury and after high-dose rEpo treatment using single-gene and gene set analysis. Although high-dose rEpo had minimal effects on hippocampal gene expression in shams, at 24-h post brain injury, high-dose rEpo treatment significantly decreased the proinflammatory and antiapoptotic response noted in saline-treated brain-injured comparison animals.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-02-15

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

  20. 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)

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  2. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nassr Nama

    2016-02-01

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

  5. 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

  6. Efficacy and Tolerability of Weekly Paclitaxel in Combination with High-dose Toremifene Citrate in Patients with Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Okita,Riki

    2009-08-01

    Full Text Available Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.

  7. Is High Dose Therapy Superior to Conventional Dose Therapy as Initial Treatment for Relapsed Germ Cell Tumors? The TIGER Trial

    Directory of Open Access Journals (Sweden)

    Darren R. Feldman, Robert Huddart, Emma Hall, Jörg Beyer, Thomas Powles

    2011-01-01

    Full Text Available Metastatic germ cell tumours (GCTs are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT and high dose therapy (HDT are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP with sequential HDT (TICE. The planned open labelled randomised phase III study (TIGER is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint. It is hoped that this large study will conclusively resolve the uncertainty which currently exists.

  8. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-08-14

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Bapu V Ravindranath

    2012-01-01

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

  11. 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

  12. Change of SPARC expression after chemotherapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yong-Yin Gao; Xin-Yuan Zhang; Yi Ba; Ding-Zhi Huang; Ru-Bing Han; Xia Wang; Shao-Hua Ge; Hong-Li Li; Ting Deng; Rui Liu; Ming Bai; Li-Kun Zhou

    2015-01-01

    Objective:The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine (SPARC) expression changes atfer chemotherapy in gastric cancer (GC) is unclear. hTis study investigated the inlfuence of chemotherapy on SPARC expression in GC. Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the inlfuence of chemotherapy on SPARC expression. Results:SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression atfer chemotherapy were independent prognostic factors. Conclusion:SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC atfer chemotherapy.

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

    Directory of Open Access Journals (Sweden)

    Mònica Pujol

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

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

    Science.gov (United States)

    Dalakas, M C

    2003-10-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Science.gov (United States)

    Tsai, Meng-Chang; Huang, Tiao-Lai

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Belka Claus

    2011-10-01

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

  19. A New Model of Biodosimetry to Integrate Low and High Doses

    Science.gov (United States)

    Pujol, Mònica; Barquinero, Joan-Francesc; Puig, Pedro; Puig, Roser; Caballín, María Rosa; Barrios, Leonardo

    2014-01-01

    Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation. PMID:25461738

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-01-01

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

  2. Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez, Rachel B., E-mail: rbjimenez@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Sethi, Roshan [Harvard Medical School, Boston, Massachusetts (United States); Depauw, Nicolas [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Pulsifer, Margaret B. [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Adams, Judith [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); McBride, Sean M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Ebb, David [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Fullerton, Barbara C.; Tarbell, Nancy J.; Yock, Torunn I.; MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.

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

    Directory of Open Access Journals (Sweden)

    Lung-Sheng Lu

    2012-01-01

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

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

    Science.gov (United States)

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

    1988-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuying; Li Huiling; Zheng Tianrong; Lin Xiangsong

    1998-01-01

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

  6. Congenital sacrococcygeal PNET and chemotherapy

    Directory of Open Access Journals (Sweden)

    Colin Patrick Hawkes

    2012-01-01

    Full Text Available We present the case of a congenital localised sacrococcygeal primitive neuroectodermal tumor treated aggressively with surgical resection and modified age-appropriate adjuvant chemotherapy. The conventional combination chemotherapy of vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide was modified to a regimen including vincristine, adriamicin, cyclophosphamide and actinomycin in order to minimise the predicted toxicity in this age group. Adjuvant "induction" chemotherapy commenced at 4 weeks of age and consisted of four cycles of vincristine, adriamycin and cyclophosphamide at 50%, 75%, 75% and 100% of recommended doses (vincristine 0.05 mg/kg, adriamycin 0.83 mg/kg daily × 2, cyclophosphamide 40 mg/kg at 3-weekly intervals. This was followed by four cycles of "maintenance" chemotherapy with vincristine (0.025 mg/kg, actinomycin (0.025 mg/kg and cyclophosphamide (36 mg/kg at full recommended doses. Cardioxane at a dose of 16.6 mg/kg was infused immediately prior to the adriamycin. Our patient is thriving at 19 months out from end of treatment.

  7. Recovery of mucosal-associated invariant T cells after myeloablative chemotherapy and autologous peripheral blood stem cell transplantation.

    Science.gov (United States)

    Novak, Jan; Dobrovolny, Jan; Brozova, Jitka; Novakova, Lucie; Kozak, Tomas

    2016-11-01

    Immune reconstitution after high-dose chemotherapy and stem cell transplantation plays a key role in restoring immunocompetence including defense against infection, immune regulation, and onco-immune surveillance. In this work, we examined the recovery of mucosal-associated invariant T (MAIT) cells, recently discovered innate-like T cells, after various types of myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in 29 patients. We show that MAIT cells are relatively resistant to myeloablative conditioning. The median amount of MAIT cells rises to 43 % around day +30 and is sustained through further measurements on days +60 and +100. Moreover, MAIT cell recovery reaches 100 % of pre-treatment values in 33 % of patients already by day +60. The only factor affecting recovery of MAIT cells is age, younger age being associated with earlier MAIT cell recovery. The pre-treatment quantity of MAIT cells carries a prognostic impact on the early post-transplantation course. Patients with high levels of MAIT cells pre-treatment have significantly lower peak CRP levels (79.45 vs. 150 mg/L) post-treatment, reflecting a clinical trend of less severe infectious complications (less febrile days and less days on intravenous antibiotics). Altogether these data suggest that a high proportion of MAIT cells survive myeloablative chemotherapy and maintain their capacity to fight against infections probably on mucosal surfaces.

  8. High dose rate interstitial brachytherapy in soft tissue sarcomas: technical aspect

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Mi Son; Kang, Seung Hee; Kim, Byoung Suck; Oh, Young Taek [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1999-03-01

    To discuss the technical aspect of interstitial brachytherapy including method of implant, insertion time of radioactive source, total radiation dose, and complication, we reviewed patients who had diagnoses of soft tissue sarcoma and were treated by conservative surgery, interstitial implant and external beam radiation therapy. Between May 1995 and Dec. 1997, the patients with primary or recurrent soft tissue sarcoma underwent surgical resection (wide margin excision) and received radiotherapy including interstitial brachytherapy. Catheters were placed with regular intervals of 1-1.5 cm immediately after tumor removal and covering the critical structures, such as neurovascular bundle or bone, with gelform, muscle, or tissue expander in the cases where the tumors were close to those structures. Brachytherapy consisted of source axis with 2-2.5 Gy/fraction, twice a day, starting on 6th day after the surgery. Within one month after the surgery, total dose of 50-55 Gy was delivered to the tumor bed with wide margin by the external beam radiotherapy. All patients completed planned interstitial brachytherapy without acute side effects directly related with catheter implantation such as infection or bleeding. With median follow up duration of 25 months (range 12-41 months), no local recurrences were observed. And there was no severe form of chromic complication (RTOG/EORTC grade 3 or 4). The high dose rate interstitial brachytherapy is easy and safe way to minimize the radiation dose delivered to the adjacent normal tissue and to decrease radiation induced chronic morbidity such as fibrosis by reducing the total dose of external radiotherapy in the management of soft tissue sarcoma with conservative surgery.

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

  13. Association between the high-dose use of benzodiazepines and rehospitalization in patients with schizophrenia: a 2-year naturalistic study

    Directory of Open Access Journals (Sweden)

    Takita Y

    2016-12-01

    Full Text Available Yukika Takita,1 Yoshikazu Takaesu,1 Kotaro Ono,1 Kunihiro Futenma,1 Akiyoshi Shimura,1 Akiko Murakoshi,1 Yoko Komada,2 Yuichi Inoue,1,2 Takeshi Inoue1 1Department of Psychiatry, 2Department of Somnology, Tokyo Medical University, Tokyo, Japan Background: High-dose use of benzodiazepines (BZPs reportedly causes adverse effects on cognitive function and quality of life in patients with schizophrenia. However, effects of BZPs on the clinical course of schizophrenia have not been clarified. This study was set out to investigate the association between BZPs and rehospitalization of patients with schizophrenia.Methods: In this retrospective study, patients with schizophrenia who were discharged from Tokyo Medical University Hospital between January 2009 and February 2012 were eligible as subjects. One hundred and eight patients who continued treatment for >2 years after hospital discharge were included in this study. Clinical characteristics, doses of prescribed medication such as BZPs and antipsychotics, and Global Assessment of Functioning scores at discharge were investigated. The primary outcome was rehospitalization of patients for any reason.Results: In a total of 108 subjects with schizophrenia, 44 subjects (40.7% experienced rehospitalization during the 2-year study period. A multivariate analysis by the Cox proportional hazards model revealed that low educational history (hazard ratio =2.43, P=0.032, younger onset age of schizophrenia (hazard ratio =2.10, P=0.021, and higher diazepam-equivalent dose (hazard ratio =6.53, P=0.011 were significantly associated with the time to rehospitalization after hospital discharge.Conclusion: The results of this study suggest that high-dose use of BZPs at discharge in patients with schizophrenia might be associated with a shorter time to rehospitalization. Keywords: schizophrenia, rehospitalization, risk factor, high-dose benzodiazepine, Cox proportional hazards model

  14. Severe multiorganic flare of systemic lupus erythematosus successfully treated with rituximab and cyclophosphamide avoiding high doses of prednisone.

    Science.gov (United States)

    Gonzalez-Echavarri, C; Pernas, B; Ugarte, A; Ruiz-Irastorza, G

    2014-03-01

    Both acute pancreatitis and diffuse alveolar haemorrhage are rare conditions associated with systemic lupus erythematosus (SLE). In this case report, a 23-year-old female with SLE was diagnosed with lupus-associated pancreatitis and, within a few days and despite initial therapy with pulse methyl-prednisolone, subsequently suffered an acute respiratory failure due to a diffuse alveolar haemorrhage. The patient was admitted to the intensive care unit and treatment was intensified with cyclophosphamide and rituximab, which shortly induced the complete remission of SLE with resolution of both clinical conditions. She completed treatment with six pulses of cyclophosphamide followed by azathioprine, hydroxychloroquine and prednisone at initial doses of 20 mg/d with rapid tapering to 5 mg/d, without relapse of the disease during the following year. This case can illustrate that, even in severe, life-threatening SLE flares, it is possible to avoid high-dose prednisone, which has been associated with severe side effects, including infections. Acute pancreatitis and diffuse alveolar haemorrhage are rare conditions caused by SLE. DAH can be a life-threatening complication, with an early mortality of at least 50%. When facing such severe SLE activity, there is a general tendency to use high doses of prednisone as the initial therapy, maintaining such high doses for long periods of time, even after the clinical situation has subsided. We report a case of a young woman with SLE, suffering from acute pancreatitis and diffuse alveolar haemorrhage, who was successfully treated with pulse methyl-prednisolone, hydroxychloroquine, cyclophosphamide and rituximab, combined with medium doses of prednisone.

  15. Radiation safety protocol for high dose 131I therapy of thyroid carcinoma in patients on hemodialysis for chronic renal failure.

    Science.gov (United States)

    Modarresifar, Homayoun; Almodovar, Samuel; Bass, William B; Ojha, Buddhiwardhan

    2007-02-01

    Iodine ablation therapy for thyroid cancer on patients receiving dialysis poses unique radiation safety challenges. Exposure to gamma and beta negative particles by the hemodialysis (HD) staff is a concern that has not been well studied. A 53-y-old male patient on HD for chronic renal failure was scheduled for 131I high dose therapy as treatment for thyroid papillary carcinoma. The patient was on HD every other day, prior to ablation. A high dose of 131I (3,607.5 MBq) was required. The patient was admitted for 131I therapy, and continued HD. Thyroid cancer ablation therapy was administered according to our institutional protocol. New radiation safety measures were developed and implemented in order to give the patient an optimal treatment dose, reduce radiation to the patient (critical organs and whole body), and to protect the HD personnel. This included placing two lead shields between the patient and the HD nurse, and HD monitoring by two alternating nurses to reduce their radiation exposure. Film badges were used to measure radiation exposure to the nursing staff. Dosimetry calculations were obtained to determine radiation absorbed doses by the optic lens, skin, and whole body. Quality control verification for this shielding arrangement proved to be effective in protecting the HD staff against gamma and beta negative radiation from recent 131I high dose therapy. Implementation of this model proved to be an effective and adequate radiation safety protocol for limiting radiation exposure to the HD staff. The patient was given 3607.5 MBq for optimal treatment after HD. Hemodialysis was repeated after approximately 48 and 96 h to remove excess 131I and reduce radiation to the patient.

  16. Chemotherapy for Soft Tissue Sarcomas

    Science.gov (United States)

    ... Stage Soft Tissue Sarcoma Treating Soft Tissue Sarcomas Chemotherapy for Soft Tissue Sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  17. Extravasation of chemotherapy

    DEFF Research Database (Denmark)

    Langer, Seppo W

    2010-01-01

    Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led...

  18. 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.

  19. Overview, prevention and management of chemotherapy extravasation.

    Science.gov (United States)

    Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

    2016-02-10

    Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.

  20. 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

  1. Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy

    Science.gov (United States)

    Campos, Luciana Tourinho; de Almeida, Carlos Eduardo Veloso

    2015-01-01

    Introduction The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®); it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21), which is also from BEBIG. Objective and Methods The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the

  2. A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

    Science.gov (United States)

    Testi, Anna Maria; Del Giudice, Ilaria; Arcese, William; Moleti, Maria Luisa; Giona, Fiorina; Basso, Giuseppe; Biondi, Andrea; Conter, Valentino; Messina, Chiara; Rondelli, Roberto; Micozzi, Alessandra; Micalizzi, Concetta; Barisone, Elena; Locatelli, Franco; Dini, Giorgio; Aricò, Maurizio; Casale, Fiorina; Comis, Margherita; Ladogana, Saverio; Lippi, Alma; Mura, Rossella; Pinta, Marie France; Santoro, Nicola; Valsecchi, Maria Grazia; Masera, Giuseppe; Mandelli, Franco

    2002-09-01

    The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

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

    Science.gov (United States)

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

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

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

    Directory of Open Access Journals (Sweden)

    Sujata Narendra Datti

    2015-01-01

    Full Text Available Failure to detect pregnancy in the emergency situations can have important consequences. These include missing of ectopic pregnancy (the leading cause of first-trimester pregnancy-related maternal death, administration of medications contraindicated in pregnancy, fetal radiation exposure, and medico legal problems. This in turn has led to the dictum to check for pregnancy in all women of child-bearing age group. Urine pregnancy (human chorionic gonadotropin [hCG] test is the commonly used test to rule out pregnancy and has been reported by Griffey et al. in their study to achieve 100% sensitivity and 99.2% specificity in a clinical setting, resulting in a positive predictive value of 98.3% and a negative predictive value of nearly 100%. However, the sensitivity is influenced not only by the quantity of β hCG but on its variants that vary with different weeks of pregnancy. β hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. In spite of its high sensitivity, in the presence of molar pregnancy that is associated with very high levels of β hCG it fails to detect the antigen (β hCG. This is explained by the phenomenon known as "high-dose hook effect" which further leads to delay in diagnosis and treatment. This can be overcome by dilution of the sample. In such cases, diagnosis will be made by serum β hCG and ultrasound (USG. Here, we present a case of gravida 2 para 1 living 1 with 2΍ months amenorrhea with bleeding p/v and pain abdomen of 20 days duration whose urine β hCG was repeatedly negative and diagnosis was made by serum β hCG and USG.

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

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2008-06-01

    Full Text Available Objective: The aim of this study was to determine the associates of marital relationship in mustard exposed veterans.Materials and Methods: Two hundred ninety two married Iranian mustard exposed veterans, who had been exposed to single high dose mustard gas in Iraq-Iran war, were assessed for marital adjustment with Revised Dyadic Adjustment Scale (RDAS. Census sampling was done. The patients' quality of life (SF-36, spirometric measures and war related data were also extracted.Results: A total of 189 subjects (65% completed our study. The mean (±SD of the RDAS Total score, RDAS Dyadic Consensus , RDAS Affectional Expression, RDAS Dyadic Satisfaction , and RDAS Dyadic Cohesion were 50.61 (8.16, 16.67 (2.77, 7.62 (1.84, 14.76 (3.39, and 11.54 (3.79, respectively. RDAS Dyadic satisfaction was correlated with SF-36 and all its sub-scores (p<0.05. RDAS total score showed significant correlation with SF-36 total score and most of its sub-scores (p<0.05. RDAS affective expression was significantly correlated with role limitation, social function, general mental health, vitality, General health perceptions, physical composite score (PCS and mental composite score (MCS (p<0.05. RDAS dyadic consensus was not correlated with any SF-36 sub-scores.Conclusion: Veterans health team including physicians, psychologists and/or psychiatrists should know that poorer marital satisfaction is linked with lower quality of life scores, late after mustard exposure, although marital relationship is independent of spirometric findings, age, duration from exposure and comorbidity score.

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

    Directory of Open Access Journals (Sweden)

    Hee Jin Shim

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

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

    Science.gov (United States)

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

    2002-12-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  9. Renal tubular function in patients treated with high-dose cisplatin

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H;

    1988-01-01

    The effect of three cycles of high-dose cisplatin (40 mg/m2 day for 5 days) on renal tubular function was evaluated in 30 patients. A significant impairment of proximal tubular salt and water reabsorption rates was observed, but also distal tubular function seemed to be affected. These changes were...... and water reabsorption during cisplatin administration....

  10. 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...

  11. 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

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

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

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

  13. 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.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yang Yang

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Afshin Fayyazi

    2011-06-01

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

  19. 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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2008-08-01

    In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerología (INCan).

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

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

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

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

    Science.gov (United States)

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

    1998-04-01

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

  4. 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.

  5. Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms

    Institute of Scientific and Technical Information of China (English)

    Wei-Dong Du; Song-Bai Zheng; Zu-Rong Yuan; Jian Sun; Jian-Xiong Tang; Ai-Qun Cheng; Da-Ming Shen; Chun-Jin Huang; Xiao-Hua Song; Xiao-Feng Yu

    2003-01-01

    those in he control group. Alter treatment, the average value of P-VC was significantly higher and the values of SIL-2R, TNF-α, IL-6 and IL-8 were significantly lower in the treatment group than in the control group (P<0.05 P-VC,P=0.045; SIL-2R, P=0.012; TNF-α, P=0.030; IL-6, P=0.015;and IL-8, P =0.043). In addition, the ratio of CD4/CD8 and CD4 positive cells in the patients of treatment group were significantly higher than that of the control group after treatment (P<0.05. CD4/CD8, P =0.039; CD4, P =0.024).CONCLUSION: High-dose vitamin C has therapeutic efficacy on acute pancreatitis. The potential mechanisms include promotion of anti-oxidizing ability of AP patients, blocking of lipid peroxidation in the plasma and improvement of cellular immune function.

  6. 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.

  7. Association between the high-dose use of benzodiazepines and rehospitalization in patients with schizophrenia: a 2-year naturalistic study

    Science.gov (United States)

    Takita, Yukika; Takaesu, Yoshikazu; Ono, Kotaro; Futenma, Kunihiro; Shimura, Akiyoshi; Murakoshi, Akiko; Komada, Yoko; Inoue, Yuichi; Inoue, Takeshi

    2016-01-01

    Background High-dose use of benzodiazepines (BZPs) reportedly causes adverse effects on cognitive function and quality of life in patients with schizophrenia. However, effects of BZPs on the clinical course of schizophrenia have not been clarified. This study was set out to investigate the association between BZPs and rehospitalization of patients with schizophrenia. Methods In this retrospective study, patients with schizophrenia who were discharged from Tokyo Medical University Hospital between January 2009 and February 2012 were eligible as subjects. One hundred and eight patients who continued treatment for >2 years after hospital discharge were included in this study. Clinical characteristics, doses of prescribed medication such as BZPs and antipsychotics, and Global Assessment of Functioning scores at discharge were investigated. The primary outcome was rehospitalization of patients for any reason. Results In a total of 108 subjects with schizophrenia, 44 subjects (40.7%) experienced rehospitalization during the 2-year study period. A multivariate analysis by the Cox proportional hazards model revealed that low educational history (hazard ratio =2.43, P=0.032), younger onset age of schizophrenia (hazard ratio =2.10, P=0.021), and higher diazepam-equivalent dose (hazard ratio =6.53, P=0.011) were significantly associated with the time to rehospitalization after hospital discharge. Conclusion The results of this study suggest that high-dose use of BZPs at discharge in patients with schizophrenia might be associated with a shorter time to rehospitalization. PMID:28008260

  8. Irradiation dose and temperature dependence of fracture toughness in high dose HT9 steel from the fuel duct of FFTF

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Thak Sang; Toloczko, Mychailo B.; Saleh, Tarik A.; Maloy, Stuart A.

    2013-01-14

    To expand the knowledge base for fast reactor core materials, fracture toughness has been evaluated for high dose HT9 steel using miniature disk compact tension (DCT) specimens. The HT9 steel DCT specimens were machined from the ACO-3 fuel duct of the Fast Flux Test Facility (FFTF), which achieved high doses in the range of 3–148 dpa at 378–504 C. The static fracture resistance (J-R) tests have been performed in a servohydraulic testing machine in vacuum at selected temperatures including room temperature, 200 C, and each irradiation temperature. Brittle fracture with a low toughness less than 50 MPa pm occurred in room temperature tests when irradiation temperature was below 400 C, while ductile fracture with stable crack growth was observed when irradiation temperature was higher. No fracture toughness less than 100 MPa pm was measured when the irradiation temperature was above 430 C. It was shown that the influence of irradiation temperature was dominant in fracture toughness while the irradiation dose has only limited influence over the wide dose range 3–148 dpa. A slow decrease of fracture toughness with test temperature above room temperature was observed for the nonirradiated and high temperature (>430 *C) irradiation cases, which indicates that the ductile–brittle transition temperatures (DBTTs) in those conditions are lower than room temperature. A comparison with the collection of existing data confirmed the dominance of irradiation temperature in the fracture toughness of HT9 steels.

  9. [Combined radio- and chemotherapy of anal cancer].

    Science.gov (United States)

    Dobrowsky, W

    1986-05-30

    The treatment regime in anal carcinoma is changing from being a mainly surgical problem. Combined radio-chemotherapy is of increasing interest as treatment of choice. The new treatment modality, including chemotherapy with Mitomycin C and 5-fluorouracil combined with percutaneous and interstitial radiotherapy is presented. The treatment regimes performed at the University Department for Radiotherapy and Radiobiology Vienna is discussed with regard to tolerance, side effects and local control.

  10. Treatment results of radical radiotherapy of carcinoma uterine cervix using external beam radiotherapy and high dose rate intracavitary radiotherapy

    Directory of Open Access Journals (Sweden)

    Azad S

    2010-01-01

    Full Text Available Aim: To report the outcome of carcinoma cervix patients treated radically by external beam radiotherapy and high dose rate intracavitary radiotherapy. Material and Methods: From January 2005 to December 2006, a total of 709 newly diagnosed cases of carcinoma cervix were reported in our department. All cases were staged according to the International Federation of Gynecologist and Oncologist staging system. Out of 709 cases, 342 completed radical radiotherapy and were retrospectively analyzed for the presence of local residual disease, local recurrence, distant metastases, radiation reaction, and disease free survival. Results: There were 11(3.22%, 82(23.98%, 232(67.83%, and 17(4.97% patients in stages I, II, III, and IV, respectively. The median follow up time for all patients was 36 months (range 3 -54 months. The overall treatment time (OTT ranged from 52 to 69 days (median 58 days. The 3 year disease free survival rate was 81.8%, 70.7%, 40.08%, and 11.76% for stages I, II, III, and IV, respectively. There were 91 (26.6% cases with local residual diseases, 27(7.9% developed distant metastasis, and 18(5.26% pts had local recurrence. Discussion: The results of this study suggest that radical radiotherapy with HDR brachytherapy was appropriate for the treatment of early staged cancer of uterine cervix. For locally advanced cancer of cervix addition of concurrent chemotherapy, higher radiation doses, reduction of overall treatment time to less than 8 weeks, and use of latest radiotherapy techniques such as IMRT is recommended to improve the results.

  11. HIGH DOSE CHEMORADIOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE TREATMENT OF ADVANCED HODGKIN'S LYMPHOMA: A REPORT OF 11 CASES

    Institute of Scientific and Technical Information of China (English)

    周生余; 石远凯; 何小慧; 韩晓红; 刘鹏; 杨建良; 周爱萍; 冯奉仪

    2002-01-01

    Objective: High dose therapy (HDT) with autologous hematopoietic stem celltransplantation (ASCT) has become one of the important salvage treatments for the Hodgkin's Lymphoma patients with relapsed or resistant disease, but its role as the primary treatment remains indefinite. This study was designed to further evaluate its status in the combined modality treatment, especially, to discuss its value in the primary treatment of the patients who had advanced disease with poor prognostic factors. Methods: Eleven patients who had advanced or relapsed disease with poor prognostic factors were enrolled in this study. Among them, 9 cases had primary treatment, and 2 cases had secondary treatment; one patient received autologous bone marrow transplantation (ABMT), and 10 patients received autologous peripheral blood stem cell transplantation (APBSCT). After induction treatment 4 cases achieved complete response (CR) and 7 cases achieved partial response (PR). High dose chemotherapy combined with total body irradiation (TBI) ortotal lymph node irradiation (TLI)/subtotallymph node irradiation (STLI) were adopted in 7 cases and only high dose chemotherapy were adopted in 4 cases as the transplant preparative regimens. 5 cases received complementary irradiation in the primary sites after transplant. Results:The patients who had CR before transplantation were given consolidative therapy. Among the rest with PR, 2 cases achieved CR, 1 case PR, and 4 cases SD. Furthermore all these patients who maintained SD had bone involvement. With a median follow-up for all patients of 13(1(80) months, all of them are alive currently. Four cases are event-free survival (EFS); 4 cases with bone involvement are progression-free survival (PFS); 3 cases experienced relapse after transplant, one ofthem is EFS for 42 months again after a local relapsed site irradiation; the other two cases are being given further salvaged treatment now. According to the Life Tables method, the cumulative probability

  12. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I; Aass, N

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor......-prognosis germ-cell cancer (GCC). Patient and methods: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-15

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

  14. Primary Central Nervous System Lymphoma (PCNSL): Analysis of Treatment by Gamma Knife Radiosurgery and Chemotherapy in a Prospective, Observational Study

    Science.gov (United States)

    Alvarez-Pinzon, Andres M; Wolf, Aizik L; Coy, Sammie R; Valerio, Jose E

    2016-01-01

    Background: Primary central nervous system lymphoma (PCNSL) is a rare cancer accounting for less than 3% of primary brain and central nervous system (CNS) tumors. Tissues involved include the brain parenchyma, leptomeninges, eyes, and spinal cord. High-dose methotrexate (MTX) is the gold standard for newly diagnosed PCNSL. However, Gamma Knife radiosurgery (GKRS) may be efficacious as a co-adjuvant treatment. The purpose of this prospective observational cohort study is to determine the effectiveness of MTX in combination with GKRS in the treatment of PCNSL. Methods: This is a prospective, observational cohort study evaluating the treatment of histologically confirmed PCNSL with MTX as a single agent in a dose of 8 g/m2 (control) and treatment with MTX, plus GKRS. Strict inclusion and exclusion criteria were employed. Primary outcomes were measured by survival rate. Secondary outcomes were assessed by the tumor’s responsiveness to treatment and reduction in size as noted on imaging. Results: Between January 2007 and January 2012, 128 charts were evaluated. Included in this evaluation were 73 chemotherapy (control) and 55 chemotherapy, plus GKRS, patients (variable). The follow-up period was 24 to 49 months (mean: 36.9 months). There were no statistically significant differences in patient demographics or histology diagnosis. Patients were treated with GK doses ranging from 11 Gy to 16 Gy (median: 11 Gy). The median survival rate from initial diagnosis was 26.8 months in the chemotherapy group and 47.6 in the chemotherapy, plus GKRS, group (p-value: 0.0034). All lesions showed a complete response after GKRS when evaluated using magnetic resonance imaging after three to eight weeks (mean range: 6.3 weeks). Conclusions: The use of GKRS is non-invasive, safe, and shows rapid success, improving the prognosis of the patient. This noninvasive treatment modality should be considered as an option for patients with PCNSL. In our study, GKRS as a co-adjuvant therapy to

  15. Chemotherapy for Melanoma.

    Science.gov (United States)

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

    Prior to the recent therapeutic advances, chemotherapy was the mainstay of treatment options for advanced-stage melanoma. A number of studies have investigated various chemotherapy combinations in order to expand on the clinical responses achieved with single-agent dacarbazine, but these have not demonstrated an improvement in overall survival. Similar objective responses were observed with the combination of carboplatin and paclitaxel as were seen with single-agent dacarbazine. The combination of chemotherapy and immunotherapy, known as biochemo-therapy, has shown high clinical responses; however, biochemo-therapy has not been shown to improve overall survival and resulted in increased toxicities. In contrast, palliation and long-term responses have been observed with localized treatment with isolated limb perfusion or infusion in limb-isolated disease. Although new, improved therapeutic options exist for first-line management of advanced-stage melanoma, chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma. We review the various chemotherapy options available for use in the treatment and palliation of advanced-stage melanoma, discuss the important clinical trials supporting the treatment recommendations, and focus on the clinical circumstances in which treatment with chemotherapy is useful.

  16. [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.

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

    CERN Document Server

    Komarov, A F

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2010-10-01

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

  20. 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.

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

    Science.gov (United States)

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

    2008-10-01

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

  2. 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.

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

    Science.gov (United States)

    Pellizzon, Antônio Cássio Assis

    2016-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-15

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

  6. 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)

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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)

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

    Science.gov (United States)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Gorlin AW

    2016-09-01

    Full Text Available Andrew W Gorlin, David M Rosenfeld, Jillian Maloney, Christopher S Wie, Johnathan McGarvey, Terrence L Trentman Department of Anesthesiology, Mayo Clinic Arizona, Phoenix, AZ, USA Abstract: The conversion of high-dose intravenous (IV opioids to an equianalgesic epidural (EP or intrathecal (IT dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted. Keywords: intrathecal pump, epidural, cancer pain

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

    Science.gov (United States)

    DeZern, Amy E.; Zahurak, Marianna; Symons, Heather; Cooke, Kenneth; Jones, Richard J.; Brodsky, Robert A.

    2017-01-01

    Severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder that is treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IST). The management of patients with refractory SAA after IST is a major challenge. Alternative donor BMT is the best chance for cure in refractory SAA, but morbidity and mortality from graft failure and complications of graft-versus-host disease (GVHD) have limited enthusiasm for this approach. Here, we employed post-transplantation high-dose cyclophosphamide in an effort to safely expand the donor pool in 16 consecutive patients with refractory SAA who did not have a matched sibling donor. Between July 2011 and August 2016, 16 patients underwent allogeneic (allo) BMT for refractory SAA from 13 haploidentical donors and 3 unrelated donors. The nonmyeloablative conditioning regimen consisted of antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation. Post-transplantation cyclophosphamide 50 mg/kg/day i.v. on days +3 and +4 was administered for GVHD prophylaxis. Additionally, patients received mycophenolate mofetil on days +5 through 35 and tacrolimus from day +5 through 1 year. The median age of the patients at the time of transplantation was 30 (range, 11 to 69) years. The median time to neutrophil recovery over 1000 × 103/mm3 for 3 consecutive days was 19 (range, 16 to 27) days, to red cell engraftment was 25 (range, 2 to 58) days, and to last platelet transfusion to keep platelets counts over 50 × 103/mm3 was 27.5 (range, 22 to 108) days. Graft failure, primary or secondary, was not seen in any of the patients. All 16 patients are alive, transfusion independent, and without evidence of clonality. The median follow-up is 21 (range, 3 to 64) months. Two patients had grade 1 or 2 skin-only acute GVHD. These same 2 also had mild chronic GVHD of the skin/mouth requiring systemic steroids. One of these GVHD patients was able to come off all IST by 15 months and the

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

    Science.gov (United States)

    Palmer, Antony; Mzenda, Bongile

    2009-12-21

    A comprehensive system characterisation was performed of the Eckert & Ziegler BEBIG GmbH MultiSource High Dose Rate (HDR) brachytherapy treatment unit with an (192)Ir source. The unit is relatively new to the UK market, with the first installation in the country having been made in the summer of 2009. A detailed commissioning programme was devised and is reported including checks of the fundamental parameters of source positioning, dwell timing, transit doses and absolute dosimetry of the source. Well chamber measurements, autoradiography and video camera analysis techniques were all employed. The absolute dosimetry was verified by the National Physical Laboratory, UK, and compared to a measurement based on a calibration from PTB, Germany, and the supplied source certificate, as well as an independent assessment by a visiting UK centre. The use of the 'Krieger' dosimetry phantom has also been evaluated. Users of the BEBIG HDR system should take care to avoid any significant bend in the transfer tube, as this will lead to positioning errors of the source, of up to 1.0 mm for slight bends, 2.0 mm for moderate bends and 5.0 mm for extreme curvature (depending on applicators and transfer tube used) for the situations reported in this study. The reason for these errors and the potential clinical impact are discussed. Users should also note the methodology employed by the system for correction of transit doses, and that no correction is made for the initial and final transit doses. The results of this investigation found that the uncorrected transit doses lead to small errors in the delivered dose at the first dwell position, of up to 2.5 cGy at 2 cm (5.6 cGy at 1 cm) from a 10 Ci source, but the transit dose correction for other dwells was accurate within 0.2 cGy. The unit has been mechanically reliable, and source positioning accuracy and dwell timing have been reproducible, with overall performance similar to other existing HDR equipment. The unit is capable of high

  15. Symptoms in Children After Chemotherapy

    Directory of Open Access Journals (Sweden)

    Sevcan Atay Turan

    2016-08-01

    Full Text Available Introduction: Identification of symptoms resulted from chemotherapy in children. Materials and Methods: In this study 46 children and adolescents who had chemotherapy in a pediatric oncology clinic of an oncology hospital were included. Sociodemographic questionnaire and Memorial Symptom Assessment Scale (10-18 years were used as data collection tool. Results: In this survey the mean age of children with cancer was 13.47±2.14 years and the majority of them (41.3% were monitored with non-Hodgkin’s lymphoma diagnosis. The most common symptoms in children who had chemotherapy in hospital were fatigue (76.1%, feeling nervous (69.6%, alopecia (65.2%, nausea (60.9% and feeling sad (60.9%, while the least common symptoms were swelling in the arms/legs (8.7% and problems in urination (6.5%. The most troublesome symptoms were dizziness (66.6%, difficulty in swallowing (64.3%, pain (47.8% and hair loss (43.4%. Conclusions: It was seen that the children still experience high prevalence of post-treatment symptoms, they had more intense psychological symptoms and physical symptoms caused more discomfort.

  16. Mechanisms of chemotherapy-induced behavioral toxicities

    Directory of Open Access Journals (Sweden)

    Elisabeth G Vichaya

    2015-04-01

    Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  17. Mechanisms of chemotherapy-induced behavioral toxicities.

    Science.gov (United States)

    Vichaya, Elisabeth G; Chiu, Gabriel S; Krukowski, Karen; Lacourt, Tamara E; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J; Walker, Adam K

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  18. Fasting and differential chemotherapy protection in patients.

    Science.gov (United States)

    Raffaghello, Lizzia; Safdie, Fernando; Bianchi, Giovanna; Dorff, Tanya; Fontana, Luigi; Longo, Valter D

    2010-11-15

    Chronic calorie restriction has been known for decades to prevent or retard cancer growth, but its weight-loss effect and the potential problems associated with combining it with chemotherapy have prevented its clinical application. Based on the discovery in model organisms that short term starvation (STS or fasting) causes a rapid switch of cells to a protected mode, we described a fasting-based intervention that causes remarkable changes in the levels of glucose, IGF-I and many other proteins and molecules and is capable of protecting mammalian cells and mice from various toxins, including chemotherapy. Because oncogenes prevent the cellular switch to this stress resistance mode, starvation for 48 hours or longer protects normal yeast and mammalian cells and mice but not cancer cells from chemotherapy, an effect we termed Differential Stress Resistance (DSR). In a recent article, 10 patients who fasted in combination with chemotherapy, reported that fasting was not only feasible and safe but caused a reduction in a wide range of side effects accompanied by an apparently normal and possibly augmented chemotherapy efficacy. Together with the remarkable results observed in animals, these data provide preliminary evidence in support of the human application of this fundamental biogerontology finding, particularly for terminal patients receiving chemotherapy. Here we briefly discuss the basic, pre-clinical, and clinical studies on fasting and cancer therapy.

  19. 盐酸帕洛诺司琼对预防含顺铂方案化疗所致恶心呕吐患者的疗效观察%Effect observation of Palonosetron hydrochloride on preventing nausea and vomiting with chemotherapy including cisplatin

    Institute of Scientific and Technical Information of China (English)

    段琼玉; 吴荣

    2012-01-01

    目的 探讨分别应用盐酸帕洛诺司琼、盐酸格拉司琼预防含顺铂方案化疗所致恶心呕吐的疗效.方法 将60例接受含顺铂方案化疗的肿瘤患者随机分为观察组(盐酸帕洛诺司琼组)及对照组(盐酸格拉司琼组),每组各30例,比较两组对预防化疗所致呕吐的临床疗效、用药后不同时间恶心的完全控制率以及恶心治疗后的有效率.结果 观察组急性呕吐的总有效率(83.3%)明显高于对照组(66.7%),两组延迟性呕吐的总有效率分别为70.0%和53.3%,差异有统计学意义(χ2=14.127,P 0.05).结论 盐酸帕洛诺司琼在预防含顺铂方案化疗所引起的恶心呕吐的疗效优于盐酸格拉司琼,安全性好,值得临床推广.%Obejective To investigate and compare effects of Palonosetron hydrochloride and granisetron hydrochloride were used to prevent the nausea and vomiting caused by chemotherapy with cisplatin. Methods 60 patients receiving chemotherapy including cisplatin were randomly divided into the observation group (palonosetron hydrochloride Group)and the control group(granisetron hydrochloride group),each group contained 30 cases. The occurrence of acute emesis, delayed vomiting, and Nausea complete control rate, nausea treatment efficiency after treatment different times were compared between two groups. Results The acute vomiting total effective rate in observation group (83.3%) was significantly higher than the control group (66.7%). Delayed vomiting total efficiency of two groups was 70.0% and 53.3% respectively, the difference was statistically significance (x2=14.127, P 0.05). Conclusion The efficacy of Palonosetron hydrochloride in the prevention and treatment of nausea and vomiting caused by chemotherapy including cisplatin is superior to the efficacy of aranisetron hydrochloride, and Palonosetron hydrochloride has its own priorities, such as convenient use, good safety and worthy of clinical application.

  20. Duloxetine and pregabalin: high-dose monotherapy or their combination? The "COMBO-DN study"--a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain.

    Science.gov (United States)

    Tesfaye, Solomon; Wilhelm, Stefan; Lledo, Alberto; Schacht, Alexander; Tölle, Thomas; Bouhassira, Didier; Cruccu, Giorgio; Skljarevski, Vladimir; Freynhagen, Rainer

    2013-12-01

    This multicentre, double-blind, parallel-group study in diabetic peripheral neuropathic pain addressed whether, in patients not responding to standard doses of duloxetine or pregabalin, combining both medications is superior to increasing each drug to its maximum recommended dose. For initial 8-week therapy, either 60 mg/day duloxetine (groups 1, 2) or 300 mg/day pregabalin (groups 3, 4) was given. Thereafter, in the 8-week combination/high-dose therapy period, only nonresponders received 120 mg/day duloxetine (group 1), a combination of 60 mg/day duloxetine and 300 mg/day pregabalin (groups 2, 3), or 600 mg/day pregabalin (group 4). Primary outcome (Brief Pain Inventory Modified Short Form [BPI-MSF] 24-hour average pain change after combination/high-dose therapy) was analyzed comparing combination (groups 2, 3 pooled) with high-dose monotherapy (groups 1, 4 pooled). Secondary end points included response rates, BPI-MSF severity items, and comparison of duloxetine and pregabalin in BPI-MSF average pain. Eight hundred four patients were evaluated for initial therapy and 339 for combination/high-dose therapy. There were no significant differences between combination and high-dose monotherapy regarding BPI-MSF average pain (mean change: combination: -2.35; high-dose monotherapy: -2.16; P = 0.370) and most secondary end points, which, however, consistently favoured combination therapy. Fifty-percent response rates were 52.1% for combination and 39.3% for high-dose monotherapy (P = 0.068). In exploratory analyses of the initial 8-week therapy uncorrected for multiple comparisons, 60 mg/day duloxetine was found superior to 300 mg/day pregabalin (P < 0.001). Both drugs and their combination were well tolerated. Although not significantly superior to high-dose monotherapy, combination therapy was considered to be effective, safe, and well tolerated.

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

    Science.gov (United States)

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

    2009-04-01

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

  2. 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

  3. Resuscitation after severe burn injury using high-dose ascorbic acid: a retrospective review.

    Science.gov (United States)

    Kahn, Steven Alexander; Beers, Ryan J; Lentz, Christopher W

    2011-01-01

    Resuscitation of burn victims with high-dose ascorbic acid (vitamin C [VC]) was reported in Japan in the year 2000. Benefits of VC include reduction in fluid requirements, resulting in less tissue edema and body weight gain. In turn, these patients suffer less respiratory impairment and reduced requirement for mechanical ventilation. Despite these results, few burn centers resuscitate patients with VC in fear that it may increase the risk of renal failure. A retrospective review of 40 patients with greater than 20% TBSA between 2007 and 2009 was performed. Patients were divided into two groups: one received only lactated Ringer's (LR) solution and another received LR solution plus 66 mg/kg/hr VC. Both groups were resuscitated with the Parkland formula to maintain stable hemodynamics and adequate urine output (>0.5 ml/kg/hr). Patients with >10-hour delay in transfer to the burn center were excluded. Data collected included age, gender, weight, %TBSA, fluid administered in the first 24 hours, urine output in the first 24 hours, and Acute Physiology and Chronic Health Evaluation II score. PaO2 in millimeters mercury:%FIO2 ratio and positive end-expiratory pressure were measured at 12-hour intervals, and hematocrit was measured at 6-hour intervals. Comorbidities, mortality, pneumonia, fasciotomies, and renal failure were also noted. After 7 patients were excluded, 17 patients were included in the VC group and 16 in the LR group. VC and LR were matched for age (42 ± 16 years vs 50 ± 20 years, P = .2), burn size (45 ± 21%TBSA vs 39 ± 15%TBSA, P = .45), Acute Physiology and Chronic Health Evaluation II (17 ± 7 vs 18 ± 8, P = .8), and gender. Fluid requirements in the first 24 hours were 5.3 ± 1 ml/kg/%TBSA for VC and 7.1 ± 1 ml/kg/%TBSA for LR (P < .05). Urine output was 1.5 ± 0.4 ml/kg/hr for VC and 1 ± 0.5 ml/kg/hr for LR (P < .05). Vasopressors were needed in four VC patients and nine LR patients (P = .07). VC patients required vasopressors to maintain mean

  4. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  5. Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea.

    Directory of Open Access Journals (Sweden)

    Yunji Hwang

    Full Text Available This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC.The Thyroid Cancer Longitudinal Study (T-CALOS included 2,258 DTC patients (449 men and 1,809 women and 22,580 healthy participants (4,490 men and 18,090 women who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs and 95% confidence intervals (95%CI were estimated using conditional regression models.While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion was associated with increased risks in men (OR = 2.22, 95%CI = 1.27-3.87 and women (OR = 3.61, 95%CI = 1.52-8.58 compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31-40 years: OR = 1.58, 95%CI = 1.10-2.28; 41+ years: OR = 3.46, 95%CI = 2.06-5.80 and women (31-40 years: OR = 2.18, 95%CI = 1.62-2.92; 41+ years: OR = 2.71, 95%CI = 1.36-5.05 compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage.The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.

  6. Computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of metastases adjacent to the liver hilum

    Energy Technology Data Exchange (ETDEWEB)

    Collettini, Federico, E-mail: federico.collettini@charite.de [Department of Radiology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany); Department of Radiation Oncology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin (Germany); Singh, Anju [Department of Medical Oncology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin (Germany); Schnapauff, Dirk [Department of Radiology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin (Germany); Department of Radiation Oncology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin (Germany); Powerski, Maciej Janusz [Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); Department of Radiation Oncology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin (Germany); and others

    2013-10-01

    Purpose: To evaluate technical feasibility and clinical outcome of computed tomography-guided high-dose-rate-brachytherapy (CT-HDRBT) ablation of metastases adjacent to the liver hilum. Materials and methods: Between November 2007 and May 2012, 32 consecutive patients with 34 metastases adjacent to the liver hilum (common bile duct or hepatic bifurcation ≤5 mm distance) were treated with CT-HDRBT. Treatment was performed by CT-guided applicator placement and high-dose-rate brachytherapy with an iridium-192 source. MRI follow-up was performed 6 weeks and every 3 months post intervention. The primary endpoint was local tumor control (LTC); secondary endpoints included time to progression (TTP) and overall survival (OS). Results: Patients were available for MRI evaluation for a mean follow-up time of 18.75 months (range: 3–56 months). Mean tumor diameter was 4.3 cm (range: 1.3–10.7 cm). One major complication was observed. Four (11.8%) local recurrences were observed after a local tumor control of 5, 8, 9 and 10 months, respectively. Twenty-two patients (68.75%) experienced a systemic tumor progression during the follow up period. Mean TTP was 12.9 months (range: 2–56 months). Nine patients died during the follow-up period. Median OS was 20.24 months. Conclusion: Minimally invasive CT-HDRBT is a safe and effective option also for unresectable liver metastases adjacent to the liver hilum that would have been untreatable by thermal ablation.

  7. Irradiation dose and temperature dependence of fracture toughness in high dose HT9 steel from the fuel duct of FFTF

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Thak Sang, E-mail: byunts@ornl.gov [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Toloczko, Mychailo B. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Saleh, Tarik A.; Maloy, Stuart A. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2013-01-15

    To expand the knowledge base for fast reactor core materials, fracture toughness has been evaluated for high dose HT9 steel using miniature disk compact tension (DCT) specimens. The HT9 steel DCT specimens were machined from the ACO-3 fuel duct of the Fast Flux Test Facility (FFTF), which achieved high doses in the range of 3-148 dpa at 378-504 Degree-Sign C. The static fracture resistance (J-R) tests have been performed in a servohydraulic testing machine in vacuum at selected temperatures including room temperature, 200 Degree-Sign C, and each irradiation temperature. Brittle fracture with a low toughness less than 50 MPa {radical}m occurred in room temperature tests when irradiation temperature was below 400 Degree-Sign C, while ductile fracture with stable crack growth was observed when irradiation temperature was higher. No fracture toughness less than 100 MPa {radical}m was measured when the irradiation temperature was above 430 Degree-Sign C. It was shown that the influence of irradiation temperature was dominant in fracture toughness while the irradiation dose has only limited influence over the wide dose range 3-148 dpa. A slow decrease of fracture toughness with test temperature above room temperature was observed for the nonirradiated and high temperature (>430 Degree-Sign C) irradiation cases, which indicates that the ductile-brittle transition temperatures (DBTTs) in those conditions are lower than room temperature. A comparison with the collection of existing data confirmed the dominance of irradiation temperature in the fracture toughness of HT9 steels.

  8. 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.

  9. 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

  10. Chemotherapy, cognitive impairment and hippocampal toxicity.

    Science.gov (United States)

    Dietrich, J; Prust, M; Kaiser, J

    2015-11-19

    Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation.

  11. Salmonella Typhi–Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone

    Directory of Open Access Journals (Sweden)

    Melissa Brosset Ugas MD

    2016-05-01

    Full Text Available Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics.

  12. 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

  13. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Holloway Cameron J

    2010-11-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mikirova Nina

    2012-09-01

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

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

    OpenAIRE

    Wiwik Misaco Yuniarti; Ira Sari Yudaniayanti; Nusdianto Triakoso

    2008-01-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

    Bauters, T; Vandenbroucke, J; Commeyne, S

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    P Pallavee

    2013-01-01

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

  4. 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.

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

    Science.gov (United States)

    Yamaguchi, Masayoshi; Weitzmann, M Neale

    2012-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-04-01

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

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

    Science.gov (United States)

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

    1989-04-01

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

  8. 20-Year Experience With Intraoperative High-Dose-Rate Brachytherapy for Pediatric Sarcoma: Outcomes, Toxicity, and Practice Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Folkert, Michael R.; Tong, William Y. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Pediatric Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wexler, Leonard H.; Chou, Alexander J.; Magnan, Heather [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-10-01

    Purpose: To assess outcomes and toxicity of high-dose-rate intraoperative radiation therapy (HDR-IORT) in the management of pediatric sarcoma. Methods and Materials: Seventy-five pediatric patients underwent HDR-IORT for sarcoma from May 1993 to November 2013. The median age was 9 years old (36 patients were ≤6 years old). HDR-IORT was part of initial therapy in 37 patients (49%) and for recurrent disease in 38 patients (51%). Forty-one patients (55%) received HDR-IORT and postoperative external beam RT (PORT), and 22 patients (29%) were previously treated with external beam radiation therapy to the IORT site. Local control (LC), overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier methods. Results: At a median follow-up of 7.8 years for surviving patients, 5-year projected rates of LC, EFS, and OS were 63% (95% confidence interval [CI] 50%-76%), 33% (95% CI 21%-45%), and 43% (95% CI 30%-55%), with a median survival of 3.1 years. The 5-year LC, EFS, and OS rates for patients with recurrent disease were 46% (95% CI, 28%-64%), 30% (95% CI, 13%-46%), and 36% (95% CI, 18%-54%). Acute toxicity ≥grade 3 occurred in 2 (2.5%) treatments; late toxicity ≥grade 3 occurred in 4 (5.3%) patients 0.3-9.9 years after HDR-IORT. The incidence of toxicity ≥grade 3 was not associated with HDR-IORT applicator size, HDR-IORT dose, prior RT or PORT, or prior or postoperative chemotherapy, but all toxicity ≥grade 3 occurred in patients ≤6 years treated with HDR-IORT doses ≥12 Gy. Conclusions: HDR-IORT is a well-tolerated component of multimodality therapy for pediatric sarcoma, allowing additional local treatment while reducing external beam exposure. Taking clinical considerations into account, doses between 8-12 Gy are appropriate for HDR-IORT in patients ≤6 years of age.

  9. High-Dose-Rate Brachytherapy Boost Effect on Local Tumor Control in Young Women With Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guinot, Jose-Luis, E-mail: jguinot@fivo.org [Department of Radiation Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain); Baixauli-Perez, Cristobal [Health Services Research Unit, Center for Public Health Research, Valencia (Spain); Soler, Pablo; Tortajada, Maria Isabel; Moreno, Araceli; Santos, Miguel Angel; Mut, Alejandro [Department of Radiation Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain); Gozalbo, Francisco [Department of Pathology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain); Arribas, Leoncio [Department of Radiation Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain)

    2015-01-01

    Purpose: To evaluate the local control rate and complications of a single fraction of high-dose-rate brachytherapy (HDR BT) boost in women aged 45 yeas and younger after breast-conserving therapy. Methods and Materials: Between 1999 and 2007, 167 patients between the ages of 26 and 45 years old (72 were 40 years old or younger), with stages T1 to T2 invasive breast cancer with disease-free margin status of at least 5 mm after breast-conserving surgery received 46 to 50 Gy whole-breast irradiation plus a 7-Gy HDR-BT boost (“fast boost”). An axillary dissection was performed in 72.5% of the patients and sentinel lymph node biopsy in 27.5%. A supraclavicular area was irradiated in 19% of the patients. Chemotherapy was used in 86% of the patients and hormone treatment in 77%. Clinical nodes were present in 18% and pathological nodes in 29%. The pathological stage was pT0: 5%, pTis: 3%, pT1: 69% and pT2: 23%. Intraductal component was present in 40% and 28% were G3. Results: At a median follow-up of 92 months, 9 patients relapsed on the margin of the implant, and 1 patient in another quadrant, resulting in a 10-year local relapse rate of 4.3% and a breast relapse rate of 4.9%, with breast preservation in 93.4%; no case of mastectomy due to poor cosmesis arose. Actuarial 5- and 10-year disease-free, cause-specific, and overall survival rates were 87.9% and 85.8%, and 92.1% and 88.4%, and 92.1% and 87.3%, respectively. In a univariate analysis, triple-negative cases and negative hormone receptors did worse, but in a multivariate analysis, only the last factor was significant for local and breast control. Asymptomatic fibrosis G2 was recorded in 3 cases, and there were no other late complications. Cosmetic results were good to excellent in 97% of cases. Conclusions: A single dose of 7 Gy using the fast-boost technique is well tolerated, with a low rate of late complications and improved local tumor control in women aged 45 and younger, compared to published data

  10. Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation.

    Science.gov (United States)

    Jabbour, E; Peslin, N; Arnaud, P; Ferme, C; Carde, P; Vantelon, J M; Bocaccio, C; Bourhis, J H; Koscielny, S; Ribrag, V

    2005-06-01

    High-dose therapy (HDT) is now recommended for patients under 60 years of age with chemosensitive relapsed aggressive non-Hodgkin's lymphoma. However, approximately half of these patients will be cured by HDT. Prognostic factors are needed to predict which patients with chemosensitive lymphoma to second-line therapy could benefit from HDT. We retrospectively investigated the prognostic value of the widely used age-adjusted International Prognostic Index (AA-IPI) calculated at the time of relapse (35 patients) or just before second-line salvage therapy for primary refractory disease (5 patients). The median age was 51 years (range 18-64 years). Thirty-six patients had diffuse large B-cell lymphoma. Salvage cytoreductive therapy before HDT was DHAP/ESHAP (cytarabine, cysplatin, etoposide, steroids) in 17 patients, VIM3-Ara-c/MAMI (high-dose cytarabine, ifosfamide, methyl-gag, amsacrine) in 17 patients, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or reinforced CHOP in 4 patients, high-dose cyclophosphamide and etoposide in 2 patients. The HDT regimen consisted of BEAM (carmusine, cytarabine, etoposide, melphalan) in all cases. Eleven patients were in partial remission and 29 in complete remission at the time of HDT. Ten patients had an IPI >1, 16 had relapsed early (6 months after first-line chemotherapy) (P=1), but the AA-IPI >1 was associated with a poor outcome (P=0.03). In conclusion, the AA-IPI could have a prognostic value in patients with chemosensitive recurrent lymphoma treated with BEAM HDT.

  11. CT-guided high-dose-rate brachytherapy of unresectable hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Collettini, Federico; Schreiber, Nadja; Schnapauff, Dirk; Denecke, Timm; Hamm, Bernd; Gebauer, Bernhard [ChariteUniversitaetsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Wust, Peter [ChariteUniversitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Schott, Eckart [Universitaetsmedizin Berlin, Department of Gastroenterology, Berlin (Germany)

    2015-05-01

    The purpose of the present study was to evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable hepatocellular carcinoma (HCC). Over a 6-year period, 98 patients with 212 unresectable HCC underwent CT-HDRBT applying a {sup 192}Ir source at our institution. Magnetic resonance imaging (MRI) follow-up was performed 6 weeks after the intervention and then every 3 months. The primary endpoint was local tumor control (LTC); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Patients were available for MRI evaluation for a mean follow-up of 23.1 months (range 4-64 months; median 20 months). Mean tumor diameter was 5 cm (range 1.8-12 cm). Eighteen of 212 (8.5 %) tumors showed local progression after a mean LTC of 21.1 months. In all, 67 patients (68.4 %) experienced distant tumor progression. The mean PFS was 15.2 months. Forty-six patients died during the follow-up period. Median OS was 29.2 months. Actuarial 1-, 2-, and 3-year OS rates were 80, 62, and 46 %, respectively. CT-HDRBT is an effective therapy to attain local tumor control in patients with unresectable HCC. Prospective randomized studies comparing CT-HDRBT with the standard treatments like Radiofrequency ablation (RFA) and chemoembolization (TACE) are mandatory. (orig.) [German] Zweck der vorliegenden Arbeit war die Analyse der klinischen Effektivitaet der CT-gesteuerten Hochdosis-Brachytherapie (CT-HDRBT) bei Patienten mit inoperablem hepatozellulaeren Karzinom (HCC). Ueber einen Zeitraum von 6 Jahren, wurden an unserer Klinik 98 Patienten mit 212 inoperablen HCC mittels CT-HDRBT mit {sup 192}Ir behandelt. MRT-Verlaufskontrollen erfolgten 6 Wochen nach der Intervention und dann alle 3 Monate. Primaerer Endpunkt der Studie war die lokale Tumorkontrolle (LTC); sekundaere Endpunkte waren das progressionsfreie Ueberleben (PFS) und Gesamtueberleben (OS). Die mittlere Nachbeobachtungszeit betrug 23,1 Monate (Spanne 4

  12. Chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Javier Sastre; Jose Angel García-Saenz; Eduardo Díaz-Rubio

    2006-01-01

    Metastatic gastric cancer remains a non-curative disease.Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed.Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116study, postoperative chemoradiation has been Accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease.Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱstudies are showing promising results. Phase Ⅲ trials are needed.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2010-11-01

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

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

    Science.gov (United States)

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

    2013-08-29

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

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

    Directory of Open Access Journals (Sweden)

    Daniel Scheiber

    2015-08-01

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

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

    Science.gov (United States)

    Asadi-Pooya, Ali A

    2015-04-01

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

  19. 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)

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

    Directory of Open Access Journals (Sweden)

    Syuichi Tetsuka

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Arun Dewan

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cordes Uwe

    2010-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Mahboob Pouraghaei

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Farshchian Mahmood

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Renaud ede Beaurepaire

    2014-10-01

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

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

    Science.gov (United States)

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

    1997-01-01

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

  9. Liver Injury Induced by Anticancer Chemotherapy and Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Y. Maor

    2013-01-01

    Full Text Available Cytotoxic chemotherapy prolongs survival of patients with advanced and metastatic tumors. This is, however, a double-edged sword with many adverse effects. Since the liver has a rich blood supply and plays an active role in the metabolism of medications, it is not surprising that there can be hepatic injury related to chemotherapy. In addition, radioembolization may affect the parenchyma of normal and cirrhotic livers. We review chemotherapy-associated liver injury in patients with colorectal liver metastases, including downsizing chemotherapy and neoadjuvant chemotherapy. We discuss the mechanism of the hepatic injury, secondary to reactive oxygen species, and the spectrum of hepatic injury including, steatosis, steatohepatitis, hepatic sinusoidal injury and highlight the pharmacogenomics of such liver insults. Methods for reducing and treating the hepatotoxicity are discussed for specific agents including tamxifen and the newly introduced targeted antibodies.

  10. Chronic low-dose radiation protects cells from high-dose radiation via increase of AKT expression by NF-{sub k}B

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyung Sun; Seong, Ki Moon; Kim, Ji Young; Kim, Cha Soon; Yang, Kwang Hee; Nam, Seon Young [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., LTD., Gyeongju (Korea, Republic of)

    2013-04-15

    Exposure to low-dose and low-dose rate of ionizing radiation is an important issue in radiation protection. Low-dose ionizing radiation has been observed to elicit distinctly different responses compared to high-dose radiation, in various biological systems including the reproductive, immune, and hematopoietic systems (Liu et al. 2006). Some data were reported that low-dose radiation could initiate beneficial effects by stimulating cell growth, DNA repair, activation of transcription factors and gene expression (Calabrese et al., 2004). Cells exposed to low-dose radiation can develop adaptive resistance to subsequent high-dose radiation induced DNA damage, gene mutation, and cell death. We previously reported that low-dose of ionizing radiation induced cell survival through the activation of AKT (protein kinase B, PKB) pathway (Park et al., 2009). AKT has been shown to be potently activated in response to a wide variety of growth factors and ionizing radiation. Cell survival against ionizing radiation seems to be associated with the activation of AKT pathway via phosphorylation of its downstream nuclear target molecules. In the present study, we examined the effects of chronic low-dose irradiation in human lung fibroblast cells. The aim was to explore the possibility of a low-dose radiation-induced adaptive cellular response against subsequent challenging high-dose irradiation. In the present study, we examined the regulatory mechanism responsible for cellular response induced by chronic low-dose of ionizing radiation in normal human cells. We found that the level of AKT protein was closely associated with cell survival. In addition, NF-{sub k}B activation by chronic low-dose radiation regulates AKT activation via gene expression and acinus expression. In conclusion, our data demonstrate that chronic low-dose radiation could inhibit the cell death induced by cytotoxic high-dose radiation through the modulation of the level of AKT and acinus proteins via NF-{sub k

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

    OpenAIRE

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

    2015-01-01

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

  12. Candesartan cilexetil/hydrochlorothiazide combination treatment versus high-dose candesartan cilexetil monotherapy in patients with mild to moderate cardiovascular risk (CHILI Triple T

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2011-02-01

    Full Text Available Gerd Bönner1, Bernhard Landers2, Peter Bramlage31Park-Klinikum Bad Krozingen, Germany; 2Internal Medicine Practice, Diabetes Center, Mayen, Germany; 3Institute for Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Candesartan cilexetil has been shown to effectively reduce blood pressure and cardiovascular risk. Whether it is advantageous to combine candesartan cilexetil with low-dose hydrochlorothiazide (HCTZ or uptitrate it in cases of insufficient blood pressure control has not been fully investigated under routine clinical conditions.Methods: CHILI Triple T is a prospective, noninterventional, observational study. Patients with uncontrolled hypertension and added cardiovascular risk received a fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg (combination therapy group or high-dose monotherapy with candesartan cilexetil 32 mg (high-dose monotherapy group.Results: A total of 4600 patients with a mean age of 63.1 ± 11.0 years, of which 44.7% were female, was included. The combination therapy group had 3337 patients, and the high-dose monotherapy group 1263 patients. Patients in both treatment groups were comparable with respect to age and gender, but patients receiving high-dose monotherapy had a slightly higher mean systolic blood pressure, more prior revascularizations, renal insufficiency, diabetic nephropathy, peripheral artery disease, and a lower ankle brachial index. The use of combination therapy resulted in a blood pressure reduction of -28.5 ± 13.8/-14.2 ± 9.4 mm Hg (P < 0.001 vs 160.2 ± 13.3/94.5 ± 8.2 mm Hg at baseline. The use of high-dose monotherapy reduced blood pressure by -29.73 ± 15.3/-14.1 ± 9.6 mm Hg (P < 0.001 vs 162.4 ± 14.7/94.7 ± 8.7 mm Hg at baseline. Differences in subgroups of patients defined by age, gender, body mass index, dyslipidemia, waist circumference, smoking, prior cardiovascular event, glomerular filtration rate, and microalbuminuria were minor

  13. Preoperative Arterial Interventional Chemotherapy on Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; LING HU-Hua; TANG Liang-dan; ZHANG Xing-hua

    2008-01-01

    Objective:To discuss the therapeutic effect of preoperative interventional chemotherapy on cervical cancer.Methods:Preoperative interventional chemotherapy by femoral intubation was performed in 25 patients with bulky cervical cancer.The patients received bleomycin 45 mg and cisplatin or oxaliplatin 80 mg/m2.Results:25 cases(including 8 cases with stage Ⅰ and 17 cases with stage Ⅱ)received one or two courses of preoperative interventional chemotherapy.The size of the focal lesions was decreased greatly and radical hysterectomy and lymphadenectomy were performed successfully in all the patients.All of the specimens were sent for pathological examination.Lymphocyte infiltration was found more obvious in the cancer tissues as compared with their counterpart before treatment.As a result,relevant vaginal bleeding was stopped completely shortly after the treatment.Conclusion:Arterial interventional chemotherapy was proved to reduce the local size of cervical cancer and thus control the hemorrhage efficiently.The patients with cervical cancer can receive radical hysterectomy therapy after the interventional chemotherapy.

  14. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  15. Cosmetic Analysis Following Breast-Conserving Surgery and Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer: A Prospective Clinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Margenthaler, Julie A. [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Naughton, Michael [Department of Medicine, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Aft, Rebecca [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Department of Surgery, John Cochran Veterans Hospital, St. Louis, Missouri (United States); Gillanders, William E.; Eberlein, Timothy [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Matesa, Melissa A. [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Zoberi, Imran, E-mail: izoberi@radonc.wustl.edu [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States)

    2013-03-15

    Purpose: To prospectively evaluate cosmetic outcomes in women treated with accelerated partial breast irradiation using high-dose-rate interstitial brachytherapy for early-stage breast cancer. Methods and Materials: Between 2004 and 2008, 151 patients with early-stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients had stage Tis-T2 tumors of ≤3 cm that were excised with negative margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. Both the patients and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). Patients also reported their satisfaction with treatment over time. Results: Median follow-up was 55 months. The rates of excellent-to-good cosmesis reported by patients and the treating radiation oncologist were 92% and 97% pretreatment, 91% and 97% at 3 to 4 months' follow-up, 87% and 94% at 2 years, and 92% and 94% at 3 years, respectively. Breast infection and adjuvant chemotherapy were independent predictors of a fair-to-poor cosmetic outcome at 3 years. Compared to pretreatment pBRA (7.35), there was no significant change in pBRA over time. The volume receiving more than 150 Gy (V150) was the only significant predictor of pBRA. The majority of patients (86.6%) were completely satisfied with their treatment. Conclusions: Patients and the treating physician reported a high rate of excellent-to-good cosmetic outcomes at all follow-up time points. Acute breast infection and chemotherapy were associated with worse cosmetic outcomes. Multicatheter interstitial brachytherapy does not significantly change breast size as measured by pBRA.

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

    Institute of Scientific and Technical Information of China (English)

    唐志清

    2013-01-01

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

  17. 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

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

    Science.gov (United States)

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

    2004-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  20. 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).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

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

    Science.gov (United States)

    Sheehan, James Robert; Keating, Liza; Chan, Antoni; Walden, Andrew

    2013-04-09

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery.

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

    CERN Document Server

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

    2002-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-12-31

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

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

    Science.gov (United States)

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

    2012-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-02-15

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-07-15

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

  10. Chemotherapy of Leishmaniasis.

    Science.gov (United States)

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...j_ = L. tropica major (Strain LV39 from USSR) and the New World cutaneous leishmaniasis by L. mexicana amazonensis (Strain LV78 from Brazil). The test

  11. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    2011-10-24

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.  Created: 10/24/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 10/24/2011.

  12. Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Jessica A. Smith

    2012-01-01

    Full Text Available Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT or intensity-modulated radiotherapy (IMRT versus high-dose-rate endorectal brachytherapy (EBT. Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P<0.001. There was a trend towards higher rate of pathologic CR for EBT (P=0.06. Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P=0.025. Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.

  13. Results of total lung irradiation and chemotherapy in comparison with partial lung irradiation in metastatic undifferentiated soft tissue sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, N.; Fuerst, G.; Pape, H.; Bannach, B.; Schmitt, G.; Molls, M.

    1988-07-01

    The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2x0,8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.

  14. Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed; Kim, Eugene; Russell, Heidi; Allen-Rhoades, Wendy; Krance, Robert; Paulino, Arnold C., E-mail: apaulino@mdanderson.org

    2014-11-15

    Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

  15. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder of the Central Nervous System with High-Dose Methotrexate

    Directory of Open Access Journals (Sweden)

    Clare J. Twist

    2013-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD of the brain and spine. IS was discontinued and HD-MTX (2.5–5 gm/m2/dose followed by intrathecal HD-MTX (2 mg/dose ×2-3 days Q 7–10 days per cycle was administered Q 4–7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy.

  16. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, J; Deasy, J O [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  17. Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients : no significant difference between granulocyte-colony stimulating growth factor or ciprofloxacin plus amphotericin B

    NARCIS (Netherlands)

    Schroder, CP; de Vries, EGE; Muder, NH; Willemse, PHB; Sleijfer, DT; Hospers, GAP; van der Graaf, WTA

    1999-01-01

    In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for

  18. Systemic chemotherapy for metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yannan Zhao; Biyun Wang

    2015-01-01

    Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer (MBC). Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metastasis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combination agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel-bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and cetuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall survival with maintenance chemotherapy according to a Korean phase Ⅲ clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy (X-based X) appears favorable based on a series of domestic studies.

  19. Oculomotor Deficits after Chemotherapy in Childhood.

    Directory of Open Access Journals (Sweden)

    Einar-Jón Einarsson

    Full Text Available Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years. Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy was markedly poorer (p<0.001 and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence (p = 0.004, whereas smooth pursuit and saccade onset times were shorter (p = 0.004 in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%, unsteadiness, light-headedness and that things around them were spinning or moving (87%. Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of

  20. Mitochondrial 12S Ribosomal RNA A1555G Mutation Associated with Cardiomyopathy and Hearing Loss following High-Dose Chemotherapy and Repeated Aminoglycoside Exposure

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Tranebjærg, Lisbeth; Jensen, Tim;

    2014-01-01

    A 19-month-old girl with the A1555G mitochondrial mutation in the 12S ribosomal RNA gene and acute myelogenous leukemia developed dilated cardiomyopathy and bilateral sensorineural hearing loss before undergoing allogeneic stem cell transplantation. She had received gentamicin during episodes of ...

  1. High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

    Science.gov (United States)

    2016-11-07

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Neuroblastoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Regional Neuroblastoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  2. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available BACKGROUND: Hand-foot syndrome (HFS is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6 has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial. METHODOLOGY//PRINCIPAL FINDINGS: Systematic literature searches were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP, WANFANG and the U.S. ClinicalTrials.gov website. We included all related randomized controlled trials (RCTs irrespective of language. Reviewers from different professions independently assessed all potential studies and extracted data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs involving 607 patients were contributed to the meta-analysis. No significant differences were found between patients receiving pyridoxine and placebo for prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR 0.96, 95%confidence interval (CI 0.86-1.06; RR0.95, 95%CI 0.73-1.24, respectively. Similarly, no significant improvement in quality of life was detected among patients. However, significant difference was found for prevention of grade 2 or worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33-0.92. CONCLUSIONS/SIGNIFICANCE: There is inadequate evidence to make any recommendation about using pyridoxine for prevention of HFS caused by chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.

  3. Dietetic management in gastrointestinal complications from antimalignant chemotherapy.

    Science.gov (United States)

    Calixto-Lima, L; Martins de Andrade, E; Gomes, A P; Geller, M; Siqueira-Batista, R

    2012-01-01

    Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.

  4. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  5. Real-time inverse high-dose-rate brachytherapy planning with catheter optimization by compressed sensing-inspired optimization strategies

    Science.gov (United States)

    Guthier, C. V.; Aschenbrenner, K. P.; Müller, R.; Polster, L.; Cormack, R. A.; Hesser, J. W.

    2016-08-01

    This paper demonstrates that optimization strategies derived from the field of compressed sensing (CS) improve computational performance in inverse treatment planning (ITP) for high-dose-rate (HDR) brachytherapy. Following an approach applied to low-dose-rate brachytherapy, we developed a reformulation of the ITP problem with the same mathematical structure as standard CS problems. Two greedy methods, derived from hard thresholding and subspace pursuit are presented and their performance is compared to state-of-the-art ITP solvers. Applied to clinical prostate brachytherapy plans speed-up by a factor of 56-350 compared to state-of-the-art methods. Based on a Wilcoxon signed rank-test the novel method statistically significantly decreases the final objective function value (p  <  0.01). The optimization times were below one second and thus planing can be considered as real-time capable. The novel CS inspired strategy enables real-time ITP for HDR brachytherapy including catheter optimization. The generated plans are either clinically equivalent or show a better performance with respect to dosimetric measures.

  6. Associations of high-dose melphalan pharmacokinetics and outcomes in the setting of a randomized cryotherapy trial.

    Science.gov (United States)

    Cho, Yu Kyoung; Sborov, Douglas W; Lamprecht, Misty; Li, Junan; Wang, Jiang; Hade, Erinn M; Gao, Yue; Tackett, Karen; Williams, Nita; Benson, Don M; Efebera, Yvonne A; Rosko, Ashley E; Devine, Steven M; Poi, Ming; Hofmeister, Craig C; Phelps, Mitch A

    2017-02-04

    High dose melphalan followed by autologous stem cell transplantation remains standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 hours) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate 2-hour is at least as effective as 6-hour cryotherapy in decreasing severe mucositis. From a population pharmacokinetic model, we identified fat free mass, hematocrit, and creatinine clearance were significant covariates, as had been reported previously. Furthermore, we observed the rs4240803 SLC7A5 polymorphism was significantly associated with pharmacokinetic variability, and pharmacokinetics was associated with both mucositis and neutropenia. However, melphalan exposure was not associated with progression-free or overall survival in our dataset. These findings contribute to ongoing efforts to personalize melphalan dosing in transplant patients. This article is protected by copyright. All rights reserved.

  7. Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation for Patients with Poor Ovarian Reserve

    Directory of Open Access Journals (Sweden)

    Tal Lazer

    2014-01-01

    Full Text Available We examined whether treatment with minimum-dose stimulation (MS protocol enhances clinical pregnancy rates compared to high-dose stimulation (HS protocol. A retrospective cohort study was performed comparing IVF and pregnancy outcomes between MS and HS gonadotropin-antagonist protocol for patients with poor ovarian reserve (POR. Inclusion criteria included patients with an anti-Müllerian hormone (AMH ≤8 pmol/L and/or antral follicle count (AFC ≤5 on days 2-3 of the cycle. Patients from 2008 exclusively had a HS protocol treatment, while patients in 2010 had treatment with a MS protocol exclusively. The MS protocol involved letrozole at 2.5 mg over 5 days, starting from day 2, overlapping with gonadotropins, starting from the third day of letrozole at 150 units daily. GnRH antagonist was introduced once one or more follicles reached 14 mm or larger. The HS group received gonadotropins (≥300 IU/day throughout their antagonist cycle. Clinical pregnancy rate was significantly higher in the MS protocol compared to the HS protocol (P=0.007. Furthermore, the live birth rate was significantly higher in the MS group compare to the HS group (P=0.034. In conclusion, the MS IVF protocol is less expensive (lower gonadotropin dosage and resulted in a higher clinical pregnancy rate and live birth rate than a HS protocol for poor responders.

  8. A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy.

    Science.gov (United States)

    Lahanas, M; Baltas, D; Zamboglou, N

    2003-02-07

    Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives.

  9. A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lahanas, M [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany); Baltas, D [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany); Zamboglou, N [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany)

    2003-02-07

    Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives.

  10. Protection against chemotherapy-induced alopecia: targeting ATP-binding cassette transporters in the hair follicle?

    Science.gov (United States)

    Haslam, Iain S; Pitre, Aaron; Schuetz, John D; Paus, Ralf

    2013-11-01

    Currently, efficacious treatments for chemotherapy-induced alopecia (hair loss) are lacking, and incidences of permanent hair loss following high-dose chemotherapy are on the increase. In this article, we describe mechanisms by which the pharmacological defense status of the hair follicle might be enhanced, thereby reducing the accumulation of cytotoxic cancer drugs and preventing or reducing hair loss and damage. We believe this could be achieved via the selective increase in ATP-binding cassette (ABC) transporter expression within the hair follicle epithelium, following application of topical agonists for regulatory nuclear receptors. Clinical application would require the development of hair follicle-targeted formulations, potentially utilizing nanoparticle technology. This novel approach has the potential to yield entirely new therapeutic options for the treatment and management of chemotherapy-induced alopecia, providing significant psychological and physical benefit to cancer patients.

  11. Starvation Based Differential Chemotherapy: A Novel Approach for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Sidra Naveed

    2014-11-01

    Full Text Available Cancer patients undergoing chemotherapy treatment are advised to increase food intake to overcome the therapy-induced side effects, and weight loss. Dietary restriction is known to slow down the aging process and hence reduce age-related diseases such as cancer. Fasting or short-term starvation is more effective than dietary restriction to prevent cancer growth since starved cells switch off signals for growth and reproduction and enter a protective mode, while cancer cells, being mutated, are not sensitized by any external growth signals and are not protected against any stress. This phenomenon is known as differential stress resistance (DSR. Nutrient signaling pathways involving growth hormone/insulin-like growth factor-1 axis and its downstream effectors, play a key role in DSR in response to starvation controlling the other cell maintenance systems, such as autophagy and apoptosis, that are related to the tumorigenesis. Yeast cells lacking these effectors are better protected against oxidative stress compared to normal cells. In the same way, starvation protects many cell lines and mice against high-dose chemotherapeutic drugs. According to a series of studies, fasting results in overall reduction in chemotherapy side effects in cancer patients. Data shows that starvation-dependent differential chemotherapy is safe, feasible and effective in cancer treatment, but the possible side effects of starvation limit its efficacy. However, further studies and clinical trials may result in its implementation in cancer treatment.

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

    Directory of Open Access Journals (Sweden)

    Takuro Nishikawa

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

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

    Directory of Open Access Journals (Sweden)

    Serkan GURGUL

    2017-03-01

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

  14. Population Pharmacokinetics of High-dose Methotrexate After Intravenous Administration in Chinese Osteosarcoma Patients from a Single Institution

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Qing Zhang; Xiaohuang Tian; Haitao Zhao; Wei Lu; Jiancun Zhen; Xiaohui Niu

    2015-01-01

    Background:High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma.The plasma concentration of MTX is closely related to efficacy and toxicity.There are large individual differences.Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances.However,no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported.The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients,and to explore the influence of patient covariates and between-occasion variability on drug disposition.Methods:An intravenous HD-MTX solution (10 g/m2) was given 274 times to 148 osteosarcoma patients.MTX plasma concentrations were measured at 0,6,12,24,48 and 72 h after commencement of the infusion,and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations.The PPK model and parameters were estimated using NONMEM software.The effects of fixed-effect factors were evaluated,and the final regression model was obtained.Results:The following population parameters were obtained using a two-compartment model:CL1 (clearance of central compartment):(CL1)i =CL1 Tv × [1-θCt-MTXNUM × MTXNUM] × [1-θCL1-CrCl1 × (CrCl1-1.89)] × eηCLi (L/h).V1 (central volume):(V11)i =V1TV × eηV1i (L).CL2 (clearance of peripheral compartment):(CL2)i =CL2TV × [1-θCL2-BODYAREA × (bodyarea-1.62)] × eηCL2i (L/h).V2 (peripheral compartment):(V2)i =V2Tv × [1-θV2-bodyarea × (bodyarea-1.62)] × eηV2i (L).The PPK parameters (RSD%) were CL1,V1,CL2 and V2 with values of 6.20 L/h (8.48%),19.6 L (extremely small),0.0172 L/h (50.9%) and 0.515 L (39.1%),respectively.Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a significant effect on the CL 1,and body

  15. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Directory of Open Access Journals (Sweden)

    Elva Jiménez-Hernández

    2015-01-01

    Full Text Available Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients, diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients, diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P=0.041. Overall survival for Group A (18, 90% was higher than that for Group B (60%. Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  16. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Science.gov (United States)

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

  17. Evolution of radiotherapy and chemotherapy practice in malignant gliomas

    Directory of Open Access Journals (Sweden)

    Anusheel Munshi

    2013-01-01

    Full Text Available Malignant astrocytomas of the brain carry a poor prognosis. This article traces the evolution of radiotherapy and chemotherapy practice including the development of concurrent chemo-radiation schedules in the context of these tumors.

  18. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  19. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim;

    2007-01-01

    the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed...... with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management...... trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Patel N

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maghraby Ahmed M.

    2014-03-01

    Full Text Available Taurine/EPR rods (3 × 10 mm have been prepared by a simple technique in the laboratory where taurine powder was mixed with a molten mixture of paraffin wax and an ethylene vinyl acetate (EVA copolymer. The binding mixture EVA/Paraffin does not present interference or noise in the EPR signal before or after irradiation. The rods show good mechanical properties for safe and multi-use handling. An EPR investigation of radiation induced radicals in taurine rods revealed that there are two types of radicals produced after exposure to gamma radiation (60Co. EPR spectra were recorded and analyzed - also the microwave power saturation and modulation amplitude were studied and optimized. Response of taurine to different radiation doses (1.5-100 kGy was studied and found to follow a linear relationship up to 100 kGy. Radiation induced radicals in taurine persists and showed a noticeable stability over 94 days following irradiation. Uncertainities associated with the evaluation of radiation doses using taurine dosimeters were discussed and tabulated. It was found that taurine possesses good dosimetric properties using EPR spectroscopy in high doses in addition to its simple spectrum.

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

    Science.gov (United States)

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

    2011-04-01

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

  5. 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.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Surjya Prasad Upadhyay

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

  11. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

    In order to monitor the neutron irradiation embrittlement of the reactor vessel material, the surveillance program should be implemented during the reactor operation through the plant life. This surveillance program requires the surveillance capsules which contain the various test specimens, thermal monitors, and neutron dosimeters. For PWRs in Korea, total six surveillance capsules are installed before plant operation and are programmed to be withdrawn and tested periodically in accordance with the surveillance program. The surveillance capsules are typically installed in the downcomer region and are located closer to the reactor core than the vessel wall in order to get more accelerated embrittlement characteristics of the vessel material. The supplemental surveillance capsules were fabricated to obtain the data of high-dose irradiation embrittlement. All test specimens in the capsules were made with the archive material of Hanbit Units 3 and 4. The supplemental capsules were designed to have the same outside dimensions as the capsules of Hanbit Unit 1 and were installed in Hanbit Unit 1. The withdrawal schedule will be calculated.

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

    Directory of Open Access Journals (Sweden)

    Wiwik Misaco Yuniarti

    2008-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tomohito Sato

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-07-07

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

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

    Science.gov (United States)

    Patel, Sarsvatkumar; Bansal, Arvind Kumar

    2011-01-17

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

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-15

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

  20. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

    Science.gov (United States)

    Hassan, M; Oberg, G; Björkholm, M; Wallin, I; Lindgren, M

    1993-01-01

    The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-08

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

  2. Retraction of colonies and structures of Aspergillus Spp. as a possible high dose sensor

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Valeria B., E-mail: valeriabborges@hotmail.com [Coordenacao dos Programas de Pos-Graduacao em Processos Quimicos e Bioquimicos (EQ/UFRJ), Rio de Janeiro, RJ (Brazil). Escola de Quimica; Vital, Helio C., E-mail: vital@ctex.eb.br [Centro Tecnologico do Exercito (DDQBN/CTEx), Rio de Janeiro, RJ (Brazil). Div. de Defesa Quimica, Biologica e Nuclear. Secao de Defesa Nuclear; Moraes, Aurea M.L., E-mail: ltbbf@ioc.fiocruz.br [Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Departamento de Micologia

    2013-07-01

    Changes in the length of macro-and microscopic structures of irradiated Aspergillus spp. colonies were investigated in this work in search for correlations with radiation dose. Effects related to growth and morphology produced by exposure to radiation doses ranging from 0.0 up to 8.0 kGy on strains of A. flavus (CMT 00079), A. parasiticus (CMT 00064) and A ochraceus (CMT 00145) were analyzed. Fungal colonies were inoculated on fresh peanut seeds and incubated for 5 days at 25°C. On the sixth day the samples were irradiated and moved to Petri dishes containing PDA culture medium where they remained incubated for 7 days at 25°C Post irradiation growth was periodically monitored by visual inspections and measurements of mycelial diameters. In addition, microscopic analyses were performed to determine the length of the major structures of the colonies. It has been found that irradiation causes a decrease in the diameter of colonies as well as in the length of microscopic structures of the fungus. The amount of retraction has been found to be strongly correlated to radiation dose. Such findings hint at the possibility of using in situ Aspergillus spp. colonies as high-dose living dosimeters in the event of massive radiation exposures. (author)

  3. 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)

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-07

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

  6. 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)

  7. High doses of gamma radiation suppress allergic effect induced by food lectin

    Science.gov (United States)

    Vaz, Antônio F. M.; Souza, Marthyna P.; Vieira, Leucio D.; Aguiar, Jaciana S.; Silva, Teresinha G.; Medeiros, Paloma L.; Melo, Ana M. M. A.; Silva-Lucca, Rosemeire A.; Santana, Lucimeire A.; Oliva, Maria L. V.; Perez, Katia R.; Cuccovia, Iolanda M.; Coelho, Luana C. B. B.; Correia, Maria T. S.

    2013-04-01

    One of the most promising areas for the development of functional foods lies in the development of effective methods to reduce or eliminate food allergenicity, but few reports have summarized information concerning the progress made with food irradiation. In this study, we investigated the relationship between allergenicity and molecular structure of a food allergen after gamma irradiation and evaluate the profile of the allergic response to irradiated allergens. Cramoll, a lectin isolated from a bean and used as a food allergen, was irradiated and the possible structural changes were accompanied by spectrofluorimetry, circular dichroism and microcalorimetry. Subsequently, sensitized animals subjected to intragastric administration of non-irradiated and irradiated Cramoll were treated for 7 days. Then, body weight, leukocytes, cytokine profiles and histological parameters were also determined. Cramoll showed complete inhibition of intrinsic activity after high radiation doses. Changes in fluorescence and CD spectra with a simultaneous collapse of the tertiary structure followed by a pronounced decrease of native secondary structure were observed after irradiation. After oral challenge, sensitized mice demonstrate an association between Cramoll intake, body weight loss, eosinophilia, lymphocytic infiltrate in the gut and Eotaxin secretion. Irradiation significantly reduces, according to the dose, the effects observed by non-irradiated food allergens. We confirm that high-dose radiation may render protein food allergens innocuous by irreversibly compromising their molecular structure.

  8. A Case of Type 2 Amiodarone-Induced Thyrotoxicosis That Underwent Total Thyroidectomy under High-Dose Steroid Administration

    Directory of Open Access Journals (Sweden)

    Koshi Hashimoto

    2015-01-01

    Full Text Available Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT and destructive thyroiditis (type 2 AIT. We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone, the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration.

  9. Why chemotherapy can fail?

    Science.gov (United States)

    Król, M; Pawłowski, K M; Majchrzak, K; Szyszko, K; Motyl, T

    2010-01-01

    There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.

  10. SU-E-T-315: The Change of Optically Stimulated Luminescent Dosimeters (OSLDs) Sensitivity by Accumulated Dose and High Dose

    Energy Technology Data Exchange (ETDEWEB)

    Han, S; Jung, H; Kim, M; Ji, Y; Kim, K [University of Science and Technology, Daejeon (Korea, Republic of); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Choi, S; Park, S; Yoo, H [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yi, C [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2014-06-01

    Purpose: The objective of this study is to evaluate radiation sensitivity of optical stimulated luminance dosimeters (OSLDs) by accumulated dose and high dose. Methods: This study was carried out in Co-60 unit (Theratron 780, AECL, and Canada) and used InLight MicroStar reader (Landauer, Inc., Glenwood, IL) for reading. We annealed for 30 min using optical annealing system which contained fluorescent lamps (Osram lumilux, 24 W, 280 ∼780 nm). To evaluate change of OSLDs sensitivity by repeated irradiation, the dosimeters were repeatedly irradiated with 1 Gy. And whenever a repeated irradiation, we evaluated OSLDs sensitivity. To evaluate OSLDs sensitivity after accumulated dose with 5 Gy, We irradiated dose accumulatively (from 1 Gy to 5 Gy) without annealing. And OSLDs was also irradiated with 15, 20, 30 Gy to certify change of OSLDs sensitivity after high dose irradiation. After annealing them, they were irradiated with 1Gy, repeatedly. Results: The OSLDs sensitivity increased up to 3% during irradiating seven times and decreased continuously above 8 times. That dropped by about 0.35 Gy per an irradiation. Finally, after 30 times irradiation, OSLDs sensitivity decreased by about 7%. For accumulated dose from 1 Gy to 5 Gy, OSLDs sensitivity about 1 Gy increased until 4.4% after second times accumulated dose compared with before that. OSLDs sensitivity about 1 Gy decreased by 1.6% in five times irradiation. When OSLDs were irradiated ten times with 1Gy after irradiating high dose (10, 15, 20 Gy), OSLDs sensitivity decreased until 6%, 9%, 12% compared with it before high dose irradiation, respectively. Conclusion: This study certified OSLDs sensitivity by accumulated dose and high dose. When irradiated with 1Gy, repeatedly, OSLDs sensitivity decreased linearly and the reduction rate of OSLDs sensitivity after high dose irradiation had dependence on irradiated dose.

  11. Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Goto, Hiroaki; Kaneko, Tetsuji; Naruto, Takuya; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Shoko; Takahashi, Hiroyuki; Mori, Masaaki; Kai, Sumio; Yokota, Shumpei

    2013-12-01

    High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

  12. Study of teflon pads as high doses dosemeters; Estudo de pastilhas de teflon como dosimetros de doses altas

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines; Caldas, Linda V.E., E-mail: miteixeira@ipen.br, E-mail: lcaldas@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-11-01

    The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ({sup 60}Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry.

  13. 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

  14. Labour induction with an intermediate-dose oxytocin regimen has advantages over a high-dose regimen.

    Science.gov (United States)

    Manjula, B G; Bagga, R; Kalra, J; Dutta, S

    2015-05-01

    A total of 200 women planned for labour induction were randomised to receive high-dose oxytocin (6 mU/min with similar increments every 45 min) or intermediate-dose oxytocin (3 mU/min with similar increments every 45 min). Oxytocin solution was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h is numerically equal to oxytocin in mU/min. We observed that the caesarean rate (18% vs 6%, p = 0.009), contraction abnormalities (35% vs 14%, p = 0.0005) and neonatal bilirubin levels (7.99 ± 2.70 vs 6.80 ± 2.65, p = 0.002) were higher with high-dose than with intermediate-dose. The induction-delivery interval (IDI) was similar (10 h 13 min with high-dose and 11 h 5 min with intermediate-dose; p = 0.237, NS). Nulliparous women benefited more with intermediate-dose as the caesarean rate was higher with high-dose (24.6% vs 7.9%, p = 0.011). Although the caesarean rate was higher in multiparous women with high-dose oxytocin, it was statistically not significant (5.7% vs 2.7%; p = 0.609). Oxytocin regimens for labour induction are usually high-dose (4-6 mU/min) or low-dose (1-1.5 mU/min). The former is associated with more contraction abnormalities and the latter with prolonged IDI; both result in an increased caesarean rate. In order to offset these disadvantages, an intermediate- dose regimen was selected. The increment interval of 45 min was selected in accordance with the pharmacokinetics of oxytocin. We observed a lower caesarean rate when compared with the high-dose regimen, without any increase in the IDI. Hence, we propose that the intermediate-dose oxytocin regimen should be preferred to the high-dose regimen for labour induction.

  15. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was perfor...

  16. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

    Directory of Open Access Journals (Sweden)

    de Visser Marianne

    2009-11-01

    Full Text Available Abstract Background High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-Tooth type 1A patients and whether this treatment is safe. Methods Patients below age 25 years were randomly assigned to receive placebo or ascorbic acid (one gram twice daily in a double-blind fashion during one year. The primary outcome measure was the change over time in motor nerve conduction velocity of the median nerve. Secondary outcome measures included changes in minimal F response latencies, compound muscle action potential amplitude, muscle strength, sensory function, Charcot-Marie-Tooth neuropathy score, and disability. Results There were no significant differences between the six placebo-treated (median age 16 years, range 13 to 24 and the five ascorbic acid-treated (19, 14 to 24 patients in change in motor nerve conduction velocity of the median nerve (mean difference ascorbic acid as opposed to placebo treatment of 1.3 m/s, confidence interval -0.3 to 3.0 m/s, P = 0.11 or in change of any of the secondary outcome measures over time. One patient in the ascorbic acid group developed a skin rash, which led to discontinuation of the study medication. Conclusion Oral high dose ascorbic acid for one year did not improve myelination of the median nerve in young Charcot-Marie-Tooth type 1A patients. Treatment was relatively safe. Trial registration Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635.

  17. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism.

    Science.gov (United States)

    Aarabi, Mahmoud; San Gabriel, Maria C; Chan, Donovan; Behan, Nathalie A; Caron, Maxime; Pastinen, Tomi; Bourque, Guillaume; MacFarlane, Amanda J; Zini, Armand; Trasler, Jacquetta

    2015-11-15

    Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility. Blood folate concentrations increased significantly after supplementation with no significant improvements in sperm parameters. Methylation levels of the differentially methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN, PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced representation bisulfite sequencing (RRBS) revealed a significant global loss of methylation across different regions of the sperm genome. The most marked loss of DNA methylation was found in sperm from patients homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common polymorphism in a key enzyme required for folate metabolism. RRBS analysis also showed that most of the differentially methylated tiles were located in DNA repeats, low CpG-density and intergenic regions. Ingenuity Pathway Analysis revealed that methylation of promoter regions was altered in several genes involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6, COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal alterations of the human sperm epigenome associated with high-dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR.

  18. Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

    Directory of Open Access Journals (Sweden)

    Kristen Ashley eHorner

    2011-05-01

    Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

  19. Chemotherapy for children with medulloblastoma

    NARCIS (Netherlands)

    Michiels, E.M.; Schouten-van Meeteren, A.Y.; Doz, F.; Janssens, G.O.R.J.; Dalen, E.C. van

    2015-01-01

    BACKGROUND: Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by delet

  20. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  1. Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass.

    Science.gov (United States)

    Baidal, D A; Ricordi, C; Garcia-Contreras, M; Sonnino, A; Fabbri, A

    2016-07-01

    Several studies have evaluated the role of inflammation in type 1 diabetes (T1D). The safety profile and anti-inflammatory properties of high dose omega-3 fatty acids combined with Vitamin D supplementation make this therapy a possible candidate for T1D intervention trials. Herein, we describe the case of a 14-year-old boy with new onset T1D treated with high dose Omega-3 and vitamin D3. By 12 months, peak C-peptide increased to 0.55 nmol/L (1.66 ng/mL) corresponding to a 20% increment from baseline and AUC C-peptide was slightly higher compared to 9 months (0.33 vs. 0.30 nmol/L/min) although remaining slightly lower than baseline. Combination high-dose Omega-3 fatty acids and high-dose vitamin D3 therapy was well tolerated and may have beneficial effects on beta-cell function. Randomized controlled trials could be of assistance to determine whether this therapy may result in the preservation of beta-cell function in patients with new onset T1D.

  2. A history of cancer chemotherapy.

    Science.gov (United States)

    DeVita, Vincent T; Chu, Edward

    2008-11-01

    The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

  3. Interstitial pneumonitis following intrapleural chemotherapy

    Directory of Open Access Journals (Sweden)

    Humphries Gary N

    2009-02-01

    Full Text Available Abstract Background Mucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy. Case presentation In this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur. Conclusion This manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

  4. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

    Energy Technology Data Exchange (ETDEWEB)

    Shwetha, Bondel [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Ravikumar, Manickam, E-mail: drravikumarm@gmail.com [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Supe, Sanjay S.; Sathiyan, Saminathan [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Lokesh, Vishwanath [Department of Radiotherapy, Kidwai, Memorial Institute of Oncology, Bangalore (India); Keshava, Subbarao L. [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India)

    2012-04-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  5. 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.

  6. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications.

    Science.gov (United States)

    Shwetha, Bondel; Ravikumar, Manickam; Supe, Sanjay S; Sathiyan, Saminathan; Lokesh, Vishwanath; Keshava, Subbarao L

    2012-01-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  7. 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.

  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. Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

    Science.gov (United States)

    Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

    2015-01-01

    Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

  10. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

    Science.gov (United States)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Furukawa, Souhei; Kakimoto, Naoya; Shimizutani, Kimishige; Inoue, Toshihiko

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n = 341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer.

  11. Dosimetry audits in Brazil for {sup 192}Ir high dose rate brachytherapy systems

    Energy Technology Data Exchange (ETDEWEB)

    Rosa, L.A.R. da; Paiva, E. de.; Goncalves, M.G.; Velasco, A.F.; Di Prinzio, R.; Dovales, A.C.M.; Freire, B.L.V.; Brito, R.R.A.; Giannoni, R.A.; Castelo, L.H.R. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Marechal, M.H.H. [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao de Instalacoes Radiativas (CORAD)

    2005-03-15

    In Brazil, among 200 radiotherapy centres, 30 have high dose rate (HDR) {sup 192}Ir brachytherapy systems. In August 2001, the Brazilian National Nuclear Energy Commission (CNEN) started a biennial audit program to those centres having HDR systems. This program consists of visiting each centre in order to investigate the radiation protection aspects of the centres and also to measure the intensity of the brachytherapy source, in terms of air kerma strength, with a well type chamber specially designed for HDR {sup 192} Ir sources. The audit dosimetry results are compared to measurements carried out by the local institution physicist and to the source intensity value provided by the manufacturer. Two methods have been used by the Brazilian physicists for HDR {sup 192}Ir brachytherapy source dosimetry, namely the employment of a farmer type chamber calibrated according to the interpolation methodology and the use of a well type chamber to provide direct intercomparison. The larger difference obtained was 18.9% and it can be explained in terms of the lack of knowledge of the institution physicist about the interpolation methodology using the farmer type chamber. Another difference of 5.82% was found as being the lack of an updated calibration factor for the clinic well type chamber. On the basis of these results, CNEN is able to establish a maximum deviation value for the dosimetry of HDR system. Additionally, with this program the radiotherapy services have an opportunity to have their HDR {sup 192}Ir sources calibrated and to test the validity of the calibration factors for their own well type chambers, using their calibrated sources. (author)

  12. Endocrine function following high dose proton therapy for tumors of the upper clivus

    Energy Technology Data Exchange (ETDEWEB)

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  13. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss.

    Science.gov (United States)

    Swift, Joshua M; Swift, Sibyl N; Smith, Joan T; Kiang, Juliann G; Allen, Matthew R

    2015-12-01

    The present study investigated the detrimental effects of non-lethal, high-dose (whole body) γ-irradiation on bone, and the impact that radiation combined with skin trauma (i.e. combined injury) has on long-term skeletal tissue health. Recovery of bone after an acute dose of radiation (RI; 8 Gy), skin wounding (15-20% of total body skin surface), or combined injury (RI+Wound; CI) was determined 3, 7, 30, and 120 days post-irradiation in female B6D2F1 mice and compared to non-irradiated mice (SHAM) at each time-point. CI mice demonstrated long-term (day 120) elevations in serum TRAP 5b (osteoclast number) and sclerostin (bone formation inhibitor), and suppression of osteocalcin levels through 30 days as compared to SHAM (p<0.05). Radiation-induced reductions in distal femur trabecular bone volume fraction and trabecular number through 120 days post-exposure were significantly greater than non-irradiated mice (p<0.05) and were exacerbated in CI mice by day 30 (p<0.05). Negative alterations in trabecular bone microarchitecture were coupled with extended reductions in cancellous bone formation rate in both RI and CI mice as compared to Sham (p<0.05). Increased osteoclast surface in CI animals was observed for 3 days after irradiation and remained elevated through 120 days (p<0.01). These results demonstrate a long-term, exacerbated response of bone to radiation when coupled with non-lethal wound trauma. Changes in cancellous bone after combined trauma were derived from extended reductions in osteoblast-driven bone formation and increases in osteoclast activity.

  14. The efficiency of high dose botulinum toxin type-A in the treatment of cerebral palsy

    Directory of Open Access Journals (Sweden)

    Alper İbrahim Dai

    2014-03-01

    Full Text Available Objective: Cerebral palsy is the most common cause of severe physical disability in childhood. Botulinum toxin type A (BTX-A, has rapidly gained acceptance as a different treatment for spasticity. However, no consensus exists among clinicians about optimal dose of BTX-A in pediatric patients. Doses of 2-6 U/ kg bodyweight with a maximum total dose of 29U/kg have been reported. This study was conducted due to uncertain dosage rage in pediatric use. Method: In this study, 12 patients with cerebral palsy and spastic eqinus foot deformity who referred to our center, were treated with BTX-A in the dosage of 25 U/kg. After treatment of BTX-A, patients were followed up total of 6 months. Three months after treatment, Gross motor functional measurement (GMFM and Modified Ashwort scale (MAS were done. At the same time, questionnaires (PCQ were filled for possible side effects. Results: Average age of 6 girls and 6 boys were 4.5 ± 2.8 years. GMFM and MAS were done before and 3 months after treatment and were found statistically significant (p<0.05. Muscle soreness was the most common symptom at PCQ forms. Conclusion: Using these two objective scales and PCQ form, high dose of BTX-A treatment was found statistically successful. Larger dose of BTX-A was used which was considered safe, effective and better tolerated by children. Titration of the dose of BTX-A, should be individualized for each patient due to different level of spasticity affecting patients in different ways. J Clin Exp Invest 2014; 5 (1: 93-97

  15. Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial

    Science.gov (United States)

    Mikkelsen, Torben S.; Sparreboom, Alex; Cheng, Cheng; Zhou, Yinmei; Boyett, James M.; Raimondi, Susana C.; Panetta, John C.; Bowman, W. Paul; Sandlund, John T.; Pui, Ching-Hon; Relling, Mary V.; Evans, William E.

    2011-01-01

    Purpose To determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m2) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG1-7) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes. Methods From June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m2) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG1-7 in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells). Results The 24-hour infusion resulted in significantly higher amounts of MTXPG1-7 in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/109 cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG1-7 accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/109 cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG1-7 but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG1-7 accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation. Conclusion Shortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes. PMID:21444869

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

    Energy Technology Data Exchange (ETDEWEB)

    Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, CA (United States); Martinez, Alvaro A.; Ghilezan, Michel [William Beaumont Hospital, Royal Oak, MI (United States); Hill, Dennis R.; Schour, Lionel; Brandt, David [California Endocurietherapy, Oakland, CA (United States); Gustafson, Gary [William Beaumont Hospital, Royal Oak, MI (United States)

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  17. High Dose Astaxanthin Lowers Blood Pressure and Increases Insulin Sensitivity in Rats: Are These Effects Interdependent?

    Directory of Open Access Journals (Sweden)

    Harry G. Preuss, Bobby Echard, Eiji Yamashita, Nicholas V. Perricone

    2011-01-01

    Full Text Available The present investigation in Sprague-Dawley rats (SD was designed to examine effects of astaxanthin (Asta at different doses on elevated blood pressure (BP and glucose-insulin perturbations produced by heavy sucrose ingestion. We also examined effects of Asta on BP during restraint stress. SD were divided into six groups each containing eight rats. All SD ate a basic diet of ground regular rat chow with sucrose added at 30% w/w. The Control group received only the basic diet containing added sucrose, while the other five groups each received the same diet with added test material: captopril, (30 mg/Kg, pioglitazone (15.0 mg/Kg, low Asta (25 mg/Kg, medium Asta (50 mg/kg or high Asta (100 mg/Kg. Many tests were carried out to examine the mechanisms behind the effects of Asta on BP (serum ACE activity, losartan challenge, and LNAME challenge and the glucose-insulin system (glucose tolerance, HOMA measurement, and insulin challenge. In SD, a relatively low dose of Asta decreased SBP, but produced no major changes in the glucose-insulin system simulating results from a previous study using Zucker Fatty Rats. Increasing the dose of Asta resulted in both a lowering of elevated systolic BP and enhanced insulin sensitivity determined by many different estimations. BP lowering was consistent with changes in the renin-angiotensin (RAS and nitric oxide (NO systems. At the examined doses of each, captopril lowered BP in SD without influencing glucose-insulin metabolism, whereas pioglitazone favorably affected glucose-insulin metabolism while showing essentially no effects on BP. Accordingly, Asta beneficially affects both sucrose-induced elevations of BP and insulin resistance at relatively high doses in SD. Also, Asta at higher doses lessens restraint stress, whereas, captopril and pioglitazone did not at the doses examined, even though they influenced the BP and glucose-insulin systems respectively.

  18. Tensile stress corrosion cracking of type 304 stainless steel irradiated to very high dose

    Energy Technology Data Exchange (ETDEWEB)

    Chung, H. M.; Ruther, W. E.; Strain, R. V.; Shack, W. J.

    2001-09-01

    Certain safety-related core internal structural components of light water reactors, usually fabricated from Type 304 or 316 austenitic stainless steels (SSs), accumulate very high levels of irradiation damage (20--100 displacement per atom or dpa) by the end of life. The data bases and mechanistic understanding of, the degradation of such highly irradiated components, however, are not well established. A key question is the nature of irradiation-assisted intergranular cracking at very high dose, i.e., is it purely mechanical failure or is it stress-commotion cracking? In this work, hot-cell tests and microstructural characterization were performed on Type 304 SS from the hexagonal fuel can of the decommissioned EBR-11 reactor after irradiation to {approximately}50 dpa at {approximately}370 C. Slow-strain-rate tensile tests were conducted at 289 C in air and in water at several levels of electrochemical potential (ECP), and microstructural characteristics were analyzed by scanning and transmission electron microcopies. The material deformed significantly by twinning and exhibited surprisingly high ductility in air, but was susceptible to severe intergranular stress corrosion cracking (IGSCC) at high ECP. Low levels of dissolved O and ECP were effective in suppressing the susceptibility of the heavily irradiated material to IGSCC, indicating that the stress corrosion process associated with irradiation-induced grain-boundary Cr depletion, rather than purely mechanical separation of grain boundaries, plays the dominant role. However, although IGSCC was suppressed, the material was susceptible to dislocation channeling at low ECP, and this susceptibility led to poor work-hardening capability and low ductility.

  19. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

    Science.gov (United States)

    Whitaker, May

    2016-01-01

    Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

  20. A Comparative Study of Vaginal Misoprostol and High Dose Intravenous Oxytocin for Second Trimester Pregnancy Termination

    Directory of Open Access Journals (Sweden)

    M. Rajaee

    2010-04-01

    Full Text Available Introduction & Objective: Second trimester labor induction is a major problem in obstetrics and is the cause of two-thirds of all abortion related complications and more than half of the maternal deaths associated with abortion. The goal of this study was to compare the effectiveness of vaginal misoprostol and intravenous oxytocin for termination of second trimester pregnancy.Materials & Methods: One hundred women were allocated in a randomized controlled way to one of the two induction groups: oxytocin group patients initially received an infusion of 50 units of oxytocin in 500 ml of ringer over 3 hours, 1 hour of no oxytocin followed by alternating 3 hours of oxytocin with 1 hour of rest. Oxytocin was increased by 50 units in each successive period until a final concentration of 300 units per 500 ml has been reached. Another group received 200 µg misoprostol tablets in posterior fornix vagina and was repeated after 12 hours if needed. The two groups were compared for induction to delivery intervals and their safety during induction. Results: The success rate within 24 hours of induction was 94% in the misoprostol group and 86% in oxytocin group (p= 0.182. The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group.(13.5 versus 9.93 hours ; P=0.0057. Retained placenta requiring curettage was lower in the misoprostol group than the oxytocin group.Conclusion: Intravaginal misoprostol is more effective than high dose intravenous oxytocin in women with second trimester termination.

  1. Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole-convulsive rats

    Directory of Open Access Journals (Sweden)

    J.G. Santos Junior

    2002-04-01

    Full Text Available Venlafaxine, an atypical antidepressant drug, has been used to treat several neurological disorders, presenting excellent efficacy and tolerability. Clinical seizures after venlafaxine treatment have occasionally been reported when the drug was used at very high doses or in combination with other medications. The aim of the present study was to investigate the convulsant effects of venlafaxine in rats under controlled laboratory conditions. Adult male Wistar rats (8 per group receiving venlafaxine or saline at the doses of 25-150 mg/kg were subjected 30 min later to injections of pentylenetetrazole at the dose of 60 mg/kg. The animals receiving 75, 100 and 150 mg/kg venlafaxine presented increased severity of convulsion when compared to controls (P = 0.02, P = 0.04, and P = 0.0004, respectively. Indeed, an increased percentage of death was observed in these groups (50, 38, and 88%, respectively when compared to the percentage of death in the controls (0%. The group receiving 150 mg/kg showed an reduction in death latency (999 ± 146 s compared to controls (1800 ± 0 s; cut-off time. Indeed, in this group, all animals developed seizures prior to pentylenetetrazole administration. Surprisingly, the groups receiving venlafaxine at the doses of 25 and 50 mg/kg showed a tendency towards an increase in the latency to the first convulsion. These findings suggest that venlafaxine at doses of 25 and 50 mg/kg has some tendency to an anticonvulsant effect in the rat, whereas doses of 75, 100 and 150 mg/kg presented clear proconvulsant effects in rats submitted to the pentylenetetrazole injection. These findings are the first report in the literature concerning the role of venlafaxine in seizure genesis in the rat under controlled conditions.

  2. Effects of the polysaccharides extracted from Ganoderma lucidum on chemotherapy-related fatigue in mice.

    Science.gov (United States)

    Ouyang, Ming-Zi; Lin, Li-Zhu; Lv, Wen-Jiao; Zuo, Qian; Lv, Zhuo; Guan, Jie-Shan; Wang, Shu-Tang; Sun, Ling-Ling; Chen, Han-Rui; Xiao, Zhi-Wei

    2016-10-01

    The weight-loaded swimming capability, tumor growth, survival time and biochemical markers of Ganoderma lucidum polysaccharides (GLPs) in a chemotherapy-related fatigue mouse model were tested in the present study. The results showed that the middle-dose GLPs (GLP-M) and the high-dose GLPs (GLP-H) could increase the exhausting swimming time, which was observed to decrease in the cisplatin control group(PCG) and the tumor control group (TCG).The GLP-M and the GLP-H had reduced serum levels of tumor necrosis factor-αand interleukin-6, which were up-regulated by cisplatin. Cisplatin and the presence of tumor significantly enhanced the malondialdehyde (MDA) content and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of GLPs at a high dose decreased the levels of MDA and up-regulated the SOD activity. The high-dose GLPs+cisplatin group presented a decreased tendency of tumor volume and a lower tumor weight compared with PCG. Moreover, the mice in the GLP-M and GLP-H groups had longer survival times compared with the mice in the TCG and PCG.The levels of creatinine and serum blood urea nitrogen, which are up-regulated by cisplatin, were significantly reduced by GLP-M and GLP-H. Therefore, these results suggest that GLPs might improve chemotherapy-related fatigue via regulation of inflammatory responses, oxidative stress and reduction of nephrotoxicity.

  3. Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lu Ban

    Full Text Available Antenatal antiepileptic drug (AED use has been found to be associated with increased major congenital anomaly (CA risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily folic acid supplementation is still unclear.We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. W