WorldWideScience

Sample records for single dose treatments

  1. [Single dose treatment of trichomoniasis].

    Science.gov (United States)

    Erb, H

    1975-01-01

    The present regiman for the treatment of trichomoniasis with Tinidazol is 150 mg. twice daily for 7 days with a total dose of 2,100 mg. The success rate of this regimen is 85-90%. With a single dosage treatment of 2,000 mg. (Four 500 mg. tablets for the patient and her sexual partner) the success rate improved to 100%. Toxic side effects were not observed. The treatment was well tolerated and well accepted.

  2. Efficacy of Single Dose Anthelminthic Treatment against Soil ...

    African Journals Online (AJOL)

    The objective of this study was to evaluate the efficacy of single dose anthelminthic treatment against soil-transmitted helminthic infections and schistosomiasis among school children in Ebonyi State. Subjects and Methods: A school-based chemotherapeutic intervention study was conducted from September 2007 to ...

  3. Single dose treatment of malaria - current status and perspectives.

    Science.gov (United States)

    Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

    2016-07-01

    Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

  4. Treatment of uncomplicated gonorrhoea with single dose aztreonam.

    OpenAIRE

    Evans, D T; Crooks, A J; Jones, C; Holman, R A; Price, S W

    1986-01-01

    Infection with Neisseria gonorrhoeae was cleared in 61 men and 26 women at all sites (except in the pharynx of one male bisexual patient with urethral and pharyngeal gonorrhoea) after treatment with aztreonam as a single 1 g intramuscular injection. Aztreonam was well tolerated with no adverse effects. This monobactam antibiotic was effective against both penicillin sensitive and resistant strains.

  5. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial.

    Science.gov (United States)

    Song, Taejong; Kim, Mi Kyoung; Kim, Mi-La; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju

    2016-02-01

    Can a two-dose methotrexate treatment protocol improve the treatment success rate compared with a single-dose protocol in women with an ectopic pregnancy? The two-dose protocol was not superior to the single-dose protocol for the treatment of ectopic pregnancy. Although the two-dose methotrexate protocol for ectopic pregnancy was recently introduced to combine the efficacy and convenience of the fixed multi-dose and single-dose protocols, studies comparing the success rates, treatment satisfaction and acceptability of the single-dose and two-dose treatment protocols for ectopic pregnancy are currently lacking. A randomized trial was conducted on 92 participants with tubal ectopic pregnancy, between May 2013 and April 2015. Patients who were diagnosed with tubal ectopic pregnancy and who elected to undergo systemic methotrexate treatment were randomly assigned to follow either the single-dose (n = 46) or two-dose protocol (n = 46). The primary outcome measure was treatment success without surgical intervention. The secondary outcome measures were the incidence of methotrexate-associated side effects, β-human chorionic gonadotrophin (β-hCG) resolution time, cost of care received and treatment satisfaction. There were no differences in baseline characteristics between the groups. The success rates between the single-dose and two-dose groups did not show a significant difference [82.6 versus 87.0%; relative risk (RR) 0.95; 95% confidence interval (CI) 0.80-1.13]. However, the success rate in a subgroup of participants with a pretreatment β-hCG level of >5000 mIU/ml appeared to be higher in the two-dose group than in the single-dose group (80.0 versus 58.8%), although the difference was not statistically significant. No significant differences in methotrexate-associated side effects, cost or treatment satisfaction were observed between the groups. The two-dose group required a lower number of days for the β-hCG level to decrease to ectopic pregnancy. None. www

  6. Efficacy and Tolerance of Single-dose Azithromycin for Treatment of Chlamydial Cervicitis During Pregnancy

    Directory of Open Access Journals (Sweden)

    Joseph M. Miller

    1995-01-01

    Full Text Available Objective: The intent of this study was to determine the efficacy and tolerance of single-dose oral azithromycin in the treatment of pregnant women with endocervical chlamydial carriage.

  7. A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin

    Directory of Open Access Journals (Sweden)

    Walter B. Junior

    Full Text Available A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001. The treatment failed in all HIV positive patients treated with azithromycin (p=0.002 and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

  8. Multiple-dose and double-dose versus single-dose administration of methotrexate for the treatment of ectopic pregnancy: a systematic review and meta-analysis.

    Science.gov (United States)

    Yang, Chun; Cai, Jing; Geng, Yuhong; Gao, Ying

    2017-04-01

    In this systematic review and meta-analysis, the effectiveness and safety among different dosage of methotrexate protocols for the treatment of unruptured tubal ectopic pregnancy was evaluated. Six studies of randomized contorlled trials were identified through searches conducted on PubMed, Embase and Cochrane Library between January 1974 and March 2016. The overall success rate of multiple-dose protocol was similar to the single-dose protocol (RR 1.07, 95% CI 0.99 to 1.17, I2 = 0%). The difference between double-dose and single-dose groups was not significant (RR 1.09, 95% CI 0.98 and 1.20, I2 = 0%). The incidence of side-effects of double-dose regimen was similar with single-dose regimen. Side-effects, however, are more common in multiple-dose regimen (RR 1.64, 95% CI 1.15 to 2.34, P = 0.006, I2 = 0%). This meta-analysis indicated that the incidence of side-effects of multiple-dose protocol was significantly higher than single-dose protocol, and the success rates between them were similar. The double-dose regimen was an efficient and safe alternative to the single-dose protocol. Further high-quality researches are needed to confirm our findings and to develop the optimal protocol. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2000-02-01

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

  10. Predictive score for the systemic treatment of unruptured ectopic pregnancy with a single dose of methotrexate.

    Science.gov (United States)

    Elito, J; Reichmann, A P; Uchiyama, M N; Camano, L

    1999-11-01

    To evaluate the efficacy of a predictive score for the systemic treatment of unruptured ectopic pregnancy with a single dose of methotrexate in order to select the best cases for the medical treatment. Our study included 40 patients. The inclusion criteria were: hemodynamic stability; adnexal mass or = 5 were treated successfully (29/30 - 97%), while those with grade or = 5. Federation of Gynecology and Obstetrics.

  11. Redefining radiotherapy for early-stage breast cancer with single dose ablative treatment : a study protocol

    OpenAIRE

    Charaghvandi, R K; van Asselen, B; Philippens, M E P; Verkooijen, H M; van Gils, C H; van Diest, P J; Pijnappel, R M; Hobbelink, M G G; Witkamp, A J; van Dalen, T; van der Wall, E; van Heijst, T C; Koelemij, R; van Vulpen, M; van den Bongard, H J G D

    2017-01-01

    Background A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy. Methods The ABLATIVE study is a prosp...

  12. Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

    Science.gov (United States)

    Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

    2017-12-01

    African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

  13. Redefining radiotherapy for early-stage breast cancer with single dose ablative treatment: a study protocol.

    Science.gov (United States)

    Charaghvandi, R K; van Asselen, B; Philippens, M E P; Verkooijen, H M; van Gils, C H; van Diest, P J; Pijnappel, R M; Hobbelink, M G G; Witkamp, A J; van Dalen, T; van der Wall, E; van Heijst, T C; Koelemij, R; van Vulpen, M; van den Bongard, H J G D

    2017-03-09

    A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy. The ABLATIVE study is a prospective, single arm, multicenter study evaluating preoperative, single dose, ablative radiation treatment in patients with early-stage breast cancer. Patients with core biopsy proven non-lobular invasive breast cancer, (estrogen receptor positive, Her2 negative, maximum tumor size 3.0 cm on diagnostic MRI) and a negative sentinel node biopsy are eligible. Radiotherapy (RT) planning will be performed using a contrast enhanced (CE) planning CT-scan, co-registered with a CE-MRI, both in supine RT position. A total of twenty-five consecutive patients will be treated with a single ablative RT dose of 20 Gy to the tumor and 15 Gy to the tumorbed. Follow-up MRIs are scheduled within 1 week, 2, 4 and 6 months after single-dose RT. Breast-conserving surgery is scheduled at six months following RT. Primary study endpoint is pathological complete response. Secondary study endpoints are the radiological response and toxicity. Furthermore, patients will fill out questionnaires on quality of life and functional status. Cosmetic outcome will be evaluated by the treating radiation oncologist, patient and 'Breast Cancer Conservation Treatment cosmetic results' software. Recurrence and survival rates will be assessed. The patients will be followed up to 10 years after diagnosis. If patients give additional informed consent, a biopsy and a part of the irradiated specimen will be stored at the local Biobank and used for future research on radiotherapy response associated genotyping. The ABLATIVE study evaluates

  14. Single-dose methotrexate for the treatment of ectopic pregnancy: Our experience from 2010 to 2015.

    Science.gov (United States)

    Tas, Emre Erdem; Akcay, Gulin Feykan Yegin; Avsar, Ayse Filiz

    2017-01-01

    To evaluate the success of systemic single-dose methotrexate (MTX) treatment in patients with ectopic pregnancy (EP) and to investigate factors related to treatment success. This retrospective study had been performed in Yildirim Beyazit University between January 2010 and December 2015. Demographic and clinical characteristics, ultrasonografic findings, pretreatment serum β-human chorionic gonadotropin (β-hCG) and progesterone levels of 58 patients with EP were retrieved from hospital records retrospectively. The patients were grouped according to MTX treatment success (response vs. failure). Single-dose MTX-treatment was successful in 72.4% (42/58) of patients. The mean pretreatment β-hCG level was significantly lower in responders than in failures (2080 ± 2322 vs. 5707 ± 3885 IU/L, p = 0.001), and 2678 IU/L was the most suitable cutoff to predict success (75% sensitivity, 73.8% specificity). Moreover, failure rate was 8.45 times more in group of patients whose β-hCG values were determined above the cutoff. The presence of fetal cardiac activity adversely affected treatment success (odds ratio = 12, p = 0.004). Treatment success was not affected by past history of ectopic pregnancy, thickness of endometrium, progesterone value or presences of pseudosac and free pelvic fluid. The success rate of single dose MTX in this study was 72.8 %, and we found that failure rate of MTX treatment was 8.45 times more in group of patients whose initial serum β-hCG values were above 2678 IU/L and 12 times more in patients with fetal cardiac activity.

  15. Single Dose IV Peramivir is Safe and Effective in the Treatment of Pediatric Influenza

    Science.gov (United States)

    Vanchiere, John; Plunkett, Stephanie; Annamalai, Rajasekaran; Julien, Katie; Peterson, James; Goisse, Marcy; Christensen, Shane; Mehta, Priyesh; Coleman, Stephen; Munoz, Flor; Flynt, Amy; Dobo, Sylvia; Nagy, Eniko; Kargl, Deborah; Mathis, Amanda; Collis, Phil; Sheridan, William

    2017-01-01

    Abstract Background Peramivir (PVR) is a potent neuraminidase inhibitor with in vitro activity against all influenza virus subtypes. Previous studies demonstrated the efficacy and safety of PVR as a single dose intravenous (IV) treatment for acute uncomplicated influenza in adults. Methods A phase 3 study compared age-appropriate doses of single dose IV PVR to 5 days of oral oseltamivir (OSE) (4:1 randomization, stratified by age) in pediatric subjects age 0 -17 years within 48 hours of onset of acute uncomplicated influenza. Plasma concentrations of PVR were measured up to 6 hours post dose. Serial viral titers were measured from nasopharyngeal swabs. Severity of influenza signs and symptoms were recorded in a diary. Results 122 subjects were enrolled up to a data cutoff of March 31, 2017 (Coleman, BioCryst Pharmaceuticals: Investigator, Research support; F. Munoz, BioCryst Pharmaceuticals: Investigator, Research support; A. Flynt, BioCryst Pharmaceuticals: Consultant, Consulting fee; S. Dobo, BioCryst Pharmaceuticals: Employee, Salary; E. Nagy, BioCryst Pharmaceuticals: Employee, Salary; D. Kargl, BioCryst Pharmaceuticals: Consultant, Consulting fee; A. Mathis, BioCryst Pharmaceuticals: Employee, Salary; P. Collis, BioCryst Pharmaceuticals: Employee, Salary; W. Sheridan, BioCryst Pharmaceuticals: Employee, Salary

  16. Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy.

    Science.gov (United States)

    Kim, Junhwan; Jung, Young Mi; Lee, Da Yong; Jee, Byung Chul

    2017-01-01

    To investigate individual pretreatment serum human chorionic gonadotropin (hCG) cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. Eighty-five women who received methotrexate for the treatment of tubal ectopic pregnancy during 2003 to 2015 were selected. Fifty-three women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. The medical treatment success rate was estimated in both regimens and the pretreatment serum hCG titer to predict the success was assessed by receiver operating characteristics curve analysis. Pretreatment clinical and laboratory parameters were similar between group of single-dose regimen and multi-dose regimen. Treatment success rate was 64.2% in the single-dose regimen group and 71.9% in the multi-dose regimen group (P>0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3,026 IU/L in single-dose regimen group and 3,711 IU/L in multi-dose regimen group. We recommend use of single-dose regimen when pretreatment serum hCG <3,026 IU/L but multi-dose regimen may be favored when initial serum hCG level between 3,026 and 3,711 IU/L.

  17. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open......-label, randomized controlled trial. Participants received intravenous iron (n = 97) or oral iron (n = 99), and completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and haematological and iron parameters were measured. Primary outcome was the aggregated change in physical...... fatigue score from baseline to 12 weeks postpartum. RESULTS: The difference in physical fatigue score was -0·97 (95% CI: -1·65; -0·28, P = 0·006) in favour of intravenous iron, but did not meet the predefined difference of 1·8. Across visits, we found statistically significant differences in fatigue...

  18. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

    Directory of Open Access Journals (Sweden)

    Maha M Eissa

    Full Text Available Miltefosine (MFS is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD. This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%, good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs

  19. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

    Science.gov (United States)

    Eissa, Maha M; El-Moslemany, Riham M; Ramadan, Alyaa A; Amer, Eglal I; El-Azzouni, Mervat Z; El-Khordagui, Labiba K

    2015-01-01

    Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting

  20. Single-day, three-dose treatment with fixed dose combination artesunate/sulfamethoxypyrazine/pyrimethamine to cure Plasmodium falciparum malaria.

    Science.gov (United States)

    Penali, Louis Koné; Jansen, Frans Herwig

    2008-07-01

    Malaria kills approximately 1.5 to 2.7 million people each year. Despite the introduction of artemisinin-based combination therapies (ACTs), the treatment of malaria is hampered by problems such as inadequate efficacy, recrudescence, early re-infection, low patient compliance, and high cost price of drugs. This study tested the hypothesis that the co-formulated fixed dose combination (FDC) artesunate/sulfamethoxypyrazine/pyrimethamine (As/SMP) administered as a 24-hour therapy with a dose interval of 12 hours is as efficacious and safe as the administration of the same drug over 3 days given with a dose interval of 24 hours, for the treatment of uncomplicated Plasmodium falciparum malaria in Ivory Coast. Two hundred and twenty-one patients presenting with uncomplicated P. falciparum malaria were randomly assigned to either one of the two dosing schemes. Treatment efficacy was assessed using the current 28-day World Health Organization protocol, success being determined by absence of recrudescence and parasitemia on day 28. Both treatment regimens were highly efficacious, with a success rate of 100% (111/111) for the 3-day therapy and 99% (109/110) for the 24-hour therapy. Only one patient in the 24-hour therapy group showed late treatment failure. No serious adverse events or significant laboratory abnormalities were seen. The 24-hour therapy is as well tolerated and efficacious as the same medicament administered over 3 days. This low cost and simplified three-pill treatment is certain to improve compliance.

  1. Total and single doses influence the effectiveness of radiotherapy in palliative treatment of plasmacytoma

    Energy Technology Data Exchange (ETDEWEB)

    Stoelting, T.; Knauerhase, H.; Klautke, G. [Dept. of Radiotherapy, Univ. of Rostock (Germany); Kundt, G. [Inst. for Medical Informatics and Biometry, Univ. of Rostock (Germany); Fietkau, R. [Dept. of Radiotherapy, Univ. of Rostock (Germany); Dept. of Radiotherapy, Univ. of Erlangen (Germany)

    2008-09-15

    Purpose: in a retrospective analysis of radiotherapy of plasmacytomas, the effectiveness and the prognostic factors in regard to pain reduction and recalcification were evaluated. Patients and methods: 138 patients (70 women, 68 men; 15-86 years, median 61 years) were irradiated at 272 target volumes (TVs) from January 1970 to December 2003. Results: in 192/225 TVs (85.3%), there was a pain reduction. The recalcification rate was 44.7% (51/114 TVs). Significant parameters for pain relief in the multivariate analysis were completeness of therapy (odds ratio [OR] 87.8; p < 0.001 vs. interruption), patients < 60 years (OR 23.0; p < 0.001 vs. {>=} 70 years), and a single dose of 2 Gy (OR 11.0; p = 0.027 vs. 4-15.0 Gy). Significant parameters for recalcification in the multivariate analysis were concurrent chemotherapy (OR 12.3; p < 0.001 vs. no chemotherapy), no fractures in the TV (OR 5.9; p < 0.004 vs. fracture), and a dose of 40-< 50 Gy (OR 21.9; p = 0.035 vs. < 30 Gy) or {>=} 50 Gy (OR 26.4; p = 0.033 vs. < 30 Gy). Conclusion: radiotherapy is a very effective palliative treatment. Patients with a reduced general condition, with multiple bone lesions and a poor prognosis profit from short-term schemes (e.g., 1 x 8 Gy to 10 x 3 Gy). Patients in good general condition with a life expectancy of > 1 year and an osteolysis at risk of fracture, should be treated with doses up to 40-50 Gy (20-25 x 2 Gy), in order to achieve the best possible recalcification and pain relief. (orig.)

  2. Single-dose methotrexate treatment for ectopic pregnancy and pregnancy of unknown location and progesterone as a predictor of success.

    Science.gov (United States)

    Wu, Joyce; Ludlow, Joanne P; De Vries, Bradley; Black, Kirsten; Beale, Philip

    2014-10-01

    The use of single-dose intramuscular administration of methotrexate in the treatment of ectopic pregnancies (EP) is a well-established practice. This study evaluates its use at a novel dose of 40 mg/m(2) body surface area (BSA). To evaluate the efficacy and safety of single-dose methotrexate treatment 40 mg/m(2) for tubal EP and persistent pregnancies of unknown location (PUL) and determine whether serum progesterone is a predictor of treatment success. Retrospective cohort study of patients receiving intramuscular methotrexate 40 mg/m(2) for the treatment of EP or PUL at Royal Prince Alfred Hospital over five years. One hundred and eighteen women received single-dose methotrexate with an overall success of 84%. Surgical intervention was needed in 16.6%. Pretreatment beta-hCG level and ectopic diagnosis were independent variables predictive of the need for surgery (P = 0.003 and 0.02, respectively). Serum progesterone level was not predictive of the need for a second dose or surgery. The sensitivity and specificity at pretreatment beta-hCG of 1202 IU/L were 84% and 74%, respectively. Commonly reported side effects included nausea, abdominal pain and heavy vaginal bleeding. Significant treatment-related adverse effects were rare. Single-dose IM methotrexate at a novel dose of 40 mg/m(2) is a safe and effective treatment for selected EP and persistent PUL. The risk of surgery was positively correlated to serum beta-hCG level and the diagnosis of EP. Progesterone was not a risk factor for surgery. Further studies are required to confirm the efficacy of this dose regimen and explore the safety of expectant management as an alternative to methotrexate treatment. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  3. The syndromic management of vaginal discharge using single-dose treatments: a randomized controlled trial in West Africa.

    Science.gov (United States)

    Pépin, Jacques; Sobela, François; Khonde, Nzambi; Agyarko-Poku, Thomas; Diakité, Soumaila; Deslandes, Sylvie; Labbé, Annie-Claude; Sylla, Mohamed; Asamoah-Adu, Comfort; Frost, Eric

    2006-09-01

    To evaluate whether single-dose treatments are as effective as standard therapy in the syndromic management of vaginal discharge. A randomized controlled effectiveness trial compared single-dose tinidazole plus fluconazole (TF) with treatment for 7 days with metronidazole plus 3 days of treatment with vaginal clotrimazole (MC) among 1570 women presenting with vaginal discharge at primary health care institutions in Ghana, Guinea, Mali and Togo. Participants were randomly allocated to one of the two treatments by research nurses or physicians using precoded envelopes. Effectiveness was assessed by symptomatic response on day 14. CLINICAL IDENTIFIER ClinicalTrials.gov NCT00313131. The two treatment regimens had similar effectiveness: complete resolution was seen in 66% (TF) and 64% (MC) and partial resolution in 33% (TF) and 34% (MC) of participants (P = 0.26). Effectiveness was similar among subgroups with vulvovaginal candidiasis, Trichomonas vaginalis vaginitis or bacterial vaginosis. The two treatment regimens had a similar effectiveness among human immunodeficiency virus (HIV)-infected (TF: n = 76, 71% complete resolution, 28% partial; MC: n = 83, 72% complete resolution, 25% partial, P = 0.76) and HIV-uninfected women (TF: n = 517, 68% complete, 32% partial; MC: n = 466, 65% complete, 33% partial, P = 0.20). Cervical infections with Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium were uncommon among women not involved in sex work, were associated with bacterial vaginosis or T. vaginalis vaginitis, and did not alter response to treatment with agents active against vaginal infections. Four-fifths of women not relieved by a single dose of TF had a favourable response when MC was administered as second-line treatment. Single-dose TF is as effective as multiple-dose MC in the syndromic management of vaginal discharge, even among women with HIV-infection. Given its low price and easier adherence, TF should be considered as a first

  4. Peripheral doses in patients undergoing Cyberknife treatment for intracranial lesions. A single centre experience

    Directory of Open Access Journals (Sweden)

    Vlachopoulou Vassiliki

    2011-11-01

    Full Text Available Abstract Background Stereotactic radiosurgery/radiotherapy procedures are known to deliver a very high dose per fraction, and thus, the corresponding peripheral dose could be a limiting factor for the long term surviving patients. The aim of this clinical study was to measure the peripheral dose delivered to patients undergoing intracranial Cyberknife treatment, using the MOSFET dosimeters. The influence of the supplemental shielding, the number of monitor units and the collimator size to the peripheral dose were investigated. Methods MOSFET dosimeters were placed in preselected anatomical regions of the patient undergoing Cyberknife treatment, namely the thyroid gland, the nipple, the umbilicus and the pubic symphysis. Results The mean peripheral doses before the supplemental shielding was added to the Cyberknife unit were 51.79 cGy, 13.31 cGy and 10.07 cGy while after the shielding upgrade they were 38.40 cGy, 10.94 cGy, and 8.69 cGy, in the thyroid gland, the umbilicus and the pubic symphysis, respectively. The increase of the collimator size corresponds to an increase of the PD and becomes less significant at larger distances, indicating that at these distances the PD is predominate due to the head leakage and collimator scatter. Conclusion Weighting the effect of the number of monitor units and the collimator size can be effectively used during the optimization procedure in order to choose the most suitable treatment plan that will deliver the maximum dose to the tumor, while being compatible with the dose constraints for the surrounding organs at risk. Attention is required in defining the thyroid gland as a structure of avoidance in the treatment plan especially in patients with benign diseases.

  5. Single-Dose Compared With Multidose Metronidazole for the Treatment of Trichomoniasis in Women: A Meta-Analysis.

    Science.gov (United States)

    Howe, Katharine; Kissinger, Patricia J

    2017-01-01

    Trichomonas vaginalis is the most common curable sexually transmitted infection worldwide. Although the Centers for Disease Control and Prevention and the World Health Organization recommend a single 2-g dose of metronidazole for the first line of treatment for T. vaginalis among human immunodeficiency virus (HIV) negative women, high rates of repeat infections are found. The purpose of this meta-analysis was to compare treatment failure between single versus multidose metronidazole for the treatment of T. vaginalis. A systematic literature search was performed using search terms including metronidazole AND trichomoniasis AND women. Embase, MEDLINE, and Clinicaltrials.gov were used to search for relevant studies as well as hand searching relevant articles. These databases were last searched on January 25, 2016. To be included in this meta-analysis, the study had to be a clinical trial, evaluate T. vaginalis, use oral metronidazole, and compare single dose metronidazole to multidose metronidazole. There were 487 articles that were assessed for relevance and quality. Of these articles, 6 met the eligibility criteria and were included in the final results. The pooled risk ratio indicated higher treatment failure for single dose compared to multidose 1.87 (95% confidence interval, 1.23-2.82; P < 0.01). When the one study that included HIV+ women was excluded from analysis, the findings were similar with a pooled risk ratio of 1.80 (95% confidence interval, 1.07-3.02; P < 0.03). Centers for Disease Control and Prevention recently changed treatment recommendations for HIV+ women to multidose rather than single-dose. These data suggest that those recommendations should be considered for all women.

  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. Efficacy of single and double doses of albendazole and mebendazole alone and in combination in the treatment of Trichuris trichiura in school-age children in Uganda

    DEFF Research Database (Denmark)

    Namwanje, Harriet; Kabatereine, Narcis B.; Olsen, Annette

    2011-01-01

    A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment of Trichu......A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment...

  8. A RANDOMIZED TREATMENT TRIAL: SINGLE VERSUS 7 DAY DOSE OF METRONIDAZOLE FOR THE TREATMENT OF TRICHOMONAS VAGINALIS AMONG HIV-INFECTED WOMEN

    Science.gov (United States)

    Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A.; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan; Myers, Leann; Martin, David H.

    2010-01-01

    Objective To determine if the metronidazole (MTZ) 2 gm single dose (recommended) is as effective as the 7 day 500 mg BID dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Methods Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2 gm single dose or MTZ 500 mg BID 7 day dose. All women were given 2 gm MTZ doses to deliver to their sex partners. Women were re-cultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again re-cultured at a 3 month visit. Repeat TV infection rates were compared between arms. Results 270 HIV+/TV+ women were enrolled (mean age = 40 years, ± 9.4; 92.2% African-American). Treatment arms were similar with respect to age, race, CD4 count, viral load, ART status, site, and loss-to-follow up. Women in the 7 day arm had: lower repeat TV infection rates at TOC [8.5% (11/130) versus 16.8% (21/125) (R.R. 0.50, 95% CI=0.25, 1.00; P<0.05)], and at 3 months [11.0% (8/73) versus 24.1% (19/79) (R.R. 0.46, 95% CI=0.21, 0.98; P=0.03)] compared to the single dose arm. Conclusions The 7 day MTZ dose was more effective than the single dose for the treatment of TV among HIV+ women. PMID:21423852

  9. A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women.

    Science.gov (United States)

    Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L; Myers, Leann; Martin, David H

    2010-12-15

    To determine if the metronidazole (MTZ) 2-gm single dose (recommended) is as effective as the 7-day 500 mg twice a day dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2-gm single dose or MTZ 500 mg twice a day 7-day dose. All women were given 2-gm MTZ doses to deliver to their sex partners. Women were recultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again recultured at a 3-month visit. Repeat TV infection rates were compared between arms. Two hundred seventy HIV+/TV+ women were enrolled (mean age = 40 years, ±9.4; 92.2% African American). Treatment arms were similar with respect to age, race, CD4 count, viral load, antiretroviral therapy status, site, and loss-to-follow up. Women in the 7-day arm had lower repeat TV infection rates at TOC [8.5% (11 of 130) versus 16.8% (21 of 125) (relative risk: 0.50, 95% confidence interval = 0.25, 1.00; P < 0.05)] and at 3 months [11.0% (8 of 73) versus 24.1% (19 of 79) (relative risk: 0.46, 95% confidence interval = 0.21, 0.98; P = 0.03)] compared with the single-dose arm. The 7-day MTZ dose was more effective than the single dose for the treatment of TV among HIV+ women.

  10. Single dose and pulsatile treatment with human growth hormone in growth hormone deficiency.

    OpenAIRE

    Smith, P J; Pringle, P J; Brook, C G

    1987-01-01

    The growth and growth hormone profiles in four children receiving three different regimens of treatment with human growth hormone (hGH) were compared. There was no significant difference in the rate of growth between the regimens; the rate of growth fell dramatically after treatment. Pulsatile administration of hGH was no better than conventional treatment.

  11. Single-dose liposomal amphotericin B (AmBisome® for the treatment of Visceral Leishmaniasis in East Africa: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Smith Peter G

    2011-03-01

    Full Text Available Abstract Background AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified. Methods/Design An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®. Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg. Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose. Discussion An effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies. Trial Registration ClinicalTrials.gov NCT00832208

  12. The impact of salpingectomy and single-dose systemic methotrexate treatments on ovarian reserve in ectopic pregnancy.

    Science.gov (United States)

    Sahin, Cagdas; Taylan, Enes; Akdemir, Ali; Ozgurel, Banu; Taskıran, Dilek; Ergenoglu, Ahmet M

    2016-10-01

    To investigate the effects of salpingectomy and methotrexate treatments on ovarian reserve in ectopic pregnancy. In this prospective study, a total of 131 patients with ectopic pregnancy were divided into 3 groups of methotrexate (MTX) only (Group-1, n: 55), salpingectomy only (Group-2, n: 61), and salpingectomy following MTX (Group-3, n: 15). Pretreatment and post-treatment anti-Müllerian hormone (AMH) levels were evaluated. Significant differences in AMH levels were detected between group 1 and group 2 (2.52±1.28 vs. 1.96±1.66, p=0.043), and group 1 and group 3 (2.52±1.28 vs. 1.77±0.76, p=0.035) at one month postoperative. However, these differences disappeared at the 3rd postoperative month. When AMH levels were compared within the same group, postoperative one month AMH levels were significantly lower than the preoperative AMH levels only in group 3 (p=0.03). However, this difference also disappeared at the 3rd postoperative month. Systemic single-dose methotrexate treatment, unilateral salpingectomy, and salpingectomy following methotrexate administration in ectopic pregnancy were reassuring based on pretreatment and post-treatment AMH levels. Current medical and surgical treatment approaches do not have an obvious negative effect on ovarian reserve. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    Charlotte Bernigaud

    2016-10-01

    Full Text Available Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM are insufficient and drug resistance is emerging. Moxidectin (MOX, with more advantageous pharmacological profiles may be a promising alternative.Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once, IVM (0.2 mg/kg twice or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47, compared to 62% (range 26-100% for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy.Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

  14. Serum β-hCG levels post-treatment of ectopic pregnancy with a single dose of intramuscular methotrexate.

    Science.gov (United States)

    Hadinata, Ignatius E; Doyle, Lex W; Thompson, Derrick; Reti, Leslie

    2015-04-01

    The cytotoxic management of ectopic pregnancy using a single dose of intramuscular methotrexate injection has been well established as effective for a select number of women with unruptured tubal ectopic pregnancy where there are minimal symptoms. The purpose of this study was to create centile curves of serum β-hCG levels following successful treatment with a single dose of 50 mg/m(2) of intramuscular methotrexate to treat ectopic pregnancy. Data were retrieved from women treated at the Royal Women's Hospital for ectopic pregnancy between 2006 and 2012. Only women with minimal symptoms, initial serum β-hCG ≤5000 IU/L and ectopic mass size of ≤35 mm on ultrasound were included. Two hundred and fifty-three cases of ectopic pregnancy were analysed. Initial β-hCG of women in the study ranged from 18 to 3995 IU/L with a median of 497 (25th to 75th centiles; 222-1160) IU/L. The median levels of β-hCG levels at day 4, 7 and 14 postmethotrexate injection were 73.8, 47.2 and 10.4% of the initial β-hCG level, respectively. The 90th centiles of β-hCG levels at day 4, 7 and 14 were 124.7, 93.8 and 40.0% of initial β-hCG level, respectively. Whilst no comparison with those unsuccessfully treated was made, pending further validation studies, the use of these curves may reduce the reliance on specialist units and streamline care for many women with ectopic pregnancy, such as those whose β-hCG regress in line with centile values without crossing a certain threshold. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  15. 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.

  16. Single-dose electron beam irradiation in treatment and prevention of keloids and hypertrophic scars

    Energy Technology Data Exchange (ETDEWEB)

    Lo, T.C.M.; Salzman, F.A. (Lahey Clinic Medical Center, Burlington (USA). Department of Radiation Oncology); Seckel, B.R. (Lahey Clinic Medical Center, Burlington (USA). Department of Plastic and Reconstructive Surgery); Wright, K.A. (Massachusetts Institute of Technology, Cambridge (USA). High Voltage Research Laboratory)

    1990-11-01

    Low megavolt electron beam irradiation was used on 354 sites in 199 patients at Lahey Clinic either for palliation of symptomatic hypertrophic scars or as post operative irradiation in an attempt to prevent formation or recurrence of hypertrophic scars. Electron energies used ranged from 1.5 to 3.5 MeV. The median age of the 59 male patients was 22 years and of the 140 female patients 35 years. All patients had at least one follow-up visit, and the median follow-up was 35 months. Of the 294 sites treated for the first time, 272 were irradiated with a single fraction with a skin dose ranging from 2 to 20 Gy. Of the 85 sites in 63 patients without excision of symptomatic hypertrophic scars, single-dose electron beam irradiation was of clinically significant value in only 41 sites. No patients have been treated without surgical excision since 1973. Because of a history of formation of hypertrophic scars elsewhere in the body, 13 patients with 19 incisions were treated prophylactically after operation for other diseases. All sites were irradiated with single doses ranging from 8 to 20 Gy, and hypertrophic scars did not subsequently develop in any patient. Altogether, 119 patients with 174 sites were irradiated after surgical excision of hypertrophic scars to prevent recurrence; 168 sites received singe-fraction irradiation, and 161 received a dose of 8 Gy greater, up to 15 Gy. No statistically significant differences were observed in complete success rates, ranging from 82 to 90 per cent with doses of 9 Gy or greater. An interval of up to 72h between excision and single-fraction irradiation satisfactorily prevented recurrence, and clinically significant chronic telangiectasia was recorded in only one patient. Postoperative low megavolt electron beam irradiation with a single dose of 9 Gy or greater is highly effective in the prevention of formation recurrence of hypertrophic scars or keloids.

  17. Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

    Directory of Open Access Journals (Sweden)

    Iyoke CA

    2017-05-01

    Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

  18. Interstitial pulsed-dose-rate brachytherapy for the treatment of squamous cell anal carcinoma: A retrospective single institution analysis.

    Science.gov (United States)

    Boukhelif, W; Ferri-Molina, M; Mazeron, R; Maroun, P; Duhamel-Oberlander, A S; Dumas, I; Martinetti, F; Guemnie-Tafo, A; Chargari, C; Haie-Meder, C

    2015-01-01

    To examine the outcome of patients receiving interstitial pulsed-dose-rate brachytherapy (PDR-BT) after pelvic radiation therapy for treatment of an anal squamous cell carcinoma. Twenty-one patients were identified: 13, six, and two with stages I, II, and III tumors, respectively. After receiving received pelvic irradiation +/- concurrent chemotherapy, patients were delivered a PDR-BT boost to the residual tumor, with intention to deliver a minimal total dose of 60 Gy. The greatest dimension of residual tumor at the time of brachytherapy procedure was 12.5 mm (range: 0-20 mm). Brachytherapy implantation was performed according to the Paris system, only one plane implant being used. Median dose delivered through BT was 20 Gy (range: 10-30 Gy). Median number of pulses was 48 (range: 20-80 pulses). Median treated volume was 9 cm(3) (range: 5-16 cm(3)). Median dose per pulse was 40 cGy (range: 37.5-50 cGy). No Grade 3 or more acute toxicity was reported. No Grade 3 or more delayed toxicity was seen among 18 patients with more than 6 months follow-up. Median followup was 47 months (range: 6-73 months). Twenty patients (95%) were alive at last follow-up. Tumor relapses were experienced in four patients (19%), including local relapse in three patients (14%). With almost 4 years median followup, this study confirms previous data suggesting that PDR-BT is effective and safe in this indication. Local control rate and toxicity were in the range of what was seen with continuous low-dose-rate BT. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  19. Comparison of peripheral and central effects of single and repeated oral dose administrations of bilastine, a new H1 antihistamine: a dose-range study in healthy volunteers with hydroxyzine and placebo as control treatments.

    Science.gov (United States)

    García-Gea, Consuelo; Martínez-Colomer, Joan; Antonijoan, Rosa M; Valiente, Román; Barbanoj, Manuel-José

    2008-12-01

    Peripheral anti-H1 and central nervous system (CNS) activities after single (day 1) and repeated (day 7) administrations of increasing doses of bilastine (BIL) were assessed in 20 healthy volunteers throughout a crossover, randomized, double-blind, placebo (PLA)-controlled study. Repeated doses of BIL 20, 40, or 80 mg and hydroxyzine 25 mg (HYD) as positive standard were administered on 7 consecutive days. Before and at several time points after drug intake, skin reactivity to the intradermal injection of histamine, objective tests of psychomotor performance, and subjective mood scales were evaluated. All active treatments led to a significant and similar reduction in the wheal reaction in relation to PLA after both the single (P Bilastine 80 mg also showed some impairment (P < 0.05). Subjectively, the only active treatment that could not be differentiated from PLA was BIL 20 mg. Hydroxyzine 25 mg showed the greatest differentiation (P < 0.01). A clear dissociation between peripheral anti-H1 and CNS activity was found after BIL treatment. Significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL. The 40-mg dose of BIL produced subjective report of sedation, whereas unwanted objective CNS side effects were observed only with the 80-mg dose.

  20. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

    2015-01-01

    BACKGROUND: Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published...... randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...... 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard...

  1. The treatment of Trichomonas vaginalis vaginitis. An open controlled prospective study comparing a single dose of metronidazole tablets, benzoyl metronidazole suspension and tinidazole tablets.

    Science.gov (United States)

    Bloch, B; Smyth, E

    1985-03-23

    Metronidazole tablets, benzoyl metronidazole suspension and tinidazole tablets each given as a single 2 g bolus dose in an open controlled prospective study were found to be effective forms of treatment for Trichomonas vaginalis vaginitis. The cure rates on wet smear preparations were 100%, 100% and 94,8% respectively, and symptomatic and observed improvements were excellent. There was a statistically significant difference between the response rates associated with both metronidazole preparations and tinidazole. The results of this study indicate that single-dosage bolus therapy can confidently be recommended in trichomonal infections and that it has a number of advantages.

  2. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    Science.gov (United States)

    Tipple, Craig; Jones, Rachael; McClure, Myra; Taylor, Graham

    2015-02-01

    Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

  3. A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

    Science.gov (United States)

    Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

    2016-10-17

    We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant

  4. MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Q [Wayne State University, Detroit, MI (United States); Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.

  5. Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

    Science.gov (United States)

    Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

    2015-07-01

    Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    Directory of Open Access Journals (Sweden)

    Craig Tipple

    2015-02-01

    Full Text Available Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum, is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene and RNA (16S rRNA quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53. The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84. From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56 after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

  7. One-Gram, Single-Dose Metronidazole (Flagyl) for Trichomonal Vaginitis.

    Science.gov (United States)

    Moore, Jennifer R.

    1979-01-01

    Effective single-dose treatment of trichomonal vaginitis is reported. Large single-dose treatment with metronidazole was found to be effective and avoided the side effects occurring with multidose treatment. (MJB)

  8. Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge

    Directory of Open Access Journals (Sweden)

    Brian B. Gowen

    2014-03-01

    Full Text Available Rift Valley fever virus (RVFV causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life, as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity.

  9. Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

    Science.gov (United States)

    Deck, Daniel H; Jordan, Jennifer M; Holland, Thomas L; Fan, Weihong; Wikler, Matthew A; Sulham, Katherine A; Ralph Corey, G

    2016-09-01

    Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. The Medicines Company

  10. AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a single-dose study in hemodialysis patients.

    Science.gov (United States)

    Martin, Kevin J; Pickthorn, Karen; Huang, Saling; Block, Geoffrey A; Vick, Andrew; Mount, Peter F; Power, David A; Bell, Gregory

    2014-01-01

    AMG 416 (velcalcetide), a novel peptide agonist of the calcium-sensing receptor, lowers plasma parathyroid hormone in preclinical uremic animal models and in normal healthy individuals. Here, we studied its efficacy in hemodialysis patients suffering from secondary hyperparathyroidism. Major inclusion criteria were hemodialysis for at least 3 months, serum parathyroid hormone over 300 pg/ml, a corrected serum calcium of 9.0 mg/dl or more, and stable doses of vitamin D analogs for at least 3 weeks prior to screening. Twenty-eight patients were enrolled in one of five cohorts (5, 10, 20, 40, 60 mg). Cohorts 1-3 (four patients each) were treated in a two-period crossover design, while cohorts 4 and 5 (eight patients each) were randomized 1:1 to AMG 416 or placebo. Patients were admitted to a clinical research unit following hemodialysis and studied for 3 days prior to discharge for hemodialysis. Single intravenous doses of AMG 416 from 5 to 60 mg were well tolerated, and plasma levels increased in a dose-related manner. AMG 416 treatment was associated with significant, dose-dependent reductions in serum parathyroid hormone and fibroblast growth factor 23. Compared with placebo, all dose groups of 10 mg or more were associated with attenuation in the rise in serum phosphate during the interdialytic period. Dose-dependent reductions in serum calcium were observed and were well tolerated. Thus, AMG 416 represents a novel therapeutic approach for the treatment of secondary hyperparathyroidism in hemodialysis patients.

  11. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections.

    Science.gov (United States)

    Goncars, Valdis; Jakobsons, Eriks; Blums, Kristaps; Briede, Ieva; Patetko, Liene; Erglis, Kristaps; Erglis, Martins; Kalnberzs, Konstantins; Muiznieks, Indrikis; Erglis, Andrejs

    2017-01-01

    The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups. A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II-III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n=28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n=28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection. A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (P<0.05) on the pain subscale (+25.44), activity and daily living subscale (+21.36), quality of life subscale (+28.83), and total KOOS (+18.25). The KSS score also demonstrated a significant improvement on the symptoms subscale (+25.42) and the function subscale (+38.32) (P<0.001). The KOOS symptoms and sports subscales improved without statistical significance. The difference between the control group treated with hyaluronic acid versus the bone marrow-derived mononuclear cells group at time points 6 and 12 months demonstrated a statistically significant (P<0.05) superiority in the KOOS pain subscale over the hyaluronic acid group. In both groups serious adverse effects were not observed. The

  12. Single oral dose of azithromycin versus 5 days of oral erythromycin or no antibiotic in treatment of campylobacter enterocolitis in children: a prospective randomized assessor-blind study.

    Science.gov (United States)

    Vukelic, Dalibor; Trkulja, Vladimir; Salkovic-Petrisic, Melita

    2010-04-01

    To evaluate efficacy of a single oral azithromycin dose versus standard oral erythromycin regimen or no antibiotic for Campylobacter enterocolitis in children younger than or equal to 12 years of age. Randomized parallel group assessor-blind trial testing for inequality in efficacy between treatments was done. Patients (N = 120) were enrolled at less than or equal to 48 hours since disease onset to receive erythromycin 50 mg kg day for 5 days, single-dose azithromycin 20 mg/kg or 30 mg/kg, or no antibiotic (no treatment control) (1: 1: 1: 1). Antibiotics were commenced 8 to 10 hours after enrollment. Patients were assessed at 24-hour intervals for 6 days. In the intent-to-treat analysis, Campylobacter eradication was achieved in 20 of 30 controls and in all of the patients treated with antibiotic. Incidence of clinical cure during the observed period was 15 of 30 in the control, 14 of 30 in the erythromycin, 20 of 30 in the lower, and 25 of 30 in the higher azithromycin dose group. With adjustment for age, sex, baseline disease severity, and disease duration before enrollment, only azithromycin 30 mg/kg was superior to no treatment: incidence ratio (IR) 1.76 (95% confidence interval [CI] 1.11-2.87). It was also superior to erythromycin (IR 1.80, 97.5% CI 1.13-2.84). Regarding time to clinical cure, only azithromycin 30 mg/kg was superior to no treatment (adjusted hazard ratio [HR] 4.90, 95% CI 2.44-9.84). It was also superior to erythromycin (HR 4.17, 97.5% CI 1.91-9.09). All treatments were well tolerated. The administration of single oral dose of azithromycin 30 mg/kg early after disease onset effectively eradicates the pathogen and accelerates clinical cure in childhood Campylobacter enterocolitis. It is clinically superior to an early commenced 5-day erythromycin regimen, which apparently conveys no clinically relevant benefit over no antibiotic treatment.

  13. Assessment of chloroquine single dose treatment of malaria due to Plasmodium vivax in Brazilian Amazon Cloroquina em dose simples no tratamento da malária por Plasmodium vivax na Amazônia brasileira

    Directory of Open Access Journals (Sweden)

    Ana Yecê das Neves Pinto

    2003-12-01

    Full Text Available Malaria regions of the Amazon basin have been characterized by difficult access and non-compliance of the patients to treatment. In an attempt to assess the schizonticide efficacy of chloroquine in a single dose of 600 mg, the authors realized a double-blind, placebo-controlled trial in 132 outpatients with vivax malaria. Patients were distributed into two groups: group CPLA, given chloroquine 600 mg (single dose on the first day of treatment, and two doses of placebo on second and third days. Group CHLO, given chloroquine 600 mg on first day and 450 mg on second and third day. Geometric means of the parasite density during the follow-up was similar in both groups. No differences were observed in the parasitological cure between the two groups (p = 0.442. There was clinical and parasitological efficacy in treatment of patients given a single-dose of chloroquine. This suggests that its restricted use could be indicated in remote areas of Brazilian Amazon Region, nevertheless the inadequate response of three patients indicates the need for further studies.As regiões malarígenas da Amazônia brasileira têm se caracterizado por dificuldades no acesso ao tratamento e não aceitação das drogas pelos doentes. Com objetivos de avaliar a eficácia da cloroquina em dose simples de 600 mg, os autores realizaram um ensaio clínico duplo cego, placebo controlado em 132 pacientes portadores de malária por P. vivax. Os pacientes foram distribuídos em dois grupos: grupo CPLA que recebia 600 mg de cloroquina em dose simples no primeiro dia de tratamento e duas doses de placebo no segundo e terceiro dias de tratamento. Grupo CLO que recebia 600 mg de cloroquina no primeiro dia e 450 mg no segundo e terceiro dias. A média geométrica da densidade parasitária durante o seguimento foi similar em ambos os grupos. Não houve diferenças de cura parasitológica em ambos os grupos (p = 0,442. Observou-se eficácia clínica e parasitológica nos indivíduos que

  14. Single dose regorafenib-induced hypertensive crisis.

    Science.gov (United States)

    Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

    2014-06-01

    Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

  15. A comparison of traditional vs. Canadian tailored prophylaxis dosing of prophylactic factor infusions in children with haemophilia A and B in a single hemophilia treatment center.

    Science.gov (United States)

    Dodd, C; Watts, R G

    2012-07-01

    Prophylactic infusion of clotting factor concentrates is a developing standard of care for individuals with haemophilia. The ideal schedule and techniques of prophylactic infusions remain incompletely defined. Our aim was to determine the optimal techniques and schedules for factor prophylaxis in paediatric patients. A retrospective electronic medical record review of all children treated with prophylactic factor infusions in a single Haemophilia Treatment Center was conducted. Comparison of traditional vs. Canadian dosing regimens and primary vs. secondary prophylaxis was made. Failure of prophylaxis was defined as the first serious bleed. A total of 58 children were identified for review. Five cases were excluded (four due to high titre inhibitors and one due to repeated non-compliance), thus there were 53 total cases: 46 with severe haemophilia, 2 with moderate haemophilia, 5 with mild haemophilia, 44 with haemophilia A and 9 with haemophilia B; 32 Traditional dosing and 21 Canadian dosing regimens. Patients on primary prophylaxis had a decreased failure rate (25%) compared to children treated with secondary prophylaxis (67%) regardless of technique of prophylaxis. When compared to a 'Traditional' factor prophylaxis schedule, the 'Canadian' tailored prophylaxis protocol was comparable with the exception of a decreased use of implanted venous devices in the 'Canadian' group. Ongoing bleeding (primarily joint bleeds) occurs with all prophylactic regimens. The lowest incidence of treatment failure was noted in children who began primary prophylaxis at a young age and before initial joint bleeds. Primary prophylaxis is superior to secondary prophylaxis regardless of dosing regimen. Traditional and Canadian dosing regimens were equivalent in outcome when measured over several years of follow-up. © 2012 Blackwell Publishing Ltd.

  16. Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.

    Science.gov (United States)

    Lijnen, Raphaël; Otters, Elsemieke; Balak, Deepak; Thio, Bing

    2016-01-01

    Mixtures of fumaric acid esters (FAE) are used as an oral systemic treatment for moderate to severe psoriasis. Large clinical studies with dimethylfumarate (DMF) monotherapy are scarce. The objective of this study is to assess the effectiveness and long-term safety of high-dose DMF monotherapy in moderate to severe psoriasis. A prospective single-blinded follow-up study was performed in a cohort of patients treated with DMF. Patients were followed-up at fixed intervals. Assessment of consecutive photographs was performed by two observers. Primary outcome was a change in static physician global assessment (PGA) score. Safety outcome was defined as incidences of (serious) adverse events. A total of 176 patients with moderate to severe psoriasis were treated with DMF for a median duration of 28 months. The median daily maintenance dosage of 480 mg was reached after a median of 8 months. Psoriasis activity decreased significantly by 1.7 out of five points. A total of 152 patients reported one or more adverse events, such as gastrointestinal complaints and flushing. High-dose DMF monotherapy is an effective and safe treatment option in moderate to severe psoriasis. It can be suggested that 50% of all patients may benefit from high-dose DMF monotherapy.

  17. The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia

    DEFF Research Database (Denmark)

    Simonsen, Paul E; Magesa, Stephen M; Meyrowitsch, Dan W

    2005-01-01

    The effect of eight half-yearly treatment rounds with diethylcarbamazine (DEC; 6mg/kg bodyweight) on Wuchereria bancrofti-specific circulating filarial antigen (CFA), a marker of adult worm infection, was followed in 79 individuals who were CFA-positive before start of treatment. Half of these were...... also microfilariae (mf)-positive. Microfilaraemia decreased rapidly after onset of treatment and became undetectable after four treatments. Circulating antigenaemia also decreased progressively, but at a much slower rate. After two, four and eight treatment rounds, the mean CFA intensity was reduced...... by 81, 94 and 98%, and the prevalence of CFA positivity was 85, 66 and 57%, compared with pre-treatment, respectively. CFA clearance rates were negatively related to pre-treatment CFA intensities, and were higher among pre-treatment mf-negative individuals than among pre-treatment mf...

  18. Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial.

    Science.gov (United States)

    Mwaiswelo, Richard; Ngasala, Billy; Jovel, Irina; Aydin-Schmidt, Berit; Gosling, Roland; Premji, Zul; Mmbando, Bruno; Björkman, Anders; Mårtensson, Andreas

    2016-08-26

    The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission settings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged ≥1 year, with the exception of pregnant and lactating women, were enrolled and treated with AL plus a single PQ dose (0.25 mg/kg) or AL alone under supervision. PQ was administered together with the first AL dose. Clinical and laboratory assessments were performed at 0, 8, 24, 36, 48, 60, and 72 h and on days 7, 14, 21, and 28. The primary end-point was a polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) on day 28. Secondary outcomes included: fever and asexual parasitaemia clearance, proportion of patients with PCR-determined parasitaemia on day 3, and proportion of patients with Pfmdr1 N86Y and Pfcrt K76T on days 0, 3 and day of recurrent infection. Overall 220 patients were enrolled, 110 were allocated AL + PQ and AL, respectively. Parasite clearance by microscopy was fast, but PCR detectable parasitaemia on day 3 was 31/109 (28.4 %) and 29/108 (26.9 %) in patients treated with AL + PQ and AL, respectively (p = 0.79). Day 28 PCR-adjusted ACPR and re-infection rate was 105/105 (100 %) and 101/102 (99 %) (p = 0.31), and 5/107 (4.7 %) and 5/8 (4.8 %) (p = 0.95), in AL + PQ and AL arm, respectively. There was neither any statistically significant difference in the proportion of Pfmdr1 N86Y or Pfcrt K76T

  19. Comparison of radiation dose spillage from the Gamma Knife Perfexion with that from volumetric modulated arc radiosurgery during treatment of multiple brain metastases in a single fraction.

    Science.gov (United States)

    McDonald, Daniel; Schuler, John; Takacs, Istvan; Peng, Jean; Jenrette, Joseph; Vanek, Kenneth

    2014-12-01

    The objective of this study was to examine radiation dose distributions created by 2 competing radiosurgery modalities for treating multiple brain metastases: single-isocenter volumetric modulated arc radiosurgery (VMAS) and Gamma Knife Perfexion (GKP). In addition, the effectiveness of multiple radiosurgery quality metrics was evaluated and compared between these advanced treatment modalities. Seven anonymized MRI data sets, each showing 2-5 metastases, were used to create plans on each system. The GammaPlan (version 10.1) program was used for planning of GKP. A neurosurgeon contoured the volumes to be treated, and no planning target volume expansion was used. A prescription dose coverage of ≥ 99% was achieved for each tumor volume. The Philips Pinnacle (version 9.2) program was used for planning of VMAS, using the SmartArc optimization algorithm for delivery on a Varian iX linear accelerator. Contours were transferred from GammaPlan, and again no planning target volume expansion was used. Between 2 and 5 arcs with table angles of 90°-270° were used. Again, a V100% of ≥ 99% was achieved for each tumor volume. After planning, the MRI scans, tumor volumes, and dose information from each plan were exported according to the Digital Imaging and Communications in Medicine standard to the VelocityAI program for analysis. Brain dose-volume histograms (DVHs) for normal brain tissues were generated, and the volume of these tissues receiving 20%-90% of the prescription dose was tabulated. Finally, the prescription isodose to tumor volume ratio (PITV; Shaw et al., 1993), conformity index (CI; Paddick, 2000), gradient index (GI, Paddick and Lippitz, 2006), and conformity/gradient index (CGI, Wagner et al. 2003) were calculated for each plan. Both the PITV and CI have ideal values of 1, while the GI and CGI have ideal values of lowest and highest achievable, respectively. The DVHs consistently showed that with VMAS a higher amount of normal brain tissues received each

  20. A Randomized controlled trial on safety and efficacy of single intramuscular versus staggered oral dose of 600 000IU Vitamin D in treatment of nutritional rickets.

    Science.gov (United States)

    Mondal, Krishanu; Seth, Anju; Marwaha, Raman K; Dhanwal, Dinesh; Aneja, Satinder; Singh, Ritu; Sonkar, Pitambar

    2014-06-01

    Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections

    National Research Council Canada - National Science Library

    Valdis Goncars; Eriks Jakobsons; Kristaps Blums; Ieva Briede; Liene Patetko; Kristaps Erglis; Martins Erglis; Konstantins Kalnberzs; Indrikis Muiznieks; Andrejs Erglis

    2017-01-01

    Objective: The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe...

  2. Single low-dose red light is as efficacious as methyl-aminolevulinate--photodynamic therapy for treatment of acne: clinical assessment and fluorescence monitoring.

    Science.gov (United States)

    Hörfelt, Camilla; Stenquist, Bo; Halldin, Christina B; Ericson, Marica B; Wennberg, Ann-Marie

    2009-01-01

    This controlled study investigated single low-dose red light photodynamic therapy and methyl-aminolevulinate (MAL) for treatment of moderate to severe facial acne in 19 patients. The right cheek was treated with MAL (160 mg/g) for 3 h prior to illumination. The left cheek received red light only. Both cheeks were illuminated with narrow-band red light (635 nm) at a light dose of 15 J/cm2. The global severity of acne was assessed at baseline and at follow-up, 10 and 20 weeks after treatment. Fluorescence images, clinical photographs and skin surface biopsies were obtained. Both MAL-photodynamic therapy and control areas showed a significant decrease in acne score at follow-up; no significant difference was found compared with control. MAL-photodynamic therapy was associated with adverse effects such as erythema and stinging. Fluorescence images revealed poor selectivity of MAL-induced fluorescence to the acne lesions, suggesting a general photoablating mechanism rather than selective destruction of sebaceous glands. No significant reduction in Propionibacterium acnes or sebum excretion was found.

  3. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections

    Directory of Open Access Journals (Sweden)

    Valdis Goncars

    2017-01-01

    Conclusions: The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed.

  4. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial.

    Science.gov (United States)

    Holm, C; Thomsen, L L; Norgaard, A; Langhoff-Roos, J

    2017-04-01

    To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. Single-centre, open-label, randomized controlled trial. Participants received intravenous iron (n = 97) or oral iron (n = 99), and completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and haematological and iron parameters were measured. Primary outcome was the aggregated change in physical fatigue score from baseline to 12 weeks postpartum. The difference in physical fatigue score was -0·97 (95% CI: -1·65; -0·28, P = 0·006) in favour of intravenous iron, but did not meet the predefined difference of 1·8. Across visits, we found statistically significant differences in fatigue and depression scores, as well as in haematological and iron parameters, all in favour of intravenous iron. There were no serious adverse reactions. A single dose of intravenous iron was associated with a statistically significant reduction in aggregated physical fatigue within 12 weeks after postpartum haemorrhage compared to standard medical care with oral iron below the prespecified criteria of clinical superiority. As patient-reported outcomes improved significantly and intravenous iron resulted in a fast hematopoietic response without serious adverse reactions, intravenous iron may be a useful alternative after postpartum haemorrhage if oral iron is not absorbed or tolerated. © 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

  5. Single dose oral diclofenac for postoperative pain.

    Science.gov (United States)

    Barden, J; Edwards, J; Moore, R A; McQuay, H J

    2004-01-01

    Diclofenac is a benzene-acetic acid derivative that acts, like other NSAIDs, by inhibiting cyclo-oxygenase isoforms that mediate the body's production of the prostaglandins implicated in pain and inflammation. Diclofenac is widely available as a sodium or potassium salt. Diclofenac potassium tablets are known as 'immediate-release' diclofenac as absorption takes place in the gastrointestinal tract whereas 'delayed-release' (enteric-coated) diclofenac tablets resist dissolution until reaching the duodenum. An existing review showed that diclofenac was an effective treatment for acute postoperative pain but did not address the distinction between potassium and sodium salts due to lack of data. The aim of this update is to gather and add appropriate information published subsequently and, data permitting, examine any potential differences between the two different diclofenac formulations. To assess single dose oral diclofenac for the treatment of acute postoperative pain and determine whether there are differences between the different formulations. We searched the Cochrane Library (Issue 2, 2003), MEDLINE (1966 to May 1996), EMBASE (1980 to 1996), Biological Abstracts (1985 to 2003), the Oxford Pain Relief Database (1950 to 1994), PubMed (1996 to 2003) and reference lists of articles. Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac sodium or diclofenac potassium for acute postoperative pain in adults. Two reviewers independently assessed trials for inclusion in the review, quality and extracted data. The area under the pain relief versus time curve was used to derive the proportion of patients prescribed diclofenac or placebo with at least 50% pain relief over four to six hours using validated equations. The number needed to treat (NNT) was calculated. Information on adverse effects was also collected. One additional trial was included and added to the six trials included in the original review. All seven trials provided

  6. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum...... haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. MATERIALS AND METHODS: Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7......) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. RESULTS: We screened 162 women and included 13 (8...

  7. Dose optimisation in single plane interstitial brachytherapy.

    Science.gov (United States)

    Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte; Nielsen, Søren Kynde; Olsen, Dag Rune; Grau, Cai; Lindegaard, Jacob Christian

    2006-10-01

    Brachytherapy dose distributions can be optimised by modulation of source dwell times. In this study dose optimisation in single planar interstitial implants was evaluated in order to quantify the potential benefit in patients. In 14 patients, treated for recurrent rectal and cervical cancer, flexible catheters were sutured intra-operatively to the tumour bed in areas with compromised surgical margin. Both non-optimised, geometrically and graphically optimised CT -based dose plans were made. The overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed. Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to 0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all). Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5% (p<0.001). The improvement in OI and HI obtained by optimisation depended on the regularity of the implant, such that the benefit of optimisation was larger for irregular implants. OI and HI correlated strongly with target volume limiting the usability of these parameters for comparison of dose plans between patients. Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.

  8. The use of modified single pencil beam dose kernels to improve IMRT dose calculation accuracy.

    Science.gov (United States)

    Bergman, Alanah M; Otto, Karl; Duzenli, Cheryl

    2004-12-01

    Intensity modulated radiation therapy (IMRT) is used to deliver highly conformal radiation doses to tumors while sparing nearby sensitive tissues. Discrepancies between calculated and measured dose distributions have been reported for regions of high dose gradients corresponding to complex radiation fluence patterns. For the single pencil beam convolution dose calculation algorithm, the ability to resolve areas of high dose structure is partly related to the shape of the pencil beam dose kernel (similar to how a photon detector's point spread function relates to imaging resolution). Improvements in dose calculation accuracy have been reported when the treatment planning system (TPS) is recommissioned using high-resolution measurement data as input. This study proposes to improve the dose calculation accuracy for IMRT planning by modifying clinical dose kernel shapes already present in the TPS, thus avoiding the need to reacquire higher resolution commissioning data. The in-house optimization program minimizes a cost-function based on a two-dimensional composite dose subtraction/distance-to-agreement (gamma) analysis. The final modified kernel shapes are reintroduced into the treatment planning system and improvements to the dose calcula tion accuracy for complex IMRT dose distributions evaluated. The central kernel value (radius =0 cm) has the largest effect on the dose calculation resolution and is the focus of this study.

  9. Cardiovascular abnormalities with single dose of tapentadol

    Directory of Open Access Journals (Sweden)

    A Vachhani

    2014-01-01

    Full Text Available This case represents the development of dizziness, palpitation, tightness in chest, flushing, and tremor on consumption of a single dose of tapentadol (100 mg for acute lower back pain. The patient was admitted in the intensive cardiac care unit for continuous monitoring. At admission, electrocardiogram showed tachycardia (140/min along with ST segment elevation in second chest lead (V 2 . The patient was monitored and advised not to take further doses of tapentadol. He was discharged after 36 hours of admission. Tapentadol should be used cautiously in patients with cardiovascular diseases and receiving sympathomimetic drugs.

  10. Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection.

    Science.gov (United States)

    Qiu, Hongjie; Sun, Shihui; Xiao, He; Feng, Jiannan; Guo, Yan; Tai, Wanbo; Wang, Yufei; Du, Lanying; Zhao, Guangyu; Zhou, Yusen

    2016-08-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Tratamiento de la neumonía del lactante con cefixima en dosis única diaria Treatment of pneumonia in infants with daily single oral dose of cefixime

    Directory of Open Access Journals (Sweden)

    María de La Luz Valencia Chávez

    1997-01-01

    Full Text Available Para evaluar la eficacia clínica y la tolerancia a la Cefixima, se trató con ella un grupo de 25 niños y niñas lactantes de 2 a 23 meses de edad, que padecían neumonías bacterianas. Se usó una dosis de 8 mg/kg/día, por vía oral, durante catorce días y en una sola toma. Los signos clínicos evaluados, los hallazgos radiológicos y los de laboratorio mejoraron en el transcurso de la terapia. Se presentaron un caso (4% de intolerancia gastrointestinal y doce (48% con aumento de las transaminasas. En el 24% se encontró el agente causal. No se detectó una diferencia significativa en el comportamiento clínico y paraclínico de los niños con neumonía de etiología conocida en comparación con aquéllos en que no se la definió. Se obtuvo un 96% de resultados muy buenos en la terapia. Se debe investigar más el efecto del medicamento sobre la función hepática. Treatment of pneumonia in infants with dail y single oral dose of cefixime Twenty five male and female Infants aged two to twenty-three months suffering from bacterial pneumonia were treated with cefixime in order to evaluate clinical efficiency and tolerance. A daily single oral dose of 8 mg kg was given for fourteen days. Clinical status and radiologic and laboratory findings improved during the course of therapy. A case of gastrointestinal intolerance (4% and twelve (48% of high levels of transaminases were observed. In 6 cases (24% the ethiologic agent was found. No significant differences were detected in clinical or paraclinical behavior between the groups of known and unknown ethiology. Therapy was quite successful in 96% of the C8ses. Hepatic effects of cefixime ought to be further Investigated.

  12. Azithromycin 1.5g Over 5 Days Compared to 1g Single Dose in Urethral Mycoplasma genitalium: Impact on Treatment Outcome and Resistance.

    Science.gov (United States)

    Read, Tim R H; Fairley, Christopher K; Tabrizi, Sepehr N; Bissessor, Melanie; Vodstrcil, Lenka; Chow, Eric P F; Grant, Mieken; Danielewski, Jennifer; Garland, Suzanne M; Hocking, Jane S; Chen, Marcus Y; Bradshaw, Catriona S

    2017-02-01

    We evaluated the impact of extended azithromycin (1.5g over 5 days) on selection of macrolide resistance and microbiological cure in men with Mycoplasma genitalium urethritis during 2013-2015 and compared this to cases treated with azithromycin 1g in 2012-2013. Microbiological cure was determined for men with M. genitalium urethritis treated with azithromycin 1.5g using quantitative polymerase chain reaction specific for M. genitalium DNA on samples 14-100 days post-treatment. Pre- and post-treatment macrolide resistance mutations were detected by sequencing the 23 S gene. There was no difference in proportions with microbiological cure between azithromycin 1.5g and 1g: 62/106 (58%; 95% confidence interval [CI], 49%, 68%) and 56/107 (52%; 95%CI 42-62%), P = .34, respectively. Also, there was no difference in the proportion of wild-type 23 S rRNA (presumed macrolide sensitive) infections cured after 1.5g and azithromycin 1g: 28/34 (82%; 95%CI 65-92%) and 49/60 (82%; 95%CI 70-90%), P=1.0, respectively. There was no difference between 1.5g and 1g in the proportions of wild-type infections with post-treatment resistance mutations: 4/34 (12%; 95%CI 3-27%) and 11/60 (18%; 95%CI 10-30%), respectively, P = .40. Pre-treatment resistance was present in 51/98 (52%; 95%CI 42-62%) cases in 2013-2015 compared to 47/107 (44%; 95%CI 34-54%) in 2012-2013, P = .25. Extended azithromycin 1.5g was no more effective than a single 1g dose at achieving cure of M. genitalium urethritis and importantly did not reduce the selection of macrolide resistance. Nonmacrolide and new approaches for the treatment of M. genitalium urethritis are required. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Single-dose trospectomycin for chlamydial urethritis in men.

    Science.gov (United States)

    Keefer, M C; Menegus, M A; Nasello, M A; Reid, J A; Long, M; Reichman, R C

    1991-01-01

    Trospectomycin is an aminocyclitol analog of spectinomycin with significant in vitro activity against Chlamydia trachomatis. A single 1-g intramuscular dose was administered to 10 men with symptomatic, culture-positive chlamydial urethritis. Trospectomycin was well tolerated but failed to eradicate chlamydial infection, as determined by cultures obtained approximately 1 week after treatment. PMID:1830196

  14. SU-F-T-132: Variable RBE Models Predict Possible Underestimation of Vaginal Dose for Anal Cancer Patients Treated Using Single-Field Proton Treatments

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, A; Underwood, T; Wo, J; Paganetti, H [Massachusetts General Hospital & Harvard Medical School, Boston, MA (United States)

    2016-06-15

    Purpose: Anal cancer patients treated using a posterior proton beam may be at risk of vaginal wall injury due to the increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the beam distal edge. We investigate the vaginal dose received. Methods: Five patients treated for anal cancer with proton pencil beam scanning were considered, all treated to a prescription dose of 54 Gy(RBE) over 28–30 fractions. Dose and LET distributions were calculated using the Monte Carlo simulation toolkit TOPAS. In addition to the standard assumption of a fixed RBE of 1.1, variable RBE was considered via the application of published models. Dose volume histograms (DVHs) were extracted for the planning treatment volume (PTV) and vagina, the latter being used to calculate the vaginal normal tissue complication probability (NTCP). Results: Compared to the assumption of a fixed RBE of 1.1, the variable RBE model predicts a dose increase of approximately 3.3 ± 1.7 Gy at the end of beam range. NTCP parameters for the vagina are incomplete in the current literature, however, inferring value ranges from the existing data we use D{sub 50} = 50 Gy and LKB model parameters a=1–2 and m=0.2–0.4. We estimate the NTCP for the vagina to be 37–48% and 42–47% for the fixed and variable RBE cases, respectively. Additionally, a difference in the dose distribution was observed between the analytical calculation and Monte Carlo methods. We find that the target dose is overestimated on average by approximately 1–2%. Conclusion: For patients treated with posterior beams, the vaginal wall may coincide with the distal end of the proton beam and may receive a substantial increase in dose if variable RBE models are applied compared to using the current clinical standard of RBE equal to 1.1. This could potentially lead to underestimating toxicities when treating with protons.

  15. Efficacy of low-dose cinacalcet on alternate days for the treatment of secondary hyperparathyroidism in hemodialysis patients: a single-center study

    Directory of Open Access Journals (Sweden)

    Gojaseni P

    2017-02-01

    Full Text Available Pongsathorn Gojaseni, Dolnapa Pattarathitinan, Anutra Chittinandana Division of Nephrology, Department of Medicine, Bhumibol Adulyadej Hospital, Directorate of Medical Services, Royal Thai Air Force, Bangkok, Thailand Introduction: Cinacalcet is effective in reducing serum parathyroid hormone (PTH in patients with secondary hyperparathyroidism (HPT. This study focused on testing whether a prescription of low-dose cinacalcet on alternate days could be an option for treatment of secondary HPT.Materials and methods: A retrospective clinical study was conducted on chronic maintenance hemodialysis patients. Patients with secondary HPT who received cinacalcet at a starting dose of 25 mg on alternate days were reviewed (low-dose group. Patients who were being treated with a standard dose of cinacalcet in the same period of time were selected as the control group. The primary outcome was difference in the percentage of patients achieving >30% reduction of intact parathyroid hormone (iPTH levels at 16 weeks. The changes of serum iPTH and other biochemical data were also tested.Results: A total of 30 patients (16 low doses and 14 controls took part in the study. Baseline iPTH levels in the low-dose and control group were 1,065.9±477.7 and 1,214.1±497.6 pg/mL, respectively (p=0.413. The analysis showed that the percentage of patients who achieved the primary outcome showed little or no difference (33.3% in the low-dose group compared with 38.5% in the control group, p=1.0. Serum iPTH reduction during 16 weeks of study period in the low-dose and control group was 253.5±316.1 and 243.4±561.3 pg/mL, respectively (p=0.957. There was no difference in the adverse events between both groups.Conclusion: Among patients with secondary HPT, initial treatment with cinacalcet 25 mg on alternate days can decrease serum PTH levels. The role of low-dose cinacalcet in secondary HPT should be further determined in large-scale, randomized controlled trials. Keywords

  16. Índice orientador do tratamento sistêmico da gravidez ectópica íntegra com dose única de metotrexato Index for the systemic treatment of unruptured ectopic pregnancy with a single dose of methotrexate

    Directory of Open Access Journals (Sweden)

    Julio Elito Junior

    1998-04-01

    iguais a cinco estiveram todas relacionadas com o fracasso do tratamento. O índice orientador ajuda-nos a indicar os melhores casos para o tratamento medicamentoso. Não o aconselhamos, portanto, quando a nota for inferior ou igual a cinco; por outro lado, podemos predizer boa evolução do tratamento, quando a nota for superior a cinco.A prospective study was performed with 42 patients with unruptured ectopic pregnancy, which intended to elaborate an index to orient the systemic treatment with the administration of a single intramuscular dose of methotrexate (50 mg/m². Patients were monitored with beta-hCG titers on days 1, 4 and 7 after the methotrexate. When the titers of beta-hCG declined more than 15%, between days 4 and 7 after methotrexate, the patients were discharged and had an outpatient follow-up monitored with beta-hCG titers weekly until the titers were less than 5 mIU/ml, which represents success of the treatment. We prepared an index for the systemic treatment with methotrexate, with five parameters: (1 initial titers of beta-hCG; (2 aspects of the image at ultrasound (hematosalpinx, gestational sac, live embryo; (3 size of the mass; (4 free fluid in cul-de-sac; (5 collor doppler. Each parameter received a grade from 0 to 2. Grade 0 represented bad prognosis, favorable parameters received grade 2 and borderline parameters received grade one. The success rate with a single dose of methotrexate was 69.0% (29/42. The color doppler was performed in 20 of the 42 patients; in this group of 20 patients the success rate was 75.0% (15/20. In the 22 patients who were not submitted to the color doppler, the average grade of the score in the successful cases was 6.6, and in the unsuccessful it was 3.1. In the group who underwent the doppler (20 patients the average was 7.9 in the successful cases and 4.2 in the cases that failed. In the present study the cut-off grade was 5, for most of the patients with grades above 5 had a successful treatment (15/16 - 93

  17. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

    Directory of Open Access Journals (Sweden)

    Galynker Igor I

    2009-05-01

    Full Text Available Abstract Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks. Methods Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS, the Hamilton Anxiety Scale (Ham-A, the Hamilton Depression Rating Scale (Ham-D, the Sheehan Panic Anxiety Scale-Patient (SPAS-P, and the Clinical Global Impression scale (CGI. Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine. Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component. Trial Registration ClinicalTrials.gov Identifier: NCT100457106

  18. The chondrotoxicity of single-dose corticosteroids.

    Science.gov (United States)

    Dragoo, Jason L; Danial, Christina M; Braun, Hillary J; Pouliot, Michael A; Kim, Hyeon Joo

    2012-09-01

    Corticosteroids are commonly injected into the joint space. However, studies have not examined the chondrotoxicity of one-time injection doses. The purpose of this study is to evaluate the effect of dexamethasone sodium phosphate (Decadron), methylprednisolone acetate (Depo-Medrol), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), and triamcinolone acetonide (Kenalog) on human chondrocyte viability in vitro. Single-injection doses of each of the corticosteroids were separately delivered to human chondrocytes for their respective average duration of action and compared to controls using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A 14-day time-controlled trial was also performed. A live/dead reduced biohazard viability/cytotoxicity assay was used to quantify chondrocyte viability. Over their average duration of action, betamethasone sodium phosphate/acetate solution and triamcinolone acetonide caused significant decreases in chondrocyte viability compared to control media (19.8 ± 2.9% vs. 5.2 ± 2.1%, P = 0.0025 and 10.2 ± 1.3% vs. 4.8 ± 0.9%, P = 0.0049, respectively). In the 14-day trial, only betamethasone sodium phosphate/acetate solution caused a significant decrease in chondrocyte viability compared to control media (21.5% vs. 4.6%, P < 0.001). A single-injection dose of betamethasone sodium phosphate and betamethasone acetate solution illustrated consistent and significant chondrotoxicity using a physiologically relevant in vitro model and should be used with caution. Given the observed chondrotoxicity of triamcinolone acetonide in a single trial, there may be some evidence that this medication is chondrotoxic. However, at 14 days, betamethasone sodium phosphate and betamethasone acetate was the only condition that caused significant cell death.

  19. Tolerance doses for treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.

  20. Single dose dipyrone for acute postoperative pain.

    Science.gov (United States)

    Edwards, Jayne; Meseguer, Fuensanta; Faura, Clara; Moore, R Andrew; McQuay, Henry J; Derry, Sheena

    2010-09-08

    Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30

  1. Incorporating quantitative single photon emission computed tomography into radiation therapy treatment planning for lung cancer: impact of attenuation and scatter correction on the single photon emission computed tomography-weighted mean dose and functional lung segmentation.

    Science.gov (United States)

    Yin, Lingshu; Shcherbinin, Sergey; Celler, Anna; Thompson, Anna; Fua, Tsien-Fei; Liu, Mitchell; Duzenli, Cheryl; Gill, Brad; Sheehan, Finbar; Powe, John; Worsley, Daniel; Marks, Lawrence; Moiseenko, Vitali

    2010-10-01

    To assess the impact of attenuation and scatter corrections on the calculation of single photon emission computed tomography (SPECT)-weighted mean dose (SWMD) and functional volume segmentation as applied to radiation therapy treatment planning for lung cancer. Nine patients with lung cancer underwent a SPECT lung perfusion scan. For each scan, four image sets were reconstructed using the ordered subsets expectation maximization method with attenuation and scatter corrections ranging from none to a most comprehensive combination of attenuation corrections and direct scatter modeling. Functional volumes were segmented in each reconstructed image using 10%, 20%, …, 90% of maximum SPECT intensity as a threshold. Systematic effects of SPECT reconstruction methods on treatment planning using functional volume were studied by calculating size and spatial agreements of functional volumes, and V(20) for functional volume from actual treatment plans. The SWMD was calculated for radiation beams with a variety of possible gantry angles and field sizes. Functional volume segmentation is sensitive to the particular method of SPECT reconstruction used. Large variations in functional volumes, as high as >50%, were observed in SPECT images reconstructed with different attenuation/scatter corrections. However, SWMD was less sensitive to the type of scatter corrections. SWMD was consistent within 2% for all reconstructions as long as computed tomography-based attenuation correction was used. When using perfusion SPECT images during treatment planning optimization/evaluation, the SWMD may be the preferred figure of merit, as it is less affected by reconstruction technique, compared with threshold-based functional volume segmentation. 2010 Elsevier Inc. All rights reserved.

  2. Single dose pharmacokinetics of mefloquine in healthy Nigerian ...

    African Journals Online (AJOL)

    Single dose pharmacokinetics of mefloquine in healthy Nigerian male subjects. A Mustapha, JA Kolawole. Abstract. Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. Mefloquine 500mg single dose was administered and blood sa mples were collected 11t intervals.

  3. Development of statistical analysis for single dose bronchodilators.

    Science.gov (United States)

    Salsburg, D

    1981-12-01

    When measurements developed for the diagnosis of patients are used to detect treatment effects in clinical trials with chronic disease, problems in definition of response and in the statistical distributions of those measurements within patients have to be resolved before the results of clinical studies can be analyzed. An example of this process is shown in the development of the analysis of single-dose bronchodilator trials.

  4. Low-Dose Radiation Treatment in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Plausible Approach? A Single-Institution Experience in 10 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Girinsky, Theodore, E-mail: girinsky@igr.fr [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France); Paumier, Amaury [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France); Ferme, Christophe; Hanna, Colette; Ribrag, Vincent [Department of Hematology, Institut Gustave Roussy, Villejuif (France); Leroy-Ladurie, Francois [Department of Thoracic Surgery, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson (France); Ghalibafian, Mithra [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France)

    2012-07-01

    Purpose: To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 Multiplication-Sign 2 Gy) delivered exclusively to tumor sites. Methods and Materials: Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Results: Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). Conclusions: Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.

  5. A single-dose conformal delivery of radiotherapy following osteoplasty : a novel approach to treatment of osteolytic metastasis in the setting of multiple myeloma.

    Science.gov (United States)

    Wernicke, A Gabriella; Sabbas, Albert; Kulidzhanov, Fridon; Shamis, Michael; Golster, Yevgeniya; Niesvizky, Ruben; Lane, Joseph

    2012-07-01

    Multiple myeloma (MM) is a very radiosensitive tumor. Fractionated external beam radiation, which takes approximately 2 weeks of therapy, is typically used to irradiate myelomatous bone lesions with the goal of palliation. However, traditional radiotherapeutic techniques are not only lengthy but they also involve a considerable amount of healthy bone marrow in the treatment ports, which may undermine the total marrow reserve of a patient. Because of the limited survival time of patients with metastatic cancer, novel treatment concepts shortening the overall treatment time is desirable. We present an innovative approach of delivering targeted intra-operative radiotherapy to a solitary osteolytic metastasis in one application, while sparing healthy bone marrow from radiation toxicity and substantially reducing the overall treatment time. A 78-year-old Caucasian male with MM, previously treated with chemotherapy, who was off chemotherapy for 2 years due to bone marrow suppression, presented with a solitary recurrence at the left anterior superior iliac spine of the left iliac wing as diagnosed by PET-CT scan. This lesion was treated with a minimally invasive osteoplasty and intra-operative brachytherapy with to a dose of 8 Gy delivered to the surgical cavity only, followed by injection of the bone cement into the cavity. Three months after the procedure, the area of treatment demonstrated no uptake on a follow-up PET-CT scan. At 1.5 years after this procedure, 100% local control continues to persist in the treated area, as evidenced on nuclear imaging. To our knowledge, this is the first case of using focal intra-operative brachytherapy confined to the area of the pelvis in a patient treated for a solitary metastasis from MM. The purpose of the article is to present a novel approach as a more convenient and focal treatment of bony lesions of MM.

  6. 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.

  7. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

    Science.gov (United States)

    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765.

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

    Science.gov (United States)

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

    2012-03-15

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

  9. Fixed Dose Combination for TB treatment

    Directory of Open Access Journals (Sweden)

    Tjandra Y. Aditama

    2003-06-01

    Full Text Available According to the World Health Organization, a third of the world’s population is infected with tuberculosis. The disease is responsible for nearly 2 million deaths each year and over 8 million were developing active diseases. Moreover, according to WHO (2000, tuberculosis deaths are estimated to increase to 35 million between 2000-2020. The majority of tuberculosis patients worldwide are still treated with single drugs, or with 2-drug fixed-dose combinations (FDCs. To improve tuberculosis treatment, 2- and 3-drug FDCs were recommended by the World Health Organization (WHO as part of the DOTS strategy. Since 1999 a 4-drug FDC was included on the WHO Model List of Essential Drugs. Today, FDCs are important tools to further improve the quality of care for people with TB, and accelerate DOTS expansion to reach the global TB control targets. Fixed dose combination TB drugs could simplifies both treatment and management of drug supply, and may prevent the emergence of drug resistance .Prevention of drug resistance is just one of the potential benefits of the use of FDCs. FDCs simplify administration of drugs by reducing the number of pills a patient takes each day and decreasing the risk of incorrect prescriptions. Most tuberculosis patients need only take 3–4 FDCs tablets per day during the intensive phase of treatment, instead of the 15–16 tablets per day that is common with single-drug formulations It is much simpler to explain to patients that they need to take four tablets of the same type and colour, rather than a mixture of tablets of different shapes, colours and sizes. Also, the chance of taking an incomplete combination of drugs is eliminated, since the four essential drugs are combined into one tablet. FDCs are also simpler for care-givers as they minimize the risk of confusion. Finally, drug procurement, in all its components (stock management, shipping, distribution, is simplified by FDCs. Adverse reactions to drugs are not more

  10. Reliable evidence for efficacy of single dose oral analgesics.

    Science.gov (United States)

    Spivakovsky, Silvia; Spivakovsky, Yael

    2016-06-01

    Data sourcesThe Cochrane library was searched for Cochrane systematic reviews.Study selectionCochrane reviews on single pain medications for the treatment of acute pain were included. Non-Cochrane reviews were included for tramadol.Data extraction and synthesisTwo reviewers independently searched, selected reviews for inclusion, assessed quality and performed data extraction. A protocol in case of disagreement was in place. Data were collected on number of included studies and participants, drug, dose and formulation and pain model. The authors concentrated on the amount of information and the potential for publication bias.Pain relief was calculated using at least 50% maximum pain relief, as a percentage, and as NNTs. Duration of analgesia was measured as mean or median and time to remedication was calculated as percentage of patients.ResultsThirty-nine reviews including 41 interventions were analysed and NNTs for at least 50% maximum pain relief were summarised in a graphic. NNTs range from almost one all the way to five. Only one intervention, codeine 60, had an NNT ≥10. Results judged to be reliable were listed in detail. Mean or median time to remedication was also presented in a graphic.The authors conclude that there is a great amount of quality information on single dose analgesics, and highlighted the potential benefit of fast acting formulations and fixed formulations to achieve good long-lasting analgesia.ConclusionsThere is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

  11. Efficacy of a single high dose versus multiple low doses of LLLT on wounded skin fibroblasts

    Science.gov (United States)

    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

    Background/purpose: In vivo studies have demonstrated that phototherapy accelerates wound healing in the clinical environment; however the exact mechanism is still not completely understood. The main focus of this study was to use in vitro laboratory results to establish an effective treatment regimen that may be practical and applicable to the clinical environment. This in vitro study aimed to compare the cellular responses of wounded fibroblasts following a single exposure of 5 J/cm2 or multiple exposures of low doses (2.5 J/cm2 or 5 J/cm2) on one day of the week to a single application of a higher dose (16 J/cm2) on day 1 and day 4. Methodology: Cellular responses to Helium-Neon (632.8 nm) laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, membrane integrity and DNA damage. Results: Wounded cells exposed to 5 J/cm2 on day 1 and day 4 showed an increase in cell viability, increase in the release of bFGF, increase in cell density, decrease in ALP enzyme activity and decrease in caspase 3/7 activity indicating a stimulatory effect. Wounded cells exposed to three doses of 5 J/cm2 on day 1 showed a decrease in cell viability and cell proliferation and an increase in LDH cytotoxicity and DNA damage indicating an inhibitory effect. Conclusion: Results indicate that cellular responses are influenced by the combination of dose administered, number of exposures and time between exposures. Single doses administered with sufficient time between exposures is more beneficial to restoring cell function than multiple doses within a short period. Although this work confirms previous reports on the cumulative effect of laser irradiation it provides essential information for the initiation of in vivo clinical studies.

  12. Can a single dose response predict the effect of montelukast on exercise-induced bronchoconstriction?

    NARCIS (Netherlands)

    Kersten, Elin T. G.; Akkerman-Nijland, Anne M.; Driessen, Jean M. M.; Diamant, Zuzana; Thio, Bernard J.

    RationaleExercise-induced bronchoconstriction (EIB) can be prevented by a single dose of montelukast (MLK). The effect is variable, similar to the variable responsiveness observed after daily treatment with MLK. We hypothesized that the effect of a single MLK-dose (5 or 10mg) on EIB could predict

  13. Single-dose azithromycin for Chlamydia in pregnant women.

    Science.gov (United States)

    Wehbeh, H A; Ruggeirio, R M; Shahem, S; Lopez, G; Ali, Y

    1998-06-01

    To assess the efficacy and occurrence of severe side effects associated with the use of a single dose of azithromycin in the treatment of Chlamydia trachomatis in pregnant women. Patients and their sexual partners were randomized into three treatment groups: both the patient and her sexual partner received a single dose of azithromycin (group 1); the patient was given a standard course of erythromycin, while her partner was given a standard course of tetracycline (group 2); and the patient was given a single dose of azithromycin with the sexual partner given a standard course of tetracycline (group 3). Group 3 was included in order to assess the relative efficacy of tetracycline with respect to the use of azithromycin among patients and to indirectly assess possible patient reinfection by sexual partners. With respect to the cure rate, 4.5% of study participants given azithromycin has positive cultures vs. 21.1% of patients given erythromycin or tetracycline (P = .018). With respect to side effects severe enough to warrant a change in medication, 7.4% of patients receiving azithromycin reported suffering such side effects vs. 38.8% of patients given erythromycin (P = .02). Among sexual partners, 28.6% given tetracycline reported severe side effects vs. none of those given azithromycin (P = .03). Azithromycin in the treatment of C trachomatis in pregnant women substantially improved the cure rates while substantially reducing the occurrence of severe side effects associated with the use of a standard course of erythromycin. Since both tetracycline and erythromycin are known to be effective against C trachomatis infection, the improved efficacy of azithromycin is probably due to noncompliance with the multidose, multiday regimen associated with the use of these two antibiotics.

  14. [Influence of compliance on the incidence of cardiovascular events and health costs when using single-pill fixed-dose combinations for the treatment of hypertension].

    Science.gov (United States)

    Sicras Mainar, Antoni; Galera Llorca, Jordi; Muñoz Ortí, Genís; Navarro Artieda, Ruth

    2011-02-26

    To determine the incidence of cardiovascular events (CVE) and health care costs in relation to compliance, persistence and level of blood pressure control when comparing patients treated with single-pill combinations (SPC) or free combinations (FC) for the treatment of hypertension. Observational, multicenter study that included patients>30 years old, from six primary care teams and two hospitals, who started pharmacological treatment for hypertension during 2006. Two study groups were established: SPC (ACEIs/diuretics; ARBs/diuretics) and FC (ACEIs+DIU; ARB+DIU, separately). Main variables studied were sociodemographic data, comorbidity, Charlson-index, compliance, persistence and achievement of therapeutic goals (ESH-ESC criteria). The cumulative incidence of CVE and a total-cost model were determined (differentiating: health/direct; non-health/indirect). Patients were followed for two years. Statistical analysis included logistic regression, Cox proportional hazards model and analysis of covariance. Statistical signification: pcerebrovascular accidents in FC was 4.6% vs 2.4% in SPC; p=0.041. The total health care costs were lower in SPC (1,650.7 € vs 1,674.8 €; phospital admissions and less loss of labour productivity (44.5 € vs 88.4 €; pcerebrovascular accidents and total health care costs. Copyright © 2009 Elsevier España, S.L. All rights reserved.

  15. Single-dose anti-CD138 radioimmunotherapy: bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model

    Directory of Open Access Journals (Sweden)

    Nolwenn eFichou

    2015-11-01

    Full Text Available Objectives: Radioimmunotherapy (RIT has emerged as a potential treatment option for multiple myeloma (MM. In humans, a dosimetry study recently showed the relevance of RIT using an antibody targeting the CD138 antigen. The therapeutic efficacy of RIT using an anti-CD138 antibody coupled to 213Bi, an α-emitter, was also demonstrated in a preclinical MM model. Since then, RIT with β-emitters has shown efficacy in treating hematologic cancer. In this paper, we investigate the therapeutic efficacy of RIT in the 5T33 murine MM model using a new anti-CD138 monoclonal antibody labeled either with 213Bi for α-RIT or 177Lu for β-RIT.Methods: A new monoclonal anti-CD138 antibody, 9E7.4, was generated by immunizing a rat with a murine CD138-derived peptide. Antibody specificity was validated by flow cytometry, biodistribution and α-RIT studies. Then, a β-RIT dose-escalation assay with the 177Lu-radiolabeled 9E7.4 mAb was performed in KalwRij C57/BL6 mice 10 days after i.v. engraftment with 5T33 MM cells. Animal survival and toxicological parameters were assessed to define the optimal activity.Results: α-RIT performed with 3.7 MBq of 213Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared to 37 days for the untreated control and effected cure in 45% of animals. β-RIT performed with 18.5 MBq of 177Lu-labeled 9E7.4 mAb was well tolerated and significantly increased mouse survival (54 versus 37 days in the control group; however, no mice were cured with this treatment.Conclusion: This study revealed the advantages of α-RIT in the treatment of MM in a preclinical model where β-RIT shows almost no efficacy.

  16. The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

    Science.gov (United States)

    Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

    2017-12-01

    Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not

  17. A single scale for comparing dose-intensity of all chemotherapy regimens in breast cancer: summation dose-intensity.

    Science.gov (United States)

    Hryniuk, W; Frei, E; Wright, F A

    1998-09-01

    To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer. First-line single-agent trials in metastatic disease were reviewed. The unit dose-intensity (UDI) that was required to produce a 30% complete response plus partial response (CR + PR) rate was determined for each drug. Randomized trials were then analyzed that prospectively tested dose-intensity. The dose-intensities of the drugs in each arm were expressed as fractions of their UDIs and added together. This yielded each arm's summation dose-intensity (SDI), which was then correlated with treatment outcomes. In the single-agent trials, dose-response relationships were linear when the studies covered a range of dose-intensities. In the randomized trials that tested dose-intensity in metastatic disease, response rates and median survival correlated linearly with the SDIs of the treatment arms. An increment of one SDI unit increased CR + PR rate by approximately 30%, CR rate by 10%, and median survival by 3.75 months. Metastatic disease trials were negative if the difference between the arms was less than 0.54 SDI units. Adjuvant trials that tested a dose-intensity difference of less than 0.65 SDI units were also negative. A single-agent dose-response database can be derived from historic literature that enables comparison of the dose-intensity of all combination regimens on one scale. The dose-intensity increase required to improve outcome can then be identified in earlier trials that tested that variable. SDI methodology should be tested prospectively in contemporary patients, and may be useful in guiding dosage increases beyond the conventional range.

  18. Pharmacokinetics of single-dose oral ponazuril in weanling goats.

    Science.gov (United States)

    Love, D; Gibbons, P; Fajt, V; Jones, M

    2016-06-01

    Ponazuril (toltrazuril sulfone) is a triazine antiprotozoal agent that targets apicomplexan organisms. Ponazuril may have clinical application in the treatment of clinical coccidiosis due to Eimeria species in goats, along with other protozoal infections. To evaluate the absorption, distribution and elimination characteristics of ponazuril in goats, a sensitive, validated high-pressure liquid chromatography and mass spectroscopy method for ponazuril in caprine plasma was developed. After a single oral dose of ponazuril at 10 mg/kg, plasma samples from seven weanling goats were collected and assayed. Plasma concentrations of ponazuril in the goats peaked at 36 ± 13 h post drug administration at a concentration of 9 ± 2 μg/mL. Concentrations declined to an average of 4.2 ± 0.8 μg/mL after 168 h with an average elimination half-life of 129 ± 72 h post drug administration. This study shows that ponazuril is relatively well absorbed after a single oral dose in goats. Efficacy trials are underway to determine clinical efficacy of ponazuril in the treatment of clinical coccidiosis in goats at 10 mg/kg dosage. © 2015 John Wiley & Sons Ltd.

  19. Efficacy and safety of single and double doses of ivermectin versus 7-day high dose albendazole for chronic strongyloidiasis.

    Directory of Open Access Journals (Sweden)

    Yupin Suputtamongkol

    2011-05-01

    Full Text Available Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined.A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight, or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up.Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively. All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range duration of follow-up were 19 (2-76 weeks in albendazole group, 39 (2-74 weeks in single dose ivermectin group, and 26 (2-74 weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of

  20. Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: an open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Kim, Bo-Hyung; Kim, Kyu-Pyo; Lim, Kyoung Soo; Kim, Jung-Ryul; Yoon, Seo Hyun; Cho, Joo-Youn; Lee, Yong-Oh; Lee, Kyung-Hee; Jang, In-Jin; Shin, Sang-Goo; Yu, Kyung-Sang

    2010-02-01

    Ginkgo biloba extract is an herbal medicine used in the treatment of vascular disorders that may be coadministered with antiplatelet agents such as ticlopidine. Regulatory authorities requested evaluation of the pharmacodynamic and pharmacokinetic interactions between these entities, according to the drug-development guidance for fixed-dose combination formulations in Korea. This study was performed to evaluate the potential pharmacodynamic and pharmacokinetic interactions between ticlopidine and Ginkgo biloba extract. An open-label, randomized, 2-period, 2-treatment, 2-sequence, single-dose crossover study was conducted in healthy Korean male volunteers. All volunteers were randomly assigned to a sequence group for the 2 treatments, which consisted of ticlopidine 250 mg alone and ticlopidine 250 mg with Ginkgo biloba extract 80 mg, separated by a 1-week washout period between the treatments. Bleeding time was determined just before dosing and at 5, 12, and 48 hours after dosing. Platelet aggregation was evaluated before dosing and at 4, 8, 26, and 48 hours after dosing. Blood samples (8 mL) from each of the volunteers were collected from an indwelling intravenous cannula inserted into a forearm vein before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after dosing. Ticlopidine concentrations were determined by a validated method using HPLC and ultraviolet detection. Adverse events were identified using general health-related questions, vital signs, physical examinations, ECGs, and laboratory tests. A total of 24 healthy men participated in the study (mean [SD] age, 24.1 [4.3] years; weight, 66.6 [7.4] kg; height, 174.7 [5.0] cm). The baseline corrected bleeding times were not significantly different between the ticlopidine-alone and ticlopidine/ Ginkgo biloba groups, and changes in platelet aggregation were not significantly different between the groups. Likewise, the pharmacokinetic parameters of ticlopidine were not significantly different

  1. Dose optimisation in single plane interstitial brachytherapy

    DEFF Research Database (Denmark)

    Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette H

    2006-01-01

    on the       regularity of the implant, such that the benefit of optimisation was       larger for irregular implants. OI and HI correlated strongly with target       volume limiting the usability of these parameters for comparison of dose       plans between patients. CONCLUSIONS: Dwell time optimisation significantly...

  2. An Open Label, Prospective, Single Centre Study to Evaluate the Efficacy and Safety of Fixed Dose Combination of Rabeprazole (Enteric-Coated, EC) 20 mg + Domperidone (Sustained Release, SR) 30 mg Capsule in Treatment of Patients with Laryngopharyngeal Reflux Disease.

    Science.gov (United States)

    Semmanaselvan, K; Mukaddam, Qayum I; Naik, Manoj

    2015-07-01

    To evaluate the efficacy, safety and tolerability of fixed dose combination of Rabeprazole (enteric-coated, EC) 20 mg + Domperidone (sustained release, SR) 30 mg for treatment of laryngopharyngeal reflux disease (LPRD). A prospective, single centre, open-label, non-comparative, observational study The study was conducted at an otolaryngology clinic in India between May 2012 and November 2012. Patients (>18 yrs) with suspicious LPR-related symptoms, reflux symptom index (RSI) score >13 and reflux finding score (RFS) >7, willing to undergo rigid laryngoscopy and requiring fixed dose combination of Rabeprazole (enteric-coated, EC) 20 mg + Domperidone (sustained release, SR) 30 mg capsule treatment according to the investigator's discretion were eligible for enrolment in the study. Fixed dose combination of Rabeprazole (enteric-coated, EC) 20 mg + Domperidone (sustained release, SR) 30 mg capsule treatment was given for a total duration of 90 days and efficacy was assessed by the change in RFS and RSI score at Day 90. The safety and tolerability of the study drug was assessed by monitoring adverse events, vital signs and physical examination. Overall, 50 patients were enrolled and completed the study. After 12 weeks of fixed dose combination of Rabeprazole (enteric-coated, EC) 20 mg + Domperidone (sustained release, SR) 30 mg capsule treatment there was a significant change in mean RSI scores [mean (SD) RSI: 19.18 (3.24) at baseline to 2.52 (2.31) at end of study; (p<0.0001)] as well as mean RFS score [mean (SD) RFS: 12.62 (1.48) at baseline to 0.30 (0.51) at end of study; (p<0.0001)]. No adverse event was reported by any patient during the study period. Twelve weeks of treatment with combination of fixed dose combination of Rabeprazole (enteric-coated, EC) 20 mg + Domperidone (sustained release, SR) 30 mg capsule significantly improved reflux symptoms in patients with LPR. The combination was found to be safe and well tolerated.

  3. Replacing the Measles Ten-Dose Vaccine Presentation with the Single-Dose Presentation in Thailand

    OpenAIRE

    Lee, Bruce Y.; Assi, Tina-Marie; Rookkapan, Korngamon; Connor, Diana L.; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Joel S. Welling; Bryan A. Norman; Chen, Sheng-I; Bailey, Rachel R; Wiringa, Ann E.; Wateska, Angela R.; Jana, Anirban; Willem G van Panhuis

    2011-01-01

    Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes entailed to deliver vaccines from manufacturers to patients). We developed a computational model of Thailand’s Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose Measles-Mumps-Rubella vaccine (which Thailand ...

  4. Pharmacokinetics of Single-Dose and Multi-Dose of Lovastatin/Niacin ER Tablet in Healthy Volunteers

    OpenAIRE

    Yan-yan Jia; Song Ying; Chen-tao Lu; Jing Yang; Li-kun Ding; Ai-dong Wen; Yan-rong Zhu

    2012-01-01

    An extended-release (ER) niacin and lovastatin fixed-dose combination has been developed for the treatment of primary hypercholesterolemia and mixed dyslipidemia. The purpose of the present study was to examine the drug interaction between niacin and lovastatin after multi-dose oral administration of lovastatin/niacin ER combination in healthy Chinese volunteers. A single-center, randomized, open-label, 5-period crossover study was conducted in thirty healthy volunteers aged 18 to 45 years wi...

  5. SU-D-207A-07: The Effects of Inter-Cycle Respiratory Motion Variation On Dose Accumulation in Single Fraction MR-Guided SBRT Treatment of Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Stemkens, B; Glitzner, M; Kontaxis, C; Prins, F; Crijns, SPM; Kerkmeijer, L; Lagendijk, J; Berg, CAT van den; Tijssen, RHN [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Denis de Senneville, B [Imaging Division, University Medical Center Utrecht, Utrecht (Netherlands); IMB, UMR 5251 CNRS/University of Bordeaux (France)

    2016-06-15

    Purpose: To assess the dose deposition in simulated single-fraction MR-Linac treatments of renal cell carcinoma, when inter-cycle respiratory motion variation is taken into account using online MRI. Methods: Three motion characterization methods, with increasing complexity, were compared to evaluate the effect of inter-cycle motion variation and drifts on the accumulated dose for an SBRT kidney MR-Linac treatment: 1) STATIC, in which static anatomy was assumed, 2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, based on the respiratory phase and 3) PCA, in which 3D volumes were generated using a PCA-model, enabling the detection of inter-cycle variations and drifts. An experimental ITV-based kidney treatment was simulated in a 1.5T magnetic field on three volunteer datasets. For each volunteer a retrospectively sorted 4D-MRI (ten respiratory phases) and fast 2D cine-MR images (temporal resolution = 476ms) were acquired to simulate MR-imaging during radiation. For each method, the high spatio-temporal resolution 3D volumes were non-rigidly registered to obtain deformation vector fields (DVFs). Using the DVFs, pseudo-CTs (generated from the 4D-MRI) were deformed and the dose was accumulated for the entire treatment. The accuracies of all methods were independently determined using an additional, orthogonal 2D-MRI slice. Results: Motion was most accurately estimated using the PCA method, which correctly estimated drifts and inter-cycle variations (RMSE=3.2, 2.2, 1.1mm on average for STATIC, AVG-RESP and PCA, compared to the 2DMRI slice). Dose-volume parameters on the ITV showed moderate changes (D99=35.2, 32.5, 33.8Gy for STATIC, AVG-RESP and PCA). AVG-RESP showed distinct hot/cold spots outside the ITV margin, which were more distributed for the PCA scenario, since inter-cycle variations were not modeled by the AVG-RESP method. Conclusion: Dose differences were observed when inter-cycle variations were taken into account. The increased inter

  6. Single dose oral etoricoxib for acute postoperative pain in adults.

    Science.gov (United States)

    Clarke, Rachel; Derry, Sheena; Moore, R Andrew

    2014-05-08

    participants with etoricoxib 120 mg and 12% with placebo reported at least 50% pain relief (NNT 1.8 (1.7 to 2.0); high-quality evidence). For dental studies only, the NNT was 1.6 (1.5 to 1.8). A single dose of 90 mg produced similar results in one large trial. Other doses (60, 180, and 240 mg) were each studied in only one treatment arm.Significantly fewer participants used rescue medication over 24 hours when taking etoricoxib 120 mg than placebo (NNT to prevent remedication 2.2 (1.9 to 2.8)), and the median time to use of rescue medication was 20 hours for etoricoxib and two hours for placebo. Adverse events were reported at a similar rate to placebo (moderate-quality evidence), with no serious events. Single-dose oral etoricoxib produces high levels of good quality pain relief after surgery, and adverse events did not differ from placebo in these studies. The 120 mg dose is as effective as, or better than, other commonly used analgesics.

  7. The pharmacokinetics of a single dose of artemisinin in patients with uncomplicated falciparum malaria

    NARCIS (Netherlands)

    de Vries, P. J.; Tran, K. D.; Nguyen, X. K.; Le Nguyen, B.; Pham, T. Y.; Dao, D. D.; van Boxtel, C. J.; Kager, P. A.

    1997-01-01

    The pharmacokinetics of artemisinin was studied in 11 Vietnamese patients with uncomplicated falciparum malaria after a single 500 mg oral dose. Curative treatment with mefloquine (15 mg/kg) was provided 24 hr after the artemisinin dose. Artemisinin concentrations were measured by high-performance

  8. Coronary vasodilatory action after a single dose of nicorandil

    NARCIS (Netherlands)

    H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)

    1988-01-01

    textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive

  9. Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

    Directory of Open Access Journals (Sweden)

    Yusuf Kale

    2015-08-01

    Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

  10. Efficacy of various single-dose regimens of ceftriaxone in ...

    African Journals Online (AJOL)

    The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

  11. Comparison of serological responses to single-dose azithromycin (2 g) versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients in an area of low prevalence of macrolide-resistant Treponema pallidum infection.

    Science.gov (United States)

    Yang, Chia-Jui; Tang, Hung-Jen; Chang, Sui-Yuan; Hsieh, Szu-Min; Lee, Kuan-Yeh; Lee, Yuan-Ti; Sheng, Wang-Huei; Yang, Shang-Ping; Hung, Chien-Ching; Chang, Shan-Chwen

    2016-03-01

    Effectiveness of single-dose azithromycin (2 g) in the treatment of early syphilis among HIV-infected patients has rarely been evaluated in the era of combination ART. Consecutive HIV-infected patients with early syphilis, who received 2 g single-dose azithromycin or 2.4 MU benzathine penicillin G, between 2007 and 2014, were prospectively observed. Genotypic resistance to macrolides was determined in Treponema pallidum isolates identified from clinical specimens using PCR assays. Rapid plasma reagin (RPR) titres were determined at baseline and every 3 months after treatment. Primary outcome was a decline of RPR titre by ≥4-fold at 12 months after treatment. During the study period, 162 HIV-infected patients with early syphilis received benzathine penicillin G and 237 patients received azithromycin. At 12 months follow-up, the serological response rate for penicillin and azithromycin groups was 61.1% and 56.5% (P = 0.41), respectively; respective response rate was 61.1% and 65.9% (P = 0.49) if we only included patients infected with T. pallidum not harbouring macrolide resistance in the azithromycin group. In multivariate analysis, RPR titres ≥1:32 (OR 2.56; 95% CI 1.55-4.21) and prior syphilis (OR 0.54; 95% CI 0.35-0.81) were predictors of serological response. Most common adverse effects of azithromycin included diarrhoea (52.7%), nausea (22.4%), abdominal pain (18.6%), bloating (17.7%) and lassitude/somnolence (27.4%). In the setting of a low prevalence of macrolide-resistant T. pallidum, 2 g single-dose azithromycin achieved a similar serological response to benzathine penicillin G in HIV-infected patients with early syphilis. Major adverse effects of azithromycin were gastrointestinal symptoms and lassitude/somnolence. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Single dose dipyrone (metamizole) for acute postoperative pain in adults.

    Science.gov (United States)

    Hearn, Leslie; Derry, Sheena; Moore, R Andrew

    2016-04-20

    placebo (236 participants). In addition to placebo, all studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen; 338 participants). Seven studies used the oral route of administration, and one study used the intramuscular route. The mean age ranged from 23 to 62 years. Six studies included both men and women, and two studies included only women. All the studies were small, but were otherwise of moderate to good quality.Over 70% of participants experienced our primary outcome of at least 50% pain relief over four to six hours with oral dipyrone 500 mg compared to 30% with placebo (five studies, 288 participants; NNT 2.4 (95% CI 1.8 to 3.1)) (moderate quality evidence). There were insufficient data to assess other doses or routes of administration of dipyrone.Fewer participants needed rescue medication within four to six hours with dipyrone 500 mg than with placebo (7% with dipyrone versus 34% with placebo; four studies, 248 participants) (low quality evidence).The data on numbers of participants experiencing any adverse event was inconsistently reported and no analysis was possible. No serious adverse events or adverse event withdrawals were reported (very low quality evidence).There were too few data to compare dipyrone directly with other active treatments. Based on very limited information, a single dose of dipyrone 500 mg provides good pain relief to about 70% of people treated, compared to about 30% with placebo. For every five people given dipyrone 500 mg, two people would experience this level of pain relief over four to six hours who would not have done with placebo, and fewer people would need rescue medication.We were unable to compare dipyrone directly with other active treatments, or to assess the effects of different doses or routes of administration, or the number of participants experiencing adverse events, because of insufficient data and inadequate reporting.

  13. Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

    Science.gov (United States)

    Martin, Elizabeth P; Mukherjee, Jean; Sharp, Claire R; Sinnott-Stutzman, Virginia B

    2017-11-01

    Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

  14. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage      I seminoma: a randomised trial

    DEFF Research Database (Denmark)

    Oliver, R. T. D.; Mason, M. D.; Mead, G. M.

    2005-01-01

    BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I       seminoma, but is associated with a risk of late non-germ-cell cancer and       cardiovascular events. After good results in initial studies with one       injection of carboplatin, we undertook a large randomised trial...... to compare       the approaches of radiotherapy with chemotherapy in seminoma treatment.       METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14       countries were randomly assigned to receive radiotherapy (para-aortic       strip or dog-leg field; n=904) or one injection of carboplatin...... was by intention to treat and       per protocol. This trial has been assigned the International Standard       Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560       patients received radiotherapy and carboplatin, respectively. With a       median follow-up of 4 years (IQR 3...

  15. Dose Escalation Using Contact X-ray Brachytherapy After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-center Experience.

    Science.gov (United States)

    Sun Myint, Arthur; Smith, Fraser McLean; Gollins, Simon; Wong, Helen; Rao, Christopher; Whitmarsh, Karen; Sripadam, Raj; Rooney, Paul; Hershman, Michael; Pritchard, D Mark

    2017-10-20

    To review the outcomes of rectal cancer patients treated with a nonsurgical approach using contact x-ray brachytherapy (CXB) when suspicious residual disease (≤3 cm) was present after external beam chemoradiation therapy/radiation therapy (EBCRT/EBRT). Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database. These patients were referred after initial local multidisciplinary team discussion because they were not suitable for, or had refused, surgery. All selected patients received a CXB boost after EBCRT/EBRT. Most patients received a total of 90 Gy of CXB delivered in 3 fractions over 4 weeks. The median follow-up period was 2.5 years (range 1.2-8.3). Of 345 consecutive patients with rectal cancer referred to us, 83 with suspicious residual disease (≤3 cm) after EBCRT/EBRT were identified for a CXB boost. Their median age was 72 years (range 36-87), and 58 (69.9%) were men. The initial tumor stages were cT2 (n = 28) and cT3 (n = 55), and 54.2% were node positive. A clinical complete response (cCR) was achieved in 53 patients (63.8%) after the CXB boost that followed EBCRT/EBRT. Of these 53 patients, 7 (13.2%) developed a relapse after achieving a cCR, and the 6 patients (11.6%) with nonmetastatic regrowth underwent salvage surgery (100%). At the end of the study period, 69 of 83 patients (83.1%) were cancer free. Our data suggest that a CXB boost for selected patients with suspicious residual disease (≤3 cm) after EBCRT/EBRT can be offered as an alternative to radical surgery. In our series, patients with a sustained cCR had a low rate of local regrowth, and those with nonmetastatic regrowth could be salvaged successfully. This approach could provide an alternative treatment option for elderly or comorbid patients who are not suitable for surgery and those with rectal cancer who wish to avoid surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    2014-09-24

    Sep 24, 2014 ... stay of the patients. Therefore, reducing the side effects associated with intrathecal anesthesia is quite helpful to support better postoperative management. Combined low dose local anesthetics and opioids versus single use of LA for transurethral urological surgery: A meta‑analysis. Y Ding, M Li, L Chen1, ...

  17. Efficacy of various single-dose regimens of ceftriaxone in ...

    African Journals Online (AJOL)

    1990-08-18

    Aug 18, 1990 ... The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), admini- stered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg.

  18. single dose pharmacokinetics of mefloquine in healthy nigerian ...

    African Journals Online (AJOL)

    BSN

    Mefloquine 500mg single dose was administered and blood samples were collected. 11t intervals. Plasma concentrations were ... total plasma clearance of. 0.453L/day/kg. The elimination was slow with a t1128 of 18. 60 days. ... Mefloquine has been assayed m biological fluids by different chromatographic methods such ...

  19. Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

    Science.gov (United States)

    Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

    2016-02-01

    Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

  20. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, Andrew S.; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely...... to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution...... also show that the dim grains in the distributions have a greater over-dispersion than the bright grains, implying that insensitive samples will have greater values of over-dispersion than sensitive samples....

  1. Adderall XR: long acting stimulant for single daily dosing.

    Science.gov (United States)

    Sallee, Floyd R; Smirnoff, Alexander V

    2004-11-01

    Adderall XR (SLI381) is the latest addition to the group of psychostimulant formulations, which provides the mixed amphetamine salts contained in Adderall as a single-daily dose formulation. Adderall XR is indicated for the treatment of attention deficit hyperactivity disorder in children and adolescents, with recent US Food and Drug Administration approval for attention deficit hyperactivity disorder in adults. Novel and important aspects of Adderall XR is its 12 h duration of action, relative superior efficacy to nonstimulant atomoxetine in a comparator trial, and significant quality of life impact in children, confirmed by the largest effectiveness trial yet to be performed for any attention deficit hyperactivity disorder therapy. Potentially important benefits of Adderall XR are proven safety and efficacy in adults with attention deficit hyperactivity disorder and positive postmarketing findings in treating oppositional defiant disorder -- the most common comorbidity in children with attention deficit hyperactivity disorder. This review summarizes the important properties of Adderall XR, to include a distinct two-stage delivery system and combination of active ingredients, offering unique advantages. Relevant clinical trials and the newest data from meeting reports are also discussed.

  2. Vaxchora: A Single-Dose Oral Cholera Vaccine.

    Science.gov (United States)

    Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

    2017-07-01

    To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

  3. Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

    Science.gov (United States)

    Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

    2017-04-01

    Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine

  4. Replacing the measles ten-dose vaccine presentation with the single-dose presentation in Thailand.

    Science.gov (United States)

    Lee, Bruce Y; Assi, Tina-Marie; Rookkapan, Korngamon; Connor, Diana L; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Chen, Sheng-I; Bailey, Rachel R; Wiringa, Ann E; Wateska, Angela R; Jana, Anirban; Van Panhuis, Willem G; Burke, Donald S

    2011-05-12

    Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes involved in distributing vaccines from manufacturers to patients). We developed a computational model of Thailand's Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose measles-mumps-rubella vaccine (which Thailand is currently considering) or a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations' storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Treatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men - a double-blind randomised controlled trial protocol.

    Science.gov (United States)

    Lau, Andrew; Kong, Fabian; Fairley, Christopher K; Donovan, Basil; Chen, Marcus; Bradshaw, Catriona; Boyd, Mark; Amin, Janaki; Timms, Peter; Tabrizi, Sepehr; Regan, David G; Lewis, David A; McNulty, Anna; Hocking, Jane S

    2017-01-06

    Rectal infection with Chlamydia trachomatis is one of the most common bacterial sexually transmissible infections among men who have sex with men (MSM) with diagnosis rates continuing to rise. Current treatment guidelines recommend either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. However, there are increasing concerns about treatment failure with azithromycin. We are conducting the first randomised controlled trial (RCT) to compare treatment efficacy of azithromycin versus doxycycline for the treatment of rectal chlamydia in MSM. The Rectal Treatment Study will recruit 700 MSM attending Australian sexual health clinics for the treatment of rectal chlamydia. Participants will be asked to provide rectal swabs and will be randomised to either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. Participants will be asked to complete questionnaires about adverse drug reactions, sexual behaviour and drug adherence via short message service and online survey. The primary outcome is the treatment efficacy as determined by a negative chlamydia nucleic acid amplification test at 4 weeks post treatment. Secondary outcomes will utilise whole genome sequencing and mRNA assay to differentiate between treatment failure, reinfection or false positive results. Rectal chlamydia is an increasing public health concern as use of pre-exposure prophylaxis against HIV becomes commonplace. Optimal, evidence-based treatment is critical to halting ongoing transmission. This study will provide the first RCT evidence comparing azithromycin and doxycycline for the treatment of rectal chlamydia. The results of this trial will establish which treatment is more efficacious and inform international management guidelines. Australian New Zealand Clinical Trials Registry ACTRN12614001125617.

  6. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Feras Sendy

    2015-01-01

    Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  7. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

    Science.gov (United States)

    Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

    2015-01-01

    Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate. PMID:25861275

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

    NARCIS (Netherlands)

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

    2017-01-01

    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

  9. A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

    CERN Document Server

    Folz, E

    1999-01-01

    In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose.

  10. Voclosporin food effect and single oral ascending dose pharmacokinetic and pharmacodynamic studies in healthy human subjects.

    Science.gov (United States)

    Mayo, Patrick R; Huizinga, Robert B; Ling, Spencer Y; Freitag, Derrick G; Aspeslet, Launa J; Foster, Robert T

    2013-08-01

    Voclosporin (VCS) is a novel calcineurin (CN) inhibitor intended for prevention of organ graft rejection and treatment of lupus nephritis. These studies evaluated the single ascending dose pharmacokinetics (PK) and pharmacodynamics (PD, CN activity) of VCS and the effect of food. VCS was administered orally in single doses of 0.25 through 4.5 mg/kg in 62 subjects in the single ascending dose study and as a single oral 1.5 mg/kg dose to 18 subjects after fasting, consumption of a low-fat and high-fat meal. Non-compartmental PK, PD, and PKPD correlation were evaluated. Following single oral doses, systemic exposure increased in a linear manner and demonstrated 1:1 dose-proportional, first-order linear PK above 1.5 mg/kg. VCS inhibited CN activity in a dose-related fashion with maximal inhibition peaking at 3.0 mg/kg. PKPD correlation indicated an EC50 of 78.3 ± 6.8 ng/mL. Administration of VCS with a low-fat and high-fat meal decreased C(max) by 29% and 53%, respectively, and AUC(inf) by 15% and 25%, respectively. Following ascending single doses of VCS, exposure increased in a linear fashion. A food effect on exposure was demonstrated, with a more pronounced effect following a high-fat meal. VCS concentrations were also found to correlate with CN activity. © The Author(s) 2013.

  11. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    OpenAIRE

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to tak...

  12. Response of mouse tongue epithelium to single doses of bleomycin and radiation.

    Science.gov (United States)

    Dörr, W; Hirler, E; Hönig, M

    1993-06-01

    Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED50) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effect curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation.

  13. A case of therapy-related acute myeloid leukemia with inv(16)(p13.1q22) after single low-dose iodine-131 treatment for thyroid cancer

    OpenAIRE

    Jeong, Ji Hun; Ahn, Jeong Yeal; Park, Soon Ho; Park, Mi Jung; Kim, Kyung Hee; Hong, Jun Shik

    2012-01-01

    Radioiodine is regularly used in the treatment of thyroid cancer to eliminate residual malignant tissue after thyroidectomy and to treat metastasis. Because of the low dose of radioiodine used to treat thyroid cancer patients, leukemia is an uncommon complication of exposure to radioiodine. Here, we present a patient who developed therapy-related acute myeloid leukemia with inv(16)(p13.1q22);CBFβ-MYH11, eosinophilia, and K-ras mutation and who had been treated with very low-dose radioiodine f...

  14. Derivation of mean dose tolerances for new fractionation schemes and treatment modalities.

    Science.gov (United States)

    Perkó, Zoltán; Bortfeld, Thomas R; Hong, Theodore S; Wolfgang, John; Unkelbach, Jan

    2017-11-03

    Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the Biologically Effective Dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone. Methods: A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available. Results: The results show that the standard BED equation - neglecting the spatial dose distribution - can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30-40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula. Conclusions: The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5-10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose. © 2017 Institute of Physics

  15. Single dose oral diclofenac for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2015-07-07

    Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'. To assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015. Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. This update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously

  16. Yaws Osteoperiostitis Treated with Single-Dose Azithromycin.

    Science.gov (United States)

    González-Beiras, Camila; Vall-Mayans, Martí; González-Escalante, Ángel; McClymont, Kelly; Ma, Li; Mitjà, Oriol

    2017-05-01

    AbstractThe etiologic agent of yaws, Treponema pallidum subsp. pertenue, causes a multistage infection transmitted by nonsexual contact with the exudates from active lesions. Bone lesions in the form of osteoperiostitis are common and occur in numerous bones simultaneously in early stages. Although a multinational eradication campaign with mass administration of intramuscular benzathine benzylpenicillin in the 1950s greatly reduced its global incidence, a resurgence of yaws has occurred since around 2000 in western and central Africa and the Pacific Islands. The finding that a single oral dose of azithromycin (30 mg/kg) was as effective as benzathine benzylpenicillin prompted renewed interest by World Health Organization in 2012 toward eradication of this infection by 2020. We previously reported the excellent response to benzathine benzylpenicillin therapy for yaws osteoperiostitis. Herein, we document a confirmed case of yaws with osteoperiostitis successfully treated with single-dose azithromycin and discuss the pathology of yaws periostitis and comment on the implications of this in light of the new campaign toward yaws eradication.

  17. Cardiac Safety of Diclofenac at a Single Dose in Ram

    Directory of Open Access Journals (Sweden)

    Ayse Er

    2013-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5 mg/kg, IM was injected to 6 rams. Blood samples were collected in before (0 hour, control and 6 hours after injection. Specific (troponin I, and creatine kinase-MB and nonspecific (lactate dehydrogenase, aspartate aminotransferase blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus parameters, and hemogram values were measured. Diclofenac increased (P<0.05 specific (troponin I and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase, hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase, and muscular (creatine kinase damage markers and high density lipoprotein level, while it decreased (P<0.05 low density lipoprotein level. Moreover, diclofenac decreased (P<0.05 white blood cell counts and increased (P<0.05 red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep.

  18. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    Science.gov (United States)

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. Results: His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. Conclusion: We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis. PMID:27442680

  19. Single-dose toxicokinetics of permethrin in broiler chickens.

    Science.gov (United States)

    Gögebakan, T; Eraslan, G

    2015-01-01

    Single-dose toxicokinetics of permethrin was investigated in broiler chickens. A total of 20 male broiler chickens were assigned at random to two groups of 10 at 30 days of age. A single dose of 10 mg/kg body weight of permethrin was administered intravenously to the first group; in the second group, the same dose was administered into the crop. Serum permethrin was measured using an electron capture detector and gas chromatography equipment. The derived serum permethrin concentration/time curve demonstrated that the distribution kinetics of permethrin was well described by a two-compartment open model. For intravenous permethrin administration, the half-life at λ phase (t1/2λ), mean residence time (MRT) and area under the concentration-time curve in 0→∞ (AUC0→∞) values respectively were 4.73 ± 1.00 h, 5.06 ± 1.05 h and 16.45 ± 3.28 mg/h/l. In contrast, the Cmax, tmax, t1/2λ, MRT and AUC0→∞ values respectively of the group given intra-crop permethrin were 0.60 ± 0.42 μg/ml, 0.55 ± 0.19 h, 5.54 ± 0.78 h, 7.06 ± 0.63 h and 1.95 ± 0.97 mg/h/l. The bioavailability of permethrin was 0.11. For both administration routes, the residence time of permethrin in the body was short and the bioavailability of permethrin was low. These results are relevant for assessing the use and safety of permethrin.

  20. Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

    NARCIS (Netherlands)

    aan het Rot, Marije; Collins, Katherine A.; Murrough, James W.; Perez, Andrew M.; Reich, David L.; Charney, Dennis S.; Mathew, Sanjay J.

    2010-01-01

    Background: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days)

  1. Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

    Directory of Open Access Journals (Sweden)

    Jaydip Ramani

    Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

  2. Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

    Science.gov (United States)

    Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

    2016-11-01

    Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Grace; Earl, Matthew A; Yu, Cedric X [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States)], E-mail: cyu002@umaryland.edu

    2009-11-07

    Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc(TM) deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to {<=}{+-} 5 deg. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was

  4. Early prediction for the requirement of second or third dose methotrexate in women with ectopic pregnancy, treated with single-dose regimen.

    Science.gov (United States)

    Yıldırım, Aysegul; Cırık, Derya Akdağ; Altay, Metin; Gelisen, Orhan

    2015-06-01

    To investigate the predictive factors for the requirement of additional doses of methotrexate in women with ectopic pregnancy treated with single-dose methotrexate regimen. This retrospective cohort study was conducted on women treated with single-dose methotrexate regimen for ectopic pregnancy at a tertiary referral center. Control group included the patients who were treated only with a single dose of methotrexate (n = 131) and study group included the patients who need a second dose or third dose methotrexate (n = 76). The sonographic variables such as size of the ectopic mass, the endometrial thickness and biochemical variables were analyzed via Chi square and student t test. Logistic regression analysis used to determine independent predictors of the additional dose requirement. The size of the ectopic mass and the endometrial thickness were similar in both groups. However, all human chorionic gonadotropin values on day 1, 4 and 7 were significantly higher in study group than the control group (p = 0.0001). Logistic regression analysis revealed that the human chorionic gonadotropin changes between day 1 and 4 is a predictive factor for requirement of additional doses of methotrexate (area under curve: 0.763, p 22% reduction from day 1 to 4. Less than 22% reduction in human chorionic gonadotropin levels from day 1 to 4 can be used as a predictive factor for the requirement of an additional dose of methotrexate in single-dose regimen. This cutoff value can be used for patients to inform about the probable longer resolution time and refer to alternative treatment modalities such as two-dose, multiple-dose regimens or surgery.

  5. Dose volume uniformity index: a simple tool for treatment plan evaluation in brachytherapy

    Directory of Open Access Journals (Sweden)

    Ramachandran Prabhakar

    2010-07-01

    Full Text Available Purpose: In radiotherapy treatment planning, dose homogeneity inside the target volume plays a significant role in the final treatment outcome. Especially in brachytherapy where there is a steep dose gradient in the dose distribution inside the target volume, comparing the plans based on the dose homogeneity helps in assessing the high dose volume inside the final treatment plan. In brachytherapy, the dose inhomogeneity inside the target volume depends on many factors such as the type of sources, placement of these radioactive sources, distance between the applicators/implanttubes, dwell time of the source, etc. In this study, a simple index, the dose volume uniformity index (DVUI, has been proposed to study the dose homogeneity inside the target volume. This index gives the total dose volume inhomogeneity inside a given prescription isoline.Material and methods: To demonstrate the proposed DVUI in this study, a single plane implant (breast: 6 catheters, a double plane implant (breast: 9 catheters and a tongue implant (5 catheters were selected. The catheters were reconstructed from the CT image datasets in the Plato treatment planning system. The doses for the single, double and tongue implants were prescribed to the reference dose rate as per the Paris technique. DVUI was computed from the cumulative dose volume histogram.Results: For a volume receiving a uniform dose inside the prescription isoline, the DVUI is 1. Any value of DVUI > 1 shows the presence of a relatively high dose volume inside the prescription isoline. In addition to the concept of DVUI, a simple conformality index, the dose volume conformality index (DVCI, has also been proposed in this study based on the DVUI.Conclusion: The DVUI and the proposed DVCI in this study provide an easy way of comparing the rival plans in brachytherapy.

  6. [Serum and tissue concentrations after a single dose of cefaclor].

    Science.gov (United States)

    Plaue, R; Müller, O; Fabricius, K; Bethke, R O

    1979-01-01

    Serum and tissue concentrations of cefaclor were determined a total of 155 and 96 times respectively in 16 volunteers after a single dose of 1 g. At this dosage peak concentrations of 13.5, 14.5 and 13.4 mcg/ml were measured after 60, 90 and 120 minutes respectively. Tissues in which concentrations were measured included cortical bone, spongy bone, muscle, fascia, cutis and subcutis. By measuring blood concentrations of the tissue samples, a division could be made for purposes of calculation into intravascular and extravascular active components. Low amounts of extravascular cefaclor could be established merely in the fascia and in the cutis. The cefaclor concentrations found in spongy bone, muscles and subcutis proved to be determined to a large extent by the intravascular antibiotic. No cefaclor could be detected in cortical bone at the given dosage.

  7. Single dose Intraoperative Antibiotics versus Postoperative Antibiotics for Patient Undergoing Laparoscopic Cholecystectomy for Symptomatic Cholelithiasis

    Directory of Open Access Journals (Sweden)

    Sagun Bahadur Thapa

    2017-04-01

    Full Text Available Introduction: Surgical site infection is a common complication shown in literature following cholecystectomies. Smaller incision and use of trocars in laparoscopic cholecystectomy lessen the contamination resulting in less chances of surgical site infection. However, in fear of postoperative infection, many opt for the prolonged postoperative use of antibiotic and there is growing consensus against it. Antibiotics not only increases the cost and hospital stay duration but it aids in emergence of multidrug resistance. Because of the controversies, we conducted this clinical trial to see whether a single prophylactic dose of antibiotic at the time of induction of anesthesia for laparoscopic cholecystectomy was equally effective in controlling post-operative infection as multi-dose antibiotics during and post-operative period. Methods: The study was conducted at the department of general surgery, Lumbini Medical College Teaching Hospital, from November  2015 to October 2016. All cases with symptomatic cholelithiasis subjected for laparoscopic cholecystectomy were enrolled. Patients were randomized into two groups; Group SD received single dose of an intravenous dose of amikacin 500 mg, at induction of anesthesia and Group MD received multiple intravenous dose of amikacin, during and postoperatively for two days. Complications, hospital stay, and treatment cost in two groups were compared and analyzed. Results: There were a total of 240 patients in the study, 118 in Group SD and 122 in Group MD. Post-operative infection rate was 4.2% (n= 5, N=118 in Group SD and 3.3% (n=4, N=122 in Group MD; the difference was not significant (p=0.75. Hospital stay was prolonged and cost was higher significantly in Group MD. Conclusion: Single dose of prophylactic antibiotic, administered at induction of anesthesia, is equally effective as multiple doses of post surgical antibiotics to prevent post-operative infection in patients undergoing elective laparoscopic

  8. Pharmacokinetics of EDP-420 after ascending single oral doses in healthy adult volunteers.

    Science.gov (United States)

    Jiang, Li-Juan; Wang, Michelle; Or, Yat Sun

    2009-05-01

    EDP-420 (EP-013420, S-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections. It has good preclinical pharmacokinetic properties across multiple species and potent in vitro and in vivo activity against respiratory tract infection pathogens, including Haemophilus influenzae, atypical organisms (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila), and multidrug-resistant streptococci. The safety, tolerability, and pharmacokinetics of an orally administered EDP-420 suspension in 40 healthy adult subjects were assessed in a randomized, double-blind, placebo-controlled, ascending single-dose study. Eligible subjects were sequentially randomized into one of five study groups (i.e., 100-, 200-, 400-, 800-, or 1,200-mg dosing groups) consisting of eight subjects (six active and two placebo) each. EDP-420 was well tolerated. There were no serious adverse events reported, nor were there any dose-limiting clinical or laboratory adverse events reported. EDP-420 was rapidly absorbed after a single oral dose. The mean plasma terminal half-life ranged from 15.6 to 20.1 h with low clearance. At the 400-mg dose, the area under the curve was 14.4 microg x h/ml, which well exceeded the required area under the concentration-time curve to cover common respiratory tract infection pathogens based on preclinical pharmacokinetic/pharmacodynamic modeling. The long half-life and high systemic exposure of EDP-420 support once-daily dosing and may allow for shorter treatment durations compared to other macrolide antibiotics. Based on its human pharmacokinetic profiles, taken together with its in vitro/in vivo activity against common respiratory pathogens, EDP-420 warrants efficacy trials for the treatment of respiratory tract infections.

  9. Pharmacokinetics of EDP-420 after Ascending Single Oral Doses in Healthy Adult Volunteers▿

    Science.gov (United States)

    Jiang, Li-Juan; Wang, Michelle; Or, Yat Sun

    2009-01-01

    EDP-420 (EP-013420, S-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections. It has good preclinical pharmacokinetic properties across multiple species and potent in vitro and in vivo activity against respiratory tract infection pathogens, including Haemophilus influenzae, atypical organisms (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila), and multidrug-resistant streptococci. The safety, tolerability, and pharmacokinetics of an orally administered EDP-420 suspension in 40 healthy adult subjects were assessed in a randomized, double-blind, placebo-controlled, ascending single-dose study. Eligible subjects were sequentially randomized into one of five study groups (i.e., 100-, 200-, 400-, 800-, or 1,200-mg dosing groups) consisting of eight subjects (six active and two placebo) each. EDP-420 was well tolerated. There were no serious adverse events reported, nor were there any dose-limiting clinical or laboratory adverse events reported. EDP-420 was rapidly absorbed after a single oral dose. The mean plasma terminal half-life ranged from 15.6 to 20.1 h with low clearance. At the 400-mg dose, the area under the curve was 14.4 μg·h/ml, which well exceeded the required area under the concentration-time curve to cover common respiratory tract infection pathogens based on preclinical pharmacokinetic/pharmacodynamic modeling. The long half-life and high systemic exposure of EDP-420 support once-daily dosing and may allow for shorter treatment durations compared to other macrolide antibiotics. Based on its human pharmacokinetic profiles, taken together with its in vitro/in vivo activity against common respiratory pathogens, EDP-420 warrants efficacy trials for the treatment of respiratory tract infections. PMID:19223626

  10. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    Energy Technology Data Exchange (ETDEWEB)

    Stambaugh, Cassandra [Department of Physics, University of South Florida, Tampa, Florida 33612 (United States); Nelms, Benjamin E. [Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States); Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida 33612 (United States)

    2013-09-15

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from

  11. Morbid obesity and outcome of ectopic pregnancy following capped single-dose regimen methotrexate.

    Science.gov (United States)

    Hoyos, Luis R; Malik, Mokerrum; Najjar, Marvin; Rodriguez-Kovacs, Javier; Abdallah, Mazen; Vilchez, Gustavo; Awonuga, Awoniyi O

    2017-02-01

    Evaluate whether morbid obesity influenced resolution, number of doses or ultimately surgical management of tubal ectopic pregnancy (TEP) when treated with single-dose regimen methotrexate (SDR-MTX) capped at 100 mg. Retrospective cohort study of patients with a diagnosis of TEP who underwent MTX treatment from 2000 to 2013. Patients were excluded if initial β-hCG <1000 mIU/mL, did not have β-hCG follow-up or were not treated with SDR-MTX. Per protocol, dose was administered at 50 mg/m2 with a capped maximum of 100 mg. Patients were divided based on their BMI (<40 and ≥40 kg/m2). Demographic variables, β-hCG before treatment, maximum diameter of ectopic size, embryonic heart tones, decrease of β-hCG, need for additional MTX doses and surgery despite treatment were recorded and compared among the groups. 151 women were included in the study, 89.4% (135/151) non-morbidly obese and 10.6% (16/151) morbidly obese. No differences in age distribution, ethnicity, pre-treatment presence of embryonic heart tones, maximum diameter of ectopic size ≥35 mm and β-hCG ≥5000 mIU/ml were found. Following treatment, the proportion of patients with at least an 80% decrease in their β-hCG levels or need for surgery were similar, however, morbidly obese patients were significantly more likely [11/134 vs. 5/16, OR 5.1 (1.5-17.3, p = 0.015)] to require an additional MTX dose. Among patients with TEP, morbidly obese patients were five times more likely to require an additional dose compared to non-morbidly obese when SDR-MTX capped at 100 mg was used for medical management.

  12. Effects of combination treatment with ketoprofen 100 mg + acetaminophen 1000 mg on postoperative dental pain: a single-dose, 10-hour, randomized, double-blind, active- and placebo-controlled clinical trial.

    Science.gov (United States)

    Akural, Ethem I; Järvimäki, Voitto; Länsineva, Ari; Niinimaa, Ahti; Alahuhta, Seppo

    2009-03-01

    A combination of analgesic drugs with different pharmacologic properties may be more effective, with fewer adverse events, than either agent used alone. This study assessed whether the combination of acetaminophen and ketoprofen is more effective and better tolerated than either drug used alone in treating postoperative pain. This single-dose randomized, double-blind, active- and placebo-controlled study was conducted at the Finnish Student Health Service, Oulu, Finland. Patients aged 18 to 40 years with moderate or severe pain (>or=3 on a numerical rating scale [NRS] of 0-10) after surgical removal of impacted third molars were randomly assigned to receive one of the following drugs in single oral doses: ketoprofen 100 mg + acetaminophen 1000 mg, ketoprofen 100 mg, acetaminophen 1000 mg, or placebo tablets. Effectiveness was assessed by the onset of analgesia, pain intensity difference (PID) from baseline, sum of PID (SPID), and duration of analgesic effect. Patients rated pain intensity on the NRS at rest and on dry swallowing. Onset of pain relief was measured using time to PID in >or=1 category at rest or on dry swallowing (PID >or=1). Patients recorded the occurrence of adverse events and the supplemental consumption of rescue medication (ibuprofen). The study included 76 patients, accounting for 78 cases (2 patients were operated on twice and were assessed as 4 individual patients) (59% women, 41% men; mean age, 22.8 years; white race, 100%; and mean weight, 68.3 kg). At 1.5 hours, mean SPIDs at rest and on swallowing were significantly greater in the combination group than in the acetaminophen, ketoprofen, and placebo groups (all, P or=1) at rest and on swallowing were significantly less in the combination group than the acetaminophen, ketoprofen, and placebo groups (all, P patient population. Adverse events were not significantly different between the study groups. These results support the clinical practice of combining ketoprofen with acetaminophen for

  13. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  14. Single dose oral celecoxib for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Moore, R Andrew

    2013-10-22

    This is an update of a review first published in The Cochrane Library in Issue 4, 2008, and updated in Issue 3, 2012. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier reviews. To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The most recent search was to 31 May 2013. We included randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain. Two review authors assessed studies for quality and extracted data. We converted summed pain relief (TOTPAR) or pain intensity difference (SPID) into dichotomous information, yielding the number of participants with at least 50% pain relief over four to six hours. We used this to calculate the relative benefit (RB) and number needed to treat to benefit (NNT), for one patient to achieve at least 50% of maximum pain relief with celecoxib who would not have done so with placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. Ten studies (1785 participants) met the inclusion criteria. The two new studies in this update had been identified in the earlier update, but data were not available. There remain three potentially relevant unpublished studies for which data are not available at this time.The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% of maximum pain

  15. Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).

    Science.gov (United States)

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Fahmy, Sahar A; Redig, Patrick

    2010-06-01

    To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.

  16. Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder.

    Science.gov (United States)

    Harada, Eiji; Shirakawa, Osamu; Satoi, Yoichi; Marangell, Lauren B; Escobar, Rodrigo

    2016-01-01

    We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder. We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final "active" doses of 40 and 60 mg (5 mg control group), with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40-120 mg/day). Tolerability was measured by rate of discontinuation due to adverse events (DCAE). The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively. This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder.

  17. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Seung-Ho Sun

    2015-06-01

    Full Text Available Objectives: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP in Sprague-Dawley (SD rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156. The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group. General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA by using statistical analysis system (SAS, version 9.2. Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

  18. PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES.

    Science.gov (United States)

    Hyatt, Michael W; Wiederhold, Nathan P; Hope, William W; Stott, Katharine E

    2017-06-01

    Aspergillosis is a common respiratory fungal disease in African penguins ( Spheniscus demersus ) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC 0-24 ) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing.

  19. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody.

    Science.gov (United States)

    Padhi, Desmond; Jang, Graham; Stouch, Brian; Fang, Liang; Posvar, Edward

    2011-01-01

    Sclerostin, an osteocyte-secreted protein, negatively regulates osteoblasts and inhibits bone formation. In this first-in-human study, a sclerostin monoclonal antibody (AMG 785) was administered to healthy men and postmenopausal women. In this phase I, randomized, double-blind, placebo-controlled, ascending, single-dose study, 72 healthy subjects received AMG 785 or placebo (3:1) subcutaneously (0.1, 0.3, 1, 3, 5, or 10 mg/kg) or intravenously (1 or 5 mg/kg). Depending on dose, subjects were followed for up to 85 days. The effects of AMG 785 on safety and tolerability (primary objectives) and pharmacokinetics, bone turnover markers, and bone mineral density (secondary objectives) were evaluated. AMG 785 generally was well tolerated. One treatment-related serious adverse event of nonspecific hepatitis was reported and was resolved. No deaths or study discontinuations occurred. AMG 785 pharmacokinetics were nonlinear with dose. Dose-related increases in the bone-formation markers procollagen type 1 N-propeptide (P1NP), bone-specific alkaline phosphatase (BAP), and osteocalcin were observed, along with a dose-related decrease in the bone-resorption marker serum C-telopeptide (sCTx), resulting in a large anabolic window. In addition, statistically significant increases in bone mineral density of up to 5.3% at the lumbar spine and 2.8% at the total hip compared with placebo were observed on day 85. Six subjects in the higher-dose groups developed anti-AMG 785 antibodies, 2 of which were neutralizing, with no discernible effect on the pharmacokinetics or pharmacodynamics. In summary, single doses of AMG 785 generally were well tolerated, and the data support further clinical investigation of sclerostin inhibition as a potential therapeutic strategy for conditions that could benefit from increased bone formation. © 2011 American Society for Bone and Mineral Research.

  20. Evaluation of acute toxicity and the effect of single injected doses of ...

    African Journals Online (AJOL)

    USER

    2010-07-12

    Jul 12, 2010 ... The animals were observed continuously for clinical change and mortality. Next, zerumbone was injected in ... evaluate the effect of single doses of zerumbone on the extent of tissue damages of liver and .... Rats serum kidney markers quantified following injected dose of cisplatin and single injected doses ...

  1. 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

  2. Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial

    Energy Technology Data Exchange (ETDEWEB)

    Ott, O.J.; Jeremias, C.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

    2013-04-15

    The aim of this work was to compare the efficacy of two different dose fractionation schedules for radiotherapy of patients with calcaneodynia. Between February 2006 and April 2010, 457 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy using the orthovoltage technique. One radiotherapy series consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, immediately after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 87 % directly after and 88 % 6 weeks after radiotherapy. The mean VAS values before, immediately after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 65.5 {+-} 22.1 and 64.0 {+-} 20.5 (p = 0.188), 34.8 {+-} 24.7 and 39.0 {+-} 26.3 (p = 0.122), and 25.1 {+-} 26.8 and 28.9 {+-} 26.8 (p = 0.156), respectively. The mean CPS before, immediately after, and 6 weeks after treatment was 10.1 {+-} 2.7 and 10.0 {+-} 3.0 (p = 0.783), 5.6 {+-} 3.7 and 6.0 {+-} 3.9 (p = 0.336), 4.0 {+-} 4.1 and 4.3 {+-} 3.6 (p = 0.257), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.216) and delayed response (p = 0.080) were found. Radiotherapy is an effective treatment option for the management of calcaneodynia. For radiation protection reasons, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  3. Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan

    Directory of Open Access Journals (Sweden)

    Takeda Ken

    2012-07-01

    Full Text Available Abstract Background Several studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT using intra-prostate fiducial markers for clinically localized prostate cancer. Methods In total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88% for a median of 11 months (range: 2–88 months. Prostate-specific antigen (PSA relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call. The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS, the 5-year overall survival (OS outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months. Results The 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score ( Conclusions These medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further

  4. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses

    Directory of Open Access Journals (Sweden)

    Wu GL

    2015-10-01

    Full Text Available Guolan Wu, Yunliang Zheng, Huili Zhou, Xingjiang Hu, Jian Liu, You Zhai, Meixiang Zhu, Lihua Wu, Jianzhong Shentu Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Background: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers.Methods: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study.Results: Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax and the corresponding values for the area under the concentration–time curve from 0 to 10 hours (AUC0–10 h increased in a dose-proportional manner. The mean elimination half-life (t1/2 was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no

  5. Single dose oral codeine, as a single agent, for acute postoperative pain in adults

    Science.gov (United States)

    Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription. Objectives To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain. Search methods We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected. Main results Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo. Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent

  6. Effect of single dose radiation therapy on weight-bearing lameness in dogs with elbow osteoarthritis.

    Science.gov (United States)

    Kapatkin, Amy S; Nordquist, Barbro; Garcia, Tanya C; Griffin, Maureen A; Theon, Alain; Kim, Sun; Hayashi, Kei

    2016-07-19

    To determine if a single low dose of radiation therapy in dogs with osteoarthritis of the elbow joint was associated with a detectable improvement in their lameness and pain as documented by force platform gait analysis. In this cohort longitudinal observational study, five Labrador Retrievers with lameness due to elbow osteoarthritis that was unresponsive to medical treatment were removed from all non-steroidal anti-inflammatory and analgesic medications. A single treatment of radiation therapy delivering 10 Gray was performed on the affected elbow joint(s). Force platform gait analysis was used to assess the ground reaction forces of a limb affected with elbow osteoarthritis both before and after radiation therapy. Significant differences occurred in the weight-bearing on an affected limb with elbow osteoarthritis after radiation therapy at weeks six and 14. Change due to treatment was particularly apparent in dogs with unilateral elbow osteoarthritis. Administering a single low dose of radiation therapy may have a short-term benefit in dogs with elbow osteoarthritis, which is similar to the evidence supporting the use of radiation therapy in horses with orthopaedic disease.

  7. Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability.

    Science.gov (United States)

    de Vries, Marjan; Van Rijckevorsel, Dagmar C M; Vissers, Kris C P; Wilder-Smith, Oliver H G; Van Goor, Harry

    2016-03-01

    We aimed to assess the analgesic efficacy, pharmacokinetics, tolerability and safety of a single dose of Δ9-THC in patients with chronic abdominal pain resulting from chronic pancreatitis (CP). This was a randomized, single dose, double-blinded, placebo-controlled, two way crossover study in patients suffering from abdominal pain as result of CP (n = 24), post hoc subdivided into opioid and non-opioid users. Δ9-THC (8 mg) or active placebo (5 mg/10 mg diazepam) was administered orally in a double dummy design. No treatment effect was shown for delta VAS pain scores after Δ9-THC compared with diazepam. Δ9-THC was well absorbed with a mean tmax of 123 min. No significant differences were found between Δ9-THC vs. diazepam for alertness, mood, calmness or balance. Feeling anxious and heart rate were significantly increased after Δ9-THC compared with diazepam. The most frequently reported adverse events (AEs) after Δ9-THC administration were somnolence, dry mouth, dizziness and euphoric mood. A single dose of Δ9-THC was not efficacious in reducing chronic pain resulting from CP, but was well tolerated with only mild or moderate AEs. The PK results in CP patients showed delayed absorption and an increased variability compared with healthy volunteers. © 2015 The British Pharmacological Society.

  8. Equivalence in dose fall-off for isocentric and nonisocentric intracranial treatment modalities and its impact on dose fractionation schemes.

    Science.gov (United States)

    Ma, Lijun; Sahgal, Arjun; Descovich, Martina; Cho, Young-Bin; Chuang, Cynthia; Huang, Kim; Laperriere, Normand J; Shrieve, Dennis C; Larson, David A

    2010-03-01

    To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for the three modalities. The derived model fitted remarkably well for all the cases (R(2) > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

  10. Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo

    Science.gov (United States)

    Khurana, Mamta; Moriyama, Eduardo H.; Mariampillai, Adrian; Samkoe, Kimberley; Cramb, David; Wilson, Brian C.

    2009-11-01

    As part of an ongoing program to develop two-photon (2-γ) photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-γ and 2-γ activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-γ cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-γ PDT of AMD.

  11. 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.

  12. Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

    Science.gov (United States)

    Nielsen, Suzanne; Gisev, Natasa; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Larance, Briony; Campbell, Gabrielle; Shanahan, Marian; Blyth, Fiona; Lintzeris, Nicholas; Pearson, Sallie; Mattick, Richard; Degenhardt, Louisa

    2017-05-01

    To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. Descriptive, cross-sectional study, utilising a 7-day medication diary. Community-based treatment settings, Australia. A sample of 1101 people prescribed opioids for chronic non-cancer pain. Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. 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

  14. 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

  15. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    Introduction: The combination of reduced dose of local anesthetics (LA) and highly lipid‑soluble synthetic opioids for patients undergoing transurethral surgery could reduce block duration and side‑effects. However, it remains unclear what are the most appropriate levels of low dose and the extent to which the side‑effects ...

  16. Radiation optic neuropathy and retinopathy with low dose (20 Gy radiation treatment

    Directory of Open Access Journals (Sweden)

    Crandall E. Peeler

    2016-10-01

    Conclusions and importance: Though cumulative radiation doses to the anterior visual pathway of less than 50 Gy are traditionally felt to be safe, it is important to consider not just the total exposure but also the size of individual fractions. The single-dose threshold for RON in proton beam treatment has yet to be defined. Our case suggests that fractions of less than 10 Gy should be delivered to minimize the risk of optic nerve injury.

  17. Effects of single dose intranasal oxytocin on social cognition in schizophrenia.

    Science.gov (United States)

    Davis, Michael C; Lee, Junghee; Horan, William P; Clarke, Angelika D; McGee, Mark R; Green, Michael F; Marder, Stephen R

    2013-07-01

    Deficits in social cognition are common in schizophrenia and predict poor community functioning. Given the current limitations of psychosocial treatments and the lack of pharmacological treatments for social cognitive deficits, the development of novel therapeutic agents could greatly enhance functional recovery in schizophrenia. This study evaluated whether a single dose of intranasal oxytocin acutely improves social cognitive functioning in schizophrenia. Twenty-three male veterans with schizophrenia completed baseline assessments of social cognition that were divided into lower-level (facial affect perception, social perception, detection of lies) and higher-level (detection of sarcasm and deception, empathy) processes. One week later, patients received the same battery after being randomized to a single dose of 40 IU intranasal oxytocin or placebo. Though the groups did not differ significantly on the social cognition composite score, oxytocin improved performance for the higher-level social cognitive tasks (Cohen's d=1.0, p=0.045). Subjects were unable to accurately guess which treatment they had received. The improvements found in higher-level social cognition encourage further studies into the therapeutic potential of oxytocin in schizophrenia. Published by Elsevier B.V.

  18. 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

  19. Pharmacokinetics and safety of single and multiple oral doses of meloxicam in adult horses.

    Science.gov (United States)

    Noble, G; Edwards, S; Lievaart, J; Pippia, J; Boston, R; Raidal, S L

    2012-01-01

    Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses. To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses. Forty-nine healthy, university-owned adult lightbreed horses. Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/kg PO q24h, n = 7) of meloxicam for 2 weeks, compared with control horses (placebo, n = 7, or phenylbutazone, 4.4 mg/kg q12h on day 1, 2.2 mg/kg q12h for 4 days, then 2.2 mg/kg q24h for 9 days, n = 5). Maximum plasma concentration following a single oral dose of meloxicam was 915.1 ± 116.9 ng/mL and elimination half-life 10.2 ± 3.0 hours. Meloxicam (0.6 mg/kg, q24h, PO for 6 weeks) yielded plasma concentrations between 100 and 1000 ng/mL and was well tolerated by healthy adult horses. Administration of 3-5 times the recommended dose of meloxicam was associated with decreased total serum protein and albumin concentrations, gastrointestinal damage, renal damage, or bone marrow dyscrasia. PBZ administration was associated with the development right dorsal colitis, gastric ulceration, and protein losing enteropathy in 2 horses. Administration meloxicam at 0.6 mg/kg q24h was well tolerated for 6 weeks, without drug accumulation in plasma. Higher doses were associated with dose-dependent adverse effects typical of class of drugs. Copyright © 2012 by the American College of Veterinary Internal Medicine.

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

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    2016-01-01

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

  1. Chemoprophylaxis of coccidiosis in lambs with a single oral dose of toltrazuril.

    Science.gov (United States)

    Gjerde, B; Helle, O

    1991-03-01

    The prophylactic efficacy of a single oral dose of toltrazuril against coccidiosis (mixed Eimeria infections) in naturally infected lambs was evaluated in two experiments. Toltrazuril at 20 mg kg-1, given on Day 7 or Day 10 after turnout on pasture, proved to be highly efficacious in preventing clinical coccidiosis under Norwegian conditions. Toltrazuril reduced the oocyst output to very low levels, prevented the development of diarrhoea and improved weight gain during the first 4-5 weeks after treatment. Treatment on Day 7 was superior to treatment on Day 10 with respect to improving weight gain and preventing the development of soft faeces. Lambs treated with toltrazuril on Day 7 seemed to be as immune as untreated lambs to natural reinfections with coccidia later in the grazing season. In one of the experiments, natural infections with the nematode Nematodirus battus produced a coccidiosis-like disease in some lambs simultaneously with the outbreak of coccidiosis.

  2. Radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line.

    Science.gov (United States)

    Djan, Igor; Solajic, Slavica; Djan, Mihajla; Vucinic, Natasa; Popovic, Dunja; Ilic, Miroslav; Lučić, Silvija; Bogdanovic, Gordana

    2014-01-01

    Aim of the study was to compare radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line. This regime is designed to be as similar as possible to fractionated tumour radiotherapy treatment, and to provide data on radiobiological effects on human tumour cells. The cell line used in the study was HT29 (human colorectal adenocarcinoma, American Type Culture Collection HTB-38™). Also, for comparison, the MRC5 cell line (human foetal lung fibroblasts, American Type Culture Collection CCL 171) was used. Four-day treatment in a 4 × 2 Gy regime was performed. Cell viability was evaluated by tetrazolium colorimetric MTT assay. Multiple low-dose pre-irradiation induced a stronger radioadaptive response compared to single low-dose application in the HT29 cell line. Multiple pre-irradiation with 0.03 Gy and 0.05 Gy caused radioadaptive effects, while in both single and multiple low-dose pre-irradiation regimes 0.07 Gy led to radiosensitivity. Radiobiological effects induced in the HT29 cell line by low-dose pre-irradiation were evidently weak during the treatment time, because a single low-dose applied only on the first day gave no radioadaptive effects. In the MRC5 cell line different effects were registered, since radioadaptive response has not been observed after multiple or single pre-irradiation. The obtained data are interesting, especially for the possible application of low-dose pre-irradiation in radiotherapy.

  3. Fully Automated Treatment Planning for Head and Neck Radiotherapy using a Voxel-Based Dose Prediction and Dose Mimicking Method

    CERN Document Server

    McIntosh, Chris; McNiven, Andrea; Jaffray, David A; Purdie, Thomas G

    2016-01-01

    Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present an atlas-based approach which learns a dose prediction model for each patient (atlas) in a training database, and then learns to match novel patients to the most relevant atlases. The method creates a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces any requirement for specifying dose-volume objectives for conveying the goals of treatment planning. A probabilistic dose distribution is inferred from the most relevant atlases, and is scalarized using a conditional random field to determine the most likely spatial distribution of dose to yield a specific dose prior (histogram) for relevant regions of interest. Voxel-based dose mimicking then converts the predicted dose distribution to a deliverable treatment plan dose distribution. In this study, we ...

  4. Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

    Science.gov (United States)

    Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

    2017-02-01

    Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

  5. Use dose bricks concept to implement nasopharyngeal carcinoma treatment planning.

    Science.gov (United States)

    Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou; Lee, Tsair-Fwu

    2014-01-01

    A "dose bricks" concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10-15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Compared with IMRT, the expenditure of planning time and costing, "dose bricks" may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed.

  6. Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Mole, R.H.; Major, I.R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1983-01-01

    The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally ..gamma..-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

  7. A single dose of kudzu extract reduces alcohol consumption in a binge drinking paradigm.

    Science.gov (United States)

    Penetar, David M; Toto, Lindsay H; Lee, David Y-W; Lukas, Scott E

    2015-08-01

    Overconsumption of alcohol has significant negative effects on an individual's health and contributes to an enormous economic impact on society as a whole. Pharmacotherapies to curb excessive drinking are important for treating alcohol use disorders. Twenty (20) men participated in a placebo-controlled, double-blind, between subjects design experiment (n=10/group) that tested the effects of kudzu extract (Alkontrol-Herbal™) for its ability to alter alcohol consumption in a natural settings laboratory. A single dose of kudzu extract (2g total with an active isoflavone content of 520mg) or placebo was administered 2.5h before the onset of a 90min afternoon drinking session during which participants had the opportunity to drink up to 6 beers ad libitum; water and juice were always available as alternative beverages. During the baseline session, the placebo-randomized group consumed 2.7±0.78 beers before treatment and increased consumption to 3.4±1.1 beers after treatment. The kudzu group significantly reduced consumption from 3.0±1.7 at baseline to 1.9±1.3 beers after treatment. The placebo-treated group opened 33 beers during baseline conditions and 38 following treatment whereas the kudzu-treated group opened 32 beers during baseline conditions and only 21 following treatment. Additionally, kudzu-treated participants drank slower. This is the first demonstration that a single dose of kudzu extract quickly reduces alcohol consumption in a binge drinking paradigm. These data add to the mounting clinical evidence that kudzu extract may be a safe and effective adjunctive pharmacotherapy for alcohol abuse and dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, double-blind, double-dummy trial.

    NARCIS (Netherlands)

    Hamza, O.J.; Matee, M.I.N.; Bruggemann, R.J.M.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Lee, H.A.L. van der; Verweij, P.E.; Ven, A.J.A.M. van der

    2008-01-01

    BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for

  9. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

    2010-04-01

    To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

  10. Effects of a Single Dose of Caffeine on Resting Cardiovascular ...

    African Journals Online (AJOL)

    The objective of this study was to determine the effect of 5mg/kg body weight dose of caffeine on cardiovascular system of normal young adult males of Black African Origin. Twenty normal young adult male volunteers participated. A repeated measures 2 randomized Crosse over (counter balanced) double blind design was ...

  11. Effects of a Single Dose of Caffeine on Resting Cardiovascular ...

    African Journals Online (AJOL)

    Administrator

    Cardiovascular System of Normal Young Black. African Adults. Lamina Sikiru and Musa Danladi I. (Prof). Abstract. The objective of this study was to determine the effect of. 5mg/kg body weight dose of caffeine on cardiovascular system of normal .... Test procedure: On arrival to the exercise Physiology Laboratory of the.

  12. Dose fractionation and single subject studies in PET

    Science.gov (United States)

    Balakrishnan, Karthikayan

    Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals

  13. Toxicity of Single-dose Intramuscular Injection of Samjeong Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Kang Kwon

    2015-06-01

    Full Text Available Objectives: This study was carried out in order to find both the single-dose intramuscular injection toxicity and the approximate lethal dose of samjeong pharmacopuncture (SP in Sprague-Dawley (SD rats. Methods: The SD rats in this study were divided into four groups, one control group (1.0 mL/animal, normal saline and three experimental groups (0.25, 0.5, and 1.0 mL/animal, SP. All groups consisted of five male and five female rats. SP was injected as a single-dose intramuscularly at the thigh. After the injection, general symptoms and weight were observed for 14 days. After the observations had ended, hematologic and serum biochemical examinations, necropsy and a local tolerance test at the injection site were performed. The experiments were carried out at the Good Laboratory Practice firm, Biotoxtech Co. (Cheongwon, Chungbuk. Animal experiments were approved by the Ethics Committee (Approval Number: 130379. Results: No deaths occurred in any of the three experimental groups. The injection of SP had no effects on the general symptoms, body weights, results of the hematologic, and serum biochemical examinations, and necropsy findings. In local tolerance tests at the injection sites, mild inflammation was observed in the experimental group, but it did not appear to be a treatment related effect. Conclusion: Under the conditions of this test, the results from the injection of SP suggest that the approximate lethal dose of SP is above 1.0 mL/animal for both male and female SD rats. Therefore, the clinical use of SP is thought to be safe.

  14. Single dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission in Cambodia: An open-label randomized trial.

    Science.gov (United States)

    Lin, Jessica T; Lon, Chanthap; Spring, Michele D; Sok, Somethy; Chann, Soklyda; Ittiverakul, Mali; Kuntawunginn, Worachet; My, Mok; Thay, Kheangheng; Rahman, Rifat; Balasubramanian, Sujata; Char, Mengchuor; Lanteri, Charlotte A; Gosi, Panita; Ubalee, Ratawan; Meshnick, Steven R; Saunders, David L

    2017-01-01

    Single low dose primaquine (SLD PQ, 0.25mg/kg) is recommended in combination with artemisinin-based combination therapy (ACT) as a gametocytocide to prevent Plasmodium falciparum transmission in areas threatened by artemisinin resistance. To date, no randomized controlled trials have measured primaquine's effect on infectiousness to Anopheline mosquitoes in Southeast Asia. Cambodian adults with uncomplicated falciparum malaria were randomized to receive a single 45mg dose of primaquine (equivalent to three SLD PQ) or no primaquine after the third dose of dihydroartemisin-piperaquine (DHP) therapy. A membrane-feeding assay measured infectiousness to Anopheles dirus on days 0, 3, 7, and 14 of blood-stage therapy. Gametocytemia was evaluated by microscopy and reverse-transcriptase PCR. Prior to trial halt for poor DHP treatment efficacy, 101 participants were randomized and 50 received primaquine. Overall microscopic gametocyte prevalence was low (9%), but gametocytemic subjects given primaquine were gametocyte-free by day 14, and significantly less likely to harbor gametocytes by day 7 compared to those treated with DHP-alone, who remained gametocytemic for a median of two weeks. Only one infectious subject was randomized to the primaquine group, precluding assessment of transmission-blocking efficacy. However, he showed a two-fold reduction in oocyst density of infected mosquitoes less than 24 hours after primaquine dosing. In the DHP-alone group, four subjects remained infectious through day 14, infecting roughly the same number of mosquitoes pre and post-treatment. Overall, microscopic gametocytemia was an excellent predictor of infectiousness, and performed better than submicroscopic gametocytemia post-treatment, with none of 474 mosquitoes infected post-treatment arising from submicroscopic gametocytes. In a setting of established ACT resistance, a single dose of 45mg primaquine added to DHP rapidly and significantly reduced gametocytemia, while DHP-alone failed

  15. Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Kirby, Mary; Robertson, Philmore; Hellriegel, Edward; Jiang, John G

    2007-01-01

    This study evaluated the single-dose and steady-state pharmacokinetics of fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day 4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours throughout the study. Plasma fentanyl concentrations were determined for 72 hours after administration of fentanyl buccal tablet 400 microg on day 1 and the last dose of fentanyl buccal tablet 400 microg on day 9. Following single- and multiple-dose administration of fentanyl buccal tablet, the median time to maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and 1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days, consistent with the observed median half-life of approximately 22 hours following multiple doses. Observed accumulation of fentanyl after multiple doses of fentanyl buccal tablet was slightly greater than would be expected based on the single-dose data. This was attributed to the redistribution of fentanyl from a deep tissue compartment into the plasma. This study indicates that fentanyl buccal tablet has predictable pharmacokinetics following multiple-dose administration.

  16. Compressed air massage: repeated treatment causes less muscle oedema than a single treatment

    Directory of Open Access Journals (Sweden)

    M. A. Gregory

    2007-02-01

    Full Text Available Compressed air massage is a new treatment modality that has been shown to cause skeletal muscle capillary dilation for up to 24 hours after a single treatment and significantly hastens healing of diabetic ulcers. This study compares the effect of one treatment of a single muscle group, with repeated treatments of several muscle groups. Methods: Four vervet monkeys underwent one, 15 min, treatment of compressed air massage at 1 Bar, to the tibialis anterior muscle and four animals received similar treatment to the whole lower leg on three consecutive days. The tibialis anterior of the treated and untreated limbs was biopsied immediately after the final treatment. Muscle fibre diameters were measured from 1µm thick toluidine blue stained resin embedded sections using light microscopy and computerized image analysis software. Results: For treatment of the whole lower limb, the mean fibre diameter increased by 6.0% from 47.31±13.4µm(95%CI:46.47-48.16 in control biopsies to 50.14±13.93µm (95%CI:49.26-51.02 in treated muscle (p<0.001.Treatment of a single muscle showed an increase in diameter of 11.3%, from 48.21±12.68µm (95%CI:47.31-49.11 to53.63+14.29µm (95%CI:52.61-54.66 (p<0.001. Treatment of a single muscle caused significantly more oedema thantreatment of the whole limb (p<0.001. Conclusions: Repeated treatment causes skeletal muscle oedema, and this appears to be dose related. Skeletal muscleoedema after three treatments is less than after a single treatment. Further studies on the use of compressed air massage on injured muscle are warranted.

  17. Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Cooper, Tess E; Phillips, Tudor

    2016-09-22

    the data came from a single study with few participants and events.Adverse events and serious adverse events were not reported consistently for the single dose phase of the studies. In the single dose study, 11% of participants experienced adverse events with dexketoprofen 25 mg plus tramadol 75 mg, which were mostly mild or moderate nausea, vomiting, or dizziness, and typical with these medicines. Rates were lower with placebo and lower doses (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Information on multiple dosing over three and five days supported a low event rate with the combination. Overall, rates were generally low in all treatment arms, as they were for withdrawals for adverse events or other reasons. A single oral dose of dexketoprofen 25 mg plus tramadol 75 mg provided good levels of pain relief with long duration of action to more people than placebo or the same dose of dexketoprofen or tramadol alone. The magnitude of the effect was similar to other good analgesics. Adverse event rates were low.There is modest uncertainty about the precision of the point estimate for efficacy, but the NNT of 3 is consistent with other analgesics considered effective and commonly used.

  18. Split-Dose Polyethylene Glycol Is Superior to Single Dose for Colonoscopy Preparation: Results of a Randomized Controlled Trial.

    Science.gov (United States)

    Mohamed, Rachid; Hilsden, Robert J; Dube, Catherine; Rostom, Alaa

    2016-01-01

    Background. The efficacy of colonoscopy in detecting abnormalities within the colon is highly dependent on the adequacy of the bowel preparation. The objective of this study was to compare the efficacy, safety, and tolerability of PEG lavage and split-dose PEG lavage with specific emphasis on the cleanliness of the right colon. Methods. The study was a prospective, randomized, two-arm, controlled trial of 237 patients. Patients between the age of 50 and 75 years were referred to an outpatient university screening clinic for colonoscopy. Patients were allocated to receive either a single 4 L PEG lavage or a split-dose PEG lavage. Results. Overall, the bowel preparation was superior in the split-dose group compared with the single-dose group (mean Ottawa score 3.50 ± 2.89 versus 5.96 ± 3.53; P < 0.05) and resulted in less overall fluid in the colon. This effect was observed across all segments of the colon assessed. Conclusions. The current study supports use of a split-dose PEG lavage over a single large volume lavage for superior bowel cleanliness, which may improve polyp detection. This trial is registered with ClinicalTrials.gov identifier NCT01610856.

  19. Split-Dose Polyethylene Glycol Is Superior to Single Dose for Colonoscopy Preparation: Results of a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Rachid Mohamed

    2016-01-01

    Full Text Available Background. The efficacy of colonoscopy in detecting abnormalities within the colon is highly dependent on the adequacy of the bowel preparation. The objective of this study was to compare the efficacy, safety, and tolerability of PEG lavage and split-dose PEG lavage with specific emphasis on the cleanliness of the right colon. Methods. The study was a prospective, randomized, two-arm, controlled trial of 237 patients. Patients between the age of 50 and 75 years were referred to an outpatient university screening clinic for colonoscopy. Patients were allocated to receive either a single 4 L PEG lavage or a split-dose PEG lavage. Results. Overall, the bowel preparation was superior in the split-dose group compared with the single-dose group (mean Ottawa score 3.50 ± 2.89 versus 5.96 ± 3.53; P<0.05 and resulted in less overall fluid in the colon. This effect was observed across all segments of the colon assessed. Conclusions. The current study supports use of a split-dose PEG lavage over a single large volume lavage for superior bowel cleanliness, which may improve polyp detection. This trial is registered with ClinicalTrials.gov identifier NCT01610856.

  20. Retrospective dosimetry: Estimation of the dose to quartz using the single-aliquot regenerative-dose protocol

    DEFF Research Database (Denmark)

    Banerjee, D.; Bøtter-Jensen, L.; Murray, A.S.

    2000-01-01

    We report on the application of the single-aliquot regenerative-dose protocol to retrospective dosimetry, using the optically stimulated luminescence (OSL) from quartz extracted from fired bricks. These bricks had previously been exposed to enhanced levels of ionising radiation while part...

  1. Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

    Science.gov (United States)

    Vizzotti, C; Pippo, T; Urueña, A; Altuna, J; Palópoli, G; Hernández, M L; Artola, M F; Fernández, H; Orellano, P; Cañero-Velasco, M C; Ciocca, M; Ramonet, M; Diosque, M

    2015-05-07

    Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the

  2. A Bayesian dose-finding design incorporating toxicity data from multiple treatment cycles.

    Science.gov (United States)

    Yin, Jun; Qin, Rui; Ezzalfani, Monia; Sargent, Daniel J; Mandrekar, Sumithra J

    2017-01-15

    Phase I oncology trials are designed to identify a safe dose with an acceptable toxicity profile. The dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle, although patients continue to receive treatment for multiple cycles. In addition, the toxicity data from multiple types and grades are typically summarized into a single binary outcome of dose-limiting toxicity. A novel endpoint, the total toxicity profile, was previously developed to account for the multiple toxicity types and grades. In this work, we propose to account for longitudinal repeated measures of total toxicity profile over multiple treatment cycles, accounting for cumulative toxicity during dosing-finding. A linear mixed model was utilized in the Bayesian framework, with addition of Bayesian risk functions for decision-making in dose assignment. The performance of this design is evaluated using simulation studies and compared with the previously proposed quasi-likelihood continual reassessment method (QLCRM) design. Twelve clinical scenarios incorporating four different locations of maximum tolerated dose and three different time trends (decreasing, increasing, and no effect) were investigated. The proposed repeated measures design was comparable with the QLCRM when only cycle 1 data were utilized in dose-finding; however, it demonstrated an improvement over the QLCRM when data from multiple cycles were used across all scenarios. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. 28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

    Science.gov (United States)

    Fedorchak, Morgan V; Conner, Ian P; Medina, Carlos A; Wingard, Jeremy B; Schuman, Joel S; Little, Steven R

    2014-08-01

    Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Single-dose Intramuscular Toxicity of Neutral Natured Blood Stasis Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    In Ho Yeo

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze the single-dose toxicity of neutral natured blood stasis pharmacopuncture extracts. Methods:All experiments were conducted at Biotoxtech, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of neutral natured blood stasis pharmacopuncture extracts, 0.1, 0.5 and 1.0 mL, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results:In all 4 groups, no deaths occurred, and the neutral natured blood stasis pharmacopuncture extracts administered by intramuscular (IM injection was over 1.0 mL/animal. No significant changes in the body weights between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any organs or tissues. Conclusion:The above findings suggest that treatment with neutral natured blood stasis pharmacopuncture extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

  5. Single Dose Toxicity of Chukyu (spine-healing Pharmacopuncture Injection in the Muscle of Rats

    Directory of Open Access Journals (Sweden)

    Jeong Hohyun

    2014-03-01

    Full Text Available Objectives: This study was performed to analyze the single dose toxicity of Chukyu (spine-healing pharmacopuncture. Methods: All experiments were conducted at the Biotoxtech, an institution authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of Chukyu (spine-healing pharmacopuncture, 0.1, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues except in one case, where interstitial infiltrating macrophages were found in one female rat in the 0.5-mL/animal experimental group. Conclusion: The above findings suggest that treatment with Chukyu (spine-healing pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  6. Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

    Science.gov (United States)

    McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

    2017-08-01

    Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

  7. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

    Science.gov (United States)

    Pardi, Norbert; Hogan, Michael J; Pelc, Rebecca S; Muramatsu, Hiromi; Andersen, Hanne; DeMaso, Christina R; Dowd, Kimberly A; Sutherland, Laura L; Scearce, Richard M; Parks, Robert; Wagner, Wendeline; Granados, Alex; Greenhouse, Jack; Walker, Michelle; Willis, Elinor; Yu, Jae-Sung; McGee, Charles E; Sempowski, Gregory D; Mui, Barbara L; Tam, Ying K; Huang, Yan-Jang; Vanlandingham, Dana; Holmes, Veronica M; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Higgs, Stephen; Hensley, Scott E; Madden, Thomas D; Hope, Michael J; Karikó, Katalin; Santra, Sampa; Graham, Barney S; Lewis, Mark G; Pierson, Theodore C; Haynes, Barton F; Weissman, Drew

    2017-03-09

    Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.

  8. Zika virus protection by a single low dose nucleoside modified mRNA vaccination

    Science.gov (United States)

    Pardi, Norbert; Hogan, Michael J.; Pelc, Rebecca S.; Muramatsu, Hiromi; Andersen, Hanne; DeMaso, Christina R.; Dowd, Kimberly A.; Sutherland, Laura L.; Scearce, Richard M.; Parks, Robert; Wagner, Wendeline; Granados, Alex; Greenhouse, Jack; Walker, Michelle; Willis, Elinor; Yu, Jae-Sung; McGee, Charles E.; Sempowski, Gregory D.; Mui, Barbara L.; Tam, Ying K.; Huang, Yan-Jang; Vanlandingham, Dana; Holmes, Veronica M.; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Higgs, Stephen; Hensley, Scott E.; Madden, Thomas D.; Hope, Michael J.; Karikó, Katalin; Santra, Sampa; Graham, Barney S.; Lewis, Mark G.; Pierson, Theodore C.; Haynes, Barton F.; Weissman, Drew

    2017-01-01

    Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins2,3. Here, we demonstrate that a single low-dose intradermal immunization with lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV. PMID:28151488

  9. Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats.

    Science.gov (United States)

    Yata, M; McLachlan, A J; Foster, D J R; Hanzlicek, A S; Beijerink, N J

    2016-12-01

    To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats. Eight healthy adult cats. A randomised, single-blinded, crossover design was used. Two oral doses of pimobendan (0.625-mg [LD], 1.25-mg [HD]) and a control substance (3-mL water) were administered to each cat. Blood collection, echocardiography, and oscillometric blood pressure measurements were performed repeatedly for 12 h following each dose. Plasma concentrations of pimobendan and the active metabolite, O-desmethylpimobendan (ODMP), were quantified using ultra-high-performance liquid chromatography tandem mass spectrometry. Cardiovascular parameters were evaluated for between- and within-treatment effects over time using linear mixed modelling. Pimobendan was rapidly absorbed and converted to ODMP with the pimobendan AUC0-∞ greater than ODMP AUC0-∞ (ODMP:pimobendan AUC0-∞ ratio 0.6 [LD] and 0.5 [HD]) despite a longer elimination half-life of ODMP (pimobendan t1/2 0.8 h vs. ODMP t1/2 1.6 h [LD]; pimobendan t1/2 0.7 h vs. ODMP t1/2 1.3 h [HD]). Averaged across all time points, pimobendan increased several measures of systolic function; however, its effect could not be further characterised. Although treatment was well-tolerated, two cats vomited following HD and another had a ventricular premature beat recorded following LD. The lower ODMP:pimobendan AUC0-∞ ratio compared to that observed previously in dogs suggests reduced metabolism in cats. Treatment effects were observed in measures of systolic function; however, the duration of action and differences in effects between the two pimobendan doses could not be characterised. Further studies are required to evaluate pimobendan in feline cardiovascular medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine.

    Science.gov (United States)

    de Hoon, Jan; Van Hecken, Anne; Vandermeulen, Corinne; Yan, Lucy; Smith, Brian; Chen, Jiyun Sunny; Bautista, Edgar; Hamilton, Lisa; Waksman, Javier; Vu, Thuy; Vargas, Gabriel

    2017-07-24

    Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  11. The pharmacokinetic and safety profiles of blonanserin in healthy Chinese volunteers after single fasting doses and single and multiple postprandial doses.

    Science.gov (United States)

    Chen, Xia; Wang, Hongyun; Jiang, Ji; Chen, Rui; Zhou, Ying; Zhong, Wen; Liu, Hongzhong; Hu, Pei

    2014-03-01

    Blonanserin is a novel atypical antipsychotic drug acting as a mixed serotonin 5-HT2A and dopamine D2 receptor antagonist. This study investigated the pharmacokinetics and safety of blonanserin in healthy Chinese males. This was an open-label trial with two parts. Twenty-four subjects were enrolled in part A to receive a single fasting dose of 4 or 8 mg blonanserin (each n = 12); part B recruited 12 subjects and administered single and sequentially twice-daily multiple postprandial doses of blonanserin 2 mg for 9 days. Serial blood samples were taken for the bioassay of plasma blonanserin and its four metabolites during both sub-studies. Safety was assessed, including repeat measurements of fasting serum prolactin, insulin, triglyceride and cholesterol. Blonanserin was rapidly absorbed, accompanied with immediate plasma concentration elevation of the N-oxide form (M2) and gradual rises of the N-deethylated form (M1) and its downstream metabolites. The mean elimination half-life of blonanserin (7.7-11.9 h) was much longer than that of M2 (1.2-1.3 h) but shorter than that of M1 (26.4-31.4 h) after single fasting doses. After food intake, a single dose of 2 mg blonanserin resulted in total exposure and peak concentrations of blonanserin similar to those observed with a single fasting dose of blonanserin 4 mg. Moreover, the relationship of metabolite over parent compound ratio was different between M1 and M2 after single and multiple postprandial administrations (single dose vs multiple dose: M1, 0.33 vs 0.75; M2, 0.13 vs 0.067). Mild but transient increases of prolactin, insulin and triglyceride were observed. The pharmacokinetics of blonanserin in Chinese subjects were similar to those observed in Japanese subjects. This study suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolites as well. The drug was safe and well tolerated in healthy Chinese males.

  12. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    2012-01-25

    Jan 25, 2012 ... Original Research: Efficacy of single dose of transdermal diclofenac patch. 194 ... period. Prevention and establishment of this hypersensitivity ... This clinical ..... International Journal Pharmaceutical Sciences Review and.

  13. Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis

    NARCIS (Netherlands)

    Loozen, C. S.; Kortram, K.; Kornmann, V. N. N.; van Ramshorst, B.; Vlaminckx, B.; Knibbe, C. A. J.; Kelder, J. C.; Donkervoort, S. C.; Nieuwenhuijzen, G. A. P.; Ponten, J. E. H.; van Geloven, A. A. W.; van Duijvendijk, P.; Bos, W. J. W.; Besselink, M. G. H.; Gouma, D. J.; van Santvoort, H. C.; Boerma, D.

    2017-01-01

    Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the

  14. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, Jens; Kjeldsen, J; Laursen, L S

    1995-01-01

    that a single oral 250 mg dose of MK-0591 results in nearly complete blockade of systemic leukotriene production and LTB4 formation in the target tissue of inflammation (the rectum). Controlled multiple-dose trials to assess the clinical efficacy of this novel 5-lipoxygenase-activating protein inhibitor seem...... and after oral administration of a 250 mg dose of MK-0591 or placebo. RESULTS: The mean LTB4 concentration in rectal dialysis fluid was lowered after MK-0591 by > 90% (p

  15. Protect Patients by Using Single- and Multi-Dose Vials Correctly

    Centers for Disease Control (CDC) Podcasts

    2014-07-10

    CDC’s One & Only Campaign urges healthcare providers to recognize the differences between single-dose and multi-dose vials, and to understand appropriate use of each container type.  Created: 7/10/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/10/2014.

  16. Determination of burial dose in incompletely bleached fluvial samples using single grains of quartz

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, Lars

    2007-01-01

    We determine the burial dose in three known-age incompletely bleached fluvial samples using single grains of quartz. Estimation of burial dose in incompletely bleached samples requires that the characteristics of the well-bleached part of the distribution are known in order to distinguish between...

  17. Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma.

    Science.gov (United States)

    Young, Joseph Y; Rhee, Thomas K; Atassi, Bassel; Gates, Vanessa L; Kulik, Laura; Mulcahy, Mary F; Larson, Andrew C; Ryu, Robert K; Sato, Kent T; Lewandowski, Robert J; Omary, Reed A; Salem, Riad

    2007-11-01

    To assess the relationship between cumulative hepatic lobar radiation dose and liver toxicities in patients with hepatocellular carcinoma (HCC) treated with multiple sessions of yttrium-90 radioembolization. Forty-one patients with HCC (age range, 46-82 years) underwent radioembolization with 90Y. Patients were classified according to the Okuda scoring system. All patients received single liver lobar treatments on two or more occasions according to standard clinical 90Y embolization protocol. Cumulative radiation dose to each liver lobe was measured and patients were followed to assess liver toxicities. Statistical analysis was performed with the Student t test and Kaplan-Meier analysis. Patients with Okuda stage I disease received more treatments than those with Okuda stage II disease (mean, 2.65 vs 2.24; Por=1 toxicity; P<.005). No correlation between cumulative radiation dose and liver toxicities existed in patients with Okuda stage II disease. The maximum tolerated dose was between 222 and 390 Gy. Median survival times were 660 and 431 days for patients with Okuda stage I and stage II disease, respectively. Patients with HCC can tolerate high cumulative radiation doses with 90Y therapy. Compared with patients with Okuda stage II disease, patients with Okuda stage I disease tolerate a higher cumulative radiation dose without liver toxicity, but liver toxicities increase with increasing cumulative radiation doses.

  18. Estimated radiation doses to different organs among patients treated for ankylosing spondylitis with a single course of X rays

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, C.A.; Smith, P.G.; Stratton, I.M.; Darby, S.C.; Doll, R.

    1988-03-01

    A follow-up study of over 14000 patients treated with a single course of X rays for ankylosing spondylitis demonstrated substantial excess risk of developing cancer. Previously the excess risk of leukaemia has been related to the estimated mean radiation dose to active bone marrow but detailed estimates were not made of the radiation doses to other organs. Data extracted from the original treatment records of a random sample of one in 15 patients have been used to make dose estimates, using Monte Carlo methods, for 30 specific organs or body regions and 12 bone marrow sites. Estimates of mean and median organ doses, standard deviations and ranges have been tabulated. Detailed distributions are presented for six organs (lung, bronchi, stomach, oesophagus, active bone marrow and total body). Comparison with the earlier bone marrow estimates and more recent theoretical estimates shows good agreement.

  19. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies.

    Science.gov (United States)

    Tal-Singer, Ruth; Cahn, Anthony; Mehta, Rashmi; Preece, Andrew; Crater, Glenn; Kelleher, Dennis; Pouliquen, Isabelle J

    2013-02-15

    To characterise the safety, tolerability, pharmacodynamics (bronchodilatory effect) and pharmacokinetics of inhaled umeclidinium in patients with chronic obstructive pulmonary disease (COPD). The first investigation was a single dose, randomised, double-blind, placebo-controlled study (clinicaltrials.gov: NCT00515502) in which ipratropium bromide-sensitive patients received umeclidinium (250μg, 500μg, and 1000μg), tiotropium bromide 18μg or placebo. Patients were randomised to receive four out of five possible treatments as an incomplete block four-way cross-over. A subsequent study (clinicaltrials.gov: NCT700732472) was focused on assessment of safety, tolerability and pharmacokinetics of umeclidinium (250μg and 1000μg) administered once-daily for 7 days in a randomised, double-blind, placebo-controlled, parallel-group design. Of the 24 patients randomised for the single dose study, 20 completed; 31 out of 38 patients completed the repeat dose study. Most adverse events were mild-to-moderate and transient. Examination of heart rate, QTc interval, blood pressure and clinical laboratory assessments raised no concern over the safety of umeclidinium. Evidence of pharmacology was demonstrated in first study by statistically significant increases in specific airway conductance (sGaw) for up to 24h for all active treatments compared with placebo. Increases in forced expiratory volume in 1s were also observed. Pharmacokinetic analysis demonstrated that maximum observed plasma umeclidinium concentration (Cmax) was reached rapidly (time to Cmax: ∼5-15min) after single and repeat doses; 1.5-1.9-fold accumulation was observed after repeat-dosing. Single and repeat doses of umeclidinium were well tolerated and produced clinically relevant lung function improvements over 24h in patients with COPD. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Single dose antidepressant administration modulates the neural processing of self-referent personality trait words

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; Papadatou-Pastou, Marietta; Cowen, Philip J

    2007-01-01

    Drugs which inhibit the re-uptake of monoamines in the brain are effective in the treatment of depression; however, the neuropsychological mechanisms which lead to the resolution of depressive symptomatology are unclear. Behavioral studies in healthy volunteers suggest that acute administration...... of the selective norepinephrine reuptake inhibitor reboxetine modulates emotional processing. The current study therefore explored the neural basis of this effect. A single dose of reboxetine (4 mg) or placebo was administered to 24 healthy volunteers in a double-blind between-group design. Neural responses during...... for positive self-referent material. These results support the hypothesis that antidepressants have early effects on the neural processing of emotional material which may be important in their therapeutic actions....

  1. 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.

  2. A dose-volume-based tool for evaluating and ranking IMRT treatment plans.

    Science.gov (United States)

    Miften, Moyed M; Das, Shiva K; Su, Min; Marks, Lawrence B

    2004-01-01

    External beam radiotherapy is commonly used for patients with cancer. While tumor shrinkage and palliation are frequently achieved, local control and cure remain elusive for many cancers. With regard to local control, the fundamental problem is that radiotherapy-induced normal tissue injury limits the dose that can be delivered to the tumor. While intensity-modulated radiation therapy (IMRT) allows for the delivery of higher tumor doses and the sparing of proximal critical structures, multiple competing plans can be generated based on dosimetric and/or biological constraints that need to be considered/compared. In this work, an IMRT treatment plan evaluation and ranking tool, based on dosimetric criteria, is presented. The treatment plan with the highest uncomplicated target conformity index (TCI+) is ranked at the top. The TCI+ is a dose-volume-based index that considers both a target conformity index (TCI) and a normal tissue-sparing index (NTSI). TCI+ is designed to assist in the process of judging the merit of a clinical treatment plan. To demonstrate the utility of this tool, several competing lung and prostate IMRT treatment plans are compared. Results show that the plan with the highest TCI+ values accomplished the competing goals of tumor coverage and critical structures sparing best, among rival treatment plans for both treatment sites. The study demonstrates, first, that dose-volume-based indices, which summarize complex dose distributions through a single index, can be used to automatically select the optimal plan among competing plans, and second, that this dose-volume-based index may be appropriate for ranking IMRT dose distributions.

  3. Measured Neutron Spectra and Dose Equivalents From a Mevion Single-Room, Passively Scattered Proton System Used for Craniospinal Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Rebecca M., E-mail: rhowell@mdanderson.org [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Burgett, Eric A.; Isaacs, Daniel [Department of Nuclear Engineering, Idaho State University, Pocatello, Idaho (United States); Price Hedrick, Samantha G.; Reilly, Michael P.; Rankine, Leith J.; Grantham, Kevin K.; Perkins, Stephanie; Klein, Eric E. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

    2016-05-01

    Purpose: To measure, in the setting of typical passively scattered proton craniospinal irradiation (CSI) treatment, the secondary neutron spectra, and use these spectra to calculate dose equivalents for both internal and external neutrons delivered via a Mevion single-room compact proton system. Methods and Materials: Secondary neutron spectra were measured using extended-range Bonner spheres for whole brain, upper spine, and lower spine proton fields. The detector used can discriminate neutrons over the entire range of the energy spectrum encountered in proton therapy. To separately assess internally and externally generated neutrons, each of the fields was delivered with and without a phantom. Average neutron energy, total neutron fluence, and ambient dose equivalent [H* (10)] were calculated for each spectrum. Neutron dose equivalents as a function of depth were estimated by applying published neutron depth–dose data to in-air H* (10) values. Results: For CSI fields, neutron spectra were similar, with a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate continuum between the evaporation and thermal peaks. Neutrons in the evaporation peak made the largest contribution to dose equivalent. Internal neutrons had a very low to negligible contribution to dose equivalent compared with external neutrons, largely attributed to the measurement location being far outside the primary proton beam. Average energies ranged from 8.6 to 14.5 MeV, whereas fluences ranged from 6.91 × 10{sup 6} to 1.04 × 10{sup 7} n/cm{sup 2}/Gy, and H* (10) ranged from 2.27 to 3.92 mSv/Gy. Conclusions: For CSI treatments delivered with a Mevion single-gantry proton therapy system, we found measured neutron dose was consistent with dose equivalents reported for CSI with other proton beamlines.

  4. Voriconazole Disposition After Single and Multiple, Oral Doses in Healthy, Adult Red-tailed Hawks ( Buteo jamaicensis ).

    Science.gov (United States)

    Gentry, Jordan; Montgerard, Christy; Crandall, Elizabeth; Cruz-Espindola, Crisanta; Boothe, Dawn; Bellah, Jamie

    2014-09-01

    Voriconazole is effective for treatment of aspergillosis, a common disease in captive red-tailed hawks ( Buteo jamaicensis ). To determine the disposition and safety of voriconazole after single and multiple, oral doses, 12 adult red-tailed hawks were studied in 2 phases. In phase 1, each bird received a single dose of voriconazole solution (10 mg/kg) by gavage. Blood samples were collected at 0, 0.5, 1, 3, 6, 9, 12, 16, 24, and 36 hours after treatment. In phase 2, each of 8 birds received voriconazole oral solution at 10 mg/kg PO q12h for 14 days. Plasma samples were collected on days 0, 5, and 10 and after the final dose and were processed as in phase 1. Plasma samples were submitted for analysis of voriconazole levels by high-performance liquid chromatography and ultraviolet spectrophotometry and for measurement of selected plasma biochemical parameters. After single dosing, voriconazole concentrations reached a (mean ± SD) peak (Cmax) of 4.7 ± 1.3 μg/mL at 2.0 ± 1.2 hours. The disappearance half-life (t1/2) was 2.8 ± 0.7 hours, and the mean residence time (MRT) was 4.6 ± 0.9 hours. After the last dose at 14 days, the mean Cmax of voriconazole was 4.5 ± 2.7 μg/mL at 2.4 ± 1.1 hours. The t1/2 was 2.1 ± 0.8 hours, and the MRT was 3.5 ± 1.1 hours. Although concentrations of several plasma biochemical parameters were significantly different at study end compared with prestudy concentrations, only plasma creatine kinase activity was outside the reference range. No adverse reactions were observed in any of the birds. After both single and multiple dosing at 10 mg/kg, voriconazole concentrations exceeded the minimum inhibitory concentration to inhibit 90% (MIC90) of Aspergillus species (1 μg/mL) by at least fourfold and remained above the MIC90 for 8.8 ± 1.1 hours after single dosing versus 6.5 ± 1.5 hours after multiple dosing (P = .003). This difference suggests that more frequent dosing (eg, up to q8h) may be necessary to maintain target

  5. Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

    2017-01-01

    AIM: We compared the iron concentration in breast milk after a single high-dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1,200mg iron isomaltoside or oral iron......-dose of intravenous iron isomaltoside for postpartum haemorrhage led to a transient increase in the iron concentration in breast milk three days after treatment compared with oral iron. The difference disappeared one week after treatment and mean iron concentrations were within the normal range in all samples...

  6. Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

    Directory of Open Access Journals (Sweden)

    Kodai Ingawa

    Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

  7. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    Science.gov (United States)

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Effect of Low-Dose (Single-Dose Magnesium Sulfate on Postoperative Analgesia in Hysterectomy Patients Receiving Balanced General Anesthesia

    Directory of Open Access Journals (Sweden)

    Arman Taheri

    2015-01-01

    Full Text Available Background and Aim. Aparallel, randomized, double blinded, placebo-controlled trial study was designed to assess the efficacy of single low dose of intravenous magnesium sulfate on post-total abdominal hysterectomy (TAH pain relief under balanced general anesthesia. Subject and Methods. Forty women undergoing TAH surgery were assigned to two magnesium sulfate (N=20 and normal saline (N=20 groups randomly. The magnesium group received magnesium sulfate 50 mg·kg−1 in 100 mL of normal saline solution i.v as single-dose, just 15 minutes before induction of anesthesia whereas patients in control group received 100 mL of 0.9% sodium chloride solution at the same time. The same balanced general anesthesia was induced for two groups. Pethidine consumption was recorded over 24 hours precisely as postoperative analgesic. Pain score was evaluated with Numeric Rating Scale (NRS at 0, 6, 12, and 24 hours after the surgeries. Results. Postoperative pain score was lower in magnesium group at 6, 12, and 24 hours after the operations significantly (P<0.05. Pethidine requirement was significantly lower in magnesium group throughout 24 hours after the surgeries (P=0.0001. Conclusion. Single dose of magnesium sulfate during balanced general anesthesia could be considered as effective and safe method to reduce postoperative pain and opioid consumption after TAH.

  9. Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

    OpenAIRE

    Barry, B.; Muffat-Joly, M; Bauchet, J; Faurisson, F; Gehanno, P; Pocidalo, J J; Carbon, C.

    1996-01-01

    We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later b...

  10. Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers.

    Science.gov (United States)

    Robertson, Philmore; Hellriegel, Edward T; Arora, Sanjay; Nelson, Michael

    2002-02-01

    Modafinil has been reported to produce a concentration-related suppression of CYP2C9 activity in vitro in primary cultures of human hepatocytes. To determine whether this effect occurs in vivo, the pharmacokinetics of (S)-warfarin was investigated after single oral doses of racemic warfarin (5 mg; COUMADIN) in a placebo-controlled, single-blind, single-period study in 28 volunteers. Subjects received an oral dose of warfarin prior to administration of modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo and they received another after 4 weeks of treatment. Treatment with modafinil did not significantly alter the pharmacokinetics of (S)- or (R)-warfarin relative to placebo. Since (S)-warfarin is predominantly metabolized via CYP2C9, the results indicate that the marked suppression of CYP2C9 activity in vitro does not translate into a similar effect clinically. However, limitations arising from investigation of single doses of warfarin preclude global conclusions about the potential for more subtle interactions after chronic warfarin administration.

  11. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  12. TSD-DOSE : a radiological dose assessment model for treatment, storage, and disposal facilities.

    Energy Technology Data Exchange (ETDEWEB)

    Pfingston, M.

    1998-12-23

    In May 1991, the U.S. Department of Energy (DOE), Office of Waste Operations, issued a nationwide moratorium on shipping slightly radioactive mixed waste from DOE facilities to commercial treatment, storage, and disposal (TSD) facilities. Studies were subsequently conducted to evaluate the radiological impacts associated with DOE's prior shipments through DOE's authorized release process under DOE Order 5400.5. To support this endeavor, a radiological assessment computer code--TSD-DOSE (Version 1.1)--was developed and issued by DOE in 1997. The code was developed on the basis of detailed radiological assessments performed for eight commercial hazardous waste TSD facilities. It was designed to utilize waste-specific and site-specific data to estimate potential radiological doses to on-site workers and the off-site public from waste handling operations at a TSD facility. The code has since been released for use by DOE field offices and was recently used by DOE to evaluate the release of septic waste containing residual radioactive material to a TSD facility licensed under the Resource Conservation and Recovery Act. Revisions to the code were initiated in 1997 to incorporate comments received from users and to increase TSD-DOSE's capability, accuracy, and flexibility. These updates included incorporation of the method used to estimate external radiation doses from DOE's RESRAD model and expansion of the source term to include 85 radionuclides. In addition, a detailed verification and benchmarking analysis was performed.

  13. Dose conformation to the spine during palliative treatments using dynamic wedges

    Energy Technology Data Exchange (ETDEWEB)

    Ormsby, Matthew A., E-mail: Matthew.Ormsby@usoncology.com [West Texas Cancer Center at Medical Center Hospital, Odessa, TX (United States); Herndon, R. Craig; Kaczor, Joseph G. [West Texas Cancer Center at Medical Center Hospital, Odessa, TX (United States)

    2013-07-01

    Radiation therapy is commonly used to alleviate pain associated with metastatic disease of the spine. Often, isodose lines are manipulated using dynamic or physical wedges to encompass the section of spine needing treatment while minimizing dose to normal tissue. We will compare 2 methods used to treat the entire thoracic spine. The first method treats the thoracic spine with a single, nonwedged posterior-anterior (PA) field. Dose is prescribed to include the entire spine. Isodose lines tightly conform to the top and bottom vertebrae, but vertebrae between these 2 received more than enough coverage. The second method uses a combination of wedges to create an isodose line that mimics the curvature of the thoracic spine. This “C”-shaped curvature is created by overlapping 2 fields with opposing dynamic wedges. Machine constraints limit the treatment length and therefore 2 isocenters are used. Each of the 2 PA fields contributes a portion of the total daily dose. This technique creates a “C”-shaped isodose line that tightly conforms to the thoracic spine, minimizing normal tissue dose. Spinal cord maximum dose is reduced, as well as mean dose to the liver, esophagus, and heart.

  14. Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

    Science.gov (United States)

    Barry, B; Muffat-Joly, M; Bauchet, J; Faurisson, F; Gehanno, P; Pocidalo, J J; Carbon, C

    1996-09-01

    We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.

  15. Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder

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    Harada E

    2016-01-01

    Full Text Available Eiji Harada,1 Osamu Shirakawa,2 Yoichi Satoi,3 Lauren B Marangell,4 Rodrigo Escobar5 1Eli Lilly Japan K.K., Medicines Development Unit Japan, Medical Science, Kobe, 2Department of Neuropsychiatry, Kinki University Faculty of Medicine, Osakasayama, 3Eli Lilly Japan K.K., Medicines Development Unit Japan, Statistical Science, Kobe, Japan; 4The University of Texas Health Science Center School of Medicine, Houston, TX, 5Eli Lilly and Company, Neuroscience, Indianapolis, IN, USA Purpose: We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder.Patients and methods: We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final “active” doses of 40 and 60 mg (5 mg control group, with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40–120 mg/day. Tolerability was measured by rate of discontinuation due to adverse events (DCAE.Results: The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively.Conclusion: This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder. Keywords: antidepressant, dose, duloxetine, major depressive disorder, titration

  16. Single-dose Toxicity of ShinYangHur Herbal Acupuncture

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    Eunhye Cha

    2015-06-01

    Full Text Available Objectives: This study was carried out to analyze the single-dose toxicity of ShinYangHur (SYH herbal acupuncture injected into the muscles of Sprague-Dawley (SD rats. Methods: The SYH herbal acupuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, Korea-Good Manufacturing Practice, K-GMP. After the mixing process with sterile distilled water, the pH was controlled to between 7.0 and 7.5. Then, NaCl was added to make a 0.9% isotonic solution by using sterilized equipment. All experiments were conducted at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP. SD rats were chosen for the pilot study. Doses of SYH herbal acupuncture, 0.25, 0.5, and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy was used to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above outcomes suggest that treatment with SYH herbal acupuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  17. Measurement of neutron dose in the compensator IMRT treatment.

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    Rezaian, Abbas; Nedaie, Hassan Ali; Banaee, Nooshin

    2017-10-01

    A radiation treatment delivery technique, intensity modulated radiation therapy (IMRT), has found widespread use in the treatment of cancers. One of IMRT implementing methods is IMRT compensator based, which the modulation are done by high Z materials. When photons with energies higher than 8MV interact with high Z material in path, Photoneutrons are produced. In this study, the effect of compensator on photoneutron production was investigated. The Monte Carlo code MCNPX was used to calculate the neutron dose equivalent as a function of the depth in phantom with and without compensator. Measurements were made using CR-39 track-etched detectors. CR-39 detectors, were cut in dimensions of 2.5×2.5 cm 2 by laser, placed in different depths of slab phantom and then irradiated by 18MV photons. Same procedure was performed with the compensator present and absent. The measured data were compared with MCNP calculations. In both experimental and simulation results, neutron dose equivalent when compensator used, was less than non-compensator field. The calculated neutron dose equivalent was maximum at surface and decreased exponentially by increasing depth, but in experimental data, the neutron dose equivalent reached a maximum at approximately 3cm depth in the phantom and beyond which decreased with depth.CR-39 calibration was carried out in air, by considering that neutron energy spectrum changes toward thermal neutrons by depth in phantom increasing, it is suggested that for measuring equivalent neutron dose at phantom depth, should have proper neutron calibration in terms of energy spectrum. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

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    Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

    2016-01-01

    Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

  19. Single intramuscular dose toxicokinetics of manganese in broiler chicks

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    Muna Al-Zubaidy

    Full Text Available Aim: Manganese (Mn produces neurobehavioral toxicity in various animal species including the young chicks. The present study examines toxicokinetics of Mn in 7-10-day old chicks after an intramuscular injection at 20 mg/kg. Materials and Methods: Samples of the blood, whole brain, liver and kidney were obtained from chicks (5/each time period at 0 time (base-line and then at times between 0.17 to 4 h. The concentrations of Mn in the plasma and tissues were determined by atomic absorption spectrometry. Toxicokinetic parameters of Mn were calculated from the mean metal concentrations in the plasma by a non-compartmental analysis using a Windows-based computer program. Results: Injection of Mn significantly increased the metal levels in the plasma, whole brain, liver and kidney of the chicks when compared to respective base-line control values at times 0.17 to 4 h after the injection (with the exception at 2 and 4 h in the brain. The highest concentration of Mn in the plasma and the whole brain appeared one h after the injection, whereas those of the liver and kidney appeared 4 h post-injection. The concentrations of Mn in the plasma ranged between 0.43 to 1.2 μg/ml within 0.17 to 4 h. Those of the whole brain, liver and kidney were 0.11– 0.46, 6.3–15 and 5.3–22.9 μg/g, respectively. The elimination half-life of Mn was 3.02 h with steady state volume of distribution 24.34 L/kg and total body clearances of 4.78 L/h/kg. The mean residence time of Mn was 5.09 h and its area under the plasma concentration-time curve (0- was 4.18 μg.h/ml. The elimination half-life of Mn from the brain was 3.12 h with an elimination rate constant of 0.22 h-1. Conclusion: The data suggest that Mn is well absorbed and rapidly distributed after an intramuscular administration in chicks and further support the reported neurobehavioral toxic effects of the metal which are observed within one h after treatment. [Vet World 2012; 5(9.000: 560-564

  20. Safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat inhaled doses of umeclidinium in healthy subjects: two randomized studies.

    Science.gov (United States)

    Cahn, Anthony; Tal-Singer, Ruth; Pouliquen, Isabelle J; Mehta, Rashmi; Preece, Andrew; Hardes, Kelly; Crater, Glenn; Deans, Amanda

    2013-07-01

    Chronic obstructive pulmonary disease (COPD) has a significant negative impact on quality of life and increases the risk of premature death. Umeclidinium is a long-acting muscarinic receptor antagonist in development for the treatment of COPD with the aim to broaden treatment options for clinicians and patients by providing improved symptom control. To characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat inhaled doses of umeclidinium in healthy subjects. Two randomized, placebo-controlled, ascending-dose studies were conducted in healthy ipratropium bromide-responsive subjects. In the single-dose study, subjects (n = 20) received umeclidinium (10-350 μg), tiotropium bromide 18 μg and placebo in a crossover dosing schedule. In this study, lung function was assessed for 24 h by measuring specific airways conductance (sGaw) and forced expiratory volume in 1 s (FEV1). In the repeat-dose study, subjects (n = 36) received umeclidinium (250-1,000 μg) and placebo for 14 days in a parallel-group schedule. Adverse events (AEs) were reported in five subjects (single-dose study) and 23 subjects (repeat-dose study); none were serious. In both studies, no abnormalities in 12-lead electrocardiogram parameters, 24-h Holter monitoring or lead II monitoring were reported as AEs. Umeclidinium was rapidly absorbed following single-dose administration [time to reach the maximum plasma concentration (tmax) 5-15 min] and repeat-dose administration (tmax 5-7 min). Following repeat dosing, the geometric mean plasma elimination half-life was approximately 27 h and statistically significant accumulation was observed for the area under the plasma concentration-time curve, maximum plasma concentration and cumulative amount of unchanged drug excreted into the urine at 24 h (range 1.5- to 4.5-fold). Umeclidinium at doses of 100 μg and above, and tiotropium bromide demonstrated statistically significant bronchodilatory effects

  1. A single cidofovir treatment rescues animals at progressive stages of lethal orthopoxvirus disease

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    Israely Tomer

    2012-06-01

    Full Text Available Abstract Background In an event of a smallpox outbreak in humans, the window for efficacious treatment by vaccination with vaccinia viruses (VACV is believed to be limited to the first few days post-exposure (p.e.. We recently demonstrated in a mouse model for human smallpox, that active immunization 2–3 days p.e. with either VACV-Lister or modified VACV Ankara (MVA vaccines, can rescue animals from lethal challenge of ectromelia virus (ECTV, the causative agent of mousepox. The present study was carried out in order to determine whether a single dose of the anti-viral cidofovir (CDV, administered at different times and doses p.e. either alone or in conjunction with active vaccination, can rescue ECTV infected mice. Methods Animals were infected intranasally with ECTV, treated on different days with various single CDV doses and monitored for morbidity, mortality and humoral response. In addition, in order to determine the influence of CDV on the immune response following vaccination, both the "clinical take”, IFN-gamma and IgG Ab levels in the serum were evaluated as well as the ability of the mice to withstand a lethal challenge of ECTV. Finally the efficacy of a combined treatment regime of CDV and vaccination p.e. was determined. Results A single p.e. CDV treatment is sufficient for protection depending on the initiation time and dose (2.5 – 100 mg/kg of treatment. Solid protection was achieved by a low dose (5 mg/kg CDV treatment even if given at day 6 p.e., approximately 4 days before death of the control infected untreated mice (mean time to death (MTTD 10.2. At the same time point complete protection was achieved by single treatment with higher doses of CDV (25 or 100 mg/kg. Irrespective of treatment dose, all surviving animals developed a protective immune response even when the CDV treatment was initiated one day p.e.. After seven days post treatment with the highest dose (100 mg/kg, virus was still detected in some

  2. A single cidofovir treatment rescues animals at progressive stages of lethal orthopoxvirus disease.

    Science.gov (United States)

    Israely, Tomer; Paran, Nir; Lustig, Shlomo; Erez, Noam; Politi, Boaz; Shafferman, Avigdor; Melamed, Sharon

    2012-06-18

    In an event of a smallpox outbreak in humans, the window for efficacious treatment by vaccination with vaccinia viruses (VACV) is believed to be limited to the first few days post-exposure (p.e.). We recently demonstrated in a mouse model for human smallpox, that active immunization 2-3 days p.e. with either VACV-Lister or modified VACV Ankara (MVA) vaccines, can rescue animals from lethal challenge of ectromelia virus (ECTV), the causative agent of mousepox. The present study was carried out in order to determine whether a single dose of the anti-viral cidofovir (CDV), administered at different times and doses p.e. either alone or in conjunction with active vaccination, can rescue ECTV infected mice. Animals were infected intranasally with ECTV, treated on different days with various single CDV doses and monitored for morbidity, mortality and humoral response. In addition, in order to determine the influence of CDV on the immune response following vaccination, both the "clinical take", IFN-gamma and IgG Ab levels in the serum were evaluated as well as the ability of the mice to withstand a lethal challenge of ECTV. Finally the efficacy of a combined treatment regime of CDV and vaccination p.e. was determined. A single p.e. CDV treatment is sufficient for protection depending on the initiation time and dose (2.5 - 100 mg/kg) of treatment. Solid protection was achieved by a low dose (5 mg/kg) CDV treatment even if given at day 6 p.e., approximately 4 days before death of the control infected untreated mice (mean time to death (MTTD) 10.2). At the same time point complete protection was achieved by single treatment with higher doses of CDV (25 or 100 mg/kg). Irrespective of treatment dose, all surviving animals developed a protective immune response even when the CDV treatment was initiated one day p.e.. After seven days post treatment with the highest dose (100 mg/kg), virus was still detected in some organs (e.g. lung and liver) yet all animals survived, suggesting

  3. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

    Science.gov (United States)

    Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Objectives Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. Search methods We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Selection criteria Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Data collection and analysis Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain

  4. Monte Carlo modeling of the MammoSite(Reg) treatments: Dose effects of air pockets

    Science.gov (United States)

    Huang, Yu-Huei Jessica

    In the treatment of early-stage breast cancer, MammoSiteRTM has been used as one of the partial breast irradiation techniques after breast-conserving surgery. The MammoSiteRTM applicator is a single catheter with an inflatable balloon at its distal end that can be placed in the resected cavity (tumor bed). The treatment is performed by delivering the Ir-192 high-dose-rate source through the center lumen of the catheter by a remote afterloader while the balloon is inflated in the tumor bed cavity. In the MammoSiteRTM treatment, it has been found that air pockets occasionally exist and can be seen and measured in CT images. Experiences have shown that about 90% of the patients have air pockets when imaged two days after the balloon placement. The criterion for the air pocket volume is less than or equal to 10% of the planning target volume in volume. The purpose of this study is to quantify dose errors occurring at the interface of the air pocket in MammoSiteRTM treatments with Monte Carlo calculations, so that the dosimetric effects from the air pocket can be fully understood. Modern brachytherapy treatment planning systems typically consider patient anatomy as a homogeneous water medium, and incorrectly model lateral and backscatter radiation during treatment delivery. Heterogeneities complicate the problem and may result in overdosage to the tissue located near the medium interface. This becomes a problem in MammoSiteRTM brachytherapy when air pocket appears during the treatment. The resulting percentage dose difference near the air-tissue interface is hypothesized to be greater than 10% when comparing Monte Carlo N-Particle (version 5) with current treatment planning systems. The specific aims for this study are: (1) Validate Monte Carlo N-Particle (Version 5) source modeling. (2) Develop phantom. (3) Calculate phantom doses with Monte Carlo N-Particle (Version 5) and investigate doses difference between thermoluminescent dosimeter measurement, treatment planning

  5. Nanoparticle-based cancer treatment: can delivered dose and biological dose be reliably modeled and quantified?

    Science.gov (United States)

    Hoopes, P. Jack; Petryk, Alicia A.; Giustini, Andrew J.; Stigliano, Robert V.; D'Angelo, Robert N.; Tate, Jennifer A.; Cassim, Shiraz M.; Foreman, Allan; Bischof, John C.; Pearce, John A.; Ryan, Thomas

    2011-03-01

    Essential developments in the reliable and effective use of heat in medicine include: 1) the ability to model energy deposition and the resulting thermal distribution and tissue damage (Arrhenius models) over time in 3D, 2) the development of non-invasive thermometry and imaging for tissue damage monitoring, and 3) the development of clinically relevant algorithms for accurate prediction of the biological effect resulting from a delivered thermal dose in mammalian cells, tissues, and organs. The accuracy and usefulness of this information varies with the type of thermal treatment, sensitivity and accuracy of tissue assessment, and volume, shape, and heterogeneity of the tumor target and normal tissue. That said, without the development of an algorithm that has allowed the comparison and prediction of the effects of hyperthermia in a wide variety of tumor and normal tissues and settings (cumulative equivalent minutes/ CEM), hyperthermia would never have achieved clinical relevance. A new hyperthermia technology, magnetic nanoparticle-based hyperthermia (mNPH), has distinct advantages over the previous techniques: the ability to target the heat to individual cancer cells (with a nontoxic nanoparticle), and to excite the nanoparticles noninvasively with a noninjurious magnetic field, thus sparing associated normal cells and greatly improving the therapeutic ratio. As such, this modality has great potential as a primary and adjuvant cancer therapy. Although the targeted and safe nature of the noninvasive external activation (hysteretic heating) are a tremendous asset, the large number of therapy based variables and the lack of an accurate and useful method for predicting, assessing and quantifying mNP dose and treatment effect is a major obstacle to moving the technology into routine clinical practice. Among other parameters, mNPH will require the accurate determination of specific nanoparticle heating capability, the total nanoparticle content and biodistribution in

  6. Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Stengel, Joel Z; Jones, David P

    2008-09-01

    Proper colonic cleansing prior to colonoscopy is paramount to ensuring complete mucosal visualization and polyp identification. In a double-blind fashion, we compared single-dose lubiprostone (24 microg) versus placebo pretreatment prior to a split-dose polyethylene glycol electrolyte (PEG-E) bowel preparation without dietary restriction to determine the efficacy, safety, and patient tolerability. Two hundred patients referred for outpatient colorectal cancer screening were randomized to receive a single-dose of unlabeled lubiprostone (24 microg) or placebo prior to a split-dose PEG-E bowel preparation without dietary restriction. The patients were surveyed prior to the colonoscopy on the tolerability of the bowel preparation, and any adverse events were recorded. The cleanliness of the colon was graded by the endoscopist during the procedure utilizing the Ottawa bowel preparation scale. One hundred ninety-one patients completed the study (95%). Split-dose PEG-E with lubiprostone pretreatment was found to be more effective at bowel cleansing in each segment of the colon when compared with split-dose PEG-E with placebo (P lubiprostone treatment arm rated the overall experience as more tolerable (P 0.003) and complained of less abdominal bloating (P 0.049). No differences were observed between the groups for treatment-emergent side effects or adverse events (P > 0.05). Single-dose lubiprostone prior to split-dose PEG-E without dietary restriction significantly improves colonic mucosa visualization during colonoscopy and is well tolerated by patients.

  7. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    Science.gov (United States)

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  8. Development of dose audits for complex treatment techniques in radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Stefanic, A. M.; Molina, L.; Vallejos, M.; Montano, G.; Zaretzky, A.; Saravi, M., E-mail: stefanic@cae.cnea.gov.ar [Centro Regional de Referencia con Patrones Secundarios para Dosimetria - CNEA, Presbitero Juan Gonzalez y Aragon 15, B1802AYA Ezeiza (Argentina)

    2014-08-15

    This work was performed in the frame of a Coordinated Research Project (CRP) with IAEA whose objective was to extend the scope of activities carried out by national TLD-based networks from dosimetry audit for rectangular radiation fields to irregular and small fields relevant to modern radiotherapy. External audit is a crucial element in QA programmes for clinical dosimetry in radiotherapy, therefore a methodology and procedures were developed and were made available for dose measurement of complex radiotherapy parameters used for cancer treatment. There were three audit steps involved in this CRP: TLD based dosimetry for irregular MLC fields for conformal radiotherapy, dosimetry in the presence of heterogeneities and 2D MLC shaped fields relevant to stereotactic radiotherapy and applicable to dosimetry for IMRT. In addition, a new development of film-based 2D dosimetry for testing dose distributions in small field geometry was included. The plan for each audit step involved a pilot study and a trial audit run with a few local hospitals. The pilot study focused on conducting and evaluation of the audit procedures with all participants. The trial audit run was the running of the audit procedures by the participants to test them with a few local radiotherapy hospitals. This work intends to provide audits which are much nearer clinical practice than previous audits as they involve significant testing of Tps methods, as well as verifications to determinate whether hospitals can correctly calculate dose delivery in radiation treatments. (author)

  9. Aphasia treatment: intensity, dose parameters, and script training.

    Science.gov (United States)

    Cherney, Leora R

    2012-10-01

    Studies of aphasia treatment have shown that intensive speech-language therapy is associated with significant improvements. However, there is no standard definition of intensity and the simplistic notion that "more is better" is not necessarily supported by the research. First, current evidence regarding intensity and aphasia treatment was briefly summarized. Second, studies that directly compare conditions of higher- and lower-intensity treatment for aphasia were reviewed with regard to the inclusion of parameters that contribute to a definition of intensity. In addition to five parameters proposed by Warren, Fey, and Yoder (2007) and highlighted by Baker (2012) , total number of sessions was also often documented. The review illustrated the complexity of quantifying the dose of comprehensive treatments that target multiple modalities and utilize a variety of different strategies. Third, data from a study reporting a relationship between intensive computer-based script training and outcomes in aphasia were examined. Results serve to illustrate Baker's contention that intensity alone is insufficient without also considering the active ingredients of the teaching episode. Information about dose, therapeutic inputs, and client acts can lead to better optimization of an intervention.

  10. Successful treatment of chronic recurrent multifocal osteomyelitis using low-dose radiotherapy : A case report.

    Science.gov (United States)

    Dietzel, Christian T; Schäfer, Christoph; Vordermark, Dirk

    2017-03-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, which lacks an infectious genesis and predominantly involves the metaphysis of long bones. Common treatments range from nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids at first onset of disease, to immunosuppressive drugs and bisphosphonates in cases of insufficient remission. The therapeutic use of low-dose radiotherapy for CRMO constitutes a novelty. A 67-year-old female patient presented with radiologically proven CRMO affecting the right tibia/talus and no response to immunosuppressive therapy. Two treatment series of radiation therapy were applied with an interval of 6 weeks. Each series contained six fractions (three fractions per week) with single doses of 0.5 Gy, thus the total applied dose was 6 Gy. Ten months later, pain and symptoms of osteomyelitis had completely vanished. Radiotherapy seems to be an efficient and feasible complementary treatment option for conventional treatment refractory CRMO in adulthood. The application of low doses per fraction is justified by the inflammatory pathomechanism of disease.

  11. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

  12. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

    Science.gov (United States)

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2013-06-24

    Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

  13. A single dose of intravenous esomeprazole decreases gastric secretion in healthy volunteers.

    Science.gov (United States)

    Nichita, C; Abdou, A E-W; Maerten, P; Herranz, M; Mouret, N; Thalmann, C; Michetti, P F; Dorta, G

    2009-11-15

    Data suggest that esomeprazole decreases gastric secretion. To assess the effect of a single i.v. esomeprazole dose on gastric secretion volume 3 h after drug administration, as a primary endpoint, and to evaluate, as secondary endpoints, the reduction 1 and 5 h after dosing; time when the gastric pH was bronchoaspiration during anaesthesia induction and in intensive care patients should be investigated in further studies.

  14. Signal quality of single dose gadobenate dimeglumine pulmonary MRA examinations exceeds quality of MRA performed with double dose gadopentetate dimeglumine.

    Science.gov (United States)

    Woodard, Pamela K; Chenevert, Thomas L; Sostman, H Dirk; Jablonski, Kathleen A; Stein, Paul D; Goodman, Lawrence R; Londy, Frank J; Narra, Vamsidhar; Hales, Charles A; Hull, Russell D; Tapson, Victor F; Weg, John G

    2012-02-01

    During a recent multi-center trial assessing gadolinium (Gd)-enhanced magnetic resonance angiography (MRA) for diagnosis of acute pulmonary embolism (PE), the Food and Drug Administration announced a risk of nephrogenic sclerosing fibrosis in patients with renal insufficiency who had received intravenous Gd-based MR contrast agents. Although no patients in this trial had renal insufficiency, in cautious response to this announcement, the trial protocol was changed from an intravenous administration of 0.2 mmol/Kg of a conventional Gd-based MR contrast agent to 0.1 mmol/Kg of gadobenate dimeglumine. The study described herein compares the signal quality of pulmonary MRA performed with double dose conventional agent to single dose gadobenate dimeglumine. This study is a retrospective analysis of data from a prospective, multicenter study in men and women ≥18 years with documented presence or absence of PE. The study was approved by the Institutional Review Board at all participating centers, and all patients provided written indication of informed consent. We performed both objective and subjective analysis of pulmonary artery image quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the main pulmonary artery were assessed in single and double dose protocols and compared. SNR and CNR of the main PA were correlated with subjective quality assessment of main/lobar, segmental and subsegmental pulmonary arteries. Although there were individual outliers, both SNR (P = 0.01) and CNR (P = 0.008) were higher in all quartiles for examinations using gadobenate dimeglumine than with gadopentetate dimeglumine. Subjective quality of vascular signal intensity at each vessel order was significantly better for gadobenate dimeglumine (P dimeglumine provides better pulmonary MRA signal quality than double dose of a conventional Gd-based MR contrast agent.

  15. Single dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission in Cambodia: An open-label randomized trial.

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    Jessica T Lin

    Full Text Available Single low dose primaquine (SLD PQ, 0.25mg/kg is recommended in combination with artemisinin-based combination therapy (ACT as a gametocytocide to prevent Plasmodium falciparum transmission in areas threatened by artemisinin resistance. To date, no randomized controlled trials have measured primaquine's effect on infectiousness to Anopheline mosquitoes in Southeast Asia.Cambodian adults with uncomplicated falciparum malaria were randomized to receive a single 45mg dose of primaquine (equivalent to three SLD PQ or no primaquine after the third dose of dihydroartemisin-piperaquine (DHP therapy. A membrane-feeding assay measured infectiousness to Anopheles dirus on days 0, 3, 7, and 14 of blood-stage therapy. Gametocytemia was evaluated by microscopy and reverse-transcriptase PCR.Prior to trial halt for poor DHP treatment efficacy, 101 participants were randomized and 50 received primaquine. Overall microscopic gametocyte prevalence was low (9%, but gametocytemic subjects given primaquine were gametocyte-free by day 14, and significantly less likely to harbor gametocytes by day 7 compared to those treated with DHP-alone, who remained gametocytemic for a median of two weeks. Only one infectious subject was randomized to the primaquine group, precluding assessment of transmission-blocking efficacy. However, he showed a two-fold reduction in oocyst density of infected mosquitoes less than 24 hours after primaquine dosing. In the DHP-alone group, four subjects remained infectious through day 14, infecting roughly the same number of mosquitoes pre and post-treatment. Overall, microscopic gametocytemia was an excellent predictor of infectiousness, and performed better than submicroscopic gametocytemia post-treatment, with none of 474 mosquitoes infected post-treatment arising from submicroscopic gametocytes.In a setting of established ACT resistance, a single dose of 45mg primaquine added to DHP rapidly and significantly reduced gametocytemia, while DHP

  16. A controlled prospective trial of the prophylactic effect of a single dose of ivermectin against onchocerca volvulus

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    Boussinesq M.

    2001-09-01

    Full Text Available A clinical trial was conducted in Cameroon in order to evaluate in humans the possible effect of a single dose of ivermectin (150 μg per kg on the pre-adult stages of Onchocerca volvulus.The incidence of the skin microfilariae was measured in two groups of patients who initially had negative biopsies, and who were subsequently treated, immediately after the seasonal peak of transmission of O. volvulus ,either with a combination of ivermectin + ferrous sulphate, or with ferrous sulphate alone. One year after the treatment, i.e. 14 months after the start of the transmission period, the proportion of patients with positive skin biopsies, and their mean microfilarial loads, did not differ significantly between the two groups. Thus a single dose of ivermectin does not seem to have any perceptible prophylactic effect against O.volvulus.

  17. An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia.

    Science.gov (United States)

    Leang, Rithea; Khu, Naw Htee; Mukaka, Mavuto; Debackere, Mark; Tripura, Rupam; Kheang, Soy Ty; Chy, Say; Kak, Neeraj; Buchy, Philippe; Tarantola, Arnaud; Menard, Didier; Roca-Felterer, Arantxa; Fairhurst, Rick M; Kheng, Sim; Muth, Sinoun; Ngak, Song; Dondorp, Arjen M; White, Nicholas J; Taylor, Walter Robert John

    2016-10-27

    In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42). This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and

  18. Effective dose to staff from interventional procedures: estimations from single and double dosimetry.

    Science.gov (United States)

    Kuipers, Gerritjan; Velders, Xandra L

    2009-09-01

    The exposure of 11 physicians performing interventional procedures was measured by means of two personal dosemeters. One personal dosemeter was worn outside the lead apron and an additional under the lead apron. The study was set up in order to determine the added value of a dosemeter worn under the lead apron. With the doses measured, the effective doses of the physicians were estimated using an algorithm for single dosimetry and two algorithms for double dosimetry. The effective doses calculated with the single dosimetry algorithm ranged from 0.11 to 0.85 mSv in 4 weeks. With the double dosimetry algorithms, the effective doses ranged from 0.02 mSv to 0.47 mSv. The statistical analysis revealed no significant differences in the accuracy of the effective doses calculated with single or double dosimetry algorithms. It was concluded that the effective dose cannot be considered a more accurate estimate when two dosemeters are used instead of one.

  19. TSD-DOSE: A radiological dose assessment model for treatment, storage, and disposal facilities

    Energy Technology Data Exchange (ETDEWEB)

    Pfingston, M.; Arnish, J.; LePoire, D.; Chen, S.-Y.

    1998-10-14

    Past practices at US Department of Energy (DOE) field facilities resulted in the presence of trace amounts of radioactive materials in some hazardous chemical wastes shipped from these facilities. In May 1991, the DOE Office of Waste Operations issued a nationwide moratorium on shipping all hazardous waste until procedures could be established to ensure that only nonradioactive hazardous waste would be shipped from DOE facilities to commercial treatment, storage, and disposal (TSD) facilities. To aid in assessing the potential impacts of shipments of mixed radioactive and chemically hazardous wastes, a radiological assessment computer model (or code) was developed on the basis of detailed assessments of potential radiological exposures and doses for eight commercial hazardous waste TSD facilities. The model, called TSD-DOSE, is designed to incorporate waste-specific and site-specific data to estimate potential radiological doses to on-site workers and the off-site public from waste-handling operations at a TSD facility. The code is intended to provide both DOE and commercial TSD facilities with a rapid and cost-effective method for assessing potential human radiation exposures from the processing of chemical wastes contaminated with trace amounts of radionuclides.

  20. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.

    Directory of Open Access Journals (Sweden)

    John A Todd

    2016-10-01

    Full Text Available Interleukin-2 (IL-2 has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs. Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs to prevent autoimmune diseases, such as type 1 diabetes (T1D. Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2, which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs.To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D, a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39 found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254 and 0.497

  1. Low-dose add-back therapy during postoperative GnRH agonist treatment

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    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  2. A Pilot Study on Single-dose Toxicity Testing of Hominis placenta Pharmacopuncture in Sprague-Dawley Rats

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    Yoo-Hwan Lee

    2015-06-01

    Full Text Available Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Hominis placenta pharmacopuncture when used as a single-dose in 6 week old, male and female Sprague-Dawley (SD rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea, an institution authorized to perform non clinical studies, under the regulations of Good Laboratory Practice (GLP. SD rats were chosen for the pilot study. Doses of Hominis placenta pharmacopuncture extracts, 0.125, 0.25 and 0.5 mL, were administered to the experimental group, and 0.5 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the groups. Also, no significant changes in body weights were observed among the groups, and no significant differences in hematology/biochemistry, necropsy, and histopathology results were noted. Hematologically, some changes in the male rats in two experimental groups were observed, but those changes had no clinical or toxicological meaning because they were not dose dependent. Histopathological tests on the injected parts showed cell infiltration in the male rats in one of the experimental groups; however, that result was due to spontaneous generation and had no toxicological meaning. Therefore, this study showed that Hominis placenta pharmacopuncture had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single-dose tests of the test substance Hominis placenta pharmacopuncture in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, the above findings suggest that treatment with Hominis placenta pharmacopuncture is relatively safe. Further studies on this subject are needed.

  3. Dual energy versus single energy MDCT: measurement of radiation dose using adult abdominal imaging protocols.

    Science.gov (United States)

    Ho, Lisa M; Yoshizumi, Terry T; Hurwitz, Lynne M; Nelson, Rendon C; Marin, Daniele; Toncheva, Greta; Schindera, Sebastian T

    2009-11-01

    The aim of this study was to measure the radiation dose of dual-energy and single-energy multidetector computed tomographic (CT) imaging using adult liver, renal, and aortic imaging protocols. Dual-energy CT (DECT) imaging was performed on a conventional 64-detector CT scanner using a software upgrade (Volume Dual Energy) at tube voltages of 140 and 80 kVp (with tube currents of 385 and 675 mA, respectively), with a 0.8-second gantry revolution time in axial mode. Parameters for single-energy CT (SECT) imaging were a tube voltage of 140 kVp, a tube current of 385 mA, a 0.5-second gantry revolution time, helical mode, and pitch of 1.375:1. The volume CT dose index (CTDI(vol)) value displayed on the console for each scan was recorded. Organ doses were measured using metal oxide semiconductor field-effect transistor technology. Effective dose was calculated as the sum of 20 organ doses multiplied by a weighting factor found in International Commission on Radiological Protection Publication 60. Radiation dose saving with virtual noncontrast imaging reconstruction was also determined. The CTDI(vol) values were 49.4 mGy for DECT imaging and 16.2 mGy for SECT imaging. Effective dose ranged from 22.5 to 36.4 mSv for DECT imaging and from 9.4 to 13.8 mSv for SECT imaging. Virtual noncontrast imaging reconstruction reduced the total effective dose of multiphase DECT imaging by 19% to 28%. Using the current Volume Dual Energy software, radiation doses with DECT imaging were higher than those with SECT imaging. Substantial radiation dose savings are possible with DECT imaging if virtual noncontrast imaging reconstruction replaces precontrast imaging.

  4. 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.

  5. [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.

  6. Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose, double dose or half-dose contrast enhanced imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kinner, Sonja, E-mail: Sonja.Kinner@uni-due.de [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Steinweg, Verena [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Maderwald, Stefan [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Radtke, Arnold; Sotiropoulos, Georgios [Department of General Surgery, University Hospital Essen (Germany); Forsting, Michael; Schroeder, Tobias [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany)

    2014-05-15

    Introduction: Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC). Materials and methods: 30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w ± IR) were acquired 20–30 min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann–Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated. Results: All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference. Conclusions: Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR.

  7. Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose, double dose or half-dose contrast enhanced imaging.

    Science.gov (United States)

    Kinner, Sonja; Steinweg, Verena; Maderwald, Stefan; Radtke, Arnold; Sotiropoulos, Georgios; Forsting, Michael; Schroeder, Tobias

    2014-05-01

    Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC). 30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w±IR) were acquired 20-30min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann-Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated. All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference. Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning

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    Mohammed Fahim

    2007-05-01

    Full Text Available Abstract Background The case fatality for intentional self-poisoning in rural Asia is 10–30 times higher than in the West, mostly due to the use of highly toxic poisons. Activated charcoal is a widely available intervention that may – if given early – bind to poisons in the stomach and prevent their absorption. Current guidelines recommend giving a single dose of charcoal (SDAC if patients arrive within an hour of ingestion. Multiple doses (MDAC may increase poison elimination at a later time by interrupting any enterohepatic or enterovascular circulations. The effectiveness of SDAC or MDAC is unknown. Since most patients present to hospital after one hour, we considered MDAC to have a higher likelihood of clinical benefit and set up a study to compare MDAC with no charcoal. A third arm of SDAC was added to help determine whether any benefit noted from MDAC resulted from the first dose or all doses. Methods/design We set up a randomised controlled trial assessing the effectiveness of superactivated charcoal in unselected adult self-poisoning patients admitted to the adult medical wards of three Sri Lankan secondary hospitals. Patients were randomised to standard treatment or standard treatment plus either a single 50 g dose of superactivated charcoal dissolved in 300 ml of water or six doses every four hours. All patients with a history of poison ingestion were approached concerning the study and written informed consent taken from each patient, or their relative (for unconscious patients or those 72 hrs post-ingestion, and previous recruitment. The primary outcome was in-hospital mortality; secondary outcomes included the occurrence of serious complications (need for intubation, time requiring assisted ventilation, fits, cardiac dysrhythmias. Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed. Discussion This trial will provide important

  9. Single-dose tinidazole for the treatment of giardiasis

    NARCIS (Netherlands)

    Speelman, P.

    1985-01-01

    Sixty-three expatriate residents and travellers in Bangladesh, infected with Giardia lamblia, participated in two studies to compare the therapeutic efficacy of tinidazole and metronidazole. In the first trial 33 randomly selected patients were treated with tinidazole (50 mg/kg of body weight to a

  10. Levamisole and low-dose prednisolone in the treatment of reccurent aphthous stomatitis.

    Science.gov (United States)

    Sharda, Neelkamal; Shashikanth, M C; Kant, Priyanka; Jain, Manika

    2014-04-01

    Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease. However, the available therapies for RAS only relieve symptoms and do not provide a cure. This study assessed the response to treatment with levamisole and low-dose prednisolone drug combination in patients with RAS. Fifty RAS subjects were enrolled in the single-blind randomized placebo-controlled trial. Study medications were administered thrice daily for 3 consecutive days/week for 3 consecutive weeks. Patients in Group 1 received placebo, Group 2 received levamisole (50 mg) and Group 3 received levamisole (50 mg) and low-dose prednisolone (5 mg). Patients were followed up for 60 days after treatment. Response to treatment was assessed using the following clinical parameters: pain due to ulcers, number of ulcers/episode, size of ulcers, duration of ulcers, and frequency of ulcers (episodes/month). Mann–Whitney U-test. A statistically significant improvement was noted in all parameters except for the size of ulcers in patients treated with levamisole alone and with combination of levamisole and low-dose prednisolone. There was no statistically significant improvement in the placebo group. Both active groups had significantly better improvement when compared to placebo group, while there was no significant difference between the two active groups. Levamisole alone and combination of levamisole and low-dose prednisolone are effective modes of therapy for RAS.

  11. Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial.

    Directory of Open Access Journals (Sweden)

    Leonore Lovis

    Full Text Available BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ is the drug of choice for morbidity control but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45 or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45. Adverse events were assessed at 3 and 24 hours posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI: 56.6-88.5% and 80.8% (95% CI: 60.6-93.4% for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60. O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4% and 96.6% (95% CI: not defined, respectively (P = 0.009. Egg reduction rates (ERRs against O. viverrini were very high for both doses (>99%, but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1% and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment. Adverse events were common (96%, mainly mild with no significant differences between the two treatment groups. CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. TRIAL REGISTRATION: Controlled

  12. Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

    Science.gov (United States)

    Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

    2013-01-01

    Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  13. Intramuscular Single-dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Kwang-Ho Lee

    2015-12-01

    Full Text Available Objectives: Bufonis venonum (BV is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. Results: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. Conclusion: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal.

  14. A dose verification tool for high-dose-rate interstitial brachytherapy treatment planning in accelerated partial breast irradiation.

    Science.gov (United States)

    Marqa, Mohamad Feras; Caudrelier, Jean-Michel; Betrouni, Nacim

    2012-01-01

    To develop a dose verification tool for high-dose-rate interstitial brachytherapy treatment planning in accelerated partial breast irradiation. We have developed a software tool for interstitial brachytherapy treatment planning assessment. The software contains a database of seven (192)Ir source models and is able to estimate the dose distribution using the Task Group 43 and the Sievert integral algorithms. Dose-volume histogram analysis and dose quality assurance (QA) criteria including conformity (COnformal INdex [COIN] and conformation number [CN]), homogeneity (homogeneity index [HI]) parameters were implemented in the software to evaluate and to compare between the doses estimated by the two algorithms and a dose extracted from an external treatment planning system (TPS). The tool was evaluated and validated on four clinical cases treated by high-dose-rate interstitial brachytherapy. The doses provided by the Task Group 43 and the Sievert integral algorithms were evaluated by establishing the dose-volume histogram analysis and then by calculating the QA criteria. The algorithms were validated by comparing the dose at different anatomic points with their corresponding dose points provided from TPS. The differences were considered in good agreement (within 5%). Pretreatment dose verification is an important step in the QA of brachytherapy accelerated partial breast irradiation. A simple, fast, and accurate method of dose verification is therefore needed. The software proposed in this study could fulfill these requirements. In addition, it is freely available for using by anyone wishing to do a QA on any TPS. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  15. 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.

  16. Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

    Directory of Open Access Journals (Sweden)

    Cui Y

    2013-12-01

    Full Text Available Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK, pharmacodynamics (PD, and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9. The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral

  17. Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR.

    Directory of Open Access Journals (Sweden)

    Phonepasong Ayé Soukhathammavong

    2012-01-01

    Full Text Available BACKGROUND: Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH infections. We assessed the efficacy of single oral doses of albendazole (400 mg and mebendazole (500 mg for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. METHODOLOGY: We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples were randomly assigned to albendazole (n=100 and mebendazole (n=100. Cure rate (CR; percentage of children who became egg-negative after treatment, and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline at 21-23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. PRINCIPAL FINDINGS: Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P=0.01, and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively and moderate ERRs (82.1% and 78.2%, respectively. CONCLUSIONS/SIGNIFICANCE: Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN29126001.

  18. Single dose spinal analgesia: Is it a good alternative to epidural analgesia in controlling labour pain?

    Directory of Open Access Journals (Sweden)

    Tarek AbdElBarr

    2014-07-01

    Conclusions: Based on the results of our study we concluded that single dose spinal analgesia is a good alternative to epidural analgesia in controlling labour pain i.e. spinal compared to epidural is more easy performed, faster, less expensive, and provide effective analgesia.

  19. Single dose of fluoxetine increases muscle activation in chronic stroke patients.

    NARCIS (Netherlands)

    van Genderen, Hanneke Irene; Nijlant, Juliette M.M.; van Putten, Michel Johannes Antonius Maria; Movig, Kris L.L.; IJzerman, Maarten Joost

    2009-01-01

    Objectives: This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients. Methods: A crossover, placebo-controlled clinical trial was conducted in 10

  20. Oral microflora and selection of resistance after a single dose of amoxicillin.

    Science.gov (United States)

    Khalil, D; Hultin, M; Rashid, M U; Lund, B

    2016-11-01

    The study aimed to determine the effects of a single-dose antibiotic prophylaxis on normal oral microflora. A single dose of 2 g amoxicillin was given to 29 healthy volunteers. Saliva was collected before antibiotic administration (day 1), and again on days 2, 5, 10, 17 and 24 and subjected to culturing and antibiotic sensitivity analysis. Twenty-one per cent (6/29) of the individuals carried penicillin-V- and amoxicillin-resistant viridans streptococci before antibiotic administration. After a single dose of amoxicillin there was a significant reduction in Streptococcus salivarius on days 2 and 5, a significant reduction in other viridans streptococci on day 2 and the proportion of viridans streptococci with reduced susceptibility to amoxicillin was significantly increased on days 2 and 5. A single dose of amoxicillin can cause an ecological disturbance and induce selection of resistant strains in the oral microflora. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

    NARCIS (Netherlands)

    Lamers, CTJ; Ramaekers, JG; Muntjewerff, ND; Sikkema, KL; Samyn, N; Read, NL; Brookhuis, KA; Riedel, WJ

    2003-01-01

    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition,

  2. Vaginal bleeding following the use of a single dose of 1.5mg ...

    African Journals Online (AJOL)

    Introduction: Recent studies have shown that a single dose of 1.5 mg levonorgestrel is an effective and safe emergency contraceptive but detailed information on its menstrual side effects is lacking. This study assessed the vaginal bleeding patterns in healthy women who used the medication for emergency contraception.

  3. Sources of variability in OSL dose measurements using single grains of quartz

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, L.

    2005-01-01

    spread. In this preliminary study, dose distributions have been studied using single grains of heated and laboratory irradiated quartz. By heating the sample, the contribution from incomplete zeroing was excluded and at the same time the sample was sensitised. The laboratory gamma irradiation...

  4. Studies on single-dose toxicity of hydrophobically modified hydroxypropyl methylcellulose in rats.

    Science.gov (United States)

    Obara, S; Muto, H; Kokubo, H; Ichikawa, N; Kawanabe, M; Tanaka, O

    1992-02-01

    Single-dose toxicological studies of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether) were conducted. A dispersion of HM-HPMC was administered to rats orally or by dermal application at doses up to 900 mg/kg. After the oral administration, the mean body weight of the 900 mg/kg group on the first day after administration was slightly but significantly lower (P less than 0.05) than that of the control group, and one rat had loose stools at 30 min. after the administration. No other abnormalities were noted. In the case of dermal application, no abnormalities were observed. No rats died, and no abnormalities in their organs were found by either route. In conclusion, there was no observed toxicity of HM-HMPC after oral or dermal administration at single dose up to 900 mg/kg under the conditions of these studies.

  5. Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

    Science.gov (United States)

    Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

  6. The influence of food on the absorption of diclofenac after single and multiple oral doses.

    Science.gov (United States)

    Willis, J V; Kendall, M J; Jack, D B

    1981-01-01

    A single dose of enteric-coated diclofenac sodium was taken fasting and immediately after a standard breakfast by twelve healthy volunteers. A considerable delay in the onset of absorption was observed, non-fasting, varying from 2.5 to 12 h compared with 1.5 to 2.75 h when fasting. Peak plasma concentrations were reduced after food but areas under plasma concentration-time curves were comparable. Six subjects then took part in a study involving single and repeated dosing under fasting and non-fasting conditions. As before, prolonged and variable delays were observed when the enteric-coated tablets were taken after food. On repeated dosing, maximum plasma concentrations were reached after 6 h non-fasting compared with 2.5 h fasting. Peak plasma levels were, however, similar.

  7. Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-06-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

  8. New polylactic acid/ cellulose acetate-based antimicrobial interactive single dose nanofibrous wound dressing mats.

    Science.gov (United States)

    Gomaa, Salma F; Madkour, Tarek M; Moghannem, Saad; El-Sherbiny, Ibrahim M

    2017-12-01

    New single dose interactive extracellular matrix (ECM) mimicking nanofibrous wound dressings based on polylactic acid (PLA) and cellulose acetate (CA) were developed, characterized and investigated for wound treatment. The antimicrobial agent, thymoquinone (TQ) was selected and incorporated into the scaffolds for preventing common clinical infections, and to accelerate the rate of wound closure and re-epithelialization. The newly fabricated TQ-loaded PLA/CA wound dressings offered many advantages such as mimicking the ECM via the 3D nanofibrous structure, and promoted the cell proliferation due to the hydrophilicity and bioactivity of CA. The wound dressings also prevented the bacterial infection in the early stages due to presence of TQ, and maintained the minimum possible bacterial load in the wound area through the sustained release of the drug for 9days. In vivo assessment demonstrated that TQ-loaded PLA: CA (7:3) scaffolds significantly promoted the wound healing process by increasing re-epithelialization and controlling the formation of granulation tissue. The obtained results suggest that the developed TQ-loaded PLA/CA nanofibrous mats could be ideal for wound dressing applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Evaluation of the effective dose and image quality of low-dose multi-detector CT for orthodontic treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Gi Chung; Han, Won Jeong; Kim, Eun Kyung [Department of Oral and Maxillofacial Radiology, School of Dentistry, Dankook University, Cheonan (Korea, Republic of)

    2010-03-15

    This study was designed to compare the effective doses from low-dose and standard-dose multi-detector CT (MDCT) scanning protocols and evaluate the image quality and the spatial resolution of the low-dose MDCT protocols for clinical use. 6-channel MDCT scanner (Siemens Medical System, Forschheim, Germany), was used for this study. Protocol of the standard-dose MDCT for the orthodontic analysis was 130 kV, 35 mAs, 1.25 mm slice width, 0.8 pitch. Those of the low-dose MDCT for orthodontic analysis and orthodontic surgery were 110 kV, 30 mAs, 1.25 mm slice width, 0.85 pitch and 110 kV, 45 mAs, 2.5 mm slice width, 0.85 pitch. Thermoluminescent dosimeters (TLDs) were placed at 31 sites throughout the levels of adult female ART head and neck phantom. Effective doses were calculated according to ICRP 1990 and 2007 recommendations. A formalin-fixed cadaver and AAPM CT performance phantom were scanned for the evaluation of subjective image quality and spatial resolution. Effective doses in {mu}Sv (E2007) were 699.1, 429.4 and 603.1 for standard-dose CT of orthodontic treatment, low-dose CT of orthodontic analysis, and low-dose CT of orthodontic surgery, respectively. The image quality from the low-dose protocol were not worse than those from the standard-dose protocol. The spatial resolutions of both standard-dose and low-dose CT images were acceptable. From the above results, it can be concluded that the low-dose MDCT protocol is preferable in obtaining CT images for orthodontic analysis and orthodontic surgery.

  10. Adverse events are rare after single-dose montelukast exposures in children.

    Science.gov (United States)

    Arnold, Donald H; Bowman, Nena; Reiss, Theodore F; Hartert, Tina V; Seger, Donna L

    2018-01-01

    Montelukast sodium is a leukotriene-receptor antagonist approved as a controller medication for chronic asthma and allergic rhinitis in children and adults. We sought to characterize adverse events associated with single montelukast exposures in children ages 5-17 years and to determine whether adverse events were dose related for all-dose and for ultra-high-dose (≥50 mg) exposures. This is a retrospective analysis of data from the National Poison Data System for exposures that included montelukast in individuals aged 5-17 years for calendar years 2000-2016. Filters were applied to identify exposure events in which montelukast was the primary exposure and for which the exact or lowest-possible ingested dose was recorded. Characteristics of adverse events were examined using descriptive statistics and multivariable logistic models were used to examine whether associations of montelukast and adverse events were dose related. During the 17-year study period, there were 17,069 montelukast exposures available for analyses. Patients were median [interquartile range] age 7 (5, 9) years, and 10,907 (64%) male gender. Abdominal pain was the most common adverse event (0.23%). There were 618 ultra-high-dose exposures (≥50 mg). These patients had median age 6 (5, 8) years, and 347 (56%) male gender. Abdominal pain was the most common adverse event (1.46%). Increasing ingested dose was associated with abdominal pain (adjusted odds ratio, 1.01, 95% confidence interval 1.01, 1.02) after adjustment for age and gender. No serious or life-threatening events were reported. Single-dose exposures of montelukast up to 445 mg are rarely associated with any adverse events and are not associated with serious or life-threatening adverse events in children aged 5-17 years.

  11. Pharmacokinetics and Safety of Single-Dose Inhaled Loxapine in Children and Adolescents.

    Science.gov (United States)

    Selim, Sally; Riesenberg, Robert; Cassella, James; Kunta, Jeevan; Hellriegel, Edward; Smith, Mark A; Vinks, Alexander A; Rabinovich-Guilatt, Laura

    2017-10-01

    This multisite open-label study sought to characterize the pharmacokinetics and safety of a single dose of inhaled loxapine in children and adolescents. Loxapine powder for oral inhalation was administered via a single-use handheld drug device to children and adolescents (aged 10-17 years) with any condition warranting chronic antipsychotic use. Patients were dosed according to body weight and cohort (<50 kg [n = 15], 2.5 or 5 mg; ≥50 kg [n = 15], 5 or 10 mg); the first 6 patients (cohort 1) enrolled in each weight group received the lower dose. Patients were enrolled in the higher-dose group (cohort 2) after an interim pharmacokinetic and safety analysis of data from cohort 1. Blood samples were collected for 48 hours after dosing to determine the pharmacokinetic profile of loxapine and its metabolites. Safety was assessed using adverse event (AE), laboratory value, physical/neurologic examination, vital sign, electrocardiogram, suicidality, and extrapyramidal symptom assessment. Thirty patients were enrolled and evaluable for pharmacokinetics. Loxapine plasma concentrations peaked by 2 to 5 minutes in most patients; systemic exposure increased with dose in both weight subgroups. Loxapine terminal elimination half-life was ∼13 to 17 hours. The most common AEs were sedation and dysgeusia. Sedation was severe in 1 patient in the <50-kg group (2.5-mg dose) and 1 patient in the ≥50-kg group (5-mg dose). No AEs indicative of bronchospasm or other serious AEs were reported. Inhaled loxapine was rapidly absorbed and generally well tolerated in pediatric patients; no new safety signals were observed. © 2017, The American College of Clinical Pharmacology.

  12. Histamine skin test reactivity following single and multiple doses of azelastine nasal spray in patients with seasonal allergic rhinitis.

    Science.gov (United States)

    Pearlman, David S; Grossman, Jay; Meltzer, Eli O

    2003-09-01

    To determine whether azelastine nasal spray suppresses the dermal response to epicutaneous histamine in allergic patients and the duration of suppression after azelastine use is discontinued. Seventy-eight patients with seasonal allergic rhinitis were entered into this randomized, double-blind, parallel-group, placebo-controlled study. Patients received either azelastine nasal spray (2 sprays per nostril twice daily) or placebo nasal spray for 14 days. Skin tests were performed 5 hours after the first dose of study drugs to determine the effect of a single dose of azelastine nasal spray on the wheal-and-flare response to histamine. At the end of the 14-day treatment period, skin tests were performed 5 hours after the last dose of study drugs and at 24-hour intervals thereafter, until each patient's wheal-and-flare response to histamine (1.0 and 5.0 mg/mL) returned to within 20% of baseline values. A single dose of azelastine nasal spray did not significantly alter the wheal-and-flare response to histamine. The wheal response was within 20% of the baseline value in 82% and 88% (1.0 and 5.0 mg/mL of histamine, respectively) of the patients 5 hours after discontinuing 14 days of treatment with azelastine nasal spray. Wheal responses were within 20% of baseline values 48 hours after treatment was discontinued, whereas flare responses returned to within 20% of baseline within 48 hours in 92% of the patients. Azelastine nasal spray should be discontinued for at least 48 hours before beginning allergy skin test procedures.

  13. Single dose oral ibuprofen plus oxycodone for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Derry, Christopher J; Moore, R Andrew

    2013-06-26

    Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Fixed-dose combinations of ibuprofen and oxycodone are available, and the drugs may be separately used in combination in some acute pain situations. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus oxycodone for moderate to severe postoperative pain. We searched the Cochrane Central Register of Controlled Trials, (CENTRAL), on The Cochrane Library, (Issue 4 of 12, 2013), MEDLINE (1950 to 21st May 2013), EMBASE (1974 to 21st May 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus oxycodone compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus oxycodone, ibuprofen alone, oxycodone alone, or placebo with at least 50% pain relief over six hours, using validated equations. We calculated relative risk (RR) and number needed to treat to benefit (NNT). We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1202 participants. All examined the same dose combination. Included studies provided data from 603 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with placebo, 717 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with ibuprofen 400 mg

  14. Antimicrobial selection and dosing in the treatment of wounds in the United Kingdom.

    Science.gov (United States)

    Ross, S E; Duz, M; Rendle, D I

    2016-11-01

    Antimicrobial stewardship within the veterinary profession is recognised by governing and professional bodies as being important; the attitudes and behaviour of veterinary surgeons merit investigation. To investigate levels of protected antimicrobial use and accuracy of antimicrobial dosing in a common clinical scenario in equine practice. Retrospective cohort study. Antimicrobial use was evaluated retrospectively in 113 cases subsequently referred to a single referral hospital for the treatment of limb wounds over a 20-month period. Antimicrobial classification (first-line, alternative or protected) was made according to guidelines produced by the British Equine Veterinary Association. These guidelines also served as the reference for recommended dose rates. Systemic antimicrobials were administered prior to referral in 94/113 (83.2%) horses, of which 8 (8.5%) received the protected third or fourth generation cephalosporins or fluoroquinolones. Forty-eight of 87 (55.2%) horses for which complete dosing data were available received antimicrobials at ≤90% of the recommended dose. Practitioners who held a postgraduate clinical qualification or worked in purely equine practice were no more or less likely to use protected antimicrobials (P = 0.06 and P = 0.64, respectively) or administer inadequate doses (P = 0.75 and P = 0.85, respectively). Veterinary surgeons with more experience were less likely to use protected antimicrobials (Pequine practitioners. Bodyweight ought to be measured or estimated using validated objective techniques prior to systemic medications being administered. © 2015 EVJ Ltd.

  15. Ledipasvir/sofosbuvir: the fixed dose combination in the new era of treatment for HCV

    Directory of Open Access Journals (Sweden)

    Alessia Ciancio

    2015-07-01

    Full Text Available Interferon-based treatment is not suitable for many patients with hepatitis C virus (HCV infection because of contraindications, other reasons for ineligibility and side-effects. The fixed dosed combination ledipasvir/sofosbuvir (LDV / SOF is the first approved regimen that doesn’t require administration with interferon or ribavirin. LDV / SOF is also the first single-pill approved for the treatment of chronic HCV genotype 1 in both treatment-naïve and treatment-experienced patients. The results of the phase III studies demonstrate the combination has been very well tolerated and SVR rates consistently above 90%. Objective of this review is to present clinical evidence of efficacy and safety of the combination LDV / SOF in different subgroups of patients with HCV.

  16. Monte Carlo systems used for treatment planning and dose verification

    Energy Technology Data Exchange (ETDEWEB)

    Brualla, Lorenzo [Universitaetsklinikum Essen, NCTeam, Strahlenklinik, Essen (Germany); Rodriguez, Miguel [Centro Medico Paitilla, Balboa (Panama); Lallena, Antonio M. [Universidad de Granada, Departamento de Fisica Atomica, Molecular y Nuclear, Granada (Spain)

    2017-04-15

    General-purpose radiation transport Monte Carlo codes have been used for estimation of the absorbed dose distribution in external photon and electron beam radiotherapy patients since several decades. Results obtained with these codes are usually more accurate than those provided by treatment planning systems based on non-stochastic methods. Traditionally, absorbed dose computations based on general-purpose Monte Carlo codes have been used only for research, owing to the difficulties associated with setting up a simulation and the long computation time required. To take advantage of radiation transport Monte Carlo codes applied to routine clinical practice, researchers and private companies have developed treatment planning and dose verification systems that are partly or fully based on fast Monte Carlo algorithms. This review presents a comprehensive list of the currently existing Monte Carlo systems that can be used to calculate or verify an external photon and electron beam radiotherapy treatment plan. Particular attention is given to those systems that are distributed, either freely or commercially, and that do not require programming tasks from the end user. These systems are compared in terms of features and the simulation time required to compute a set of benchmark calculations. (orig.) [German] Seit mehreren Jahrzehnten werden allgemein anwendbare Monte-Carlo-Codes zur Simulation des Strahlungstransports benutzt, um die Verteilung der absorbierten Dosis in der perkutanen Strahlentherapie mit Photonen und Elektronen zu evaluieren. Die damit erzielten Ergebnisse sind meist akkurater als solche, die mit nichtstochastischen Methoden herkoemmlicher Bestrahlungsplanungssysteme erzielt werden koennen. Wegen des damit verbundenen Arbeitsaufwands und der langen Dauer der Berechnungen wurden Monte-Carlo-Simulationen von Dosisverteilungen in der konventionellen Strahlentherapie in der Vergangenheit im Wesentlichen in der Forschung eingesetzt. Im Bemuehen, Monte

  17. SINGLE- VERSUS DOUBLE-DOSE RABIES VACCINATION IN CAPTIVE AFRICAN WILD DOGS (LYCAON PICTUS).

    Science.gov (United States)

    Connolly, Maren; Thomas, Patrick; Woodroffe, Rosie; Raphael, Bonnie L

    2015-12-01

    The immune responses of 35 captive African wild dogs (Lycaon pictus) to an inactivated rabies virus vaccine were evaluated. Seventeen animals received one 1-ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. Sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. Rabies neutralizing serum antibody titers were measured by rapid fluorescent focus inhibition testing. Within 3 mo postvaccination, all 28 animals that were tested within that time period had seroconverted. Overall, titers were significantly higher among animals given two doses of vaccine than among those given a single dose, although this difference was no longer significant by 15 mo postvaccination. Regardless of initial dose, a single administration of inactivated rabies virus vaccine resulted in long-term elevation of titers in the African wild dogs in this study. In the two individuals followed for greater than 36 mo, both (one from each group) maintained detectable titers.

  18. PaxVax CVD 103-HgR single-dose live oral cholera vaccine.

    Science.gov (United States)

    Levine, Myron M; Chen, Wilbur H; Kaper, James B; Lock, Michael; Danzig, Lisa; Gurwith, Marc

    2017-03-01

    Cholera remains a problem in developing countries and a risk for travelers. Hypochlorhydria, blood group O, cardiac and renal disease increase the risk of developing cholera gravis. Oral vaccines containing inactivated Vibrio cholerae and requiring two doses are available in some countries. No cholera vaccine had been available for U.S. travelers for decades until 2016 when CVD 103-HgR (VAXCHORA™), an oral live attenuated vaccine, was licensed by the U.S. FDA. Areas covered: Enduring protection following wild-type cholera provided the rationale to develop a single-dose live oral vaccine. CVD 103-HgR is well-tolerated and protects against cholera caused by V. cholerae O1 of either serotype (Inaba, Ogawa) and biotype (El Tor, Classical). Since 90% vaccine efficacy is evident 10 days post-ingestion of a single dose, CVD 103-HgR can rapidly protect travelers. Vibriocidal antibody seroconversion correlates with protection; >90% of U.S. adult (including elderly) vaccinees seroconvert. The U.S. Public Health Service's Advisory Committee on Immunization Practices recommends CVD 103-HgR for U.S. travelers to areas of ongoing cholera transmission. Expert commentary: Next steps include evaluations in children, post-licensure safety and effectiveness monitoring, diminishing cold chain constraints, optimizing a 'high-dose' formulation for developing countries, and diminishing/eliminating the need for water to administer a dose.

  19. The treatment of autism with low-dose phenytoin: a case report.

    Science.gov (United States)

    Bird, Philip D

    2015-01-16

    The drug treatment of autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions (such as inattention or irritability) that frequently coexist, with limited benefit for the core social deficits. Here, I describe the novel use of a low dose of the anti-epileptic phenytoin to enhance social functioning in a patient with an autism spectrum disorder. I present the case of a 19-year-old Caucasian man with autism spectrum disorder treated with stimulant medication since early childhood. He experienced long-standing difficulties in establishing and maintaining relationships and reading social cues, and was socially isolated. Within 10 minutes of a single sublingual low dose of phenytoin there was an immediate observable improvement in his eye contact and integration of both verbal and non-verbal communication. This enhanced social functioning associated with his adherence to the low-dose phenytoin therapy was maintained for over 18 months of follow-up. These clinical observations were supported by ratings using the Autism-Spectrum Quotient and the Depression, Anxiety and Stress Scales, recorded pre-treatment and after seven months on 5mg phenytoin. This case report provides the first potential evidence that a low dose of phenytoin, a widely used and well tolerated anti-epileptic medication, may be capable of modifying the core social cognitive deficits associated with autism spectrum disorders. While acknowledging this is a single case study, the lack of availability of safe and effective treatments to address the important core deficits associated with autism spectrum disorders makes this case noteworthy.

  20. Effect of lactation on single-dose pharmacokinetics of norfloxacin nicotinate in ewes.

    Science.gov (United States)

    Soback, S; Gips, M; Bialer, M; Bor, A

    1994-01-01

    In a three-way crossover trial, six healthy Finnish-Merino-Awassi ewes were given a single intravenous injection of norfloxacin nicotinate (in a dose equivalent to 25 mg of norfloxacin base per kg of body weight) during nursing, 1 day after weaning, and 1 month after weaning. Blood and milk samples were collected at different time intervals following dosing, and norfloxacin concentrations were determined by a high-performance liquid chromatography assay. The serum drug concentration versus time data were analyzed by a noncompartmental approach which was based on the statistical-moment theory. The total body clearance values were 4.2 +/- 1.3 (injection during nursing), 1.6 +/- 0.3 (injection 1 day after weaning), and 3.1 +/- 0.8 ml/min/kg (injection 1 month after weaning). The mean residence times were 335 +/- 83, 797 +/- 129, and 481 +/- 102 min and terminal half-lives were 266 +/- 51, 603 +/- 94, and 372 +/- 68 min for the respective treatments. The estimated volumes of distribution at steady state were 1.3 +/- 0.1, 1.2 +/- 0.1, and 1.4 +/- 0.2 liter/kg for the respective treatments. Milk norfloxacin concentrations were up to 40 times higher than the corresponding concentrations in serum during lactation. Accordingly, in ewes with 1.5 liter of milk in the udder more than half of the drug in the animal appeared to be in the milk. Therapeutic concentrations of norfloxacin could be detected in the sera of suckling lambs, implicating that fluoroquinolone therapy should be discouraged during breast feeding. In lactating ewes and in ewes with full udders, moment analysis calculations did not show a significant difference between the system moment mean residence time and the system matrix mean residence time values. Thus, the pharmacokinetics of norfloxacin in the three groups could be described by the classical two-compartment open-body model with input and output occurring from the central compartment. The results did not support the existence of a distinguishable milk

  1. Development of a synthetic single crystal diamond dosimeter for dose measurement of clinical proton beams

    Science.gov (United States)

    Moignier, Cyril; Tromson, Dominique; de Marzi, Ludovic; Marsolat, Fanny; García Hernández, Juan Carlos; Agelou, Mathieu; Pomorski, Michal; Woo, Romuald; Bourbotte, Jean-Michel; Moignau, Fabien; Lazaro, Delphine; Mazal, Alejandro

    2017-07-01

    The scope of this work was to develop a synthetic single crystal diamond dosimeter (SCDD-Pro) for accurate relative dose measurements of clinical proton beams in water. Monte Carlo simulations were carried out based on the MCNPX code in order to investigate and reduce the dose curve perturbation caused by the SCDD-Pro. In particular, various diamond thicknesses were simulated to evaluate the influence of the active volume thickness (e AV) as well as the influence of the addition of a front silver resin (250 µm in thickness in front of the diamond crystal) on depth-dose curves. The simulations indicated that the diamond crystal alone, with a small e AV of just 5 µm, already affects the dose at Bragg peak position (Bragg peak dose) by more than 2% with respect to the Bragg peak dose deposited in water. The optimal design that resulted from the Monte Carlo simulations consists of a diamond crystal of 1 mm in width and 150 µm in thickness with the front silver resin, enclosed by a water-equivalent packaging. This design leads to a deviation between the Bragg peak dose from the full detector modeling and the Bragg peak dose deposited in water of less than 1.2%. Based on those optimizations, an SCDD-Pro prototype was built and evaluated in broad passive scattering proton beams. The experimental evaluation led to probed SCDD-Pro repeatability, dose rate dependence and linearity, that were better than 0.2%, 0.4% (in the 1.0-5.5 Gy min-1 range) and 0.4% (for dose higher than 0.05 Gy), respectively. The depth-dose curves in the 90-160 MeV energy range, measured with the SCDD-Pro without applying any correction, were in good agreement with those measured using a commercial IBA PPC05 plane-parallel ionization chamber, differing by less than 1.6%. The experimental results confirmed that this SCDD-Pro is suitable for measurements with standard electrometers and that the depth-dose curve perturbation is negligible, with no energy dependence and no significant dose rate

  2. Successful Treatment of Acute Lethal Dose of Acrylamide Poisoning

    Directory of Open Access Journals (Sweden)

    Ali Banagozar Mohammadi

    2015-03-01

    Full Text Available Background: Acrylamide (C3H5NO is a vinyl monomer. This water-soluble crystalline solid is a colorless, odorless agent which is used in scientific laboratories and some industries. Acrylamide has cellular oxidative effects. Acute or chronic poisoning with this agent happens as a result of skin, respiratory, or oral contacts. Clinical manifestations depend on the dose, duration, and frequency of contact. Management of these patients consists of conservative and palliative therapies to reduce the oxidative effects. Case: The case was a 29-year-old girl with a Master of Sciences degree in genetics who worked in a university research center with previous history of depression. She had ingested 100cc of 30% Acrylamide solution for intentional suicide attempt. The patient was successfully managed using N-acetyl cysteine, vitamin C, and melatonin. Conclusion: Early diagnosis and appropriate treatment with recommended agents together with supportive therapies can save the life of patients exposed to potentially lethal doses of acrylamide, although intentional or accidental.

  3. ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.

    Science.gov (United States)

    Miley, Galen P; Pou, Sovitj; Winter, Rolf; Nilsen, Aaron; Li, Yuexin; Kelly, Jane X; Stickles, Allison M; Mather, Michael W; Forquer, Isaac P; Pershing, April M; White, Karen; Shackleford, David; Saunders, Jessica; Chen, Gong; Ting, Li-Min; Kim, Kami; Zakharov, Lev N; Donini, Cristina; Burrows, Jeremy N; Vaidya, Akhil B; Charman, Susan A; Riscoe, Michael K

    2015-09-01

    ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing. While these low blood concentrations are sufficient for therapy, the levels are too low to establish an acceptable safety margin required by regulatory agencies for clinical development. One way to address the challenging physicochemical properties of ELQ-300 is through the development of prodrugs. Here, we profile ELQ-337, a bioreversible O-linked carbonate ester prodrug of the parent molecule. At the molar equivalent dose of 3 mg/kg of body weight, the delivery of ELQ-300 from ELQ-337 is enhanced by 3- to 4-fold, reaching a maximum concentration of drug in serum (C max) of 5.9 μM by 6 h after oral administration, and unlike ELQ-300 at any dose, ELQ-337 provides single-dose cures of patent malaria infections in mice at low-single-digit milligram per kilogram doses. Our findings show that the prodrug strategy represents a viable approach to overcome the physicochemical limitations of ELQ-300 to deliver the active drug to the bloodstream at concentrations sufficient for safety and toxicology studies, as well as achieving single-dose cures. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

    Science.gov (United States)

    Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford

    2017-01-31

    To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. NCT02178995. This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. © 2016 American Academy of Neurology.

  5. Pharmacologic Treatment Reduces Pressure Times Time Dose and Relative Duration of Intracranial Hypertension.

    Science.gov (United States)

    Colton, Katharine; Yang, S; Hu, P F; Chen, H H; Bonds, B; Stansbury, L G; Scalea, T M; Stein, D M

    2016-05-01

    Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated. A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05. Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration.

  6. The Comparison 2D and 3D Treatment Planning in Breast Cancer Radiotherapy with Emphasis on Dose Homogeneity and Lung Dose

    Directory of Open Access Journals (Sweden)

    Zahra Falahatpour

    2010-09-01

    Full Text Available Introduction: Breast conserving radiotherapy is one of the most common procedures performed in any radiation oncology department. A tangential parallel-opposed pair is usually used for this purpose. This technique is performed using 2D or 3D treatment planning systems. The aim of this study was to compare 2D treatment planning with 3D treatment planning in tangential irradiation in breast conserving radiotherapy. In this comparison, homogeneity of isodoses in the breast volume and lung dose were considered. Material and Methods: Twenty patients with breast cancer treated with conservative surgery were included in this study. The patients were CT scanned. Two-dimensional treatment planning with the Alfard 2D TPS was performed for each patient using a single central CT slice. The data used on the Alfard 2D TPS was imported into the Eclipse 3D TPS, on which 3D treatment planning was performed. Cobalt-60 beams were used in all plans. Results: Comparing 2D and 3D treatment planning, homogeneity of isodoses was improved in 3D treatment planning (p30Gy was increased in 3D treatment planning (p< 0.01. Discussion and Conclusion: 3D treatment planning is a more suitable option for patients with breast cancer treated with conservative surgery because of improved dose homogeneity in 3D treatment planning. The results of the treatment can be improved with reduced recurrence probability and skin problems.

  7. Sensitivity of doping biomarkers after administration of a single dose testosterone gel.

    Science.gov (United States)

    Mullen, Jenny; Börjesson, Annica; Hopcraft, Oscar; Schulze, Jenny J; Ericsson, Magnus; Rane, Anders; Lehtihet, Mikael; Ekström, Lena

    2017-11-18

    Micro-doping with testosterone (T) is challenging to detect with the current doping tests. Today, the methods available to detect T are longitudinally monitoring of urine biomarkers in the Athlete Biological Passport (ABP) and measuring the isotopic composition of excreted biomarkers to distinguish the origin of the molecule. In this study, we investigated the detectability of a single dose of 100 mg T gel in 8 healthy male subjects. We also studied which biomarkers were most sensitive to T gel administration, including blood biomarkers. The ABP successfully detected T gel administration in all 8 subjects. The most sensitive ratio was 5αAdiol/E, however, also T/E and 5αAdiol/5βAdiol showed atypical findings. IRMS was performed on 5 subjects and only two met all the criteria for a positive test according to the rules set by WADA. The other three showed inconclusive results. Other markers that were affected by T gel administration, not used for this detection today, were serum dihydrotestosterone (DHT) and T as well as reticulocyte count and percentage in whole blood. miRNA-122 was not significantly affected by the single T dose. A single dose of 100 mg T gel is possible to detect with today's doping tests. Since a single dose of T gel has an impact on some hematological biomarkers, access to both modules of the ABP when evaluating the athletes' profiles will increase the possibility to detect micro-doses of T. In addition, serum DHT and T may be a useful addition to the future endocrine module of the biological passport. This article is protected by copyright. All rights reserved.

  8. Efficacy of standard doses of Ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children.

    Science.gov (United States)

    Paul, Ian M; Sturgis, Sarah A; Yang, Chengwu; Engle, Linda; Watts, Heidi; Berlin, Cheston M

    2010-12-01

    Many pediatricians recommend, and many parents administer, alternating or combined doses of ibuprofen and acetaminophen for fever. Limited data support this practice with standard US doses. This study compared the antipyretic effect of 3 different treatment regimens in children, using either ibuprofen alone, ibuprofen combined with acetaminophen, or ibuprofen followed by acetaminophen over a single 6-hour observation period. Febrile episodes from children aged 6 to 84 months were randomized into the 3 treatment groups: a single dose of ibuprofen at the beginning of the observation period; a single dose of ibuprofen plus a single dose of acetaminophen at the beginning of the observation period; or ibuprofen followed by acetaminophen 3 hours later. Ibuprofen was administered at 10 mg/kg; acetaminophen at 15 mg/kg. Temperatures were measured hourly for 6 hours using a temporal artery thermometer. The primary outcome was temperature difference between treatment groups. Adverse-event data were not collected in this single treatment period study. Sixty febrile episodes in 46 children were assessed. The mean (SD) age of the children was 3.4 (2.2) years, and 31 (51.7%) were girls. Differences among temperature curves were significant (P ibuprofen-alone group at hours 4 to 6 (hour 4, P children in the combined and alternating groups were afebrile at hours 4, 5, and 6. In contrast, for those receiving ibuprofen alone, 30%, 40%, and 50% had temperatures >38.0 °C at hours 4, 5, and 6, respectively (hour 4, P = 0.002; hours 5 and 6, P children, combined and alternating doses of ibuprofen and acetaminophen provided greater antipyresis than ibuprofen alone at 4 to 6 hours. ClinicalTrials.gov identifier: NCT00267293. Copyright © 2010 Elsevier HS Journals, Inc. All rights reserved.

  9. Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model

    Directory of Open Access Journals (Sweden)

    Carole eGrasso

    2014-12-01

    Full Text Available Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM, is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy of radiation combined with a one hour exposure to ascorbate (5 mM sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.

  10. Peripheral nervous system injury after high-dose single-fraction image-guided stereotactic radiosurgery for spine tumors.

    Science.gov (United States)

    Stubblefield, Michael D; Ibanez, Katarzyna; Riedel, Elyn R; Barzilai, Ori; Laufer, Ilya; Lis, Eric; Yamada, Yoshiya; Bilsky, Mark H

    2017-03-01

    OBJECTIVE The object of this study was to determine the percentage of high-dose (1800-2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury. METHODS All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified. RESULTS Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4-32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected. CONCLUSIONS Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.

  11. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Karlin, Samuel M; Moore, R Andrew

    2015-02-05

    This is an update of the original Cochrane review published in Issue 3, 2013. There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific effects are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations and when tested in the same and different trials. Some combinations of ibuprofen and codeine are available without prescription (but usually only from a pharmacy) where the dose of codeine is lower, and with a prescription when the dose of codeine is higher.Use of combination analgesics that contain codeine has been a source of some concern because of misuse from over-the-counter preparations. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus codeine for acute moderate-to-severe postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and the reference lists of articles. The date of the most recent search was 1 December 2014. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus codeine, placebo, or the same dose of ibuprofen alone with at least 50% pain relief over six hours, using validated equations. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use

  12. Immunogenicity and safety of single-dose, 13-valent pneumococcal conjugate vaccine in pediatric and adolescent oncology patients.

    Science.gov (United States)

    Hung, Te-Yu; Kotecha, Rishi S; Blyth, Christopher C; Steed, Sarah K; Thornton, Ruth B; Ryan, Anne L; Cole, Catherine H; Richmond, Peter C

    2017-11-01

    Children receiving immunosuppressive treatment for cancer are at high risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate vaccine (PCV13) can prevent pneumococcal disease in healthy children; however, there is an absence of literature regarding the benefit of PCV13 in immunocompromised children with cancer. A prospective, open-label cohort study recruited children between ages 1 and 18 years who were receiving active immunosuppressive therapy (AIT) or were within 12 months after completing immunosuppressive therapy (CIT). Blood samples were taken before and 4 weeks after the administration of single-dose PCV13. Serotype-specific immunoglobulin G antibody titers were measured, and titers ≥0.35 μg/mL were considered protective. Solicited side effects were recorded in a 7-day diary after vaccination. Eighty-five children were recruited. At baseline, ≤50% had protective antibody titers against Streptococcus pneumoniae for 10 serotypes in the AIT group and for 8 serotypes in the CIT group. Postvaccination, ≥70% had protective antibody titers for 9 and 11 serotypes in the AIT and CIT groups, respectively. Both groups had comparable responses to PCV7 serotypes, whereas a significantly higher proportion in the CIT group achieved protective antibody titers to PCV13 serotypes. There was a low rate of serious adverse events (3.5%). A single-dose of PCV13 is safe and immunogenic in children diagnosed with cancer. All children who are receiving therapy for cancer should receive a single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV exposure. The current data support the recommendation for an additional dose of PCV13 after the completion of immunosuppressive therapy to provide additional protection against invasive pneumococcal disease. Cancer 2017;123:4215-4223. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Evaluation of the single-dose pharmacokinetics of bilastine in subjects with various degrees of renal insufficiency.

    Science.gov (United States)

    Lasseter, Kenneth C; Sologuren, Ander; La Noce, Anna; Dilzer, Stacy C

    2013-09-01

    Bilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries. This study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin. The study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18-80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m(2)]; (2) mild renal insufficiency (GFR 50-80 mL/min/1.73 m(2)); (3) moderate renal insufficiency (GFR 30-50 mL/min/1.73 m(2)); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m(2)). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics. There was a clear trend of increasing area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) through the groups 1-4. The mean AUC from time zero to infinity (AUC(∞)) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among

  14. Ledipasvir/sofosbuvir fixed-dose combination for treatment of hepatitis C virus genotype 4 infection.

    Science.gov (United States)

    Nehra, V; Tan, E M; Rizza, S A; Temesgen, Z

    2016-02-01

    Hepatitis C virus (HCV) genotype 4 accounts for 8-13% of all chronic HCV infections worldwide. Patients with HCV genotype 4 have been reported to have poor treatment responses to PEGylated interferon and ribavirin regimens. Recently a single tablet, fixed-dose combination of sofosbuvir, an RNA-directed RNA polymerase (NS5B) inhibitor, and ledipasvir, a nonstructural protein 5A (NS5A) inhibitor, has been approved for treatment of chronic HCV infection. Two studies using the fixed-dose combination in chronic HCV genotype 4 for 12 weeks reported sustained virologic response rates at 12 weeks (SVR12) of 93-95%. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 and HIV co-infection. Administered as a single once-daily oral regimen, this ribavirin- and interferon-free regimen is well tolerated, with low potential for adverse effects and represents a significant advancement in the treatment of chronic HCV genotype 4 infection. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

  15. Electrophysiological and biochemical effects of single and multiple doses of the organophosphate diazinon in the mouse.

    Science.gov (United States)

    de Blaquière, G E; Waters, L; Blain, P G; Williams, F M

    2000-07-15

    Diazinon is an organophosphorus compound (OP) widely used in pesticides. The relationship between dose of diazinon, inhibition of acetylcholinesterase, and effect on neuromuscular transmission has been studied in a mouse model. Inhibition of acetylcholinesterase activity occurred within 1 h, was maximal by 3 h and remained inhibited for at least 24 h. Blood, brain, diaphragm, and soleus acetylcholinesterase activities were differentially affected by diazinon. Brain and soleus activities were not affected by low doses. Multiple daily dosing of diazinon caused a cumulative decrease in acetylcholinesterase activity, although to a lesser extent in brain and soleus. Diazinon had no effect on the activity of neuropathy target esterase. Plasma and brain levels of diazinon peaked at 15 min after dosing and declined with a half-life of 2.5 h. Metabolic products of diazinon were cleared from the urine within 24 h. Increased miniature end-plate current half decay times occurred in a dose-dependent manner. Single doses of diazinon caused an increase in the jitter (variability of latencies) of evoked action potentials recorded in the diaphragm but did not affect end-plate potential (EPP) jitter. Multiple lower doses of diazinon caused an increase in EPP jitter after 28 days. This effect on nerve function was delayed and occurred when acetylcholinesterase activity had returned to control levels. The results indicate that diazinon produces long-term electrophysiological changes in neurotransmission following repeated dosing in the mouse. This has implications for the current use of diazinon; however, there is a need to further define the mechanism of this effect. Copyright 2000 Academic Press.

  16. Effects of Age, Sex, and Obesity on the Single-Dose Pharmacokinetics of Omarigliptin in Healthy Subjects.

    Science.gov (United States)

    Addy, Carol; Tatosian, Daniel A; Glasgow, Xiaoli S; Iii, Isaias Noel Gendrano; Sisk, Christine McCrary; Kauh, Eunkyung A; Stoch, S Aubrey; Wagner, John A

    2016-09-01

    Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential. Plasma was collected at selected postdose times for evaluation of omarigliptin concentrations. Pharmacokinetic parameters were compared with historical data from a previously-conducted single-dose study in young, healthy, nonobese men. There were no clinically significant differences in omarigliptin AUC0-∞ , the primary pharmacokinetic parameter for assessing efficacy and safety, based on age, sex, or BMI (pooled nonobese elderly versus pooled nonobese young, young nonobese female versus young nonobese male, and pooled young obese versus pooled young nonobese). There were no serious adverse events or hypoglycemic events attributable to omarigliptin administration. Demographic factors and BMI had no meaningful effect on omarigliptin pharmacokinetics, suggesting that dose adjustment based on age, sex, or obesity is not required. © 2016, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  17. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

    Directory of Open Access Journals (Sweden)

    Spencer C. Greene, MD, FACEP, FACMT

    2016-01-01

    Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

  18. Single and multiple dose pharmacokinetic evaluation of flutamide in normal geriatric volunteers.

    Science.gov (United States)

    Radwanski, E; Perentesis, G; Symchowicz, S; Zampaglione, N

    1989-06-01

    Single dose and steady-state pharmacokinetics of flutamide (F) and its active plasma metabolite, hydroxyflutamide (HF) were studied in twelve healthy geriatric volunteers administered 250 mg flutamide capsules on day 1 and 250 mg flutamide capsules three times a day on days 2 through 9. After oral administration, F was rapidly absorbed and metabolized. It was present in the plasma in small and variable concentrations, which precluded quantitative assessment of pharmacokinetic parameters for individual subjects. Steady-state plasma concentrations were reached on or before Day 6. The mean steady state Cmax (Day 9), 112.7 ng/ml, occurred at 1.3 hr. Pharmacokinetic analysis of mean data at steady-state gave a distribution and elimination half-life of 0.8 hr and 7.8 hours, respectively. The plasma levels for HF were much higher and less variable than F. The mean Cmax for HF averaged 894 ng/ml at 2.7 hours after a single dose and 1719 ng/ml (Day 9) at 1.9 hr after multiple doses. The distribution and elimination half-lives of HF at steady-state were 1.9 and 9.6 hours, respectively. The steady-state HF plasma concentrations were also achieved on or before Day 6 and were approximately twice those obtained after a single dose. From this study, it has been demonstrated that the pharmacokinetics of F and HF do not change appreciably upon multiple dosing of 250 mg F capsule given three times a day.

  19. The pharmacokinetics of a single intramuscular dose of amikacin in red-tailed hawks (Buteo jamaicensis).

    Science.gov (United States)

    Bloomfield, R B; Brooks, D; Vulliet, R

    1997-03-01

    The pharmacokinetic parameters of amikacin were determined in red-tailed hawks (Buteo jamaicensis) following the i.m. administration of a single 20 mg/kg dose. After a rapid absorption phase, mean amikacin serum concentrations peaked at 65 +/- 12 micrograms/ML 30-45 min following injection. The serum amikacin concentrations decreased to 2.3 +/- 2 micrograms/ml at 12 hr postinjection. Amikacin was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.02 +/- 0.63 hr. The volume of distribution was estimated to be 0.28 +/- 0.03 L/kg. Forty-two isolates of gram-negative bacteria and coagulase-positive Staphylococcus species were cultured from birds of prey presented to the Veterinary Medical Teaching Hospital at the University of California-Davis. The minimum inhibitory concentration (MICs) of amikacin ranged from 0.5 to 8.0 micrograms/ml (mean = 2.5 micrograms/ml). The 20 mg/kg dose used in this study resulted in serum concentrations at or above the MICs for > 12 hr for most of the isolates examined. The heaviest birds had the lowest peak serum amikacin concentrations, and the lightest birds had the highest, despite exact volume replacement for each sample drawn. This observation suggests that doses should be based on factors other than weight alone. Amikacin administered at 15-20 mg/kg/day, either as a single dose or divided into two or three doses, is effective in treating sensitive pathogens of the red-tailed hawk.

  20. Aspirin (single dose) for perineal pain in the early postpartum period.

    Science.gov (United States)

    Molakatalla, Sujana; Shepherd, Emily; Grivell, Rosalie M

    2017-02-09

    Perineal trauma (due to spontaneous tears, surgical incision (episiotomy) or in association with operative vaginal birth) is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain and its effectiveness and safety should be assessed. To determine the efficacy of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. We searched Cochrane Pregnancy and Childbirth's Trials Register (30 August 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 May 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol/acetaminophen for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion in this review. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The quality of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. We included 17 RCTs, with 16 involving 1132 women randomised to aspirin or placebo (one RCT did not report numbers of women). Two RCTs (of 16) did not contribute data to review meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear due to poor

  1. SU-E-J-36: Combining CBCT Dose Into IMRT Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Grelewicz, Z; Wiersma, R [The University of Chicago, Chicago, IL (United States)

    2014-06-01

    Purpose: Cone beam CT (CBCT) is increasingly used in patient setup for IMRT. Daily CBCT may provide effective localization, however, it introduces concern over excessive imaging dose. Previous studies investigated the calculation of excess CBCT dose, however, no study has yet treated this dose as a source of therapeutic radiation, optimized in consideration of PTV and OARs constrains. Here we present a novel combined MV+kV inverse optimization engine to weave the CBCT and MV dose together such that CBCT dose is used for both imaging and therapeutic purposes. This may mitigate some of the excess imaging dose effects of daily CBCT and allow complete evaluation of the CBCT dose prior to treatment. Methods: The EGSnrc Monte Carlo system was used to model a Varian Trilogy CBCT system and 6 MV treatment beam. Using the model, the dose to patient from treatment beam and imaging beam was calculated for ten patients. The standard IMRT objective function was modified to include CBCT dose. Treatment plan optimization using the MOSEK optimization tool was performed retrospectively with and without assuming kV radiation dose from CBCT, assuming one CBCT per fraction. Results: Across ten patients, the CBCT delivered peaks of between .4% and 3.0% of the prescription dose to the PTV, with average CBCT dose to the PTV between .3% and .8%. By including CBCT dose to skin as a constraint during optimization, peak skin dose is reduced by between 1.9% and 7.4%, and average skin dose is reduced by .2% to 3.3%. Conclusions: Pre-treatment CBCT may deliver a substantial amount of radiation dose to the target volume. By considering CBCT dose to skin at the point of treatment planning, it is possible to reduce patient skin dose from current clinical levels, and to provide patient treatment with the improved accuracy that daily CBCT provides.

  2. Single dose myocardial protection technique utilizing del Nido cardioplegia solution during congenital heart surgery procedures.

    Science.gov (United States)

    Charette, K; Gerrah, R; Quaegebeur, J; Chen, J; Riley, D; Mongero, L; Corda, R; Bacha, E

    2012-03-01

    The single dose cardioplegia technique for myocardial protection during congenital heart surgery is a viable alternative to multidose protocols. Thirty-four pediatric patients with aortic cross clamp times greater than 90 minutes were grouped by modified adult (MA) multidose solution or del Nido (dN) single dose solution. Also, data from eight patients where the cross clamp times were greater than two hours on one dose of dN solution were included. In the 90-minute plus arm of the study, there were no significant differences between the groups when comparing the risk adjustment for congenital heart surgery (RACHS) (p=0.6), cardiopulmonary bypass times (CPB) (p=0.5), aortic cross camp times (p=0.5), weights (p=0.7) and number of intraoperative exogenous blood units (p=0.5). There were significant differences between the groups (p<0.05) in the number of cardioplegia doses and with perioperative glucose levels. In the greater than two hours group, the incidence of complete heart block (CHB) was 0.125% and there were no deaths or mechanical circulatory support (MCS) devices used. del Nido cardioplegia solution is a reasonable tool for myocardial protection during congenital heart surgery that significantly decreased the number of cardioplegic interventions and perioperative glucose values in our study groups.

  3. Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

    Directory of Open Access Journals (Sweden)

    Robinson William

    2011-04-01

    Full Text Available Abstract Background Melanoma and renal cell carcinoma (RCC are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies. Methods The records of patients with metastatic melanoma (n = 17 patients, 28 lesions or RCC (n = 13 patients, 25 lesions treated with SBRT were reviewed. Local control (LC was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED to characterize the dose-control relationship using a logistic tumor control probability (TCP model. Additionally, the kinetics of decline in maximum SUV (SUVmax were analyzed. Results The SBRT regimen was 40-50 Gy/5 fractions (n = 23 or 42-60 Gy/3 fractions (n = 30 delivered to lung (n = 39, liver (n = 11 and bone (n = 3 metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68. The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p max was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3. Conclusions An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.

  4. Optimization algorithm for absorbed dose calculation during single intake of 131І to rats

    Directory of Open Access Journals (Sweden)

    I. P. Drozd

    2016-02-01

    Full Text Available Original calculation algorithms are proposed for absorbed doses in the thyroid gland and thymus of rats at single income of 131I that enable to simplify the calculations and at the same time ensure high reliability of results in the range of input activities of 1 - 115000 Bq. According to the algorithms, the program is developed in the MATLAB environment, adapted for use on Windows running PC. Relative error of calculations is ±2 %.

  5. Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release Tablet.

    Science.gov (United States)

    Christopher, Ronald; Morgan, Mike; Ferry, Jim; Rege, Bhaskar; Tang, Yong; Kristensen, Allan; Shanahan, William

    2016-10-01

    Lorcaserin is a serotonin 2C receptor agonist indicated for chronic weight management as an adjunct to diet and exercise. The initial approved formulation is a 10-mg, immediate-release (IR) tablet for administration BID. These studies investigated the single- and multiple-dose pharmacokinetic properties of a new, recently US Food and Drug Administration-approved, extended-release, 20-mg once-daily formulation. We performed 2 separate 2-period, 2-sequence crossover studies in 36 healthy adults: a study comparing the IR formulation to the extended-release formulation under fasting conditions and a study comparing the extended-release formulation under fed and fasted conditions. Compared with lorcaserin IR, the T max after a single dose of lorcaserin extended-release was greater (median, 12 vs 3 hours), and the C max was 26% lower (38.8 vs 52.3 ng/mL). AUC data were bioequivalent for the 2 formulations in both single- and multiple-dose regimens, confirming no formulation effect on lorcaserin bioavailability. In fasted and fed conditions, T max after a single dose was identical (median, 12 hours), but C max was approximately 45% higher in the fed state (mean, 38.5 ng/mL fasted vs 56.1 ng/mL fed). However, at steady state, C max and AUC were determined to be bioequivalent between the fasted and fed states, indicating no clinically relevant food effect on the pharmacokinetic properties of lorcaserin extended-release. The safety profile was consistent between the 2 formulations. Overall, the results indicate that lorcaserin extended-release is a suitable once-daily alternative to the approved IR BID formulation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Lethal effect of a single dose of rasburicase in a preterm newborn infant.

    Science.gov (United States)

    Zaramella, Patrizia; De Salvia, Alessandra; Zaninotto, Martina; Baraldi, Maura; Capovilla, Giovanni; De Leo, Domenico; Chiandetti, Lino

    2013-01-01

    This case report describes a preterm newborn infant who was treated with a single dose of rasburicase for an increase in uric acid level. He died on the third day as a result of complications of hemolysis, which appeared to be precipitated by rasburicase. The patient's death was preceded by progressive respiratory insufficiency, lactic acidosis, and hyperbilirubinemia, culminating in refractory hypoxia and hypotension. A postmortem assay for glucose-6-phosphate dehydrogenase showed deficiency and the glucose-6-phosphate dehydrogenase Mediterranean genotype.

  7. Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children.

    Science.gov (United States)

    Kearns, G L; Reed, M D; Jacobs, R F; Ardite, M; Yogev, R D; Blumer, J L

    1991-01-01

    Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of CFB in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral CFB dose of either 4.5 or 9.0 mg/kg of body weight. CFB was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average CFB pharmacokinetic parameters (+/- standard deviations) were as follows: apparent elimination half-life, 2.0 +/- 0.5 h; mean residence time, 3.9 +/- 1.1 h; apparent steady-state volume of distribution, 0.4 +/- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5 +/- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P 10 years of age (2.0 +/- 0.6 ml/min/kg; P < 0.005). The increased CL/f for CFB (3.0 +/- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0 +/- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3 +/- 0.6 ml/min/kg) of CFB occurred in children, a

  8. THERE IS NO DIFFERENCE OF SURGICAL SITE INFECTION BETWEEN SINGLE-DOSE AND MULTIPLE-DOSE OF PROPHYLAXIS ANTIBIOTIC IN OPEN APPENDECTOMY OF NON-PERFORATED ACUTE APPENDICITIS

    Directory of Open Access Journals (Sweden)

    B Tiono

    2012-09-01

    Full Text Available Objective: Acute appendicitis is the most common surgical emergency encountered compared with other non-traumatic acute abdomens. Sanglah General Hospital recorded there were 470 cases of acute appendicitis in the year 2006. This study aims to determine the effectiveness of a single-dose antibiotic prophylaxis in prevention of surgical site infection in open appendectomy of non-perforated acute appendicitis. Method: A single blind randomized controlled trial in 110 nonperforated acute appendicitis patients that underwent open appendectomy at Sanglah General Hospital emergency operating theatre from April to June 2012 was conducted. Cefazolin 1 g and Metronidazole 500 mg were administered intravenously prior operation. Samples were divided intotwo groups by permuted block. Following operation, the single-dose group was administered placebo, while the multiple-dose group received two additional doses of antibiotics. Surgical site infection (SSI of both groups in every week for one month was evaluated. Surgical site infection wasdetermined based on Hulton’s criteria. Risk of surgical site infection of both groups was analyzed with Relative Risk (chi-square.Results: In the single-dose group 49.1% were males and 50.9% were females with a mean age of 28.71 years old, and in the multiple-dose group 40% were males and 60%were females with a mean age of 29.07 years old. Risk of SSI in single-dose group was 7.3% and multiple-dose group was 5.5% with Relative Risk (RR = 1.33% (95% CI RR: 0.31-5.68, p= 1.000.Conclusion: There is no difference of SSI risk between single and multiple-dose antibiotic prophylaxisinopen appendectomy of non-perforated acute appendicitis.

  9. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    Science.gov (United States)

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  10. Acute and persistent iatrogenic Cushing's syndrome after a single dose of triamcinolone acetonide.

    Science.gov (United States)

    Iglesias, P; González, J; Díez, J J

    2005-12-01

    Iatrogenic Cushing's syndrome is a well-known adverse effect of glucocorticoids. It usually develops after prolonged exposure to excessive amounts of synthetic glucocorticolds. The development of iatrogenic Cushing's syndrome (ICS) after a single and low dose of synthetic glucocorticoid is an exceptional event. Up to now, only a few number of cases have been associated with triamcinolone acetonide and they have always been related to local administration. We report, for the first time, a patient who developed ICS after a single low dose of parenterally (im) administered triamcinolone acetonide. She was a 45-yr-old woman who referred to us because of cushingoid appearance, whose hormonal determinations were suggestive of secondary adrenal insufficiency. Clinical features were developed one month after the administration of a 40 mg single-dose of im triamcinolone acetonide because of acute laryngitis. Endocrinological evaluation confirmed the hypothalamic-pituitary-adrenal (HPA) axis suppression. Eight months later, cushingoid phenotype had completely disappeared and HPA function had spontaneously recovered. We review clinical features and comment on the possible pathogenic mechanisms of this particular and new form of ICS.

  11. Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs.

    Science.gov (United States)

    Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders; Herrero-Fresno, Ana; Larsen, Inge; Holm, Anders; Nielsen, Jens Peter; Christiansen, Lasse Engbo; Angen, Øystein; Ahmed, Shahana; Folkesson, Anders; Olsen, John Elmerdahl

    2017-06-15

    production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment. Copyright © 2017 American Society for Microbiology.

  12. Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs

    Science.gov (United States)

    Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders; Herrero-Fresno, Ana; Larsen, Inge; Holm, Anders; Nielsen, Jens Peter; Christiansen, Lasse Engbo; Angen, Øystein; Ahmed, Shahana

    2017-01-01

    livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment. PMID:28389548

  13. A phase I open-label study to investigate the potential drug-drug interaction between single-dose dacomitinib and steady-state paroxetine in healthy volunteers.

    Science.gov (United States)

    Ruiz-Garcia, Ana; Giri, Nagdeep; LaBadie, Robert R; Ni, Grace; Boutros, Tanya; Richie, Nicole; Kocinsky, Hetal S; Checchio, Tina M; Bello, Carlo L

    2014-05-01

    Dacomitinib is currently in development for the treatment of non-small cell lung cancer. Formation of the major circulating metabolite (PF-05199265) is mediated by cytochrome P450 (CYP) 2D6 and CYP2C9. This phase I, single fixed-sequence, two-period study evaluated the effect of paroxetine, a CYP2D6 inactivator, on dacomitinib pharmacokinetics in healthy volunteers who were extensive CYP2D6 metabolizers. Subjects received a single 45-mg dacomitinib dose alone and in combination with paroxetine (30 mg/day for 10 consecutive days, with dacomitinib administered on day 4) at steady-state levels. Blood samples were collected through 240 hours post-dacomitinib dosing. Dacomitinib exposure (area under the concentration-time curve from 0 to infinity; AUCinf) increased 37%; however a reduction in PF-05199265 AUCinf of approximately 90% was observed during the paroxetine treatment period. The maximum concentration of dacomitinib changed minimally. Adverse events reported with single-dose dacomitinib administered alone or in the presence of steady-state levels of paroxetine were mostly mild, and no serious adverse events were reported. While paroxetine significantly inhibited CYP2D6-mediated metabolism of a single dose of dacomitinib, the modest effect on dacomitinib exposure is unlikely to be clinically relevant when dacomitinib is given daily. Dose adjustment of dacomitinib may therefore not be required upon coadministration with a CYP2D6 inhibitor. © 2013, The American College of Clinical Pharmacology.

  14. Treatment planning using MRI data: an analysis of the dose calculation accuracy for different treatment regions

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    Karlsson Mikael

    2010-06-01

    Full Text Available Abstract Background Because of superior soft tissue contrast, the use of magnetic resonance imaging (MRI as a complement to computed tomography (CT in the target definition procedure for radiotherapy is increasing. To keep the workflow simple and cost effective and to reduce patient dose, it is natural to strive for a treatment planning procedure based entirely on MRI. In the present study, we investigate the dose calculation accuracy for different treatment regions when using bulk density assignments on MRI data and compare it to treatment planning that uses CT data. Methods MR and CT data were collected retrospectively for 40 patients with prostate, lung, head and neck, or brain cancers. Comparisons were made between calculations on CT data with and without inhomogeneity corrections and on MRI or CT data with bulk density assignments. The bulk densities were assigned using manual segmentation of tissue, bone, lung, and air cavities. Results The deviations between calculations on CT data with inhomogeneity correction and on bulk density assigned MR data were small. The maximum difference in the number of monitor units required to reach the prescribed dose was 1.6%. This result also includes effects of possible geometrical distortions. Conclusions The dose calculation accuracy at the investigated treatment sites is not significantly compromised when using MRI data when adequate bulk density assignments are made. With respect to treatment planning, MRI can replace CT in all steps of the treatment workflow, reducing the radiation exposure to the patient, removing any systematic registration errors that may occur when combining MR and CT, and decreasing time and cost for the extra CT investigation.

  15. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

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    Satoshi Takahashi

    2014-04-01

    Full Text Available To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33. The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43 and 37.2% (16/43, respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50. The microbiological eradication rates for the pathogens were 90.9% (30/33 for Neisseria gonorrhoeae, 91.5% (43/47 for Chlamydia trachomatis, 71.4% (5/7 for Mycoplasma genitalium, and 100% (13/13 for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120. The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  16. Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus

    Directory of Open Access Journals (Sweden)

    Donnan Alison A

    2011-03-01

    Full Text Available Abstract Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days, the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum.

  17. Single versus double dose praziquantel comparison on efficacy and Schistosoma mansoni re-infection in preschool-age children in Uganda

    DEFF Research Database (Denmark)

    Nalugwa, Allen; Nuwaha, Fred; Tukahebwa, Edridah Muheki

    2015-01-01

    (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially......BACKGROUND: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel......, abdominal pain and bloody diarrhea. Overall re-infection rate 8 months post treatment was 44.5%. CONCLUSIONS: PZQ is efficacious and relatively safe to use in preschool-age children but there is still an unmet need to improve its formulation to suit small children. Two PZQ doses lead to significant...

  18. [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

  19. 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.

  20. Single- and repeated-dose toxicities of aloe fermentation products in rats

    Science.gov (United States)

    Kim, Hyun-Kyoung; Baik, Soon-Ok; Choi, Soo-Young; Lee, Jae-Young

    2011-01-01

    In this study, aloe fermentation products were derived from mycelia from 3 mushrooms: Ganoderma lucidum (AG), Hericium erinaceum (AH), and Phellinus linteus (AP). Levels of aloin A and B increased with fermentation time. The highest levels were measured on the fifth day of fermentation. β-Glucan levels decreased with fermentation time. The safety of aloe fermentation products were examined in male and female Sprague-Dawley rats. Rats were orally administered the three aloe fermentation products at dose levels of 1, 2 or 5 g/kg for single-dose toxicity test and 0.5, 1, or 2 g/kg for repeated-dose toxicity test. There were no significant differences in body weight gain between vehicle control and AG-, AH- or AP-treated rats. Also, significant changes in daily feed intake and water consumption were not observed. In hematological analysis, none of the parameters were affected by aloe fermentation products with mushroom mycelia. This suggests that there are no negative effects on homeostasis and immunity. In blood biochemistry analysis, none of the markers were affected by feeding rats with AG, AH or AP. Similarly, there were no significant effects on markers for liver, kidney, skeletal and heart muscle functions. No remarkable lesions were observed in these organs at histopathology. Since there were no adverse effects of AG, AH and AP in single- or repeated-dose toxicity tests, even at higher doses than normal, we conclude that the aloe fermentation products with mushroom mycelia possess long-term safety and could be candidates as multifunctional nutrients for the improvement of intestinal function and immunity. PMID:21998613

  1. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: a geographical comparison from a single arm, open-label study.

    Science.gov (United States)

    Rubio-Aurioles, Eusebio; Glina, Sidney; Abdo, Carmita H N; Hernandez-Serrano, Ruben; Rampazzo, Claudia; Sotomayor, Mariano; West, Teena M; Gallagher, Gabrielle L; Lenero, Enrique

    2009-10-01

    Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of > or =6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use.

  2. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.

    Science.gov (United States)

    Kim, Yo Han; Choi, Hee Youn; Lim, Hyeong-Seok; Lee, Shi Hyang; Jeon, Hae Sun; Hong, Donghyun; Kim, Seong Su; Choi, Young Kweon; Bae, Kyun-Seop

    2015-01-01

    Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer's disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), or 175 mg/50 cm(2). Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch) were assessed throughout the study. The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax) and the area under the curve (AUC) increased in a dose-proportional manner. Median time to Cmax was ~74-76 hours (~2-4 hours after patch removal), and mean t1/2β was ~63.77-93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%-86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. The donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics.

  3. Benign painful shoulder syndrome. Initial results of a single-center prospective randomized radiotherapy dose-optimization trial

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    Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Department of Radiation Oncology

    2012-12-15

    Background and purpose: To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome. Patients and methods: Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). Results: The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 {+-} 23.7 and 53.2 {+-} 21.8 (p = 0.158), 38.2 {+-} 26.1 and 34.0 {+-} 24.5 (p = 0.189), and 33.0 {+-} 27.2 and 23.7 {+-} 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 {+-} 3.0 and 9.5 {+-} 2.7 (p = 0.309), 6.1 {+-} 3.6 and 5.4 {+-} 3.6 (p = 0.096), 5.3 {+-} 3.7 and 4.1 {+-} 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380). Conclusion: Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  4. Benign painful shoulder syndrome: initial results of a single-center prospective randomized radiotherapy dose-optimization trial.

    Science.gov (United States)

    Ott, O J; Hertel, S; Gaipl, U S; Frey, B; Schmidt, M; Fietkau, R

    2012-12-01

    To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome. Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.158), 38.2 ± 26.1 and 34.0 ± 24.5 (p = 0.189), and 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.309), 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.096), 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380). Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy.

  5. Generation of composite dose and biological effective dose (BED) over multiple treatment modalities and multistage planning using deformable image registration.

    Science.gov (United States)

    Zhang, Geoffrey; Huang, Tzung-Chi; Feygelman, Vladimir; Stevens, Craig; Forster, Kenneth

    2010-01-01

    Currently there are no commercially available tools to generate composite plans across different treatment modalities and/or different planning image sets. Without a composite plan, it may be difficult to perform a meaningful dosimetric evaluation of the overall treatment course. In this paper, we introduce a method to generate composite biological effective dose (BED) plans over multiple radiotherapy treatment modalities and/or multistage plans, using deformable image registration. Two cases were used to demonstrate the method. Case I was prostate cancer treated with intensity-modulated radiation therapy (IMRT) and a permanent seed implant. Case II involved lung cancer treated with two treatment plans generated on two separate computed tomography image sets. Thin-plate spline or optical flow methods were used as appropriate to generate deformation matrices. The deformation matrices were then applied to the dose matrices and the resulting physical doses were converted to BED and added to yield the composite plan. Cell proliferation and sublethal repair were considered in the BED calculations. The difference in BED between normal tissues and tumor volumes was accounted for by using different BED models, alpha/beta values, and cell potential doubling times. The method to generate composite BED plans presented in this paper provides information not available with the traditional simple dose summation or physical dose summation. With the understanding of limitations and uncertainties of the algorithms involved, it may be valuable for the overall treatment plan evaluation. 2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  6. Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients.

    Science.gov (United States)

    Zhu, Tong; Keirns, James; Howieson, Corrie; Kaibara, Atsunori; Goldwater, Ronald; Kivitz, Alan J; Chindalore, Vishala; Cohen, Stanley; Santos, Vicki; Akinlade, Bolanle; Kernstock, Robert; Delgado-Herrera, Leticia; Blahunka, Paul C; Karrer, Erik E; Garg, Jay P; Samberg, Nancy; Zeiher, Bernhardt G

    2016-09-01

    ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half-life with increasing doses, consistent with target-mediated disposition. The apparent bioavailability was 36.3%-56.7% across single subcutaneous doses. Sixteen RA patients (n = 8/treatment) on stable methotrexate received 3 × 3.0 mg/kg subcutaneously every 4 weeks or every 2 weeks. Similar to single-dose treatment, ASP2408 concentrations peaked 2 to 3 days postdose, with a median t1/2 of approximately 8 days. Using CD86 receptor occupancy (RO) as a mechanistic biomarker, ASP2408 demonstrated dose-dependent binding to its target. ASP2408 3.0 mg/kg subcutaneously every 4 weeks and every 2 weeks led to a mean %CD86 RO ≥ 74.7% and ≥ 81.5%, respectively, within each dosing interval. ASP2408 was well tolerated across studies with no evidence of dose-limiting toxicity or clinically significant changes in clinical laboratory test results, vital signs, or 12-lead electrocardiograms. ASP2408 elicited antidrug antibodies in the majority of patients, but with no clinical sequelae. © 2016, The American College of Clinical Pharmacology.

  7. Myocardial damage following cardiac surgery: comparison between single-dose Celsior cardioplegic solution and cold blood multi-dose cardioplegia.

    Science.gov (United States)

    Giordano, P; Scrascia, G; D'Agostino, D; Mastro, F; Rotunno, C; Conte, M; Rociola, R; Paparella, D

    2013-11-01

    Myocardial protection during cardiac surgery can be accomplished by different cardioplegic solutions. The aim of this study was to assess myocardial damage after heart valve surgery performed with myocardial protection of a single dose of Celsior cardioplegia or with repeated cold blood cardioplegia. After the stratification of 139 valvular patients by means of matching according to cross-clamp and cardiopulmonary bypass time, 32 patients were retained for comparison (16 patients received Celsior and 16 patients received cold blood cardioplegia). Creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) release were evaluated until six days after the operation. Pre-operative characteristics were similar in both groups. In the Celsior group, CK-MB and cTnI values were significantly higher from the first up to the sixth post-operative day. Peak cTnI values were 19.4 ± 13.4 and 9.7 ± 7 ng/mL (p=0.01) in the Celsior and the Cold Blood group, respectively. Peak CK-MB values were 79.6 ± 58.8 and 45.9 ± 20.6 U/L (p=0.07) in the Celsior and the Cold Blood group, respectively. Cold blood cardioplegia reduces perioperative myocardial damage compared to the Celsior solution in elective cardiac valve operations.

  8. Single dose of 1% tropicamide and 10% phenylephrine for pupil dilation.

    Science.gov (United States)

    Ratanapakorn, Tanapat; Yospaiboon, Yosanan; Chaisrisawadsuk, Natthira

    2006-11-01

    To compare the efficacy of pupil dilation between a single dose and three doses of 1% tropicamide and 10% phenylephrine for binocular indirect ophthalmoscopy. A prospective randomized double-blind clinical controlled trial was conducted. All patients underwent the binocular indirect ophthalmoscopy and met the inclusion criteria were randomized into two groups using block randomization. Group A received a single dose of 1% tropicamide and 10% phenylephrine eye drops, and Group B received three doses of the same drugs. The primary outcome was the horizontal pupil diameter measured by slit-lamp biomicroscope (Haag-Streit model 900) before and at 10, 15, 20, 25 and 30 minutes after eye drop instillation. The clinical equivalence of the efficacy of pupil dilation between the two groups was defined as the difference of less than or equal to 1 mm (-1 mm to + 1 mm). Eighty patients (160 eyes) were randomized into 40 patients (80 eyes) in group A and 40 patients (80 eyes) in group B. The mean pupil sizes at baseline of group A were 3.51 +/- 0.63 mm in the right eye and 3.39 +/- 0.67 mm in the left eye. Those in group B were 3.61 +/- 0.67 mm in the right eye and 3.66 +/- 0.72 mm in the left eye. The mean pupil diameters at 30 minutes of group A were 7.34 +/- 0.51 mm in the right eye and 7.41 +/- 0.56 mm in the left eye, whereas those of group B were 7.49 +/- 0.45 mm in the right eye and 7.51 +/- 0.40 mm in the left eye. The mean difference of the pupil size between the two groups was 0.15 mm (p = 0.175) in the right eye and 0.l0 mm (p = 0.362) in the left eye. The 95% confidence intervals of the difference in pupil size were -0.36 to 0.07 mm in the right eye and -0.32 to 0.12 mm in the left eye. The 95% confidence interval of the difference in pupil size lay entirely within the range of equivalence. The single dose of 1% tropicamide and 10% phenylephrine was clinically equivalent to the three doses of the same drugs.

  9. Comparison the Analgesic Effects of Single Dose Administration of Tramadol or Piroxicam on Postoperative Pain after Cesarean Delivery

    Directory of Open Access Journals (Sweden)

    Amir Farshchi

    2010-05-01

    Full Text Available "nA multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. We investigated postoperative pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and µ-opioid agonist tramadol, 100 mg (Group T and piroxicam 20 mg (Group P given IM alone- single dose in 150 patients who had elective cesarean delivery. All patients were assessed at 0, 6, 12 and 24 hours post operation for pain degree (by Visual Analogue Score: VAS 1-10, nausea and vomiting. Pain degree was classified as: Painless: 0, Mild: 1-4, Moderate: 5-8, Severe: 9-10. There was no significant difference between the efficacy of tramadol and piroxicam injections (P>0.05. Pain intensity decreased markedly over time in both groups. Mean±SEM pain degrees were as follows: P=7.7±0.5, T=8.2±0.8 after 0 hours; P=5.4±0.6, T=6.1±0.5 after 6 hours; P=3.3±0.4, T=3.4±0.7 after 12 hours; P=1.1±0.4, T=1.3±0.5 after 24 hours of surgery. Side effects were similarly minimal with all treatments. It might be concluded that i.m. injections of 20 mg piroxicam (single dose therapy could relieve postoperative pain after cesarean section as well as tramadol and it could reduce opioid analgesic requirements with less adverse side effects during the first postoperative 24 h.

  10. Comparison the analgesic effects of single dose administration of tramadol or piroxicam on postoperative pain after cesarean delivery.

    Science.gov (United States)

    Farshchi, Amir; Ghiasi, Golbarg

    2010-01-01

    A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. We investigated postoperative pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and mu-opioid agonist tramadol, 100 mg (Group T) and piroxicam 20 mg (Group P) given IM alone--single dose in 150 patients who had elective cesarean delivery. All patients were assessed at 0, 6, 12 and 24 hours post operation for pain degree (by Visual Analogue Score: VAS 1-10), nausea and vomiting. Pain degree was classified as: Painless: 0, Mild: 1-4, Moderate: 5-8, Severe: 9-10. There was no significant difference between the efficacy of tramadol and piroxicam injections (P > 0.05). Pain intensity decreased markedly over time in both groups. Mean +/- SEM pain degrees were as follows: P = 7.7 +/- 0.5, T = 8.2 +/- 0.8 after 0 hours; P=5.4 +/- 0.6, T = 6.1 +/- 0.5 after 6 hours; P=3.3 +/- 0.4, T = 3.4 +/- 0.7 after 12 hours; P = 1.1 +/- 0.4, T = 1.3 +/- 0.5 after 24 hours of surgery. Side effects were similarly minimal with all treatments. It might be concluded that i.m. injections of 20 mg piroxicam (single dose therapy) could relieve postoperative pain after cesarean section as well as tramadol and it could reduce opioid analgesic requirements with less adverse side effects during the first postoperative 24 h.

  11. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy.

    Science.gov (United States)

    Naviaux, J C; Schuchbauer, M A; Li, K; Wang, L; Risbrough, V B; Powell, S B; Naviaux, R K

    2014-06-17

    Autism spectrum disorders (ASDs) now affect 1-2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg(-1) intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 μM pmol μl(-1) (±0.50) and 5.15 pmol mg(-1) (±0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults.

  12. Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage following grass pollen challenge.

    Science.gov (United States)

    Erin, E M; Leaker, B R; Zacharasiewicz, A S; Higgins, L A; Williams, T J; Boyce, M J; de Boer, P; Durham, S R; Barnes, P J; Hansel, T T

    2005-12-01

    Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.

  13. Ovarian development in Wistar rat treated prenatally with single dose diisobutyl phthalate.

    Science.gov (United States)

    Ray, B; D'Souza, A S; Kumar, V; Pugazhandhi, B; D'Souza, M R; Nayak, D; Sushma, R K; Shetty, P; Singh, H; Krishna, L; Bhat, K M; Rao, A C; Chakraborti, S; Kumar, N; Saxena, A

    2012-01-01

    Phthalates are a class of industrial compounds with an array of toxicological properties used in day to day life. Diisobutyl phthalate on (DIBP) is used as an additive to keep the plastics soft or flexible (plasticizer) in nitrocellulose plastic, nail polish, explosives, lacquer manufacturing etc. Although DIBP exposure in humans is generally low, people in adhesive industries and pharmaceutical industries are exposed to higher levels. The aim of this study was to determine the effect of single dose of DIBP on developing ovary of Wistar rat. One hundred and eight adult pregnant Wistar rats were divided into control and experimental groups. Rats in experimental group were given DIBP on day 10, 12 and 14 of gestation at 0.375, 0.75 and 1.25 ml/kg body weight dose intraperitoneally in a single dose. Sections of ovaries collected on day 21 of gestation were stained with hematoxylin and eosin and examined and Masson's trichrome histologically. Sections belonging to the control group showed the presence of oocytes in clusters separated by thin fibrous septa. Degeneration oocytes, empty follicles surrounded by follicular cells without gonocytes in the center were observed in ovarian stroma. Blood vessels in the ovarian stroma were prominent and congested. Around a bunch of follicles total architectural disarray was observed although on special staining fibrosis was not evident. As pregnant women are constantly exposed, effect of DIBP on ovary of a developing fetus would denote the long term consequence in future generations (Fig. 5, Ref. 39).

  14. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  15. A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

    Science.gov (United States)

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

    2017-05-01

    MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The

  16. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Pharmacokinetics of (/sup 14/C)teicoplanin in male rats after single intravenous dose

    Energy Technology Data Exchange (ETDEWEB)

    Bernareggi, A.; Cavenaghi, L.; Assandri, A.

    1986-11-01

    The pharmacokinetic profile of (/sup 14/C)teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total /sup 14/C in plasma was similar to that of the microbiological activity. The cumulative recovery of total /sup 14/C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of (/sup 14/C)teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen.

  18. Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

    Science.gov (United States)

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-01-01

    Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio® treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  19. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  20. Dose Mapping after Endoradiotherapy with (177)Lu-DOTATATE/-TOC by One Single Measurement after Four Days.

    Science.gov (United States)

    Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

    2017-06-06

    Dosimetry of organs and tumors helps to assess risks and benefit of treatment with (177)Lu-DOTATATE/ TOC. However, it is often not performed in clinical routine because of additional efforts, the complexity of data collection and analysis, and the additional burden for the patients. Aiming at a simplification of dosimetry, we analyzed the accuracy of a theoretically substantiated approximation, which allows to calculate absorbed doses from a single measurement of the abdominal activity distribution. Methods: Activity kinetics were retrospectively assessed from planar images in 29 patients with neuroendocrine tumors (NET, n = 21) or meningioma (n = 8) after the administration of (177)Lu-DOTATATE (n = 22) or (177)Lu-DOTATOC (n = 7). Mono- or bi-exponential functions were fitted to measured data in 54 kidneys, 25 livers, 27 spleens, and 30 NET lesions. It was evaluated for each fit function how well the integral over time was represented by an approximation calculated as the product of the time tl of a single measurement, the expected reading at time tl, and the factor 2/ln(2). Tissue specific deviations of the approximation from the time integral were calculated for time points tl = 24, 48, 72, 96, 120, and 144 hours. Results: Correlation between time integral and approximation improved with increasing time tl. Pearson's r exceeded 0.95 for tl ≥ 96 hours in all tissues. Lowest maximum errors were observed at tl = 96 hours with deviations of the approximation from the time integral of median +5% (range, -9% to +17%) for kidneys, +6% (range, -7% to +12%) for livers, +8% (range, +2% to +20%) for spleens, and +6% (range, -11% to +16%) for NET lesions. Accuracy is reduced for measurements after 72 or 120 hours. For measurements after 24, 48, and 144 hours, the approximation leads to large deviations for some of the patients, in particular unacceptable underestimates of the absorbed dose to the kidneys. Conclusion: A single quantitative measurement of the abdominal

  1. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris.

    Science.gov (United States)

    Blasiak, Rachel C; Stamey, Christopher R; Burkhart, Craig N; Lugo-Somolinos, Aida; Morrell, Dean S

    2013-12-01

    Isotretinoin is the most effective treatment for acne. The ideal dosing regimen is unknown. To determine the rates of relapse of acne vulgaris and retrial of isotretinoin after high cumulative-dose treatment and the changes to the adverse effect profile. A prospective, observational, intervention study was conducted from August 1, 2008, to August 31, 2010, in a single academic tertiary care center with multiple providers. A total of 180 patients with acne resistant to other treatments were enrolled. Of these, 116 participated in the 12-month follow-up survey, for a response rate of 64.4%. Patients received isotretinoin, with dosing based on the providers' judgment. Patients were divided into 2 groups on the basis of cumulative dosing (treatment with a prescription topical or oral acne medication after a course of isotretinoin) or retrial (retreatment with isotretinoin) at 12-month follow-up and adverse effects experienced during and after 12 months of treatment. RESULTS The mean age of the participants was 19.3 years, 51.9% were female, and 74.1% were white. At 12 months' follow-up, 97.4% of the patients reported that their acne was improved. Overall, acne in 32.7% of patients in the study relapsed at 12 months, and 1.72% of the patients required a retrial. In the lower-dose treatment group (treatment groups developed cheilitis and xerosis during treatment. Retinoid dermatitis was significantly more common in the high-dose treatment group (53.8% vs 31.6%; P = .02). None of the other adverse effects was significantly different between the 2 groups. The dosing regimen used in the present study is considerably higher than that used in previous studies of isotretinoin. At 1 year after completion of isotretinoin treatment, we found that patients receiving 220 mg/kg or more had a significantly decreased risk of relapse. Rash was the only adverse effect that was significantly more common in the high-dose group during treatment. This study suggests that significantly

  2. Single dose oral analgesics for postoperative pain have few adverse events.

    Science.gov (United States)

    Wong, Yin J

    2016-09-01

    Data sourcesThe Cochrane Database of Systematic Reviews on the Cochrane Library.Study selectionAll Cochrane reviews of RCTs between 1999 to 2015, conducted in adults examining the adverse events associated with single dose oral analgesics used for acute post-operative pain were considered.Data extraction and synthesisStudies were searched, reviewed and assessed independently by two reviewers and standard data items extracted. Methodological quality was assessed using criteria adapted from AMSTAR (Assessing the Methodological Quality of Systematic Reviews).ResultsData from 39 Cochrane reviews of 41 different analgesics or analgesic combinations involving a total of 350 studies involving 35,000 adults were included. Most analgesics were tested in a narrow dose range. For most NSAIDs, paracetamol (acetaminophen), and combinations not containing opioids, the rates of adverse events were similar to that of placebos (NSAID 3% - 44% vs 4 - 46%; paracetamol 7-18% vs 6-16%; combination 11-30% vs 6-48%). However, for higher dosages, like 1000 mg aspirin, 1000 mg diflunisal, and opioids or drug combinations containing opioids, there was a statistically significant difference in the incidence of adverse events reported (NNH 7.7(95%CI; 4.8 - 20) for 1000 mg aspirin; 7.5(95%CI; 4.8-17) for 1000 mg diflunisal; 3.5-8.6 for opioids and combinations). Serious adverse events were rare, occurring at about 1 in 3,200.ConclusionsDespite ongoing problems with the measurement, recording and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.

  3. Benzodiazepine dependence and its treatment with low dose flumazenil.

    Science.gov (United States)

    Hood, Sean David; Norman, Amanda; Hince, Dana Adelle; Melichar, Jan Krzysztof; Hulse, Gary Kenneth

    2014-02-01

    Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  4. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Science.gov (United States)

    Ferrer, Patricia; Tripathi, Abhai K; Clark, Martha A; Hand, Carla Cerami; Rienhoff, Hugh Young; Sullivan, David J

    2012-01-01

    Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S)3"-(HO)-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50)) of 6 µM for Plasmodium falciparum in contrast to the IC(50) for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  5. Pharyngeal Gonorrhea in female sex workers: Response to a single 2-g dose of azithromycin.

    Science.gov (United States)

    Dan, Michael; Poch, Francesca; Amitai, Ziva; Gefen, Dana; Shohat, Tamy

    2006-08-01

    A sharp increase in the incidence of gonorrhea has been observed in Tel Aviv, Israel, since 1999. Almost one half of interviewed patients admitted contracting the infection from a sex worker. In two thirds of the cases, oral sex (fellatio) was the most probable route of acquiring the disease. In the current study, we assessed the prevalence of pharyngeal gonorrhea among sex workers in Tel Aviv and evaluated the efficacy of a single 2-g dose of azithromycin in eradicating the infection. Throat specimens were obtained for gonococcal culture from 301 female sex workers practicing in brothels. A questionnaire covering demographic and sexual behavior information was administered to all participants, and a single 2-g dose was administered orally under supervision. Women with positive cultures were reexamined a week later for eradication of Neisseria gonorrhoeae. N gonorrhoeae was isolated from 27 women (9%). The median age of women with pharyngeal gonorrhea was 23 years (range, 18-32 years); 85% were born in former Soviet Union (mostly Russia, Ukraine, Moldavia). Regular condom use in vaginal sex was reported by 88% of the participants, whereas only 60% reported always using condoms in oral sex. All isolates were susceptible to azithromycin (MIC < or = 0.5 microg/ml). Gonococci were eradicated in 20/21 individuals (95%). A high carriage rate of gonococci in the throat and a low rate of condom use in oral sex were documented among sex workers in Tel Aviv. A single 2 g dose of azithromycin was very effective in eradicating gonococci from the throat.

  6. Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men

    Science.gov (United States)

    Liem-Moolenaar, Marieke; Rad, Mandana; Zamuner, Stefano; Cohen, Adam F; Lemme, Francesca; Franson, Kari L; van Gerven, Joop M A; Pich, Emilio Merlo

    2011-01-01

    AIM Several lines of evidence suggest a possible role of 5-HT6receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT6 antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P = 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P = 0.016). No significant effects of SB-742457 alone were found. CONCLUSION The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established. PMID:21223356

  7. Intravenous Hydroxypropyl β-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial.

    Science.gov (United States)

    Erb-Zohar, K; Kropeit, D; Scheuenpflug, J; Stobernack, H-P; Hulskotte, Egj; van Schanke, A; Zimmermann, H; Rübsamen-Schaeff, H

    2017-07-04

    Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two-part, single-center, randomized, double-blind, placebo-controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl β-cyclodextrin (HPβCD)-based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once-daily doses (240 mg; 8 letermovir, 4 placebo) of HPβCD-formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single-dose and multiple-dose regimens were generally well tolerated. Single-dose escalation resulted in a slightly more-than-dose-proportional increase in the area under the letermovir plasma concentration-time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (Cmax ) was dose proportional. After once-daily dosing, accumulation ratios in AUC and Cmax were 1.22 and 1.03, respectively. The terminal half-life was 28.3 h, supporting once-daily dosing (EudraCT Number: 2012-001603-20). © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  8. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2017-05-25

    This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50

  9. Using the OSL single-aliquot regenerative-dose protocol with quartz extracted from building materials in retrospective dosimetry

    DEFF Research Database (Denmark)

    Bøtter-Jensen, L.; Solongo, S.; Murray, A.S.

    2000-01-01

    We report on the application of the single-aliquot regenerative-dose (SAR) protocol to the optically stimulated luminescence signal from quartz extracted from fired bricks acid unfired mortar in retrospective dosimetry. The samples came from a radioactive materials storage facility, with ambient...... dose rates of about 0.1 mGy/h. A detailed dose-depth profile was analysed from one brick, and compared with dose records from area TL dosemeters. Small-aliquot dose-distributions were analysed from the mortar samples; one associated with the exposed brick, and one from a remote site exposed only...

  10. Single- and multiple-dose pharmacokinetics and tolerability of a paroxetine controlled-release tablet in healthy Chinese subjects
.

    Science.gov (United States)

    Chen, Rui; Shen, Kai; Hu, Pei

    2017-03-01

    To evaluate the pharmacokinetics of paroxetine controlled-release (CR) tablets after single and multiple oral administrations and to evaluate its safety profile in healthy Chinese subjects. This was a phase 1, open-label, single- and multiple-dose combined study. All 12 healthy subjects received a single oral dose of 25-mg paroxetine CR, followed by a washout period of 5 days. Then, the subjects received multiple oral doses of 25-mg paroxetine CR for 14 consecutive days. Serial venous blood samples were collected 96 hours after single dosing and 24 hours after the last dose in multiple-dosing. Blood samples were analyzed using LC-MS/MS. Pharmacokinetic parameters of paroxetine were calculated via noncompartmental analysis using the WinNonlin software (Pharsight Corp., Mountain View, CA, USA). For both single- and multiple-dose regimens, a lag time of ~ 4 hours was observed before the absorption of paroxetine CR tablet with a tmax of ~ 7 - 9 hours. From single- to multiple-dose regimens, the mean Cmax increased from 7.08 to 36.95 ng/mL, the mean AUC0-24h increased from 100.91 to 706.75 h×ng/mL, and the mean t1/2 increased from 12.3 to 83.6 hours (all p trough ratio indicated that the concentration of paroxetine reached steady state after 14 days of repeated dosing. The point estimate of the accumulation factor indicated that the extent of drug exposure at steady state was ~ 9 times that of single dosing. All reported adverse events were considered to be mild. Paroxetine CR tablet is absorbed with a delay of ~ 4 hours after oral administration, and the accumulation factor is ~ 9 at steady state. Paroxetine CR tablet is well tolerated by healthy Chinese subjects.
.

  11. Pharmacokinetics of a single oral dose of baclofen in pediatric patients with gastroesophageal reflux disease.

    Science.gov (United States)

    Wiersma, H E; van Boxtel, C J; Butter, J J; van Aalderen, W M C; Omari, T; Benninga, M A

    2003-02-01

    Transient relaxation of the lower esophageal sphincter (TLESR) is the predominant mechanism of gastroesophageal reflux (GER) in adults and children. Baclofen [4-amino-3-(p-chlorophenyl)-butanoic acid], a gamma-aminobutyric acid (GABA)-B receptor agonist used for the management of spasticity, has been recently shown to significantly inhibit GER in healthy adults without any relevant side effects. The objective of this study was to evaluate the pharmacokinetics of baclofen in a pediatric population with GER disease. In an open-label single-dose pharmacokinetic study, eight children with the diagnosis of GER made on clinical grounds received an oral dose of baclofen, 2.5 mg. Blood samples were drawn from an indwelling venous catheter, and urine was collected during a postdose period of 8 hours. The concentration of baclofen in these body fluids was determined using a validated high-performance liquid chromatography (HPLC) method with electrochemical detection after OPA-sulfite derivatization. Pharmacokinetic data were analyzed using the nonlinear regression program Scientist. Serum concentration-time curves could be best described using a two-compartment open model with a lag time. Mean plasma clearance (Cl) was 315.9 mL/h/kg; volume of distribution (Vd) was 2.58 L/kg; and half-life (T(1/2)beta) was 5.10 hours. No side effects were noted. As half-lives were comparable with those found in adult studies, the risk for accumulation seems not greater in children than in adults. Body composition can have a strong influence on the Vd of baclofen and, therefore, on the dose needed to obtain therapeutic plasma levels. Dosing according to clearly defined age groups with the help of therapeutic drug monitoring seems preferable. In view of the negative correlation between body weight and Vd, dosing according to body weight using adult pharmacokinetic data does not seem an effective way for using baclofen in children.

  12. The Occurrence of Priapism as a Result of the Use of a Single Dose of Quetiapine

    OpenAIRE

    Ozkaya, Fatih; Ziypak, Tevfik; Adanur, Senol; Yucel, Atakan; Aydinoglu, Unsal

    2012-01-01

    Priapism is a prolonged pathologic erection situation that occurs after sexual stimulation or without sexual stimulation. This condition is divided into two types, ischemic (low-flow, veno-occlusive) and non-ischemic (high-flow, arterial). A 68-year-old male patient applied to our clinic with the complaints of hardness and pain in the penis. Three days before he applied to our clinic, he was prescribed a single dose of 200 mg quetiapine by a psychiatry polyclinic for the complication of insom...

  13. A luminescence imaging system for the routine measurement of single-grain OSL dose distributions

    DEFF Research Database (Denmark)

    Kook, Myung Ho; Lapp, Torben; Murray, Andrew

    2015-01-01

    In optically stimulated luminescence (OSL) dating and other retrospective dosimetry studies there is considerable demand for the ability to measure luminescence from individual dosimeters in the size range 50e500 mm diameter, either as separate grains or as part of a matrix. This work tests...... the potential of an electron multiplying charge-coupled device (EMCCD), providing extremely low level light detection. We characterize the performance of the device by discussing reproducibility and evaluating uncertainties in OSL signals. Finally we derive a typical single grain natural dose distribution...

  14. Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

    Directory of Open Access Journals (Sweden)

    Wust Peter

    2010-05-01

    Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

  15. TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Pinkham, D.W.; Shultz, D.; Loo, B.W.; Sung, A.; Diehn, M.; Fahimian, B.P. [Stanford University, Stanford, CA (United States)

    2015-06-15

    Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions in various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.

  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. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  18. Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

    Science.gov (United States)

    Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

    2016-12-01

    Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance.

    Science.gov (United States)

    Lamers, C T J; Ramaekers, J G; Muntjewerff, N D; Sikkema, K L; Samyn, N; Read, N L; Brookhuis, K A; Riedel, W J

    2003-12-01

    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

  20. The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women.

    Science.gov (United States)

    Hämmerle, Sibylle P; Mindeholm, Linda; Launonen, Aino; Kiese, Beate; Loeffler, Rolf; Harfst, Evita; Azria, Moise; Arnold, Michel; John, Markus R

    2012-04-01

    Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients. In this single-center, partially-blinded, incomplete cross-over study, the safety, tolerability, and exposure of oral PTH134 (teriparatide combined with 2 different quantities of the absorption enhancer 5-CNAC) were assessed in 32 healthy postmenopausal women. 16 subjects were randomized to receive 4 single doses out of 6 different treatments: placebo, teriparatide 20 μg sc, or 1, 2.5, 5 or 10 mg of oral PTH134 formulated with 200 mg 5-CNAC. Subsequently, another 16 subjects were randomized to receive 4 out of 6 different treatments: placebo, teriparatide 20 μg sc, or 2.5 or 5 mg of oral PTH134 formulated with either 100 or 200 mg 5-CNAC. Doses were given ≥6 days apart. All doses of PTH134 were rapidly absorbed, and showed robust blood concentrations in a dose-dependent manner. Interestingly, PTH1-34 disappeared from blood faster after oral than after sc administration. Specifically, 2.5 and 5 mg PTH134 (containing 200 mg 5-CNAC) demonstrated Cmax and AUC0-last values closest to those of sc teriparatide 20 μg (Forsteo®). Mean+/-SD hPTH134 Cmax values were, respectively, 74+/-59, 138+/-101, 717+/-496, and 1624+/-1579 pg/mL for 1, 2.5, 5, and 10 mg doses of this peptide administered with 200 mg 5-CNAC; while mean+/-SD AUC (0-last) values were, respectively, 30+/-40, 62+/-69, 320+/-269, and 627+/-633 h*pg/mL. The corresponding estimates for teriparatide 20 μg sc were 149+/-35 for Cmax and 236+/-58 for AUC (0-last) Ionized calcium remained within normal limits in all treatment groups except for 3 isolated events. Nine subjects withdrew due to treatment-related AEs. Of those, seven were taking PTH

  1. Antipsychotic treatment dosing profile in patients with schizophrenia evaluated with electronic monitoring (MEMS®).

    Science.gov (United States)

    Acosta, Francisco J; Ramallo-Fariña, Yolanda; Bosch, Esperanza; Mayans, Teresa; Rodríguez, Carlos J; Caravaca, Ana

    2013-05-01

    Although the Medication Event Monitoring System (MEMS®) device offers accurate information on treatment dosing profile, such profile has never been studied in patients with schizophrenia. Enhancing our knowledge on this issue would help in developing intervention strategies to improve adherence to antipsychotic treatment in these patients. 74 outpatients with schizophrenia were monitored with the MEMS device for a 3-month period, for evaluation of antipsychotic treatment dosing profile, possible influence of medication schedule-related variables, adherence to treatment--considering dose intake within prescribed timeframes--and possible Hawthorne's effect of using the MEMS device. Dose-omission gaps occurred in 18.7% of monitoring days, most frequently during weekends, almost significantly. Almost one-third of prescribed doses were taken out of prescribed time. Neither the prescribed number of daily doses nor the indicated time of the day for dose intake (breakfast, dinner), were associated with correct antipsychotic dosing. Excess-dose was rare in general, and more frequent out of prescribed dose timeframe. No Hawthorne's effect was found for the MEMS device. Adherence reached only 35% according to a definition that included dose intake within prescribed timeframes. Antipsychotic treatment dosing was considerably irregular among patients with schizophrenia. Strategies to reduce dose-omission gaps and increase dosing within prescribed timeframes seem to be necessary. Gaining knowledge on precise oral antipsychotic dosing profiles or the influence of schedule-related variables may be useful to design strategies towards enhancing adherence. There appears to be no Hawthorne's effect associated with the use of MEMS devices in outpatients with schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

    NARCIS (Netherlands)

    D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

    2017-01-01

    markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

  3. Evaluation of a single preoperative dose of etoricoxib for postoperative pain relief in therapeutic knee arthroscopy: a randomized trial

    National Research Council Canada - National Science Library

    Lierz, Peter; Losch, Holger; Felleiter, Peter

    2012-01-01

    BACKGROUND AND PURPOSE Analgesics can have undesirable effects. We assessed whether a single preoperative dose of 120 mg etoricoxib reduces the need for additional opioids after therapeutic arthroscopic knee surgery...

  4. A Systematic Review on Effect of Single-Dose Preoperative Antibiotics at Surgical Osteotomy Extraction of Lower Third Molars

    DEFF Research Database (Denmark)

    Marcussen, Karoline Brørup; Laulund, Anne Sofie; Jørgensen, Henrik L

    2016-01-01

    PURPOSE: We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally, intravenously, intramuscularly, or topically for preventing infection and alveolar osteitis in lower third molar surgi...

  5. Compendium of Single-Event Latchup and Total Ionizing Dose Test Results of Commercial Analog to Digital Converters

    Science.gov (United States)

    Irom, Farokh; Agarwal, Shri G.

    2012-01-01

    This paper reports single-event latchup and total dose results for a variety of analog to digital converters targeted for possible use in NASA spacecraft's. The compendium covers devices tested over the last 15 years.

  6. Single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

    Science.gov (United States)

    Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

    2015-09-28

    This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data. To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic. We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design

  7. Hemodynamic effects of spinal anesthesia in the elderly: single dose versus titration through a catheter.

    Science.gov (United States)

    Favarel-Garrigues, J F; Sztark, F; Petitjean, M E; Thicoïpé, M; Lassié, P; Dabadie, P

    1996-02-01

    Sixty elderly patients (> 70 yr old) undergoing surgery for hip fracture were prospectively studied in order to compare hemodynamic tolerance of titrated doses of hyperbaric bupivacaine using continuous spinal anesthesia (CSA) versus single-dose spinal anesthesia (SDSA). Patients were randomized into two groups (CSA group: n = 30; SDSA group: n = 30). The SDSA patients received 10-15 mg of 0.5% hyperbaric bupivacaine (based on age and height), and the CSA patients received a starting dose of 5 mg of 0.5% hyperbaric bupivacaine, followed after 15 min by optional reinjection of 2.5 mg every 5 min until a T10 level sensory block was reached. Onset of anesthesia, noninvasive hemodynamic variables and the need for ephedrine were studied for 4 h after induction of anesthesia. Spinal anesthesia was successful in all patients. Decreases in mean arterial pressure were significantly less frequent and less pronounced in the CSA group (19.9% +/- 1.6% of the baseline value) than in the SDSA group (40.2% +/- 1.9%, P SDSA group (19.4 +/- 3.3 mg administered to all patients, P SDSA in elderly patients.

  8. Distribution, elimination, and renal effects of single oral doses of europium in rats.

    Science.gov (United States)

    Ohnishi, Keiko; Usuda, Kan; Nakayama, Shin; Sugiura, Yumiko; Kitamura, Yasuhiro; Kurita, Akihiro; Tsuda, Yuko; Kimura, Motoshi; Kono, Koichi

    2011-11-01

    Single doses of europium (III) chloride hexahydrate were orally administered to several groups of rats. Cumulative urine samples were taken at 0-24 h, and blood samples were drawn after 24-h administration. The europium concentration was determined in these samples by inductively coupled plasma atomic emission spectroscopy. The volume, creatinine, ß-2-microglobulin, and N-acetyl-ß-D-glucosaminidase were measured in the urine samples to evaluate possible europium-induced renal effects. The blood samples showed low europium distribution, with an average of 77.5 μg/L for all groups. Although the urinary concentration and excretion showed dose-dependent increases, the percentage of europium excreted showed a dose-dependent decrease, with an average of 0.31% in all groups. The administration of europium resulted in a significant decrease of creatinine and a significant increase of urinary volume, N-acetyl-ß-D-glucosaminidase, and ß-2-microglobulin. Rare earth elements, including europium, are believed to form colloidal conjugates that deposit in the reticuloendothelial system and glomeruli. This specific reaction may contribute to low europium bioavailability and renal function disturbances. Despite low bioavailability, the high performance of the analytical method for determination of europium makes the blood and urine sampling suitable tools for monitoring of exposure to this element. The results presented in this study will be of great importance in future studies on the health impacts of rare earth elements.

  9. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Horton, Janet K., E-mail: janet.horton@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Blitzblau, Rachel C.; Yoo, Sua [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Geradts, Joseph [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Chang, Zheng [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Baker, Jay A. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Georgiade, Gregory S. [Department of Surgery, Duke University Medical Center, Durham, North Carolina (United States); Chen, Wei [Department of Bioinformatics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Siamakpour-Reihani, Sharareh; Wang, Chunhao [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Department of Biostatistics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Groth, Jeff [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha; Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Barry, William T. [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Duffy, Eileen A. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); and others

    2015-07-15

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  10. A single versus multiple doses of dexamethasone in infants wheezing for the first time.

    Science.gov (United States)

    Schuh, Suzanne; Coates, Allan L; Dick, Paul; Stephens, Derek; Lalani, Amina; Nicota, Erika; Mokanski, Matthew; Khaikin, Svetlana; Allen, Upton

    2008-09-01

    Corticosteroid therapy is not routinely recommended in true bronchiolitis. However, since bronchiolitis and the first asthma attack are impossible to distinguish, some infants with the first wheezing episode receive corticosteroids. Optimal duration of corticosteroid therapy in this scenario is unknown. This study compared efficacy of multiple administrations and a single dose of dexamethasone in bronchiolitis. In this randomized double blind trial, previously healthy outpatients 2-23 months of age with bronchiolitis and Respiratory Disease Assessment Instrument (RDAI) score 6 or more received 1 mg/kg of oral dexamethasone in the Emergency Department. Prior to discharge at 4 hr they were randomized to either 4 daily doses of dexamethasone 0.15 mg/kg or placebo equivalent. Primary outcome was the proportion of subsequent hospitalizations or prescribed trials of bronchodilator/corticosteroid therapy for dyspnea by day 6 in the groups. Secondary outcomes were changes in the RDAI to day 6, and proportions with unscheduled visits by days 6 and 28. The rate of primary outcome in the single dose group (SDG, N = 64) was 9/64 or 14.1% versus 7/61 or 11.5% in the multiple dose group (MDG, N = 61) [95% CI 0.09; 0.14]. Twelve (18.8%) children in the SDG had unscheduled medical visits by day 6 versus 11 (18.0%) children in the MDG [95% CI 0.13; 0.14]. On day 6 the RDAI decreased from 9.5 +/- 2.1 to 2.1 +/- 2.4 in the SDG and from 9.8 +/- 2.2 to 1.6 +/- 2.3 in the MDG [95% CI 0.36; 2.06]. Between days 7-28, 24/64 (37.5%) SDG infants returned for care versus 20/61 (32.8%) of the MDG [95% CI 0.12; 0.21]. Our study suggests that, in outpatients with bronchiolitis who receive dexamethasone, continuation of this agent beyond the initial dose does not provide significant benefit. (c) 2008 Wiley-Liss, Inc.

  11. Pharmacokinetics of Single Oral Dose Extended-Release Levetiracetam in Healthy Cats.

    Science.gov (United States)

    Barnard, L; Barnes Heller, H; Boothe, D M

    2018-01-01

    Repeated PO dosing of anti-epileptic drugs may contribute to poor compliance in treated cats. Intermediate-release levetiracetam has been used safely in cats, but must be given q8h to maintain serum concentrations in the therapeutic interval for humans (5-45 μg/mL). Approved extended-release levetiracetam (XRL) for human use may require less frequent dosing, but the large dosing unit has limited its use in cats. In healthy cats, serum levetiracetam concentration will remain above 5 μg/mL for at least 24 hours after administration of a single dose of XRL PO and will be well tolerated. 7 healthy cats. Extended-release levetiracetam (500 mg) was administered PO. Blood was collected and neurologic examination findings recorded at scheduled times over 30 hours. Serum levetiracetam concentration was quantitated by an immunoassay validated in cats. Data were subjected to noncompartmental analysis. Descriptive statistics were reported. The median dosage of 86.2 mg/kg, (range, 80-94.3) achieved a mean maximum concentration (Cmax ) of 89.8 ± 25.8 μg/mL at 4.9 ±1.57 hours. Serum levetiracetam was >5 μg/mL in all cats by 90 minutes. Mean concentrations were 43.7 ± 18.4 and 4.9 ± 3.4 μg/mL at 12 and 24 hours, respectively. The half-life was 4.1 ± 1.0 hours. The drug was well tolerated. A single 500 mg PO dose of XRL safely maintained serum levetiracetam concentration ≥5 μg/mL in healthy cats for at least 21 hours. Clinical efficacy studies in epileptic cats receiving XRL are indicated; however, monitoring should be implemented for individual cats. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  12. Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin.

    Science.gov (United States)

    Ahmad, Hesham M

    2015-01-01

    Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.

  13. Safety and pharmacokinetics of the anti-orthopoxvirus compound ST-246 following a single daily oral dose for 14 days in human volunteers.

    Science.gov (United States)

    Chinsangaram, Jarasvech; Honeychurch, Kady M; Tyavanagimatt, Shanthakumar R; Leeds, Janet M; Bolken, Tove' C; Jones, Kevin F; Jordan, Robert; Marbury, Thomas; Ruckle, Jon; Mee-Lee, Denis; Ross, Eric; Lichtenstein, Israel; Pickens, Margaret; Corrado, Michael; Clarke, Jean M; Frimm, Annie M; Hruby, Dennis E

    2012-09-01

    ST-246 is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. To this end, a phase 2, double-blind, randomized, placebo-controlled, multicenter trial was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of ST-246 when administered as a single daily oral dose (400 mg or 600 mg) for 14 days in fed adult volunteers. ST-246 was safe and well tolerated, with no deaths or serious adverse events reported during the study. There was a low incidence of treatment-emergent adverse events (TEAEs), the most common of which were mild nausea and headache. There were no clinically significant results from laboratory assessments, vital sign measurements, physical examinations, or electrocardiograms. The PK and dose proportionality of ST-246 were determined. The PK analysis showed that steady state was achieved by day 5 for the ST-246 400-mg treatment group and by day 6 for the 600-mg group. The dose proportionality analysis showed that the 400- and 600-mg ratio of dose-normalized peak drug concentration in plasma (C(max)) and relative exposure for each dosing interval (AUC(τ)) ranged from 80% to 85%. However, the 90% confidence intervals did not include 1.0, so dose proportionality could not be concluded. Overall, ST-246 was shown to be safe, and the PK was predictable. These results support further testing of ST-246 in a multicenter pivotal clinical safety study for licensure application.

  14. Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide.

    Science.gov (United States)

    Riddle, Mark S; Connor, Patrick; Fraser, Jamie; Porter, Chad K; Swierczewski, Brett; Hutley, Emma J; Danboise, Brook; Simons, Mark P; Hulseberg, Christine; Lalani, Tahaniyat; Gutierrez, Ramiro L; Tribble, David R

    2017-11-29

    Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations. A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool. Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events. Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea. NCT01618591.

  15. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-03-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Hyeong-Seok Lim,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Donghyun Hong,2 Seong Su Kim,2 Young Kweon Choi,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea; 2iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea Background: Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer’s disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Methods: Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods of 43.75 mg/12.5 cm2, 87.5 mg/25 cm2, or 175 mg/50 cm2. Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch were assessed throughout the study. Results: The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax and the area under the curve (AUC increased in a dose-proportional manner. Median time to Cmax was ~74–76 hours (~2–4 hours after patch removal, and mean t1/2ß was ~63.77–93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%–86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. Conclusion: The donepezil patch

  16. Prescribing and evaluating target dose in dose-painting treatment plans

    DEFF Research Database (Denmark)

    Håkansson, Katrin; Specht, Lena; Aznar, Marianne C

    2014-01-01

    of such plans. A quality volume histogram (QVH) tool for history-based evaluation is proposed. MATERIAL AND METHODS: Twenty head and neck cancer dose-painting plans with five prescription levels were evaluated, as well as clinically delivered simultaneous integrated boost (SIB) plans from 2010 and 2012. The QVH...

  17. Plasma levels and pharmacokinetics of single and multiple dose of tetrazepam in healthy volunteers.

    Science.gov (United States)

    Bun, H; Philip, F; Berger, Y; Necciari, J; Al-Mallah, N R; Serradimign, A; Cano, J P

    1987-02-01

    The pharmacokinetics of tetrazepam (Myolastan, Musaril), were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg and repeated administration for 5 consecutive days of 50 mg at 12-h intervals, in tablet form. Tetrazepam was measured in plasma using a selective and sensitive GLC method. Tetrazepam is rapidly absorbed after oral administration with a peak plasma level of 0.49 +/- 0.10 mg/l at 0.94 +/- 0.47 h. The drug is widely distributed in the organism with an apparent volume of distribution of 6.7 +/- 2.1 l/kg. Tetrazepam is eliminated with a half-life of 22 +/- 4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed. No differences were observed between the pharmacokinetic values after a single dose or after repeated administration.

  18. Blood pressure and heart rate effects following a single dose of bitter orange.

    Science.gov (United States)

    Bui, Linda T; Nguyen, DiemThuy T; Ambrose, Peter J

    2006-01-01

    The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p bitter orange versus placebo for hours 2-5 (p bitter orange versus placebo in young, healthy adults.

  19. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration: A case report.

    Science.gov (United States)

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-07-01

    Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of Tc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis.

  20. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    Science.gov (United States)

    Herzog, Christian

    2016-01-01

    Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Decline of HIV antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine

    NARCIS (Netherlands)

    de Gans, J.; Lange, J. M.; Derix, M. M.; de Wolf, F.; Eeftinck Schattenkerk, J. K.; Danner, S. A.; Ongerboer de Visser, B. W.; Cload, P.; Goudsmit, J.

    1988-01-01

    Six HIV-antigenaemic patients with AIDS or AIDS-related complex were studied to assess the effect of treatment with low-dose zidovudine (250 mg) in 6-hourly doses on HIV antigen (HIV-Ag) levels in cerebrospinal fluid (CSF). HIV-Ag was detected in CSF of three patients before treatment. These

  2. 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

  3. Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding.

    OpenAIRE

    Potel, G.; Chau, N P; Pangon, B; Fantin, B; Vallois, J M; Faurisson, F; Carbon, C.

    1991-01-01

    The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escher...

  4. Pharmacokinetics of Colistin Following a Single Dose of Intravenous Colistimethate Sodium in Critically Ill Neonates.

    Science.gov (United States)

    Nakwan, Narongsak; Usaha, Siripa; Chokephaibulkit, Kulkanya; Villani, Paola; Regazzi, Mario; Imberti, Roberto

    2016-11-01

    In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (±SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 ± 0.7 µg/mL and 25.3 ± 10.4 µg·h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 ± 0.9 hours, 9.0 ± 6.5 hours, 7.7 ± 9.3 L/kg and 0.6 ± 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 ± 0.4 µg/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient.

  5. The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

    Science.gov (United States)

    Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

    2016-12-01

    Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P dexamethasone group. Impaired wound healing was not observed in either group. A single low-dose of dexamethasone prevents intraoperative vomiting for awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

  6. Haemodynamic changes during spinal anaesthesia with slow continuous infusion or single dose of plain bupivacaine.

    Science.gov (United States)

    Pitkänen, M; Rosenberg, P; Silvanto, M; Tuominen, M

    1992-08-01

    Forty elderly patients, scheduled for orthopaedic surgery of the hip or knee were studied. Twenty patients received a single-dose spinal anaesthesia with 3 ml of plain 0.5% bupivacaine (SDSA group). Twenty patients received continuous spinal anaesthesia using a 32- or 22-gauge catheter. A bolus of 1.0 ml of plain 0.5% bupivacaine was given to ten patients and 0.5 ml to another ten, continued by an infusion at a rate of 2 ml/h. The spread of analgesia and haemodynamic changes (central venous pressure, arterial pressures, need for sympathomimetic medication) were registered. The mean dose of bupivacaine was 2.9 ml (range 1.5-5 ml) in the CSA group (3.0 ml in the SDSA group). Eight patients in the CSA group needed medication for pain during surgery compared to five patients in the SDSA group (n.s.). The median level of pinprick analgesia at 60 min was T11 in the CSA and T6.5 in the SDSA group (P less than 0.01). The mean maximum decreases in CVP and MAP were quite similar in the CSA and SDSA group (2.1 vs 2.8 mmHg (0.3 vs 0.4 kPa) and 17 vs 21 mmHg (2.3 vs 2.8 kPa), respectively) (n.s.). Six patients in the SDSA group and four patients in the CSA group needed sympathomimetic medication. It is concluded that titration of bupivacaine for spinal anaesthesia caused only minor haemodynamic changes which were similar to those after single-dose spinal bupivacaine.

  7. Pharmacokinetic indices for cefovecin after single-dose administration to adult sea otters (Enhydra lutris).

    Science.gov (United States)

    Lee, E A; Byrne, B A; Young, M A; Murray, M; Miller, M A; Tell, L A

    2016-12-01

    Seven sea otters received a single subcutaneous dose of cefovecin at 8 mg/kg body weight. Plasma samples were collected at predetermined time points and assayed for total cefovecin concentrations using ultra-performance liquid chromatography and tandem mass spectrometry. The mean (±SD) noncompartmental pharmacokinetic indices were as follows: CMax (obs) 70.6 ± 14.6 μg/mL, TMax (obs) 2.9 ± 1.5 h, elimination rate constant (kel ) 0.017 ± 0.002/h, elimination half-life (t1/2kel) 41.6 ± 4.7 h, area under the plasma concentration-vs.-time curve to last sample (AUClast) 3438.7 ± 437.7 h·μg/mL and AUC extrapolated to infinity (AUC0→∞ ) 3447.8 ± 439.0 h·μg/mL. The minimum inhibitory concentrations (MIC) for select isolates were determined and used to suggest possible dosing intervals of 10 days, 5 days, and 2.5 days for gram-positive, gram-negative, and Vibrio parahaemolyticus bacterial species, respectively. This study found a single subcutaneous dose of cefovecin sodium in sea otters to be clinically safe and a viable option for long-acting antimicrobial therapy. © 2016 John Wiley & Sons Ltd.

  8. A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1β3 in Patients With Systolic Dysfunction and Heart Failure

    Directory of Open Access Journals (Sweden)

    Daniel J. Lenihan, MD

    2016-12-01

    Full Text Available A first-in-human, phase 1, double blind, placebo-controlled, single ascending dose study examined the safety, tolerability, and exploratory efficacy of intravenous infusion of a recombinant growth factor, cimaglermin alfa, in patients with heart failure and left ventricular systolic dysfunction (LVSD. In these patients on optimal guideline-directed medical therapy, cimaglermin treatment was generally tolerated except for transient nausea and headache and a dose-limiting toxicity was noted at the highest planned dose. There was a dose-dependent improvement in left ventricular ejection fraction lasting 90 days following infusion. Thus, cimaglermin is a potential therapy to enhance cardiac function in LVSD and warrants further investigation.

  9. 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.

  10. Comparison Of The Pharmacokinetics And Pharmacodynamics Of Single-Dose Tenofovir Vaginal Film And Gel Formulation (Fame-05).

    Science.gov (United States)

    Robinson, Jennifer A; Marzinke, Mark A; Fuchs, Edward J; Bakshi, Rahul P; Spiegel, Hans M L; Coleman, Jenell S; Rohan, Lisa C; Hendrix, Craig W

    2017-11-07

    While pre-exposure prophylaxis with oral tenofovir (TFV) disoproxil fumarate/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of daily vaginal gels has led to development of vaginal film formulations to improve adherence and, potentially, enable episodic use. In this two-arm, cross-over study of a fast-dissolving tenofovir film (40 mg) compared to a previously studied semisolid tenofovir 1% gel (40 mg), 10 healthy women received a single vaginal dose of each study product. Clinical, pharmacokinetic, and antiviral assessments were performed over one week post-dose. Nine of 10 participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or events attributed to study products. TFV concentrations after film dosing exceeded concentrations after gel dosing in plasma between 8 and 24 hours (pfilm dosing (all p values film nor gel demonstrated reduced cervical tissue biopsy infectivity after ex vivo HIV challenge. Single dose tenofovir film demonstrated consistently higher concentrations in plasma and cervicovaginal samples when compared to gel during the first day following dosing. Single dose cervical tissue TFV-DP concentrations at 5 hours exceeded steady-state concentrations previously reported with daily oral Truvada dosing. Tenofovir film may provide an alternative to tenofovir oral and gel formulations. Clinical efficacy remains to be tested.

  11. Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects.

    Science.gov (United States)

    Anthanont, Pimjai; Lumlerdkij, Natchagorn; Akarasereenont, Pravit; Vannasaeng, Sathit; Sriwijitkamol, Apiradee

    2016-03-01

    Herbal medicine has long been used as an alternative medicine for treatment of type 2 diabetes mellitus (T2DM). Recently, Moringa oleifera (MO or ma-rum in Thai) leaf has been widely used in T2DM patients. Several studies in diabetes rat model have shown that MO had effect on glucose metabolism. However study in humans is lacking. Examine effects of MO on plasma glucose and insulin secretion. Ten healthy volunteers were enrolled in this study (mean age 29 ± 5 years; BMI 20.6 ± 1.5 kg/m2; FPG 81 ± 5 mg/dl). After an overnight fast and every two weeks, subjects received an oral dose of MO at increasing dosages of 0, 1, 2, and 4 g. Plasma glucose (PG) and insulin were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 6 hours after each MO dosage administration. Insulin secretion rate was measured using area under the curve (AUC) of insulin and AUC of insulin/glucose ratio. After doses of 0, 1, 2, and 4 g MO, mean plasma insulin increased (2.3 ± 0.9, 2.7 ± 1.0, 3.3 ± 1.4, and 4.1 ± 1.7 μU/ml, respectively) despite there being no differences in mean PG (77 ± 6, 78 ± 5, 79 ± 6, and 79 ± 5 mg/dl, respectively). AUC of insulin was greater after high-dose MO (4 g) than after baseline or low-dose MO capsule (1 g) (24.0 ± 3.5 vs. 14.5 ± 1.8 or 16.1 ± 2.0, respectively; p = 0.03), while there was no difference in AUC of glucose. Accordingly, insulin secretion rate represented by AUC of insulin/glucose ratio after high-dose MO was significantly increased by 74% (P = 0.041), as compared with that of baseline. We concluded that high-dose (4 g) MO leaf powder capsules significantly increased insulin secretion in healthy subjects. These results suggest that MO leaf may be a potential agent in the treatment of type 2 diabetes. Further studies of MO in patients with T2DM are needed.

  12. Treatment of hyperthyroidism by 131-iodine; Traitement des hyperthyroidies par l'iode 131: dose calculee versus dose fixe

    Energy Technology Data Exchange (ETDEWEB)

    Fieffe, S.; Cuif-Joba, A.; Testard, A.; Fortuna, I.; Pocharta, J.M.; Papathanassioua, D.; Schvartz, C. [Service d' endocrinologie et medecine nucleaires, institut Jean-Godinot, 1, rue du General Koeing, 51056 Reims, (France)

    2009-05-15

    In a first time, we chose to modify the dose to be administered, on using always the Marinelli formula but on increasing the absorbed dose. In a second time, we wanted to simplify the determination of the dose to be administered by modulating it only in function of the thyroid volume. Two groups of patients were managed for hyperthyroidism recurrence. In a first group the iodine dose ({sup 131}I) was determined with the help of the simplified Marinelli formula: chosen absorbed dose was 150 Gy, gland volume determined by echography, measurement of the fixation at the sixth hour. In the second group, the thyroid volume was determined by echography. The patients with a thyroid from 5 to 30 g received 185 MBq, from 30 to 50 g 370 MBq and superior to 50 g 555 MBq of iodine 131. The two groups of patients have the same characteristics. the results of treatment by iodine 131, evaluated on the dosages of T4L and TSH at three and six months, show the preservation of euthyroidism or the passage in hypothyroidism among 94% of patients in the group 1 and 80% of patients in the group 2. These results are not significantly different. The easiness of the realisation of the treatment in the group 2 lead us to continue this simplified therapy scheme that allows equally to improve the radiation protection of medical personnel by avoiding the use of iodine 131. (N.C.)

  13. Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with 99mTc-annexin V.

    Science.gov (United States)

    Mochizuki, Takafumi; Kuge, Yuji; Zhao, Songji; Tsukamoto, Eriko; Hosokawa, Masuo; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara

    2003-01-01

    Annexin V, a human protein with a high affinity for phosphatidylserine, has been labeled with (99m)Tc to detect apoptosis in vivo. To determine the effectiveness of imaging with this agent as a reflection of the degree of apoptosis after the first dose of chemotherapy, we studied rats with an engrafted hepatoma. Annexin V was labeled with (99m)Tc (specific activity, 3.0 MBq/ micro g protein). Eleven days after being inoculated with allogenic hepatoma cells (KDH-8) in the left calf muscle, the rats were randomized to receive a single dose of cyclophosphamide (150 mg/kg intraperitoneally) or to serve as controls. (99m)Tc-annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h after injection of (99m)Tc-annexin V. Tumor uptake of (14)C-iodoanitpyrine was determined as a marker of tumor blood flow. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) of tissue harvested at necropsy was performed to detect apoptosis in the tumor. Cyclophosphamide treatment significantly increased the tumor uptake (percentage activity of injected dose per gram of tissue after normalization to the animal's weight [%ID/g/kg]) of (99m)Tc-annexin V (0.070 +/- 0.007 %ID/g/kg for treated rats and 0.046 +/- 0.009 %ID/g/kg for controls, P < 0.001). (14)C-iodoantipyrine uptake was similar in the treated and untreated groups. The number of TUNEL-positive cells in the tumor was significantly larger in the treated rats (297.70 +/- 50.34 cells/mm(2)) than in the control rats (168.45 +/- 23.60 cells/mm(2), P < 0.001). Tumor uptake of (99m)Tc-annexin V correlated with the number of TUNEL-positive cells in the tumor (r = 0.712; P < 0.001). Tumor uptake of (99m)Tc-annexin V was significantly increased by a single dose of cyclophosphamide treatment, and the increase was concordant with the number of TUNEL-positive cells in the tumor. The current results are suggestive of the utility of (99m)Tc-annexin V as a noninvasive means to assess

  14. Early response assessment in gastrointestinal stromal tumors with FDG PET scan 24 hours after a single dose of imatinib.

    Science.gov (United States)

    Shinto, Ajit; Nair, Narendra; Dutt, Anil; Baghel, Nawab S

    2008-07-01

    Gastrointestinal stromal tumors (GIST), rare mesenchymal tumors of the gastrointestinal tract, are gaining the interest of researchers because of the impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. FDG PET is now routinely used to assess treatment response in cases of GIST because this has proven to give metabolic information, which demonstrates response earlier than anatomic imaging modalities. A 50-year-old man presented with abdominal pain and the CT scan showed a large lobulated heterogeneously enhancing mass in the abdomen. Fine needle aspiration cytology (FNAC) confirmed GIST with strong immunoreactivity to C-Kit protein. A baseline FDG PET done before initiation of therapy showed intense nonhomogenous FDG uptake in the mass (standard uptake value maximum, SUVmax of 13.45). A whole body FDG PET, repeated 24 hours after a single dose of imatinib mesylate 400 mg, showed a significant reduction in FDG uptake with a SUVmax of 4.26.

  15. Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

    Science.gov (United States)

    Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

    2018-01-01

    Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  16. Efficacy of single dose albendazole on the prevalence and intensity of infection of soil-transmitted helminths in Orang Asli children in Malaysia.

    Science.gov (United States)

    Norhayati, M; Oothuman, P; Azizi, O; Fatmah, M S

    1997-09-01

    The efficacy of a single-dose 400 mg albendazole to treat Ascaris, Trichuris and hookworm infection was studied in Orang Asli community. Kato-Katz examination was performed on fecal samples which were collected before treatment, 1 and 4 months after treatment. A total of 123 children were involved in all three surveys. The cure rate of Ascaris infection was 97.4% and the egg reduction after treatment was 99.9%. The cure rate for hookworm infection was 93.1% with 96.6% egg reduction. Although the cure rate was low in Trichuris infection (5.5%), egg reduction was more evident (49.1%). The reinfection rate at 4 months after treatment was 54.5%, 3.6% and 10.3% for Ascaris, Trichuris and hookworm infection, respectively. Within 4 months after treatment almost one-fifth children with Ascaris and hookworm infection reached pre-treatment intensity infection. In Trichuris infection, however more than half of the children reached their pre-treatment intensity infection at 4 months after treatment. Findings suggest that 4-monthly targeted periodic treatment with 400 mg single-dose albendazole in highly endemic areas can have a significant impact on intensity infection of Ascaris and hookworm, but not on Trichuris infection.

  17. Successful treatment of chronic recurrent multifocal osteomyelitis using low-dose radiotherapy. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Dietzel, Christian T.; Vordermark, Dirk [Klinikum der Martin-Luther-Universitaet Halle-Wittenberg, Universitaetslinik und Poliklinik fuer Strahlentherapie, Halle (Saale) (Germany); Schaefer, Christoph [Klinikum der Martin-Luther-Universitaet Halle-Wittenberg, Universitaetsklinik und Poliklinik fuer Innere Medizin II, Halle (Saale) (Germany)

    2017-03-15

    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, which lacks an infectious genesis and predominantly involves the metaphysis of long bones. Common treatments range from nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids at first onset of disease, to immunosuppressive drugs and bisphosphonates in cases of insufficient remission. The therapeutic use of low-dose radiotherapy for CRMO constitutes a novelty. A 67-year-old female patient presented with radiologically proven CRMO affecting the right tibia/talus and no response to immunosuppressive therapy. Two treatment series of radiation therapy were applied with an interval of 6 weeks. Each series contained six fractions (three fractions per week) with single doses of 0.5 Gy, thus the total applied dose was 6 Gy. Ten months later, pain and symptoms of osteomyelitis had completely vanished. Radiotherapy seems to be an efficient and feasible complementary treatment option for conventional treatment refractory CRMO in adulthood. The application of low doses per fraction is justified by the inflammatory pathomechanism of disease. (orig.) [German] Die chronisch rekurrierende multifokale Osteomyelitis (CRMO) ist eine seltene autoimmunologische Erkrankung und befaellt vorzugsweise die Metaphysen der langen Roehrenknochen. Die Therapie umfasst nichtsteroidale Antirheumatika (NSAIDs) und Kortikosteroide bei Erstbefall und reicht bis hin zu Immunsuppressiva und Bisphosphonaten bei insuffizientem Ansprechen. Die Anwendung einer niedrigdosierten Radiatio stellt ein therapeutisches Novum dar. Eine 67-jaehrige Patientin stellte sich mit einem radiologisch gesicherten Befall im Sinne einer CRMO im Bereich des rechten Talus und der Tibia vor. Eine initiale Behandlung mit Immunsuppressiva verblieb erfolglos. Wir fuehrten zwei Bestrahlungsserien im Intervall von 6 Wochen durch. Jede Serie bestand aus 6 Fraktionen (3 Fraktionen/Woche), mit einer Einzeldosis von jeweils 0,5 Gy. Die

  18. Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats.

    Science.gov (United States)

    Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo; Ruibal, Álvaro; Sobrino, Tomás; Aguiar, Pablo

    2016-12-01

    Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Twelve Sprague-Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Our analysis revealed a significant reduction of global FDG uptake after acute (-16.2%) and chronic (-23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p<0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this medication. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effect of a single dose of Saccharomyces cerevisiae var. boulardii on the occurrence of porcine neonatal diarrhoea.

    Science.gov (United States)

    Hancox, L R; Le Bon, M; Richards, P J; Guillou, D; Dodd, C E R; Mellits, K H

    2015-11-01

    Piglet neonatal diarrhoea is an important issue in modern pig production and is linked to increased mortality and poor growth rates, affecting long-term pig health, increasing use of medication and cost of production. Saccharomyces cerevisiae var. boulardii (SB) is a probiotic yeast with documented clinical efficacy in the prevention and treatment of diarrhoeal diseases in humans. The objectives of the current study were to evaluate the effect of SB on occurrence and severity of neonatal diarrhoea in piglets, mortality and growth rate. Forty-six litters (606 piglets) were randomly allocated to a control or SB treatment (n=23 per treatment). Within 24 h of farrowing, piglets assigned to the SB treatment received a single oral dose of a paste containing 3.3×10(9) CFU of SB CNCM I-107(9). Piglets from the control litters received a placebo paste. Piglet weight, mortality and diarrhoea were recorded up to day 7 of age. It was shown that numbers of diarrhoea days were significantly correlated with increased mortality rate and reduced weight gain (Pweaning performance and suggest that SB, by reducing diarrhoea duration and severity, has the potential of improving enteric health in the early stages of life in pigs.

  20. Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2015-07-14

    There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific benefits are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations, and when tested in the same and different trials. Adding caffeine to analgesics also increases the number of people obtaining good pain relief. Combinations of ibuprofen and caffeine are available without prescription in some parts of the world. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus caffeine for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 1 February 2015. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus caffeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either ibuprofen plus caffeine or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. We identified five randomised, double-blind studies with 1501 participants, but

  1. Decreasing Methadone Dose Via Anxiety Reduction: A Treatment Manual.

    Science.gov (United States)

    Kushner, Marlene; And Others

    This manual describes a Relaxation-Information Presentation program based on the clinical observation that anxiety is a serious barrier to detoxification for many methadone clients, and on experimental evidence indicating that expectations may play a greater role in the discomfort experienced during detoxification than the actual methadone dose.…

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-01

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