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Sample records for high-dose poly-epitope vaccine

  1. Fluzone High-Dose Seasonal Influenza Vaccine

    Science.gov (United States)

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Asima Banu

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-10-21

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

  5. Efficacy and safety of high-dose influenza vaccine in elderly adults: A systematic review and meta-analysis.

    Science.gov (United States)

    Wilkinson, Krista; Wei, Yichun; Szwajcer, Andrea; Rabbani, Rasheda; Zarychanski, Ryan; Abou-Setta, Ahmed M; Mahmud, Salaheddin M

    2017-05-15

    Older adults are prioritized for influenza vaccination but also have lowered antibody responses to the vaccine. Higher-doses of influenza antigen may increase immune response and thus be more effective. Our objectives were to compare the efficacy and safety of the high-dose influenza vaccine to the standard-dose influenza vaccine in the elderly (age>65). Data sources: Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), ClinicalTrials.gov, reference lists of relevant articles, and gray literature. Two reviewers independently identified RCTs comparing high-dose influenza vaccine (60μg of hemagglutinin per strain) to standard-dose influenza vaccine (15μg of hemagglutinin per strain) in adults over the age of 65years. Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias tool. We included seven eligible trials; all were categorized as having a low (n=3) or unclear (n=4) risk of bias. Patients receiving the high-dose vaccine had significantly less risk of developing laboratory-confirmed influenza infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I 2 0%, 2 trials, 41,141 patients). Post-vaccination geometric mean titres and seroprotection rates were also higher in high-dose vaccine recipients. There were no protocol-defined serious adverse events in the included trials in either group. In elderly adults, the high-dose influenza vaccine was well-tolerated, more immunogenic, and more efficacious in preventing influenza infections than the standard-dose vaccine. Further pragmatic trials are needed to determine if the higher efficacy translates into higher vaccine effectiveness in adults over the age of 65. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Trial of high-dose Edmonston-Zagreb measles vaccine in Guinea-Bissau

    DEFF Research Database (Denmark)

    Aaby, Peter; Jensen, T G; Hansen, H L

    1988-01-01

    In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units......) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against...... measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine....

  7. Effect of high-dose ciclosporin on the immune response to primary and booster vaccination in immunocompetent cats.

    Science.gov (United States)

    Roberts, Elizabeth S; VanLare, Karen A; Roycroft, Linda M; King, Stephen

    2015-02-01

    Ciclosporin (Atopica oral solution for cats 100 mg/ml; Novartis Animal Health) was recently approved for use in cats with feline hypersensitivity dermatitis. The immunosuppressant effect of ciclosporin on the ability of cats to mount an immune response following vaccination was determined. Thirty-two healthy, immunocompetent adult cats (16 cats/group) were treated with either ciclosporin for 56 days at a dose of 24 mg/kg once daily or sham dosed. Prior to treatment, cats had an adequate antibody response to primary vaccination against feline calicivirus (FCV), feline herpesvirus-1 (FHV-1), feline panleukopenia virus (FPV), feline leukemia virus (FeLV) and rabies. Booster vaccination or novel vaccination with feline immunodeficiency virus (FIV) was administered 28 days after initiation of treatment with ciclosporin. There were no differences between the ciclosporin-treated and control cats for FCV and FPV antibody titers following booster vaccination. There were delays/reductions in antibody response to FHV-1, FeLV and rabies in treated cats; however, adequate protection was achieved in response to all booster vaccinations. Following primary vaccination with FIV, control cats showed a response, but treated cats showed no antibody production. Adverse events commonly associated with ciclosporin treatment, including diarrhea/loose stool, vomiting, salivation and regurgitation, were reported. In adult cats treated with 24 mg/kg/day of ciclosporin (more than three times the therapeutic dose), vaccine titer levels were adequate for protection following booster vaccination. In contrast, treated cats failed to mount a humoral response to a novel (FIV) vaccination, suggesting that memory B-cell immune responses remain intact during repeated high-dose ciclosporin administration in cats, but that primary immune responses are impaired. © ISFM and AAFP 2014.

  8. High-dose vitamin A supplementation administered with vaccinations after 6 months of age

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Bale, Carlito; Jørgensen, Mathias Jul

    2013-01-01

    WHO recommends vitamin A supplementation (VAS) at vaccination contacts after six months of age. The effect of this recommendation on mortality has not been evaluated.......WHO recommends vitamin A supplementation (VAS) at vaccination contacts after six months of age. The effect of this recommendation on mortality has not been evaluated....

  9. High-dose vitamin A with vaccination after 6 months of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Bale, Carlito; Rodrigues, Amabelia

    2014-01-01

    BACKGROUND: The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortal...

  10. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

    Science.gov (United States)

    Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

    2016-06-08

    Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Safety and immunogenicity of high-dose trivalent inactivated influenza vaccine in adults 50-64 years of age.

    Science.gov (United States)

    DiazGranados, Carlos A; Saway, William; Gouaux, James; Baron, Mira; Baker, Jeffrey; Denis, Martine; Jordanov, Emilia; Landolfi, Victoria; Yau, Eddy

    2015-12-16

    Individuals 50-64 years of age have reduced immune responses to influenza vaccines. The current study examined whether a high-dose inactivated trivalent influenza vaccine (IIV3-HD) might improve immune responses over a standard-dose inactivated influenza vaccine (IIV3-SD) in this age group. This was a multicenter, observer-blinded, randomized, active-controlled phase II trial. Adults 50-64 years of age were randomized 1:1 to receive IIV3-HD or IIV3-SD. Hemagglutination inhibition titers were measured before and 28 days after vaccination. Reactogenicity was recorded for 7 days after vaccination and adverse events for 28 days. 148 participants received IIV3-HD and 152 received IIV3-SD. For all vaccine strains, day 28 geometric mean hemagglutination inhibition titers were significantly higher in the IIV3-HD group than in the IIV3-SD group (geometric mean titer ratio [95% confidence interval (CI)]=1.43 [1.04-1.97] for A/H1N1, 1.65 [1.21-2.25] for A/H3N2, and 1.60 [1.23-2.08] for B). Seroconversion rates were significantly higher in the IIV3-HD group than in the IIV3-SD group for strains A/H3N2 and B but not A/H1N1 (difference [95% CI]=13.5% [4.76-22.0] for A/H3N2, 23.1% [11.7-33.6] for B, and -0.2% [-9.66 to 9.18] for A/H1N1). The post-vaccination seroprotection rate was significantly higher in the IIV3-HD group than in the IIV3-SD group for strain B but not for strains A/H1N1 or A/H3N2 (difference=9.1% [2.95-15.7] for B, 2.0% [-0.907 to 5.68] for A/H1N1, and 0.6% [-3.14 to 4.43] for A/H3N2). Reactogenicity was higher in the IIV3-HD group than in the IIV3-SD group, but reactions were mostly of low intensity, transient, and self-limited. Rates of unsolicited adverse events were similar between groups. No serious AEs, AEs leading to early withdrawal, or deaths were reported. The study suggests that in adults 50-64 years of age, IIV3-HD may improve immunogenicity compared to IIV3-SD while maintaining an acceptable safety profile. Copyright © 2015 The Authors. Published

  12. Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: a cluster-randomised trial.

    Science.gov (United States)

    Gravenstein, Stefan; Davidson, H Edward; Taljaard, Monica; Ogarek, Jessica; Gozalo, Pedro; Han, Lisa; Mor, Vincent

    2017-09-01

    Immune responses to influenza vaccines decline with age, reducing clinical effectiveness. We compared the effect of the more immunogenic high-dose trivalent influenza vaccine with a standard-dose vaccine to identify the effect on reducing hospital admissions of nursing home residents in the USA. We did a single-blind, pragmatic, comparative effectiveness, cluster-randomised trial with a 2 × 2 factorial design. Medicare-certified nursing homes in the USA located within 50 miles of a Centers for Disease Control and Prevention influenza reporting city were recruited, so long as the facilities were not located in a hospital, had more than 50 long-stay residents, had less than 20% of the population aged under 65 years, and were not already planning to administer the high-dose influenza vaccine to residents. Enrolled nursing homes were randomised to a facility-wide standard of care for the residents of either high dose or standard dose as the vaccine for the 2013-14 influenza season and half of each group were randomly allocated to free vaccines for staff. Individual residents were included in the analysis group if they were aged 65 years or older and were long-stay residents (ie, had been in the facility 90 days or more before commencing the influenza vaccination programme). The analysts and investigators with access to the raw data were masked to study group by coding the groups until after the analyses were complete. The primary outcome was hospital admissions related to pulmonary and influenza-like illness between Nov 1, 2013, and May 31, 2014, identified from Medicare hospital claims available for residents who were without private health insurance (ie, those who were considered Medicare fee-for-service). We obtained data from the Centers for Medicare & Medicaid Services (CMS) and enrolled facilities. The analyses used marginal Poisson and Cox proportional hazards regression, accounting for clustering of residents within homes, on an intention-to-treat basis

  13. Improved immunogenicity of high-dose influenza vaccine compared to standard-dose influenza vaccine in adult oncology patients younger than 65 years receiving chemotherapy: A pilot randomized clinical trial.

    Science.gov (United States)

    Jamshed, Saad; Walsh, Edward E; Dimitroff, Lynda J; Santelli, Jeanine Seguin; Falsey, Ann R

    2016-01-27

    Patients undergoing chemotherapy often fail to develop robust responses to influenza vaccination. Compared to standard-dose influenza vaccine (SD), high-dose influenza vaccine (HD) has shown improved immunogenicity and protection against influenza illness in adults 65 years and older. This study compared the immunogenicity and tolerability of HD to SD in adults younger than 65 years of age receiving chemotherapy. This double-blind study randomized patients receiving chemotherapy to vaccination with either SD or HD influenza vaccine. Hemagglutination inhibition assays (HAI) were performed prior to and 4 weeks after vaccination. HAI were summarized as geometric mean titers (GMT), seroconversion rates, and seroprotection rates. A total of 105 subjects were enrolled in the trial (51 received SD and 54 received HD). Subjects were well matched for demographic and medical conditions. Both vaccines were well tolerated with no SAEs. Of the 100 subjects with evaluable data, seroconversion rates for all 3 influenza antigens & post-vaccination GMTs for H3N2 & B strains were significantly improved with HD compared to SD. Seroprotection was excellent and equivalent in both groups. Trivalent high-dose influenza vaccine can be safely administered to patients receiving chemotherapy with improved immunogenicity and seroconversion compared to standard-dose vaccine. Post-vaccination seroprotection rates were similar in both groups. A larger study is needed to show clinical benefits with HD in this population. This study was registered at ClinicalTrials.gov as NCT01666782. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine

    DEFF Research Database (Denmark)

    Diness, Birgitte R; Fisker, Ane B; Roth, Adam

    2007-01-01

    BACKGROUND: Vitamin A supplementation (VAS) at birth has been associated with decreased mortality in Asia. Bacille Calmette-Guérin (BCG) vaccine is given at birth in tuberculosis-endemic countries. Previous studies suggest that VAS may influence the immune response to vaccines. OBJECTIVE: Our...... objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine. DESIGN: Within a randomized trial of 50,000 IU vitamin A or placebo given with BCG vaccine at birth in Guinea-Bissau, 2710 infants were examined for BCG scar formation and delayed...

  15. Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine

    DEFF Research Database (Denmark)

    Diness, Birgitte R; Fisker, Ane B; Roth, Adam

    2007-01-01

    BACKGROUND: Vitamin A supplementation (VAS) at birth has been associated with decreased mortality in Asia. Bacille Calmette-Guérin (BCG) vaccine is given at birth in tuberculosis-endemic countries. Previous studies suggest that VAS may influence the immune response to vaccines. OBJECTIVE: Our...... objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine. DESIGN: Within a randomized trial of 50,000 IU vitamin A or placebo given with BCG vaccine at birth in Guinea-Bissau, 2710 infants were examined for BCG scar formation and delayed...... scar was not affected by VAS. The ex vivo interferon-gamma response to PPD was increased by VAS (means ratio: 1.40; 95% CI: 1.03, 1.91). CONCLUSIONS: VAS with BCG vaccination does not appear to interfere with the long-term immune response to BCG. However, VAS temporarily altered the DTH reaction to PPD...

  16. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    Science.gov (United States)

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-02

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

  17. Immunogenicity and safety of a high-dose hepatitis B vaccine among patients receiving methadone maintenance treatment: A randomized, double-blinded, parallel-controlled trial.

    Science.gov (United States)

    Shi, Jing; Feng, Yongliang; Gao, Linying; Feng, Dan; Yao, Tian; Shi, Shan; Zhang, Yawei; Liang, Xiaofeng; Wang, Suping

    2017-04-25

    To explore whether the immunization with high-dose (60μg) hepatitis B vaccines in patients receiving methadone maintenance treatment (MMT) could yield a superior protection against hepatitis B infection than did the standard dose (20μg). We conducted a randomized, double-blinded, parallel-controlled trial in MMT patients. Patients with serologically negative hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were randomized in a ratio of 1:1 to receive three intramuscular injections of 20μg or 60μg recombinant hepatitis B vaccine at months 0, 1, and 6. Serum HBsAg and anti-HBs were measured at months 7 and 12 post-vaccination to assess the immunogenicity. A total of 196 MMT patients were randomized and 195 received at least one injection (98 and 97 in 20 and 60μg vaccine groups, respectively). The 60μg vaccine group showed a seroconversion of anti-HBs of 87.3%, high-level response rate of 56.3%, and GMC of 742.9mIU/mL at month 7. While these results were numerically higher than the 20μg group, a statistical difference was not found. HIV infection and concomitant drug abuse were negatively associated with the robust immune responses. 7.7% of MMT patients receiving at least one dose of vaccine reported solicited adverse reactions within 7days after vaccination, 2.6% reported unsolicited adverse reactions within 28days after vaccination. None of the MMT patients reported serious adverse events or became HBsAg positive during the follow-up. The three-dose regimen of 60μg recombinant hepatitis B vaccine at months 0, 1, and 6 can yield a similar immunogenicity among MMT patients as compared to the 20μg vaccine. ClinicalTrials.gov identifier: NCT02991599. Copyright © 2017. Published by Elsevier Ltd.

  18. The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Rodrigues, Amabelia; Yazdanbakhsh, Maria

    2009-01-01

    Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria-tetanus-pertussis (DTP......) vaccinations had modified the effect of VAS at birth. VAS was associated with a weak tendency for decreased mortality as long as BCG was the most recent vaccination, the mortality rate ratio being 0.86 (0.48-1.54); 0.82 (0.32-2.08) in girls and 0.89 (0.43-1.88) in boys. However, after DTP vaccination VAS...... at birth was associated with increased mortality in girls (2.19 (1.09-4.38)), whereas no difference was seen for boys (0.90 (0.44-1.82)) (p=0.08 for equal effect of VAS in the two sexes if DTP is the last vaccine). The explanation for the lack of beneficial effect in our setting may have been that VAS...

  19. Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines.

    Science.gov (United States)

    DiazGranados, Carlos A; Robertson, Corwin A; Talbot, H Keipp; Landolfi, Victoria; Dunning, Andrew J; Greenberg, David P

    2015-09-11

    A recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection. The original study was a double-blind, randomized, active-controlled, multicenter trial. Participants were adults ≥65 years randomized to receive IIV-HD or IIV-SD, and followed for 6-8 months post-vaccination for the occurrence of influenza and serious adverse events (SAEs). SAEs were events: leading to death or hospitalization (or its prolongation); considered life-threatening or medically important; or resulting in disability. For the present analysis, reported SAEs were classified as possibly related to influenza by three blinded physicians and rates per 1000 participant-seasons were calculated. Relative vaccine effectiveness (rVE) was estimated as (1-Rate Ratio)×100. 31,989 participants were enrolled, with 15,991 and 15,998 randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly more effective than IIV-SD in preventing SAEs possibly related to influenza overall (rVE, 17.7%; 95% confidence interval [CI], 6.6-27.4%) and serious pneumonia (rVE, 39.8%; 95% CI, 19.3-55.1%). Borderline significance was observed for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause hospitalizations (rVE, 6.9%; 95% CI, 0.5-12.8%). Compared to IIV-SD, IIV-HD reduced the risk of SAEs possibly related to influenza. The observed relative effectiveness against serious pneumonia is particularly noteworthy considering the burden of influenza and pneumonia in older adults. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

    Science.gov (United States)

    Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

    2017-06-03

    Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

  1. Routine High Dose Excretory Urography

    Science.gov (United States)

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

    1967-01-01

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

  2. High dose irradiation with hyperfractionation

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-10-01

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

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

    African Journals Online (AJOL)

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

  4. High-Dose Phenobarbital for Ohtahara Syndrome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-05-01

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

  5. 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.

  6. High dose rate brachytherapy for oral cancer

    Science.gov (United States)

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

    2013-01-01

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

  7. Vaccinations

    Science.gov (United States)

    ... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...

  8. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-03-31

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

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

  12. 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)

  13. 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

  14. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

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

    Science.gov (United States)

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

    2014-09-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

  17. High-dose chemotherapy regimens for solid tumors

    NARCIS (Netherlands)

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

    1995-01-01

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

  18. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

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

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 6...

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    ajl yemi

    2011-11-28

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

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

    African Journals Online (AJOL)

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  3. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

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

  4. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

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

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

  5. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

    2000-01-01

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

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

    Science.gov (United States)

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

    2014-01-28

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

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Chiappini, Bruno; El Khoury, Gebrine

    2006-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-02-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

    Feliciano, Chitho P.

    2018-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-15

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

  14. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

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

  15. 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.

  16. 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.

  17. Dose determination in high dose-rate brachytherapy.

    Science.gov (United States)

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

    1992-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

  19. Impact of high dose vitamin C on platelet function.

    Science.gov (United States)

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

    2017-02-04

    To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of VitC used here correspond to plasma VitC levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography (TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate (ATP) secretion in response to collagen or adenosine diphosphate (ADP); and flow cytometry, for changes in expression of CD-31, CD41a, CD62p and CD63. In addition, PLT intracellular VitC content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time (PT), partial thrombplastin time (PTT), functional fibrinogen] and Lipidomics analysis (UPLC ESI-MS/MS). VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle (P 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups (P > 0.05). Finally, VitC at the higher dose (3 mmol/L) also induced the release of several eicosanoids including thromboxane B2 and prostaglandin E2, as well as products of

  20. High-dose radiation sensor with wireless optical detection

    Science.gov (United States)

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

    2017-05-01

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

  1. 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.

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

    Science.gov (United States)

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

    2009-07-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    1998-11-01

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

  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. Tolerance of the Brachial Plexus to High-Dose Reirradiation

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  9. "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.

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

    Science.gov (United States)

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

    2014-10-23

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

  11. 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

  12. Protective Immunity against Lethal F. tularensis holarctica LVS Provided by Vaccination with Selected Novel CD8+ T Cell Epitopes

    Science.gov (United States)

    Bar-Haim, Erez; Bar-On, Liat; Ehrlich, Sharon; Shafferman, Avigdor

    2014-01-01

    Recently we described an unbiased bacterial whole-genome immunoinformatic analysis aimed at selection of potential CTL epitopes located in “hotspots” of predicted MHC-I binders. Applying this approach to the proteome of the facultative intra-cellular pathogen Francisella tularensis resulted in identification of 170 novel CTL epitopes, several of which were shown to elicit highly robust T cell responses. Here we demonstrate that by DNA immunization using a short DNA fragment expressing six of the most prominent identified CTL epitopes a potent and specific CD8+ T cell responses is being induced, to all encoded epitopes, a response not observed in control mice immunized with the DNA vector alone Moreover, this CTL-specific mediated immune response prevented disease development, allowed for a rapid clearance of the bacterial infection and provided complete protection against lethal challenge (10LD50) with F. tularensis holarctica Live Vaccine Strain (LVS) (a total to 30 of 30 immunized mice survived the challenge while all control DNA vector immunized mice succumbed). Furthermore, and in accordance with these results, CD8 deficient mice could not be protected from lethal challenge after immunization with the CTL-polyepitope. Vaccination with the DNA poly-epitope construct could even protect mice (8/10) against the more demanding pulmonary lethal challenge of LVS. Our approach provides a proof-of-principle for selecting and generating a multi-epitpoe CD8 T cell-stimulating vaccine against a model intracellular bacterium. PMID:24400128

  13. Protective immunity against lethal F. tularensis holarctica LVS provided by vaccination with selected novel CD8+ T cell epitopes.

    Science.gov (United States)

    Rotem, Shahar; Cohen, Ofer; Bar-Haim, Erez; Bar-On, Liat; Ehrlich, Sharon; Shafferman, Avigdor

    2014-01-01

    Recently we described an unbiased bacterial whole-genome immunoinformatic analysis aimed at selection of potential CTL epitopes located in "hotspots" of predicted MHC-I binders. Applying this approach to the proteome of the facultative intra-cellular pathogen Francisella tularensis resulted in identification of 170 novel CTL epitopes, several of which were shown to elicit highly robust T cell responses. Here we demonstrate that by DNA immunization using a short DNA fragment expressing six of the most prominent identified CTL epitopes a potent and specific CD8+ T cell responses is being induced, to all encoded epitopes, a response not observed in control mice immunized with the DNA vector alone Moreover, this CTL-specific mediated immune response prevented disease development, allowed for a rapid clearance of the bacterial infection and provided complete protection against lethal challenge (10LD50) with F. tularensis holarctica Live Vaccine Strain (LVS) (a total to 30 of 30 immunized mice survived the challenge while all control DNA vector immunized mice succumbed). Furthermore, and in accordance with these results, CD8 deficient mice could not be protected from lethal challenge after immunization with the CTL-polyepitope. Vaccination with the DNA poly-epitope construct could even protect mice (8/10) against the more demanding pulmonary lethal challenge of LVS. Our approach provides a proof-of-principle for selecting and generating a multi-epitpoe CD8 T cell-stimulating vaccine against a model intracellular bacterium.

  14. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  15. 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...

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2010-12-01

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

  18. High-dose IL2 in metastatic melanoma: better survival in patients immunized with antigens from autologous tumor cell lines.

    Science.gov (United States)

    Dillman, Robert O; Depriest, Carol; McClure, Stephanie E

    2014-03-01

    Abstract Various published data show that in patients with metastatic melanoma, high-dose interleukin-2 (IL2) is associated with 5-year survival rates of 15% from treatment initiation. We previously reported a median survival of 15.6 months, and a 20% 5-year survival rate for 150 patients who were treated with inpatient IL2 (Cancer Biother Radiopharm 2012;27:337). In the current study, we sought to determine whether treatment with active specific immunotherapy (ASI) with patient-specific tumor stem cell vaccines derived from autologous tumor cell (TC) lines contributed to the survival result. Existing databases revealed that 32/149 IL2-treated patients also received ASI, while 117 did not. ASI was given within 12 months of IL2 therapy in 19/32 patients. Patients who received IL2 plus ASI had better overall survival (pIL2-alone patients who died before 12 months of follow-up (p=0.12). In subset analyses, survival was longer for 25 patients who received ASI after IL2 than for 7 who received ASI before IL2 (5-year survival 46% vs. 14%, pIL2 followed by a patient-specific melanoma stem cell vaccine is associated with better survival than IL2 alone.

  19. 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.

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

    Science.gov (United States)

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

    2017-01-04

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

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

    National Research Council Canada - National Science Library

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The patient was treated with high-dose chemotherapy and autologous stem cell transplantation. She developed a severe treatment-related encephalopathy which affected her quality of life and neurocognitive functioning for the rest of her life. Possible causative factors are discussed and central nervous system toxicity by high-dose chemotherapy in brain tumour patients is reviewed. Case reports on severe central nervous system toxicity have been reported, but data from prospective studies on neurocognitive functioning are not available. These data strongly support a systematic long-term follow-up of brain tumour patients treated with high-dose chemotherapy with emphasis on neurocognitive function tests.

  5. 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)

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

    OpenAIRE

    Tülay Kaçar Güvel; Sezer Özkan; Müge Öner Tamam

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Goichi Kageyama

    2017-06-01

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

  11. 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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2011-10-25

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

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

    Directory of Open Access Journals (Sweden)

    Che Lin

    2011-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Inrig Jula K

    2011-12-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-02-15

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2009-09-01

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

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

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

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

  1. The effect of vitamin A supplementation administered with missing vaccines during national immunization days in Guinea-Bissau

    OpenAIRE

    Benn, Christine Stabell; Martins, Cesario; Rodrigues, Amabelia; Ravn, Henrik; Fisker, Ane B?rent; Christoffersen, Dorthe; Aaby, Peter

    2008-01-01

    Background WHO recommends high-dose Vitamin A supplementation (VAS) at vaccination contacts after 6 months of age. It has not been studied whether the effect of VAS on mortality depends on the type of vaccine. We have hypothesized that VAS administered with measles vaccine (MV) is more beneficial than VAS with diphtheria?tetanus?pertussis (DTP) vaccine. We assessed the effect of VAS administered with different vaccines during national immunization days (NIDs). Methods In 2003, VAS was distrib...

  2. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-01-01

    Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (purticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    NARCIS (Netherlands)

    Veen, Ronald E.; Kal, Henk B.

    2007-01-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2016-10-27

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

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

    Science.gov (United States)

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

    2018-01-10

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

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

    Science.gov (United States)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    Bruce Charles Baguley

    2014-11-01

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

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

    DEFF Research Database (Denmark)

    Lindell, G; Bukhave, Klaus; Lilja, I

    1997-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    DEFF Research Database (Denmark)

    Buus, Simon; Rylander, Susanne; Hokland, Steffen

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

    Nieboer, Peter

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    NARCIS (Netherlands)

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

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...... to the AB0 blood type system....

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

    African Journals Online (AJOL)

    DR. AMINU

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

  9. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

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

    Directory of Open Access Journals (Sweden)

    Francesco Ventrella

    2013-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

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

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

    OpenAIRE

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

    2015-01-01

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

  13. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

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

    Directory of Open Access Journals (Sweden)

    Ali Güneş

    2013-12-01

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

  15. [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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-06-01

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

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

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    2016-01-01

    PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated...... with immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission....... After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours...

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Varney VA

    2011-09-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    D'Angelo, Armando; Valsecchi, Luca

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  5. 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)

  6. 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.

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

    Science.gov (United States)

    Kelly, Tammas

    2016-12-01

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

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

    Science.gov (United States)

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

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

  9. 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.

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

    Science.gov (United States)

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

    2006-12-21

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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    OpenAIRE

    Umesh, Shreekantiah; Sinha, Vinod Kumar

    2014-01-01

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

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

    Science.gov (United States)

    Epstein, R B; Sarpel, S C

    1980-07-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Vijaya Sarathi

    2017-01-01

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

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

    Science.gov (United States)

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

    2010-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-15

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

  18. 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)

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

    Science.gov (United States)

    Kordiš, Špela; Battelino, Saba

    2017-11-21

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

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

    Science.gov (United States)

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

    2015-10-01

    The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

  1. 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)

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

    Directory of Open Access Journals (Sweden)

    Cui Lihong

    2015-07-01

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

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

    Science.gov (United States)

    Day, Troy; Read, Andrew F.

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

    Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ 2 tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low-dose-requiring women. Nine nonsynonymous variants were unique to the high-dose-requiring group. These included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V, R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173

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

    Science.gov (United States)

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

    2013-07-13

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

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

    Science.gov (United States)

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

    2004-01-01

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

  7. [Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously].

    Science.gov (United States)

    Fievet, Patrick; Coppin, Mathilde; Brazier, François; Lefèvre, Magali; Stephan, Robin; Demontis, Renato

    2012-02-01

    Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self-limiting myalgia and arthralgia. No venous inflammatory reaction was noted. The administration of high doses of LMWID is effective in treating anemia of CKD in the predialysis stage with a satisfactory tolerance, without affecting kidney function and helps preserve the venous capital. It should be reserved for patients whose serum ferritin is less than or equal to 150 μg/L. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights

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

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    Tülay Kaçar Güvel

    2014-10-01

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

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

    Science.gov (United States)

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

    2014-10-05

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

  10. 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

  11. 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

  12. High doses of ethylene diurea (EDU) are not toxic to willow and act as nitrogen fertilizer.

    Science.gov (United States)

    Agathokleous, Evgenios; Paoletti, Elena; Saitanis, Costas J; Manning, William J; Shi, Cong; Koike, Takayoshi

    2016-10-01

    Ethylene diurea (EDU) is synthetic chemical which protects plants against damage caused by ground level O3 and is used experimentally as a biomonitoring tool at doses usually ranging from 200 to 400mgL(-1) a.i. Although several studies have investigated the protective action of EDU, this mechanism remains unclear. Important uncertainties in EDU action are whether EDU acts as a source of nitrogen (N) to plants and whether high doses are phytotoxic. In order to answer these questions, we conducted an open-field experiment where potted willow (Salix sachalinensis Fr. Schm) plants were exposed to ambient O3 conditions and treated with 0, 800 or 1600mgL(-1) EDU as a soil drench, every nine days, for about 2.5months. We examined approximately 50 response variables. Based on N content in different plant organs, we found that (a) all EDU was transferred to the leaves and (b) high doses of EDU increased the leaf N content. However, EDU did not affect the C content and distribution within the plant body. Still, even at the highest dose, EDU was not toxic to this fast-growing species (however such a high dose should not be applied in uncontrolled environments); and there was no EDU persistence in the soil, as indicated by soil N content. Notably, our soil was free from organic matter and N-poor. EDU per se does not cause toxicity to willow plants when applied as drench to a soil with no organic matter, rather, high EDU doses may act as nitrogen fertilizer in a nitrogen-poor soil. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-10-21

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-15

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ray Monika

    2012-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Shabani Ramin

    2016-08-01

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

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

    Science.gov (United States)

    Qi, Wei; Gevonden, Martin; Shalev, Arieh

    2017-02-01

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

  20. High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

    Science.gov (United States)

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Hall, Kathi; Stein, C Michael

    2017-02-01

    Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects. The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point. We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline.

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

    Science.gov (United States)

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

    2014-06-01

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

  2. Prior methamphetamine self-administration attenuates serotonergic deficits induced by subsequent high-dose methamphetamine administrations.

    Science.gov (United States)

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

    2012-11-01

    Pre-clinical studies indicate that high-dose, non-contingent methamphetamine (METH) administration both rapidly and persistently decreases serotonergic neuronal function. Despite research indicating the hippocampus plays an important role in METH abuse and is affected by METH use, effects of METH self-administration on hippocampal serotonergic neurons are not well understood, and were thus an important focus of the current study. Because humans often administer METH in a binge-like pattern, effects of prior METH self-administration on a subsequent "binge-like" METH treatment were also examined. Rats were treated as described above, and sacrificed 1 or 8d after self-administration or 1h or 7d after the final binge METH or saline exposure. Hippocampal serotonin (5-hydroxytryptamine; 5HT) content and transporter (SERT) function were assessed. METH self-administration per se had no persistent effect on hippocampal 5HT content or SERT function. However, this treatment attenuated the persistent, but not acute, hippocampal serotonergic deficits caused by a subsequent repeated, high-dose, non-continent METH treatment administered 1 d the last self-administration session. No attenuation in persistent deficits were seen when the high-dose administration of METH occurred 15d after the last self-administration session. The present findings demonstrate that METH self-administration alters serotonergic neurons so as to engender "tolerance" to the persistent serotonergic deficits caused by a subsequent METH exposure. However, this "tolerance" does not persist. These data provide a foundation to investigate complex questions including how the response of serotonergic neurons to METH may contribute to contingent-related disorders such as dependence and relapse. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Enhanced neurodegeneration after a high dose of methamphetamine in adenosine A3 receptor null mutant mice.

    Science.gov (United States)

    Shen, H; Luo, Y; Yu, S-J; Wang, Y

    2011-10-27

    Previous reports have indicated that adenosine A3 receptor (A3R) knockout mice are more sensitive to ischemic or hypoxic brain injury. The purpose of this study was to examine if suppression of A3R expression is associated with increase in sensitivity to injury induced by a high dose of methamphetamine (Meth). Adult male A3R null mutant (-/-) mice and their controls (+/+) were injected with four doses (2 h apart) of Meth (10 mg/kg) or saline. Animals were placed in a behavioral activity chamber, equipped with food and water, for 52 h starting from one day after injections. The first 4 h were used for studying exploratory behaviors, and the next 48 h were used to measure locomotor activity. High doses of Meth equally reduced the 4-h exploratory behavior in -/- and +/+ mice. Meth suppressed locomotor activity between 4 and 52 h in both groups, with a greater reduction being found in the -/- mice. Brain tissues were collected at 3 days after the Meth or saline injections. Meth treatment reduced striatal dopamine (DA) levels in both +/+ and -/- mice with an increase in 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio being found only in -/- animals. Meth also significantly increased ionized calcium-binding adaptor molecule 1 (Iba-1) and cleaved caspase-3 level in striatum, as well as Iba-1 and TNFα mRNA expression in nigra in -/-, compared to +/+, mice. Previous studies have shown that pharmacological suppression of vesicular monoamine transport 2 (VMAT2) by reserpine enhanced Meth toxicity by increasing cytosolic DA and inflammation. A significant reduction in striatal VMAT2 expression was found in -/- mice compared to +/+ mice, suggesting that increase in sensitivity to Meth injury in -/- mice may be related to a reduction in VMAT2 expression in these mice. In conclusion, our data suggest that A3R -/- mice are more sensitive to high doses of Meth. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  6. [Reversible lactic acidosis in a diabetic on high dose metformin (author's transl)].

    Science.gov (United States)

    Beaudot, C; Merceron, R E; Lavieuville, M; Noël, M; Brohon, J; Raymond, J P

    1980-09-01

    In a diabetic, who took a high dose of 5.85 g metformin daily for 75 days, urinary retention caused by a prostatic adenoma induced functional renal insufficiency and hyperlactacidemia, rapidly reversed with treatment. Plasma and urine levels of metformin were measured at the same time as lactate and pyruvate levels, until all returned to normal. Clinical and biological improvement occured at the same time. The case is discussed in the context of lactic acidosis in diabetics with functional or organic renal insufficiency, treated with metformin.

  7. Intermittent high-dose vitamin C therapy in patients with HTLV-I associated myelopathy.

    Science.gov (United States)

    Kataoka, A; Imai, H; Inayoshi, S; Tsuda, T

    1993-11-01

    The efficacy of intermittent high-dose vitamin C therapy was evaluated in seven patients with HTLV-I-associated myelopathy (HAM). All HAM patients responded well to this therapy without serious side effects. Grade of disability score improved at 9.7 (SD 5.8) months after the therapy from 7.1 (3.3) to 3.6 (2.0) (p < 0.01). Serum immunosuppressive acidic protein was elevated before and decreased after the therapy from 747 (316) to 398 (86) micrograms/ml (p < 0.05), suggesting favourable immunomodulatory action of vitamin C therapy in HAM patients.

  8. 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

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

    Science.gov (United States)

    Pettersen, Jacqueline A

    2017-04-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    .006-0.027), fever (OR = 2.65; P = 0.037) and interruption of maintenance treatment (OR = 3.04; P = 0.032). No convincing associations were found between the MTHFR C677T or A1298C polymorphisms and toxicity. CONCLUSION: Our findings demonstrate that toxicity after HDMTX is influenced by coadministrated...... in the methylene tetrahydrofolate reductase (MTHFR) gene and coadministration of antimetabolites on post-HDMTX toxicity. METHODS: Toxicity was retrospectively analysed after 656 HDMTX courses administered to 88 paediatric ALL patients at a single treatment centre. RESULTS: High-dose methotrexate with high...

  11. High-dose omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia.

    Science.gov (United States)

    Van Biervliet, S; Van Winckel, M; Robberecht, E; Kerremans, I

    2001-09-01

    The authors describe 4 children with recurrent stenosis and persistent esophagitis after secondary repair of a long gap esophageal atresia. They underwent an esophageal reconstruction by elongation of the lesser gastric curvature according to Schärli at the age of 11 to 14 months. All had esophagitis grade III to IV (Savary-Miller classification), esophageal stenosis, and failure to thrive. Effective treatment of the esophagitis and prevention of stenosis consisted in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment, the need for esophageal dilatation disappeared, and nutritional status normalized. Copyright 2001 by W.B. Saunders Company.

  12. A model for low dose effects of low-LET radiation delivered at high dose rates

    Science.gov (United States)

    Schöllnberger, H.; Stewart, R.D.; Mitchel, R.E.J.

    2011-01-01

    In vitro studies show that protective tumour-reducing effects occur for low dose rates (mGy per minute). To account for these phenomena, we have previously developed stochastic and deterministic multi-stage cancer models that include radiation-induced adaptations in DNA repair processes and radical scavenging. Here, these models are extended to account for the induction of radioprotective mechanisms for low doses of low LET radiation delivered at high dose rates. Cellular adaptations in DNA repair are related to temporal changes in the amount of DNA damage in a cell. The combined effects of endogenous DNA damage, background radiation and artificial irradiation are considered. PMID:22318364

  13. Chronical cervical infections and dysplasia (CIN I, CIN II): Vaginal vitamin D (high dose) treatment

    OpenAIRE

    Schulte-Uebbing, C; Schlett, S; Craiut, ID; Antal, L; Olah, H

    2014-01-01

    In a small praxis/ambulance study we evaluated data of 200 women with chronical recurrent cervical infections and with a cervix dysplasia (CIN 1, CIN 2). who got after the primary therapy a treatment with vitamin D vaginal suppositories (12.500 IU, 3 nights a week, for 6 weeks). We found that - when compared with the lactobacillus vaginal suppositories - the high dose vitamin D vaginal treatment might be more effective. Vitamin D showed very good anti-inflammatory effects. In the survey after...

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines [Instituto de Pesquisas Energeticas e Nucleares/Comissao Nacional de Energia Nuclear Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo (Brazil)], E-mail: miteixei@ipen.br; Melo, Adeilson P. [Instituto de Pesquisas Energeticas e Nucleares/Comissao Nacional de Energia Nuclear Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo (Brazil); Centro Federal de Educacao Tecnologica de Sergipe, Aracaju (Brazil)], E-mail: adeilson_pessoa_melo@yahoo.com.br; Ferraz, Gilberto M. [Depto. de Fisica Nuclear, Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil)], E-mail: gmarconf@if.usp.br; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares/Comissao Nacional de Energia Nuclear Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo (Brazil)], E-mail: lcaldas@ipen.br

    2010-04-15

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

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

    Science.gov (United States)

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

    2017-09-01

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

  17. Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery

    Directory of Open Access Journals (Sweden)

    Satu Lakio

    2015-12-01

    Full Text Available In this study a carrier-free dry powder inhalation (DPI containing L-arginine (ARG was developed. As such, it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis. Various processing methods were used to manufacture high-dose formulation batches consisting various amounts of ARG and excipients. The formulations were evaluated using several analytical methods to assess suitability for further investigation. Several batches had enhanced in vitro aerolization properties. Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.

  18. Polio Vaccine

    Science.gov (United States)

    ... doctorMost kids have no problems with the polio vaccine. However, call your doctor if your child has any reaction after getting the vaccine. Call ... Tell the doctor when (day and time) your child received the vaccine. You also should file a Vaccine Adverse Event ...

  19. 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.

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

    Science.gov (United States)

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

    2016-09-01

    Associations between criminal activity and the use of psychotropic substances are well established. Flunitrazepam, specifically, has been suspected of triggering, per se, violent criminal behavior and severe memory disturbances in the form of anterograde amnesia. However, data from investigations of this relationship are scarce and have been primarily derived from forensic institutions, where there may be a reporting bias. This study was a qualitative exploration of high-dose benzodiazepine users' experiences of anterograde amnesia symptoms and their beliefs about their behavior during the phases of memory impairment in a nonforensic setting. Users subjectively reported experiencing symptoms of anterograde amnesia, especially after combining short-acting benzodiazepines with alcohol, but only rarely when using slow-onset, long-acting compounds. They perceived their experiences as unpleasurable, unpredictable, and embarrassing. Their awareness developed with time, triggered by descriptions of disinhibited and erratic behavior by others. Users described being victimized during phases of anterograde amnesia in addition to engaging in violent and criminal activities themselves. Although unable to recall, many participants believed that they had been able to make rational decisions while intoxicated with flunitrazepam, disregarding notions of diminished insight. In light of the varying terminology used for the phases of memory disturbance and these findings, we suggest that forensic experts additionally explore evaluees' beliefs about amnestic periods and their self-perceptions about their behaviors during these episodes, when evaluating high-dose benzodiazepine-dependent patients. © 2016 American Academy of Psychiatry and the Law.

  1. 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)

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

    Science.gov (United States)

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

    2010-04-01

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

  3. High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction.

    Science.gov (United States)

    Adamek, Anna; Hu, Kai; Bayer, Barbara; Wagner, Helga; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan

    2007-07-01

    Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.

  4. 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)

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

    Science.gov (United States)

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

    2000-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Mahboob Pouraghaei

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Aysel Kükner

    2008-12-01

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

  8. Geriatric-oriented high dose nutraceutical ODTs: Formulation and Physicomechanical characterization.

    Science.gov (United States)

    Agiba, Ahmed M; Abdel-Hamid, Sameh; Nasr, Maha; Geneidi, Ahmed S

    2017-03-20

    Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance. Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment. Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburstTM C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems. Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. PharmaburstTM C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets. The improved disintegration and dissolution properties of our prepared ODTs is expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. [Optimal way of administration of high dose intravenous furosemide - continuous infusion or bolus?].

    Science.gov (United States)

    Gallusová, Jana; Halačová, Milada; Cerný, Dalibor

    2014-10-01

    Furosemide is a loop diuretic used in states of volume overload. The need for high doses is due to its reduced efficacy caused by lower concentration of furosemide achieved at the site of action in the renal tubule lumen and adaptation mechanisms. High doses have been associated with the development of ionic dysbalance, direct toxicity and intravascular volume fluctuations. The way of furosemide administration (intermitent versus continuously) to influence efficacy and safety is contradictory evaluated in EBM. The aim of this study is to analyze the available data for evaluation of the efficacy and safety of intermittent versus continuous dose regimens. A systematic search on PubMed from 1990 to 2013 using the keywords - furosemide, loop diuretic, bolus, continuous infusion, efficacy, safety, heart failure, ICU, critical care. The pharmacokinetic and pharmacodynamic knowledge of furosemide create a theoretical assumption for the preference of continuous infusions before intermittent boluses. Assessement of available studies, however, yet in clinical practice did not proof the advantage of one over the other route of administration.

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

    Science.gov (United States)

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

    2003-04-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Akira Ouchi

    2014-01-01

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

  13. Ureteral stent insertion for gynecologic interstitial high-dose-rate brachytherapy.

    Science.gov (United States)

    Demanes, D Jeffrey; Banerjee, Robyn; Cahan, Benjamin L; Lee, Steve P; Park, Sang-June; Fallon, Julia M; Reyes, Paula; Van, Thanh Q; Steinberg, Michael L; Kamrava, Mitchell R

    2015-01-01

    To determine the utility of ureteral stents in interstitial gynecological brachytherapy. We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined. There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D(0.1cc)) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan 3. Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk. Copyright © 2015. Published by Elsevier Inc.

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2011-08-01

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

  17. Quality of life in a cohort of high-dose benzodiazepine dependent patients.

    Science.gov (United States)

    Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

    2014-09-01

    Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Initial High-Dose Prednisolone Combination Therapy Using COBRA and COBRA-Light in Early Rheumatoid Arthritis

    NARCIS (Netherlands)

    Rasch, L.A.; van Tuyl, L.H.D.; Lems, W.F.; Boers, M.

    2015-01-01

    Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very

  19. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy

    NARCIS (Netherlands)

    de Jonge, M. E.; Mathôt, R. A. A.; Dalesio, O.; Huitema, A. D. R.; Rodenhuis, S.; Beijnen, J. H.

    2002-01-01

    Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated

  20. Haloperidol Treatment after High-Dose Methamphetamine Administration Is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata

    National Research Council Canada - National Science Library

    Hatzipetros, Theo; Raudensky, Jamie G; Soghomonian, Jean-Jacques; Yamamoto, Bryan K

    2007-01-01

    .... We report here that subchronic haloperidol administration after a high-dose regimen of METH produces a heretofore unrecognized toxicity to GABAergic cells, as reflected by GAD67 mRNA expression...

  1. High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jenny E. Han

    2016-06-01

    Conclusions: In this pilot study, high-dose vitamin D3 safely increased plasma 25(OHD concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes.

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

    National Research Council Canada - National Science Library

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

    2011-01-01

    ... to evaluate its effect in the treatment of metastatic breast cancer. We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support...

  3. 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

  4. [Amniotic membrane transplantation and high-dose systemic cyclosporin A (Sandimmun optoral) for Mooren's ulcer].

    Science.gov (United States)

    Spelsberg, H; Sundmacher, R

    2007-02-01

    Mooren's ulcer is a rare, severe corneal autoimmune inflammation leading to blindness if treated insufficiently. High-dose systemic cyclosporin A (Sandimmun optoral) was shown to markedly reduce inflammation and stop corneal destruction. We report on three cases in which this immunosuppressive regimen required additional AM transplantation for complete healing. One 37-year-old male (M) and two 49- (F1) and 58-year-old females (F2) presented with unilateral Mooren's ulcer in different stages of the disease, which deteriorated despite high-dose systemic cyclosporin A (Sandimmun optoral M, F1) or treatment with topical cyclosporin A 2 % (F2). After surgical removal of all grossly affected corneal stroma, amniotic membrane was made to cover the entire cornea and fixed with episcleral sutures in two patients (M, F2). In one patient (F1) a deep marginal ulcer was covered with a fitted AM glap. All patients were treated postoperatively up to 6 months with high-dose systemic cyclosporin A (Sandimmun optoral). Blood trough levels aimed at 150 to 200 ng/mL. Topical cyclosporin A was administered in addition in two patients (M, F2) postoperatively for at least 6 months. Due to incompatibility, one patient (F1) was treated with topical steroids instead. Follow-up time was 42 months (M), 50 months (F1) and 54 months (F2). All three eyes exhibited clinical healing with stable corneal surfaces thereafter. Depending on the stage of Mooren's ulcer at the time of surgery, visual acuity remained at hand motions in one patient (M) and recovered to 1.0 and 0.6, respectively, in two patients (F1, F2). Due to its anti-inflammatory potential, coverage by AM seems to trigger a therapeutic turnaround in cases of Mooren's ulcer which do not heal with intensive immunosuppressive regimens alone. In order to maintain or restore as much visual function as possible, additional amniotic membrane surgery should be performed early enough in the course of the disease.

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

    Science.gov (United States)

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

    2011-01-01

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

  6. 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

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

    OpenAIRE

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

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, hig...

  8. Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

    Science.gov (United States)

    Shiga, Yuhei; Miura, Shin-Ichiro; Norimatsu, Kenji; Hitaka, Yuka; Nagata, Itsuki; Koyoshi, Rie; Morii, Joji; Kuwano, Takashi; Uehara, Yoshinari; Inoue, Asao; Shirotani, Tetsuro; Fujisawa, Kazuaki; Matsunaga, Eiyu; Saku, Keijiro

    2015-12-01

    We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients. © The Author(s) 2014.

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

    Science.gov (United States)

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

    2013-07-01

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

  10. High-dose rate Ir-192 interstitial brachytherapy for recurrent pelvic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tsukiyama, Iwao; Katano, Susumu; Kotake, Kenjiro; Yamamoto, Seiichiro; Kamata, Hiroyuki; Sekiguchi, Isao [Tochigi Cancer Center, (Japan); Furuta, Masaya; Ohno, Tatsuya

    1999-06-01

    Recurrent pelvic tumors are difficult to control with external irradiation alone. We have conducted phase I and II clinical trials against recurrent pelvic tumors. From January 1995 through March 1997, 13 recurrent pelvic tumors in 10 patients were treated with high-dose rate Ir-192 interstitial brachytherapy. Complete responses were achieved for 2 tumors, partial responses for 5 tumors, and no response for 6 tumors; therefore, the response rate was 61% (8 of 13 tumors). Treatment-related morbidity was noted in 5 patients and included one case each of skin ulcer, rectovaginal fistula, sacral abscess, rectal bleeding, and vesicovaginal fistula. In January 1999, four patients were alive and had survived for 17, 18, 28, and 46 months. Six patients had died but had survived 4, 13, 15, 16, and 27 months. (author)

  11. 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).

  12. High-dose inhaled corticosteroids or addition of theophylline in patients with poorly controlled asthma?

    Science.gov (United States)

    Celis, Pilar; Rada, Gabriel

    2015-08-19

    There are several management strategies for patients with poorly controlled asthma despite usual treatment. Increasing doses of inhaled corticosteroids or adding theophylline are among the therapeutic alternatives. However, the latter is associated with important adverse effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether theophylline or high-dose inhaled corticosteroids constitute a better alternative for symptomatic control or reduction in exacerbations in poorly controlled asthmatic patients because the certainty of the evidence is very low.

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

    Science.gov (United States)

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

    2017-10-01

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

  14. High doses of (-)-epigallocatechin-3-gallate from green tea induces cardiac fibrosis in mice.

    Science.gov (United States)

    Cai, Yi; He, Shu-Qiao; Hong, Hui-Qi; Cai, Yue-Peng; Zhao, Li; Zhang, Mei

    2015-12-01

    Tea is the most consumed beverage in the world. (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, is effective in the prevention of several chronic diseases, and is marketed as part of many dietary supplements. We have now examined the myocardiotoxic effect of high doses of EGCG in mice. EGCG (500 and 1000 mg/kg·d) induced cardiac collagen synthesis and fibrosis-related protein expression, such as connective tissue growth factor (CTGF) and fibronectin (FN) in mice. Moreover, EGCG decreased the protein expression of p-AMPK and increased the levels of p-p70S6 K and p-S6. This is the first evidence that high oral doses of EGCG could induce cardiac fibrosis, and shed new light on the understanding of EGCG-mediated myocardiotoxicity.

  15. 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.

  16. 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.

  17. Metabolic effects of feeding high doses of propanol and propylacetate to lactating Holstein cows

    DEFF Research Database (Denmark)

    Raun, Birgitte Marie Løvendahl; Kristensen, Niels Bastian

    2012-01-01

    , hepatic portal vein, and hepatic vein samples were collected at day 14 of each period. Milk fat yield decreased for P and PPA compared with C, however, dry matter intake and milk yield were not affected by treatment. Portal uptake of propanol accounted for 48 to 61% of ingested propanol and differed among......Three lactating Holstein cows implanted with ruminal cannulas and permanent indwelling catheters in major splanchnic blood vessels were used to investigate alcohol metabolism and metabolic effects of feeding high doses of propanol and propylacetate. Cows were fed three diets control (basal ration...... all 3 treatments C ≪ PPA treatments including decreased proportion of ruminal acetate to total VFA; increased proportions of ruminal propionate, isovalerate, valerate, and caproate; increased arterial glucose concentration; decreased arterial...

  18. 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.

  19. Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal.

    Science.gov (United States)

    Murphy, J A; Savage, C M; Alpard, S K; Deyo, D J; Jayroe, J B; Zwischenberger, J B

    2001-11-01

    The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep (n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300s, n = 6) and LD heparin (ACT heparin (ACT heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep.

  20. A phantom for verification of dwell position and time of a high dose rate brachytherapy source.

    Science.gov (United States)

    Madebo, M; Pillainayagam, J; Kron, T; Franich, R

    2012-09-01

    Accuracy of dwell position and reproducibility of dwell time are critical in high dose rate (HDR) brachytherapy. A phantom was designed to verify dwell position and dwell time reproducibility for an Ir-192 HDR stepping source using Computed Radiography (CR). The central part of the phantom, incorporating thin alternating strips of lead and acrylic, was used to measure dwell positions. The outer part of the phantom features recesses containing different absorber materials (lead, aluminium, acrylic and polystyrene foam), and was used for determining reproducibility of dwell times. Dwell position errors of dwell time as low as 0.1 s, the minimum dwell time of the treatment unit, could be detected by choosing dwell times over the four materials that produce identical exposure at the CR detector.

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

    Directory of Open Access Journals (Sweden)

    Robert Whitfield

    2011-03-01

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

  2. Use of ultrasound in image-guided high-dose-rate brachytherapy: enumerations and arguments

    Science.gov (United States)

    Kataria, Tejinder; Gupta, Deepak; Goyal, Shikha; Bisht, Shyam Singh; Basu, Trinanjan; Abhishek, Ashu

    2017-01-01

    Inherently, brachytherapy is the most conformal radiotherapeutic technique. As an aid to brachytherapy, ultrasonography (USG) serves as a portable, inexpensive, and simple to use method allowing for accurate, reproducible, and adaptive treatments. Some newer brachytherapy planning systems have incorporated USG as the sole imaging modality. Ultrasonography has been successfully used to place applicator and dose planning for prostate, cervix, and anal canal cancers. It can guide placement of brachytherapy catheters for all other sites like breast, skin, and head and neck cancers. Traditional USG has a few limitations, but recent advances such as 3-dimensional (3D) USG and contrast USG have enhanced its potential as a dependable guide in high-dose-rate image-guided brachytherapy (HDR-IGBT). The authors in this review have attempted to enumerate various aspects of USG in brachytherapy, highlighting its use across various sites. PMID:28533803

  3. 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.

  4. [Proton Pump Inhibitor and High-dose Methotrexate: Two Cases Reports].

    Science.gov (United States)

    Evrard, Julien; Farnier, Elodie; Carcel, Corine; Lachenal, Florence; Vial, Thierry; Pont, Emmanuelle

    2015-01-01

    Methotrexate (MTX) is a cytotoxic agent prescribed at high dose in treatment of malignancy. Association of MTX to proton pump inhibitor (PPI) is not recommended if doses are more than 20 mg per weeks and only to take into account for smaller doses. Review relate some cases of delayed elimination of methotrexate in patients taking PPI, which increase risk of toxic event. However, currently there is no status quo on interaction between PPI and MTX according to available data. We report two clinical cases illustrating one more time a toxic event to MTX in presence of PPI. In absence of risk/benefit ratio set correctly, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  5. Use of ultrasound in image-guided high-dose-rate brachytherapy: enumerations and arguments

    Directory of Open Access Journals (Sweden)

    Susovan Banerjee

    2017-04-01

    Full Text Available Inherently, brachytherapy is the most conformal radiotherapeutic technique. As an aid to brachytherapy, ultrasonography (USG serves as a portable, inexpensive, and simple to use method allowing for accurate, reproducible, and adaptive treatments. Some newer brachytherapy planning systems have incorporated USG as the sole imaging modality. Ultrasonography has been successfully used to place applicator and dose planning for prostate, cervix, and anal canal cancers. It can guide placement of brachytherapy catheters for all other sites like breast, skin, and head and neck cancers. Traditional USG has a few limitations, but recent advances such as 3-dimensional (3D USG and contrast USG have enhanced its potential as a dependable guide in high-dose-rate image-guided brachytherapy (HDR-IGBT. The authors in this review have attempted to enumerate various aspects of USG in brachytherapy, highlighting its use across various sites.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-07-15

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

  7. Designing malaria vaccines to circumvent antigen variability✩

    Science.gov (United States)

    Ouattara, Amed; Barry, Alyssa E.; Dutta, Sheetij; Remarque, Edmond J.; Beeson, James G.; Plowe, Christopher V.

    2016-01-01

    Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines. PMID:26475447

  8. Designing malaria vaccines to circumvent antigen variability.

    Science.gov (United States)

    Ouattara, Amed; Barry, Alyssa E; Dutta, Sheetij; Remarque, Edmond J; Beeson, James G; Plowe, Christopher V

    2015-12-22

    Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines. Copyright © 2015. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    Sretenovic Jasmina

    2016-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-06-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

  12. Effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats.

    Science.gov (United States)

    Henriques, Helene Nara; de Carvalho, Ana Carolina Bergmann; Soares Filho, Porphirio José; Pantaleão, José Augusto Soares; Guzmán-Silva, Maria Angélica

    2011-08-01

    The aim of this study was evaluate the effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats. Bilateral ovariectomy was performed on 14 rats weighing 250 g. Thirty days later, vaginal smears were collected verifying the menopause status by anoestrus cytology. Rats were divided randomly into groups: experimental rats (n = 9) received 1 mg tibolone/day orally and control rats (n = 6) received placebo (carboxymethylcellulose). After 150 days, all rats were sedated and euthanized by cervical displacement. The vagina was removed, fixed in 10% buffered formalin, sampled and processed for paraffin embedding. Histological sections were stained with haematoxylin and eosin, picrosirius red, periodic acid Schiff (PAS) and PAS-diastase, and Weigert's resorcin-fuchsin. Cell proliferation was analysed by immunohistochemistry to detect Ki67. Histomorphometric analyses were performed for epithelial thickness, per cent area of collagen fibres and blood vessels, mast cells and Ki67-positive nuclei per mm of basal membrane. Means and standard error of means were calculated, and data were compared using the Mann-Whitney test, with significance level at P vagina, epithelial thickness, number of Ki67-positive nuclei per mm of basal membrane, number of vessels and number of mast cells were significantly higher in the tibolone group when compared with the control group. Furthermore, the content of glycogen and glycoproteins in the vaginal epithelium was modified by tibolone. Tibolone administered in high dose and for a long period has a trophic effect, reversing vaginal atrophy, and has no dysplastic or neoplastic effect in the vagina of ovariectomized rats. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

  13. High dose rate brachytherapy with customized applicators for malignant facial skin lesions.

    Science.gov (United States)

    Jumeau, R; Renard-Oldrini, S; Courrech, F; Buchheit, I; Oldrini, G; Vogin, G; Peiffert, D

    2016-07-01

    Brachytherapy is a well-known treatment in the management of skin tumors. For facial or scalp lesions, applicators have been developed to deliver non-invasive treatment. We present cases treated with customized applicators with high dose rate system. Patients with poor performance status treated for malignant skin lesions of the scalp or the facial skin between 2011 and 2014 were studied. Afterloading devices were chosen between Freiburg(®) Flap, silicone-mold or wax applicators. The clinical target volume (CTV) was created by adding margins to lesions (10mm to 20mm). The dose schedules were 25Gy in five fractions for postoperative lesions, 30Gy in six fractions for exclusive treatments and a single session of 8Gy could be considered for palliative treatments. In 30 months, 11 patients received a treatment for a total of 12 lesions. The median age was 80 years. The median follow-up was 17 months and the 2-year local control rate was 91%. The mean CTV surface was 41.1cm(2) with a mean thickness of 6.1mm. We conceived three wax applicators, used our silicone-mold eight times and the Freiburg(®) Flap one time. We observed only low-grade radiodermitis (grade I: 50%, grade II: 33%), and no high-grade skin toxicity. High dose rate brachytherapy with customized applicators for facial skin and scalp lesions is efficient and safe. It is a good modality to treat complex lesions in patients unfit for invasive treatment. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  14. Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

    Science.gov (United States)

    Peng, Rui-Rui; Wu, Juan; Zhao, Wei; Qi, Tengfei; Shi, Mei; Guan, Zhifang; Lu, Haikong; Long, Fuquan; Gao, Zixiao; Zhang, Sufang; Zhou, Pingyu

    2017-03-01

    Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2012-09-01

    Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 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 h. 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/70 kg 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. High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

  17. 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.

  18. 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

  19. High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive endobronchial granulation tissue.

    Science.gov (United States)

    Madu, Chika N; Machuzak, Michael S; Sterman, Daniel H; Musani, Ali; Ahya, Vivek; McDonough, James; Metz, James M

    2006-12-01

    Severe airway obstruction can occur in the setting of benign granulation tissue forming at bronchial anastomotic sites after lung transplantation in up to 20% of patients. Many of these benign lesions respond to stent placement, laser ablation, or balloon bronchoplasty. However, in certain cases, proliferation of granulation tissue may persist despite all therapeutic attempts. This study describes a series of refractory patients treated with high-dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue, causing airway compromise. Between April 2002 and June 2005, 5 patients with significant airway compromise from recurrent granulation tissue were treated with HDR brachytherapy. All patients had previously failed to maintain a patent airway despite multiple bronchoscopic interventions. Treatment was delivered using an HDR brachytherapy afterloader with (192)Ir. Dose prescription was to a depth of 1 cm. All patients were treated weekly, with total doses ranging from 10 Gy to 21 Gy in two to three fractions. The median follow-up was 12 months. All patients experienced a reduction in therapeutic bronchoscopic procedures after HDR brachytherapy compared with the pretreatment period. With the exception of possible radiation-induced bronchitis in 1 patient, there were no other treatment related complications. At the time of this report, 2 patients have died and the other 3 are alive with marked symptomatic improvement and reduced bronchoscopic procedures. High-dose-rate brachytherapy is an effective treatment for benign proliferation of granulation tissue causing airway obstruction. The early response to therapy is encouraging and further follow-up is necessary to determine long-term durability and late effects.

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

    Science.gov (United States)

    2013-01-01

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

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

    Science.gov (United States)

    Attumi, Taraq A; Graham, David Y

    2014-08-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

  3. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Joost Smolders

    2010-12-01

    Full Text Available A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS. Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.Fifteen RRMS patients were supplemented with 20,000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175 at week 0 to 380 nmol/L (151-535 at week 12 (P<0.001. During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P=0.143. An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P=0.021. Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P=0.035.Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.Clinicaltrials.gov NCT00940719.

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

    Science.gov (United States)

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

    2016-12-01

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

  5. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock.

    Science.gov (United States)

    Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein

    2016-01-01

    Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies.

  6. Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats.

    Science.gov (United States)

    Aksoy, Asude; Karaoglu, Aziz; Akpolat, Nusret; Naziroglu, Mustafa; Ozturk, Turkan; Karagoz, Zuhal Karaca

    2015-01-01

    Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Durim Delishaj

    2016-12-01

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

  10. Comparable cell survival between high dose rate flattening filter free and conventional dose rate irradiation.

    Science.gov (United States)

    Verbakel, Wilko F A R; van den Berg, Jaap; Slotman, Ben J; Sminia, Peter

    2013-04-01

    Investigation of clonogenic cell survival and cell proliferation following single dose and fractionated delivery of high dose rate flattening filter free (FFF) irradiation compared to conventional dose rates. The human astrocytoma D384, glioma T98 and lung carcinoma SW1573 cell lines were irradiated using either a single dose (0-12 Gy) or a fractionated protocol of 5 daily fractions of 2 Gy (D384) or 3 Gy (SW1573). Cells were irradiated inside a phantom using fixed gantry beams of a linear accelerator. A sliding window technique created homogeneous dose distributions over the surface of the cell cultures. Irradiations using standard beams (6 MV, 600 MU/min.) and high dose rate FFF beams (10 MV, 2400 MU/min.) were compared. Cell survival was determined by clonogenic assay. In the fractionated irradiation set-up, the number of clonogenic cells was estimated by including tumor cell proliferation during the overall treatment time in the analysis. All cell lines showed equal cell survival following irradiation using either the FFF beams or conventional flattened (FF) beams. This was observed after single dose exposure (0-12 Gy) as well as after fractionated irradiation (p = 0.08 for D384 and 0.20 for SW1373 cell lines). FFF irradiation with a dose rate of 2400 MU/min and four times higher dose per pulse compared to irradiation with FF beams did not change cell survival for three human cancer cell lines up to a fraction dose of 12 Gy compared to irradiation using FF beams.

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

    Science.gov (United States)

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

    2014-10-09

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

  12. Vaccine Finder

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    ... list . Showing availability for 25,354 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...

  13. Vaccine Safety

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    ... Search Form Controls Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... CDC.gov . Recommend on Facebook Tweet Share Compartir Vaccine Adverse Events Reporting System (VAERS) New website and ...

  14. Rotavirus Vaccine

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    ... are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common and serious health ... to 60 died. Since the introduction of the rotavirus vaccine, hospitalizations and emergency visits for rotavirus have dropped ...

  15. Contraceptive Vaccines

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Yanina Dubrovskaya

    2015-10-01

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

  19. High-dose regimen to achieve novel target trough concentration in teicoplanin.

    Science.gov (United States)

    Ueda, Takashi; Takesue, Yoshio; Nakajima, Kazuhiko; Ichki, Kaoru; Wada, Yasunao; Komatsu, Miyuki; Tsuchida, Toshie; Takahashi, Yoshiko; Ishihara, Mika; Kimura, Takeshi; Uchino, Motoi; Ikeuchi, Hiroki

    2014-01-01

    In the treatment of severe MRSA infections such as endocarditis, more than 20 mg/L of plasma trough concentration (C(min)) is recommended for teicoplanin; however, in the treatment of common MRSA infections, recommended C(min) remains more than 10 mg/L. In this study, we set C(min) as 15-30 mg/L to obtain a favorable clinical outcome in the treatment of common MRSA infections, and investigated the optimal loading regimen that achieved the target C(min) in patients with normal renal function. Seventy-eight patients received the high-dose regimen A (6 mg/kg every 12-h for initial two days) and 60 patients received the high-dose regimen B (the first five loading doses of 10-12 mg/kg at 12-h intervals for initial three days, followed by 6 mg/kg once daily). The mean C(min) on the 4th day was 13.7 ± 5.3 mg/L in regimen A, and 20.0 ± 6.6 mg/L in regimen B (P < 0.001), and the proportion of patients achieving the 15-30 mg/L was 25.6% and 68.3% (P < 0.001). Clinical response at end-of treatment were 66.7% and 85.0% (P = 0.014). The patients of initial C(min) with ≥15 mg/L had tended to be higher clinical response than those with <15 mg/L (80.9% vs 68.6%, P = 0.084). There were no significant differences in the occurrence of adverse effects in regimen A and B (nephrotoxicity; 1.3% vs 3.3%, P = 0.413, hepatotoxicity; 5.1% vs 3.3%, P = 0.608). In conclusion, to obtain C(min) 15-30 mg/L, the first five loading doses of 10-12 mg/kg at 12-h intervals was required in patients with normal renal function. Copyright © 2013 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

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

    2013-07-15

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

  1. 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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2015-05-13

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

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

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    Anbar Ran D

    2004-09-01

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

  5. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  6. Rotavirus vaccines.

    Science.gov (United States)

    Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.

    2000-10-01

    The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-01

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

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

    Science.gov (United States)

    Patel, N P; Majumdar, B; Vijayan, V

    2010-07-01

    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 (Λ), radial dose function g(L)(r) and anisotropy function F(r, θ) 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.

  10. Postoperative single-dose interstitial high-dose-rate brachytherapy in therapy-resistant keloids.

    Science.gov (United States)

    Hafkamp, C J H; Lapid, O; Dávila Fajardo, R; van de Kar, A L; Koedooder, C; Stalpers, L J; Pieters, B R

    Patients with keloids complain of the cosmetic aspect, pain, and pruritus. Many different therapies are being used for keloids. The aim of this study was to evaluate the recurrence rate and outcome after resection followed by a single-dose brachytherapy. Patients treated by resection of the keloid plus a single dose of 13 Gy high-dose-rate brachytherapy were evaluated at least 1 year after treatment. Clinical response and cosmesis were assessed by a plastic surgeon and by the patients using the Patient and Observer Scar Assessment Scale. Only 24 of the 61 invited patients responded to participate with the study; 29 keloids were evaluated. The recurrence rate was 24.1% after a median followup of 53 months (19-95 months). Patients scored on average 24.3 for their total Patient and Observer Scar Assessment Scale score (range 6-52), whereas the observer scored on average 14.6 (range 6-42). This treatment has a higher recurrence rate than that reported in most other studies. This may be explained by differences in recurrence definition, differences in followup time among studies, and selection bias because of not contributing to the study. The cosmetic outcome for evaluated patients is relatively good. This treatment policy has the advantage that patients are treated in a single day. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  11. 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)

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Influence of high-dose cortisol on the biomechanics of incubated porcine corneal strips.

    Science.gov (United States)

    Spoerl, Eberhard; Zubaty, Viktoria; Terai, Naim; Pillunat, Lutz E; Raiskup, Frederik

    2009-09-01

    To investigate the change in biomechanical properties of the cornea induced by high-dose hydrocortisone. The influence of hydrocortisone was investigated in 12 fresh porcine corneas incubated in culture medium of 2.5 muM of hydrocortisone for 7 days. Twelve additional porcine corneas incubated in culture medium without hydrocortisone for the same time served as the control group. Strips of cornea were cut and the stress-strain relationship was measured in a biomaterial tester. Young's modulus was calculated. After incubation, the thickness of the cornea was 1120+/-130 mum in the control group and 1320+/-90 mum in the hydrocortisone group. The hydrocortisone-treated corneas were 18% thicker compared to the control corneas. However, the difference in the biomechanical stress value at 10% strain was significantly larger. In the control group, the stress value measured 122+/-40 kPa, and in the hydrocortisone group, it measured 77+/-19 kPa (P=.003), representing a reduction of the corneal stiffness by 37% due to hydrocortisone treatment. Young's modulus was reduced by 42.8% from 2.90+/-1.10 MPa in the control group to 1.66+/-0.49 in the hydrocortisone group. Hydrocortisone is a modulating factor of the biomechanical properties of the cornea. The significance of the cortisol status of the patient and its influence on the biomechanical stability of the cornea should be considered in the development of keratectasia in keratoconus or after refractive surgery. Copyright 2009, SLACK Incorporated.

  14. Radiolysis of confined water: hydrogen production at a high dose rate.

    Science.gov (United States)

    Le Caër, Sophie; Rotureau, Patricia; Brunet, Francine; Charpentier, Thibault; Blain, Guillaume; Renault, Jean Philippe; Mialocq, Jean-Claude

    2005-12-09

    The production of molecular hydrogen in the radiolysis of dried or hydrated nanoporous controlled-pore glasses (CPG) has been carefully studied using 10 MeV electron irradiation at high dose rate. In all cases, the H2 yield increases when the pore size decreases. Moreover, the yields measured in dried materials are two orders of magnitude smaller than those obtained in hydrated glasses. This proves that the part of the H2 coming from the surface of the material is negligible in the hydrated case. Thus, the measured yields correspond to those of nanoconfined water. Moreover, these yields are not modified by the presence of potassium bromide, which is a hydroxyl radical scavenger. This experimental observation shows that the back reaction between H2 and HO* does not take place in such confined environments. These porous materials have been characterized before and after irradiation by means of Fourier-transform infrared (FT-IR) spectroscopy, electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) techniques, which helps to understand the elementary processes taking place in this type of environment, especially the protective effect of water on the surface in the case of hydrated glasses.

  15. Assessment of dose uniformity around high dose rate 192Ir and 60Co stepping sources.

    Science.gov (United States)

    Farhood, Bagher; Ghorbani, Mahdi

    2017-12-01

    This study aimed to evaluate dose uniformity for 192Ir and 60Co stepping sources. High dose rate 192Ir and 60Co stepping sources were simulated by the MCNPX Monte Carlo code. To investigate dose uniformity, treatment lengths of 30, 50, 100, and 150 mm with stepping distances of 3, 5, 7, and 10 mm were considered. Finally, dose uniformity for the 192Ir and 60Co stepping sources with increasing distances from the source were assessed at these treatment lengths and steps. The findings showed that the dose distribution was non-uniform for regions in close vicinity of the source, especially in the high source steps, but for most points at distances >10 mm from the center of the source, the dose distribution was uniform. For most points, the dose uniformity increased with reduction of the source steps and increments of the transverse distance from the source. The dose non-uniformity was similar for most of the corresponding points of 60Co and 192Ir sources with the same treatment lengths and source steps, except at the distance of 150 mm. When using stepping technique for the treatment of tumors, more attention should be focused on treatment planning, especially with higher stepping distances and lower transverse distances from the source.

  16. 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.)

  17. 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.

  18. 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.

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

    Science.gov (United States)

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

    2016-02-15

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

  20. Novel Use of the Contura for High Dose Rate Cranial Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Scanderbeg, Daniel J., E-mail: dscanderbeg@ucsd.edu [Department of Radiation Oncology, University of California at San Diego, La Jolla, CA (United States); Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California at San Diego, La Jolla, CA (United States); Alksne, John F. [Division of Neurological Surgery, University of California at San Diego, La Jolla, CA (United States); Lawson, Joshua D. [Department of Radiation Oncology, University of California at San Diego, La Jolla, CA (United States); Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California at San Diego, La Jolla, CA (United States); Murphy, Kevin T. [Department of Radiation Oncology, University of California at San Diego, La Jolla, CA (United States)

    2011-01-01

    A popular choice for treatment of recurrent gliomas was cranial brachytherapy using the GliaSite Radiation Therapy System. However, this device was taken off the market in late 2008, thus leaving a treatment void. This case study presents our experience treating a cranial lesion for the first time using a Contura multilumen, high-dose-rate (HDR) brachytherapy balloon applicator. The patient was a 47-year-old male who was diagnosed with a recurrent right frontal anaplastic oligodendroglioma. Previous radiosurgery made him a good candidate for brachytherapy. An intracavitary HDR balloon brachytherapy device (Contura) was placed in the resection cavity and treated with a single fraction of 20 Gy. The implant, treatment, and removal of the device were all completed without incident. Dosimetry of the device was excellent because the dose conformed very well to the target. V90, V100, V150, and V200 were 98.9%, 95.7%, 27.2, and 8.8 cc, respectively. This patient was treated successfully using the Contura multilumen balloon. Contura was originally designed for deployment in a postlumpectomy breast for treatment by accelerated partial breast irradiation. Being an intracavitary balloon device, its similarity to the GliaSite system makes it a viable replacement candidate. Multiple lumens in the device also make it possible to shape the dose delivered to the target, something not possible before with the GliaSite applicator.

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

    Science.gov (United States)

    Wang, Lin; Zhu, Yong; Wang, Danyang

    2016-12-01

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

  2. Colour removal and carbonyl by-production in high dose ozonation for effluent polishing.

    Science.gov (United States)

    Mezzanotte, V; Fornaroli, R; Canobbio, S; Zoia, L; Orlandi, M

    2013-04-01

    Experimental tests have been conducted to investigate the efficiency and the by-product generation of high dose ozonation (10-60 mg O3 L(-1)) for complete colour removal from a treated effluent with an important component of textile dyeing wastewater. The effluent is discharged into an effluent-dominated stream where no dilution takes place, and, thus, the quality requirement for the effluents is particularly strict. 30, 60 and 90 min contact times were adopted. Colour was measured as absorbance at 426, 558 and 660 nm wavelengths. pH was monitored throughout the experiments. The experimental work showed that at 50 mg L(-1) colour removal was complete and at 60 mg O3 L(-1) the final aldehyde concentration ranged between 0.72 and 1.02 mg L(-1). Glyoxal and methylglyoxal concentrations were directly related to colour removal, whereas formaldehyde, acetaldehyde, acetone and acrolein were not. Thus, the extent of colour removal can be used to predict the increase in glyoxal and methylglyoxal concentrations. As colour removal can be assessed by a simple absorbance measurement, in contrast to the analysis of specific carbonyl compounds, which is much longer and complex, the possibility of using colour removal as an indicator for predicting the toxic potential of ozone by-products for textile effluents is of great value. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. [Effects of high dose ambroxol on lung injury induced by paraquat in rats].

    Science.gov (United States)

    Ma, Yu-teng; Tian, Ying-ping; Shi, Han-wen; Lv, Cui-huan; Liu, Jian-hui; Sun, Zhi-ping

    2007-09-01

    To evaluate the protective effect of high dose ambroxol, a mucoactive drug, on acute lung injury caused by paraquat in rats. One hundred and thirty-six healthy male Sprague-Dawley rats were randomly divided into three groups: control group (n = 24) injected with normal saline intraperitoneally, PQ group (n = 56) [(2% paraquat (25 mg/kg) injected into peritoneal cavity on the first day)] and AT group (n = 56) ambroxol 35 mg/kg was injected into peritoneum daily after paraquat intoxication once daily for 7 consecutive days. The arterial gas was determined and the extent of lung injury was assessed by measuring the ratio of wet to dry weight (W/D) and protein content in BALF, the WBC count, the percentage of PMN, the content of malondialdehyde (MDA) and the levels of superoxide dismutase (SOD) in the blood and BALF respectively. Left lung tissue was observed through both light microscope and electron microscope (TEM). The white cell count and the content of protein in the blood and the BALF of PQ group were significantly higher than those of the control group (P ambroxol was administered. Treatment with ambroxol (35 mg/kg) could influence the status of oxidative stress in lung and alleviate lung injury induced by paraquat. Ambroxol has obviously therapeutic effect on paraquat poisoning.

  4. 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. PMID:25651298

  5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  7. A Retrospective Evaluation of Inpatient Transfer from High-Dose Methadone to Buprenorphine Substitution Therapy.

    Science.gov (United States)

    Oretti, Rossana

    2015-10-01

    The product license of buprenorphine/naloxone for opioid substitution therapy indicates reducing methadone concentrations to 30 mg or less per day for a minimum of 1 week before transferring patients to buprenorphine and no sooner than 24 hours after the last methadone dose, because of the risk of precipitated withdrawal and a corresponding high risk of relapse to opioid use. There are few studies describing high-dose methadone transfers. This retrospective case review assessed the feasibility of transferring patients on methadone doses above 30 mg/day to buprenorphine or buprenorphine/naloxone in the inpatient setting. Six of seven patients on 60-120 mg/day of methadone successfully completed the transfer, and four cases tested negative for opiates at long-term follow-up (6-15 months). This suggests that methadone transfer to buprenorphine can be performed rapidly without the need to taper methadone doses in patients indicated for a therapeutic switch. This small study is hypothesis-generating; larger, well-designed trials are needed to define a protocol that can be used routinely to improve and widen transfers to buprenorphine when indicated. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. 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.

  9. 3D-printed applicators for high dose rate brachytherapy: Dosimetric assessment at different infill percentage.

    Science.gov (United States)

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

    2016-12-01

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

  10. Fertility After Treatment With High Dose Melphalan in Women With Acute Myelogenous Leukemia.

    Science.gov (United States)

    Even-Or, Ehud; Ben-Haroush, Avi; Yahel, Anat; Yaniv, Isaac; Stein, Jerry

    2016-02-01

    High-dose melphalan (HDM) is an integral component of conditioning regimens for autologous and allogeneic hematopoietic stem cell transplantation for patients with malignant and non-malignant diseases. The gonadotoxic effects of HDM are often obscured by previous or concurrent administration of alkylating agents. From April 1996 to January 2006 our acute myeloid leukemia treatment regimen included induction and consolidation therapy with cytosine arabinoside, anthracyclines and etoposide, followed by HDM and autologous stem cell infusion. We explored gonadal function in surviving female patients so treated, who represent a unique group of patients exposed to HDM as a single gonadotoxic agent. The fertility assessment included a questionnaire, blood tests for luteinizing hormone, follicle stimulating hormone and anti mullerian hormone (AMH), and a gynecological ultrasound exam for antral follicular count (AFC). Eight female survivors participated. Although fertility assessment showed considerable damage to ovarian reserve in all participants, four of the eight female survivors conceived and bore children without medical intervention. In this cohort, HDM treatment reduced fertility potential but did not preclude fecundity. Early referral to a fertility clinic and long term follow-up including serial measurements of AMH levels and AFC for female patients receiving HDM are recommended. © 2015 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2002-12-01

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

  12. On the use of particle filters for electromagnetic tracking in high dose rate brachytherapy

    Science.gov (United States)

    Götz, Th I.; Lahmer, G.; Brandt, T.; Kallis, K.; Strnad, V.; Bert, Ch; Hensel, B.; Tomé, A. M.; Lang, E. W.

    2017-10-01

    Modern radiotherapy of female breast cancers often employs high dose rate brachytherapy, where a radioactive source is moved inside catheters, implanted in the female breast, according to a prescribed treatment plan. Source localization relative to the patient’s anatomy is determined with solenoid sensors whose spatial positions are measured with an electromagnetic tracking system. Precise sensor dwell position determination is of utmost importance to assure irradiation of the cancerous tissue according to the treatment plan. We present a hybrid data analysis system which combines multi-dimensional scaling with particle filters to precisely determine sensor dwell positions in the catheters during subsequent radiation treatment sessions. Both techniques are complemented with empirical mode decomposition for the removal of superimposed breathing artifacts. We show that the hybrid model robustly and reliably determines the spatial positions of all catheters used during the treatment and precisely determines any deviations of actual sensor dwell positions from the treatment plan. The hybrid system only relies on sensor positions measured with an EMT system and relates them to the spatial positions of the implanted catheters as initially determined with a computed x-ray tomography.

  13. Salvage high-dose-rate brachytherapy for esophageal cancer in previously irradiated patients: A retrospective analysis.

    Science.gov (United States)

    Wong Hee Kam, Stéphanie; Rivera, Sofia; Hennequin, Christophe; Lourenço, Nelson; Chirica, Mircea; Munoz-Bongrand, Nicolas; Gornet, Jean-Marc; Quéro, Laurent

    2015-01-01

    To evaluate outcomes after exclusive salvage high-dose-rate (HDR) intraluminal esophageal brachytherapy given to previously irradiated patients with recurrent esophageal cancer. We reviewed medical records of 30 patients who were treated by salvage HDR brachytherapy for local esophageal cancer. Brachytherapy delivered four to six fractions of 5-7 Gy at 5 mm from the applicator surface and 20 mm above and below the macroscopic tumor volume. Eighty percentage of patients received treatment as initially planned. Complete response rate, evaluated 1 month after brachytherapy by endoscopy and biopsy, was 53%. Squamous histology and complete endoscopic tumor response at 1 month were significantly associated with better local tumor control. Median local progression-free survival was 9.8 months. Overall survival was 31.5% and 17.5% at 1 and 2 years, respectively. On univariate analysis, preserved performance status and limited weight loss (brachytherapy were associated with better overall survival. Severe toxicity (Grade ≥3) occurred in 7 patients (23%). Although esophageal cancer in previously irradiated patients is associated with poor outcomes, HDR brachytherapy may be a valuable salvage treatment for inoperable patients with locally limited esophageal cancer, particularly in the subset of patients with preserved performance status and limited weight loss (≤10%) before salvage brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment.

    Science.gov (United States)

    Arenas, Meritxell; Arguís, Monica; Díez-Presa, Lorena; Henríquez, Ivan; Murcia-Mejía, Mauricio; Gascón, Marina; Gómez, David; Lafuerza, Anna; Mur, Encarna; Azón, Antoni; Rovirosa, Àngels; Sabater, Sebastià

    2015-01-01

    Nonmelanoma skin cancer (NMSC) is the commonest cancer in humans. NMSC treatment currently includes surgery, radiation therapy, and topical approaches. The objective was to analyze and compare the outcomes, toxicity, and cosmesis of NMSC treated by two hypofractionated high-dose-rate (HDR) plesiotherapy techniques. A retrospective institutional clinical study of 134 basal cell or squamous cell skin carcinomas treated at Radiation Oncology Department. Lesions were treated from November 2006 to December 2011 with a moderate hypofractionated HDR plesiotherapy using a fixed applicator or a customized mold. After a median follow-up of 33 months, overall disease-free survival at 3 and 5 years was 95.12% and 93.36%, respectively. For Leipzig applicator, disease-free survival at 3 years was 94.9% and 94.9% at 5 years, for customized mold was 93.1% at 3 years and 88% at 5 years. Complete regression was achieved in 98% of lesions. Two lesions persisted after treatment; both had been treated by a Leipzig applicator. Six lesions suffered local recurrence (five Leipzig applicators and three molds, p = 0.404). Grade skin toxicity. The cosmesis outcomes were excellent or good in 82% of patients, fair in 13%, and not available in 5%. Hypofractionated HDR plesiotherapy is an effective and well-tolerated treatment for NMSC with different toxicity levels depending on the plesiotherapy technique used. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-12-01

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

  16. Successful Treatment of Rubral Tremor by High-Dose Trihexyphenidyl: A Case Report

    Directory of Open Access Journals (Sweden)

    Li-Min Liou

    2006-03-01

    Full Text Available A 24-year-old male suffered from acute-onset right-sided hemiparesis, dysarthria, and ophthalmoplegia in February 2001. Brain magnetic resonance imaging revealed a cavernous angioma with hemorrhage over the left thalamus. Moreover, some rhythmic, coarse, low-frequency (2-3 Hz oscillation over the right wrist and elbow was noted 1 month later. Action tremor was more predominant than resting tremor. Rubral tremor was diagnosed on the basis of the clinical presentation and tremography analysis. Rubral tremor is not unusual, and pharmacotherapy is nearly always ineffective in clinical practice. Deep brain stimulation, thalamotomy, and pallidotomy are all considered effective according to recent research. However, they are either very expensive or invasive, and involve surgical risks. In our patient, we tried valproate, clonazepam, and verapamil one after another, but all in vain. Finally, titration of trihexyphenidyl provided significant benefit. The tremor was successfully controlled by a single high daily dose of trihexyphenidyl (38 mg without severe or uncomfortable side effects. Here, we report a case of successful monotherapy of rubral tremor with high-dose trihexyphenidyl.

  17. Probable Nonconvulsive Status Epilepticus With the Use of High-Dose Continuous Infusion Ceftazidime.

    Science.gov (United States)

    Collins, Reagan D; Tverdek, Frank P; Bruno, Jeffrey J; Coyle, Elizabeth A

    2016-12-01

    Multidrug resistant (MDR) bacterial infections are a major concern of health care providers due to their increasing incidence and associated mortality. In some cases, few or no antibiotics have preserved activity. Beta-lactam administration via continuous infusion can optimize time over minimum inhibitory concentration (MIC). In some cases, use of high-dose continuous infusion (HDCI) may be necessary to achieve serum levels in excess of nonsusceptible MIC values. The use of HDCI beta-lactams is not without risk, specifically neurotoxic adverse effects, which appear dose related. We describe a 64-year-old male who experienced myoclonus and nonconvulsive status epilepticus while receiving HDCI ceftazidime for treatment of multidrug resistant Pseudomonas aeruginosa bacteremia. This report serves as a cautionary example of the potential toxicities associated with HDCI beta-lactams and supports the importance of risk-benefit analysis prior to and during treatment. Additionally, the use of serum drug level monitoring may be necessary to better prevent or predict toxicity. © The Author(s) 2015.

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

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Bangsbo, Jens

    2014-01-01

    PURPOSE: The purpose of the present study was to investigate the effect of high-dose inhaled terbutaline on muscle strength, maximal sprinting, and time-trial performance in trained men. METHODS: Nine non-asthmatic males with a [Formula: see text] of 58.9 ± 3.1 ml min(-1) kg(-1) (mean ± SEM......) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test...... = 0.019) and 3.3 ± 1.0 % (P = 0.009) higher for terbutaline than placebo. Net accumulation of plasma lactate was higher (P = 0.003) for terbutaline than placebo during the Wingate test, whereas [Formula: see text] above baseline was unchanged by terbutaline (P = 0.882). Time-trial performance...

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

    Science.gov (United States)

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

    2016-04-01

    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A. © The Author(s) 2016.

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

    Science.gov (United States)

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

    2003-05-01

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

  1. A dose verification method for high-dose-rate brachytherapy treatment plans.

    Science.gov (United States)

    Kumar, Rajesh; Sharma, S D; Vijaykumar, C; Deshpande, Sudesh; Sharma, P K; Vandana, S; Philomena, A; Chilkulwar, Ravi H

    2008-01-01

    To evolve a fast dose verification method for high-dose-rate (HDR) brachytherapy treatment plans and to demonstrate its applicability in different clinical cases. We developed a software tool in VC++ for the Varisource HDR unit for HDR dosimetry plan verification using TG-43 parameters. HDR treatment dosimetry of a number clinical cases using Varisource was verified by comparison with the treatment planning system (TPS). A number of different types of clinical cases treated by Varisource were evaluated. TPS calculated dose values and verification code calculated dose values were found to agree to within 3% for most of the dose calculation points. We have validated with clinical cases a fast and independent dose verification method of the dosimetry at selected points for HDR brachytherapy treatments plan using TG-43 parameters. This can be used for the verification of the TPS calculated dose at various points. The code is written to work with Varisource, but it can conceivably be modified for other sources also by using the fitted constant of the respective source.

  2. 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)

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  5. High dose rate 192Ir source calibration: A single institution experience

    Science.gov (United States)

    Abdullah, R.; Abdullah, N. H.; Mohamed, M.; Idris, N. R. N.; Yusoff, A. L.; Chen, S. C.; Zakaria, A.

    2017-05-01

    Measurement of source strength of new high dose rate (HDR) 192Ir supplied by the manufacturer is part of quality assurance recommended by Radiation Safety Section, Ministry of Health of Malaysia. The source strength is determined in reference air kerma rate (RAKR). The purpose of this study was to evaluate RAKR measurement of 192Ir using well-type ionisation chamber with RAKR stated in the certificate provided by the manufacturer. A retrospective study on 19 MicroSelectron HDR 192Ir Classic from 2001 to 2009 and 12 MicroSelectron HDR 192Ir V2 sources from 2009 to 2016 supplied by manufacturer were compared. From the study, the agreement between measured RAKR and RAKR stated in the certificate by manufacturer for all 32 sources supplied were within ±2.5%. As a conclusion, a threshold level of ±2.5% can be used as suitable indicator to spot problems of the brachytherapy system in Department of Nuclear Medicine Radiotherapy and Oncology, Hospital USM.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    1996-01-01

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

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

    Science.gov (United States)

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

    2015-02-01

    To characterize a new function of the water-soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats. © 2014 Japanese Teratology Society.

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

    Directory of Open Access Journals (Sweden)

    Alexander Olawaiye

    2011-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  11. 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)

  12. 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.

  13. High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients.

    Science.gov (United States)

    Amigoni, A; Vettore, E; Brugnolaro, V; Brugnaro, L; Gaffo, D; Masola, M; Marzollo, A; Pettenazzo, A

    2014-12-01

    Critically ill children can develop withdrawal syndrome after prolonged analgesia and sedation in a paediatric intensive care unit (PICU), when treatment is stopped abruptly or reduced quickly. The aim of this study was to evaluate the incidence of withdrawal syndrome in patients after three or more days of analgesic or sedative drug therapy, using a validated scale. We also analysed the association between withdrawal syndrome and the patients' outcome and factors related to analgesia and sedation treatment. This prospective observational study analysed 89 periods of weaning from analgesia and sedation in 60 children between October 2010 and October 2011. Of these, 65% were less than six months old and 45% were admitted to the PICU after heart surgery. Withdrawal syndrome was assessed using the Withdrawal Assessment Tool-1 (WAT-1) scale. The incidence of withdrawal syndrome was 37%, and the only variable that predicted its presence was the highest administered dose of benzodiazepine. The duration of weaning, Sophia Observational Withdrawal Symptom scale score and nurse judgment were also associated with positive WAT-1 scores. Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  14. An unusual finding of massive pulmonary embolism in a patient during treatment with high-dose ibuprofen.

    Science.gov (United States)

    Bilora, Franca; Adamo, Angelo; Pomerri, Fabio; Prandoni, Paolo

    2016-02-01

    Non-steroidal anti-inflammatory drugs have been associated with an increased risk of venous thromboembolism. We report for the first time, the case of a patient who developed massive pulmonary embolism after a long period of treatment with high doses of ibuprofen. A 65-year-old woman was admitted with severe dyspnea while on treatment with high doses of ibuprofen for diffuse spine pain due to arthrosis. A spiral computed tomography showed a massive pulmonary embolism. No other explanation for the thromboembolic disorder was found. She was successfully treated with therapeutic doses of low-molecular-weight heparin followed by rivaroxaban. Ibuprofen was discontinued and replaced by tramadol. High-dose ibuprofen is likely to have accounted for the life-threatening thromboembolic disorder.

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

    Science.gov (United States)

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

    2014-10-01

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

  16. Vaccine allergies.

    Science.gov (United States)

    Chung, Eun Hee

    2014-01-01

    Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered.

  17. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Association between thimerosal-containing vaccine and autism.

    Science.gov (United States)

    Hviid, Anders; Stellfeld, Michael; Wohlfahrt, Jan; Melbye, Mads

    2003-10-01

    Mercuric compounds are nephrotoxic and neurotoxic at high doses. Thimerosal, a preservative used widely in vaccine formulations, contains ethylmercury. Thus it has been suggested that childhood vaccination with thimerosal-containing vaccine could be causally related to neurodevelopmental disorders such as autism. To determine whether vaccination with a thimerosal-containing vaccine is associated with development of autism. Population-based cohort study of all children born in Denmark from January 1, 1990, until December 31, 1996 (N = 467 450) comparing children vaccinated with a thimerosal-containing vaccine with children vaccinated with a thimerosal-free formulation of the same vaccine. Rate ratio (RR) for autism and other autistic-spectrum disorders, including trend with dose of ethylmercury. During 2 986 654 person-years, we identified 440 autism cases and 787 cases of other autistic-spectrum disorders. The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine (RR, 0.85 [95% confidence interval [CI], 0.60-1.20] for autism; RR, 1.12 [95% CI, 0.88-1.43] for other autistic-spectrum disorders). Furthermore, we found no evidence of a dose-response association (increase in RR per 25 microg of ethylmercury, 0.98 [95% CI, 0.90-1.06] for autism and 1.03 [95% CI, 0.98-1.09] for other autistic-spectrum disorders). The results do not support a causal relationship between childhood vaccination with thimerosal-containing vaccines and development of autistic-spectrum disorders.

  20. Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Christina [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany); Engenhart-Cabillic, Rita; Vorwerk, Hilke [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre [Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany)

    2017-02-15

    Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed. From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy. PFT data were collected before treatment and 6 weeks, 12 weeks, and 6 months after RT. The influence of patient- and treatment-related factors on PFT was analyzed. Mean forced expiratory volume in 1 s (FEV1) constantly declined during follow-up (p = 0.001). In total, 68% of patients had a reduced FEV1 at 6 months. Mean vital capacity (VC) didn't change during follow-up (p > 0.05). Mean total lung capacity (TLC) showed a constant decline after RT (p = 0.026). At 6 months, 60% of patients showed a decline in VC and 73% in TLC. The mean diffusion capacity for carbon monoxide (DLCO) declined at 6 and 12 weeks, but recovered slightly at 6 months (p < 0.0005). At 6 months, 86% of patients had a reduced DLCO. After treatment, the partial pressure of CO{sub 2} in the blood (pCO{sub 2}) was increased and pO{sub 2} was decreased (p > 0.05). Only the pretreatment PFT classification had a significant influence on the post-RT FEV1. DLCO seems to be the most reliable indicator for lung tissue damage after thoracic RT. Ventilation parameters appear to be less reliable. Concerning patient- or treatment-related factors, no reliable conclusion can be drawn regarding which factors may be relevant. (orig.) [German] Patientenbezogene, therapiebezogene und Lungenfunktionsdaten (''pulmonary function test'', PFT) wurden vor Radiotherapie (RT) und an verschiedenen Nachsorgeterminen nach RT prospektiv gesammelt, um PFT-Veraenderungen sowie Einflussfaktoren nach Hochdosis-Radio(chemo)therapie zu

  1. Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy. Efficacy and outcome

    Energy Technology Data Exchange (ETDEWEB)

    Mohnike, K. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Radiologie und Nuklearmedizin, Magdeburg (Germany); DTZ am Frankfurter Tor, Berlin (Germany); Neumann, K.; Seidensticker, M.; Seidensticker, R.; Pech, M.; Streitparth, T.; Ricke, J. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Radiologie und Nuklearmedizin, Magdeburg (Germany); Hass, P.; Gademann, G. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Strahlentherapie, Magdeburg (Germany); Klose, S. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Nieren- und Hochdruckkrankheiten, Diabetologie und Endokrinologie, Magdeburg (Germany); Garlipp, B.; Benckert, C. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Allgemein-, Viszeral- und Gefaesschirurgie, Magdeburg (Germany); Wendler, J.J.; Liehr, U.B.; Schostak, M. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Urologie und Kinderurologie, Magdeburg (Germany); Goeppner, D. [Universitaetsklinikum Magdeburg A.oe.R., Otto-von-Guericke-Universitaet, Klinik fuer Dermatologie, Magdeburg (Germany)

    2017-08-15

    To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment. (orig.) [German] Beurteilung der Effektivitaet, Sicherheit und Ergebnisse nach bildgefuehrter High-dose-rate-(HDR-)Brachytherapie bei Patienten mit Nebennierenmetastasen. Von Januar 2007 bis April 2014 wurden 37 Patienten (7 weiblich, 30 maennlich; mittleres Alter 66,8 Jahre, Spanne 41,5-82,5 Jahre) mit Nebennierenmetastasen verschiedener Primarien mit CT-gesteuerter interstitieller HDR-Brachytherapie (iBT) behandelt. Der primaere Endpunkt war die lokale Tumorkontrolle (LTC). Sekundaere Endpunkte umfassten die Zeit bis zum nicht mehr behandelbaren Progress (TTUP), die Zeit bis zum Progress (TTP), das Gesamtueberleben (OS) und die Sicherheit der Methode. In einer sekundaeren Analyse wurden Risikofaktoren

  2. 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

  3. FLU VACCINATION

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  4. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  5. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  6. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

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

    Science.gov (United States)

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

    2009-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2011-10-01

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

  10. 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.

  11. High-dose treatment with pergolide in Parkinson's disease patients with motor fluctuations and dyskinesias.

    Science.gov (United States)

    Storch, Alexander; Trenkwalder, Claudia; Oehlwein, Christian; Winkelmann, Juliane; Polzer, Ulrich; Hundemer, Hans-Peter; Schwarz, Johannes

    2005-09-01

    Motor complications arising after long-term treatment with levodopa remain one of the main challenges in the treatment of patients with Parkinson's disease (PD). Monotherapy with dopamine agonists may delay the onset of motor complications or reduce their severity when added to levodopa treatment. Here, we retrospectively analyzed data from 62 patients with advanced PD who presented with moderate to severe response fluctuations in whom we increased the dose of oral treatment with pergolide beyond 4.5mg daily. Patients had been treated with levodopa for 10.7+/-4.8 years. Pergolide was increased to 8.2+/-4.3 mg per day over a median titration period of 13.5 weeks. Mean daily dose of levodopa prior to pergolide high-dose treatment was 733+/-468 mg and decreased to 348+/-186 mg after pergolide titration. The duration of OFF times decreased from 7.3+/-3.8 to 1.7+/-0.9 h per day (p patients' diaries. Dyskinesias, present for 5.0+/-3.3 h per day at baseline, were reduced to 1.4+/-0.8 h per day (p motor fluctuations (off-time duration plus dyskinesia duration) decreased from 10.5+/-7.0 to 2.8+/-2.2 h (p patients required concomitant treatment with domperidone. Seven patients developed hallucinations during the titration period, six patients required treatment with clozapine. Our data indicate that increasing the dose of pergolide above 5mg per day can dramatically reduce the need for levodopa, motor fluctuations and severity of clinical symptoms. Controlled trials are needed to further substantiate the efficacy and safety of this treatment strategy.

  12. 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.

  13. 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.

  14. 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.

  15. Online pretreatment verification of high-dose rate brachytherapy using an imaging panel

    Science.gov (United States)

    Fonseca, Gabriel P.; Podesta, Mark; Bellezzo, Murillo; Van den Bosch, Michiel R.; Lutgens, Ludy; Vanneste, Ben G. L.; Voncken, Robert; Van Limbergen, Evert J.; Reniers, Brigitte; Verhaegen, Frank

    2017-07-01

    Brachytherapy is employed to treat a wide variety of cancers. However, an accurate treatment verification method is currently not available. This study describes a pre-treatment verification system that uses an imaging panel (IP) to verify important aspects of the treatment plan. A detailed modelling of the IP was only possible with an extensive calibration performed using a robotic arm. Irradiations were performed with a high dose rate (HDR) 192Ir source within a water phantom. An empirical fit was applied to measure the distance between the source and the detector so 3D Cartesian coordinates of the dwell positions can be obtained using a single panel. The IP acquires 7.14 fps to verify the dwell times, dwell positions and air kerma strength (Sk). A gynecological applicator was used to create a treatment plan that was registered with a CT image of the water phantom used during the experiments for verification purposes. Errors (shifts, exchanged connections and wrong dwell times) were simulated to verify the proposed verification system. Cartesian source positions (panel measurement plane) have a standard deviation of about 0.02 cm. The measured distance between the source and the panel (z-coordinate) have a standard deviation up to 0.16 cm and maximum absolute error of  ≈0.6 cm if the signal is close to sensitive limit of the panel. The average response of the panel is very linear with Sk. Therefore, Sk measurements can be performed with relatively small errors. The measured dwell times show a maximum error of 0.2 s which is consistent with the acquisition rate of the panel. All simulated errors were clearly identified by the proposed system. The use of IPs is not common in brachytherapy, however, it provides considerable advantages. It was demonstrated that the IP can accurately measure Sk, dwell times and dwell positions.

  16. Effects of Intratympanic Dexamethasone on High-Dose Radiation Ototoxicity In Vivo.

    Science.gov (United States)

    Dinh, Christine T; Chen, Si; Dinh, John; Goncalves, Stefania; Bas, Esperanza; Padgett, Kyle; Johnson, Perry; Elsayyad, Nagy; Telischi, Fred; Van De Water, Thomas

    2017-02-01

    Stereotactic radiosurgery for lateral skull base tumors can cause hearing loss when the cochleae are exposed to high doses of single-fraction radiation. Currently, there are no known nondosimetric preventative treatments for radiation-induced ototoxicity. Intratympanic (IT) dexamethasone (DXM), a synthetic steroid, protects against radiation-induced auditory hair cell (HC) and hearing losses in rats in vivo. Seven rats received radiation (12 Gy) to both cochleae. In irradiated rats and six nonirradiated rats, IT DXM was randomized to one ear, while tympanic puncture without DXM was performed on the contralateral ear. Baseline and 4-week postradiation auditory-evoked potential tests were performed. The cochleae were processed for HC viability. Cochleae exposed to radiation demonstrated more outer HC (OHC) loss in all turns than nonirradiated ears (p <0.05). OHCs were more susceptible to radiation injury than inner HCs in the middle and basal turns (p <0.05). In irradiated cochleae, there was a nonsignificant trend for less OHC loss with IT DXM in the basal turn when compared with placebo. IT DXM did not improve radiation-induced hearing threshold shifts; however, a high rate of tympanic membrane perforations occurred with irradiated ears which may contribute to this finding. Radiation induced loss of OHCs in all turns of the cochlea. IT DXM reduced OHC loss in the basal turn of irradiated ears; however, this finding did not achieve statistical significance. Although IT DXM did not affect radiation-induced hearing threshold shifts in adult rats in vivo, this may be due to a high rate of tympanic membrane perforations.

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

    Science.gov (United States)

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

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

  18. High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D.

    Science.gov (United States)

    Davidson, Mayer B; Duran, Petra; Lee, Martin L; Friedman, Theodore C

    2013-02-01

    Low vitamin D levels predict the development of diabetes. This double-blind, randomized, control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion, insulin sensitivity, and the development of diabetes. A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels. Subjects with A1C levels of 5.8-6.9% underwent an oral glucose tolerance test (OGTT). Subjects with prediabetes and 25-OH vitamin D (25-OHD) levels <30 ng/mL were randomized to receive weekly placebo (n = 53) or vitamin D (n = 56) with doses based on body weight and baseline 25-OHD levels. OGTTs were performed 3, 6, 9, and 12 months later. Insulin secretion and sensitivity were measured, and the proportion of subjects developing diabetes was assessed. 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU. There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose, 2-h glucose, or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance. No subjects experienced increased serum or urinary calcium levels. At 12 months, A1C levels were significantly slightly less (0.2%) in the vitamin D group. In individuals with prediabetes and hypovitaminosis D, doses of vitamin D supplementation designed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion, insulin sensitivity, or the development of diabetes compared with placebo administration.

  19. Bystander effect between zebrafish embryos in vivo induced by high-dose X-rays.

    Science.gov (United States)

    Choi, V W Y; Ng, C Y P; Kobayashi, A; Konishi, T; Suya, N; Ishikawa, T; Cheng, S H; Yu, K N

    2013-06-18

    We employed embryos of the zebrafish, Danio rerio, for our studies on the in vivo bystander effect between embryos irradiated with high-dose X-rays and naive unirradiated embryos. The effects on the naive whole embryos were studied through quantification of apoptotic signals at 25 h post fertilization (hpf) through the terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay followed by counting the stained cells under a microscope. We report data showing that embryos at 5 hpf subjected to a 4-Gy X-ray irradiation could release a stress signal into the medium, which could induce a bystander effect in partnered naive embryos sharing the same medium. We further demonstrated that this bystander effect (induced through partnering) could be successfully suppressed through the addition of the nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) into the medium but not through the addition of the CO liberator tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). This shows that NO was involved in the bystander response between zebrafish embryos induced through X-ray irradiation. We also report data showing that the bystander effect could be successfully induced in naive embryos by introducing them into the irradiated embryo conditioned medium (IECM) alone, i.e., without partnering with the irradiated embryos. The IECM was harvested from the medium that had conditioned the zebrafish embryos irradiated at 5 hpf with 4-Gy X-ray until the irradiated embryos developed into 29 hpf. NO released from the irradiated embryos was unlikely to be involved in the bystander effect induced through the IECM because of the short life of NO. We further revealed that this bystander effect (induced through IECM) was rapidly abolished through diluting the IECM by a factor of 2× or greater, which agreed with the proposal that the bystander effect was an on/off response with a threshold.

  20. 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.

  1. Intracranial hypertension secondary to high dose cytosine arabinoside - A case study.

    Science.gov (United States)

    Nurgat, Z A; Alzahrani, H; Lawrence, M; Mannan, A; Ashour, M; Rasheed, W; Aljurf, M

    2017-05-01

    We report a rare case of intracranial hypertension following high dose cytosine arabinoside (HiDAC) in a 20-year-old man, with precursor B-cell acute lymphoblastic leukemia (ALL). A five drug induction protocol for ALL was initiated; post induction consolidation was with HiDAC (3 g/m2 IV every 12 h on days 1, 3 and 5). Post consolidation, cytogenetic remission was attained and he received an intensification and maintenance regimen for ALL, for a period of approximately 24 months. Four months following the completion of his treatment, the patient relapsed within the central nervous system (CNS). Intravenous salvage chemotherapy was initiated using a combination of fludarabine 30 mg/m2, followed by cytarabine 2 g/m2 4 h later on days 1 through 5 (FA). On day # 23 of FA, he developed a severe headache. A gadolinium-enhanced brain magnetic resonance imaging (MRI) revealed increased intracranial pressure. On day # 25, ophthalmology examination suggested bilateral papilledema. He was started on acetazolamide 250 mg twice daily. He had spontaneous resolution of his symptoms. The patient had no recurrence of papilledema or any other neurological symptoms. Intracranial hypertension secondary to HiDAC, is an exceedingly rare complication and is not regularly associated as a common side effect of cytarabine administration. Prompt action in diagnosing and treating intracranial hypertension will save the patient from consequences, such as loss of vision, that are prevalent in this condition. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets.

    Science.gov (United States)

    Taipale-Kovalainen, Krista; Karttunen, Anssi-Pekka; Ketolainen, Jarkko; Korhonen, Ossi

    2018-03-30

    The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental design was used to generate a structured study plan which involved 19 runs. The formulation variables studied were the type of lubricant (magnesium stearate or stearic acid) and its concentration (0.5, 1.0 and 1.5%). Process variables were total production feed rate (5, 10.5 and 16kg/h), mixer speed rpm (500, 850 and 1200rpm), and mixer inlet port for lubricant (A or B). The continuous direct compression tableting line consisted of loss-in-weight feeders, a continuous mixer and a tablet press. The Quality Target Product Profile (QTPP) was defined for the final product, as the flowability of powder blends (2.5s), tablet strength (147N), dissolution in 2.5min (90%) and ejection force (425N). A design space was identified which fulfilled all the requirements of QTPP. The type and concentration of lubricant exerted the greatest influence on the design space. For example, stearic acid increased the tablet strength. Interestingly, the studied process parameters had only a very minor effect on the quality of the final product and the design space. It is concluded that the continuous direct compression tableting process itself is insensitive and can cope with changes in lubrication, whereas formulation parameters exert a major influence on the end product quality. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Automated high-dose rate brachytherapy treatment planning for a single-channel vaginal cylinder applicator

    Science.gov (United States)

    Zhou, Yuhong; Klages, Peter; Tan, Jun; Chi, Yujie; Stojadinovic, Strahinja; Yang, Ming; Hrycushko, Brian; Medin, Paul; Pompos, Arnold; Jiang, Steve; Albuquerque, Kevin; Jia, Xun

    2017-06-01

    High dose rate (HDR) brachytherapy treatment planning is conventionally performed manually and/or with aids of preplanned templates. In general, the standard of care would be elevated by conducting an automated process to improve treatment planning efficiency, eliminate human error, and reduce plan quality variations. Thus, our group is developing AutoBrachy, an automated HDR brachytherapy planning suite of modules used to augment a clinical treatment planning system. This paper describes our proof-of-concept module for vaginal cylinder HDR planning that has been fully developed. After a patient CT scan is acquired, the cylinder applicator is automatically segmented using image-processing techniques. The target CTV is generated based on physician-specified treatment depth and length. Locations of the dose calculation point, apex point and vaginal surface point, as well as the central applicator channel coordinates, and the corresponding dwell positions are determined according to their geometric relationship with the applicator and written to a structure file. Dwell times are computed through iterative quadratic optimization techniques. The planning information is then transferred to the treatment planning system through a DICOM-RT interface. The entire process was tested for nine patients. The AutoBrachy cylindrical applicator module was able to generate treatment plans for these cases with clinical grade quality. Computation times varied between 1 and 3 min on an Intel Xeon CPU E3-1226 v3 processor. All geometric components in the automated treatment plans were generated accurately. The applicator channel tip positions agreed with the manually identified positions with submillimeter deviations and the channel orientations between the plans agreed within less than 1 degree. The automatically generated plans obtained clinically acceptable quality.

  7. High Dose Oral Furosemide with Salt Ingestion in the Treatment of Refractory Ascites of Liver Cirrhosis.

    Science.gov (United States)

    Yakar, Tolga; Demir, Mehmet; Dogan, Ozlem; Parlakgumus, Alper; Ozer, Birol; Serin, Ender

    2016-12-01

    We aimed to evaluate and compare the efficacy and safety of high-dose furosemide+salt orally by comparing HSS+ furosemide (i.v.) and repeated paracentesis in patients with RA. This was a prospective study of 78 cirrhotic patients with RA, randomized into three groups: Group A (n= 25) i.v. furosemide (200-300 mg bid) and 3% hypotonic saline solution (HSS) (once or twice a day); Group B (n= 26) oral furosemide tablets (360-520 mg bid) and salt (2.5 g bid); and, Group C (n= 27) repeated large-volume-paracentesis (RLVP) with albumin infusion. Patients without hyperkalemia were administrated 100 mg of spironolactone/day. During the follow-up; INR, creatinine, and total bilirubin levels were measured to determine the change in MELD (model of end stage liver disease) score. Hepatic encephalopathy (HE), severe episodes of spontaneous bacterial peritonitis (SBP) and pleural effusions (PE) occurred more frequently in Group C. Improvement in Child-Pugh and MELD score was better in Group A and B than Group C. In Group B, improvements were seen in the Child-Pugh and MELD score, reduction in body weight, duration and number of hospitalization. In Groups A and B, remarkable increases in diuresis were observed (706±116 to 2425±633 mL and 691±111 to 2405±772 mL) and serum sodium levels also improved. HE and SBP were occurred more often in group C (pfurosemide with salt ingestion may be an alternative, effective, safe and well-tolerated method of therapy for RA.

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

    Science.gov (United States)

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

    2018-01-01

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

  9. Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer.

    Science.gov (United States)

    Fiorino, Claudio; Sanguineti, Giuseppe; Cozzarini, Cesare; Fellin, Gianni; Foppiano, Franca; Menegotti, Loris; Piazzolla, Anna; Vavassori, Vittorio; Valdagni, Riccardo

    2003-11-15

    To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.

  10. Chronical cervical infections and dysplasia (CIN I, CIN II): Vaginal vitamin D (high dose) treatment

    Science.gov (United States)

    Schulte-Uebbing, C; Schlett, S; Craiut, ID; Antal, L; Olah, H

    2014-01-01

    In a small praxis/ambulance study we evaluated data of 200 women with chronical recurrent cervical infections and with a cervix dysplasia (CIN 1, CIN 2). who got after the primary therapy a treatment with vitamin D vaginal suppositories (12.500 IU, 3 nights a week, for 6 weeks). We found that - when compared with the lactobacillus vaginal suppositories - the high dose vitamin D vaginal treatment might be more effective. Vitamin D showed very good anti-inflammatory effects. In the survey after six weeks therapy 79% of the women had “less vaginal problems,” “less discharge” and “less problems with the sexual intercourse.” Objectively after six weeks therapy only 7% of the patients still had bacterial and/or fungal vaginal infections that required a treatment. We found that vitamin D is reabsorbed by the vaginal mucosa, but the reabsorption may be individually very different. In the CIN 1 group we found six weeks after treatment good antidysplastic effects, in the CIN 2 group we often found no or only temporary antidysplastic effects. So this vaginal vitamin D treatment method might be an option for the therapy and prevention of chronical cervical infections and maybe of a cervic dysplasia CIN 1 (good antiinflammatory effects, antidysplastic effects). This small study is not representative. We need much bigger studies with much more dates and with a longer follow up. Caution: At the moment we do not know, if the vaginal vitamin D treatment with 12500 IE is possible in pregnancy. We have no experience. Therefore we recommend an effective contraception during the application. PMID:24605180

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

    Science.gov (United States)

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

    We have retrospectively analyzed the outcomes of high-dose-rate (HDR) brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer. From 1997 to 2012, salvage HDR brachytherapy was performed in 43 patients. The median age was 64 years (range, 41-88 years). HDR brachytherapy was performed by interstitial brachytherapy in 34 patients (79%) and by intracavity brachytherapy in nine patients (21%). Seventeen (40%) of the 43 patients were treated with external beam radiotherapy. The median followup period was 58 months (range, 6-179 months). The 5-year overall survival (OS), progression-free survival (PFS), and local control rates (LC) were 84%, 52%, and 78%, respectively. Patients who received brachytherapy with external beam radiotherapy experienced no nodal recurrence (0 of 17 patients), whereas 23% of the patients (6 of 26 patients) who received brachytherapy alone experienced nodal recurrence (p = 0.047). The pathologic grade at the time of initial surgery (G1-2 vs. G3) was found to be a significant prognostic factor for both OS and PFS. The respective 5-year OS was 96% vs. 40% (p brachytherapy vs. intracavity brachytherapy) were significant prognostic factors for LC. The respective 5-year LC was 74% vs. 100% (p = 0.020) and 85% vs. 56% (p = 0.035). HDR brachytherapy is effective and feasible in patients with isolated vaginal recurrence of endometrial cancer. Pathologic grade, age, and modality were significant prognostic factors. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  12. High-dose-rate brachytherapy of rhabdomyosarcoma limited to the external auditory canal.

    Science.gov (United States)

    King, Martin T; Voros, Laszlo; Cohen, Gil'ad N; Lanning, Ryan M; Ganly, Ian; O'Suoji, Chibuzo C; Wolden, Suzanne L

    To report on the single-catheter high-dose-rate brachytherapy treatment of a 21-month-old girl child with an embryonal, botryoid-type, rhabdomyosarcoma limited to the external auditory canal (EAC). A 2.4-mm diameter catheter was inserted into the right EAC and placed against the tympanic membrane. A computed tomography simulation scan was acquired. A brachytherapy treatment plan, in which 21 Gy in seven fractions was prescribed to a 1-mm depth along the distal 2 cm of the catheter, was generated. Treatments were delivered under anesthesia without complication. A dosimetric comparison between this plan and an intensity-modulated radiation therapy (IMRT) plan was then conducted. A clinical target volume (CTV), which encompassed a 1-mm margin along the distal 2 cm of the catheter, was delineated for both plans. Given positioning uncertainty under image guidance, a planning target volume (PTV = CTV + 3-mm margin) was defined for the IMRT plan. The IMRT plan was optimized for maximal CTV coverage but subsequently normalized to the same CTV volume receiving 100% of the prescription dose (V100) of the brachytherapy plan. The IMRT plan was normalized to the brachytherapy CTV V100 of 82.0%. The PTV V100 of this plan was 34.1%. The PTV exhibited dosimetric undercoverage within the middle ear and toward the external ear. Mean cochlea doses for the IMRT and brachytherapy plans were 26.7% and 10.5% of prescription, respectively. For rhabdomyosarcomas limited to the EAC, a standard brachytherapy catheter can deliver a highly conformal radiation plan that can spare the nearby cochlea from excess radiation. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  13. Radiochromic film-based quality assurance for CT-based high-dose-rate brachytherapy.

    Science.gov (United States)

    Asgharizadeh, Saeid; Bekerat, Hamed; Syme, Alasdair; Aldelaijan, Saad; DeBlois, François; Vuong, Té; Evans, Michael; Seuntjens, Jan; Devic, Slobodan

    2015-01-01

    In the past, film dosimetry was developed into a powerful tool for external beam radiotherapy treatment verification and quality assurance. The objective of this work was the development and clinical testing of the EBT3 model GafChromic film based brachytherapy quality assurance (QA) system. Retrospective dosimetry study was performed to test a patient-specific QA system for preoperative endorectal brachytherapy that uses a radiochromic film dosimetry system. A dedicated phantom for brachytherapy applicator used for rectal cancer treatment was fabricated enabling us to compare calculated-to-measured dose distributions. Starting from the same criteria used for external beam intensity-modulated radiation therapy QA (3%, 3 mm), passing criteria for high- and low-dose gradient regions were subsequently determined. Finally, we investigated the QA system's sensitivity to controlled source positional errors on selected patient plans. In low-dose gradient regions, measured dose distributions with criteria of 3%, 3 mm barely passed the test, as they showed 95% passing pixels. However, in the high-dose gradient region, a more stringent condition could be established. Both criteria of 2%, 3 mm and 3%, 2 mm with gamma function calculated using normalization to the same absolute dose value in both measured and calculated dose distributions, and matrix sizes rescaled to match each other showed more than 95% of pixels passing, on average, for 15 patient plans analyzed. Although the necessity of the patient-specific brachytherapy QA needs yet to be justified, we described a radiochromic film dosimetry-based QA system that can be a part of the brachytherapy commissioning process, as well as yearly QA program. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Impact of source position on high-dose-rate skin surface applicator dosimetry.

    Science.gov (United States)

    Jeong, Jeho; Barker, Christopher A; Zaider, Marco; Cohen, Gil'ad N

    2016-01-01

    Skin surface dosimetric discrepancies between measured and treatment planning system predicted values were traced to source position sag inside the applicator and to source transit time. We quantified their dosimetric impact and propose corrections for clinical use. We measured the dose profiles from the Varian Leipzig-style high-dose-rate (HDR) skin applicator, using EBT3 film, photon diode, and optically stimulated luminescence dosimeter for three different GammaMedplus HDR afterloaders. The measured dose profiles at several depths were compared with BrachyVision Acuros calculated profiles. To assess the impact of the source sag, two different applicator orientations were considered. The dose contribution during source transit was assessed by comparing diode measurements using an HDR timer and an electrometer timer. Depth doses measured using the three dosimeters were in good agreement, but were consistently higher than the Acuros dose calculations. Measurements with the applicator face up were significantly (exceeding 10%) lower than those in the face down position, due to source sag inside the applicator. Based on the inverse square law, the effective source sag was evaluated to be about 0.5 mm from the planned position. The additional dose during source transit was evaluated to be about 2.8% for 30 seconds of treatment with a 40700 U (10 Ci) source. With a very short source-to-surface distance, the small source sag inside the applicator has a significant dosimetric impact. This effect is unaccounted for in the vendor's treatment planning template and should be considered before the clinical use of the applicator. Further investigation of other applicators with large source lumen diameter may be warranted. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Graeme M Doodnaught

    2017-10-01

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

  16. 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.

  17. 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.

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

    Science.gov (United States)

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

    2011-05-01

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

  19. 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.

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

    Science.gov (United States)

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

    2010-06-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Ivan M. Buzurovic

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Metha Maenhout

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Daya Nand Sharma

    2016-01-01

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

  5. Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer

    Directory of Open Access Journals (Sweden)

    Ivan M. Buzurovic

    2016-08-01

    Full Text Available Purpose : In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA and the initial clinical experience in high-dose-rate (HDR brachytherapy treatment of esophageal cancer, using this applicator. Material and methods: Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient’s response to the treatment were elaborated as well. Results : The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. Conclusions : The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can

  6. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT be ... What is live, attenuated influenza vaccine-LAIV (nasal spray)?A dose of flu vaccine is recommended every flu season. Children younger ...

  7. Introduction of translation stop condons into the viral glycoprotein gene in a fish DNA vaccine eliminates induction of protective immunity

    Science.gov (United States)

    Garver, Kyle A.; Conway, Carla M.; Kurath, Gael

    2006-01-01

    A highly efficacious DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was mutated to introduce two stop codons to prevent glycoprotein translation while maintaining the plasmid DNA integrity and RNA transcription ability. The mutated plasmid vaccine, denoted pIHNw-G2stop, when injected intramuscularly into fish at high doses, lacked detectable glycoprotein expression in the injection site muscle, and did not provide protection against lethal virus challenge 7 days post-vaccination. These results suggest that the G-protein itself is required to stimulate the early protective antiviral response observed after vaccination with the nonmutated parental DNA vaccine.

  8. Introduction of translation stop codons into the viral glycoprotein gene in a fish DNA vaccine eliminates induction of protective immunity

    Science.gov (United States)

    Garver, K.A.; Conway, C.M.; Kurath, G.

    2006-01-01

    A highly efficacious DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was mutated to introduce two stop codons to prevent glycoprotein translation while maintaining the plasmid DNA integrity and RNA transcription ability. The mutated plasmid vaccine, denoted pIHNw-G2stop, when injected intramuscularly into fish at high doses, lacked detectable glycoprotein expression in the injection site muscle, and did not provide protection against lethal virus challenge 7 days post-vaccination. These results suggest that the G-protein itself is required to stimulate the early protective antiviral response observed after vaccination with the nonmutated parental DNA vaccine. ?? Springer Science+Business Media, Inc. 2006.

  9. High dose adenosine for suboptimal myocardial reperfusion after primary PCI : A randomized placebo-controlled pilot study

    NARCIS (Netherlands)

    Stoel, Martin G.; Marques, Koen M. J.; de Cock, Carel C.; Bronzwaer, Jean G. F.; von Birgelen, Clemens; Zijlstra, Felix

    2008-01-01

    Objectives: This study was designed to investigate the influence of high dose intracoronary adenosine on persistent ST-segment elevation after primary percutaneous coronary intervention (PCI). Background: After successful PCI for acute myocardial infarction 40-50% of patients show persistent

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

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Barker

    2017-07-01

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

  11. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas

    2015-01-01

    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

  12. In vitro effect of hemodilution on activated clotting time and high-dose thrombin time during cardiopulmonary bypass

    NARCIS (Netherlands)

    Huyzen, RJ; vanOeveren, W; Wei, FY; Stellingwerf, P; Boonstra, PW; Gu, YJ

    Background. Extreme dilution of clotting factors, as may occur during pediatric or neonatal cardiopulmonary bypass, often leads to inadequate monitoring of anticoagulation with activated dotting time (ACT). In this study we postulate that the high-dose thrombin time (HiTT) is less influenced by

  13. Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole

    NARCIS (Netherlands)

    Bunskoek, P.E.; Seyedmousavi, S.; Gans, S.J.; Vierzen, P.B. van; Melchers, W.J.G.; Elk, C.E. van; Mouton, J.W.; Verweij, P.E.

    2017-01-01

    Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose

  14. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer (TM) disposable high-dose dry powder inhaler

    NARCIS (Netherlands)

    de Boer, Anne H.; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

    Objectives To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer (TM) dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Methods Comparison

  15. The Role of Audiometry prior to High-Dose Cisplatin in Patients with Head and Neck Cancer.

    Science.gov (United States)

    Caballero, Miguel; Mackers, Paula; Reig, Oscar; Buxo, Elvira; Navarrete, Pilar; Blanch, Jose L; Grau, Juan J

    2017-01-01

    To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. A total of 103 patients were included; the median age of the patients was 59 years (range 18-75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab. Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population. © 2017 S. Karger AG, Basel.

  16. Effect of high-dose dexamethasone on perioperative lactate levels and glucose control : a randomized controlled trial

    NARCIS (Netherlands)

    Ottens, Thomas H.; Nijsten, Maarten W. N.; Hofland, Jan; Dieleman, Jan M.; Hoekstra, Miriam; van Dijk, Diederik; van der Maaten, Joost M. A. A.

    2015-01-01

    Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of

  17. Switching from high doses of pure μ-opioid agonists to transdermal buprenorphine in patients with cancer

    DEFF Research Database (Denmark)

    Lundorff, Lena; Sjøgren, Per; Hansen, Ole Bo

    2013-01-01

    BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain...

  18. Pharmacokinetics of cyclophosphamide and thiotepa in a conventional fractionated high-dose regimen compared with a novel simplified unfractionated regimen

    NARCIS (Netherlands)

    Ekhart, Corine; Rodenhuis, Sjoerd; Beijnen, Jos H.; Huitema, Alwin D. R.

    2009-01-01

    High-dose alkylating chemotherapy with cyclophosphamide (4000 or 6000 mg/m2) and thiotepa (320 or 480 mg/m2) has commonly been administered in a fractionated regimen over 4 days. A simplified unfractionated regimen would be preferable, especially because cyclophosphamide and thiotepa have been shown

  19. Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

    NARCIS (Netherlands)

    Boekel, G.A.J van; Loves, S.; Sorge, A van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

    2008-01-01

    OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

  20. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma : Randomized phase III EORTC study

    NARCIS (Netherlands)

    Kluin-Nelemans, HC; Zagonel, [No Value; Anastasopoulou, A; Bron, D; Roozendaal, KJ; Noordijk, EM; Musson, H; Teodorovic, [No Value; Maes, B; Carbone, A; Carde, P

    2001-01-01

    Background: The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently; the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Ichinomiya Taiga

    2012-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Bruno Kosa Lino Duarte

    2011-12-01

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

  4. A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats.

    Science.gov (United States)

    Xi, Z-X; Kleitz, H K; Deng, X; Ladenheim, B; Peng, X-Q; Li, X; Gardner, E L; Stein, E A; Cadet, J L

    2009-06-30

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10-20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kgx1 or 10 mg/kg/2 hx4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in "break-point" levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10-20 mg/kg) produced large DA release (4000%-6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior.

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

    Science.gov (United States)

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

    2015-01-01

    Viscum album extract (European mistletoe), containing immuno-active compounds with dose-dependent cytotoxic activity, is being used as an adjuvant cancer treatment in Europe. Few studies have yet been done with high-dose, fever-inducing Viscum album treatment. To explore whether subcutaneous injections of high-dose Viscum album have a preventive effect on risk of recurrence of bladder cancer. We retrospectively analyzed the case records of patients with resectable bladder cancer who underwent initiation of high-dose Viscum album treatment at our clinic between January 2006 and December 2012. We calculated tumor recurrence and progression risk and explored case records to assess whether treatment had a likely, possible, or unlikely beneficial effect. Eight patients were identified, 7 of whom had nonmuscle-invasive bladder cancer and 1 with muscle-invasive cancer. Four patients had frequently recurring tumors before treatment. Among the 8 patients, 28 episodes of recurrence were observed. Median tumor-free follow-up duration was 48.5 months. High-dose Viscum album showed a possible beneficial effect in 5 of 8 patients, could not be assessed in 2 patients, and had an uncertain effect in 1 patient. No tumor progression was observed. Treatment was generally well tolerated and no patient stopped treatment because of side effects. High-dose Viscum album treatment may have interrupted frequently recurring tumors in individual patients with recurrent bladder cancer. Prospective studies are needed to assess whether this treatment offers an additional, bladder-sparing preventive option for patients with intermediate- to high-risk nonmuscle-invasive bladder cancer.. Treatment was generally well tolerated and no patient stopped treatment because of side effects.

  6. Direction-Modulated Brachytherapy for High-Dose-Rate Treatment of Cervical Cancer. I: Theoretical Design

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dae Yup [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, California (United States); Webster, Matthew J. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Physics, University of California San Diego, La Jolla, California (United States); Scanderbeg, Daniel J.; Yashar, Catheryn; Choi, Dongju; Song, Bongyong [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Devic, Slobodan [Medical Physics Unit, McGill University, Montréal, Québec (Canada); Department of Radiation Oncology, Jewish General Hospital, Montréal, Québec (Canada); Ravi, Ananth [Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Song, William Y., E-mail: wyjsong@gmail.com [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-07-01

    Purpose: To demonstrate that utilization of the direction-modulated brachytherapy (DMBT) concept can significantly improve treatment plan quality in the setting of high-dose-rate (HDR) brachytherapy for cervical cancer. Methods and Materials: The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter, grooved along a nonmagnetic tungsten-alloy rod (ρ = 18.0 g/cm{sup 3}), enclosed in Delrin tubing (polyoxymethylene, ρ = 1.41 g/cm{sup 3}), with a total thickness of 6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic {sup 192}Ir dose distributions. An in-house-developed inverse planning platform, geared with simulated annealing and constrained-gradient optimization algorithms, was used to replan 15 patient cases (total 75 plans) treated with a conventional tandem and ovoids (T and O) applicator. Prescription dose was 6 Gy. For replanning, we replaced the conventional tandem with that of the new DMBT tandem for optimization but left the ovoids in place and kept the dwell positions as originally planned. All DMBT plans were normalized to match the high-risk clinical target volume V100 coverage of the T and O plans. Results: In general there were marked improvements in plan quality for the DMBT plans. On average, D2cc for the bladder, rectum, and sigmoid were reduced by 0.59 ± 0.87 Gy (8.5% ± 28.7%), 0.48 ± 0.55 Gy (21.1% ± 27.2%), and 0.10 ± 0.38 Gy (40.6% ± 214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%), 2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical target volume D90 was similar, with 6.55 ± 0.96 Gy and 6.59 ± 1.06 Gy for T and O and DMBT, respectively. Conclusions: Application of the DMBT concept to cervical cancer allowed for improved organ at risk sparing while achieving similar target coverage on a sizeable patient population, as intended, by maximally utilizing the anatomic information contained in 3-dimensional

  7. Colza cell autophagy induced of high dose of industrial sewage sludge

    Science.gov (United States)

    Lasoued, Najla; Guenole Bilal, Issam; Rejeb, Saloua; Bilal, Essaid; Rejeb, Nejib

    2013-04-01

    This preliminary study is to evaluate the effects on colza of land application of industrial sludge containing heavy metals especially lead and chromium. We are interested in high doses spreading 100t/ha to better observe the phenomena of induced transformations on colza by the absorption of heavy metals. We used the technique for ultrastructural observation in a transmission electron microscope. The colza cells show a compaction and marginalization of nuclear chromatin, nuclear membrane and cytoplasmic convolution and condensation of cytoplasm. The kernel then fragments, each fragment are surrounded by a jacket. Some cytoplasmic and nuclear elements are released and are phagocytized by neighboring cells. We observed vacuolation of the cytoplasm and the formation of autophagic vesicles. The two main ways to cell death are apoptosis and autophagy. Apoptosis was not seen in plant yet. At the nucleus level cell death main characteristics are the nuclear blebbing and fragmentation. At the molecular level, caspases activity (VPE for plants, or metacaspases I and II), chromatin condensation, degradation of DNA detected by TUNEL assay and DNA laddering detected by comet test are the main events. Autophagy is the major degradation and recycling process in cells. Its aim is to address part of the cytoplasm or organelles to the proteasome. In macro-Autophagy a specific feature is the double membrane structure that we can see in electron microscopy. This membrane is known to fusion with the lysosome/vacuole where this is in process. As a rule, the vacuole grows more and more until no organelles remains. Small lytic vacuoles appear in increasing quantity also. Autophagosomes tend to be pushed against the membrane and wall of the cell. Sometime in the literature it was describe a permeabilization or a tonoplast disruption; this is the last stage called mega-autophagy. The stress generated by heavy metals in industrial sludge spreading, produces in colza cells programmed death

  8. Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Larissa J. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

    2012-12-01

    Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-09-15

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

  10. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Granero, Domingo, E-mail: dgranero@eresa.com [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain); Perez-Calatayud, Jose [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain); Vijande, Javier [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain); Ballester, Facundo [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)

    2014-02-15

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about −3%. When the source was positioned at the skin surface, dose differences were smaller than −1% for {sup 60}Co and {sup 192}Ir, yet −3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were −7% for {sup 60}Co, −0.6% for {sup 192}Ir, and −2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For

  13. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Directory of Open Access Journals (Sweden)

    Daniel G Zhang

    Full Text Available MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF and conventional flattened 6MV photon beams were used. High dose rate (HDR brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL would be needed.

  14. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Science.gov (United States)

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

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

    Science.gov (United States)

    Palmer, Antony; Mzenda, Bongile

    2009-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-01

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

  17. Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

    Directory of Open Access Journals (Sweden)

    Y. Sobita Devi

    2011-12-01

    Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

  18. High-Dose Micafungin for Preterm Neonates and Infants with Invasive and Central Nervous System Candidiasis.

    Science.gov (United States)

    Auriti, Cinzia; Falcone, Marco; Ronchetti, Maria Paola; Goffredo, Bianca Maria; Cairoli, Sara; Crisafulli, Rosamaria; Piersigilli, Fiammetta; Corsetti, Tiziana; Dotta, Andrea; Pai, Manjunath P

    2016-12-01

    High doses of micafungin are advocated in neonates with systemic candidiasis, but limited pharmacokinetic (PK) and safety data are available to support their use. Eighteen preterm neonates and infants with systemic candidiasis, three of whom had meningitis, were treated for at least 14 days with 8 to 15 mg/kg of body weight/day of intravenous micafungin. Plasma micafungin concentrations (four measurements for each patient) were determined after the third dose, and the cerebrospinal fluid (CSF) micafungin concentrations in three patients were also obtained. Population PK analyses were used to identify the optimal model, and the model was further validated using external data (n = 5). The safety of micafungin was assessed by measurement of the levels of liver and kidney function biomarkers. The mean age and weight at the initiation of treatment were 2.33 months (standard deviation [SD], 1.98 months) and 3.24 kg (SD, 1.61 kg), respectively. The optimal PK model was one that scaled plasma clearance to weight and the transaminase concentration ratio. The CSF of three patients was sampled, and the observed concentrations were between 0.80 and 1.80 mg/liter. The model-predicted mean micafungin area under the concentration-time curve over 24 h was 336 mg · h/liter (SD, 165 mg · h/liter) with the 10-mg/kg/day dosage. Eighteen of the 23 subjects (78.2%) had clinical resolution of their infection, but 5 had neurologic impairments. Among the transaminases, alkaline phosphatase measurements were significantly higher posttreatment, with a geometric mean ratio of 1.17 (90% confidence interval, 1.01, 1.37). Furthermore, marked elevations in the gamma-glutamyltransferase (GGT) level were observed in three patients treated with 10- to 15-mg/kg/day doses, and improvement of the GGT level was noted after a dose reduction. Higher weight-based doses of micafungin were generally well tolerated in neonates and infants and achieved pharmacokinetic profiles predictive of an effect

  19. High-dose-rate brachytherapy monotherapy without androgen deprivation therapy for intermediate-risk prostate cancer.

    Science.gov (United States)

    Patel, Shyamal; Demanes, D Jeffrey; Ragab, Omar; Zhang, Mingle; Veruttipong, Darlene; Nguyen, Kristine; Park, Sang-June; Marks, Leonard; Pantuck, Allan; Steinberg, Michael; Kamrava, Mitchell

    Outcomes using high-dose-rate (HDR) brachytherapy monotherapy (without androgen deprivation therapy or external beam radiation therapy) for National Comprehensive Cancer Network-defined intermediate-risk (IR) patients are limited. We report our long-term data using HDR monotherapy for this patient population. One-hundred ninety IR prostate cancer patients were treated 1996-2013 with HDR monotherapy. Biochemical prostate-specific antigen (PSA) failure was per the Phoenix definition. Acute and late genitourinary and gastrointestinal toxicities were graded according to Common Toxicity Criteria of Adverse Events, version 4. Kaplan-Meier (KM) biochemical progression-free survival (BPFS), cause-specific survival, and overall survival rates were calculated. Univariate analyses were performed to determine relationships with BPFS. The median patient age was 66 years (43-90), and the median initial PSA was 7.4 ng/mL. The Gleason score was ≤6 in 26%, 3 + 4 in 62%, and 4 + 3 in 12%. The median treatment BED1.5 was 254 Gy; 83% of patients were treated with a dose of 7.25 Gy × six fractions delivered in two separate implants. With a median follow-up of 6.2 years, KM BPFS at 5/8 years was 97%/90%, cause-specific survival at 8 years was 100%, and overall survival at 5/8 years was 93%/88%. Late genitourinary toxicities were 36.3% Grade 1, 18.9% Grade 2, and 3.7% Grade 3. Late gastrointestinal toxicities were 6.3% Grade 1, 1.1% Grade 2, and no Grade ≥3. Of the patients with no sexual dysfunction before treatment, 68% maintained potency. Age, initial PSA, T stage, Gleason score, prostate volume, and percent positive cores did not correlate with BPFS. Stratifying by favorable vs. unfavorable IR groups did not affect BPFS. HDR brachytherapy monotherapy represents a safe and highly effective treatment for IR prostate cancer patients with long-term follow-up. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-02-01

    In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR(60)Co and (192)Ir sources and a hypothetical (169)Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. For a 5 cm × 5 cm(192)Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about -3%. When the source was positioned at the skin surface, dose differences were smaller than -1% for (60)Co and (192)Ir, yet -3% for (169)Yb. For the interstitial implant, dose differences at the skin surface were -7% for (60)Co, -0.6% for (192)Ir, and -2.5% for (169)Yb. This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either (60)Co and (192)Ir. For lower energy radionuclides like (169)Yb, bolus may be needed; and (iii) for the interstitial case, at

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

    Science.gov (United States)

    Lee, Larissa J; Viswanathan, Akila N

    2012-12-01

    To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the

  2. Patient-specific dose calculation methods for high-dose-rate iridium-192 brachytherapy

    Science.gov (United States)

    Poon, Emily S.

    In high-dose-rate 192Ir brachytherapy, the radiation dose received by the patient is calculated according to the AAPM Task Group 43 (TG-43) formalism. This table-based dose superposition method uses dosimetry parameters derived with the radioactive 192Ir source centered in a water phantom. It neglects the dose perturbations caused by inhomogeneities, such as the patient anatomy, applicators, shielding, and radiographic contrast solution. In this work, we evaluated the dosimetric characteristics of a shielded rectal applicator with an endocavitary balloon injected with contrast solution. The dose distributions around this applicator were calculated by the GEANT4 Monte Carlo (MC) code and measured by ionization chamber and GAFCHROMIC EBT film. A patient-specific dose calculation study was then carried out for 40 rectal treatment plans. The PTRAN_CT MC code was used to calculate the dose based on computed tomography (CT) images. This study involved the development of BrachyGUI, an integrated treatment planning tool that can process DICOM-RT data and create PTRAN_CT input initialization files. BrachyGUI also comes with dose calculation and evaluation capabilities. We proposed a novel scatter correction method to account for the reduction in backscatter radiation near tissue-air interfaces. The first step requires calculating the doses contributed by primary and scattered photons separately, assuming a full scatter environment. The scatter dose in the patient is subsequently adjusted using a factor derived by MC calculations, which depends on the distances between the point of interest, the 192Ir source, and the body contour. The method was validated for multicatheter breast brachytherapy, in which the target and skin doses for 18 patient plans agreed with PTRAN_CT calculations better than 1%. Finally, we developed a CT-based analytical dose calculation method. It corrects for the photon attenuation and scatter based upon the radiological paths determined by ray tracing

  3. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-09-01

    Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

  5. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ost, Piet, E-mail: piet.ost@ugent.be [Department of Radiotherapy, Ghent University Hospital (Belgium); Cozzarini, Cesare [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital (Belgium); Fiorino, Claudio [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Potter, Bruno [Department of Radiotherapy, Ghent University Hospital (Belgium); Briganti, Alberto [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Nagler, Evi V.T. [Department of Nephrology, Ghent University Hospital (Belgium); Montorsi, Francesco [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Fonteyne, Valerie [Department of Radiotherapy, Ghent University Hospital (Belgium); Di Muzio, Nadia [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy)

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  6. In vivo dose verification method in catheter based high dose rate brachytherapy.

    Science.gov (United States)

    Jaselskė, Evelina; Adlienė, Diana; Rudžianskas, Viktoras; Urbonavičius, Benas Gabrielis; Inčiūra, Arturas

    2017-12-01

    In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-01

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

  8. Concomitant cervical and transperineal parametrial high-dose-rate brachytherapy boost for locally advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Caroline Bailleux

    2016-01-01

    Full Text Available Purpose: There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB boost for locally advanced cervical cancer. Material and methods: From 01.2011 to 12.2014, 33 patients (pts presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results: Median age was 56.4 years (27-79. Clinical stages were: T2b = 23 pts (69.7%, T3a = 1 pt (3%, T3b = 6 pts (18.2%, and T4a = 3 pts (9.1%. Median HDRB prescribed dose was 21 Gy (21-27. Median CTVCT (16 pts and HR-CTV MRI (17 pts were 52.6 cc (28.5-74.3, 31.9 cc (17.1-58, respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5, 84.8 Gy (80.6-91.4, respectively. Median EQD2αβ3 (CT/MRI for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9, 64.4 Gy (51.9-77.4, and 60.4 Gy (50.9-81.1, respectively. Median follow-up was 14 months (ranged 6-51. Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pt, G3 infection = 2 pts, and 27% (G1 diarrhea = 9 pts, respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion; no bleeding was

  9. Cancer Vaccines

    Science.gov (United States)

    ... foreign. Most preventive vaccines, including those aimed at cancer-causing viruses ( hepatitis B virus and human papillomavirus ), stimulate the ... 9 through 25 for the prevention of cervical cancer caused by HPV. Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to ...

  10. BCG Vaccines.

    Science.gov (United States)

    Tran, Vanessa; Liu, Jun; Behr, Marcel A

    2014-02-01

    BCG is the collective name for a family of live attenuated strains of Mycobacterium bovis that are currently used as the only vaccine against tuberculosis (TB). There are two major reasons for studying the genome of these organisms: (i) Because they are attenuated, BCG vaccines provide a window into Mycobacterium tuberculosis virulence, and (ii) because they have provided protection in several clinical trials and case-control studies, BCG vaccines may shed light on properties required of a TB vaccine. Since the determination of the M. tuberculosis genome in 1998, the study of BCG vaccines has accelerated dramatically, offering data on the genomic differences between virulent M. tuberculosis, M. bovis, and the vaccine strains. While these findings have been rewarding for the study of virulence, there is unfortunately less accrued knowledge about protection. In this chapter, we review briefly the history of BCG vaccines and then touch upon studies over the past two decades that help explain how BCG underwent attenuation, concluding with some more speculative comments as to how these vaccines might offer protection against TB.

  11. Combination vaccines

    Directory of Open Access Journals (Sweden)

    David AG Skibinski

    2011-01-01

    Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.

  12. [The efficacy and safety of high-dose irbesartan in treatment of clinical proteinuria in patients with chronic kidney disease].

    Science.gov (United States)

    Li, Xin; Chen, Xiang-dong; Li, Zhong-xin

    2011-12-01

    To evaluate the efficacy and safety of high-dose irbesartan in the treatment of mild and moderate proteinuria in patients with chronic kidney disease (CKD). A single center, prospective, observational study was performed. A total of 96 subjects were given irbesartan 150 mg/d for 4 weeks. Twenty-six were divided into single-dose (150 mg/d) irbesartan group when their clinical efficacy were eligible for improvement criteria and 70 were divided into high-dose (300 - 600 mg/d) irbesartan group when there were no effect for single-dose treatment. Both groups received treatment for 48 weeks. Then 24-hour quantitative urine protein, systolic pressure, diastolic pressure, TC, LDL-C, plasma albumin, serum creatinine, blood urea nitrogen, blood uric acid, serum potassium and ALT were determined. The proteinuria level after treatment in the single-dose irbesartan group was decreased by 68.3% with a statistically significant difference (P proteinuria was decreased by 63.4% (P proteinuria in high-dose group was 72.9% (51/70). Among the blood pressure sub-groups, the effective rates for the normal blood pressure group and hypertension group in treating proteinuria were 68.2% and 76.9% respectively (P > 0.05). However, in the normal blood pressure group and hypertension group, the proteinuria was decreased by 61.9% and 67.5% respectively after treatment (P 0.05). The effective rates of high doses of 300, 450 and 600 mg/d of irbesartan in treating proteinuria were 70.8%, 63.6% and 66.7%, respectively. The difference in effective rates of treating proteinuria among different doses had no statistical significance (P > 0.05). No obvious increase of SCr value before and after treatment in high-dose group (P = 0.583). The increasing level of serum potassium in high-dose group after treatment was higher than that in the single-dose group (P proteinuria in CKD patients with a good safety and tolerance and the efficacy is independent of lowering blood pressure.

  13. Response to Hepatitis A Vaccination in Immunocompromised Travelers.

    Science.gov (United States)

    Garcia Garrido, Hannah M; Wieten, Rosanne W; Grobusch, Martin P; Goorhuis, Abraham

    2015-08-01

    Hepatitis A vaccines are highly immunogenic in healthy patients, but there is uncertainty about their immunogenicity in immunocompromised patients. Our study included immunocompromised patients who received 1 or 2 hepatitis A vaccinations between January 2011 and June 2013. We assessed factors that influenced the serologic response to vaccination. We performed a literature review of previous studies on hepatitis A vaccination in immunocompromised patients. Of 85 immunocompromised patients, 65 used immunosuppressive drugs, 13 had received stem cell transplants, and 7 were infected with human immunodeficiency virus. After vaccination, 65 of 85 (76.5%) developed antibodies. Tumor necrosis factor α blocker use was associated with better serologic responses than other immunosuppressive drugs. Female patients were more compliant than male patients with postvaccination antibody titer measurements. In 11 relevant studies, antibody responses after the first and second vaccination averaged 37% and 82%, respectively. Factors that negatively influenced serologic response rates were high doses of immunosuppressive drugs, fewer hepatitis A vaccinations, and a short interval between vaccination and antibody measurement. Immunocompromised patients showed moderate to good serologic responses to hepatitis A vaccination, but may need more time to develop immunity. Tumor necrosis factor α blocker use was associated with better antibody responses than other drugs. Specifically, male patients should be motivated to return for antibody titer measurements. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Adaptation of the CVT algorithm for catheter optimization in high dose rate brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Poulin, Eric; Fekete, Charles-Antoine Collins; Beaulieu, Luc [Département de Physique, de Génie Physique et d’Optique et Centre de recherche sur le cancer de l’Université Laval, Université Laval, Québec, Québec G1V 0A6, Canada and Département de Radio-Oncologie et Axe oncologie du Centre de Recherche du CHU de Québec, CHU de Québec, 11 Côte du Palais, Québec, Québec G1R 2J6 (Canada); Létourneau, Mélanie [Département de Radio-Oncologie, CHU de Québec, 11 Côte du Palais, Québec, Québec G1R 2J6 (Canada); Fenster, Aaron [Imaging Research Laboratories, Robarts Research Institute, 100 Perth Drive, London, Ontario N6A 5K8 (United Kingdom); Pouliot, Jean [Department of Radiation Oncology, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, San Francisco, California 94143-1708 (United States)

    2013-11-15

    Purpose: An innovative, simple, and fast method to optimize the number and position of catheters is presented for prostate and breast high dose rate (HDR) brachytherapy, both for arbitrary templates or template-free implants (such as robotic templates).Methods: Eight clinical cases were chosen randomly from a bank of patients, previously treated in our clinic to test our method. The 2D Centroidal Voronoi Tessellations (CVT) algorithm was adapted to distribute catheters uniformly in space, within the maximum external contour of the planning target volume. The catheters optimization procedure includes the inverse planning simulated annealing algorithm (IPSA). Complete treatment plans can then be generated from the algorithm for different number of catheters. The best plan is chosen from different dosimetry criteria and will automatically provide the number of catheters and their positions. After the CVT algorithm parameters were optimized for speed and dosimetric results, it was validated against prostate clinical cases, using clinically relevant dose parameters. The robustness to implantation error was also evaluated. Finally, the efficiency of the method was tested in breast interstitial HDR brachytherapy cases.Results: The effect of the number and locations of the catheters on prostate cancer patients was studied. Treatment plans with a better or equivalent dose distributions could be obtained with fewer catheters. A better or equal prostate V100 was obtained down to 12 catheters. Plans with nine or less catheters would not be clinically acceptable in terms of prostate V100 and D90. Implantation errors up to 3 mm were acceptable since no statistical difference was found when compared to 0 mm error (p > 0.05). No significant difference in dosimetric indices was observed for the different combination of parameters within the CVT algorithm. A linear relation was found between the number of random points and the optimization time of the CVT algorithm. Because the

  15. 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

  16. 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

  17. 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

  18. Optimal bladder filling during high-dose-rate intracavitary brachytherapy for cervical cancer: a dosimetric study

    Directory of Open Access Journals (Sweden)

    Umesh Mahantshetty

    2017-04-01

    Full Text Available Purpose: The aim of this study is to compare 3D dose volume histogram (DVH parameters of bladder and other organs at risk with different bladder filling protocol during high-dose-rate intracavitary brachytherapy (HDR-ICBT in cervical cancer, and to find optimized bladder volume. Material and methods : This dosimetric study was completed with 21 patients who underwent HDR-ICBT with computed tomography/magnetic resonance compatible applicator as a routine treatment. Computed tomography planning was done for each patient with bladder emptied (series 1, after 50 ml (series 2, and 100 ml (series 3 bladder filling with a saline infusion through the bladder catheter. Contouring was done on the Eclipse Planning System. 7 Gy to point A was prescribed with the standard loading patterns. Various 3D DVH parameters including 0.1 cc, 1 cc, 2 cc doses and mean doses to the OAR’s were noted. Paired t-test was performed. Results : The mean (± SD bladder volume was 64.5 (± 25 cc, 116.2 (± 28 cc, and 172.9 (± 29 cc, for series 1, 2, and 3, respectively. The 0.1 cm 3 ,1 cm 3 , 2 cm 3 mean bladder doses for series 1, series 2, and series 3 were 9.28 ± 2.27 Gy, 7.38 ± 1.72 Gy, 6.58 ± 1.58 Gy; 9.39 ± 2.28 Gy, 7.85 ± 1.85 Gy, 7.05 ± 1.59 Gy, and 10.09 ± 2.46 Gy, 8.33 ± 1.75 Gy, 7.6 ± 1.55 Gy, respectively. However, there was a trend towards higher bladder doses in series 3. Similarly, for small bowel dose 0.1 cm 3 , 1 cm 3 , and 2 cm 3 in series 1, 2, and 3 were 5.44 ± 2.2 Gy, 4.41 ± 1.84 Gy, 4 ± 1.69 Gy; 4.57 ± 2.89 Gy, 3.78 ± 2.21 Gy, 3.35 ± 2.02 Gy, and 4.09 ± 2.38 Gy, 3.26 ± 1.8 Gy, 3.05 ± 1.58 Gy. Significant increase in small bowel dose in empty bladder (series 1 compared to full bladder (series 3 (p = 0.03 was noted. However, the rectal and sigmoid doses were not significantly affected with either series. Conclusions : Bladder filling protocol with 50 ml and 100 ml was well tolerated and achieved a reasonably reproducible bladder volume

  19. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... Educators Search English Español Your Child's Immunizations: Meningococcal Vaccines KidsHealth / For Parents / Your Child's Immunizations: Meningococcal Vaccines Print The meningococcal vaccines protect ...

  20. Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

    Directory of Open Access Journals (Sweden)

    Isabelle Corre

    2013-11-01

    Full Text Available Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation.

  1. Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental Escherichia coli infections in poultry

    DEFF Research Database (Denmark)

    Kromann, Sofie; Kudirkiene, Egle; Li, Lili

    2017-01-01

    infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline...... combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens....... the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending...

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

    Science.gov (United States)

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

    2014-07-31

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

  3. Immune responses and immune-related gene expression profile in orange-spotted grouper after immunization with Cryptocaryon irritans vaccine.

    Science.gov (United States)

    Dan, Xue-Ming; Zhang, Tuan-Wei; Li, Yan-Wei; Li, An-Xing

    2013-03-01

    In order to elucidate the immune-protective mechanisms of inactivated Cryptocaryon irritans vaccine, different doses of C. irritans theronts were used to immunize orange-spotted grouper (Epinephelus coioides). We measured serum immobilization titer, blood leukocyte respiratory burst activity, serum alternative complement activity, and serum lysozyme activity weekly. In addition, the expression levels of immune-related genes such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), major histocompatibility complexes I and II (MHC I and II), and transforming growth factor-β1 (TGF-β1) were determined in spleen and gills. The results showed that the immobilization titer, respiratory burst activity, and alternative complement activity of immunized fish were significantly increased, and the levels of the last two immune parameters in the high-dose vaccine group were significantly higher than in the low-dose vaccine group. Serum lysozyme activity in the high-dose vaccine group was significantly higher than in the PBS control group. Vaccination also regulated host immune-related gene expression. For example, at 2- and 3- weeks post immunization, IL-1β expression in the high-dose vaccine group spleen was significantly increased. At 4-weeks post immunization, the fish were challenged with a lethal dose of parasite, and the survival rates of high-dose vaccine group, low-dose vaccine group, PBS control group, and adjuvant control group were 80%, 40%, 0%, and 10% respectively. These results demonstrate that inactivated C. irritans vaccination improves specific and nonspecific immune responses in fish, enhancing their anti-parasite ability. These effects are vaccine antigen dose-dependent. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    OpenAIRE

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-11-01

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

  6. Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions

    DEFF Research Database (Denmark)

    Mikkelsen, Torben Stamm; Mamoudou, Aissata Diop; Tuckuviene, Ruta

    2014-01-01

    Alkalized hydration is used as supportive care to prevent renal toxicity during infusions with high-dose methotrexate (HDMTX). In children with acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours before start of the methotrexate (MTX) infusion. To test if longer duration...... of prehydration would prevent MTX-induced renal toxicity, we preformed a randomized cross-over study comparing 12-4 hours of hydration before the infusion of HDMTX....

  7. Image-Guided High-Dose-Rate (HDR) Boost Localization Using MRI/MR Spectroscopy: A Correlation Study with Biopsy

    OpenAIRE

    Vigneault, Eric; Mbodji, Khaly; Racine, Louis G; Chevrette, Eric; Lavallee, Marie C; Martin, Andr?-Guy; Despres, Philippe; Beaulieu, Luc

    2016-01-01

    Purpose: The purpose of this study is to compare the blind interpretations of magnetic resonance imaging (MRI) sequences, diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), mapping, and magnetic resonance spectroscopy (MRS) of the prostate, in comparison to prostate biopsy to identify a valid dominant intraprostatic lesion (DIL) for dose escalation using high-dose rate brachytherapy. Methods: MRI/MRS were performed on 20 patients with intermediate risk adenocarcinoma of t...

  8. High-Dose Aspirin Is Required to Influence Plasma Fibrin Network Structure in Patients With Type 1 Diabetes

    OpenAIRE

    Tehrani, Sara; Antovic, Aleksandra; Mobarrez, Fariborz; Mageed, Koteiba; Lins, Per-Eric; Adamson, Ulf; Wall?n, H?kan N.; J?rneskog, Gun

    2012-01-01

    OBJECTIVE Patients with type 1 diabetes form a less permeable fibrin network, which could contribute to their increased risk of cardiovascular disease (CVD). Low-dose aspirin treatment is the standard in the management of CVD; however, the effect seems reduced in patients with diabetes. We investigated the effects of low- and high-dose aspirin treatment on fibrin network formation in patients with type 1 diabetes (primary aim) and the possible interaction between the treatment effects of aspi...

  9. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

    Directory of Open Access Journals (Sweden)

    Alan T Clarke

    Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

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

    Science.gov (United States)

    Li, Qiang; Yao, Gaiqi; Zhu, Xi

    2012-04-01

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

  11. The Effects of Methamphetamine Self-Administration on Cortical Monoaminergic Deficits Induced by Subsequent High-Dose Methamphetamine Administrations

    OpenAIRE

    McFadden, Lisa M.; Hanson, Glen R.; Fleckenstein, Annette E.

    2013-01-01

    Preclinical models suggest that repeated high-dose methamphetamine (METH) exposures, administered in a “binge-like” pattern, acutely decrease norepinephrine (NE), and acutely and persistently decrease serotonin (5-hydroxytryptamine; 5HT) content in the frontal cortex. However, the impact of METH self-administration on this region is unknown. Because of the importance of the monoaminergic neurons in the frontal cortex to a variety of cognitive and addictive processes, effects of METH self-admi...

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

    OpenAIRE

    Sassoon, Catherine SH; Caiozzo, Vincent J

    2009-01-01

    Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and o...

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

    Science.gov (United States)

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

    2007-06-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  15. Effects of high dose olive leaf extract on haemodynamic and oxidative stress parameters in normotensive and spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Dekanski Dragana

    2014-01-01

    Full Text Available Antihypertensive activity of natural antioxidant, olive leaf extract (OLE is known, but its influence on cardiovascular system when administered in a high dose has not been investigated yet. Our aim was to determine the acute effects of excessive intake of standardized OLE on blood pressure, heart rate and oxidative status in both spontaneously hypertensive rats and normotensive Wistar rats. Systolic arterial pressure and heart rate were measured using a tail-cuff, pneumatic pulse detector, before, 60 and 120 minutes after intragastric OLE administration. Activities of catalase, glutathione peroxidase, superoxide dismutase (SOD and glutathione reductase in erythrocytes, as well as lipid peroxidation in plasma (pTBARS were measured at the same time points, spectrophotometrically. High-dose OLE did not influence blood pressure, heart rate and pTBARS in normotensive rats, while SOD, catalase, and glutathione reductase activities significantly increased. The same dose significantly decreased blood pressure in hypertensive rats, but increased pTBARS and SOD activity. Excessive oral intake of OLE induced moderate hypotensive effects in spontaneously hypertensive rats only, suggesting absence of harmful haemodynamic effects after oral overdose in both rats strain. However, its prooxidative role when given in high dose in hypertensive organism should not be neglected. [Projekat Ministarstva nauke Republike Srbije, br. 175096

  16. 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

  17. Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep

    Directory of Open Access Journals (Sweden)

    Alistair J. Gunn

    2012-05-01

    Full Text Available Hypoxic-ischaemic brain injury at birth is associated with 1–3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 µmol/kg/h for 1 h, followed by 50 µmol/kg/24 h (low dose or 50 µmol/kg/h for 25 h (high dose or vehicle only (control group, starting 90 min after the end of ischaemia, following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation. Both peptide infusion groups were associated with a transient significant increase in EEG power between 2–12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling, as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium.

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

    Directory of Open Access Journals (Sweden)

    João Soares Felício

    2017-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-03-01

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

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

    Science.gov (United States)

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

    2012-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Sassoon, Catherine Sh; Caiozzo, Vincent J

    2009-01-01

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

  3. The apoptotic effect of a high dose of toluene on liver tissue during the acute phase: an experimental study.

    Science.gov (United States)

    Ayan, Murat; Tas, Ufuk; Sogut, Erkan; Kuloglu, Tuncay; Cayli, Sevil; Kocaman, Nevin; Karaca, Zafer Ismail; Sahin, Mehmet

    2013-09-01

    The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200-220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 μm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin-biotin-peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-01-15

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

  8. SU-E-T-165: Characterization of Dose Distributions in High-Dose-Rate Surface Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Buzurovic, I; Hansen, J; Bhagwat, M; O’Farrell, D; Damato, A; Friesen, S; Devlin, P; Cormack, R [Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, MA (United States)

    2015-06-15

    Purpose: To characterize dose distributions in high-dose-rate(HDR) surface brachytherapy using an Ir-125 source for different geometries, field sizes and topology of the clinical targets(CT). To investigate the depth doses at the central axis(CAX), edges of the treatment fields(E), and lateral dose distributions(L) present when using flap applicators in skin cancer treatments. Methods: When malignancies diagnosed on the skin are treated, various geometries of the CT require proper adaptation of the flap or custom-made applicators to the treatment site. Consequently, the dose at the depth on CAX and field edges changes with variation of the curvatures and size of the applicators. To assess the dose distributions, we created a total of 10 treatment plans(TP) for 10×10 and 20×20 field sizes(FS) with a step size of 1cm. The geometry of the applicators was: planar(PA), curved to 30(CA30) and 60(CA60) degrees with respect to the CAX, half-cylinder(HC), and cylindrical shape(CS). One additional TP was created in which the applicators were positioned to form a dome shape(DS) with a diameter of 16cm. This TP was used to emulate treatment of the average sized scalp. All TPs were optimized to deliver a prescription dose at 8mm equidistantly from the planes containing the dwell positions. This optimization is equivalent to the clinical arrangement since the SSD for the flap applicators is 5mm and the prescription depth is 3mm in the majority of clinical cases. Results: The depths (in mm) of the isodose lines were: FS(10×10):PA[90%(9.1CAX,8.0E,7.6L),50%(28.3CAX,20E,17.3L), 25%(51.1CAX,40E,27L)],CA30[90%(10.3CAX,8.2E,7.9L),50%(32.1CAX, 16.2E,15.8L),25%(61.3CAX,36.7E,31.8L)],CA60[90%(12.2CAX,6.1E,6.3L ),50%(47CAX,14E,16.6L),25%(70.8CAX,31.9E,35.4L)],HC[90%(11.1CA X,6.3E,7.3L),50%(38.3CAX,14.6E,16.1L),25%(66.2CAX,33.8E,34.2L)];FS (20×20):PA[90%(11.1CAX,9.0E,7.0L),50%(34.4CAX,21.9E,15.3L),25%(7 0.4CAX,50.9E,34.8L)],CA30[90%(10.9CAX,7.5E,7.1L),50%(38.8CAX,16. 7E,15.4L),25

  9. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  10. High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

    Science.gov (United States)

    Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

    2017-08-17

    High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m2. Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

  11. Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration.

    Science.gov (United States)

    Boucher, Bradley A; Hudson, Joanna Q; Hill, David M; Swanson, Joseph M; Wood, G Christopher; Laizure, S Casey; Arnold-Ross, Angela; Hu, Zhe-Yi; Hickerson, William L

    2016-12-01

    High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. Prospective clinical pharmacokinetic study. Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CLTotal ), CL by CVVH (CLHF ), half-life during CVVH, volume of distribution at steady state (Vdss ), and the percentage of drug eliminated by CVVH. In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CLHF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CLTotal (14.74 ± 4.75 L/hr). Cilastatin CLHF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CLTotal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vdss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen. © 2016 Pharmacotherapy Publications, Inc.

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

    Directory of Open Access Journals (Sweden)

    Ho-Chang Kuo

    Full Text Available Kawasaki disease (KD is also known as multiple mucocutaneous lymph node syndrome of systemic vasculitis and is a leading cause of coronary artery lesions (CAL in childhood. Intravenous immunoglobulin (IVIG has been proven to effectively reduce the incidence of CAL, but the role and effect dose of aspirin in KD is still unclear. Moreover, overt bleeding and anemia are associated with the use of aspirin, and anemia is common in patients with KD. Thus, the aim of this study was conducted to compare the treatment efficacy, degree of anemia