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Sample records for multiple daily doses

  1. Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

    International Nuclear Information System (INIS)

    Kal, H.B.; Bijman, J.Th.

    1981-01-01

    Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min -1 . The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

  2. Comparison between a single dose of goserelin (depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: a clinical endocrinological study of the ovarian response.

    Science.gov (United States)

    Geber, Selmo; Sales, Liana; Sampaio, Marcos A C

    2002-07-01

    Compare the efficacy and safety of two different GnRHa, used for pituitary suppression in IVF cycles. A total of 292 patients using depot goserelin (Group 1) and 167 using daily leuprolide acetate (Group 2) were compared. Days required to achieve pituitary function suppression, duration of ovarian stimulation, total dose of HMG, number of aspirated follicles, number of oocytes retrieved, and presence of functional ovarian cyst were analyzed. The time taken to achieve downregulation was similar. The mean number of ampoules used for superovulation was higher in Group 1; however, this difference was observed only for patients >40 years old that started GnRHa in the follicular phase. There was no difference between the two groups in the duration of superovulation, in the number of follicles aspirated, and the number of oocytes retrieved. In the group of patients with >40 years the incidence of ovarian cysts was higher in Group 2. Both routes of GnRHa have similar effects for pituitary suppression and ovulation induction in assisted reproductive technology. Therefore the long-acting GnRHa is an excellent option, as only a single subcutaneous dose is necessary, decreasing the risk of the patient to forget its use and, most important, it does not interfere in the patient's quality of life.

  3. Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

    Science.gov (United States)

    Su, Fang-Yi; Chuang, Er-Yuan; Lin, Po-Yen; Chou, Yi-Chun; Chen, Chiung-Tong; Mi, Fwu-Long; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

    2014-04-01

    Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Control of hypertension with single daily doses of sotalol hydrochloride.

    Science.gov (United States)

    Gabriel, R

    A study was carried out in 12 previously untreated hypertensive patients to assess the efficacy of sotalol given in a once-daily dosage regimen. After an initial dosage titration period (mean 3 weeks) during which diastolic pressure was stabilized at less than 100 mmHg, all patients were satisfactorily maintained on a constant once-daily dose of sotalol for 3 months. Eight of the 12 patients required 320 mg or less daily (mean dose 190 mg). Whilst blood pressure remained controlled for at least 26 hours after daily doses the pulse rate, counted at the same time, showed escape from beta-blockade. Side-effects (vivid dreams) were reported in only 1 patient.

  5. Pathological consequences of chronic low daily dose gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Miller, A.C.; Ramakrishnan, N. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States); Fritz, T.E.

    2000-07-01

    The quantitative relationships between the chronic radiation exposure parameters of dose-rate and total dose in relation to associated health risks was examined in dogs. At a dose-rate of 75, 128, and 263 mGy/d the incidence of acute lymphohematopoietic suppression (aplastic anemia) and associated septic complications was 73%, 87%, and 100%, respectively, and it increased in dose-dependent manner. By contrast, at dose-rates below 75 mGy/d, late cancers contributed significantly to the death of relatively long-lived animals, whose mean survival time was 1800 days. Myeloproliferative disease (MPD), mainly myeloid leukemia, was the dominant pathology seen at the higher daily dose-rates (18.8-75 mGy/d). When daily exposure was carried out continuously, the incidence of MPD was quite high. It should be noted that the induction radiation-induced MPD in this study was highly significant, because spontaneous MPD is exceedingly rare in the dog. However, when the daily dose-rate was reduced further or exposure was discontinued, the incidence of MPD declined significantly. At these lower dose-rates, solid tumors contributed heavily to the life-shortening effects of chronic irradiation. The induction and progression of these survival-compromising, late forms of pathology appeared to be driven by the degree of hematopoietic suppression that occurred early during the exposure phase, and in turn by the capacity of hematopoietic system to repair itself, recover, and to accommodate under chronic radiation stress. (K.H.)

  6. Once versus twice daily gentamicin dosing for infective endocarditis

    DEFF Research Database (Denmark)

    Buchholtz, Kristine; Larsen, Carsten Toftager; Schaadt, Bente

    2011-01-01

    Objectives: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Methods: Seventy-one IE patients needing gentamicin treatment according...

  7. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  8. Multiple daily fractionation in radiotherapy: biological rationale and preliminary clinical experiences

    Energy Technology Data Exchange (ETDEWEB)

    Arcangeli, G [Instituto Medico Scientifico, Rome (Italy). Dept. of Oncology; Mauro, F; Morelli, D; Nervi, C

    1979-09-01

    The biological bases of radiation dose fractionation are reviewed and discussed with special emphasis on reassortment. Experimental data on animal model systems are presented to clarify that reassortment has to be added to sublethal damage repair and reoxygenation in the rationale for an optimized radiotherapy course according to tumor cell kinetics. Clinical results on several human tumors treated with twice or thrice daily fractions are described. These results show that some clinically radioresistant tumors (especially if not characterized by a relatively long clinical doubling line) can be satisfactorily dealt with using multiple daily fractionation. Clinical observations indicate that a relatively high cumulative daily dose (200 + 150 + 150 rad) can be safely administered.

  9. Dose Estimation from Daily and Weekly Dosimetry Data

    Energy Technology Data Exchange (ETDEWEB)

    Ostrouchov, G.

    2001-11-16

    Statistical analyses of data from epidemiologic studies of workers exposed to radiation have been based on recorded annual radiation doses (yearly dose of record). It is usually assumed that the dose values are known exactly, although it is generally recognized that the data contain uncertainty due to measurement error and bias. In our previous work with weekly data, a probability distribution was used to describe an individual's dose during a specific period of time and statistical methods were developed for estimating it from weekly film dosimetry data. This study showed that the yearly dose of record systematically underestimates doses for Oak Ridge National Laboratory (ORNL) workers. This could result in biased estimates of dose-response coefficients and their standard errors. The results of this evaluation raise serious questions about the suitability of the yearly dose of record for direct use in low-dose studies of nuclear industry workers. Here, we extend our previous work to use full information in Pocket meter data and develop the Data Synthesis for Individual Dose Estimation (DSIDE) methodology. Although the DSIDE methodology in this study is developed in the context of daily and weekly data to produce a cumulative yearly dose estimate, in principle it is completely general and can be extended to other time period and measurement combinations. The new methodology takes into account the ''measurement error'' that is produced by the film and pocket-meter dosimetry systems, the biases introduced by policies that lead to recording left-censored doses as zeros, and other measurement and recording practices. The DSIDE method is applied to a sample of dose histories obtained from hard copy dosimetry records at ORNL for the years 1945 to 1955. First, the rigorous addition of daily pocket-meter information shows that the negative bias is generally more severe than was reported in our work based on weekly film data only, however, the

  10. Dose Estimation from Daily and Weekly Dosimetry Data

    International Nuclear Information System (INIS)

    Ostrouchov, G.

    2001-01-01

    Statistical analyses of data from epidemiologic studies of workers exposed to radiation have been based on recorded annual radiation doses (yearly dose of record). It is usually assumed that the dose values are known exactly, although it is generally recognized that the data contain uncertainty due to measurement error and bias. In our previous work with weekly data, a probability distribution was used to describe an individual's dose during a specific period of time and statistical methods were developed for estimating it from weekly film dosimetry data. This study showed that the yearly dose of record systematically underestimates doses for Oak Ridge National Laboratory (ORNL) workers. This could result in biased estimates of dose-response coefficients and their standard errors. The results of this evaluation raise serious questions about the suitability of the yearly dose of record for direct use in low-dose studies of nuclear industry workers. Here, we extend our previous work to use full information in Pocket meter data and develop the Data Synthesis for Individual Dose Estimation (DSIDE) methodology. Although the DSIDE methodology in this study is developed in the context of daily and weekly data to produce a cumulative yearly dose estimate, in principle it is completely general and can be extended to other time period and measurement combinations. The new methodology takes into account the ''measurement error'' that is produced by the film and pocket-meter dosimetry systems, the biases introduced by policies that lead to recording left-censored doses as zeros, and other measurement and recording practices. The DSIDE method is applied to a sample of dose histories obtained from hard copy dosimetry records at ORNL for the years 1945 to 1955. First, the rigorous addition of daily pocket-meter information shows that the negative bias is generally more severe than was reported in our work based on weekly film data only, however, the amount of bias also varies

  11. [Evaluation of methods to calculate dialysis dose in daily hemodialysis].

    Science.gov (United States)

    Maduell, F; Gutiérrez, E; Navarro, V; Torregrosa, E; Martínez, A; Rius, A

    2003-01-01

    Daily dialysis has shown excellent clinical results because a higher frequency of dialysis is more physiological. Different methods have been described to calculate dialysis dose which take into consideration change in frequency. The aim of this study was to calculate all dialysis dose possibilities and evaluate the better and practical options. Eight patients, 6 males and 2 females, on standard 4 to 5 hours thrice weekly on-line hemodiafiltration (S-OL-HDF) were switched to daily on-line hemodiafiltration (D-OL-HDF) 2 to 2.5 hours six times per week. Dialysis parameters were identical during both periods and only frequency and dialysis time of each session were changed. Time average concentration (TAC), time average deviation (TAD), normalized protein catabolic rate (nPCR), Kt/V, equilibrated Kt/V (eKt/V), equivalent renal urea clearance (EKR), standard Kt/V (stdKt/V), urea reduction ratio (URR), hemodialysis product and time off dialysis were measured. Daily on-line hemodiafiltration was well accepted and tolerated. Patients maintained the same TAC although TAD decreased from 9.7 +/- 2 in baseline to a 6.2 +/- 2 mg/dl after six months, p time off dialysis was reduced to half. Dialysis frequency is an important urea kinetic parameter which there are to take in consideration. It's necessary to use EKR, stdKt/V or weekly URR to calculate dialysis dose for an adequate comparison between different frequency dialysis schedules.

  12. A Semiempirical Approach to the Determination of Daily Erythemal Doses.

    Science.gov (United States)

    Silva, Abel A; Yamamoto, Ana L C; Corrêa, Marcelo P

    2018-02-15

    The maintenance of ground-based instruments to measure the incidence of ultraviolet radiation (UVR) from the Sun demands strict and well-developed procedures. A piece of equipment can be out of service for a couple of weeks or months for calibration, repair or even the improvement of the facilities where it has been set up. However, the replacement of an instrument in such circumstances can be logistically and financially prohibitive. On the other hand, the lack of data can jeopardize a long-term experiment. In this study, we introduce a semiempirical approach to the determination of the theoretical daily erythemal dose (DED t ) for periods of instrumental absence in a tropical site. The approach is based on 5 years of ground-based measurements of daily erythemal dose (DED) linearly correlated with parameters of total ozone column (TOC) and reflectivity (R PC ) from the Ozone Monitoring Instrument (OMI) and the cosine of solar zenith angle at noon (SZA n ). Seventeen months of missing ground-based data were replaced with DED t , leading to a complete 5-year series of data. The lowest and the highest values of typical DED were 2411 ± 322 J m -2 (1σ) (winter) and 5263 ± 997 J m -2 (summer). The monthly integrated erythemal dose (mED) varied from 59 kJ m -2 (winter) to 162 kJ m -2 (summer). Both of them depended mainly on cos(SZA n ) and R PC . The 12-month integrated erythemal dose (12-ED) ranged from 1350 kJ m -2 to 1546 kJ m -2 , but it can depend significantly on other atmospheric parameter (maybe aerosols) not explicitly considered here. © 2018 The American Society of Photobiology.

  13. Further experience with radiotherapy by multiple daily sessions

    Energy Technology Data Exchange (ETDEWEB)

    Svoboda, V H.J. [Saint Mary' s Hospital, Portsmouth (UK). Dept. of Radiotherapy and Oncology

    1978-05-01

    Since 1972 over 100 patients have been treated by frequent daily sessions of radiotherapy with a short overall time. Cobalt 60 teletherapy and 250 kV X-ray beams have been used with radical or palliative dosage. The tolerance to these regimes of the skin, breast, chest wall, neck, lung and pelvis is discussed and the tumour responses described. Radiotherapy by multiple daily sessions is clinically possible and often an advantage. Its therapeutic ratio is not inferior to comparable regimes using longer intervals.

  14. Multiple anatomy optimization of accumulated dose

    International Nuclear Information System (INIS)

    Watkins, W. Tyler; Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated

  15. Multiple anatomy optimization of accumulated dose

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Moore, Joseph A. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Gordon, James [Henry Ford Health System, Detroit, Michigan 48202 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Hugo, Geoffrey D. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States)

    2014-11-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  16. Multiple anatomy optimization of accumulated dose.

    Science.gov (United States)

    Watkins, W Tyler; Moore, Joseph A; Gordon, James; Hugo, Geoffrey D; Siebers, Jeffrey V

    2014-11-01

    To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  17. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    Seed, T.M.

    1994-01-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d -1 ). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

  18. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Wit, F. W.; Lange, J. M.; Danner, S. A.; Foudraine, N. A.; Kwakkelstein, M. O.; Reiss, P.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    OBJECTIVE: To investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DESIGN: Open-label, randomized, cross-over study. METHODS: Twenty HIV-1-infected individuals who already

  19. Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Lange, J. M.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    To investigate the steady-state pharmacokinetics of a once-daily dosing regimen of saquinavir soft gelatin capsules in combination with a low dose of ritonavir in HIV-1-infected individuals. Open-label, multi-dose, pharmacokinetic pilot study. Seven HIV-1-infected individuals who were treated with

  20. Impact of a daily exercise dose on knee joint cartilage

    DEFF Research Database (Denmark)

    Bricca, A; Juhl, C B; Grodzinsky, A J

    2017-01-01

    -analysis of 14 studies investigating cartilage thickness showed no effect in the low dose exercise group (SMD -0.02; 95% CI -0.42 to 0.38; I(2) = 0.0%), large but non-significant cartilage thickening in the moderate dose exercise group (SMD 0.95; 95% CI -0.33 to 2.23; I(2) = 72.1%) and non-significant cartilage...... thinning in the high dose exercise group (SMD -0.19; 95% CI -0.49 to 0.12; I(2) = 0.0%). Results were independent of analyzed covariates. The overall quality of the studies was poor because of inadequate reporting of data and high risk of bias. CONCLUSIONS: Our results suggest that the relationship between...

  1. Modifications of S-phase cell distribution in the intestinal crypts after multiple daily fractionation

    Energy Technology Data Exchange (ETDEWEB)

    Becciolini, A; Cremonini, D; Fabbrica, D; Balzi, M [Florence Univ. (Italy). Ist. di Radiologia

    1983-01-01

    The effects obtained by multiple daily fractionation (3 Gy x2 or 3 Gy x2x2) on the distribution of S-phase cells along the crypt of the small intestine were investigated. The frequency of labelled cell distribution was reduced at early intervals; then the proliferating compartment gradually extended to the villus junctions. During recovery labelled cell frequency in the lower half of the crypts returned to control levels, while labelled cells were present in the differentiating area. With lower total dose modifications were milder and, as early as 72 h before exposure, distribution was already similar to controls. Invertase activity showed an initial increase and a higher reduction during acute damage when fractionation with higher doses was used. A lack of return to normal activity was present even 11 days after exposure when, however, the characteristic circadian pattern was observed.

  2. High daily doses of benzodiazepines among Quebec seniors: prevalence and correlates

    Directory of Open Access Journals (Sweden)

    Moride Yola

    2001-11-01

    Full Text Available Abstract Background Use of high daily doses of benzodiazepines is generally contraindicated for seniors. While both patient and physician factors may influence the use of high daily doses, previous research on the effect of patient factors has been extremely limited. The objectives of this study were to determine the one year prevalence of use of high daily doses of benzodiazepines, and examine physician and patient correlates of such use among Quebec community-dwelling seniors. Methods Patient information for 1423 community-dwelling Quebec seniors who participated in the Canadian Study of Health and Aging was linked to provincial health insurance administrative data bases containing detailed information on prescriptions received and prescribers. Results The standardized one year period prevalence of use of high daily doses of benzodiazepines was 7.9%. Use of high daily doses was more frequent among younger seniors and those who had reported anxiety during the previous year. Patients without cognitive impairment were more likely to receive high dose prescriptions from general practitioners, while those with cognitive impairment were more likely to receive high dose prescriptions from specialists. Conclusion High dose prescribing appears to be related to both patient and physician factors.

  3. Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

    Directory of Open Access Journals (Sweden)

    Shen J

    2017-09-01

    Full Text Available Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP, but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans, suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid

  4. Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

    Science.gov (United States)

    Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

    2017-01-01

    Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

  5. Health effects of daily airborne particle dose in children: Direct association between personal dose and respiratory health effects

    International Nuclear Information System (INIS)

    Buonanno, Giorgio; Marks, Guy B.; Morawska, Lidia

    2013-01-01

    Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35 × 10 3 mm 2 . The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child's activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles. -- Highlights: •Particle dose was estimated through personal monitoring on more than 100 children. •We focused on real-time daily dose of particle alveolar deposited surface area. •Spirometry, skin prick and exhaled Nitric Oxide tests were performed. •Negative link was found between changes in pulmonary functions and individual doses. •A child's lifestyle appeared to have a strong impact on health respiratory outcomes. -- The respiratory health effects of daily airborne particle dose on children through personal monitoring

  6. Influence of Daily Set-Up Errors on Dose Distribution During Pelvis Radiotherapy

    International Nuclear Information System (INIS)

    Kasabasic, M.; Ivkovic, A.; Faj, D.; Rajevac, V.; Sobat, H.; Jurkovic, S.

    2011-01-01

    An external beam radiotherapy (EBRT) using megavoltage beam of linear accelerator is usually the treatment of choice for the cancer patients. The goal of EBRT is to deliver the prescribed dose to the target volume, with as low as possible dose to the surrounding healthy tissue. A large number of procedures and different professions involved in radiotherapy process, uncertainty of equipment and daily patient set-up errors can cause a difference between the planned and delivered dose. We investigated a part of this difference caused by daily patient set-up errors. Daily set-up errors for 35 patients were measured. These set-up errors were simulated on 5 patients, using 3D treatment planning software XiO (CMS Inc., St. Louis, MO). The differences in dose distributions between the planned and shifted ''geometry'' were investigated. Additionally, an influence of the error on treatment plan selection was checked by analyzing the change in dose volume histograms, planning target volume conformity index (CI P TV) and homogeneity index (HI). Simulations showed that patient daily set-up errors can cause significant differences between the planned and actual dose distributions. Moreover, for some patients those errors could influence the choice of treatment plan since CI P TV fell under 97 %. Surprisingly, HI was not as sensitive as CI P TV on set-up errors. The results showed the need for minimizing daily set-up errors by quality assurance programme. (author)

  7. The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Geller Jack

    2002-01-01

    Full Text Available Abstract Background Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year. Methods In an open label, prospective study, 40 men with benign prostatic hyperplasia, previously treated for at least one year with 5 mg of finasteride, took 2.5 mg of finasteride daily for one year. Measurements included AUA symptom score, maximum flow rate, voided volume and PSA. Results There were no significant changes in maximum flow rate, voided volume, or AUA symptom score after one year of finasteride 2.5 mg daily therapy. PSA increased significantly, p Conclusions The daily dose of finasteride can be reduced to 2.5 mg daily without significant effect on subjective and objective measures of urinary obstruction. Although statistically significant increases in PSA are noted when reducing the daily finasteride dose from 5 mg to 2.5 mg, the clinical significance of a mean .6 ng/ml increase in PSA is questionable.

  8. Daily variations in delivered doses in patients treated with radiotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Kupelian, Patrick A.; Langen, Katja M.; Zeidan, Omar A.; Meeks, Sanford L.; Willoughby, Twyla R.; Wagner, Thomas H.; Jeswani, Sam; Ruchala, Kenneth J.; Haimerl, Jason; Olivera, Gustavo H.

    2006-01-01

    Purpose: The aim of this work was to study the variations in delivered doses to the prostate, rectum, and bladder during a full course of image-guided external beam radiotherapy. Methods and Materials: Ten patients with localized prostate cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39 fractions. Daily target localization was performed using intraprostatic fiducials and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total of 390 CT scans. The prostate, rectum, and bladder were manually contoured on each CT by a single physician. Daily dosimetric analysis was performed with dose recalculation. The study endpoints were D95 (dose to 95% of the prostate), rV2 (absolute rectal volume receiving 2 Gy), and bV2 (absolute bladder volume receiving 2 Gy). Results: For the entire cohort, the average D95 (±SD) was 2.02 ± 0.04 Gy (range, 1.79-2.20 Gy). The average rV2 (±SD) was 7.0 ± 8.1 cc (range, 0.1-67.3 cc). The average bV2 (±SD) was 8.7 ± 6.8 cc (range, 0.3-36.8 cc). Unlike doses for the prostate, there was significant daily variation in rectal and bladder doses, mostly because of variations in volume and shape of these organs. Conclusion: Large variations in delivered doses to the rectum and bladder can be documented with daily megavoltage CT scans. Image guidance for the targeting of the prostate, even with intraprostatic fiducials, does not take into account the variation in actual rectal and bladder doses. The clinical impact of techniques that take into account such dosimetric parameters in daily patient set-ups should be investigated

  9. Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

    Directory of Open Access Journals (Sweden)

    Inder S Anand

    2010-06-01

    Full Text Available Inder S Anand1, Anita Deswal2, Dean J Kereiakes3, Das Purkayastha4, Dion H Zappe41Veterans Administration Medical Center, Minneapolis, MN, USA; 2Michael E DeBakey VA Medical Center, Houston, TX, USA; 3The Christ Hospital Heart and Vascular Center, Cincinnati, OH, USA; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Clinical trial registration information: www.clinicaltrials.gov/ct2/show/NC T00294086 Unique identification number: NC T00294086Background: The safety of once-daily (qd dosing of valsartan in heart failure (HF patients is not known. Hypothesis: This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid.Methods: HF patients (NYHA class II–III receiving diuretics (87%, angiotensin-converting enzyme inhibitors (98%, beta-blockers (92%, aldosterone antagonists (25%, or digoxin (32% were randomized to valsartan 40 mg bid (n = 60 or 80 mg qd (n = 55 and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10.Results: The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS. Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%. Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K+, creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points.Conclusion: Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II–III heart failure

  10. Daily fraction dose recalculation based on rigid registration using Cone Beam CT

    Directory of Open Access Journals (Sweden)

    Courtney Bosse

    2014-03-01

    Full Text Available Purpose: To calculate the daily fraction dose for CBCT recalculations based on rigid registration and compare it to the planned CT doses.Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. Pinnacle was used to re-contour the regions of interest (ROI for the specific CBCT by copying the contours from the original CT plan, planned by the prescribing physician, onto each daily CBCT and then manually reshaping contours to match the ROIs. A new plan is then created with the re-contoured CBCT as primary image in order to calculate the daily dose delivered to each ROI. The DVH values are then exported into Excel and overlaid onto the original CT DVH to produce a graph.Results: For the SBRT lung patients, we found that there were small daily volume changes in the lungs, trachea and esophagus. For almost all regions of interest we found that the dose received each day was less than the predicted dose of the planned CT while the PTV dose was relatively the same each day. The results for the prostate patients were similar, showing slight differences in the DVH values for different days in the rectum and bladder but similar PTV.Conclusion: By comparing daily fraction dose between the re-contoured CBCT images and the original planned CT show that PTV coverage for both prostate and SBRT, it has been shown that for PTV coverage, a planned CT is adequate. However, there are differences between the dose for the organs surrounding the PTV. The dose difference is less than the planned in most instances.-----------------------Cite this article as: Bosse C, Tuohy R, Mavroidis P, Shi Z, Crownover R, Gutierrez A, Papanikolaou N, Stathakis S. Daily fraction dose recalculation based on rigid registration using Cone Beam CT. Int J Cancer Ther Oncol 2014; 2(2:020217. DOI: 10.14319/ijcto.0202.17

  11. Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

    Science.gov (United States)

    Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

    2018-04-01

    To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

  12. Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

    Science.gov (United States)

    Miller, Aaron E

    2015-10-01

    The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors

  13. The multiple languages in the daily of the children

    Directory of Open Access Journals (Sweden)

    Cristiane Januário Gonçalves

    2008-04-01

    Full Text Available The language permeates the work in the infantile education and with the game and the interaction, constitutes one of the axes of the pedagogic action close to the children. When we spoke in language it is common we send ourselves to the verbal language and writing that, without a doubt, is fundamental for the infantile development, however, some pedagogic proposals end up just prioritizing those two language forms in the work with the children, in detriment of another possibilities.So, they end up depriving them of new existences and new experiences that favor the amplification of their knowledge. In that sense, they exist proposed in infantile education that have been looking for to just overcome the most restricted understanding of language as oral and writing, trying to enlarge it face to the perception that the child communicates and expressed himself by means of multiple languages, “a hundred languages”, as writes Loris Malaguzzi in his poetry. The content of that article seeks to present and to promote the reflection on some of the multiple present languages in the children's expression. It approaches the importance and the possibilities of working those communication forms and expression as possible languages in the small children's education.

  14. Reparative processes in spleen of rats irradiated with higher daily dose rates of continuous irradiation

    International Nuclear Information System (INIS)

    Mackova, N.; Praslicka, M.; Misurova, E.

    1975-01-01

    Histological and DNA content values were used in evaluating repair processes in the spleen of rats at various intervals following continuous irradiation with daily doses of 50 R, 100 R, 200 R and 500 R (a total dose of 1000 R), and following a single exposure to 1000 R. Histological changes found immediately after irradiation indicated the induction of significant injuries, this mainly as a result of daily doses of 200 R and 500 R. The complete repair of the DNA content and of a number of erythroid elements and also a 70 to 80% regeneration of the white pulp took place within 25 days. The same period was found to be insufficient for the complete repair of megakaryocytes. No signs of repair were observed in spleen in the histological picture or DNA content after a single irradiation with a dose of 1000 R. (author)

  15. Reparative processes in spleen of rats irradiated with higher daily dose rates of continuous irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mackova, N; Praslicka, M; Misurova, E [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Prirodovedecka Fakulta

    1975-01-01

    Histological and DNA content values were used in evaluating repair processes in the spleen of rats at various intervals following continuous irradiation with daily doses of 50 R, 100 R, 200 R and 500 R (a total dose of 1000 R), and following a single exposure to 1000 R. Histological changes found immediately after irradiation indicated the induction of significant injuries, this mainly as a result of daily doses of 200 R and 500 R. The complete repair of the DNA content and of a number of erythroid elements and also a 70 to 80% regeneration of the white pulp took place within 25 days. The same period was found to be insufficient for the complete repair of megakaryocytes. No signs of repair were observed in spleen in the histological picture or DNA content after a single irradiation with a dose of 1000 R.

  16. Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

    Science.gov (United States)

    Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

    2012-01-01

    Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

  17. Dose evaluation from multiple detector outputs using convex optimisation

    International Nuclear Information System (INIS)

    Hashimoto, M.; Iimoto, T.; Kosako, T.

    2011-01-01

    A dose evaluation using multiple radiation detectors can be improved by the convex optimisation method. It enables flexible dose evaluation corresponding to the actual radiation energy spectrum. An application to the neutron ambient dose equivalent evaluation is investigated using a mixed-gas proportional counter. The convex derives the certain neutron ambient dose with certain width corresponding to the true neutron energy spectrum. The range of the evaluated dose is comparable to the error of conventional neutron dose measurement equipments. An application to the neutron individual dose equivalent measurement is also investigated. Convexes of particular dosemeter combinations evaluate the individual dose equivalent better than the dose evaluation of a single dosemeter. The combinations of dosemeters with high orthogonality of their response characteristics tend to provide a good suitability for dose evaluation. (authors)

  18. Dynamic interactions between hydrogeological and exposure parameters in daily dose prediction under uncertainty and temporal variability

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Vikas, E-mail: vikas.kumar@urv.cat [Department of Chemical Engineering, Rovira i Virgili University, Tarragona 43007 (Spain); Barros, Felipe P.J. de [Sonny Astani Department of Civil and Environmental Engineering, University of Southern California, Los Angeles 90089, CA (United States); Schuhmacher, Marta [Department of Chemical Engineering, Rovira i Virgili University, Tarragona 43007 (Spain); Fernàndez-Garcia, Daniel; Sanchez-Vila, Xavier [Hydrogeology Group, Department of Geotechnical Engineering and Geosciences, University Politècnica de Catalunya-BarcelonaTech, Barcelona 08034 (Spain)

    2013-12-15

    Highlights: • Dynamic parametric interaction in daily dose prediction under uncertainty. • Importance of temporal dynamics associated with the dose. • Different dose experienced by different population cohorts as a function of time. • Relevance of uncertainty reduction in the input parameters shows temporal dynamism. -- Abstract: We study the time dependent interaction between hydrogeological and exposure parameters in daily dose predictions due to exposure of humans to groundwater contamination. Dose predictions are treated stochastically to account for an incomplete hydrogeological and geochemical field characterization, and an incomplete knowledge of the physiological response. We used a nested Monte Carlo framework to account for uncertainty and variability arising from both hydrogeological and exposure variables. Our interest is in the temporal dynamics of the total dose and their effects on parametric uncertainty reduction. We illustrate the approach to a HCH (lindane) pollution problem at the Ebro River, Spain. The temporal distribution of lindane in the river water can have a strong impact in the evaluation of risk. The total dose displays a non-linear effect on different population cohorts, indicating the need to account for population variability. We then expand the concept of Comparative Information Yield Curves developed earlier (see de Barros et al. [29]) to evaluate parametric uncertainty reduction under temporally variable exposure dose. Results show that the importance of parametric uncertainty reduction varies according to the temporal dynamics of the lindane plume. The approach could be used for any chemical to aid decision makers to better allocate resources towards reducing uncertainty.

  19. Multiple cost criteria for occupational dose reduction

    International Nuclear Information System (INIS)

    James, J.Z.

    1983-01-01

    This paper describes a simple, feasible procedure for deciding if a proposed dose reduction measure is justified under ALARA, based on engineering economic principles of project feasibility analysis. Particular attention is given to the fixing of cost criteria: the importance of melding disparate objectives into a single parameter, and the distinction between a cost criterion and a cost consideration. (author)

  20. Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

    Science.gov (United States)

    Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

    2017-10-01

    Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHDvitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Determination of 210Po concentration in commercially available infant formulae and assessment of daily ingestion dose

    Directory of Open Access Journals (Sweden)

    Ravi K. Prabhath

    2015-07-01

    Full Text Available A study has been conducted to estimate the concentration of natural radioactive polonium in commercially available packaged infant food formulae available in Mumbai, India and the corresponding daily dose normalized based on its shelf life. Eleven most popular international brands of infant formulae were sourced from market and three aliquots from each sample were analysed for concordant results. Autodeposition method onto a silver planchet from hot dilute acid solution followed by alpha spectrometry was performed for estimation of polonium. Radiochemical recovery was ascertained by the addition of 209Po tracer. Radiochemical recovery of 209Po tracer was ranged from 14.7 to 98.1 %. The 210Po concentration in the samples was in the range of 0.08–0.23 Bq kg−1 on measured date and the corresponding daily dose, calculated on normalized date which is at mid-point of the shelf life of the sample, was ranged from 0.04 to 0.89 μSv d−1 as per the recommended daily consumption. The annual committed effective dose estimated based on the average of daily dose was found to be 150 μSv.

  2. Radiation therapy in cancer patients with psoriasis. The fractionated daily dose and the Koebner phenomenon

    International Nuclear Information System (INIS)

    Ben-Yosef, Rami; Soyfer, Vyacheslav; Vexler, Akiva

    2005-01-01

    Skin side effects following XRT take place more often in patients with skin disorders. In this study six patients with psoriatic lesions were evaluated. The total/daily XRT dose to the tumor site was 50-70/1.8-2.0 Gy. No debilitating effect of XRT was observed in both the psoriatic lesions and in the surrounding normal skin

  3. Daily dose and shielding optimization in work performance at 'Ukrytie' object

    International Nuclear Information System (INIS)

    Batij, V.G.; Derengovskij, V.V.; Egorov, V.V.; Kuz'menko, V.A.; Rud'ko, V.M.; Sizov, A.A.; Stoyanov, A.I.

    2000-01-01

    The procedure of daily dose and shielding optimization in work performance at 'Ukryttia' object is offered. The recommendations allowing reducing collective effective doze according to the optimization principle are submitted. The technique of shielding optimization is given at stabilization works realization. The optimum shielding calculation example for the strengthening support is given

  4. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

    Science.gov (United States)

    Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

    2010-01-01

    Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

  5. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

    2013-05-15

    Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

  6. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

    International Nuclear Information System (INIS)

    Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

    2013-01-01

    Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

  7. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

    Science.gov (United States)

    Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

    2013-05-01

    Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

  8. Cumulative radiation dose of multiple trauma patients during their hospitalization

    International Nuclear Information System (INIS)

    Wang Zhikang; Sun Jianzhong; Zhao Zudan

    2012-01-01

    Objective: To study the cumulative radiation dose of multiple trauma patients during their hospitalization and to analyze the dose influence factors. Methods: The DLP for CT and DR were retrospectively collected from the patients during June, 2009 and April, 2011 at a university affiliated hospital. The cumulative radiation doses were calculated by summing typical effective doses of the anatomic regions scanned. Results: The cumulative radiation doses of 113 patients were collected. The maximum,minimum and the mean values of cumulative effective doses were 153.3, 16.48 mSv and (52.3 ± 26.6) mSv. Conclusions: Multiple trauma patients have high cumulative radiation exposure. Therefore, the management of cumulative radiation doses should be enhanced. To establish the individualized radiation exposure archives will be helpful for the clinicians and technicians to make decision whether to image again and how to select the imaging parameters. (authors)

  9. Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

    International Nuclear Information System (INIS)

    Rucinski, Antoni; Brons, Stephan; Richter, Daniel; Habl, Gregor; Debus, Jürgen; Bert, Christoph; Haberer, Thomas; Jäkel, Oliver

    2015-01-01

    Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90 Rectum ), respectively. The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90 Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal

  10. HALF-DOSE DEPOT TRIPTORELIN COMPARABLE TO REDUCED DAILY BUSERELIN: A RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    L. Safdarian

    2007-09-01

    Full Text Available Pituitary suppression by depot GnRH agonist may be excessive for ovarian stimulation. This study compares the efficacy of a single half-dose depot triptorelin and reduced-dose daily buserelin in a long protocol ICSI/ET. METHODS: A total of 182 patients were randomized into two groups using sealed envelopes. Pituitary desensitization was obtained in group 1 (91 patients with half-dose (1.87 mg depot triptorelin in the mid-luteal phase of their menstrual cycle, and in group 2 (91 patients with standard daily dose (0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotropin (HMG stimulation. RESULTS: No significant differences were found among those who received HCG in terms of clinical pregnancy rate (34.4% in both groups, implantation rate (14.8% in group 1 versus 11.1% in group 2, fertilization rate (93.3 versus 95.6%, poor response rate (11.1 versus 6.7%, and miscarriage rate (11.1 versus 7.8%. No significant differences were seen in number of HMG ampoules used, follicles at HCG administration, and oocytes retrieved. The number of days of stimulation was significantly reduced in group 2 (11.2 +/- 1.8 in group 1 versus 10.6 +/- 1.9, p = 0.030. CONCLUSION: A half-dose of depot triptorelin can be successfully used in ovarian stimulation instead of reduced-dose daily buserelin, with more patient comfort and reduced stress and cost of injections.

  11. Marijuana’s Dose-Dependent Effects in Daily Marijuana Smokers

    OpenAIRE

    Ramesh, Divya; Haney, Margaret; Cooper, Ziva D.

    2013-01-01

    Active marijuana produces significant subjective, psychomotor, and physiological effects relative to inactive marijuana, yet demonstrating that these effects are dose-dependent has proven difficult. This within-subject, double-blind study was designed to develop a smoking procedure to obtain a marijuana dose–response function. In four outpatient laboratory sessions, daily marijuana smokers (N = 17 males, 1 female) smoked six 5-s puffs from 3 marijuana cigarettes (2 puffs/cigarette). The numbe...

  12. Determination of 210Po concentration in commercially available infant formulae and assessment of daily ingestion dose

    OpenAIRE

    Prabhath, Ravi K.; Sreejith, Sathyapriya R.; Nair, Madhu G.; Rao, D.D.; Pradeepkumar, K.S.

    2015-01-01

    A study has been conducted to estimate the concentration of natural radioactive polonium in commercially available packaged infant food formulae available in Mumbai, India and the corresponding daily dose normalized based on its shelf life. Eleven most popular international brands of infant formulae were sourced from market and three aliquots from each sample were analysed for concordant results. Autodeposition method onto a silver planchet from hot dilute acid solution followed by alpha spec...

  13. Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma

    International Nuclear Information System (INIS)

    Hoebers, Frank J.P.; Heemsbergen, Wilma; Balm, Alfons J.M.; Zanten, Mathilde van; Schornagel, Jan H.; Rasch, Coen R.N.

    2007-01-01

    Background and purpose: To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin. Materials and methods: 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m 2 i.v. x20, daily before RT). After 47 patients, the treatment protocol (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were given to the subsequent 74 patients (Hydr-Ac-RT Group). Results: Mean follow-up was 29 months (range 7-62). More chemotherapy could be administered in the Hydr-Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of patients, p = 0.008), with less renal toxicity (p < 0.001) and less hospital admissions (p < 0.02). However, mucositis was more pronounced and tubefeeding more frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from 74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p = 0.06), although this did not lead to an improvement in loco-regional control. Conclusions: Concurrent chemoradiation with daily low dose cisplatin is feasible and effective for selected patients with advanced HNSCC. Although the addition of accelerated RT resulted in more mucositis and tubefeeding, the introduction of prehydration led to better compliance to therapy with more chemotherapy administered and less hospital admissions

  14. Evaluation of delivered dose for a clinical daily adaptive plan selection strategy for bladder cancer radiotherapy

    International Nuclear Information System (INIS)

    Lutkenhaus, Lotte J.; Visser, Jorrit; Jong, Rianne de; Hulshof, Maarten C.C.M.; Bel, Arjan

    2015-01-01

    Purpose: To account for variable bladder size during bladder cancer radiotherapy, a daily plan selection strategy was implemented. The aim of this study was to calculate the actually delivered dose using an adaptive strategy, compared to a non-adaptive approach. Material and methods: Ten patients were treated to the bladder and lymph nodes with an adaptive full bladder strategy. Interpolated delineations of bladder and tumor on a full and empty bladder CT scan resulted in five PTVs for which VMAT plans were created. Daily cone beam CT (CBCT) scans were used for plan selection. Bowel, rectum and target volumes were delineated on these CBCTs, and delivered dose for these was calculated using both the adaptive plan, and a non-adaptive plan. Results: Target coverage for lymph nodes improved using an adaptive strategy. The full bladder strategy spared the healthy part of the bladder from a high dose. Average bowel cavity V30Gy and V40Gy significantly reduced with 60 and 69 ml, respectively (p < 0.01). Other parameters for bowel and rectum remained unchanged. Conclusions: Daily plan selection compared to a non-adaptive strategy yielded similar bladder coverage and improved coverage for lymph nodes, with a significant reduction in bowel cavity V30Gy and V40Gy only, while other sparing was limited

  15. Assessment of postoperative changes in antihypertensive drug consumption in patients with primary aldosteronism using the defined daily dose

    Directory of Open Access Journals (Sweden)

    Takanobu Utsumi

    2014-10-01

    Conclusion: The defined daily dose is a useful tool for assessing total changes in the consumption of antihypertensive drugs in patients with primary aldosteronism. Using the defined daily dose, clinicians could explain in detail to patients with primary aldosteronism the predicted postoperative change in antihypertensive drug consumption.

  16. Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors.

    Science.gov (United States)

    Camacho, Luis H; Olson, Jon; Tong, William P; Young, Charles W; Spriggs, David R; Malkin, Mark G

    2007-04-01

    Phenylbutyrate (PBA), and its metabolite phenylacetate (PAA), induce growth inhibition and cellular differentiation in multiple tumor models. However, despite their potential anti-cancer properties, several pharmacodynamic aspects remain unknown. We conducted a dose escalating trial to evaluate twice-daily intravenous PBA infusions for two consecutive weeks (Monday through Friday) every month at five dose levels (60-360 mg/kg/day). Twenty-one patients with the following malignancies were treated: colon carcinoma 4, non-small cell lung carcinoma 4; anaplastic astrocytoma 3, glioblastoma multiforme 3, bladder carcinoma 2, sarcoma 2, and ovarian carcinoma, rectal hemangiopericytoma, and pancreatic carcinoma 1 each. Conversion of PBA to PAA and phenylacetylglutamine (PAG) was documented without catabolic saturation. Plasma content of PBA > or =1 mM was documented for only 3 h following each dose at the top two dosages. The therapy was well tolerated overall. Common adverse effects included grade 1 nausea/vomiting, fatigue, and lightheadedness. Dose limiting toxicities were short-term memory loss, sedation, confusion, nausea, and vomiting. Two patients with anaplastic astrocytoma and a patient with glioblastoma remained stable without tumor progression for 5, 7, and 4 months respectively. Administration of PBA in a twice-daily infusion schedule is safe. The maximum tolerated dose is 300 mg/kg/day. Study designs with more convenient treatment schedules and specific molecular correlates may help to further delineate the mechanism of action of this compound. Future studies evaluating PBA's ability to induce histone acetylation and cell differentiation alone or in combination with other anti-neoplastics are recommended.

  17. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

    Science.gov (United States)

    Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

    2013-02-01

    Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy

    Directory of Open Access Journals (Sweden)

    Samuel L Washington III

    2010-08-01

    Full Text Available Samuel L Washington III1, Alan W Shindel21School of Medicine, University of California at San Francisco, San Francisco, California, USA; 2Department of Urology, University of California at San Francisco, San Francisco, California, USAAbstract: Selective phosphodiesterase type 5 inhibitors (PDE5Is have revolutionized the ­treatment of erectile dysfunction (ED in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.Keywords: PDE5 inhibitor, on-demand therapy, side effects, daily dosing

  19. The response of mouse skin to multiple small doses of radiation

    International Nuclear Information System (INIS)

    Denekamp, J.; Harris, S.R.

    1975-01-01

    The response of mouse skin has been tested by irradiating the foot of albino mice and scoring erythema and desquamation during the following month. Multiple small doses of 150, 250 and 350 rad have been given 'daily', and the test dose necessary to achieve a given reaction has been determined one day after the last small fraction. This test dose has been compared with the single dose necessary to produce the same reaction level in previously untreated mice, in order to determine the ratio of the slopes of the dose-response curve at low and high doses: Slope ratio = (single dose - test dose)/total fractionated priming dose. In three separate experiments the slope ratio decreased as the dose per fraction was reduced from 350 to 150 rad. This conflicts with the data of Dutreix et al, who found a constant slope ratio over this dose range. The present data are compared with those obtained by Denekamp using 4, 9 and 14 fractions of 300 rad and by Douglas et al, using the same experimental technique, over the dose range 45 to 200 rad/fraction. In addition, the results from multifraction experiments in which equal dose increments were administered until the requisite skin reaction was achieved are also analysed in terms of their slope ratio (Fowler et al. Douglas et al). When all these results are plotted it is impossible to be sure whether the slope ratio is decreasing over the range 300 to 45 rad per fraction, although it seems likely. Most of the values at low doses lie in the range 0.15 to 0.25, indicating that at low doses the radiation is only 15 to 25% as effective per rad in causing cell death as at higher doses. (author)

  20. Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

    Science.gov (United States)

    Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María

    2014-01-01

    Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  1. Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

    Science.gov (United States)

    Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

    2015-05-01

    Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels 50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p 75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

  2. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  3. Effect of sensor-augmented pump treatment vs. multiple daily injections on albuminuria

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Willum Hansen, Tine; Rossing, Peter

    2015-01-01

    CONTEXT: The effect of glycaemic control on persisting albuminuria remains unclear. Insulin delivery and glucose variability may be important Objective: To investigate the effect of 1 year treatment with sensor-augmented insulin pump (SAP) or multiple daily injections (MDI) on albuminuria. DESIGN...

  4. Continuous subcutaneous insulin infusion versus multiple daily injections: the impact of baseline A1c

    NARCIS (Netherlands)

    Retnakaran, Ravi; Hochman, Jackie; DeVries, J. Hans; Hanaire-Broutin, Helene; Heine, Robert J.; Melki, Vincent; Zinman, Bernard

    2004-01-01

    Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be

  5. Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

    Science.gov (United States)

    Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

    2016-01-01

    The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

  6. Modification of the biologic dose to normal tissue by daily fraction

    Energy Technology Data Exchange (ETDEWEB)

    Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

    1976-12-01

    A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

  7. Estimation of the effectivity of gamma teletherapy with fractionated daily doses in inoperable malignant tumors

    International Nuclear Information System (INIS)

    Mardynskij, Yu.S.; Leskov, V.P.

    1982-01-01

    131 patients with lung, esophagus, rectum and mandibulofacial tumors, most of them being inoperable, were treated with fractionated gamma teletherapy. The daily focus dose of 2-2.2 Gy was applied in 2 fractions with an interval of 4-6 h. The total focus dose of one course of treatment was 40-70 Gy. In 56 patients (42.7%) a complete regression of the tumors and of the increased regional lymph nodes was obtained. The irradiation by the mentioned technique showed the highest effectivity for tumors of the lung and the esophagus. The diminished frequency and an easier progress of the radiation reactions are important because they often prevent to carry out a radical therapy. (author)

  8. Escalating dose, multiple binge methamphetamine regimen does not impair recognition memory in rats.

    Science.gov (United States)

    Clark, Robert E; Kuczenski, Ronald; Segal, David S

    2007-07-01

    Rats exposed to methamphetamine (METH) in an acute high dose "binge" pattern have been reported to exhibit a persistent deficit in a novel object recognition (NOR) task, which may suggest a potential risk for human METH abusers. However, most high dose METH abusers initially use lower doses before progressively increasing the dose, only eventually engaging in multiple daily administrations. To simulate this pattern of METH exposure, we administered progressively increasing doses of METH to rats over a 14 day interval, then treated them with daily METH binges for 11 days. This treatment resulted in a persistent deficit in striatal dopamine (DA) levels of approximately 20%. We then tested them in a NOR task under a variety of conditions. We could not detect a deficit in their performance in the NOR task under any of the testing conditions. These results suggest that mechanisms other than or additional to the decrement in striatal DA associated with an acute METH binge are responsible for the deficit in the NOR task, and that neuroadaptations consequential to prolonged escalating dose METH pretreatment mitigate against these mechanisms.

  9. Gemfibrozil is a strong inactivator of CYP2C8 in very small multiple doses.

    Science.gov (United States)

    Honkalammi, J; Niemi, M; Neuvonen, P J; Backman, J T

    2012-05-01

    Therapeutic doses of gemfibrozil cause mechanism-based inactivation of CYP2C8 via formation of gemfibrozil 1-O-β-glucuronide. We investigated the extent of CYP2C8 inactivation caused by three different doses of gemfibrozil twice dailyfor 5 days, using repaglinide as a probe drug, in 10 healthy volunteers. At the end of this 5-day regimen, there were dose-dependent increases in the area under the plasma concentration–time curve from 0 to infinity (AUC0–∞) of repaglinide by3.4-, 5.5-, and 7.0-fold corresponding to 30, 100, and 600 mg of gemfibrozil, respectively, as compared with the control phase (P gemfibrozil 1-O-β-glucuronide, a gemfibrozil dose of 30 mg twice daily was estimated to inhibit CYP2C8 by >70% and 100 mg twice daily was estimated to inhibit it by >90%. Hence, gemfibrozil is a strong inactivator of CYP2C8 even in very small, subtherapeutic, multiple doses. Administration of small gemfibrozil doses may be useful in optimizing the pharmacokinetics of CYP2C8 substrate drugs and in reducing the formation of their potentially toxic metabolites via CYP2C8.

  10. Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

    Directory of Open Access Journals (Sweden)

    Daniel T. C. Cox

    2017-02-01

    Full Text Available Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a nature dose type, that is the frequency and duration (time spent in private green space and intensity (quantity of neighbourhood vegetation cover of nature exposure and (b health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  12. Estimation of rectal dose using daily megavoltage cone-beam computed tomography and deformable image registration.

    Science.gov (United States)

    Akino, Yuichi; Yoshioka, Yasuo; Fukuda, Shoichi; Maruoka, Shintaroh; Takahashi, Yutaka; Yagi, Masashi; Mizuno, Hirokazu; Isohashi, Fumiaki; Ogawa, Kazuhiko

    2013-11-01

    The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CT value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R(2)=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R(2)=0.61±0.16). We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Estimation of Rectal Dose Using Daily Megavoltage Cone-Beam Computed Tomography and Deformable Image Registration

    Energy Technology Data Exchange (ETDEWEB)

    Akino, Yuichi, E-mail: akino@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Department of Radiology, Osaka University Hospital, Suita, Osaka (Japan); Yoshioka, Yasuo [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Fukuda, Shoichi [Department of Radiation Oncology, Osaka General Medical Center, Osaka (Japan); Maruoka, Shintaroh [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Takahashi, Yutaka [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota (United States); Yagi, Masashi [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Mizuno, Hirokazu [Department of Radiology, Osaka University Hospital, Suita, Osaka (Japan); Isohashi, Fumiaki [Oncology Center, Osaka University Hospital, Suita, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)

    2013-11-01

    Purpose: The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Methods and Materials: Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CT value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. Results: The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R{sup 2}=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R{sup 2}=0.61±0.16). Conclusion: We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume.

  14. SU-E-T-139: Automated Daily EPID Exit Dose Analysis Uncovers Treatment Variations

    Energy Technology Data Exchange (ETDEWEB)

    Olch, A [University of Southern California, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To evaluate a fully automated EPID exit dose system for its ability to detect daily treatment deviations including patient setup, delivery, and anatomy changes. Methods: PerFRACTION (Sun Nuclear Corporation) software is a system that uses integrated EPID images taken during patient treatment and automatically pulled from the Aria database and analyzed based on user-defined comparisons. This was used to monitor 20 plans consisting of a total of 859 fields for 18 patients, for a total of 251 fractions. Nine VMAT, 5 IMRT, and 6 3D plans were monitored. The Gamma analysis was performed for each field within a plan, comparing the first fraction against each of the other fractions in each treatment course. A 2% dose difference, 1 mm distance-to-agreement, and 10% dose threshold was used. These tight tolerances were chosen to achieve a high sensitivity to treatment variations. The field passed if 93% of the pixels had a Gamma of 1 or less. Results: Twenty-nine percent of the fields failed. The average plan passing rate was 92.5%.The average 3D plan passing rate was less than for VMAT or IMRT, 84%, vs. an average of 96.2%. When fields failed, an investigation revealed changes in patient anatomy or setup variations, often also leading to variations of transmission through immobilization devices. Conclusion: PerFRACTION is a fully automated system for determining daily changes in dose transmission through the patient that requires no effort other than for the imager panel to be deployed during treatment. A surprising number of fields failed the analysis and can be attributed to important treatment variations that would otherwise not be appreciated. Further study of inter-fraction treatment variations is possible and warranted. Sun Nuclear Corporation provided a license to the software described.

  15. High-dose contrast-enhanced MRI in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Koudriavtseva, T. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Pozzilli, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Di Biasi, C. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Iannilli, M. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Trasimeni, G. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Gasperini, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Argentino, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Gualdi, G.F. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy)

    1996-05-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs.

  16. High-dose contrast-enhanced MRI in multiple sclerosis

    International Nuclear Information System (INIS)

    Koudriavtseva, T.; Pozzilli, C.; Di Biasi, C.; Iannilli, M.; Trasimeni, G.; Gasperini, C.; Argentino, C.; Gualdi, G.F.

    1996-01-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs

  17. Radiotherapy combined with daily administration of low dose cisplatin for head and neck cancer

    International Nuclear Information System (INIS)

    Fujita, Masahiro; Murayama, Shigeyuki; Matayoshi, Yoshinobu; Ikeda, Hiroshi; Shimizutani, Kimishige; Inoue, Toshihiko; Kozuka, Takahiro; Masaki, Norie.

    1990-01-01

    Serum concentrations of cisplatin (CDDP) and acute complications were studied in patients treated for head and neck cancer by radiotherapy combined with daily administration of low doses of CDDP (5 mg/m 2 or 6 mg/body) at Osaka University Hospital between March 1988 and December 1989. Serum concentrations of total-CDDP (6 patients) and free-CDDP (2 patients) were studied in cases injected intravenously with 5 mg/m 2 daily. Total-CDDP determined just before daily administration of CDDP was increased gradually (0.35 to 0.64 μg/ml by the 7th day, 0.42 to 0.91 μg/ml by the 14th day and 0.60 to 0.82 μg/ml by the 20th or 21st day) and still observed in the serum for more than two weeks after cessation of the chemotherapy. Serum concentrations of free-CDDP were about 0.35 μg/ml at 5 minutes and 0.15 μg/ml at 30 minutes after the intravenous injection of CDDP. Incidence of the acute complications more severe than grade 2 were nausea and vomiting: 4/52 (8%), leukopenia: 11/52 (21%) and thrombocytopenia: 4/52 (8%). Incidence of myelosuppression (leukopenia and/or thrombocytopenia) was 11/26(42%) when the total dose of CDDP exceeded 120 mg, and 3/26 (12%) when it was less than 120 mg. Transient renal dysfunction (increase of serum creatinine) of grade 1 was seen in only 3 patients. (author)

  18. Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose.

    Science.gov (United States)

    Kör, Deniz; Yılmaz, Berna Şeker; Bulut, Fatma Derya; Ceylaner, Serdar; Mungan, Neslihan Önenli

    2017-07-26

    Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.

  19. Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

    NARCIS (Netherlands)

    Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

    2012-01-01

    Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

  20. Urinary steroid hormone patterns: III. Effect of continuous daily administration of low dose megestrol acetate.

    Science.gov (United States)

    Kumari, G L; Roy, S; Allag, I S; Ghosal, J

    1975-12-01

    The effect of megestrol acetate, administered in daily doses of .5 mg, on urinary steroid levels was studied before, during, and after therapy in 4 women volunteers. In each case, pregnanediol levels were reduced, though ovulatory biphasic patterns, as reflected in basal body temperature patterns, were apparent in the majority of the cycles, which suggests that corpus luteum function, but not ovulation, was impaired. 17-ketosteroid levels were significantly (p less than .001) increased either during or after treatment, while 17-hydroxycorticoid levels were reduced in 3 of the women. 2 subjects showed a marked reduction in levels of 17-ketogenic steroids and corticoid levels. Total estrogen levels seemed to correlate with the levels of corticoid excretion.

  1. The economics of 4 grams once daily mesalazine dosing compared with 4 grams twice daily in active ulcerative colitis

    NARCIS (Netherlands)

    Connolly, M.; Kuyvenhoven, J.; Postma, M.; Nielsen, S.

    2013-01-01

    Background: Dosing frequency is an important treatment consideration that has been shown to influence adherence and outcomes when treating ulcerative colitis (UC). In this analysis we evaluate the economic consequences of outcome differences observed in the study comparing mesalazine 4g per day once

  2. 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

  3. Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

    Science.gov (United States)

    Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

    2014-12-01

    Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

  4. The daily radon dose in body organs caused by drinking milk and water

    International Nuclear Information System (INIS)

    Mansoureh Mansour Bahmani; Mohammad Reza Rezaie; Elham Rezvan Nejad; Hassan Reza Dehghan

    2014-01-01

    Milk is considered as the richest nutrition, being used by people. When drinking milk or water the radon gas will transfer from air to them rapidly. Since milk is majorly composed of water, probably radon existence in livestock consumable water could be the main cause of its presence in milk. Different portion of milk changed by radon gamma ray and consumption of radon included water or milk has its effects on the human body. For investigation the effect of radon in water or milk on human organs, this study has been done in two phases with MCNPX software. In the first phase, the dose rate of absorbed gamma ray by different portion of milk which is indoctrinated by 1 Bq/m 3 of radon during a day is calculated. Moreover, the effects shown by milk and its components in radon gamma spectrum, which is demonstrator of milk absorption spectrum, are also surveyed. In the second phase as well, according to the human body phantom, the absorbed gamma dose caused by daily consumption of indoctrinated water or milk with 1 Bq/m 3 radon is calculated. The production rate of free radicals in milk and its different components are derived according to escape data of MCNPX code. (author)

  5. Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole.

    Science.gov (United States)

    Sahara, S; Sugimoto, M; Uotani, T; Ichikawa, H; Yamade, M; Iwaizumi, M; Yamada, T; Osawa, S; Sugimoto, K; Umemura, K; Miyajima, H; Furuta, T

    2013-11-01

    Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan. To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype. We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily. Although median pH values with esomeprazole, omeprazole, lansoprazole and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5-7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI. In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily. © 2013 John Wiley & Sons Ltd.

  6. Influence of daily setup measurements and corrections on the estimated delivered dose during IMRT treatment of prostate cancer patients

    International Nuclear Information System (INIS)

    Haaren, Paul M.A. van; Bel, Arjan; Hofman, Pieter; Vulpen, Marco van; Kotte, Alexis N.T.J.; Heide, Uulke A. van der

    2009-01-01

    Purpose: To evaluate the impact of marker-based position verification, using daily imaging and an off-line correction protocol, by calculating the delivered dose to prostate, rectum and bladder. Methods: Prostate cancer patients (n = 217) were treated with IMRT, receiving 35 daily fractions. Plans with five beams were optimized taking target coverage (CTV, boost) and organs-at-risk (rectum and bladder) into account. PTV margins were 8 mm. Prostate position was verified daily using implanted fiducial gold markers by imaging the first segment of all the five beams on an EPID. Setup deviations were corrected off-line using an adapted shrinking-action-level protocol. The estimated delivered dose, including daily organ movements, was calculated using a version of PLATO's dose engine, enabling batch processing of large numbers of patients. The dose was calculated ± inclusion of setup corrections, and was evaluated relative to the original static plan. The marker-based measurements were considered representative for all organs. Results: Daily organ movements would result in an underdosage of 2-3 Gy to CTV and boost volume relative to the original plan, which was prevented by daily setup corrections. The dose to rectum and bladder was on average unchanged, but a large spread was introduced by organ movements, which was reduced by including setup corrections. Conclusions: Without position verification and setup corrections, margins of 8mm would be insufficient to account for position uncertainties during IMRT of prostate cancer. With the daily off-line correction protocol, the remaining variations are accommodated adequately

  7. Blood responses under chronic low daily dose gamma irradiation: Pt.1

    International Nuclear Information System (INIS)

    Seed, T.M.; Carnes, B.A.; Tolle, D.V.; Fritz, T.E.

    1989-01-01

    Male beagles chronically exposed to low daily doses of 60 Co γ rays show one of three hematopoietic patterns, which reflect three different distinctly responding subgroups: (1) low radioresistance with progressing aplastic anemia and shortened survival ( -S -AA subgroup); (2) high radioresistance with a complex of progressing myeloproliferative disorders ( + R-MPD group); or (3) high radioresistance with other nonMPD syndromes ( + R-nonMPD group). Blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes, and platelets) were assessed and fitted to a flexible polynomial spline model. Results showed that relative to the overall magnitude of blood cell loss as well as to the maximum rate of suppression during the initial phase, the subgroups were generally ranked - S-AA >> + R-MPD > + R-nonMPD. Relative to the overall strength of the recovery response, the subgroups were generally ranked + R-MPD > + R-nonMPD >>> - S-AA. In terms of overall maintenance levels of circulating blood cells during the recovery phase, however, the + R-nonMPD subgroup consistently exhibited stronger responses than the + R-MPD subgroup. These results support our contention that selected subgroups of dogs have strong propensities to specific hematopathologies (i.e. aplastic anemia and myeloid leukemia) under chronic irradiation and that these pathology-prone animals exhibit a series of marked differential hematopoietic responses during early preclinical phases, which serve effectively to prognosticate subsequent pathological progression. (author)

  8. A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation

    Directory of Open Access Journals (Sweden)

    Farrauto Leonardo

    2011-06-01

    Full Text Available Abstract Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels. Methods In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD was measured at baseline, discharge from acute care (approximately 4-weeks, and 3-months. Results Sixty-five patients were enrolled in the study (44% male. An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15 and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09, respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L, and 44% of the 100,000 group. Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D. Trial registration Clinical

  9. V-Go Insulin Delivery System Versus Multiple Daily Insulin Injections for Patients With Uncontrolled Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Winter, Abigail; Lintner, Michaela; Knezevich, Emily

    2015-04-21

    Type 2 diabetes mellitus affects over 29.1 million Americans, diagnosed and undiagnosed. Achieving and maintaining glycemic control for these patients is of extreme importance when working to prevent complications and improve quality of life for patients. The V-Go is a newly developed insulin delivery system. The push of a button inserts a needle into the patient once daily and remains attached for 24 hours. The V-Go is designed to release a set basal rate throughout the day, while allowing patients to provide up to 36 units of on-demand bolus insulin with the manual click of 2 buttons. It is a spring-loaded device filled daily with rapid-acting insulin that runs without the use of batteries or computer software. The main objective of this prospective active comparator study was to observe the A1C lowering effects of multiple daily insulin injections (MDII) versus the use of the V-Go insulin delivery system for patients with uncontrolled type 2 diabetes mellitus over a 3-month period. In addition, the effect on insulin requirement for these patients was assessed with secondary comparisons of weight, blood pressure, prevalence of hypoglycemic events, and quality of life before and after 3 months of intensified insulin therapy with regular monitoring by a clinical pharmacist at an internal medicine clinic. The average A1C lowering experienced by the 3 patients in the V-Go group was 1.5%, while the average A1C change in the 3 patients in the MDII group was an increase of 0.2%. All patients in the V-Go group experienced a decrease in insulin total daily dose (TDD), with an average decrease of 26.3 units. All patients in the MDII group experienced an increase in insulin TDD with an average of 15 units daily to achieve therapeutic goals individualized for each patient. All patients who underwent intensification of insulin therapy experienced an increase in subjective quality of life (QOL) as determined using the Diabetes-39 (D-39) questionnaire, though QOL results lacked

  10. Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Saffian, S M; Duffull, S B; Wright, Dfb

    2017-08-01

    There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  11. A single daily dose enhances the adherence to immunosuppressive treatment in kidney transplant recipients: a cross-sectional study.

    Science.gov (United States)

    Obi, Yoshitsugu; Ichimaru, Naotsugu; Kato, Taigo; Kaimori, Jun-Ya; Okumi, Masayoshi; Yazawa, Koji; Rakugi, Hiromi; Nonomura, Norio; Isaka, Yoshitaka; Takahara, Shiro

    2013-04-01

    Nonadherence to treatment regimens for immunosuppressive agents is one of the major risk factors for allograft failure in kidney transplant recipients. The aim of this study was to estimate the relative effect of daily dosing on treatment adherence, not to identify how patients are non-adherent, in long-term kidney transplant recipients. In January 2009, a cross-sectional, anonymous, and voluntary questionnaire survey was given to kidney transplant recipients who regularly visited Inoue Hospital. A self-reporting questionnaire underestimates nonadherence, but we reasoned that the effect of the dosing regimen should be estimated with relative accuracy by using the generalized ordered logit/partial proportional hazard odds model given that the distribution patterns in the degree of nonadherence have been shown to be similar with other measures. Of 336 eligible patients, 312 (92.9 %) participated in this study. Two hundred seventy-four patients (87.8 %) were more than 3 years post-transplant. Univariate analysis revealed that a single daily dose was significantly associated with better adherence. After controlling for age, sex, time since transplantation, and the number of prescribed drugs, the effect of a single daily dose still remained significant [odds ratio, 0.40 (95 % confidence interval, 0.19-0.81); p = 0.011]. Several sensitivity analyses yielded similar results. To our knowledge, this is the first report that, in long-term kidney transplant recipients, a single daily regimen-one of few modifiable factors-might improve treatment adherence and allograft survival.

  12. High-dose erythropoietin in patients with progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

    2017-01-01

    BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS. METHODS: This was a single-center, randomized......, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6......: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS....

  13. Lyssavirus infection: 'low dose, multiple exposure' in the mouse model.

    Science.gov (United States)

    Banyard, Ashley C; Healy, Derek M; Brookes, Sharon M; Voller, Katja; Hicks, Daniel J; Núñez, Alejandro; Fooks, Anthony R

    2014-03-06

    The European bat lyssaviruses (EBLV-1 and EBLV-2) are zoonotic pathogens present within bat populations across Europe. The maintenance and transmission of lyssaviruses within bat colonies is poorly understood. Cases of repeated isolation of lyssaviruses from bat roosts have raised questions regarding the maintenance and intraspecies transmissibility of these viruses within colonies. Furthermore, the significance of seropositive bats in colonies remains unclear. Due to the protected nature of European bat species, and hence restrictions to working with the natural host for lyssaviruses, this study analysed the outcome following repeat inoculation of low doses of lyssaviruses in a murine model. A standardized dose of virus, EBLV-1, EBLV-2 or a 'street strain' of rabies (RABV), was administered via a peripheral route to attempt to mimic what is hypothesized as natural infection. Each mouse (n=10/virus/group/dilution) received four inoculations, two doses in each footpad over a period of four months, alternating footpad with each inoculation. Mice were tail bled between inoculations to evaluate antibody responses to infection. Mice succumbed to infection after each inoculation with 26.6% of mice developing clinical disease following the initial exposure across all dilutions (RABV, 32.5% (n=13/40); EBLV-1, 35% (n=13/40); EBLV-2, 12.5% (n=5/40)). Interestingly, the lowest dose caused clinical disease in some mice upon first exposure ((RABV, 20% (n=2/10) after first inoculation; RABV, 12.5% (n=1/8) after second inoculation; EBLV-2, 10% (n=1/10) after primary inoculation). Furthermore, five mice developed clinical disease following the second exposure to live virus (RABV, n=1; EBLV-1, n=1; EBLV-2, n=3) although histopathological examination indicated that the primary inoculation was the most probably cause of death due to levels of inflammation and virus antigen distribution observed. All the remaining mice (RABV, n=26; EBLV-1, n=26; EBLV-2, n=29) survived the tertiary and

  14. Development of evaluation method of collective dose of general public considering the daily life activity and time use

    International Nuclear Information System (INIS)

    Nagaoka, Toshi; Saito, Kimiaki; Sakamoto, Ryuichi; Tsutsumi, Masahiro; Moriuchi, Shigeru

    1994-11-01

    A code for evaluation of collective dose of general public to natural radiation has been developed, in which the variation of dose rate due to place of stay is taken into consideration. Only external exposure to natural radiation is subject to discussion in this report. Strict manner of dose evaluation requires the dose rate and the time period of stay for each place and for each person. It is possible to know (measure) them all, but not practicable. In this code, dose rate information was obtained from actually measured data by the authors and estimation based on the environmental conditions. Information on the time period of stay was obtained from a Survey Data on Time Use and Leisure Activities by Management and Coordination Agency, and from Statistical Yearbook of Tokyo with some realistic assumptions. By using them, collective dose was evaluated taking both the daily life style and dose rate varying place by place into consideration. In this report, the dose evaluation code and the results about doses for Tokyo citizens are mentioned. (author)

  15. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    Full Text Available BACKGROUND: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. METHODS: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. RESULTS: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002. While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra, an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08. CONCLUSIONS: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than

  16. Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

    Science.gov (United States)

    Keller, Marla J.; Carpenter, Colleen A.; Lo, Yungtai; Einstein, Mark H.; Liu, Congzhou; Fredricks, David N.; Herold, Betsy C.

    2012-01-01

    Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. Results The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Conclusions Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels

  17. Daily dose monitoring with atlas-based auto-segmentation on diagnostic quality CT for prostate cancer

    International Nuclear Information System (INIS)

    Li, Wen; Vassil, Andrew; Xia, Ping; Zhong, Yahua

    2013-01-01

    Purpose: To evaluate the feasibility of daily dose monitoring using a patient specific atlas-based autosegmentation method on diagnostic quality verification images.Methods: Seven patients, who were treated for prostate cancer with intensity modulated radiotherapy under daily imaging guidance of a CT-on-rails system, were selected for this study. The prostate, rectum, and bladder were manually contoured on the first six and last seven sets of daily verification images. For each patient, three patient specific atlases were constructed using manual contours from planning CT alone (1-image atlas), planning CT plus first three verification CTs (4-image atlas), and planning CT plus first six verification CTs (7-image atlas). These atlases were subsequently applied to the last seven verification image sets of the same patient to generate the auto-contours. Daily dose was calculated by applying the original treatment plans to the daily beam isocenters. The autocontours and manual contours were compared geometrically using the dice similarity coefficient (DSC), and dosimetrically using the dose to 99% of the prostate CTV (D99) and the D5 of rectum and bladder.Results: The DSC of the autocontours obtained with the 4-image atlases were 87.0%± 3.3%, 84.7%± 8.6%, and 93.6%± 4.3% for the prostate, rectum, and bladder, respectively. These indices were higher than those from the 1-image atlases (p 0.05). Daily prostate D99 of the autocontours was comparable to those of the manual contours (p= 0.55). For the bladder and rectum, the daily D5 were 95.5%± 5.9% and 99.1%± 2.6% of the planned D5 for the autocontours compared to 95.3%± 6.7% (p= 0.58) and 99.8%± 2.3% (p < 0.01) for the manual contours.Conclusions: With patient specific 4-image atlases, atlas-based autosegmentation can adequately facilitate daily dose monitoring for prostate cancer

  18. Daily dose monitoring with atlas-based auto-segmentation on diagnostic quality CT for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen; Vassil, Andrew; Xia, Ping [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio 44106 (United States); Zhong, Yahua [Department of Radiation Oncology, Zhongnan Hospital, Wuhan 430071 (China)

    2013-11-15

    Purpose: To evaluate the feasibility of daily dose monitoring using a patient specific atlas-based autosegmentation method on diagnostic quality verification images.Methods: Seven patients, who were treated for prostate cancer with intensity modulated radiotherapy under daily imaging guidance of a CT-on-rails system, were selected for this study. The prostate, rectum, and bladder were manually contoured on the first six and last seven sets of daily verification images. For each patient, three patient specific atlases were constructed using manual contours from planning CT alone (1-image atlas), planning CT plus first three verification CTs (4-image atlas), and planning CT plus first six verification CTs (7-image atlas). These atlases were subsequently applied to the last seven verification image sets of the same patient to generate the auto-contours. Daily dose was calculated by applying the original treatment plans to the daily beam isocenters. The autocontours and manual contours were compared geometrically using the dice similarity coefficient (DSC), and dosimetrically using the dose to 99% of the prostate CTV (D99) and the D5 of rectum and bladder.Results: The DSC of the autocontours obtained with the 4-image atlases were 87.0%± 3.3%, 84.7%± 8.6%, and 93.6%± 4.3% for the prostate, rectum, and bladder, respectively. These indices were higher than those from the 1-image atlases (p < 0.01) and comparable to those from the 7-image atlases (p > 0.05). Daily prostate D99 of the autocontours was comparable to those of the manual contours (p= 0.55). For the bladder and rectum, the daily D5 were 95.5%± 5.9% and 99.1%± 2.6% of the planned D5 for the autocontours compared to 95.3%± 6.7% (p= 0.58) and 99.8%± 2.3% (p < 0.01) for the manual contours.Conclusions: With patient specific 4-image atlases, atlas-based autosegmentation can adequately facilitate daily dose monitoring for prostate cancer.

  19. Effect of the cooling suit method applied to individuals with multiple sclerosis on fatigue and activities of daily living.

    Science.gov (United States)

    Özkan Tuncay, Fatma; Mollaoğlu, Mukadder

    2017-12-01

    To determine the effects of cooling suit on fatigue and activities of daily living of individuals with multiple sclerosis. Fatigue is one of the most common symptoms in people with multiple sclerosis and adversely affects their activities of daily living. Studies evaluating fatigue associated with multiple sclerosis have reported that most of the fatigue cases are related to the increase in body temperature and that cooling therapy is effective in coping with fatigue. This study used a two sample, control group design. The study sample comprised 75 individuals who met the inclusion criteria. Data were collected with study forms. After the study data were collected, cooling suit treatment was administered to the experimental group. During home visits paid at the fourth and eighth weeks after the intervention, the aforementioned scales were re-administered to the participants in the experimental and control groups. The analyses performed demonstrated that the severity levels of fatigue experienced by the participants in the experimental group wearing cooling suit decreased. The experimental group also exhibited a significant improvement in the participants' levels of independence in activities of daily living. The cooling suit worn by individuals with multiple sclerosis was determined to significantly improve the participants' levels of fatigue and independence in activities of daily living. The cooling suit therapy was found to be an effective intervention for the debilitating fatigue suffered by many multiple sclerosis patients, thus significantly improving their level of independence in activities of daily living. © 2017 John Wiley & Sons Ltd.

  20. Early reoxygenation in tumors after irradiation: Determining factors and consequences for radiotherapy regimens using daily multiple fractions

    International Nuclear Information System (INIS)

    Crokart, Nathalie; Jordan, Benedicte F.; Baudelet, Christine; Ansiaux, Reginald; Sonveaux, Pierre; Gregoire, Vincent; Beghein, Nelson; Wever, Julie de; Bouzin, Caroline; Feron, Olivier; Gallez, Bernard

    2005-01-01

    Purpose: To characterize changes in the tumor microenvironment early after irradiation and determine the factors responsible for early reoxygenation. Methods and Materials: Fibrosarcoma type II (FSaII) and hepatocarcinoma transplantable liver tumor tumor oxygenation were determined using electron paramagnetic resonance oximetry and a fiberoptic device. Perfusion was assessed by laser Doppler, dynamic contrast-enhanced MRI, and dye penetration. Oxygen consumption was determined by electron paramagnetic resonance. The interstitial fluid pressure was evaluated by the wick-in-needle technique. Results: An increase in oxygen partial pressure was observed 3-4 h after irradiation. This increase resulted from a decrease in global oxygen consumption and an increase in oxygen delivery. The increase in oxygen delivery was due to radiation-induced acute inflammation (that was partially inhibited by the antiinflammatory agent diclofenac) and to a decrease in interstitial fluid pressure. The endothelial nitric oxide synthase pathway, identified as a contributing factor at 24 h after irradiation, did not play a role in the early stage after irradiation. We also observed that splitting a treatment of 18 Gy into two fractions separated by 4 h (time of maximal reoxygenation) had a greater effect on tumor regrowth delay than when applied as a single dose. Conclusion: Although the cell cycle redistribution effect is important for treatment protocols using multiple daily radiation fractions, the results of this work emphasize that the oxygen effect must be also considered to optimize the treatment strategy

  1. Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

    Science.gov (United States)

    Yap, Felix Boon-Bin

    2017-09-01

    Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

  2. Adaptive Liver Stereotactic Body Radiation Therapy: Automated Daily Plan Reoptimization Prevents Dose Delivery Degradation Caused by Anatomy Deformations

    Energy Technology Data Exchange (ETDEWEB)

    Leinders, Suzanne M. [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Breedveld, Sebastiaan; Méndez Romero, Alejandra [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Schaart, Dennis [Delft University of Technology, Delft (Netherlands); Seppenwoolde, Yvette, E-mail: y.seppenwoolde@erasmusmc.nl [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Heijmen, Ben J.M. [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2013-12-01

    Purpose: To investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientations were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery.

  3. Daily radionuclide ingestion and internal radiation doses in Aomori prefecture, Japan.

    Science.gov (United States)

    Ohtsuka, Yoshihito; Kakiuchi, Hideki; Akata, Naofumi; Takaku, Yuichi; Hisamatsu, Shun'ichi

    2013-10-01

    To assess internal annual dose in the general public in Aomori Prefecture, Japan, 80 duplicate cooked diet samples, equivalent to the food consumed over a 400-d period by one person, were collected from 100 volunteers in Aomori City and the village of Rokkasho during 2006–2010 and were analyzed for 11 radionuclides. To obtain average rates of ingestion of radionuclides, the volunteers were selected from among office, fisheries, agricultural, and livestock farm workers. Committed effective doses from ingestion of the diet over a 1-y period were calculated from the analytical results and from International Commission on Radiological Protection dose coefficients; for 40K, an internal effective dose rate from the literature was used. Fisheries workers had significantly higher combined internal annual dose than the other workers, possibly because of high rates of ingestion of marine products known to have high 210Po concentrations. The average internal dose rate, weighted by the numbers of households in each worker group in Aomori Prefecture, was estimated at 0.47 mSv y-1. Polonium-210 contributed 49% of this value. The sum of committed effective dose rates for 210Po, 210Pb, 228Ra, and 14C and the effective dose rate of 40K accounted for approximately 99% of the average internal dose rate.

  4. Fast, multiple optimizations of quadratic dose objective functions in IMRT

    International Nuclear Information System (INIS)

    Breedveld, Sebastiaan; Storchi, Pascal R M; Keijzer, Marleen; Heijmen, Ben J M

    2006-01-01

    Inverse treatment planning for intensity-modulated radiotherapy may include time consuming, multiple minimizations of an objective function. In this paper, methods are presented to speed up the process of (repeated) minimization of the well-known quadratic dose objective function, extended with a smoothing term that ensures generation of clinically acceptable beam profiles. In between two subsequent optimizations, the voxel-dependent importance factors of the quadratic terms will generally be adjusted, based on an intermediate plan evaluation. The objective function has been written in matrix-vector format, facilitating the use of a recently published, fast quadratic minimization algorithm, instead of commonly applied gradient-based methods. This format also reduces the calculation time in between subsequent minimizations, related to adjustment of the voxel-dependent importance factors. Sparse matrices are used to limit the required amount of computer memory. For three patients, comparisons have been made with a gradient method. Mean speed improvements of up to a factor of 37 have been achieved

  5. A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

    Science.gov (United States)

    Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

    1989-12-01

    Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

  6. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose.

    Science.gov (United States)

    Ero, Michael Penfield; Ng, Connie M; Mihailovski, Tamara; Harvey, Nathaniel R; Lewis, Brad Howard

    2013-01-01

    Nattokinase is a serine protease and is derived from natto, a traditional Japanese, fermented, soybean food meal. Multiple authors have described the significant fibrinolytic, antithrombotic, and antihypertensive effects of natto. Nattokinase has been growing in popularity for use as a dietary supplement for the benefit of cardiovascular health. Little is known regarding the pharmacokinetic and pharmacodynamic properties of this enzyme, and the bioavailability of nattokinase is currently unknown. This study intended to (1) detect nattokinase directly and immunologically, (2) show that nattokinase and/or its metabolites were detectable in human blood following ingestion of a commercial preparation, and (3) chart a pharmacokinetic dosing effect for nattokinase. The research team designed the pilot study as an in vivo, human clinical trial. Healthy human subjects responded to an advertisement and were screened. Subjects who satisfied both inclusion and exclusion criteria were enrolled into the study. Subjects were then instructed to orally ingest a single capsule containing a known concentration of nattokinase immediately following a baseline blood draw. Subsequent blood draws occurred over a 24-h period. This study was conducted in Oakland, California, at a clinical reference laboratory and was performed with the approval of an institutional review board (IRB) to ensure that appropriate ethical standards were met. Eleven healthy participants (five male, six female, ages 21-65), who met eligibility criteria, were enrolled. Administration of nattokinase occurred orally with the ingestion of a single daily dose (2000 FU) of nattokinase. Capsules, each containing approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science Laboratory, Osaka, Japan), were used in the study. Baseline blood samples were collected, and participants were observed swallowing a single capsule of the nattokinase supplement before returning at 2, 4, 8, 12, 24, and 48 h post

  7. Merging daily sea surface temperature data from multiple satellites using a Bayesian maximum entropy method

    Science.gov (United States)

    Tang, Shaolei; Yang, Xiaofeng; Dong, Di; Li, Ziwei

    2015-12-01

    Sea surface temperature (SST) is an important variable for understanding interactions between the ocean and the atmosphere. SST fusion is crucial for acquiring SST products of high spatial resolution and coverage. This study introduces a Bayesian maximum entropy (BME) method for blending daily SSTs from multiple satellite sensors. A new spatiotemporal covariance model of an SST field is built to integrate not only single-day SSTs but also time-adjacent SSTs. In addition, AVHRR 30-year SST climatology data are introduced as soft data at the estimation points to improve the accuracy of blended results within the BME framework. The merged SSTs, with a spatial resolution of 4 km and a temporal resolution of 24 hours, are produced in the Western Pacific Ocean region to demonstrate and evaluate the proposed methodology. Comparisons with in situ drifting buoy observations show that the merged SSTs are accurate and the bias and root-mean-square errors for the comparison are 0.15°C and 0.72°C, respectively.

  8. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

    Science.gov (United States)

    Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

    2008-01-01

    To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

  9. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

    2003-05-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  10. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    International Nuclear Information System (INIS)

    Slatter, J.G.; Sams, J.P.; Easter, J.A.

    2003-01-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [ 14 C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [ 14 C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [ 14 C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled 14 CO 2 . After 7 daily [ 14 C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C max and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  11. Influence of the number of daily pills and doses on adherence to antiretroviral treatment: a 7-year study.

    Science.gov (United States)

    Hernández Arroyo, M J; Cabrera Figueroa, S E; Sepúlveda Correa, R; Valverde Merino, M P; Luna Rodrigo, G; Domínguez-Gil Hurlé, A

    2016-02-01

    Antiretroviral treatment (ART) is hampered by complicated regimens, high pill burden, drug-drug interactions, and frequent short- and long-term adverse effects, leading to decreased adherence. Over recent years, considerable effort has been directed at developing regimens that are less burdening. We undertook a 7-year retrospective study of the records of 264 HIV-infected subjects enrolled in a pharmaceutical care programme to document the progress made and to study the influence of the number of ART pills and doses on the level of treatment adherence. Antiretroviral dispensing records were analysed for the number of pills and doses administered and the ART adherence rate estimated. In 2005, the patients took a mean of 6·2 pills daily (CI 95%: 5·9-6·6), and 92·9% of them were on a twice-a-day (BID) dosage regimen. By 2012, the mean number of pills was reduced to 4·1 (CI 95%: 3·8-4·4), and only 50·9% were on a BID regimen. No statistically significant relation was observed between number of daily pills and doses and ART adherence reached by the patients in any of the analyses performed. There has been a continuous reduction in the number of pills and doses of antiretrovirals taken by individual patients over the last 7 years due largely to the introduction of improved treatments and regimens. More daily pills or doses was not associated with worse ART adherence in our pharmaceutical care programme. © 2015 John Wiley & Sons Ltd.

  12. 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.

  13. Doses from pediatric CT examinations in Norway: are pediatric scan protocols developed and in daily use?

    International Nuclear Information System (INIS)

    Friberg, Eva G.

    2008-01-01

    Doses to pediatric patients from CT examinations are known to be unnecessarily high if scan protocols developed for adult patients are adopted. This overexposure is most often not recognized by the operating radiographer, due to the digital behavior of the imaging system. Use of optimized size-specific pediatric scan protocols is therefore essential to keep the doses at an appropriate level. The aim of this study was to investigate the doses to pediatric patients from CT examinations and to evaluate the level of optimization of the scan protocols. Patient data, applied scan parameters together with the dose parameters volume computed tomography dose index (CTD vol ) and dose length product (DLP) for examinations of the head, chest and abdomen were collected by means of a questionnaire from five university hospitals. The effective dose was estimated from the total DLP by use of region-specific conversion coefficients (E DLP ). Totally 136, 108 and 82 questionnaires were received for examinations of the head, chest and abdomen, respectively. Large variations in patient doses between the hospitals were observed, addressing the need for optimization of the scan protocols in general. Most of the hospitals applied successive lower mAs with decreasing patient age for all scan areas, while the use of lower tube voltage for small patients and a higher tube voltage for large patients were more rarely. This indicates the presence, to a certain level, of size specific scan protocols at some Norwegian hospitals. Focus on developing size-specific scan protocols for pediatric patients are important to reduce the doses and risks associated with pediatric CT examinations. (author)

  14. Reducing dosing frequency of carbidopa/levodopa: double-blind crossover study comparing twice-daily bilayer formulation of carbidopa/levodopa (IPX054) versus 4 daily doses of standard carbidopa/levodopa in stable Parkinson disease patients.

    Science.gov (United States)

    Hinson, Vanessa K; Goetz, Christopher G; Leurgans, Sue; Fan, Wenqing; Nguyen, Tiffany; Hsu, Ann

    2009-01-01

    We compared IPX054, a bilayer tablet of immediate- and extended-release carbidopa/levodopa (CD/LD) given twice daily to standard CD/LD given 4 times daily in patients with stable Parkinson disease (PD). Twelve PD patients with no or mild fluctuations on CD/LD 25/100 mg 4 times daily were randomized to a double-blind crossover comparison with IPX054 (50/200 mg) twice daily. At the end of each 2-week treatment, patients were video recorded while performing a modified Unified Parkinson's Disease Rating Scale motor examination and Rush Dyskinesia Rating Scale at 30-minute intervals over 8.5 hours. The primary outcome measure was the number of videotape epochs rated as "ON" without troublesome dyskinesia by a blinded observer (Wilcoxon signed rank tests). The 9 men and 3 women had a mean age of 69 years and mean PD duration of 6 years. IPX054 and CD/LD showed no significant differences in the primary outcome measure (mean number of video epochs rated as ON without troublesome dyskinesia; P = 0.14). The mean time to ON was improved with IPX054 (P = 0.014), and the mean modified Unified Parkinson's Disease Rating Scale scores slightly favored IPX054 (14.4 vs 16.9; P = 0.052). Mean Rush Dyskinesia Rating Scale scores were not significantly different between IPX054 and CD/LD (0.45 vs 0.69; P = 0.25). No patient developed troublesome dyskinesias. In stable PD patients, no difference was detected between twice-daily treatment with IPX054 and CD/LD given 4 times daily. In this group, substitution with IPX054 reduced dosing frequency while maintaining CD/LD efficacy. In clinical practice, this ease of administration may offer improved treatment compliance.

  15. Daily Suspended Sediment Discharge Prediction Using Multiple Linear Regression and Artificial Neural Network

    Science.gov (United States)

    Uca; Toriman, Ekhwan; Jaafar, Othman; Maru, Rosmini; Arfan, Amal; Saleh Ahmar, Ansari

    2018-01-01

    Prediction of suspended sediment discharge in a catchments area is very important because it can be used to evaluation the erosion hazard, management of its water resources, water quality, hydrology project management (dams, reservoirs, and irrigation) and to determine the extent of the damage that occurred in the catchments. Multiple Linear Regression analysis and artificial neural network can be used to predict the amount of daily suspended sediment discharge. Regression analysis using the least square method, whereas artificial neural networks using Radial Basis Function (RBF) and feedforward multilayer perceptron with three learning algorithms namely Levenberg-Marquardt (LM), Scaled Conjugate Descent (SCD) and Broyden-Fletcher-Goldfarb-Shanno Quasi-Newton (BFGS). The number neuron of hidden layer is three to sixteen, while in output layer only one neuron because only one output target. The mean absolute error (MAE), root mean square error (RMSE), coefficient of determination (R2 ) and coefficient of efficiency (CE) of the multiple linear regression (MLRg) value Model 2 (6 input variable independent) has the lowest the value of MAE and RMSE (0.0000002 and 13.6039) and highest R2 and CE (0.9971 and 0.9971). When compared between LM, SCG and RBF, the BFGS model structure 3-7-1 is the better and more accurate to prediction suspended sediment discharge in Jenderam catchment. The performance value in testing process, MAE and RMSE (13.5769 and 17.9011) is smallest, meanwhile R2 and CE (0.9999 and 0.9998) is the highest if it compared with the another BFGS Quasi-Newton model (6-3-1, 9-10-1 and 12-12-1). Based on the performance statistics value, MLRg, LM, SCG, BFGS and RBF suitable and accurately for prediction by modeling the non-linear complex behavior of suspended sediment responses to rainfall, water depth and discharge. The comparison between artificial neural network (ANN) and MLRg, the MLRg Model 2 accurately for to prediction suspended sediment discharge (kg

  16. An observational study evaluating tacrolimus dose, exposure, and medication adherence after conversion from twice- to once-daily tacrolimus in liver and kidney transplant recipients.

    Science.gov (United States)

    Bäckman, Lars; Persson, Carl-Axel

    2014-03-17

    Immunosuppression regimens in transplantation medicine are complex. Drugs with extended release action have simplified medication dosing without affecting efficacy. This prospective, observational, multicenter study, conducted in a routine medical practice setting, evaluated changes in tacrolimus daily dose and trough levels and patient-reported medication adherence at day 90 after 1:1 (mg: mg) conversion to once-daily tacrolimus in adult liver and kidney transplant recipients. Data from 224 recipients of a liver (n=19) or kidney (n=205) transplant, average age 51±14.5 years, were evaluated. The mean change in tacrolimus daily dose was +0.04 mg/day. Dose remained stable after conversion in 62.5%, was lower in 15.6%, and higher in 22% of patients. Trough level after conversion was lower in 62.6% and higher in 36.5%; generally, levels were 12.8% lower than pre-conversion levels. No acute rejection, graft loss, or serious safety events were observed. Two deaths occurred due to myocardial infarction. Conversion helped 19% to less frequently forget medications and 55% reported no difference in remembering to take the once-daily dose after conversion. The change in dosing frequency was identified as "better" for 55%. Tacrolimus daily dose remained stable while trough levels were significantly lower after conversion to once-daily dosing. Safety and efficacy were maintained; reduced dosing frequency had no apparent influence on patient-reported medication adherence.

  17. Effect of daily low dose gamma irradiation on growth and differentiation of human myeloid leukaemic bone marrow in diffusion chambers

    Energy Technology Data Exchange (ETDEWEB)

    Greenberger, J S [Joint Center for Radiation Therapy, Department of Radiation and Sidney Farber Cancer Institute; Chang, J M; King, V; Fulmer, S; Balzuno, S; Moloney, W C [Division of Hematology, Department of Medicine, Brigham and Women' s Hospital Harvard Medical School, Boston, USA

    1981-01-01

    Bone marrow from each of 8 untreated patients with myeloproliferative disorders was grown in diffusion chambers in 760 rad total body irradiated rats. Rats were exposed to 11.5, 57.5, or 108.5 rad daily for 14-21 and cell growth compared to that detected in unirradiated chambers. Cells from acute myelogenous leukaemia patients exposed to 11.5 rad per d grew for 11-21 d and there was no consistent stimulation of differentiation of immature granulocytic cells to mature granulocytes that was attributable to irradiation. Cells from a chronic myeloid leukaemia patient in chronic phase or blast crisis, and a polycythaemia vera patient with myeloid metaplasia showed signigicant morphologic differentiation from immature to mature granulocytes in control chambers with no additional effect of daily irradiation. Marrow specimens from 2 AML patients exposed to each of 3 daily dose fractions over 14 d revealed a dose-dependent decrease in immature granulocytes with no persistent increase in mature granulocytes. In both irradiated and control chambers, macrophages increased over 21 d. Thus, cells from patients with myeloprofilerative disorders may not necessarily differentiate to mature granulocytes following in vivo exposure to ionizing irradiation.

  18. Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule

    DEFF Research Database (Denmark)

    Jensen, H.V.; Plenge, P; Stensgaard, A

    1996-01-01

    The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate......-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple...... linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic...

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

    NARCIS (Netherlands)

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

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

  20. Microfluidic thrombosis under multiple shear rates and antiplatelet therapy doses.

    Directory of Open Access Journals (Sweden)

    Melissa Li

    Full Text Available The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s(-1 and therapy concentrations (0-2.4 µM for eptifibatide, 0-2 mM for acetyl-salicylic acid (ASA, 3.5-40 Units/L for heparin using a microfluidic device. We also measured complete blood counts (CBC and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose. Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment.

  1. Changes of some serum proteins in rats continuously irradiated with daily dose rate of 0. 0258 C/kg

    Energy Technology Data Exchange (ETDEWEB)

    Chlebovska, K; Chlebovsky, O; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

    1976-01-01

    Changes of serum albumin, haptoglobin, hemopexin and IgG in rats during chronic /sup 60/Co gamma irradiation with a daily dose rate of 0.0258 C/kg within 44 days were investigated by the method of two-dimensional quantitative immunoelectrophoresis. In comparison with normal levels, the values of albumin and IgG in rats during irradiation decreased until the death of animals to 50%, the values of haptoglobin increased till the 39th day of irradiation to 250% and hemopexin values increased to 150%.

  2. Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.

    Science.gov (United States)

    Ozcan, Levent; Polat, Emre Can; Onen, Efe; Kocaaslan, Ramazan; Otunctemur, Alper; Cekmen, Mustafa; Eraldemir, Ceyla; Ozbek, Emin

    2017-01-01

    In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE. © 2016 S. Karger AG, Basel.

  3. Rationale and design of the worldwide prospective multicenter registry on radiation dose estimates of cardiac CT angiography in daily practice in 2017 (PROTECTION VI)

    DEFF Research Database (Denmark)

    Stocker, Thomas J; Deseive, Simon; Chen, Marcus

    2018-01-01

    -randomized and randomized studies have been performed to reduce the associated radiation exposure. Currently, it is unclear if the advances in technology and knowledge about radiation reduction translated into reduced levels of cardiac CTA radiation dose in daily clinical practice as well as a wide utilization of dose......-saving strategies. METHODS: The PROTECTION VI study is a multicenter, prospective, worldwide registry designed to evaluate radiation dose exposure, utilization of dose-saving strategies and diagnostic image quality during cardiac CTA in current daily practice. Assessment of image quality will be addressed...... median radiation dose levels, image quality, frequency of use and efficacy of algorithms for dose reduction, and patient and study-related predictors associated with radiation dose. CONCLUSIONS: The PROTECTION VI study is designed to provide a reliable estimate of current radiation dose for cardiac CTA...

  4. Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Zuur, Charlotte L.; Simis, Yvonne J.W.; Verkaik, Roxanna S.; Schornagel, Jan H.; Balm, Alfons J.M.; Dreschler, Wouter A.; Rasch, Coen R.N.

    2008-01-01

    Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m 2 , daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

  5. Assessment of Parotid Gland Dose Changes During Head and Neck Cancer Radiotherapy Using Daily Megavoltage Computed Tomography and Deformable Image Registration

    International Nuclear Information System (INIS)

    Lee, Choonik; Langen, Katja M.; Lu Weiguo; Haimerl, Jason; Schnarr, Eric; Ruchala, Kenneth J.; Olivera, Gustavo H.; Meeks, Sanford L.; Kupelian, Patrick A.; Shellenberger, Thomas D.; Manon, Rafael R.

    2008-01-01

    Purpose: To analyze changes in parotid gland dose resulting from anatomic changes throughout a course of radiotherapy in a cohort of head-and-neck cancer patients. Methods and Materials: The study population consisted of 10 head-and-neck cancer patients treated definitively with intensity-modulated radiotherapy on a helical tomotherapy unit. A total of 330 daily megavoltage computed tomography images were retrospectively processed through a deformable image registration algorithm to be registered to the planning kilovoltage computed tomography images. The process resulted in deformed parotid contours and voxel mappings for both daily and accumulated dose-volume histogram calculations. The daily and cumulative dose deviations from the original treatment plan were analyzed. Correlations between dosimetric variations and anatomic changes were investigated. Results: The daily parotid mean dose of the 10 patients differed from the plan dose by an average of 15%. At the end of the treatment, 3 of the 10 patients were estimated to have received a greater than 10% higher mean parotid dose than in the original plan (range, 13-42%), whereas the remaining 7 patients received doses that differed by less than 10% (range, -6-8%). The dose difference was correlated with a migration of the parotids toward the high-dose region. Conclusions: The use of deformable image registration techniques and daily megavoltage computed tomography imaging makes it possible to calculate daily and accumulated dose-volume histograms. Significant dose variations were observed as result of interfractional anatomic changes. These techniques enable the implementation of dose-adaptive radiotherapy

  6. The relative importance of ingestion for multiple pathway dose assessments

    International Nuclear Information System (INIS)

    Wicker, W.; Grogan, H.; Bergstroem, U.; Hoffman, O.

    1991-01-01

    The general purpose of this report is to examine the relative importance of ingestion pathways, and particularly food chain transport in overall dose assessment. The importance of ingestion pathways is examined for various release scenarios and radionuclides because the findings are expected to differ with circumstances. The degree to which contaminated food products contribute to the total dose will affect the importance of accuracy and uncertainty of food chain model predictions, which is the main thrust of the Biospheric Model Validation Study (BIOMOVS). This analysis requires that all modes of radiation exposure be examined, including inhalation, external exposure, and the various ingestion pathways. (2 figs., 2 tabs.)

  7. Near real-time automated dose restoration in IMPT to compensate for daily tissue density variations in prostate cancer

    Science.gov (United States)

    Jagt, Thyrza; Breedveld, Sebastiaan; van de Water, Steven; Heijmen, Ben; Hoogeman, Mischa

    2017-06-01

    Proton therapy is very sensitive to daily density changes along the pencil beam paths. The purpose of this study is to develop and evaluate an automated method for adaptation of IMPT plans to compensate for these daily tissue density variations. A two-step restoration method for ‘densities-of-the-day’ was created: (1) restoration of spot positions (Bragg peaks) by adapting the energy of each pencil beam to the new water equivalent path length; and (2) re-optimization of pencil beam weights by minimizing the dosimetric difference with the planned dose distribution, using a fast and exact quadratic solver. The method was developed and evaluated using 8-10 repeat CT scans of 10 prostate cancer patients. Experiments demonstrated that giving a high weight to the PTV in the re-optimization resulted in clinically acceptable restorations. For all scans we obtained V 95%  ⩾  98% and V 107%  ⩽  2%. For the bladder, the differences between the restored and the intended treatment plan were below  +2 Gy and  +2%-point. The rectum differences were below  +2 Gy and  +2%-point for 90% of the scans. In the remaining scans the rectum was filled with air, which partly overlapped with the PTV. The air cavity distorted the Bragg peak resulting in less favorable rectum doses.

  8. Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

    Science.gov (United States)

    Orbelo, Diana M; Enders, Felicity T; Romero, Yvonne; Francis, Dawn L; Achem, Sami R; Dabade, Tushar S; Crowell, Michael D; Geno, Debra M; DeJesus, Ramona S; Namasivayam, Vikneswaran; Adamson, Steven C; Arora, Amindra S; Majka, Andrew J; Alexander, Jeffrey A; Murray, Joseph A; Lohse, Matthew; Diehl, Nancy N; Fredericksen, Mary; Jung, Kee Wook; Houston, Margaret S; O'Neil, Angela E; Katzka, David A

    2015-01-01

    Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

  9. OMI/Aura Surface UVB Irradiance and Erythemal Dose Daily L2 Global 0.25 deg Lat/Lon Grid V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The Version 003 of Aura-OMI Spectral Surface UVB Irradiance and Erythemal Dose Level-2G data product (Daily level-2 data binned into global 0.25 deg Lat/Lon grids)...

  10. 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.

  11. Toward daily monitoring of vegetation conditions at field scale through fusing data from multiple sensors

    Science.gov (United States)

    Vegetation monitoring requires remote sensing data at fine spatial and temporal resolution. While imagery from coarse resolution sensors such as MODIS/VIIRS can provide daily observations, they lack spatial detail to capture surface features for crop and rangeland monitoring. The Landsat satellite s...

  12. Is Daily Low-Dose Aspirin Safe to Take Following Laparoscopic Roux-en-Y Gastric Bypass for Obesity Surgery?

    Science.gov (United States)

    Kang, Xian; Hong, Dennis; Anvari, Mehran; Tiboni, Maria; Amin, Nalin; Gmora, Scott

    2017-05-01

    Laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery is a safe and effective procedure for patients with severe obesity. One potential complication of LRYGB is the development of marginal ulcers (MUs). Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to significantly increase the likelihood of developing marginal ulcers after surgery. However, the risk associated with low-dose aspirin consumption is not well defined. We examined the impact of daily low-dose aspirin (81 mg) on the development of marginal ulcers following LRYGB. A retrospective cohort design studied patients undergoing LRYGB surgery, between January 2009 and January 2013, at a single, high-volume bariatric center in Ontario, Canada. The marginal ulcer rate of patients taking low-dose aspirin after surgery was compared to that of the control patients who did not take any NSAID. Diagnosis of MU was confirmed by upper endoscopy in patients presenting with symptoms and a history indicative of marginal ulceration. A chi-square test of independence was performed to examine the difference in marginal ulcer rates. A total of 1016 patients underwent LRYGB. Patients taking aspirin were more likely to be male, older, and have diabetes than patients not taking NSAIDs. Of the 1016 patients, 145 (14.3%) took low-dose aspirin following LRYGB and the rest did not (n = 871, 85.7%). The incidence of marginal ulceration was not significantly different between the two treatment groups (12/145, 8.3% versus 90/871, 10.3%; p = 0.45). Patients treated with LRYGB at our institution were not at increased risk of marginal ulcer formation when taking low-dose aspirin after surgery.

  13. SU-E-T-86: Comparison of Two Commercially Available Programs for the Evaluation of Delivered Daily Dose Using Cone Beam CT (CBCT)

    International Nuclear Information System (INIS)

    Tuohy, R; Bosse, C; Mavroidis, P; Shi, Z; Crownover, R; Papanikolaou, N; Stathakis, S

    2014-01-01

    Purpose: In this study, two commercially available programs were compared for the evaluation of delivered daily dose using cone beam CT (CBCT). Methods: Thirty (n=30) patients previously treated in our clinic (10 prostate, 10 SBRT lung and 10 abdomen) were used in this study. The patients' plans were optimized and calculated using the Pinnacle treatment planning system. The daily CBCT scans were imported into Velocity and RayStation along with the corresponding planning CTs, structure sets and 3D dose distributions for each patient. The organs at risk (OAR) were contoured on each CBCT by the prescribing physician and were included in the evaluation of the daily delivered dose. Each CBCT was registered to the planning CT, once with rigid registration and then again, separately, with deformable registration. After registering each CBCT, the dose distribution from the planning CT was overlaid and the dose volume histograms (DVH) for the OAR and the planning target volumes (PTV) were calculated. Results: For prostate patients, we observed daily volume changes for the OARs. The DVH analysis for those patients showed variation in the sparing of the OARs while PTV coverage remained virtually unchanged using both Velocity and RayStation systems. Similar results were observed for abdominal patients. In contrast, for SBRT lung patients, the DVH for the OARs and target were comparable to those from the initial treatment plan. Differences in organ volume and organ doses were also observed when comparing the daily fractions using deformable and rigid registrations. Conclusion: By using daily CBCT dose reconstruction, we proved PTV coverage for prostate and abdominal targets is adequate. However, there is significant dosimetric change for the OARs. For lung SBRT patients, the delivered daily dose for both PTV and OAR is comparable to the planned dose with no significant differences

  14. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis

    Directory of Open Access Journals (Sweden)

    Aidan G.C. Wright

    2015-12-01

    Full Text Available Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days of maladaptive behaviors collected from a sample (N = 101 of individuals diagnosed with personality disorders. Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days we found support for a two-factor Internalizing-Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Impulsivity structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic.

  15. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis

    Science.gov (United States)

    Wright, Aidan G. C.; Beltz, Adriene M.; Gates, Kathleen M.; Molenaar, Peter C. M.; Simms, Leonard J.

    2015-01-01

    Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days) of maladaptive behaviors collected from a sample (N = 101) of individuals diagnosed with personality disorders (PDs). Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days) we found support for a two-factor Internalizing–Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals) we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Disinhibition structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic. PMID:26732546

  16. Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients

    International Nuclear Information System (INIS)

    Doemer, Anthony; Chetty, Indrin J; Glide-Hurst, Carri; Nurushev, Teamour; Hearshen, David; Pantelic, Milan; Traughber, Melanie; Kim, Joshua; Levin, Kenneth; Elshaikh, Mohamed A; Walker, Eleanor; Movsas, Benjamin

    2015-01-01

    This study describes initial testing and evaluation of a vertical-field open Magnetic Resonance Imaging (MRI) scanner for the purpose of simulation in radiation therapy for prostate cancer. We have evaluated the clinical workflow of using open MRI as a sole modality for simulation and planning. Relevant results related to MRI alignment (vs. CT) reference dataset with Cone-Beam CT (CBCT) for daily localization are presented. Ten patients participated in an IRB approved study utilizing MRI along with CT simulation with the intent of evaluating the MRI-simulation process. Differences in prostate gland volume, seminal vesicles, and penile bulb were assessed with MRI and compared to CT. To evaluate dose calculation accuracy, bulk-density-assignments were mapped onto respective MRI datasets and treated IMRT plans were re-calculated. For image localization purposes, 400 CBCTs were re-evaluated with MRI as the reference dataset and daily shifts compared against CBCT-to-CT registration. Planning margins based on MRI/CBCT shifts were computed using the van Herk formalism. Significant organ contour differences were noted between MRI and CT. Prostate volumes were on average 39.7% (p = 0.002) larger on CT than MRI. No significant difference was found in seminal vesicle volumes (p = 0.454). Penile bulb volumes were 61.1% higher on CT, without statistical significance (p = 0.074). MRI-based dose calculations with assigned bulk densities produced agreement within 1% with heterogeneity corrected CT calculations. The differences in shift positions for the cohort between CBCT-to-CT registration and CBCT-to-MRI registration are −0.15 ± 0.25 cm (anterior-posterior), 0.05 ± 0.19 cm (superior-inferior), and −0.01 ± 0.14 cm (left-right). This study confirms the potential of using an open-field MRI scanner as primary imaging modality for prostate cancer treatment planning simulation, dose calculations and daily image localization

  17. Evaluation of preclinical single and multiple dose toxicity and efficacy of 213 Bi-labeled plasminogen activator inhibitor 2 for breast and prostate cancer

    International Nuclear Information System (INIS)

    Rizvi, S.; Li, Y.; Allen, B.; Littlejohn, T.; Ranson, M.; Links, M.; Irving, D.; Andrews, J.

    2003-01-01

    The aim of the study was to evaluate the single and multiple dose toxicity (maximum tolerated dose or MTD) regimes for 213 Bi-labeled PAI2. Dose range of 2-8 mCi/kg was used for the single dose toxicity studies. It was found that end point (20% weight loss and/or distressed behaviour) was not reached for the highest dose either with single or multiple dose injections. For multiple dose toxicity studies, the dose levels ranged between 0.4 - 2 mCi/kg, and were administered daily for 5 days. The highest level tested (2mCi/kg/day x 5) was the maximum tolerated dose as 3/6 mice succumbed to the endpoints. However, histological examination of major organs showed no adverse morphological changes. From these toxicity studies, we concluded that either a dose of 1.6mCi/kg of 213 Bi-PAI2 per day for 5 days or a single injection of 8 mCi/kg can be administered without reaching the endpoints. These dose levels were used for efficacy trials. The efficacy studies were conducted to examine if the 1.6mCi/kgday x 5 multiple dose schedule (sub-maximum tolerated dose) showed efficacy against established and early stage human breast and prostate tumours in mice. Statistical analyses of the data indicate a significant tumour growth rate delay and increased time to reach tumour size endpoint for alpha-PAI2 treatment compared to control tumours, in both pre-tumour stage and established tumour models

  18. SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Narayana, V; McLaughlin, P [Providence Cancer Center, Southfield, MI (United States); University of Michigan, Ann Arbor, MI (United States); Ealbaj, J [University of Michigan, Ann Arbor, MI (United States)

    2015-06-15

    Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients were set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.

  19. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.

    Science.gov (United States)

    Farrar, Diane; Tuffnell, Derek J; West, Jane; West, Helen M

    2016-06-07

    Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin. Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII). To compare CSII with MDI of insulin for pregnant women with pre-existing and gestational diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists of retrieved studies. Randomised trials comparing CSII with MDI for pregnant women with diabetes. Three review authors independently assessed studies and two review authors extracted data. Disagreements were resolved through discussion with the third author. We assessed the quality of the evidence using the GRADE approach. We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review.There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability

  20. Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Liu, Dongzhou J; Collaku, Agron

    2018-01-01

    Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

  1. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers

    NARCIS (Netherlands)

    Aarnoutse, Rob E; Kleinnijenhuis, Johanneke; Koopmans, Peter P; Touw, Daan J; Wieling, Jaap; Hekster, Yechiel A; Burger, David M

    2005-01-01

    OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

  2. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers.

    NARCIS (Netherlands)

    Aarnoutse, R.E.; Kleinnijenhuis, J.; Koopmans †, P.P.; Touw, D.J.; Wieling, J.; Hekster, Y.A.; Burger, D.M.

    2005-01-01

    OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

  3. Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding.

    Science.gov (United States)

    Potel, G; Chau, N P; Pangon, B; Fantin, B; Vallois, J M; Faurisson, F; Carbon, C

    1991-10-01

    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 Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.

  4. 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.

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

    Science.gov (United States)

    Grasso, Carole; Fabre, Marie-Sophie; Collis, Sarah V; Castro, M Leticia; Field, Cameron S; Schleich, Nanette; McConnell, Melanie J; Herst, Patries M

    2014-01-01

    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 tumor environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionizing radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitizing GBM cells will improve survival of GBM patients. Here, we demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells 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 intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a second group received daily intraperitoneal 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 tumor progression, intraperitoneal ascorbate alone had no effect on tumor progression. Tumor progression was faster in tumor-bearing mice treated with radiation and daily ascorbate than in those treated with radiation alone. Histological analysis showed less necrosis in tumors 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 tumor microenvironment, 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.

  6. The guinea pig maximization test--with a multiple dose design

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Vølund, A; Frankild, S

    1995-01-01

    The guinea pig maximization test (GPMT) is usually performed with one moderately irritant induction dose of the allergen and gives a qualitative assessment-hazard identification-of the allergenicity of the chemical. We refined the GPMT by applying a multiple dose design and used 30 guinea pigs in...

  7. The guinea pig maximization test--with a multiple dose design

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Vølund, A; Frankild, S

    1995-01-01

    The guinea pig maximization test (GPMT) is usually performed with one moderately irritant induction dose of the allergen and gives a qualitative assessment-hazard identification-of the allergenicity of the chemical. We refined the GPMT by applying a multiple dose design and used 30 guinea pigs...

  8. Open-Label Single-Sequence Crossover Study Evaluating Pharmacokinetics, Efficacy, and Safety of Once-Daily Dosing of Nitisinone in Patients with Hereditary Tyrosinemia Type 1.

    Science.gov (United States)

    Guffon, Nathalie; Bröijersén, Anders; Palmgren, Ingrid; Rudebeck, Mattias; Olsson, Birgitta

    2018-01-01

    Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529). Well-controlled patients of dry blood spots by tandem mass spectrometry. The primary endpoint was C min of nitisinone after ≥4 weeks of treatment on each dosing regimen. Secondary objectives were evaluation of efficacy and safety during each dosing regimen. In total, 19 patients were enrolled and 17 included in the per-protocol analysis set. The mean (SD) nitisinone C min decreased by 23%, from 26.4 (10.2) to 21.2 (9.9) μmol/L in dry blood spot samples (not equivalent to plasma concentrations), when patients switched from twice- to once-daily dosing. There was no apparent age- or bodyweight-related trend in the degree of C min decrease. No patient had quantifiable succinylacetone levels during the once-daily treatment period, indicating efficacious treatment. All adverse events were mild or moderate and judged unrelated to nitisinone. The switch to once-daily treatment with nitisinone appeared efficacious and safe in the treatment of patients with HT-1.

  9. Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.

    Science.gov (United States)

    Filippi, M; Capra, R; Campi, A; Colombo, B; Prandini, F; Marcianò, N; Gasparotti, R; Comi, G

    1996-01-01

    OBJECTIVES--To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS--T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS--Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS--More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous. Images PMID:8778257

  10. Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

    Science.gov (United States)

    Yanagisawa, Katsuyuki; Ashihara, Junya; Obara, Shinji; Wada, Norio; Takeuchi, Masayoshi; Nishino, Yuri; Maeda, Sayaka; Ishibashi, Yuji; Yamagishi, Sho-ichi

    2014-11-01

    Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.

  11. CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material

    International Nuclear Information System (INIS)

    Spiegel, S.M.; Vinuela, F.; Fox, A.J.; Pelz, D.M.

    1985-01-01

    A prospective study involving 87 patients was carried out to evaluate the necessity for a high dose of contrast material in addition to delayed computed tomographic (CT) scanning for optimal detection of the lesions of multiple sclerosis in the brain. In patients with either clinically definite multiple sclerosis or laboratory-supported definite multiple sclerosis, CT scans were obtained with a uniform protocol. Lesions consistent with multiple sclerosis were demonstrated on the second scan in 54 patients. In 36 of these 54 patients, the high-dose delayed scan added information. These results are quite similar to those of a previous study from this institution using different patients, in whom the second scan was obtained immediately after the bolus injection of contrast material containing 40 g of organically bound iodine. The lack of real difference in the results of the two studies indicate that the increased dose, not just the delay in scanning, is necessary for a proper study

  12. Investigating CT to CBCT image registration for head and neck proton therapy as a tool for daily dose recalculation

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Guillaume, E-mail: g.landry@lmu.de [Department of Medical Physics, Ludwig-Maximilians-University, Munich D85748, Germany and Department of Radiation Oncology, Ludwig-Maximilians-University, Munich D81377 (Germany); Nijhuis, Reinoud; Thieke, Christian; Reiner, Michael; Ganswindt, Ute; Belka, Claus [Department of Radiation Oncology, Ludwig-Maximilians-University, Munich D81377 (Germany); Dedes, George; Handrack, Josefine; Parodi, Katia [Department of Medical Physics, Ludwig-Maximilians-University, Munich D85748 (Germany); Janssens, Guillaume; Orban de Xivry, Jonathan [ICTEAM, Université Catholique de Louvain, Louvain-La-Neuve B1348 (Belgium); Kamp, Florian; Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Munich D81675, Germany and Physik-Department, Technische Universität München, Garching D85748 (Germany); Paganelli, Chiara; Riboldi, Marco; Baroni, Guido [Dipartimento di Elettronica Informazione e Bioingegneria, Politecnico di Milano, Milan 20133 (Italy)

    2015-03-15

    Purpose: Intensity modulated proton therapy (IMPT) of head and neck (H and N) cancer patients may be improved by plan adaptation. The decision to adapt the treatment plan based on a dose recalculation on the current anatomy requires a diagnostic quality computed tomography (CT) scan of the patient. As gantry-mounted cone beam CT (CBCT) scanners are currently being offered by vendors, they may offer daily or weekly updates of patient anatomy. CBCT image quality may not be sufficient for accurate proton dose calculation and it is likely necessary to perform CBCT CT number correction. In this work, the authors investigated deformable image registration (DIR) of the planning CT (pCT) to the CBCT to generate a virtual CT (vCT) to be used for proton dose recalculation. Methods: Datasets of six H and N cancer patients undergoing photon intensity modulated radiation therapy were used in this study to validate the vCT approach. Each dataset contained a CBCT acquired within 3 days of a replanning CT (rpCT), in addition to a pCT. The pCT and rpCT were delineated by a physician. A Morphons algorithm was employed in this work to perform DIR of the pCT to CBCT following a rigid registration of the two images. The contours from the pCT were deformed using the vector field resulting from DIR to yield a contoured vCT. The DIR accuracy was evaluated with a scale invariant feature transform (SIFT) algorithm comparing automatically identified matching features between vCT and CBCT. The rpCT was used as reference for evaluation of the vCT. The vCT and rpCT CT numbers were converted to stopping power ratio and the water equivalent thickness (WET) was calculated. IMPT dose distributions from treatment plans optimized on the pCT were recalculated with a Monte Carlo algorithm on the rpCT and vCT for comparison in terms of gamma index, dose volume histogram (DVH) statistics as well as proton range. The DIR generated contours on the vCT were compared to physician-drawn contours on the rp

  13. SU-F-BRCD-06: Multiple Anatomy Optimization of Accumulated Dose.

    Science.gov (United States)

    Watkins, W T; Moore, J A; Sharma, M; Dial, C; Xu, H; Hugo, G D; Gordon, J J; Siebers, J V

    2012-06-01

    Multiple anatomy optimization (MAO) utilizing deformable dose accumulation on entire 4DCT data sets is implemented to overcome ambiguity between optimal dose defined on a single anatomy and optimal accumulated dose resulting from dose delivery to moving and deforming anatomy. Six lung cancer patients are planned using two methods of radiotherapy optimization: the internal target volume (ITV) envelope method and MAO, which simultaneously optimizes a single fluence for delivery to all 10 breathing phases such that the accumulated dose satisfies the plan objectives. Target dose is constrained to 70 Gy. The ITV-plan is optimized on a single breathing phase with the planning target volume defined as the ITV; the MAO target is the moving CTV. MAO is compared to single image ITV optimization based on the accumulated dose assuming equal monitor-units to each phase. Dose-volume differences between single image estimations and 10-image accumulation are examined. Single image optimal dose distributions overestimate target V70 by 4.2%±3.1% (average, one standard deviation) and in five of six cases ipsilateral lung V20 is underestimated (1.4%±0.9%). For these five cases, MAO increases V70 by 2.8%±2.5% (maximum of 6% increase in V70) and reduces ipsilateral lung V20 by up to 3% (average decrease of 1.2%±1.3%). Contralateral lung V20, esophagus V25, and heart V30 are also reduced by up to 5%, 3%, and 3%. For the sixth case, lung tumor motion is on the order of the dose voxel size (3mm), and MAO did not improve upon the ITV plan. Dose-volume optimization on a stationary image does not ensure accumulated dose coverage to the moving CTV. Multiple anatomy optimization can remove dose ambiguity and improve plan quality. P01CA11602 and Philips Medical Systems. © 2012 American Association of Physicists in Medicine.

  14. Examining Margin Reduction and Its Impact on Dose Distribution for Prostate Cancer Patients Undergoing Daily Cone-Beam Computed Tomography

    International Nuclear Information System (INIS)

    Hammoud, Rabih; Patel, Samir H.; Pradhan, Deepak; Kim, Jinkoo; Guan, Harrison; Li Shidong; Movsas, Benjamin

    2008-01-01

    Purpose: To examine the dosimetric impact of margin reduction and quantify residual error after three-dimensional (3D) image registration using daily cone-beam computed tomography (CBCT) for prostate cancer patients. Methods and Materials: One hundred forty CBCTs from 5 prostate cancer patients were examined. Two intensity-modulated radiotherapy plans were generated on CT simulation on the basis of two planning target volume (PTV) margins: 10 mm all around the prostate and seminal vesicles except 6 mm posteriorly (10/6) and 5 mm all around except 3 mm posteriorly (5/3). Daily CBCT using the Varian On-Board Imaging System was acquired. The 10/6 and 5/3 simulation plans were overlaid onto each CBCT, and each CBCT plan was calculated. To examine residual error, PlanCT/CBCT intensity-based 3D image registration was performed for prostate localization using center of mass and maximal border displacement. Results: Prostate coverage was within 2% between the 10/6 and 5/3 plans. Seminal vesicle coverage was reduced with the 5/3 plan compared with the 10/6 plan, with coverage difference within 7%. The 5/3 plan allowed 30-50% sparing of bladder and rectal high-dose regions. For residual error quantification, center of mass data show that 99%, 93%, and 96% of observations fall within 3 mm in the left-right, anterior-posterior, and superior-inferior directions, respectively. Maximal border displacement observations range from 79% to 99%, within 5 mm for all directions. Conclusion: Cone-beam CT dosimetrically validated a 10/6 margin when soft-tissue localization is not used. Intensity-based 3D image registration has the potential to improve target localization and to provide guidelines for margin definition

  15. Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat(®) in Asthma Using Standardized Sample-Contamination Avoidance

    DEFF Research Database (Denmark)

    Beeh, Kai-Michael; Kirsten, Anne-Marie; Dusser, Daniel

    2016-01-01

    BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(®) 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacoki...

  16. Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

    1997-01-01

    The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

  17. Concurrent chemoradiotherapy for esophageal cancer. Comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil

    International Nuclear Information System (INIS)

    Sai, Heitetsu; Mitsumori, Michihide; Yamauchi, Chikako; Araki, Norio; Okumura, Setsuko; Nagata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    2004-01-01

    Although current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation. Concurrent chemoradiotherapy, using 60 Gy of radiation and ISD-FP or CLD-FP was non-randomly scheduled for 29 patients between June 1994 and March 2001. Complete response in the irradiated volume at the end of primary treatment was shown by 8 of 15 and 9 of 14 patients in the ISD-FP and CLD-FP groups, respectively. The projected overall survival rate at 2 years was 55% for stage III patients and 13% for stage IV. Median survival times were 14 months versus 15 months in the ISD-FP and CLD-FP groups, with no significant difference. Toxicities were similar, including two treatment-related deaths in each group. Chemotherapy was completed for 10 of 15 and 11 of 14 patients in the ISD-FP and CLD-FP groups, respectively. Modification of the planned regimen was more often required for the CLD-FP group. CLD-FP therapy has no apparent advantage over ISD-FP therapy from the perspective of compliance and safety. A randomized phase II clinical trial comparing ISD-FP and CLD-FP, currently being performed, is expected to provide further information. (author)

  18. Prescription Dose Guideline Based on Physical Criterion for Multiple Metastatic Brain Tumors Treated With Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Sahgal, Arjun; Barani, Igor J.; Novotny, Josef; Zhang Beibei; Petti, Paula; Larson, David A.; Ma Lijun

    2010-01-01

    Purpose: Existing dose guidelines for intracranial stereotactic radiosurgery (SRS) are primarily based on single-target treatment data. This study investigated dose guidelines for multiple targets treated with SRS. Methods and Materials: A physical model was developed to relate the peripheral isodose volume dependence on an increasing number of targets and prescription dose per target. The model was derived from simulated and clinical multiple brain metastatic cases treated with the Leksell Gamma Knife Perfexion at several institutions, where the total number of targets ranged from 2 to 60. The relative increase in peripheral isodose volumes, such as the 12-Gy volume, was studied in the multitarget treatment setting based on Radiation Therapy Oncology Group 90-05 study dose levels. Results: A significant increase in the 12-Gy peripheral isodose volumes was found in comparing multiple target SRS to single-target SRS. This increase strongly correlated (R 2 = 0.92) with the total number of targets but not the total target volumes (R 2 = 0.06). On the basis of the correlated curve, the 12-Gy volume for multiple target treatment was found to increase by approximately 1% per target when a low target dose such as 15 Gy was used, but approximately 4% per target when a high dose such as 20-24 Gy was used. Reduction in the prescription dose was quantified for each prescription level in maintaining the 12-Gy volume. Conclusion: Normal brain dose increases predictably with increasing number of targets for multitarget SRS. A reduction of approximately 1-2 Gy in the prescribed dose is needed compared with single target radiosurgery.

  19. Generation of Composite Dose and Biological Effective Dose (BED) Over Multiple Treatment Modalities and Multistage Planning Using Deformable Image Registration

    International Nuclear Information System (INIS)

    Zhang, Geoffrey; Huang, T-C; 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, α/β 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.

  20. Dose accumulation of multiple high dose rate prostate brachytherapy treatments in two commercially available image registration systems.

    Science.gov (United States)

    Poder, Joel; Yuen, Johnson; Howie, Andrew; Bece, Andrej; Bucci, Joseph

    2017-11-01

    The purpose of this study was to assess whether deformable image registration (DIR) is required for dose accumulation of multiple high dose rate prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on two different CT datasets. DIR was applied to 20 HDRPBT patients' planning CT images who received two treatment fractions on sequential days, on two different CT datasets, with the same implant. Quality of DIR in Velocity and MIM image registration systems was assessed by calculating the Dice Similarity Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra and rectum contours. Accumulated doses from each system were then calculated using the same DIR technique and dose volume histogram (DVH) parameters compared to manual addition with no DIR. The average DSC was found to be 0.83 (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and 0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The average difference in calculated DVH parameters between the two systems using dose accumulation was less than 1%, and there was no statistically significant difference found between deformably accumulated doses in the two systems versus manual DVH addition with no DIR. Contour propagation using DIR in velocity and MIM was shown to be at least equivalent to inter-observer contouring variability on CT. The results also indicate that dose accumulation through manual addition of DVH parameters may be sufficient for HDRPBT treatments treated with the same catheter pattern on two different CT datasets. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  1. Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE).

    Science.gov (United States)

    2017-03-30

    Objective  To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment. Design  Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial). Setting  Eight secondary care centres in England and Scotland. Participants  Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment ("dose adjustment for normal eating," DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections. Interventions  Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years. Main outcome measures  The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was -0.24% (-2.7 mmol/mol) in favour of pump users (95% confidence interval -0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24

  2. 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

  3. SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

    International Nuclear Information System (INIS)

    Zhao, J; Hu, W; Xing, Y; Wu, X; Li, Y

    2016-01-01

    Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, position and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.

  4. SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, J; Hu, W [Fudan University Shanghai Cancer Center, Shanghai, Shanghai (China); Xing, Y [Fudan univercity shanghai proton and heavy ion center, Shanghai (China); Wu, X [Fudan university shanghai proton and heavy ion center, Shanghai, shagnhai (China); Li, Y [Department of Medical physics at Shanghai Proton and Heavy Ion Center, Shanghai, Shanghai (China)

    2016-06-15

    Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, position and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.

  5. Influence of low-dose daily cisplatin on the distant metastasis-free survival of patients with locally advanced nonmetastatic head and neck cancer treated with radiation therapy

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Milicic, Biljana

    2008-01-01

    We investigated the impact of low dose daily cisplatin on distant metastasis-free survival (DMFS) in locally advanced head and neck cancer treated with hyperfractionated radiotherapy (77 Gy in 70 fractions in 35 treatment days). In locally controlled tumors cisplatin led to better DMFS (p = 0.0272); Cisplatin may have acted independently of micrometastasis in locally advanced H and N cancer

  6. High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS

    Directory of Open Access Journals (Sweden)

    Hui-Min Chang

    2016-06-01

    Conclusion: We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

  7. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

    Science.gov (United States)

    Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

    2016-11-01

    Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2014-01-01

    BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose du...... for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol...

  9. Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials.

    Science.gov (United States)

    Inaba, Naoko; Sato, Toshiro; Yamashita, Takatoshi

    2015-01-01

    Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin γ-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 μg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 μg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 μg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 μg groups compared with the 0 μg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 μg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake ≥100 μg was suggested to improve osteocalcin γ-carboxylation.

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

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

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

  11. IsoGeneGUI : Multiple approaches for dose-response analysis of microarray data using R

    NARCIS (Netherlands)

    Otava, Martin; Sengupta, Rudradev; Shkedy, Ziv; Lin, Dan; Pramana, Setia; Verbeke, Tobias; Haldermans, Philippe; Hothorn, Ludwig A.; Gerhard, Daniel; Kuiper, Rebecca M.; Klinglmueller, Florian; Kasim, Adetayo

    2017-01-01

    The analysis of transcriptomic experiments with ordered covariates, such as dose-response data, has become a central topic in bioinformatics, in particular in omics studies. Consequently, multiple R packages on CRAN and Bioconductor are designed to analyse microarray data from various perspectives

  12. Multiple dose study of the combined radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole)

    International Nuclear Information System (INIS)

    Bleehen, N.M.; Newman, H.F.; Maughan, T.S.; Workman, P.

    1989-01-01

    The hypoxic cell radiosensitizers Ro 03-8799 and SR 2508 have different clinical toxicities. The former produces an acute but transient central nervous system syndrome, whereas the latter produces cumulative peripheral neuropathy. Following single dose studies, an escalating multiple dose schedule using both drugs in combination showed no unexpected adverse reactions at lower doses. This study identifies the clinical tolerance and pharmacokinetics when doses in the region of the maximal tolerated dose are given to 26 patients receiving infusions of 0.75 g/m2 Ro 03-8799 and 2 g/m2 SR 2508 three times per week. At 15 doses, 3/4 patients experienced WHO grade 2 peripheral neuropathy, whereas at 12 doses 1/9 developed grade 2 and 6/9 developed grade 1 neuropathies. This represents a lower dose of SR 2508 than can be given alone suggesting that some interaction between the two drugs does exist in terms of chronic peripheral neurotoxicity. Pharmacokinetic studies show no adverse interactions between the two drugs and minimal inter-patient variation. From bivariate analysis, cumulative AUC for Ro 03-8799 has the most significant correlation with the development of peripheral neuropathy. Tumor drug concentrations normalized to the administered dose show mean values of 34 micrograms/g Ro 03-8799 and 76 micrograms/g SR 2508 30 minutes after infusion. These could be expected to produce a single dose sensitizer enhancement ratio of 1.5. The combination of the two sensitizers at the maximum tolerable dose may be expected to give an increased therapeutic efficacy over either drug alone

  13. Using synthetic data to evaluate multiple regression and principal component analyses for statistical modeling of daily building energy consumption

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, T.A. (Energy Systems Lab., Texas A and M Univ., College Station, TX (United States)); Claridge, D.E. (Energy Systems Lab., Texas A and M Univ., College Station, TX (United States))

    1994-01-01

    Multiple regression modeling of monitored building energy use data is often faulted as a reliable means of predicting energy use on the grounds that multicollinearity between the regressor variables can lead both to improper interpretation of the relative importance of the various physical regressor parameters and to a model with unstable regressor coefficients. Principal component analysis (PCA) has the potential to overcome such drawbacks. While a few case studies have already attempted to apply this technique to building energy data, the objectives of this study were to make a broader evaluation of PCA and multiple regression analysis (MRA) and to establish guidelines under which one approach is preferable to the other. Four geographic locations in the US with different climatic conditions were selected and synthetic data sequence representative of daily energy use in large institutional buildings were generated in each location using a linear model with outdoor temperature, outdoor specific humidity and solar radiation as the three regression variables. MRA and PCA approaches were then applied to these data sets and their relative performances were compared. Conditions under which PCA seems to perform better than MRA were identified and preliminary recommendations on the use of either modeling approach formulated. (orig.)

  14. Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

    Science.gov (United States)

    Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

    2014-09-01

    Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

  15. Low-dose multiple-information retrieval algorithm for X-ray grating-based imaging

    International Nuclear Information System (INIS)

    Wang Zhentian; Huang Zhifeng; Chen Zhiqiang; Zhang Li; Jiang Xiaolei; Kang Kejun; Yin Hongxia; Wang Zhenchang; Stampanoni, Marco

    2011-01-01

    The present work proposes a low dose information retrieval algorithm for X-ray grating-based multiple-information imaging (GB-MII) method, which can retrieve the attenuation, refraction and scattering information of samples by only three images. This algorithm aims at reducing the exposure time and the doses delivered to the sample. The multiple-information retrieval problem in GB-MII is solved by transforming a nonlinear equations set to a linear equations and adopting the nature of the trigonometric functions. The proposed algorithm is validated by experiments both on conventional X-ray source and synchrotron X-ray source, and compared with the traditional multiple-image-based retrieval algorithm. The experimental results show that our algorithm is comparable with the traditional retrieval algorithm and especially suitable for high Signal-to-Noise system.

  16. Daily organ tracking in intensity-modulated radiotherapy of prostate cancer using an electronic portal imaging device with a dose saving acquisition mode

    International Nuclear Information System (INIS)

    Vetterli, Daniel; Thalmann, Sandrine; Behrensmeier, Frank; Kemmerling, Ludger; Born, Ernst J.; Mini, Roberto; Greiner, Richard H.; Aebersold, Daniel M.

    2006-01-01

    Background and purpose: Daily use of conventional electronic portal imaging devices (EPID) for organ tracking is limited due to the relatively high dose required for high quality image acquisition. We studied the use of a novel dose saving acquisition mode (RadMode) allowing to take images with one monitor unit per image in prostate cancer patients undergoing intensity-modulated radiotherapy (IMRT) and tracking of implanted fiducial gold markers. Patients and methods: Twenty five patients underwent implantation of three fiducial gold markers prior to the planning CT. Before each treatment of a course of 37 fractions, orthogonal localization images from the antero-posterior and from the lateral direction were acquired. Portal images of both the setup procedure and the five IMRT treatment beams were analyzed. Results: On average, four localization images were needed for a correct patient setup, resulting in four monitor units extra dose per fraction. The mean extra dose delivered to the patient was thereby increased by 1.2%. The procedure was precise enough to reduce the mean displacements prior to treatment to ≤0.3 mm. Conclusions: The use of a new dose saving acquisition mode enables to perform daily EPID-based prostate tracking with a cumulative extra dose of below 1 Gy. This concept is efficiently used in IMRT-treated patients, where separation of setup beams from treatment beams is mandatory

  17. SIGMA/B, Doses in Space Vehicle for Multiple Trajectories, Various Radiation Source

    International Nuclear Information System (INIS)

    Jordan, T.M.

    2003-01-01

    1 - Description of problem or function: SIGMA/B calculates radiation dose at arbitrary points inside a space vehicle, taking into account vehicle geometry, heterogeneous placement of equipment and stores, vehicle materials, time-weighted astronaut positions and many radiation sources from mission trajectories, e.g. geomagnetically trapped protons and electrons, solar flare particles, galactic cosmic rays and their secondary radiations. The vehicle geometry, equipment and supplies, and man models are described by quadric surfaces. The irradiating flux field may be anisotropic. The code can be used to perform simultaneous dose calculations for multiple vehicle trajectories, each involving several radiation sources. Results are presented either as dose as a function of shield thickness, or the dose received through designated outer sections of the vehicle. 2 - Method of solution: Automatic sectoring of the vehicle is performed by a Simpson's rule integration over angle; the dose is computed by a numerical angular integration of the dose attenuation kernels about the dose points. The kernels are curve-fit functions constructed from input data tables. 3 - Restrictions on the complexity of the problem: The code uses variable dimensioning techniques to store data. The only restriction on problem size is the available core storage

  18. Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Chun-xiu Gong

    2014-01-01

    Full Text Available Aims. To determine whether multiple daily injections (MDIs or continuous subcutaneous insulin infusion (CSII contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (≤1 year after disease onset; 1A or late (1–3 years after onset; 2A MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2: 7.37% versus 8.21%; 12 months (T3: 7.61% versus 8.41%; 24/36 months (T4/T5: 7.61% versus 8.72%; all P<0.05, but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; P=0.04. Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; P<0.05. Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management.

  19. Fear of needles in children with type 1 diabetes mellitus on multiple daily injections and continuous subcutaneous insulin infusion.

    Science.gov (United States)

    Cemeroglu, Ayse Pinar; Can, Argun; Davis, Alan T; Cemeroglu, Ozlem; Kleis, Lora; Daniel, Maala S; Bustraan, Jessica; Koehler, Tracy J

    2015-01-01

    To assess the prevalence of fear of needles and its effect on glycemic control in children with type 1 diabetes mellitus (T1DM) on multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Patients aged 6 to 17 years with T1DM on MDI or CSII (n = 150) were enrolled. All caregivers and patients aged ≥11 years completed a "Diabetes Fear of Injecting and Self-testing Questionnaire" (D-FISQ). Needle phobia was defined as a score ≥6 for fear of self-testing (FST), fear of injections (FI), and fear of infusion-site changes (FISC). Positive FST scores were noted in 10.0% and positive FI or FISC scores in 32.7% (caregivers' responses). Patients aged 6 to 10 years on CSII had greater fear (FISC) than those on MDI (FI) (P = .010). FST was inversely related to the number of daily blood sugar checks (P = .003). Patients with positive scores for FI/FISC or FST had significantly higher glycated hemoglobin (HbA1c) levels than those without. An inverse association was noted between positive FI/FISC scores and age of the patient (P = .029). Based on patient responses, FST severity was directly related to the age of the patient (P = .013). Needle phobia is common in children with T1DM. Although FI/FISC are more common in younger children, especially in those on CSII, FST is more often encountered in older patients. Patients with a more intense fear of needles have higher HbA1c levels and less frequent blood sugar monitoring. Identifying these patients may help improve glycemic control.

  20. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

    Science.gov (United States)

    Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

    2015-01-01

    Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily

  1. Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

    Science.gov (United States)

    Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

    2018-05-01

    The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  2. Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin Injections.

    Science.gov (United States)

    Holmes-Walker, Deborah Jane; Gunton, Jenny E; Hawthorne, Wayne; Payk, Marlene; Anderson, Patricia; Donath, Susan; Loudovaris, Tom; Ward, Glenn M; Kay, Thomas Wh; OʼConnell, Philip J

    2017-06-01

    The aim was to compare efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with severe hypoglycemia. This was a within-subject, paired comparison of MDI and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes subjects referred with severe hypoglycemia, suitable for islet transplantation. Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore), continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose variability using standard deviation of glucose (SD glucose) from CGM and continuous overlapping net glycemic action using a 4 hour interval (CONGA4). After changing from MDI to CSII before transplantation, 10 subjects reduced median HYPOscore from 2028 to 1085 (P transplantation, there were significant reductions in all baseline parameters versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085), mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6 cf 3.0). In subjects with severe hypoglycemia suitable for islet transplantation, CSII decreased hypoglycemia frequency and glycemic variability compared with MDI whereas islet transplantation resolved hypoglycemia and further improved glycemic variability regardless of insulin independence.

  3. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    Science.gov (United States)

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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

  5. Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

    Science.gov (United States)

    Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

    2013-10-01

    To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP

  6. Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Klose, Marianne Christina; Hansen, Mette

    2011-01-01

    Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives......: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD). Subjects and Methods: Thirty-three adult patients with GHD, age 20-65 yr, body mass index 18.5-35.0 kg/m(2), and glycated...... to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed. Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed...

  7. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

    International Nuclear Information System (INIS)

    Boutry, Nathalie; Dutouquet, Bastien; Cotten, Anne; Leleu, Xavier; Vieillard, Marie-Helene; Duhamel, Alain

    2013-01-01

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  8. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Boutry, Nathalie [University Hospital of Jeanne de Flandre and University of Lille 2, Departments of Pediatric and Musculoskeletal Imaging, Lille (France); University Hospital of Jeanne de Flandre and University of Lille 2, Department of Pediatric Imaging, Lille (France); Hopital Jeanne de Flandre, Service de Radiopediatrie, Lille (France); Dutouquet, Bastien; Cotten, Anne [University Hospital of Roger Salengro and University of Lille 2, Department of Musculoskeletal Imaging, Lille (France); Leleu, Xavier [University Hospital of Claude Huriez and University of Lille 2, Clinical Hematology Department, Lille (France); Vieillard, Marie-Helene [University Hospital of Roger Salengro and University of Lille 2, Rheumatology Department, Lille (France); Duhamel, Alain [University of Lille 2, Department of Medical Statistics, Lille (France)

    2013-08-15

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  9. Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

    Science.gov (United States)

    van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

    2014-01-01

    Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

  10. Multiple local minima in IMRT optimization based on dose-volume criteria

    International Nuclear Information System (INIS)

    Wu Qiuwen; Mohan, Radhe

    2002-01-01

    Multiple local minima traps are known to exist in dose-volume and dose-response objective functions. Nevertheless, their presence and consequences are not considered impediments in finding satisfactory solutions in routine optimization of IMRT plans using gradient methods. However, there is often a concern that a significantly superior solution may exist unbeknownst to the planner and that the optimization process may not be able to reach it. We have investigated the soundness of the assumption that the presence of multiple minima traps can be ignored. To find local minima, we start the optimization process a large number of times with random initial intensities. We investigated whether the occurrence of local minima depends upon the choice of the objective function parameters and the number of variables and whether their existence is an impediment in finding a satisfactory solution. To learn about the behavior of multiple minima, we first used a symmetric cubic phantom containing a cubic target and an organ-at-risk surrounding it to optimize the beam weights of two pairs of parallel-opposed beams using a gradient technique. The phantom studies also served to test our software. Objective function parameters were chosen to ensure that multiple minima would exist. Data for 500 plans, optimized with random initial beam weights, were analyzed. The search process did succeed in finding the local minima and showed that the number of minima depends on the parameters of the objective functions. It was also found that the consequences of local minima depended on the number of beams. We further searched for the multiple minima in intensity-modulated treatment plans for a head-and-neck case and a lung case. In addition to the treatment plan scores and the dose-volume histograms, we examined the dose distributions and intensity patterns. We did not find any evidence that multiple local minima affect the outcome of optimization using gradient techniques in any clinically

  11. Development of a Monte Carlo multiple source model for inclusion in a dose calculation auditing tool.

    Science.gov (United States)

    Faught, Austin M; Davidson, Scott E; Fontenot, Jonas; Kry, Stephen F; Etzel, Carol; Ibbott, Geoffrey S; Followill, David S

    2017-09-01

    The Imaging and Radiation Oncology Core Houston (IROC-H) (formerly the Radiological Physics Center) has reported varying levels of agreement in their anthropomorphic phantom audits. There is reason to believe one source of error in this observed disagreement is the accuracy of the dose calculation algorithms and heterogeneity corrections used. To audit this component of the radiotherapy treatment process, an independent dose calculation tool is needed. Monte Carlo multiple source models for Elekta 6 MV and 10 MV therapeutic x-ray beams were commissioned based on measurement of central axis depth dose data for a 10 × 10 cm 2 field size and dose profiles for a 40 × 40 cm 2 field size. The models were validated against open field measurements consisting of depth dose data and dose profiles for field sizes ranging from 3 × 3 cm 2 to 30 × 30 cm 2 . The models were then benchmarked against measurements in IROC-H's anthropomorphic head and neck and lung phantoms. Validation results showed 97.9% and 96.8% of depth dose data passed a ±2% Van Dyk criterion for 6 MV and 10 MV models respectively. Dose profile comparisons showed an average agreement using a ±2%/2 mm criterion of 98.0% and 99.0% for 6 MV and 10 MV models respectively. Phantom plan comparisons were evaluated using ±3%/2 mm gamma criterion, and averaged passing rates between Monte Carlo and measurements were 87.4% and 89.9% for 6 MV and 10 MV models respectively. Accurate multiple source models for Elekta 6 MV and 10 MV x-ray beams have been developed for inclusion in an independent dose calculation tool for use in clinical trial audits. © 2017 American Association of Physicists in Medicine.

  12. Ecological Momentary Assessment of Pain, Fatigue, Depressive, and Cognitive Symptoms Reveals Significant Daily Variability in Multiple Sclerosis.

    Science.gov (United States)

    Kratz, Anna L; Murphy, Susan L; Braley, Tiffany J

    2017-11-01

    To describe the daily variability and patterns of pain, fatigue, depressed mood, and cognitive function in persons with multiple sclerosis (MS). Repeated-measures observational study of 7 consecutive days of home monitoring, including ecological momentary assessment (EMA) of symptoms. Multilevel mixed models were used to analyze data. General community. Ambulatory adults (N=107) with MS recruited through the University of Michigan and surrounding community. Not applicable. EMA measures of pain, fatigue, depressed mood, and cognitive function rated on a 0 to 10 scale, collected 5 times a day for 7 days. Cognitive function and depressed mood exhibited more stable within-person patterns than pain and fatigue, which varied considerably within person. All symptoms increased in intensity across the day (all Pfatigue showing the most substantial increase. Notably, this diurnal increase varied by sex and age; women showed a continuous increase from wake to bedtime, whereas fatigue plateaued after 7 pm for men (wake-bed B=1.04, P=.004). For the oldest subgroup, diurnal increases were concentrated to the middle of the day compared with younger subgroups, which showed an earlier onset of fatigue increase and sustained increases until bed time (wake-3 pm B=.04, P=.01; wake-7 pm B=.03, P=.02). Diurnal patterns of cognitive function varied by education; those with advanced college degrees showed a more stable pattern across the day, with significant differences compared with those with bachelor-level degrees in the evening (wake-7 pm B=-.47, P=.02; wake-bed B=-.45, P=.04). Findings suggest that chronic symptoms in MS are not static, even over a short time frame; rather, symptoms-fatigue and pain in particular-vary dynamically across and within days. Incorporation of EMA methods should be considered in the assessment of these chronic MS symptoms to enhance assessment and treatment strategies. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier

  13. Evaluation of Total Daily Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the Hospital

    Science.gov (United States)

    2016-05-20

    regular insulin has significantly increased in recent years. These patients are severely insulin resistant requiring high doses of insulin to achieve...on U-500 Insulin Admitted to the Hospital presented at SURF Conference, San Antonio, TX 20 May 201 6 with MDWI 41-108, and has been assigned local...59th CSPG/SGVU) C.201 4 . I 52d PROTOCOL TITLE Evaluation of Total Dai ly Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the

  14. Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of constipation and encopresis in children.

    Science.gov (United States)

    Pashankar, D S; Bishop, W P

    2001-09-01

    To determine efficacy, safety, and optimal dose of a laxative, polyethylene glycol (PEG) 3350, in children with chronic constipation. Children with chronic constipation (n = 24) were treated with PEG for 8 weeks at an initial dose of 1 g/kg/d. The dose was adjusted every 3 days as required to achieve 2 soft stools per day. A diary was kept to monitor dose, stool frequency and consistency, soiling, and other symptoms. Stool consistency was rated from 1 (hard) to 5 (watery). Subjects were examined for fecal retention. The Student t test and the Fisher exact test were used for data analysis. All 20 children who completed the study found PEG to be palatable and were satisfied with the treatment. There were no significant adverse effects. Weekly stool frequency increased from 2.3 +/- 0.4 to 16.9 +/- 1.6 (P PEG at a mean dose of 0.8 g/kg is an effective, safe, and palatable treatment for constipation.

  15. Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice

    International Nuclear Information System (INIS)

    Iwai, Hiroyuki; Matsuno, Etsuko; Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta

    1994-01-01

    In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab

  16. Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures.

    Science.gov (United States)

    Nielsen, Jace C; Hutmacher, Matthew M; Wesche, David L; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G

    2015-01-01

    Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. © 2014, The American College of Clinical Pharmacology.

  17. Comparison of treatment with continuous subcutaneous insulin infusion versus multiple daily insulin injections with bolus calculator in patients with type 1 diabetes.

    Science.gov (United States)

    Pérez-García, L; Goñi-Iriarte, M J; García-Mouriz, M

    2015-01-01

    A study of the glycemic control, quality of life, and fear and perception of hypoglycemia by comparing continuous subcutaneous insulin infusion (CSII) group with multiple daily inyections (MDI) with bolus calculator group. This is a retrospective cohort study with following up during the first 12 months that CSII group (n=30) begins the use of "bolus wizard" and the MDI-calculator (n=30) group begins the use of the bolus calculator (Accu-Chek(®) Aviva Expert). HbA1c (3, 6 and 12 months). Questionnaires used: EsDQOL (quality of life), FH-15 (fear of hypoglycemia), and Clarke (perception of hypoglycemia). T Student and nonparametric tests. The average reduction in HbA1c during the study was significantly higher in CSII group (-0.56±0.84%) compared with the MDI group (0.097±0.94%), P=.028. The average basal insulin dose was significantly higher in the MDI group (at baseline, 6 and 12 months). No significant differences were found between the 2 treatment groups after analyzing the EsDQOL, FH-15 and Clarke questionnaires. In the CSII group, perceived quality of life assessed by the EsDQOL questionnaire was found to be better at the end of the study than at the beginning of using the insulin pump. The average reduction in HbA1c was significantly higher in the CSII group. In the CSII group, perceived quality of life was better at the end of the study than at the beginning. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  18. Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

    International Nuclear Information System (INIS)

    Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K.

    2004-01-01

    An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 ∼ 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 ∼ 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively (ρ = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively (ρ = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively (ρ = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively (ρ = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia (≥ 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively (ρ = 0.02). There were no statistical differences

  19. Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K. [Inha University Medical College, Inchon (Korea, Republic of)

    2004-09-15

    An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 {approx} 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 {approx} 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia ({>=} 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively ({rho} = 0.02). There were

  20. Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

    Science.gov (United States)

    Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

    2011-05-01

    The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

    Science.gov (United States)

    Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

    2012-11-01

    To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; Plunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

  3. Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

    Science.gov (United States)

    Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

    2018-01-01

    Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  5. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  6. SU-F-J-62: Assessment of Dose Changes Due to Anterior-Posterior Patient Separation During Daily MVCT Scans

    Energy Technology Data Exchange (ETDEWEB)

    Leney, M [Wayne State University, Detroit, MI (United States); Nalichowski, A; Patel, S [Karmanos Cancer Institute, Detroit, MI (United States)

    2016-06-15

    Purpose: To determine the effects of patient separation on absolute dose and dose distribution in patients undergoing pelvic radiotherapy on TomoTherapy. Methods: An Alderson RANDO phantom with 4cm of bolus was imaged on a CT simulator and the resulting scans were contoured as a whole pelvic case. Using TomoTherapy Planning Station, the plan was designed to give 45 Gy to 95% of the treatment volume in 25 fractions. TomoTherapy MVCT scans were performed on the RANDO phantom with 2cm and 4cm of bolus removed to simulate visible changes in a patient’s anatomy. The MVCT images were rigidly registered with planning CT images on TomoTherapy Planned Adaptive. The original fluence was recalculated on the MVCT images and changes in dose distribution due to patient separation were quantified by the changes in DVHs for the target volume and the organs at risk. Results: Patient separation difference equivalent to 2cm and 4cm in anterior-posterior direction resulted in an increase of the PTV D50 and maximum PTV dose of 5.6%, 6.2% for 2cm and 7.7%, 10.4% for 4cm, respectively. For the 2cm change, D50 and maximum doses to organs at risk increased by 6.5%, 7.1% in the bladder, 4.9%, 4.8% in the rectum, and 5.3%, 6.6% in the bowel. For the 4cm change, D50 and maximum doses increased by 10.7%, 12.2% in the bladder, 5.9%, 6.1% in the rectum, and 7.7%, 10.1% in the bowel. Conclusion: This research indicates that, without any changes to the structures, patient separation in the anterior-posterior direction can affect the dose distribution for the PTV and organs at risk. These results can assist physicians in determining if obtaining a new CT simulation set and replanning is necessary for pelvic patients on TomoTherapy.

  7. Separation of the Galactic Cosmic Rays and Inner Earth Radiation Belt Contributions to the Daily Dose Onboard the International Space Station in 2005-2011

    Science.gov (United States)

    Lishnevskii, A. E.; Benghin, V. V.

    2018-03-01

    The DB-8 detectors of the ISS radiation monitoring system (RMS) have operated almost continuously onboard the ISS service module since August 2001 till December 2014. The RMS data obtained were used for the daily monitoring of the radiation environment aboard the station. This paper considers the technique of RMS data analysis that allows one to distinguish the contributions of galactic cosmic rays and the Earth's inner radiation belt to the daily dose based on the dosimetry data obtained as a result of the station's passage in areas of the highest geomagnetic latitudes. The paper presents the results of an analysis of the dosimetry data based on this technique for 2005-2011, as well as a comparison with similar results the authors obtained previously using the technique based on an analysis of the dosimetry data obtained during station passages in the area of the South Atlantic Anomaly.

  8. Dosimetric comparison of stereotactic body radiotherapy using 4D CT and multiphase CT images for treatment planning of lung cancer: Evaluation of the impact on daily dose coverage

    International Nuclear Information System (INIS)

    Wang Lu; Hayes, Shelly; Paskalev, Kamen; Jin Lihui; Buyyounouski, Mark K.; Ma, Charlie C.-M.; Feigenberg, Steve

    2009-01-01

    Purpose: To investigate the dosimetric impact of using 4D CT and multiphase (helical) CT images for treatment planning target definition and the daily target coverage in hypofractionated stereotactic body radiotherapy (SBRT) of lung cancer. Materials and methods: For 10 consecutive patients treated with SBRT, a set of 4D CT images and three sets of multiphase helical CT scans, taken during free-breathing, end-inspiration and end-expiration breath-hold, were obtained. Three separate planning target volumes (PTVs) were created from these image sets. A PTV 4D was created from the maximum intensity projection (MIP) reconstructed 4D images by adding a 3 mm margin to the internal target volume (ITV). A PTV 3CT was created by generating ITV from gross target volumes (GTVs) contoured from the three multiphase images. Finally, a third conventional PTV (denoted PTV conv ) was created by adding 5 mm in the axial direction and 10 mm in the longitudinal direction to the GTV (in this work, GTV = CTV = clinical target volume) generated from free-breathing helical CT scans. Treatment planning was performed based on PTV 4D (denoted as Plan-1), and the plan was adopted for PTV 3CT and PTV conv to form Plan-2 and Plan-3, respectively, by superimposing 'Plan-1' onto the helical free-breathing CT data set using modified beam apertures that conformed to either PTV 3CT or PTV conv . We first studied the impact of PTV design on treatment planning by evaluating the dosimetry of the three PTVs under the three plans, respectively. Then we examined the effect of the PTV designs on the daily target coverage by utilizing pre-treatment localization CT (CT-on-rails) images for daily GTV contouring and dose recalculation. The changes in the dose parameters of D 95 and D 99 (the dose received by 95% and 99% of the target volume, respectively), and the V p (the volume receiving the prescription dose) of the daily GTVs were compared under the three plans before and after setup error correction

  9. The effect of Self-Care Program Base on the Orem Frame Work on Fatigue and Activity of Daily Living in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Reza Masoudi

    2009-10-01

    Full Text Available Objective: Fatigue is one of the tormentest symptom of the Multiple Sclerosis that decrease self care ability and role performance of patients and potential of activity of daily living. The purpose of this study was to assess the effect of Orem self- care program on fatigue and activity of daily living (ADL in Multiple Sclerosis clients. Materials & Methods: This quasi experimental study was a clinical trial research that was done on seventy multiple sclerosis patients whom were selected randomly from M.S. association and assigned to experimental and control group by balanced randomized method. The experimental group was treated with 8 sessions of self-care program based on Orem self-care framework and the program belonged for three months in experimental group and followed up with self-report questionnaire. Score of fatigue and activity of daily living of two groups were assessed at first of research and three months later by Payper and Barthel scales. Data were analyzed using Chi square, Independent T and Paired T test and Variance analysis. Results: There was no significant difference between two group in fatigue (P=0.48 and activity of daily living (P= 0.24 befor intervention, but these differences were significant after intervention (P<0.001. There were significant differences in experimental group between before and after score of fatigue and ADL (P<0.001, whereas there was no significant difference in fatigue (P=0.086 and ADL (P=0.33 of control group. Conclusion: Utilizing self care program base on the Orem frame work and the educational needs as a safe and inexpensive nursing intervention, it might be effective on fatigue decrease and activity of daily living enhance in Multiple Sclerosis patients.

  10. Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

    Science.gov (United States)

    Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

    2017-03-28

    Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

  11. Evaluation of Total Daily Dose and Glycemic Control for Patients Taking U-500 Insulin Admitted to the Hospital

    Science.gov (United States)

    2016-04-27

    mail:jack.e.lewi.mil@mail.mil Key Words: U-500 regular insulin , inpatient diabetes mellitus, insulin resistance Conflict of Interest Statements...500 regular insulin are severely insulin resistant requiring high doses of insulin . It has been observed that a patient’s insulin requirements may...concentrated than U-100 regular insulin and is generally used in patients with severe insulin resistance requiring greater than 200 units of insulin

  12. Computed tomography in multiple trauma patients. Technical aspects, work flow, and dose reduction

    International Nuclear Information System (INIS)

    Fellner, F.A.; Krieger, J.; Floery, D.; Lechner, N.

    2014-01-01

    Patients with severe, life-threatening trauma require a fast and accurate clinical and imaging diagnostic workup during the first phase of trauma management. Early whole-body computed tomography has clearly been proven to be the current standard of care of these patients. A similar imaging quality can be achieved in the multiple trauma setting compared with routine imaging especially using rapid, latest generation computed tomography (CT) scanners. This article encompasses a detailed view on the use of CT in patients with life-threatening trauma. A special focus is placed on radiological procedures in trauma units and on the methods for CT workup in routine cases and in challenging situations. Another focus discusses the potential of dose reduction of CT scans in multiple trauma as well as the examination of children with severe trauma. Various studies have demonstrated that early whole-body CT positively correlates with low morbidity and mortality and is clearly superior to the use of other imaging modalities. Optimal trauma unit management means a close cooperation between trauma surgeons, anesthesiologists and radiologists, whereby the radiologist is responsible for a rapid and accurate radiological workup and the rapid communication of imaging findings. However, even in the trauma setting, aspects of patient radiation doses should be kept in mind. (orig.) [de

  13. SU-F-J-203: Retrospective Assessment of Delivered Proton Dose in Prostate Cancer Patients Based On Daily In-Room CT Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Stuetzer, K; Paessler, T [OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Valentini, C; Thiele, J; Hoelscher, T [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Techenische Universitaet Dresden (Germany); Exner, F [OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); now with: University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Krause, M; Richter, C [OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Techenische Universitaet Dresden (Germany); Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden (Germany); German Cancer Consortium (DKTK), Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2016-06-15

    Purpose: Retrospective calculation of the delivered proton dose in prostate cancer patients based on a unique dataset of daily CT images. Methods: Inter-fractional motion in prostate cancer patients treated at our proton facility is counteracted by water-filled endorectal ballon and bladder filling protocol. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective iCTV. Stability of fiducial markers and anatomy were checked in 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning according to bony anatomy utilizing orthogonal X-ray. In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98%>95%, D2%<107%), bladder (V75Gy<15%, V70Gy<25%, V65Gy<30%), rectum (V70Gy<10%, V50Gy<40%) and femoral heads (V50Gy<5%) are compared to those in the treatment plan. Intra-therapy variation is represented in DVH bands. Results: No alarming differences were observed between planned and retrospectively accumulated dose: iCTV constraints were met, except for one patient (D98%=94.6% in non-boosted iCTV). Considered bladder and femoral head values were below the limits. Rectum V70Gy was slightly exceeded (<11.3%) in two patients. First intra-therapy variability analysis in 4 patients showed no timedependent parameter drift, revealed strongest variability for bladder dose. In some fractions, iCTV coverage (D98%) and rectum V70Gy was missed. Conclusion: Double scattered proton plans are accurately delivered to prostate cancer patients due to fractionation effects and the applied precise positioning and immobilization protocols. As a result of rare

  14. Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin

    DEFF Research Database (Denmark)

    Nicoletti, F; Di Marco, R; Conget, I

    2000-01-01

    We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every...... induced in vivo by ConA, reducing the levels of IFN-gamma, IL-2 and TNF-alpha and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-gamma seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease...... other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice...

  15. Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

    International Nuclear Information System (INIS)

    Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

    1986-01-01

    The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism

  16. Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Benson, D; Arthur, R M

    2016-08-01

    Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses. © 2016 John Wiley & Sons Ltd.

  17. Daily Dose effect of Valerian root extract on some Neurotransmitter contents in different Brain areas of male Albino Rats

    International Nuclear Information System (INIS)

    Waggas, Abeer M

    2007-01-01

    The aim of the present study was to investigate the daily effect of valerian (Valeriana officinalis L .) root extract on epinephrine (E), norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) , and gamma-aminobutyric acid (GABA) contents in different brain areas (cerebellum , pons plus medulla oblongata , striatum , cerebral cortex, hypothalamus, midbrain and hippocampus) of male albino rats .The daily intraperitoneal ( i.p.) injection of 300 mg/kg body wt valerian for 30 days caused a significant increase in epinephrine ( E ) content in pons plus medulla oblongata, cerebral cortex , hypothalamus and in midbrain . Norepinephrine (NE ) content was significantly increased in all brain areas tested except in cerebellum and cerebral cortex . Dopamine (DA) content was significantly increased in all tested brain areas except in cerebral cortex and hippocampus . moreover , there was also a significant increase in serotonin (5-HT ) and 5-hydroxyindol acetic acid (5-HIAA) contents in all tested brain areas . However, gamma-aminobutyric acid (GABA) content was significantly decreased in all tested brain areas . After the extract withdrawal, the increase in ( E, NE, DA , 5-HT ) contents and the decrease in GABA content persisted in pons plus medulla oblongata , striatum , midbrain and hippocampus , and this might be due to regional differences toward the effect. The increase in E, NE, DA , 5-HT and 5-HIAA contents, at the same time the decrease in GABA content in the different brain areas of albino rats may be due to the presence of both valepotriates and valerenic acid in the extract which mediated the GABA ergic mechanisms including the inhibition of GABA metabolism and the increase in GABA synthesis and release , although agonized the GABAA receptors which led to the inhibit of the neurotransmitter release. Valerian root extract may be useful as a herbal medicine having sedative effect and it is safe. (author)

  18. A randomised clinical trial on the efficacy of oxytetracycline dose through water medication of nursery pigs on diarrhoea, faecal shedding of Lawsonia intracellularis and average daily weight gain.

    Science.gov (United States)

    Larsen, Inge; Hjulsager, Charlotte Kristiane; Holm, Anders; Olsen, John Elmerdahl; Nielsen, Søren Saxmose; Nielsen, Jens Peter

    2016-01-01

    Oral treatment with antimicrobials is widely used in pig production for the control of gastrointestinal infections. Lawsonia intracellularis (LI) causes enteritis in pigs older than six weeks of age and is commonly treated with antimicrobials. The objective of this study was to evaluate the efficacy of three oral dosage regimens (5, 10 and 20mg/kg body weight) of oxytetracycline (OTC) in drinking water over a five-day period on diarrhoea, faecal shedding of LI and average daily weight gain (ADG). A randomised clinical trial was carried out in four Danish pig herds. In total, 539 animals from 37 batches of nursery pigs were included in the study. The dosage regimens were randomly allocated to each batch and initiated at presence of assumed LI-related diarrhoea. In general, all OTC doses used for the treatment of LI infection resulted in reduced diarrhoea and LI shedding after treatment. Treatment with a low dose of 5mg/kg OTC per kg body weight, however, tended to cause more watery faeces and resulted in higher odds of pigs shedding LI above detection level when compared to medium and high doses (with odds ratios of 5.5 and 8.4, respectively). No association was found between the dose of OTC and the ADG. In conclusion, a dose of 5mg OTC per kg body weight was adequate for reducing the high-level LI shedding associated with enteropathy, but a dose of 10mg OTC per kg body weight was necessary to obtain a maximum reduction in LI shedding. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. radioactivity analysis in food-stuffs and evaluation of annual effective doses from intakes of radionuclides through daily diets

    International Nuclear Information System (INIS)

    Alam, M.N.; Chowdhury, M. I.; Kamal, M.; Ghose, S.; Islam, M. N.; Mustafa, M. N.; Islam, Al Amin S.

    1996-01-01

    The concentrations of natural and anthropogenic gamma emitting radionuclides in different vegetables, grains,fishes, sugar and common salt samples were measured by using high purity germanium ( HPGe ) detector coupled with Personal Computer Analyzer ( PCA ) and thereby the effective doses from the consumption of these diet were evaluated. The activities of 232 Th in vegetable, grains, salt, sugar and fish samples ranged from 0.13±0.02 to 1.49±0.32 Bq. kg -1 . The concentration of 238 U in these food-stuffs ranged from 0.07±0.01 to 0.95±0.26 Bq Kg -1 . The observed activity of 40 K ranged between 5.04±1.05 and 196.60±41.0 Bq Kg -1 . Caesium was not detected in any of the samples, Assessment of annual intake of these radionuclides has been made on the basis of the average annual intake of these food-stuffs by the population of Bangladesh.The annual effective dose equivalent due to ingestion of different naturally occurring radionuclides ( 232 Th, 238 U, and 40 K) by intake food-stuffs ranged from 0.2 to 113.62 μ Sv. y'-1. The annual effective doses observed in the present study for various types of food-stuffs were less than the ICRP-60 (1990) recommendation, which is 1 m Sv. y -1 for the members of the public. The result and knowledge of this study, would be helpful in making a yardstick comparing with which an appropriate radiation control limit may be imposed on food materials for public consumption in Bangladesh. 1 fig., 2 tables, 13 refs. (Author)

  20. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

    Science.gov (United States)

    Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

    2014-11-01

    Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included

  1. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

    Science.gov (United States)

    Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

    2016-01-01

    Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

  2. A comparison in young and elderly subjects of the pharmacokinetics and pharmacodynamics of single and multiple doses of benazepril.

    Science.gov (United States)

    Macdonald, N J; Elliott, H L; Hughes, D M; Reid, J L

    1993-01-01

    1. The pharmacokinetics and pharmacodynamics of single and multiple oral doses of the ACE inhibitor benazepril were investigated in young and elderly normotensive subjects. 2. Following multiple doses the trough concentrations were significantly higher in the elderly and the areas under the plasma concentration-time curves (AUC0-24) were significantly greater, by approximately 23%. 3. The fall in blood pressure tended to be greater in the elderly subjects but this is likely to be attributable to their higher initial blood pressures, although it may reflect the small differences in pharmacokinetics. 4. The age related differences in kinetics and dynamics following multiple dosing are quantitatively similar to those obtained with single doses. However, there appears to be a quantitative difference between benazepril and other ACE inhibitors in that the age related increases were of a relatively smaller magnitude. PMID:9114904

  3. Prospective Trial of High-Dose Reirradiation Using Daily Image Guidance With Intensity-Modulated Radiotherapy for Recurrent and Second Primary Head-and-Neck Cancer

    International Nuclear Information System (INIS)

    Chen, Allen M.; Farwell, D. Gregory; Luu, Quang; Cheng, Suzan; Donald, Paul J.; Purdy, James A.

    2011-01-01

    Purpose: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and Materials: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60-70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment. Results: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651 daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 ± 1.25 mm, 1.79 ± 1.45 mm, and 1.98 ± 1.75 mm for the medial-lateral, superior-inferior, and anterior-posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial-lateral, 27% in the superior-inferior, and 33% in the anterior-posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy. Conclusions: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck.

  4. Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects.

    Science.gov (United States)

    Zhang, Dan; Zhang, Yanan; Liu, Man; Wang, Xiaolin; Yang, Man; Han, Jing; Liu, Huichen

    2013-09-01

    The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.

  5. Absence of multiple local minima effects in intensity modulated optimization with dose-volume constraints

    Energy Technology Data Exchange (ETDEWEB)

    Llacer, Jorge [EC Engineering Consultants, LLC 130, Forest Hill Drive, Los Gatos, CA (United States); Deasy, Joseph O [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Bortfeld, Thomas R [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 30 Fruit Street, Boston, MA (United States); Solberg, Timothy D [Department of Radiation Oncology, University of California, Los Angeles, CA (United States); Promberger, Claus [BrainLAB AG, Ammerthalstrasse 8, 85551 Heimstetten (Germany)

    2003-01-21

    This paper reports on the analysis of intensity modulated radiation treatment optimization problems in the presence of non-convex feasible parameter spaces caused by the specification of dose-volume constraints for the organs-at-risk (OARs). The main aim was to determine whether the presence of those non-convex spaces affects the optimization of clinical cases in any significant way. This was done in two phases: (1) Using a carefully designed two-dimensional mathematical phantom that exhibits two controllable minima and with randomly initialized beamlet weights, we developed a methodology for exploring the nature of the convergence characteristics of quadratic cost function optimizations (deterministic or stochastic). The methodology is based on observing the statistical behaviour of the residual cost at the end of optimizations in which the stopping criterion is progressively more demanding and carrying out those optimizations to very small error changes per iteration. (2) Seven clinical cases were then analysed with dose-volume constraints that are stronger than originally used in the clinic. The clinical cases are two prostate cases differently posed, a meningioma case, two head-and-neck cases, a spleen case and a spine case. Of the 14 different sets of optimizations (with and without the specification of maximum doses allowed for the OARs), 12 fail to show any effect due to the existence of non-convex feasible spaces. The remaining two sets of optimizations show evidence of multiple minima in the solutions, but those minima are very close to each other in cost and the resulting treatment plans are practically identical, as measured by the quality of the dose-volume histograms (DVHs). We discuss the differences between fluence maps resulting from those similar treatment plans. We provide a possible reason for the observed results and conclude that, although the study is necessarily limited, the annealing characteristics of a simulated annealing method may not be

  6. Long-term evacuation after the nuclear accident in Fukushima. Different daily living under low-dose radioactive suffering

    International Nuclear Information System (INIS)

    Ishikawa, Kazunobu

    2013-01-01

    One year has passed since the Great East Japan Earthquake and the Fukushima No. 1 nuclear power plant accident. Even currently, more than 150,000 evacuees in Fukushima Prefecture are forced to leave their home and to move throughout Japan. Because of the limited space of temporary housing and the weakening of personal ties in local communities, many families need to move and have separate lives. As a consequence, Fukushima has a serious shortage of caregivers for the elderly. There have been more than 1,300 disaster-related deaths due to shock and stress after long-distance drifts from town to town. Most of the victims were the elderly, who collapsed, caught pneumonia, suffered stroke and heart attack. Concerns about the safety of low-dose radiation exposure deprived the elderly of important contact with playing outside with their grandchildren in Fukushima. Fear of invisible radioactive contamination inactivated outdoor activities such as farming, dairy, fishing, gardening, hiking and wild-vegetable/mushroom hunting, although most of these activities have been traditionally supported by the wisdom of the elderly. Several recent questionnaire investigations revealed that older evacuees wish to go home even if the environment has significant contamination. In contrast, more than half of younger generation with small children have a different attitude. Nuclear accident brought serious social pains although it did not acutely hurt our bodies. (author)

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

    Science.gov (United States)

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

    2015-03-01

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

  8. Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study.

    Science.gov (United States)

    Kaplan, Volkan; Eroğlu, Cennet Neslihan

    2016-10-01

    The aim of the present study was to compare the effects of daily single-dose use of flurbiprofen, diclofenac sodium, and tenoxicam on pain, swelling, and trismus that occur after surgical extraction of impacted wisdom teeth using local anesthesia. The present study included 3 groups with 30 patients in each group. Those volunteering to participate in this double-blind randomized study (n = 90) were selected from a patient population with an indication for extraction of impacted wisdom teeth. Group 1 patients received 200 mg flurbiprofen, group 2 patients received 100 mg diclofenac sodium, and group 3 patients received 20 mg tenoxicam. All doses were once a day, starting preoperatively. Pain was evaluated postoperatively at 1, 2, 3, 6, 8, and 24 hours and at 2 and 7 days using a visual analog scale (VAS). For comparison with the preoperative measurements, the patients were invited to postoperative follow-up visits 2 and 7 days after extraction to evaluate for swelling and trismus. The statistical analysis was performed using descriptive statistics in SAS, version 9.4 (SAS Institute, Cary, NC), software. Statistical analysis of the pain, swelling, and trismus data was performed using the Kruskal-Wallis, Dunn, and Wilcoxon-Mann-Whitney U tests. The statistical level of significance was accepted at P = .05 and power of 0.80. Clinically, tenoxicam showed better analgesic and anti-inflammatory efficacy compared with diclofenac sodium and, in particular, flurbiprofen. Although the VAS scores in the evaluation of pain showed statistically significant differences at 2 days, no statistically significant difference was found for swelling and trismus. Our study evaluated the analgesic and anti-inflammatory effects with a daily single dose of flurbiprofen, diclofenac sodium, and tenoxicam. Daily 20 mg tenoxicam can be accepted as an adequate and safe option for patients after a surgical procedure. Copyright © 2016 American Association of Oral and Maxillofacial

  9. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

    Science.gov (United States)

    Rao, Shripada C; Srinivasjois, Ravisha; Moon, Kwi

    2016-12-06

    Animal studies and trials in older children and adults suggest that a 'one dose per day' regimen of gentamicin is superior to a 'multiple doses per day' regimen. To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 8 April 2016), MEDLINE (1966 to 8 April 2016), Embase (1980 to 8 April 2016), and CINAHL (December 1982 to 8 April 2016). All randomised or quasi-randomised controlled trials comparing one dose per day ('once a day') compared to multiple doses per day ('multiple doses a day') of gentamicin to newborn infants. Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. Eleven RCTs were included (N = 574) and 28 excluded. All except one study enrolled infants of more than 32 weeks' gestation. Limited information suggested that infants in both 'once a day' as well as 'multiple doses a day' regimens showed adequate clearance of sepsis (typical RR 1.00, 95% CI 0.84 to 1.19; typical RD 0.00, 95% CI -0.19 to 0.19; 3 trials; N = 37). 'Once a day' gentamicin regimen was associated with fewer failures to attain peak level of at least 5 µg/ml (typical RR 0.22, 95% CI 0.11 to 0.47; typical RD -0.13, 95% CI -0.19 to -0.08; number needed to treat for an additional beneficial outcome (NNTB) = 8; 9 trials; N = 422); and fewer failures to achieve trough levels of 2 µg/ml or less (typical RR 0.38, 95% CI 0.27 to 0.55; typical RD -0.22, 95% CI -0.29 to -0.15; NNTB = 4; 11 trials; N = 503). 'Once a day' gentamicin achieved higher peak levels (MD 2.58, 95% CI 2.26 to 2.89; 10 trials; N = 440) and lower trough levels (MD -0.57, 95% CI -0.69 to -0.44; 10 trials; N = 440) than 'multiple doses a day' regimen. There was no significant difference in ototoxicity between two groups

  10. Vertebral lesion distribution in multiple myeloma - assessed by reduced-dose whole-body MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Bier, Georg; Kloth, Christopher; Schabel, Christoph; Bongers, Malte; Nikolaou, Konstantin; Horger, Marius [Eberhard-Karls-University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany)

    2016-01-15

    To observe the distribution and potential distribution patterns of osteolytic and sclerotic vertebral involvement in a representative collective of multiple myeloma patients. A total of 66 consecutive patients with a diagnosis of multiple myeloma at initial diagnosis or during follow-up were examined by multidetector reduced-dose computed tomography to evaluate the distribution of bone lesions along the spine with focus on size, location, and lesion character. Confirmation of diagnosis was performed by comparison to follow-up computed tomography or magnetic resonance tomography. If >50 % of all detected malignant lesions occurred in one spinal segment, the distribution pattern was called cervical, thoracic, lumbar, or sacral, otherwise a ''mixed'' pattern was classified. Of a total number of 933 osseous spine lesions, 632 (67.7 %) were classified as malignant (98.9 % of them osteolytic) and 293 (31.5 %) as benign. The distribution pattern analysis yielded two patients (3.8 %) with a cervical, 26 (50 %) with a thoracic, 4 (7.7 %) with a lumbar, one (1.9 %) with a sacral pattern, and 19 cases (36.6 %) showed a mixed distribution pattern. Segment-wise, the mean lesion size was 6.52 ± 2.76 mm (cervical), 8.97 ± 5.43 mm (thoracic), 11.97 ± 7.11 mm (lumbar), and 17.5 ± 16.465 (sacral), whilst, related to the vertebra size, the lesion/vertebra size ratio is decreasing through the whole spine beginning from the top. Multiple myeloma bone lesions occur preferably and are larger in the thoracic and lumbar spine. Moreover, a specific distribution pattern is present in about 60 %. (orig.)

  11. Vertebral lesion distribution in multiple myeloma - assessed by reduced-dose whole-body MDCT

    International Nuclear Information System (INIS)

    Bier, Georg; Kloth, Christopher; Schabel, Christoph; Bongers, Malte; Nikolaou, Konstantin; Horger, Marius

    2016-01-01

    To observe the distribution and potential distribution patterns of osteolytic and sclerotic vertebral involvement in a representative collective of multiple myeloma patients. A total of 66 consecutive patients with a diagnosis of multiple myeloma at initial diagnosis or during follow-up were examined by multidetector reduced-dose computed tomography to evaluate the distribution of bone lesions along the spine with focus on size, location, and lesion character. Confirmation of diagnosis was performed by comparison to follow-up computed tomography or magnetic resonance tomography. If >50 % of all detected malignant lesions occurred in one spinal segment, the distribution pattern was called cervical, thoracic, lumbar, or sacral, otherwise a ''mixed'' pattern was classified. Of a total number of 933 osseous spine lesions, 632 (67.7 %) were classified as malignant (98.9 % of them osteolytic) and 293 (31.5 %) as benign. The distribution pattern analysis yielded two patients (3.8 %) with a cervical, 26 (50 %) with a thoracic, 4 (7.7 %) with a lumbar, one (1.9 %) with a sacral pattern, and 19 cases (36.6 %) showed a mixed distribution pattern. Segment-wise, the mean lesion size was 6.52 ± 2.76 mm (cervical), 8.97 ± 5.43 mm (thoracic), 11.97 ± 7.11 mm (lumbar), and 17.5 ± 16.465 (sacral), whilst, related to the vertebra size, the lesion/vertebra size ratio is decreasing through the whole spine beginning from the top. Multiple myeloma bone lesions occur preferably and are larger in the thoracic and lumbar spine. Moreover, a specific distribution pattern is present in about 60 %. (orig.)

  12. Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with primary progressive multiple sclerosis.

    Science.gov (United States)

    Filippi, M; Campi, A; Martinelli, V; Colombo, B; Yousry, T; Canal, N; Scotti, G; Comi, G

    1995-01-01

    This study was performed to evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) increases the sensitivity of brain MRI for detecting enhancing lesions in patients with primary progressive multiple sclerosis (PPMS). T1 weighted brain MRI was obtained for 10 patients with PPMS in two sessions. In the first session, one scan was obtained five to seven minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, one scan before and two scans five to seven minutes and one hour after the injection of 0.3 mmol/kg Gd-DTPA (triple dose) were obtained. Four enhancing lesions were detected in two patients when the standard dose of Gd-DTPA was used. The numbers of enhancing lesions increased to 13 and the numbers of patients with such lesions to five when the triple dose of Gd-DTPA was used and to 14 and six in the one hour delayed scans. The mean contrast ratio for enhancing lesions detected with the triple dose of Gd-DTPA was higher than those for lesions present in both the standard dose (P DTPA many more enhancing lesions can be detected in patients with PPMS. This is important both for planning clinical trials and for detecting the presence of inflammation in vivo in the lesions of such patients. Images PMID:8530944

  13. Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

    Science.gov (United States)

    Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

    2018-04-01

    Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

  14. Estimation of effective dose and lifetime attributable risk from multiple head CT scans in ventriculoperitoneal shunted children

    International Nuclear Information System (INIS)

    Aw-Zoretic, J.; Seth, D.; Katzman, G.; Sammet, S.

    2014-01-01

    Purpose: The purpose of this review is to determine the averaged effective dose and lifetime attributable risk factor from multiple head computed tomography (CT) dose data on children with ventriculoperitoneal shunts (VPS). Method and materials: A total of 422 paediatric head CT exams were found between October 2008 and January 2011 and retrospectively reviewed. The CT dose data was weighted with the latest IRCP 103 conversion factor to obtain the effective dose per study and the averaged effective dose was calculated. Estimates of the lifetime attributable risk were also calculated from the averaged effective dose using a conversion factor from the latest BEIR VII report. Results: Our study found the highest effective doses in neonates and the lowest effective doses were observed in the 10–18 years age group. We estimated a 0.007% potential increase risk in neonates and 0.001% potential increased risk in teenagers over the base risk. Conclusion: Multiple head CTs in children equates to a slight potential increase risk in lifetime attributable risk over the baseline risk for cancer, slightly higher in neonates relative to teenagers. The potential risks versus clinical benefit must be assessed

  15. Motor activation in people with profound intellectual and multiple disabilities: research in daily practice in residential facilities

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2014-01-01

    Aim: The total study aims at generating knowledge about the best way to motor activate persons with profound intellectual and multiple disabilities (PIMD) in residential facilities. The purpose of the current poster presentation is to present the results of the first step executed in this project

  16. Effect of intermittent versus daily calorie restriction on changes in weight and patient reported outcomes in people with multiple sclerosis

    Science.gov (United States)

    An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding stud...

  17. Comparison of the evolution of tumor cells after unique and multiple (accelerated) daily irradiation in mammary carcinoma of C3H mice

    International Nuclear Information System (INIS)

    Pfersdorff, J.; Sack, H.

    1986-01-01

    The comparison of two fractionation schemes, i.e. the usual irradiation once a day with 2 Gy (SDF) and the fractionation with 3 times 1.6 Gy per day (MDF) at intervals of at least four hours shows the stronger action of higher fractionation on the destruction of tumor cells and the inhibition of their proliferation kinetics. So the number of pycnotic cells is considerably increased in case of multiple daily irradiation, and the mitosis rate as well as the labelling index show a more significant decrease. In case of one irradiation per day, the number of pycnotic cells increases during radiotherapy, too, but the mitosis rate and the labelling index only decrease until the fifth or sixth treatment day, remaining then unchanged or increasing slightly. This suggests a recurring multiplication of tumor cells already during radiotherapy. The higher efficacy of multiple daily fractionation in rapidly proliferating tumors is proved by the measurements of changing tumor volumes in the living animal during irradiation as well as by the observation of the survival time after irradiation. (orig.) [de

  18. Yoga Training Has Positive Effects on Postural Balance and Its Influence on Activities of Daily Living in People with Multiple Sclerosis: A Pilot Study.

    Science.gov (United States)

    de Oliveira, Gerson; Tavares, Maria da Consolação Cunha Gomes Fernandes; de Faria Oliveira, Jane Domingues; Rodrigues, Marcos Rojo; Santaella, Danilo Forghieri

    2016-01-01

    There is a little evidence about the influence of yoga as a complementary therapy for postural balance and its influence on activities of daily living in multiple sclerosis (MS) patients. To evaluate the influence of a six-month yoga program on postural balance and subjective impact of postural balance impairment on activities of daily living in people with MS. Randomized controlled pilot study. Protocol developed at the Adaptive Physical Activity Study Department, College of Physical Education, State University of Campinas, Brazil. A total of 12 (11 women) yoga naive people with MS randomly divided into two groups as follows: Control (C-waiting list, n = 6) and Yoga (Y-Yoga training, n = 6). Yoga group practiced postures, breathing exercises, meditation, and relaxation on weekly 60-min classes for a six-month period. The following evaluations were performed at study entry (baseline), and after six months (six months): Berg Balance Scale (BBS), Expanded Disability Status Scale (EDSS), and self-reported postural balance quality and influence of postural balance on activities of daily living. There was a significant improvement in BBS score from baseline to six months only in the Yoga group, especially in subjects with higher EDSS score, with increased quality of self-reported postural balance, and decreased influence of postural balance impairment on activities of daily living. In conclusion, a six-month yoga training is beneficial for people with MS, since it improves postural balance and decreases the influence of postural balance impairment on activities of daily living. A greater sample size is necessary to increase generalization, but it seems that yoga could be included as a feasible complementary therapy for people with MS. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Modulation of radiation injuries in rats receiving multiple doses of Aloe Vera

    International Nuclear Information System (INIS)

    Azab, Kh.SH.

    2007-01-01

    This study has been performed to examine the efficacy of Aloe vera juice (Aloe barbadensis Miller) against radiation injuries of 7 Gy whole body gamma irradiation (single dose). Inductions of lipid peroxidation (thiobarbituric acid reactive substances, (TBARS)) of biomembranes lipids as well as the subsequent changes in the activities of subcellular organelle marker enzymes were discussed. Activities of glutamate dehydrogenase (GDH), acid phosphatase and glucose-6-phosphatase (marker enzymes of mitochondria, lysosome and microsomes, respectively) were estimated. The activities of these enzymes were also measured in cytosol. Subcellular fractionation's were performed in liver, heart and spleen tissues. Aloe vera was supplemented daily to rats (0.25 ml/kg body wt/day) by gavage, 5 days before irradiation and treatment was extended for 10 days post irradiation. Experimental investigations were performed on the 3 rd and 10 th day after exposure to radiation. The results obtained indicated that, Aloe vera administration has significantly minimized the radiation-induced increase in the amount of TBARS in different cell fractions as compared with control rats. Significant amelioration in the activities of organelles marker enzymes GDH, acid phosphatase and glucose-6-phosphatase was observed from 3 rd up to 10 th days for the 3 tissues. The results also detected improvement in cytosolic enzyme activities due to Aloe vera intake. It could be suggested that the diverse active constituents of Aloe vera play a significant role in decreasing the peroxidation of subcellular membrane lipids induced by radiation exposure, prevent diffusion of organelle enzymes to cytosol and consequently salvage the integrity of living cell

  20. Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients

    International Nuclear Information System (INIS)

    Loven, David; B e'Ery, Einat; Yerushalmi, Rinat; Koren, Claude; Sulkes, Aaron; Fenig, Eyal; Lavi, Idit; Shaked, Yuval

    2008-01-01

    Metronomic low-dose chemotherapy regimen was found to have an antiangiogenic effect in tumors. However, its effect on levels of circulating pro-angiogenic and anti-angiogenic factors is not fully explored. Materials and methods. The levels of both VEGF and PDGF-BB were measured in three time points, in the serum of 32 rectal carcinoma patients receiving daily reduced-dose/continuous capecitabine in combination with preoperative pelvic irradiation. Results. We found a significant decrease in VEGF and PDGF-BB serum levels during the combination treatment (p<0.0001), followed by an increase in the successive rest-period (p<0.0001). In addition, substantial changes in platelets counts were observed during treatment in correlation with the changes of VEGF and PDGF-BB serum levels. Discussion. These results suggest that combined chemo-irradiation affect levels of pro-angiogenic factors during treatment, and may reflect an anti-angiogenic window induced during this treatment. The potential implications of this inducible phenomenon, including a possible clinical benefit from the administration of long lasting metronomic chemotherapy immediately following combined chemo-irradiation, would warrant further investigation

  1. Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

    Science.gov (United States)

    Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

    2015-06-01

    Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

  2. Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

    Science.gov (United States)

    Kremenchutzky, Marcelo; O'Connor, Paul; Hohlfeld, Reinhard; Zhang-Auberson, Lixin; von Rosenstiel, Philipp; Meng, Xiangyi; Grinspan, Augusto; Hashmonay, Ron; Kappos, Ludwig

    2014-05-01

    Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis. This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history. Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration. Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo). Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  3. A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Hansson, Markus; Gimsing, Peter; Badros, Ashraf

    2015-01-01

    PURPOSE: This multicenter, first-in-human study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-505, a human anti-ICAM-1 monoclonal antibody, in advanced relapsed/refractory multiple myeloma patients. EXPERIMENTAL DESIGN: BI-505 was given intravenously, every 2 weeks...... generally mild to moderate, and those attributed to study medication were mostly limited to the first dose and manageable with premedication and slower infusion. No maximum tolerated dose was identified. BI-505's half-life increased with dose while clearance decreased, suggesting target-mediated clearance...

  4. Evaluation of the CT dose index for scans with an ECG using a 320-row multiple-detector CT scanner

    International Nuclear Information System (INIS)

    Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Koshida, Kichiro; Suzuki, Shouichi; Matsunaga, Yuta; Kawaguchi, Ai; Haba, Tomonobu; Katada, Kazuhiro; Toyama, Hiroshi

    2015-01-01

    The relationship between heart rate (HR) and computed tomography dose index (CTDI) was evaluated using an electrocardiogram (ECG) gate scan for scan applications such as prospective triggering, Ca scoring, target computed tomography angiography (CTA), prospective CTA and retrospective gating, continuous CTA/CFA (cardiac functional analysis) and CTA/CFA modulation. Even in the case of a volume scan, doses for the multiple scan average dose were similar to those for CTDI. Moreover, it was found that the ECG gate scan yields significantly different doses. When selecting the optimum scan, the doses were dependent on many factors such as HR, scan rotation time, active time, pre-specified cardiac phase and modulation rate. Therefore, it is necessary to take these results into consideration when selecting the scanning parameters. (authors)

  5. Cumulative effective and individual organ dose levels in paediatric patients undergoing multiple catheterizations for congenital heart disease

    International Nuclear Information System (INIS)

    Jones, T.P.; Brennan, P.C.; Ryan, E.

    2017-01-01

    This study examines the cumulative radiation dose levels received by a group of children who underwent multiple cardiac catheterisation procedures during the investigation and management of congenital heart disease (CHD). The purpose is to calculate cumulative doses, identify higher dose individuals, outline the inconsistencies with risk assessment and encourage the establishment of dose databases in order to facilitate the longitudinal research necessary to better understand health risks. A retrospective review of patient records for 117 paediatric patients who have undergone two or more cardiac catheterizations for the investigation of CHD was undertaken. This cohort consisted of patients who were catheterised over a period from September 2002 to August 2014. The age distribution was from newborn to 17 y. Archived kerma-area product (P KA ) and fluoroscopy time (T) readings were retrieved and analysed. Cumulative effective and individual organ doses were determined. The cumulative P KA levels ranged from 1.8 to 651.2 Gycm 2 , whilst cumulative effective dose levels varied from 2 to 259 mSv. The cumulative fluoroscopy time was shown to vary from 8.1 to 193.5 min. Median cumulative organ doses ranged from 3 to 94 mGy. Cumulative effective dose levels are highly variable but may exceed 250 mSv. Individual organ and effective dose measurements remain useful for comparison purposes between institutions although current methodologies used for determining lifetime risks are inadequate. (authors)

  6. Pharmacokinetic Properties of Three Forms of Vaginal Progesterone Administered in Either Single Or Multiple Dose Regimen in Healthy Post-menopausal Chinese Women

    Directory of Open Access Journals (Sweden)

    Jianzhong Shentu

    2017-04-01

    Full Text Available Objective: A generic vaginal progesterone gel has recently been developed in China. Little is known about its pharmacokinetic properties in Chinese subjects. The purpose of our study was to investigate the pharmacokinetics of three forms of vaginal progesterone gel (test formulations at 4 and 8% strength vs. a reference formulation: Crinone 8% in Chinese healthy post-menopausal women.Methods: This study consisted of two parts study. The part 1 study was a single-center, open-label, 3-period study. Twelve healthy post-menopausal women were to evaluate the safety and pharmacokinetics of 45 mg vaginal progesterone gel (Test 4% following single dose and multiple doses administered once every other day (q.o.d. for six times or once daily (q.d. for 6 days. The part 2 study was a randomized, open-label, 3-stage crossover study. Twelve post-menopausal women received 90 mg vaginal progesterone gel (Test 8% or 90 mg Crinone (Reference 8% following single dose and multiple doses (q.o.d. or q.d.. Plasma concentrations of progesterone were measured up to 72 h by using a validated liquid chromatography tandem-mass spectrometry method. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0-t and extrapolated to infinity (AUC0-∞ were compared by an analysis of variance using log-transformed data.Results: Totally 24 subjects were enrolled in and completed the study. Following single dose, The geometric mean Cmax values for Test 4%, Test 8%, and Crinone 8% were 6.35, 10.34, 10.45 ng/mL, and their geometric mean AUC0-t (AUC0-∞ were 113.73 (118.00, 169.39 (173.98, and 190.07 (201.13 ng⋅h/mL, respectively. The mean T1/2 values of progesterone were 11.00, 10.92, and 11.40 h, respectively. For 8% test formulation vs. reference, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 78.32–124

  7. Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

    International Nuclear Information System (INIS)

    Amirshahrokhi, K.; Dehpour, A.R.; Hadjati, J.; Sotoudeh, M.; Ghazi-Khansari, M.

    2008-01-01

    Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of β cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a μ-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of β cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of β cells and insulitis in the MLDS model of type 1 diabetes

  8. Taenia crassiceps Infection Attenuates Multiple Low-Dose Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Arlett Espinoza-Jiménez

    2010-01-01

    Full Text Available Taenia crassiceps, like other helminths, can exert regulatory effects on the immune system of its host. This study investigates the effect of chronic T. crassiceps infection on the outcome of Multiple Low Dose Streptozotocin-Induced Diabetes (MLDS. Healthy or previously T. crassiceps-infected mice received MLDS and type 1 diabetes (T1D symptoms were evaluated for 6 weeks following the induction of MLDS. T. crassiceps-infected mice displayed lower blood glucose levels throughout the study. A significantly lower percentage of T. crassiceps-infected mice (40% developed T1D compared to the uninfected group (100%. Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-α. Therefore, infection with T. crassiceps causes an immunomodulation that modifies the incidence and development of MLDS-induced autoimmune diabetes.

  9. Esclerosis múltiple: alteraciones cognitivas y actividades de la vida diaria = Multiple sclerosis : cognitive impairments and activities of daily living

    Directory of Open Access Journals (Sweden)

    Alegre Ayala, Jorge

    2008-02-01

    Full Text Available RESUMENLas alteraciones cognitivas ocasionadas por la Esclerosis Múltiple (EM dificultan el desempeño ocupacional de estos pacientes. No existe un patrón específico de deterioro cognitivo aunque son comunes las afectaciones de la memoria, los procesos atencionales, la velocidad de procesamiento de la información, las funciones ejecutivas, la fluidez verbal y la capacidad visuoespacial. Pese a no ser tan conocidos como los problemas físicos, los déficit cognitivos provocan limitaciones en la capacidad de estas personas para realizar sus actividades de la vida diaria (AVD. El artículo muestra explicaciones sobre las principales alteraciones cognitivas de la enfermedad y ejemplos de actividades de la vida diaria dañadas por éstas. SUMMARY Cognitive impairments caused by Multiple Sclerosis make these patients´ occupational performance difficult. It is not exist a specific pattern of cognitive injury although they are usual the affections in memory, attention process, speed of information processing, executive functions, verbal fluency and visual and spatial skills. Though are not so known like physical problems, the cognitive deficits provokes limitations in the ability of these persons to realize their activities of daily living. Article shows explains about principal cognitive impairments and examples of damage in the activities of daily living caused by Multiple Sclerosis.

  10. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

    Science.gov (United States)

    Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

    2011-12-01

    A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

  11. Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes

    DEFF Research Database (Denmark)

    Roze, S.; Smith-Palmer, J.; Valentine, W.

    2015-01-01

    Aim: Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically...... to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. Methods: A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11...... cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. Results: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95...

  12. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    International Nuclear Information System (INIS)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 ± 0.62 Gy and 6.29 ± 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 ± 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 ± 0.7 Gy and 32.7 ± 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 ± 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  13. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    Science.gov (United States)

    Ramiro, Miguel A; Llibre, Josep M

    2014-11-01

    The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiolog

  14. Multiple myeloma among atomic bomb survivors in Hiroshima and Nagasaki, 1950-76: relationship to radiation dose absorbed by marrow

    International Nuclear Information System (INIS)

    Ichimaru, M.; Ishimaru, T.; Mikami, M.; Matsunaga, M.

    1982-01-01

    The relationship between atomic bomb exposure and the incidence of multiple myeloma has been examined in a fixed cohort of atomic bomb survivors and controls in the life-span study sample for Hiroshima and Nagasaki. From October 1950 to December 1976, 29 cases of multiple myeloma were confirmed in this sample. Our analysis shows that the standardized relative risk (RR) adjusted for city, sex, and age at the time of bombings (ATB) increased with marrow-absorbed radiation dose. The increased RR does not appear to differ between cities or sexes and is demonstrable only for those survivors whose age ATB was between 20 and 59 years. The estimated risk in these individuals is approximately 0.48 cases/million person-years/rad for bone marrow total dose. This excess risk did not become apparent in individuals receiving 50 rad or more in marrow total dose until 20 years or more after exposure

  15. Decreased antimicrobial resistance and defined daily doses after implementation of a clinical culture-guided antimicrobial stewardship program in a local hospital

    Directory of Open Access Journals (Sweden)

    Chang-Teng Wu

    2017-12-01

    Full Text Available Background: We aimed to report the implementation of an antimicrobial stewardship program (ASP guided by clinically significant cultures in a hospital to assess its pharmaceutical, microbiological, financial, and outcome effects. Methods: A 3-year cohort study of an antimicrobial restriction policy implementation was performed. The ASP with culture-guided de-escalation of antibiotics was instituted in a local hospital since January 1, 2012. The cost of antimicrobials, defined daily dose (DDD, susceptibility to antimicrobials, and outcome of all admitted patients were calculated and evaluated before and after the ASP implementation. Results: Average monthly length of stay of admitted patients decreased from 7.8 ± 0.5 days in 2011 to 6.9 ± 0.3 days in 2013 (p < 0.001. The average monthly cost of antimicrobials decreased 46.9% from US$30,146.8 in 2011 to US$16,021.3 in 2013 (p < 0.001. Total intravenous antimicrobial DDDs per 100 bed-days of the inpatients were 66.9, 54.1 and 48.4 in 2011, 2012 and 2013, respectively. A total of 18.6 DDDs per 100 bed-days of inpatients (27.7% decreased from 2011 to 2013. By comparing data in 2013 to those in 2011, the ASP reduced antimicrobial resistance of Gram-positive bacteria (p = 0.013, Gram-negative bacteria (p < 0.001, and predominant species (all p < 0.05. The yearly mortality also decreased from 1.3% in 2011 to 1.1% in 2012 and 1.0% in 2013. Conclusions: The ASP with a culture-guided de-escalation of antibiotics successfully reduced length of stay, mortality, the cost of antimicrobials, DDDs, and antimicrobial resistance rate, and that is highly recommended for local hospitals. Keywords: antimicrobial resistance, antimicrobial restriction policy, antimicrobial stewardship program, defined daily dose

  16. Cognitive performance in relapsing remitting multiple sclerosis: A longitudinal study in daily practice using a brief computerized cognitive battery

    Directory of Open Access Journals (Sweden)

    Jacquerye Philippe

    2011-06-01

    Full Text Available Abstract Background There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS. In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR battery, we longitudinally assessed cognition in patients with relapsing remitting (RR MS. Methods Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST, Paced Auditory Serial Addition Test (PASAT and five composite scores derived from the CDR computerized cognitive test system (CDR System: Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC and Expanded Disability Status Scale (EDSS measured disability. Results The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT and were also strongly related to disability (EDSS and MSFC. Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention], and a moderate impairment both to sustained attention (Continuity of Attention d 0.6 and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory], when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory and episodic memory (Quality of Episodic Memory

  17. Coupling Poisson rectangular pulse and multiplicative microcanonical random cascade models to generate sub-daily precipitation timeseries

    Science.gov (United States)

    Pohle, Ina; Niebisch, Michael; Müller, Hannes; Schümberg, Sabine; Zha, Tingting; Maurer, Thomas; Hinz, Christoph

    2018-07-01

    To simulate the impacts of within-storm rainfall variabilities on fast hydrological processes, long precipitation time series with high temporal resolution are required. Due to limited availability of observed data such time series are typically obtained from stochastic models. However, most existing rainfall models are limited in their ability to conserve rainfall event statistics which are relevant for hydrological processes. Poisson rectangular pulse models are widely applied to generate long time series of alternating precipitation events durations and mean intensities as well as interstorm period durations. Multiplicative microcanonical random cascade (MRC) models are used to disaggregate precipitation time series from coarse to fine temporal resolution. To overcome the inconsistencies between the temporal structure of the Poisson rectangular pulse model and the MRC model, we developed a new coupling approach by introducing two modifications to the MRC model. These modifications comprise (a) a modified cascade model ("constrained cascade") which preserves the event durations generated by the Poisson rectangular model by constraining the first and last interval of a precipitation event to contain precipitation and (b) continuous sigmoid functions of the multiplicative weights to consider the scale-dependency in the disaggregation of precipitation events of different durations. The constrained cascade model was evaluated in its ability to disaggregate observed precipitation events in comparison to existing MRC models. For that, we used a 20-year record of hourly precipitation at six stations across Germany. The constrained cascade model showed a pronounced better agreement with the observed data in terms of both the temporal pattern of the precipitation time series (e.g. the dry and wet spell durations and autocorrelations) and event characteristics (e.g. intra-event intermittency and intensity fluctuation within events). The constrained cascade model also

  18. Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

    Science.gov (United States)

    Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

    1993-03-15

    To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

  19. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    Science.gov (United States)

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  20. 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

    International Nuclear Information System (INIS)

    Algan, Ozer; 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_1_0_0. All of the other measured dosimetric parameters including the V_9_5, V_9_9, and D_1_0_0 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.

  1. 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.

    Science.gov (United States)

    Algan, Ozer; 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 2.63mL, 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 V100. All of the other measured dosimetric parameters including the V95, V99, and D100 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. Copyright © 2015 American Association of

  2. 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.

  3. Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

    Science.gov (United States)

    Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

    2015-01-01

    We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

  4. Advantage of multiple spot urine collections for estimating daily sodium excretion: comparison with two 24-h urine collections as reference.

    Science.gov (United States)

    Uechi, Ken; Asakura, Keiko; Ri, Yui; Masayasu, Shizuko; Sasaki, Satoshi

    2016-02-01

    Several estimation methods for 24-h sodium excretion using spot urine sample have been reported, but accurate estimation at the individual level remains difficult. We aimed to clarify the most accurate method of estimating 24-h sodium excretion with different numbers of available spot urine samples. A total of 370 participants from throughout Japan collected multiple 24-h urine and spot urine samples independently. Participants were allocated randomly into a development and a validation dataset. Two estimation methods were established in the development dataset using the two 24-h sodium excretion samples as reference: the 'simple mean method' estimated by multiplying the sodium-creatinine ratio by predicted 24-h creatinine excretion, whereas the 'regression method' employed linear regression analysis. The accuracy of the two methods was examined by comparing the estimated means and concordance correlation coefficients (CCC) in the validation dataset. Mean sodium excretion by the simple mean method with three spot urine samples was closest to that by 24-h collection (difference: -1.62  mmol/day). CCC with the simple mean method increased with an increased number of spot urine samples at 0.20, 0.31, and 0.42 using one, two, and three samples, respectively. This method with three spot urine samples yielded higher CCC than the regression method (0.40). When only one spot urine sample was available for each study participant, CCC was higher with the regression method (0.36). The simple mean method with three spot urine samples yielded the most accurate estimates of sodium excretion. When only one spot urine sample was available, the regression method was preferable.

  5. Blood responses under chronic low daily dose gamma irradiation: Pt. 2; Differential preclinical responses of irradiated female dogs in progression to either aplastic anemia or myeloproliferative disease

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.; Carnes, B.; Tolle, D.; Fritz, T. (Argonne National Lab., IL (United States). Biological and Medical Research Div.)

    1993-05-01

    Female beagle dogs were chronically exposed to low daily doses of [sup 60]Co gamma rays and responded in one of three distinct hemopathological patterns. These patterns, reflective of distinct subgroups, were characterized by (a) low radioresistance resulting in progressive hematopoietic suppression, terminal aplastic anemia (AA), and relatively short (<400 days) survival ([sup -]S-AA subgroups); (b) high radioresistance, initially coupled with strong but aberrant regenerative hematopoiesis, and later with the development of myeloproliferative disease (MPD) ([sup +]-R-MPD subgroup); and (c) high radioresistance, coupled with an early phase of strong regenerative hematopoiesis, but later with no myeloproliferative disease ([sup +]R-nonMPD subgroup). In this study, the changes in circulating blood cells levels (granulocytes, monotcytes, erythrocytes, lymphocytes and platelets) were sequentially assessed in time and fitted to a flexible, quadratic-linear-type response model previously developed. The results are consistent with our earlier observations of blood responses of chronically irradiated male dogs, in the subgroups of female dogs prone to specific radiogenic hematopathologies (i.e. AA and MPD) can be readily identified and staged in specific preclinical periods by a series of marked differential blood responses. (Author).

  6. Blood responses under chronic low daily dose gamma irradiation: Pt. 1; Differential preclinical responses of irradiated male dogs in progression to either aplastic anemia or myeloproliferative disease

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Carnes, B.A.; Tolle, D.V.; Fritz, T.E. (Argonne National Lab., IL (USA))

    1989-01-01

    Male beagles chronically exposed to low daily doses of {sup 60}Co {gamma} rays show one of three hematopoietic patterns, which reflect three different distinctly responding subgroups: (1) low radioresistance with progressing aplastic anemia and shortened survival ({sup -S}-AA subgroup); (2) high radioresistance with a complex of progressing myeloproliferative disorders ({sup +}R-MPD group); or (3) high radioresistance with other nonMPD syndromes ({sup +}R-nonMPD group). Blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes, and platelets) were assessed and fitted to a flexible polynomial spline model. Results showed that relative to the overall magnitude of blood cell loss as well as to the maximum rate of suppression during the initial phase, the subgroups were generally ranked {sup -}S-AA >> {sup +}R-MPD > {sup +}R-nonMPD. Relative to the overall strength of the recovery response, the subgroups were generally ranked {sup +}R-MPD > {sup +}R-nonMPD >>> {sup -}S-AA. In terms of overall maintenance levels of circulating blood cells during the recovery phase, however, the {sup +}R-nonMPD subgroup consistently exhibited stronger responses than the {sup +}R-MPD subgroup. These results support our contention that selected subgroups of dogs have strong propensities to specific hematopathologies (i.e. aplastic anemia and myeloid leukemia) under chronic irradiation and that these pathology-prone animals exhibit a series of marked differential hematopoietic responses during early preclinical phases, which serve effectively to prognosticate subsequent pathological progression. (author).

  7. Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections: The GOLD Randomized Clinical Trial.

    Science.gov (United States)

    Lind, Marcus; Polonsky, William; Hirsch, Irl B; Heise, Tim; Bolinder, Jan; Dahlqvist, Sofia; Schwarz, Erik; Ólafsdóttir, Arndís Finna; Frid, Anders; Wedel, Hans; Ahlén, Elsa; Nyström, Thomas; Hellman, Jarl

    2017-01-24

    The majority of individuals with type 1 diabetes do not meet recommended glycemic targets. To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections. Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections. Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks. Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied. Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, -0.43% [95% CI, -0.57% to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer

  8. TH-AB-207A-03: Skin Dose to Patients Receiving Multiple CTA and CT Exams of the Head

    International Nuclear Information System (INIS)

    Nawfel, RD; Young, G

    2016-01-01

    Purpose: To measure patient skin dose from CT angiography (CTA) and CT exams of the head, and determine if patients having multiple exams could receive cumulative doses that approach or exceed deterministic thresholds. Methods: This study was HIPAA compliant and conducted with IRB approval. Patient skin doses were measured over a 4 month period using nanoDot OSL dosimeters placed on the head of 52 patients for two CT scanners. On each scanner, 26 patients received CT exams (scanner 1: 10 females, 16 males, mean age 64.2 years; scanner 2: 18 females, 8 males, mean age 61.2 years). CT exam dose metrics, CTDIvol and dose-length product (DLP) were recorded for each exam. Additionally, skin dose was measured on an acrylic skull phantom in each scanner and on a neuro-interventional imaging system using clinical protocols. Measured dose data was used to estimate peak skin dose (PSD) for 4 patients receiving multiple exams including CTA, head CT, and cerebral angiography. Results: For scanner 1, the mean PSD for CTA exams (98.9 ± 5.3 mGy) and for routine head CT exams (39.2 ± 3.7 mGy) agreed reasonably well with the PSD measured on the phantom, 105.4 mGy and 40.0 mGy, respectively. Similarly for scanner 2, the mean PSD for CTA exams (98.8 ± 7.4 mGy) and for routine head CT exams (42.9 ± 9.4 mGy) compared well with phantom measurements, 95.2 mGy and 37.6 mGy, respectively. In addition, the mean PSD was comparable between scanners for corresponding patient exams, CTA and routine head CT respectively. PSD estimates ranged from 1.9 – 4.5 Gy among 4 patients receiving multiple exams. Conclusion: Patients having several exams including both CTA and routine head CT may receive cumulative doses approaching or exceeding the threshold for single dose deterministic effects.

  9. TH-AB-207A-03: Skin Dose to Patients Receiving Multiple CTA and CT Exams of the Head

    Energy Technology Data Exchange (ETDEWEB)

    Nawfel, RD; Young, G [Brigham & Women’s Hospital, Boston, MA (United States)

    2016-06-15

    Purpose: To measure patient skin dose from CT angiography (CTA) and CT exams of the head, and determine if patients having multiple exams could receive cumulative doses that approach or exceed deterministic thresholds. Methods: This study was HIPAA compliant and conducted with IRB approval. Patient skin doses were measured over a 4 month period using nanoDot OSL dosimeters placed on the head of 52 patients for two CT scanners. On each scanner, 26 patients received CT exams (scanner 1: 10 females, 16 males, mean age 64.2 years; scanner 2: 18 females, 8 males, mean age 61.2 years). CT exam dose metrics, CTDIvol and dose-length product (DLP) were recorded for each exam. Additionally, skin dose was measured on an acrylic skull phantom in each scanner and on a neuro-interventional imaging system using clinical protocols. Measured dose data was used to estimate peak skin dose (PSD) for 4 patients receiving multiple exams including CTA, head CT, and cerebral angiography. Results: For scanner 1, the mean PSD for CTA exams (98.9 ± 5.3 mGy) and for routine head CT exams (39.2 ± 3.7 mGy) agreed reasonably well with the PSD measured on the phantom, 105.4 mGy and 40.0 mGy, respectively. Similarly for scanner 2, the mean PSD for CTA exams (98.8 ± 7.4 mGy) and for routine head CT exams (42.9 ± 9.4 mGy) compared well with phantom measurements, 95.2 mGy and 37.6 mGy, respectively. In addition, the mean PSD was comparable between scanners for corresponding patient exams, CTA and routine head CT respectively. PSD estimates ranged from 1.9 – 4.5 Gy among 4 patients receiving multiple exams. Conclusion: Patients having several exams including both CTA and routine head CT may receive cumulative doses approaching or exceeding the threshold for single dose deterministic effects.

  10. Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study.

    Science.gov (United States)

    Demirol, Aygul; Gurgan, Timur

    2009-08-01

    To compare the efficacy of the microdose flare-up and multiple-dose antagonist protocols for poor-responder patients in intracytoplasmic sperm injection-ET cycles. A randomized, prospective study. Center for assisted reproductive technology in Turkey. Ninety patients with poor ovarian response in a minimum of two previous IVF cycles. All women were prospectively randomized into two groups by computer-assisted randomization. The patients in group 1 were stimulated according to the microdose flare-up protocol (n = 45), while the patients in group 2 were stimulated according to antagonist multiple-dose protocol (n = 45). The mean number of mature oocytes retrieved was the primary outcome measure, and fertilization rate, implantation rate per embryo, and clinical pregnancy rates were secondary outcome measures. The mean age of the women, the mean duration of infertility, basal FSH level, and the number of previous IVF cycles were similar in both groups. The total gonadotropin dose used was significantly higher in group 2, while the number of oocytes retrieved was significantly greater in group 1. Although the fertilization and clinical pregnancy rates were nonsignificantly higher in group 1 compared with group 2, the implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (22% vs. 11%). The microdose flare-up protocol seems to have a better outcome in poor-responder patients, with a significantly higher mean number of mature oocytes retrieved and higher implantation rate.

  11. Comparison of single-dose and multiple-dose antibiotics for lower urinary tract infection in pregnancy.

    Science.gov (United States)

    Usta, Taner A; Dogan, Ozgur; Ates, Ugur; Yucel, Burak; Onar, Zehra; Kaya, Erdal

    2011-09-01

    To compare the efficacy of fosfomycin trometamol, cefuroxime axetil, and amoxicillin clavulanate antibiotics, and to assess the difference in patient compliance, in the treatment of urinary tract infections during pregnancy. Between September 2007 and May 2008, 90 out of 324 pregnant women with complaints of lower urinary tract infection, who were followed at the outpatient clinic or referred to the emergency department of Vakif Gureba Education and Research Hospital, were enrolled in a prospective study. Patients were randomized into 3 equal groups for treatment with single-dose fosfomycin trometamol, or 5-day courses of amoxicillin clavulanate or cefuroxime axetil. After follow-up, study data were obtained for 28, 27, and 29 patients, respectively. The treatment groups did not differ significantly in terms of demographics, clinical success rate, microbiological cure rate, or adverse effects. Significantly higher drug compliance was observed in the fosfomycin trometamol group than in the other 2 groups (PUTI as the standard course of treatment with amoxicillin clavulanate or cefuroxime axetil. Fosfomycin trometamol may be a preferable treatment for UTI because of its simpler use and better rates of compliance. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Reduced dose uncertainty in MRI-based polymer gel dosimetry using parallel RF transmission with multiple RF sources

    International Nuclear Information System (INIS)

    Sang-Young Kim; Jung-Hoon Lee; Jin-Young Jung; Do-Wan Lee; Seu-Ran Lee; Bo-Young Choe; Hyeon-Man Baek; Korea University of Science and Technology, Daejeon; Dae-Hyun Kim; Jung-Whan Min; Ji-Yeon Park

    2014-01-01

    In this work, we present the feasibility of using a parallel RF transmit with multiple RF sources imaging method (MultiTransmit imaging) in polymer gel dosimetry. Image quality and B 1 field homogeneity was statistically better in the MultiTransmit imaging method than in conventional single source RF transmission imaging method. In particular, the standard uncertainty of R 2 was lower on the MultiTransmit images than on the conventional images. Furthermore, the MultiTransmit measurement showed improved dose resolution. Improved image quality and B 1 homogeneity results in reduced dose uncertainty, thereby suggesting the feasibility of MultiTransmit MR imaging in gel dosimetry. (author)

  13. Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

    2017-01-01

    New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

  14. Quality of life in Danish children and adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections

    DEFF Research Database (Denmark)

    Birkebæk, Niels; Kristensen, Lene Juel; Mose, Anne

    2014-01-01

    ), and to investigate whether HRQoL assessments were influenced by treatment duration. METHODS: Participants were recruited through the Danish Registry for Diabetes in Childhood and Adolescence. A total of 700 children and adolescents (360 girls), 8-17 years, were included. Of these, 295 were treated with CSII (160......AIMS: The aims of the study were to compare health-related quality of life (HRQoL) in a National Danish population of children and adolescents with type 1 diabetes (T1D) treated with either continuous subcutaneous insulin injection (CSII) or multiple daily insulin injections (MDI...... for more than one year) and 405 with MDI (238 for more than one year). Participants and their parents completed the Pediatric Quality of Life Inventory Diabetes and Generic Module. HbA1c was analyzed centrally. RESULTS: Parents reported children and adolescents on CSII for more than one year to have less...

  15. The expression and evolution of virulence in multiple infections: the role of specificity, relative virulence and relative dose.

    Science.gov (United States)

    Ben-Ami, Frida; Routtu, Jarkko

    2013-05-03

    Multiple infections of the same host by different strains of the same microparasite species are believed to play a crucial role during the evolution of parasite virulence. We investigated the role of specificity, relative virulence and relative dose in determining the competitive outcome of multiple infections in the Daphnia magna-Pasteuria ramosa host-parasite system. We found that infections by P. ramosa clones (single genotype) were less virulent and produced more spores than infections by P. ramosa isolates (possibly containing multiple genotypes). We also found that two similarly virulent isolates of P. ramosa differed considerably in their within-host competitiveness and their effects on host offspring production when faced with coinfecting P. ramosa isolates and clones. Although the relative virulence of a P. ramosa isolate/clone appears to be a good indicator of its competitiveness during multiple infections, the relative dose may alter the competitive outcome. Moreover, spore counts on day 20 post-infection indicate that the competitive outcome is largely decided early in the parasite's growth phase, possibly mediated by direct interference or apparent competition. Our results emphasize the importance of epidemiology as well as of various parasite traits in determining the outcome of within-host competition. Incorporating realistic epidemiological and ecological conditions when testing theoretical models of multiple infections, as well as using a wider range of host and parasite genotypes, will enable us to better understand the course of virulence evolution.

  16. Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

    Science.gov (United States)

    Hagen, Kerry B; Bedi, Raman; Blackie, Caroline A; Christenson-Akagi, Kellie J

    2018-01-01

    The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD). This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining. In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53), SPEED score (11.00±3.30 to 5.42±2.15), TBUT (6.26±2.01 to 8.44±1.81), corneal staining (0.38±0.50 to 0.12±0.33) and conjunctival staining (1.69±1.93 to 0.62±0.85). In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91), SPEED score (13.42±4.17 to 9.42±5.47) and conjunctival staining (2.38±1.88 to 1.13±1.51), but the improvement in TBUT (6.90±2.56 to 7.59±2.03) and corneal staining (0.21±0.41 to 0.13±0.34) was not statistically significant ( p =0.262 and p =0.414, respectively). At 3 months, SPEED score was significantly better in the VTP group ( p oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single VTP presents a favorable alternative to long-term antibiotic use.

  17. Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction

    Directory of Open Access Journals (Sweden)

    Hagen KB

    2018-01-01

    Full Text Available Kerry B Hagen,1 Raman Bedi,2 Caroline A Blackie,3 Kellie J Christenson-Akagi1 1EyeHealth Northwest, Portland, OR, USA; 2Iris Advanced Eye Centre, Chandigarh, India; 3TearScience, Inc., Morrisville, NC, USA Purpose: The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD.Methods: This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED], meibomian gland (MG function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE, tear breakup time (TBUT and corneal and conjunctival staining.Results: In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53, SPEED score (11.00±3.30 to 5.42±2.15, TBUT (6.26±2.01 to 8.44±1.81, corneal staining (0.38±0.50 to 0.12±0.33 and conjunctival staining (1.69±1.93 to 0.62±0.85. In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91, SPEED score (13.42±4.17 to 9.42±5.47 and conjunctival staining (2.38±1.88 to 1.13±1.51, but the improvement in TBUT (6.90±2.56 to 7.59±2.03 and corneal staining (0.21±0.41 to 0.13±0.34 was not statistically significant (p=0.262 and p=0.414, respectively. At 3 months, SPEED score was significantly better in the VTP group (p<0.05; other parameters were comparable between the two groups.Conclusion: A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single

  18. The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Yara Dadalti Fragoso

    2014-09-01

    Full Text Available Fingolimod is a new and efficient treatment for multiple sclerosis (MS. The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

  19. Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100-mg twice-daily dose regimen of sitafloxacin.

    Science.gov (United States)

    Ito, Shin; Yasuda, Mitsuru; Seike, Kensaku; Sugawara, Takashi; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

    2012-06-01

    Several microorganisms cause non-gonococcal urethritis (NGU). Failure to eradicate Mycoplasma genitalium from the urethra could be associated with persistent or recurrent urethritis; thus, the choice of antibiotics with activities potent enough to eradicate M. genitalium is crucial in the treatment of NGU. In in vitro studies, sitafloxacin has been shown to be highly active against Chlamydia trachomatis and M. genitalium. We treated 89 males with NGU, including 15 patients with persistent or recurrent NGU and 1 patient with post-gonococcal urethritis, with a 100-mg twice-daily dose regimen of sitafloxacin to assess its efficacy against NGU. We examined first-void urine samples for the presence of C. trachomatis, M. genitalium, Ureaplasma parvum, and Ureaplasma urealyticum. After treatment, we evaluated 73 patients for clinical outcomes and 44 for microbiological outcomes. Symptoms were alleviated in 62 (84.9%) patients, who were judged clinically cured. Microorganisms detected before treatment were eradicated in 42 (95.5%) patients, who were judged microbiologically cured. Regarding microbiological outcomes of specific microorganisms, eradication rates of C. trachomatis (n = 33), M. genitalium (n = 11), and U. urealyticum (n = 10) were 100%, 100%, and 80.0%, respectively. In all 5 patients with M. genitalium-positive persistent or recurrent NGU who had experienced treatment failures with antibiotics, the mycoplasma was eradicated. These results suggested that the sitafloxacin regimen used, which was effective on both M. genitalium and C. trachomatis infections, could be useful as an appropriate option as first- and second-line treatment of NGU.

  20. An explanation for the multiplicative and the additive dose-effect relationship with the single-hit model

    International Nuclear Information System (INIS)

    Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

    1997-01-01

    For solid tumors and for leukemia the excess cancer rate after a single radiation dose D is different. The multiplicative model describes the excess solid tumor probability rate which is proportional to the background rate of cancer and dependent on dose D. The additive model describes the excess probability rate for leukaemia which is proportional to the dose D but unrelated to the spontaneous rate of cancer. A second great difference between the two models is the duration of the increased cancer probability rate. The multiplicative mode predicts that the additional cancer risk persist the whole lifetime after exposure and the additive model predicts excess risk over a period of time. With the Single-hit model (SHM) which is a multistage cancer model both dose-response relationships can be described. It will be shown that only small differences in the derivation will lead to the different relationships. We then analyze the incidence data of leukemia (1950-1987) and of all solid tumors (1958-1987) of the atomic bomb survivors. (author)

  1. Dose-rate effects in synchronous mammalian cells in culture. II. A comparison of the life cycle of HeLa cells during continuous irradiation or multiple-dose fractionation

    International Nuclear Information System (INIS)

    Mitchell, J.B.; Bedford, J.S.

    1977-01-01

    The life cycle of synchronized S3 HeLa cells was examined during continuous irradiation at a dose rate of approximately 37 rad/hr and during multiple dose fractionation schedules of the same average dose rate (total dose / overall time = average dose rate). For all regimes given at this dose rate the effects on the life cyclee were similar. Cells progressed through G1 and S without appreciable delay and experienced a minimum G2 delay of about 10 hr. Cells eventually entered mitosis but virtually none were able to complete a successful division

  2. Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection-embryo transfer cycle.

    Science.gov (United States)

    Kahraman, Korhan; Berker, Bulent; Atabekoglu, Cem Somer; Sonmezer, Murat; Cetinkaya, Esra; Aytac, Rusen; Satiroglu, Hakan

    2009-06-01

    To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. Prospective, randomized, clinical study. University hospital. Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

  3. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2013-08-01

    Full Text Available Peter Bramlage,1 Claudia Zemmrich,1 Reinhard Ketelhut,2 Wolf-Peter Wolf,3 Eva-Maria Fronk,4 Roland E Schmieder5 1Institut für Pharmakologie und Präventive Medizin, Mahlow, Germany; 2Institut für Sportmedizin, Universitätsklinikum Charité, Humboldt Universität zu Berlin, Berlin, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Daiichi Sankyo Europe GmbH, Munich, Germany; 5Universitätsklinikum Erlangen, Klinik für Nephrologie und Hypertensiologie, Erlangen, Germany Background: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods: In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results: The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19, and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001, but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients

  4. Clinical trial: single- and multiple-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects.

    Science.gov (United States)

    Pelham, R W; Nix, L C; Chavira, R E; Cleveland, M Vb; Stetson, P

    2008-07-01

    The pharmacokinetics of polyethylene glycol 3350 (PEG-3350) have not been fully described because of lack of a sufficiently sensitive analytical method. To describe the pharmacokinetics of PEG-3350 in humans. A highly sensitive, high performance liquid chromatography with mass spectrometry (HPLC/MS/MS) method was developed for PEG-3350 in urine, plasma and faeces with quantification limits of 30 ng/mL, 100 ng/mL and 500 microg/g respectively. Noncompartmental pharmacokinetics methods were used and the effects of gender, age, renal status and dosing frequency were examined after the oral administration of 17 g to healthy volunteers. Peak PEG-3350 plasma concentrations occurred at 2-4 h and declined to nonquantifiable levels usually within 18 h after single and multiple doses, with a half-life of about 4-6 h. Steady state was reached within 5 days of dosing. Mean urinary excretion of the administered dose ranged from 0.19% to 0.25%. Age, gender or mild kidney impairment did not alter the pharmacokinetics of PEG-3350. Mean faecal excretion of the administered dose was 93% in young subjects. For the first time, a highly sensitive assay allowed comprehensive pharmacokinetics studies of PEG-3350 in humans. These studies confirmed that orally administered PEG-3350 is minimally absorbed, rapidly excreted and primarily eliminated via faeces.

  5. Multiple methods for assessing the dose to skin exposed to radioactive contamination

    International Nuclear Information System (INIS)

    Dubeau, J.; Heinmiller, B.E.; Corrigan, M.

    2017-01-01

    There is the possibility for a worker at a nuclear installation, such as a nuclear power reactor, a fuel production facility or a medical facility, to come in contact with radioactive contaminants. When such an event occurs, the first order of business is to care for the worker by promptly initiating a decontamination process. Usually, the radiation protection personnel performs a G-M pancake probe measurement of the contamination in situ and collects part or all of the radioactive contamination for further laboratory analysis. The health physicist on duty must then perform, using the available information, a skin dose assessment that will go into the worker's permanent dose record. The contamination situations are often complex and the dose assessment can be laborious. This article compares five dose assessment methods that involve analysis, new technologies and new software. The five methods are applied to 13 actual contamination incidents consisting of direct skin contact, contamination on clothing and contamination on clothing in the presence of an air gap between the clothing and the skin. This work shows that, for the cases studied, the methods provided dose estimates that were usually within 12% (1σ) of each other, for those cases where absolute activity information for every radionuclide was available. One method, which relies simply on a G-M pancake probe measurement, appeared to be particularly useful in situations where a contamination sample could not be recovered for laboratory analysis. (authors)

  6. The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

    Science.gov (United States)

    Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

    2015-06-18

    Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

  7. Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

    DEFF Research Database (Denmark)

    Milman, Nils; Bergholt, Thomas; Eriksen, Lisbeth

    2005-01-01

    To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.......To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy....

  8. SU-E-J-66: Significant Anatomical and Dosimetric Changes Observed with the Pharyngeal Constrictor During Head and Neck Radiotherapy Elicited From Daily Deformable Image Registration and Dose Accumulation

    International Nuclear Information System (INIS)

    Kumarasiri, A; Siddiqui, F; Liu, C; Kamal, M; Fraser, C; Chetty, I; Kim, J

    2015-01-01

    Purpose: To evaluate the anatomical changes and associated dosimetric consequences to the pharyngeal constrictor (PC) that occurs during head and neck radiotherapy (H&N RT). Methods: A cohort of 13 oro-pharyngeal cancer patients, who had daily CBCT’s for localization, was retrospectively studied. On every 5th CBCT, PC was manually delineated by a radiation oncologist. The anterior-posterior PC thickness was measured at the C3 level. Delivered dose to PC was estimated by calculating daily doses on CBCT’s, and accumulating to corresponding planning CT images. For accumulation, a parameter-optimized B- spline-based deformable image registration algorithm (Elastix) was used, in conjunction with an energy-mass mapping dose transfer algorithm. Mean and maximum dose (Dmean, Dmax) to PC was determined and compared with corresponding planned quantities. Results: The mean (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54±33% (11.9±7.6 cc), and 63±39% (2.9±1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PC (ΔDmean) was 1.4±1.3% (0.9±0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0±1.6% (0.0±1.1 Gy). Patients with adaptive replanning (n=6) showed a smaller mean dose increase than those without (n=7); 0.5±0.2% (0.3±0.1 Gy) vs. 2.2±1.4% (1.4±0.9 Gy). There was a statistically significant (p<0.0001) strong correlation between ΔDmean and Δt (Pearson coefficient r=0.78), and a moderate-to-strong correlation (r=0.52) between ΔDmean and ΔV. Correlation between ΔDmean and weight loss ΔW (r=0.1), as well as ΔV and ΔW (r=0.2) were negligible. Conclusion: Patients were found to undergo considerable anatomical changes to pharyngeal constrictor during H&N RT, resulting in non-negligible dose deviations from intended dose. Results are indicative that pharyngeal constrictor thickness, measured at C3 level, is a good predictor for the dose change to

  9. SU-E-J-66: Significant Anatomical and Dosimetric Changes Observed with the Pharyngeal Constrictor During Head and Neck Radiotherapy Elicited From Daily Deformable Image Registration and Dose Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Kumarasiri, A; Siddiqui, F; Liu, C; Kamal, M; Fraser, C; Chetty, I; Kim, J [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To evaluate the anatomical changes and associated dosimetric consequences to the pharyngeal constrictor (PC) that occurs during head and neck radiotherapy (H&N RT). Methods: A cohort of 13 oro-pharyngeal cancer patients, who had daily CBCT’s for localization, was retrospectively studied. On every 5th CBCT, PC was manually delineated by a radiation oncologist. The anterior-posterior PC thickness was measured at the C3 level. Delivered dose to PC was estimated by calculating daily doses on CBCT’s, and accumulating to corresponding planning CT images. For accumulation, a parameter-optimized B- spline-based deformable image registration algorithm (Elastix) was used, in conjunction with an energy-mass mapping dose transfer algorithm. Mean and maximum dose (Dmean, Dmax) to PC was determined and compared with corresponding planned quantities. Results: The mean (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54±33% (11.9±7.6 cc), and 63±39% (2.9±1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PC (ΔDmean) was 1.4±1.3% (0.9±0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0±1.6% (0.0±1.1 Gy). Patients with adaptive replanning (n=6) showed a smaller mean dose increase than those without (n=7); 0.5±0.2% (0.3±0.1 Gy) vs. 2.2±1.4% (1.4±0.9 Gy). There was a statistically significant (p<0.0001) strong correlation between ΔDmean and Δt (Pearson coefficient r=0.78), and a moderate-to-strong correlation (r=0.52) between ΔDmean and ΔV. Correlation between ΔDmean and weight loss ΔW (r=0.1), as well as ΔV and ΔW (r=0.2) were negligible. Conclusion: Patients were found to undergo considerable anatomical changes to pharyngeal constrictor during H&N RT, resulting in non-negligible dose deviations from intended dose. Results are indicative that pharyngeal constrictor thickness, measured at C3 level, is a good predictor for the dose change to

  10. Quantitative MR changes in Gd-DTPA enhancement after high dose intravenous methylprednisolone in multiple sclerosis

    International Nuclear Information System (INIS)

    Barkhof, F.; Valk, J.; Hommes, O.R.; Scheltens, P.

    1991-01-01

    The purpose of this study was to investigate the effect of high dose intravenous methylprednisolone (MP) on gadolinium-DTPA enhancement in MS-lesions. By means of this the influence of MP on the permeability of the blood-brain barrier can be studied. (author). 19 refs.; 1 fig

  11. Lung tuberculosis in children, and radiation doses imported during multiple exposures

    International Nuclear Information System (INIS)

    Milkovic, Dj.; Ranogajec Komor, M.; Knezevic, Z.; Milkovic, I.

    1996-01-01

    Most of the artificial ionizing radiation sources are located in medical institutions. The largest contribution to popular irradiation, apart from natural sources, also originates from their use. The application of ionizing radiation in medicine is continuously developing and spreading. Not only the individual absorbed dose is steadily growing, the whole population is more and more exposed. By lung radiogram analysis, important diagnostic data are obtained for tuberculosis treatment. So chest radiography remains the most important method at diagnosing and attending TB patients, children or adults equally. Unfortunately, radiological treatment is accompanied by the risk of radiation doses being received on organs which are unprotectable during examination. It should be remembered that TB patients are frequently x-rayed, whereby the accumulated dose, and the damage risk increase. To make the risk as small, and the benefit of ionizing radiation use as big as possible, certain principles have to be followed: a) Treat a patient with x-rays only if there is a positive and justified medical indication. b) If it is unavoidable, it has to be performed in an institution where technique and protection methods are well known to the staff. c) Monitor the received radiation doses by using suitable and precise dosimetry equipment. (author)

  12. Theoretical estimation of absorbed dose to organs in radioimmunotherapy using radionuclides with multiple unstable daughters

    International Nuclear Information System (INIS)

    Hamacher, K.A.; Sgouros, G.

    2001-01-01

    The toxicity and clinical utility of long-lived alpha emitters such as Ac-225 and Ra-223 will depend upon the fate of alpha-particle emitting unstable intermediates generated after decay of the conjugated parent. For example, decay of Ac-225 to a stable element yields four alpha particles and seven radionuclides. Each of these progeny has its own free-state biodistribution and characteristic half-life. Therefore, their inclusion for a more accurate prediction of absorbed dose and potential toxicity requires a formalism that takes these factors into consideration as well. To facilitate the incorporation of such intermediates into the dose calculation, a previously developed methodology (model 1) has been extended. Two new models (models 2 and 3) for allocation of daughter products are introduced and are compared with the previously developed model. Model 1 restricts the transport to a function that yields either the place of origin or the place(s) of biodistribution depending on the half-life of the parent radionuclide. Model 2 includes the transient time within the bloodstream and model 3 incorporates additional binding at or within the tumor. This means that model 2 also allows for radionuclide decay and further daughter production while moving from one location to the next and that model 3 relaxes the constraint that the residence time within the tumor is solely based on the half-life of the parent. The models are used to estimate normal organ absorbed doses for the following parent radionuclides: Ac-225, Pb-212, At-211, Ra-223, and Bi-213. Model simulations are for a 0.1 g rapidly accessible tumor and a 10 g solid tumor. Additionally, the effects of varying radiolabled carrier molecule purity and amount of carrier molecules, as well as tumor cell antigen saturation are examined. The results indicate that there is a distinct advantage in using parent radionuclides such as Ac-225 or Ra-223, each having a half-life of more than 10 days and yielding four alpha

  13. Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

    2000-01-01

    Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

  14. Relative efficacy of weekly and two differing doses of daily iron-folate supplementation in improving hemoglobin in mild and moderately anemic children between 3 and 5 years of age: a cluster randomized trial.

    Science.gov (United States)

    Kapil, U; Sachdev, H P S; Dwivedi, S N; Pandey, R M; Upadhyay, A D; Sareen, N

    2013-04-01

    In India, 75% of children hemoglobin response with two dosages of daily (20 mg iron and 100 μg folic acid, or 40 mg iron and 200 μg folic acid) and weekly (40 mg iron and 200 μg folic acid) IFA supplementation in children of 3-5 years of age with mild or moderate anemia (hemoglobin 7-10 g/dl). Community-based cluster randomized control trial in nine adjoining Anganwadi Centers. Four hundred twenty six enrolled participants received directly supervised IFA tablet supplementation as per the above three groups. After 100 days, the number of available subjects in the NNACP daily dose (A), daily dose doubled (B) and weekly dose (C) groups were 112, 114 and 110, respectively. Hemoglobin was estimated at baseline, 50 and 100 days by the Cynmeth hemoglobin method. At 50 days, there were no differences between the three groups, but at 100 days, adjusted hemoglobin was lowered with weekly supplementation. The mean (95% confidence interval) hemoglobin (g/dl) differences were: (i) A-B: -0.05 (-0.17, 0.05), (ii) A-C: -0.38 (-0.50, -0.27) and (iii) B-C: -0.33, (-0.45, -0.21). Anemia reduction was 18.8%, 18.4% and 10.9%, respectively, in the three groups. Directly supervised IFA supplementation at the NNACP or double dose is equally efficacious but superior to weekly regimen.

  15. Effects of multiple low dose radiation on spleen T lymphocyte subgroups in eight-week diabetic rats

    International Nuclear Information System (INIS)

    Guan Feng; Li Yanbo; Zhao Hongguang; Guo Wei; Wang Zhicheng; Gong Shouliang; Guo Caixia

    2008-01-01

    Objective: To explore the changes of spleen lymphocyte subgroups in diabetic rats after multiple low dose radiation (LDR). Methods: The experiment was divided into normal control group, pure diabetes mellitus (DM) group, and DM plus different doses of irradiation groups (the irradiation doses were 0.025, 0.050 and 0.075 Gy, respectively). The diabetic rat model was induced by intraperitoneal injection of streptozotocin. After the diabetic rats were irradiated 15 times, the percentages of spleen CD4 + and CD8 + T cells and ratio of CD4 + /CD8 + T cells were detected with flow cytometry on the fourth weekend. Results: The diabetic rats manifested obvious polydipsia, polyphagia, polyuria and weight loss. On the fourth weekend after irradiation, as compared with normal control group, the percentage of spleen CD4 + T cells increased significantly (P + T cells decreased significantly (P + /CD8 + T cells was increased significantly (P + T cells were declined markedly in both 0.050 and 0.075 Gy plus DM groups (P + T cells increased significantly in LDR plus DM groups (P + /CD8 + T cells was declined obviously (P<0.01). Conclusion: The multiple LDR could regulate the immune function in diabetic rats, and rectificate the immunological imbalance in order to protect body. (authors)

  16. Using 'component multiplication' in MONK to reduce pessimism in the dose rate assessment for water-filled (ullaged) transport packages

    International Nuclear Information System (INIS)

    Dean, M.H.

    2002-01-01

    The external dose rates from spent fuel packages consist of gamma ray and neutron components. The source of gamma rays is from fission products and actinides in the spent fuel and from activation products in structural components of the fuel element. Neutrons originate from spontaneous fission in actinides (for example from curium isotopes) within the spent fuel and from (alpha, n) reactions in oxide fuel. However, a significant number of neutrons are produced due to further fission within the fuel. This is known as neutron enhancement or multiplication (M). To treat the effects of enhancement, the neutron source may be scaled within the dose rate calculation. In a wet package, it has been customary to determine k effective (k eff ) for a completely water-filled package or a package with a defined water level (for the horizontal transport condition). The irradiation of the fuel is normally taken into account in calculating k eff for this purpose. The neutron enhancement is then obtained by calculating M=1/(1-k eff ), which is then applied as a source scaling factor throughout each fuel assembly. In a wet package, there is normally an ullage volume above the water level, the package only being partially flooded. The ullage volume is designed to accommodate pressure build-up within the package. Typically the top row of fuel assemblies may be partially covered and partially uncovered by water. When the above value of M is used for fuel within the dry part of the package, dose rates above the package tend to be overestimated and can limit the carrying capability of the package. (Also, a single value of M will tend to over-predict dose rate contributions from all assemblies around the periphery). Use of component multiplication (a new feature available in the MONK computer code) enables two separate values of 'k eff ' to be determined for the wet and dry parts of the package. These typically differ by a factor of three, leading to differences in the enhancement, M. Use

  17. Continuous subcutaneous insulin infusion therapy and multiple daily insulin injections in type 1 diabetes mellitus: a comparative overview and future horizons.

    Science.gov (United States)

    Thabit, Hood; Hovorka, Roman

    2016-01-01

    Continuous subcutaneous insulin infusion (CSII) therapy is currently accepted as a treatment strategy for type 1 diabetes. Transition from multiple daily injection therapy (MDI; including basal-bolus regimens) to CSII is based on expectations of better metabolic control and fewer hypoglycaemic events. Evidence to date has not been always conclusive. Evidence for CSII and MDI in terms of glycaemic control, hypoglycaemia and psychosocial outcomes is reviewed in the adult and paediatric population with type 1 diabetes. Findings from studies on threshold-based insulin pump suspension and predictive low glucose management (PLGM) are outlined. Limitations of current CSII application and future technological developments are discussed. Glycaemic control and quality of life (QOL) may be improved by CSII compared to MDI depending on baseline HbA1c and hypoglycaemia rates. Future studies are expected to provide evidence on clinical and cost effectiveness in those who will benefit the most. Training, structured education and support are important to benefit from CSII. Novel technological approaches linking continuous glucose monitoring (CGM) and CSII may help mitigate against frequent hypoglycaemia in those at risk. Development of glucose-responsive automated closed-loop insulin delivery systems may reduce the burden of disease management and improve outcomes in type 1 diabetes.

  18. Modeling daily soil temperature over diverse climate conditions in Iran—a comparison of multiple linear regression and support vector regression techniques

    Science.gov (United States)

    Delbari, Masoomeh; Sharifazari, Salman; Mohammadi, Ehsan

    2018-02-01

    The knowledge of soil temperature at different depths is important for agricultural industry and for understanding climate change. The aim of this study is to evaluate the performance of a support vector regression (SVR)-based model in estimating daily soil temperature at 10, 30 and 100 cm depth at different climate conditions over Iran. The obtained results were compared to those obtained from a more classical multiple linear regression (MLR) model. The correlation sensitivity for the input combinations and periodicity effect were also investigated. Climatic data used as inputs to the models were minimum and maximum air temperature, solar radiation, relative humidity, dew point, and the atmospheric pressure (reduced to see level), collected from five synoptic stations Kerman, Ahvaz, Tabriz, Saghez, and Rasht located respectively in the hyper-arid, arid, semi-arid, Mediterranean, and hyper-humid climate conditions. According to the results, the performance of both MLR and SVR models was quite well at surface layer, i.e., 10-cm depth. However, SVR performed better than MLR in estimating soil temperature at deeper layers especially 100 cm depth. Moreover, both models performed better in humid climate condition than arid and hyper-arid areas. Further, adding a periodicity component into the modeling process considerably improved the models' performance especially in the case of SVR.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Acute hematological tolerance to multiple fraction, whole body, low dose irradiation in an experimental murine system

    International Nuclear Information System (INIS)

    Melamed, J.S.; Chen, M.G.; Brown, J.W.; Katagiri, C.A.

    1980-01-01

    Using a dose fractionation scheme patterned after the current regimen for treatment of disseminated non-Hodgkin lymphoma, the authors studied the effects of irradation on progenitor and effector cells for hematopoiesis in five-month-old BC3F 1 mice. Fractions of 20 or 50 rad (0.2 or 0.5 Gy) total body irradation were given twice weekly to a final total dose of 200 or 500 rad (2 or 5 Gy), respectively. Weekly assays revealed a marked, sustained depression of stem cell activity, measured as numbers of spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFU-C), without corresponding depression of effector cells (red and white cells, and platelets). The lack of correlation between numbers of stem cells and peripheral elements is relevant to clinical assessment of marrow reserve

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

    Directory of Open Access Journals (Sweden)

    Cui Y

    2014-03-01

    Full Text Available Cui Y, Song Y, Wang J, et al. Clinical Pharmacology: Advances and Applications. 2013;5(1:177–184.Note that on page 182, Figure 3 should be corrected as follows, with the line for mean anti-Xa activity extended through to 72 hours post dose on Day 9, and the Day 1 plasma apixaban concentration-time profile rendering error bars and symbols more visually apparent.Read the original article

  2. Demonstration of a stimulating effect of natural ionizing radiation and of very low radiation doses on cell multiplication

    International Nuclear Information System (INIS)

    Planel, G.; Soleilhavoup, J.P.; Tixador, R.; Croute, F.; Richoilley, G.

    1976-01-01

    Experiments have been carried out to demonstrate a possible effect of natural ionizing radiation. Using lead shielding devices or an underground laboratory, it was shown that a decrease in background irradiation induces a decrease in cell growth rate (experiments carried out on Paramecia). On the other hand, the recovery of a normal irradiation level in shielding devices induces a quite normal cell proliferation. Moreover, small doses of γ rays from 60 Co exhibit a stimulating effect. Variations in cell radiosensitivity to these low doses are reported. Experiments carried out in the underground laboratory and at high altitude show that both telluric radioactivity and cosmic rays contribute to this stimulating effect on cell multiplication. (author)

  3. OMI/Aura Surface UVB Irradiance and Erythemal Dose Daily L3 Global 1.0x1.0 deg Grid V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The Aura-OMI Daily Gridded Surface UV Irradiance Product (OMUVBd) is now available from the NASA Goddard Earth Sciences Data and Information Services Center (GES...

  4. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

    DEFF Research Database (Denmark)

    Fazekas, F.; Lublin, F.D.; Li, D.

    2008-01-01

    OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. W...

  5. Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

    DEFF Research Database (Denmark)

    Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

    2018-01-01

    Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

  6. Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice.

    Science.gov (United States)

    Cetkovic-Cvrlje, Marina; Thinamany, Sinduja; Bruner, Kylie A

    2017-12-01

    Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4 + T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action - in the context of T-cell immunity - that seemed to be dose

  7. Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

    Science.gov (United States)

    Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

    2017-05-01

    Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

  8. Single and multiple dose Fluconazole in the treatment of candidia vulvovaginitis: a prospective comparative study

    Directory of Open Access Journals (Sweden)

    Ashrafinia M

    2007-09-01

    Full Text Available  Background: Vulvovaginal candidiasis, the most common type of vaginitis, is usually caused by Candidia albicans. Patients experience a variety of symptoms. There are many types of vulvovaginal candidiasis with various microbial causes, symptoms, host circumstances, recurrence rates, and responses to treatment. The purpose of this study was to find the best method of treatment of complicated vaginitis as determined by its high prevalence, varying symptoms and signs and patient complaints.Methods: In this open clinical trial without placebo control, we studied all patients aged 18 to 65 years, suffering from vaginitis symptoms that presented at the gynecological clinic of Arash Hospital, Tehran, Iran, during the year 2004. After obtaining informed consent, we assessed the response to a treatment of single 150 mg dose of fluconazole in one group, and sequential 150 mg doses of fluconazole in the other. The analysis was performed using SPSS statistical software (version 11.Results: With regard to symptom severity, no significant difference was found between the groups. The rate of excoriation and fissure formation demonstrated significant difference between the two groups (p=0.048. Assessment of clinical and mycological response proved that patients with severe vaginitis treated with sequential doses of fluconazole had a better general status than those in the other group. The difference between the severity of vaginitis and positive response to the treatment in culture was not significant among patients with recurrent vaginitis.Conclusion: Patients with mild to moderate recurrent vaginitis show better response to treatment. The high rate of positive culture on day 35 reconfirms the limitation of fluconazole and other azoles as fungistatic drugs.

  9. Evaluation of multiple scan average dose (MSAD) levels in computerized tomography in Minas Gerais state, Brazil

    International Nuclear Information System (INIS)

    Alonso, Thessa C.; Vieira, Leandro de A.; Barbosa, Nayra V.; Oliveira, Jeyselaine R. de; Cesar, Adriana C.Z.; Silva, Teogenes A. da

    2014-01-01

    Computed Tomography (CT) grows every year and is a diagnostic method that has revolutionized radiology with advances in procedures for obtaining image. However, the indiscriminate use of this method generates relatively high doses in patients. The diagnostic reference levels (DRLs) is a practical tool to promote the evaluation of existing protocols. The optimization and the periodic review of the protocols are important to balance the risk of radiation. The present study aims to conduct a survey of levels of MSAD of Minas Gerais following the procedures recommended by current Brazilian law. (author)

  10. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

    2016-11-01

    Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

  11. Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebo-controlled, parallel-group, multiple-dose study.

    Science.gov (United States)

    Boulton, Craig; Meiser, Karin; David, Olivier J; Schmouder, Robert

    2012-12-01

    Fingolimod, a first-in-class oral sphingosine 1-phosphate receptor (S1PR) modulator, is approved in many countries for relapsing-remitting multiple sclerosis, at a once-daily 0.5-mg dose. A reduction in peripheral lymphocyte count is an expected consequence of the fingolimod mechanism of S1PR modulation. The authors investigated if this pharmacodynamic effect impacts humoral and cellular immunogenicity. In this double-blind, parallel-group, 4-week study, 72 healthy volunteers were randomized to steady state, fingolimod 0.5 mg, 1.25 mg, or to placebo. The authors compared T-cell dependent and independent responses to the neoantigens, keyhole limpet hemocyanin (KLH), and pneumococcal polysaccharides vaccine (PPV-23), respectively, and additionally recall antigen response (tetanus toxoid [TT]) and delayed-type hypersensitivity (DTH) to KLH, TT, and Candida albicans. Fingolimod caused mild to moderate decreases in anti-KLH and anti-PPV-23 IgG and IgM levels versus placebo. Responder rates were identical between placebo and 0.5-mg groups for anti-KLH IgG (both > 90%) and comparable for anti-PPV-23 IgG (55% and 41%, respectively). Fingolimod did not affect anti-TT immunogenicity, and DTH response did not differ between placebo and fingolimod 0.5-mg groups. Expectedly, lymphocyte count reduced substantially in the fingolimod groups versus placebo but reversed by study end. Fingolimod was well tolerated, and the observed safety profile was consistent with previous reports.

  12. [Clinical study of the influence of daily sedation interruption on fluctuation of blood glucose level and mortality of critical patients with multiple trauma].

    Science.gov (United States)

    Li, Yong; Jin, Zhaochen; Cai, Yan; Ji, Musen; Kong, Xianru; Liu, Jing; Yang, Hongfeng; Wang, Chenglong

    2014-04-01

    To assess the influence of a protocol of routine daily interruption of sedation on fluctuation of blood glucose level and mortality of critical patients with multiple trauma. A prospective study involving 68 critical patients with multiple trauma admitted to intensive care unit (ICU) was performed. Finger blood glucose level was measured after the implementation of daily interruption of sedation, and the results were recorded every 2 hours during the first 24 hours. Mean (MEAN), standard deviation (SD) and coefficient of variability (CV) of blood glucose level, glycemic liability index (GLI), mean amplitude of glycemic excursion (MAGE) and largest amplitude of glycemic excursions (LAGE) were calculated respectively, and 30-day mortality was recorded. The patients under study were divided into four groups according to the median values of MEAN and GLI, group A with patients of low MEAN+low GLI (n=34), group B with patients of low MEAN+high GLI (n=14), group C with patients of high MEAN+low GLI (n=12), and group D with patients of high MEAN+high GLI (n=8). Glucose levels, their range of fluctuation, and the prognosis were compared among groups. Five of the 68 patients died, with a gross mortality rate of 7.4%. Group analysis demonstrated that the patients in group A had the best prognosis with the 30-day mortality rate of 0 (0/34), while that of the group D was worst with the 30-day mortality rate of 37.5% (3/8). The MEAN levels of glucose were relatively lower in groups A and B (6.7±1.3 mmol/L, 7.6±0.8 mmol/L) and higher in groups C and D (9.3±1.4 mmol/L, 10.7±1.3 mmol/L). Indicators of glucose level fluctuation, including SD, CV, GLI, LAGE, and MAGE, were lower in groups A and C (SD: 1.6±0.4 mmol/L, 1.7±0.6 mmol/L; CV: 0.2±0.1, 0.2±0.1; GLI: 26.5±19.5, 40.1±17.6; LAGE: 4.6±2.3 mmol/L, 6.5±1.9 mmol/L; MAGE: 2.7±0.8 mmol/L, 3.1±0.80 mmol/L), and higher in groups B and D (SD: 2.9±0.7 mmol/L, 3.9±0.8 mmol/L; CV: 0.4±0.1, 0.4±0.1; GLI: 120.5±33.2, 184

  13. Neutron/gamma dose separation by the multiple-ion-chamber technique

    International Nuclear Information System (INIS)

    Goetsch, S.J.

    1983-01-01

    Many mixed n/γ dosimetry systems rely on two dosimeters, one composed of a tissue-equivalent material and the other made from a non-hydrogenous material. The paired chamber technique works well in fields of neutron radiation nearly identical in spectral composition to that in which the dosimeters were calibrated. However, this technique is drastically compromised in phantom due to the degradation of the neutron spectrum. The three-dosimeter technique allows for the fall-off in neutron sensitivity of the two non-hydrogenous dosimeters. Precise and physically meaningful results were obtained with this technique with a D-T source in air and in phantom and with simultaneous D-T neutron and 60 Co gamma ray irradiation in air. The MORSE-CG coupled n/γ three-dimensional Monte Carlo code was employed to calculate neutron and gamma doses in a water phantom. Gamma doses calculated in phantom with this code were generally lower than corresponding ion chamber measurements. This can be explained by the departure of irradiation conditions from ideal narrow-beam geometry. 97 references

  14. Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2016-10-01

    Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose. © 2016 John Wiley & Sons Ltd.

  15. Open-label phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L

    Directory of Open Access Journals (Sweden)

    Tarakanovskaya MG

    2017-04-01

    Full Text Available Marina G Tarakanovskaya,1 Jigjidsuren Chinburen,2 Purev Batchuluun,2 Chogsom Munkhzaya,2 Genden Purevsuren,2 Dorjiin Dandii,3 Tsogkhuu Hulan,3 Dandii Oyungerel,4 Galyna A Kutsyna,5 Alan A Reid,6 Vika Borisova,6 Allen I Bain,7 Vichai Jirathitikal,7 Aldar S Bourinbaiar6–8 1Ekomed LLC, 2National Cancer Center, 3Monserum LLC, 4National Center for Public Health, Ulaanbaatar, Mongolia; 5Department of Infectious Diseases, Luhansk State Medical University, Luhansk, Ukraine; 6Immunitor China Ltd, Beijing, People’s Republic of China; 7Immunitor Inc, Vancouver, BC, Canada; 8Immunitor LLC, Ulaanbaatar, Mongolia Background: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5]—an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA as an orphan drug for treatment of hepatocellular carcinoma (HCC. V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis.Methods: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7% females and 46 (61.3% males with a median age of 60 years (mean 61.6±8.1 years. Out of these, 23 (30.7% had hepatitis B and 34 (45.3% had hepatitis C infections, including 9 (12% with dual infection, 4 (5.3% negative for both viruses, and 5 (6.7% without established viral diagnosis. Most patients (94.7% had underlying liver cirrhosis of varying severity.Results: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP (66.7%; P=0.006 by Wilcoxon signed rank test. Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2–92,407; 95% confidence interval [CI] 1,186–7,280 and post-treatment values were 102.3 IU

  16. Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

    Directory of Open Access Journals (Sweden)

    Shadi Baniasadi

    Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

  17. Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

    Directory of Open Access Journals (Sweden)

    Shadi Baniasadi

    2013-02-01

    Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

  18. Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.

    Science.gov (United States)

    Lin, Marvin; Yin, Na; Murphy, Barbara; Medof, M Edward; Segerer, Stephan; Heeger, Peter S; Schröppel, Bernd

    2010-09-01

    The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.

  19. Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kirsch Lee E

    2009-12-01

    Full Text Available Abstract Background The population pharmacokinetics of artesunate (AS and its active metabolite dihydroartemisinin (DHA were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka of 3.85 h-1. The population estimates of apparent clearance (CL/F and volume of distribution (V2/F for AS were 1190 L/h with 36.2% inter-individual variability (IIV and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F and central volume of distribution (V3/F were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F and peripheral volume of distribution (V4/F for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in

  20. Use and Effectiveness of Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Insulin Injection Therapy (MIT) in Children, Adolescents and Young Adults with Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Schiel, R; Burgard, D; Perenthaler, T; Stein, G; Kramer, G; Steveling, A

    2016-02-01

    Today continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents with type 1 diabetes mellitus. The present cross-sectional trial aimed to document current practice, quality of diabetes control and incidence of acute complications in different age-groups under CSII vs. multiple daily insulin injection therapy (MIT). Moreover the survey analyzed socio-demographic backgrounds of the patients. A total of 901 patients (age 11.5±4.0, diabetes duration 4.0±3.6 years) was entered in the database. Clinical data, laboratory parameters and, using a standardized questionnaire, socio-demographic data were assessed. For age-related analyses patients were allocated to 4 groups: pre-school children (MIT. Patients with CSII vs. MIT had a longer diabetes duration, they used more frequently insulin analogues, performed more frequently blood-glucose self-tests and had a lower insulin dosage per kilogram body weight. In respect of HbA1c, the mean amplitude of blood-glucose excursions, but also of lipids, creatinine, microalbuminuria and blood pressure, there were no differences in neither age-group between patients with CSII and MIT. In patients with CSII and MIT, there was a tendency (pMIT there is an increase of HbA1c towards adolescence. It must also highlighted that CSII seems to be expansive and that CSII is more frequently used in patients with better educational levels and deriving from higher social classes. © Georg Thieme Verlag KG Stuttgart · New York.

  1. The Multiple Object Test as a Performance Based Tool to Assess Cognitive Driven Activity of Daily Living Function in Parkinson's Disease.

    Science.gov (United States)

    Glonnegger, Hannah; Beyle, Aline; Cerff, Bernhard; Gräber, Susanne; Csoti, Ilona; Berg, Daniela; Liepelt-Scarfone, Inga

    2016-07-06

    There is need for multidimensional quantitative assessment of cognitive driven activities of daily living (ADL) functions in Parkinson's disease (PD). To determine whether there is an ADL profile related to cognitive impairment in PD assessed by the Multiple Object Test (MOT). We assumed MOT performance to be lower in PD patients versus controls and in PD patients with more severe cognitive impairment. 50 PD patients with no cognitive impairment (PD-NC), 54 patients with PD-mild cognitive impairment (PD-MCI), 29 with Parkinson's disease dementia (PDD), and 40 healthy controls (HC) were investigated. Besides comprehensive cognitive testing, the MOT, a performance based test consisting of five routine tasks (e.g., preparing a cup of coffee), was applied. Quantitative (total errors and time) and qualitative (error type) MOT parameters were analyzed. Total time and number of MOT errors was increased in PD patients compared to controls (p < 0.001). These parameters also differentiated PDD patients from other cognitive groups (p < 0.05). No control subject had ≥ 4 errors in the MOT, but 30% of PD patients, especially PDD, scored above this cut-off. Omission (p < 0.001) and mislocation (p < 0.03) errors were more prominent in PDD than other cognitive groups. Perplexity errors did not differ between PD-MCI and PDD but between PD-NC and PDD (p = 0.01). MOT parameters discriminating between cognitive groups correlated mainly with lower test performance in psychomotor speed and executive function. Performance based testing is promising to identify quantitative and qualitative ADL aspects differentiating between different cognitive groups which might be helpful for an early detection of PDD.

  2. The development of a methodology to assess population doses from multiple sources and exposure pathways of radioactivity

    International Nuclear Information System (INIS)

    Hancox, J.; Stansby, S.; Thorne, M.

    2002-01-01

    The Environment Agency (EA) has new duties in accordance with the Basic Safety Standards Directive under which it is required to ensure that doses to individuals received from exposure to anthropogenic sources of radioactivity are within defined limits. In order to assess compliance with these requirements, the EA needs to assess the doses to members of the most highly exposed population groups ('critical' groups) from all relevant potential sources of anthropogenic radioactivity and all relevant potential exposure pathways to such radioactivity. The EA has identified a need to develop a methodology for the retrospective assessment of effective doses from multiple sources of radioactive materials and exposure pathways associated with those sources. Under contract to the EA, AEA Technology has undertaken the development of a suitable methodology as part of EA R and D Project P3-070. The methodology developed under this research project has been designed to support the EA in meeting its obligations under the Euratom Basic Safety Standards Directive and is consistent with UK and international approaches to radiation dosimetry and radiological protection. The development and trial application of the methodology is described in this report

  3. Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

    Science.gov (United States)

    Miceli Sopo, S; Greco, M; Monaco, S; Varrasi, G; Di Lorenzo, G; Simeone, G

    2015-01-01

    Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  4. Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

    Science.gov (United States)

    Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

    2013-10-01

    To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically

  5. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  6. Estimation of effective dose for the diagnosis and follow-up of multiple myeloma using conventional radiology

    International Nuclear Information System (INIS)

    Tsalafoutas, I.; Kostopoulou, H.; Steinhauer, G.; Koukourakis, G.; Yakoumakis, E.

    2012-01-01

    Background and objective: Multiple myeloma (MM) is a haemolytic neoplasm which produces osteolytic lesions and necessitates the periodical radiological examination of the skeleton for monitoring the disease progression. This involves the acquisition of multiple radiographs every 3 to 6 months, depending on the extent and the stage of the disease. Our objective was to estimate the cumulative patient dose during the radiographic investigation of MM. Materials and methods: Sixty eight MM radiographic examinations performed with a digital X-ray unit were recorded on a CD-rom in DICOM format. The DICOM data were extracted using appropriate software (DICOM Info Extractor) and were input into a Microsoft Excel based spreadsheet, containing embedded algorithms for the identification of the radiological examination type and the estimation of entrance surface air kerma (ESAK), dose area product (DAP) and effective dose (E) in each radiograph. The DAP to E conversion coefficients for each examination type were derived using the PCXMC 2.0 Monte Carlo simulation software for the case of a standard adult patient utilizing the irradiation geometry as this was perceived from the images and the DICOM data. Results: The mean values [and ranges] were: for number of radiographs= 14 [7-23], for cumulative ESAK 13 [2-44] mGy, for cumulative DAP= 6 [1.35-16.5] Gycm 2 and for E= 0. [0.14-2.4] mSv. Conclusion: The average E value calculated is smaller than the values of 1.7 and 2.4 mSv reported in the literature and even smaller than the values of 4.8 and 4.1 mSv reported for MM diagnosis using whole-body CT. (authors)

  7. A randomised clinical trial on the efficacy of oxytetracycline dose through water medication of nursery pigs on diarrhoea, faecal shedding of Lawsonia intracellularis and average daily weight gain

    DEFF Research Database (Denmark)

    Larsen, Inge-Lise; Hjulsager, Charlotte Kristiane; Holm, Anders

    2016-01-01

    the efficacy of three oral dosage regimens (5, 10 and 20mg/kg body weight) of oxytetracycline (OTC) in drinking water over a five-day period on diarrhoea, faecal shedding of LI and average daily weight gain (ADG). A randomised clinical trial was carried out in four Danish pig herds. In total, 539 animals from...

  8. Evaluation of radiation dose in 64-row whole-body CT of multiple injured patients compared to 4-row CT

    International Nuclear Information System (INIS)

    Harrieder, A.; Geyer, L.L.; Koerner, M.; Deak, Z.; Wirth, S.; Reiser, M.; Linsenmaier, U.

    2012-01-01

    Purpose: To evaluate radiation exposure in whole-body CT (WBCT) of multiple injured patients comparing 4-row multidetector computed tomography (MDCT) to 64-row MDCT. Materials and Methods: 200 WBCT studies were retrospectively evaluated: 92 4-row MDCT scans and 108 64-row MDCT scans. Each CT protocol was optimized for the particular CT system. The scan length, CT dose index (CTDI), and dose length product (DLP) were recorded and analyzed for radiation exposure. The mean effective dose was estimated based on conversion factors. Student's t-test was used for statistical analysis. Results: The mean CTDI vol values (mGy) of the thorax and abdomen were significantly reduced with 64-row MDCT (10.2 ± 2.5 vs. 11.4 ± 1.4, p < 0.001; 14.2 ± 3.7 vs. 16.1 ± 1.7, p < 0.001). The DLP values (mGy x cm) of the head and thorax were significantly increased with 64-row MDCT (1305.9 ± 201.1 vs. 849.8 ± 90.9, p < 0,001; 504.4 ± 134.4 vs. 471.5 ± 74.1, p = 0.030). The scan lengths (mm) were significantly increased with 64-row MDCT: head 223.6 ± 35.8 vs. 155.5 ± 12.3 (p < 0.001), thorax 427.4 ± 44.5 vs. 388.3 ± 57.5 (p < 0.001), abdomen 520.3 ± 50.2 vs. 490.8 ± 51.6 (p < 0.001). The estimated mean effective doses (mSv) were 22.4 ± 2.6 (4-row MDCT) and 24.1 ± 4.6 (64-row MDCT; p = 0.001), resulting in a percentage increase of 8 %. Conclusion: The radiation dose per slice of the thorax and abdomen can be significantly decreased by using 64-row MDCT. Due to the technical advances of modern 64-row MDCT systems, the scan field can be adapted to the clinical demands and, if necessary, enlarged without time loss. As a result, the estimated mean effective dose might be increased in WBCT. (orig.)

  9. Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

    Science.gov (United States)

    Mukherjee, Kanchan Kumar; Kumar, Narendra; Tripathi, Manjul; Oinam, Arun S; Ahuja, Chirag K; Dhandapani, Sivashanmugam; Kapoor, Rakesh; Ghoshal, Sushmita; Kaur, Rupinder; Bhatt, Sandeep

    2017-01-01

    To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume

  10. Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure.

    Directory of Open Access Journals (Sweden)

    Andrew D Govus

    Full Text Available To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass and iron parameters after 2-4 weeks of moderate altitude exposure.Hematological data collected from 178 athletes (98 males, 80 females exposed to moderate altitude (1,350-3,000 m were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII and blood iron parameters [ferritin and transferrin saturation (TSAT].Altitude exposure (mean ± s: 21 ± 3 days increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d = -2.87 [-3.88, -1.66].Oral iron supplementation during 2-4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores.

  11. Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    Deise Riba Coelho

    2014-07-01

    Full Text Available Meglumine antimoniate (MA and sodium stibogluconate are pentavalent antimony (SbV drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous. Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h and a slow (t1/2 >> 24 h elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain. The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

  12. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase

    Directory of Open Access Journals (Sweden)

    Milena V. Oliveira

    2016-10-01

    Full Text Available Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking the changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across 2 groups. Emphysema (ELA animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU with a 1-week interval between them. Controls (C received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma was increased compared to C (p = 0.0001. The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p=0.0197. Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways were increased, whereas static lung elastance was reduced compared to C (p=0.0094. After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1beta, keratinocyte-derived chemokine, hepatocyte growth factor, and vascular endothelial growth factor; and collagen fiber content in the pulmonary vessel wall were increased compared to C (p=0.0096. At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during controlled

  13. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  14. Effects of multiple low dose radiation on the apoptosis of splenocytes and immune factor in male diabetic rats

    International Nuclear Information System (INIS)

    Li Yanbo; Guo Caixia; Dong Lihua; Wang Jianfeng; Liu Shuchun; Lu Zhe; Gong Shouliang

    2009-01-01

    Objective: To explore the effect of multiple low dose radiation (LDR) on the apoptosis of splenocytes and immune factors in diabetes mellitus (DM) rats. Methods: The rats were randomly divided into control, DM and DM + LDR groups. The irradiation doses were 25, 50 and 75 mGy, and the irradiated times were 15. At the fourth weekend after the DM rats irradiated, the apoptotic rate and TCRαβ percentage of splenocytes were detected by flow cytometry, and the content of IL-2 in both serum and supernatant of cultured splenocytes were detected by ELISA. Results: Compared with that in the control, the body weight (BW) decreased in the DM and DM + LDR groups,particularly in DM group. The blood glucose (BG) level in the DM + LDR groups was higher than that in the control, but decreased significantly as compared with that in the DM group (P < 0.01). As compared with those in the control, the apoptotic rate in DM + 50 mGy (P < 0.05) and the content of serum IL-2 in DM + 75 mGy group (P < 0.01) all increased significantly, while the content of IL-2 in supernatant of cultured splenocytes decreased significantly in the DM + LDR groups. Compared with those in the DM group, the apoptotic rate and the percentage of TCRαβ in splenocytes in the DM + LDR groups (P < 0.01-P < 0.001) and the content of IL-2 in serum in DM + 50 mGy group (P < 0.01) decreased significantly. Conclusions: The multiple LDR could weaken the loss of BW and increase of BG caused by DM, decrease the splenocyte apoptosis induced by DM, and regulate the immune factors. (authors)

  15. Anti-CD20 Cell Therapies in Multiple Sclerosis—A Fixed Dosing Schedule for Ocrelizumab is Overkill

    Directory of Open Access Journals (Sweden)

    Jagannadha Avasarala

    2017-10-01

    Full Text Available Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS. Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this—Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.

  16. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  17. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Fu J

    2016-04-01

    Full Text Available Jie Fu,1 Lilei Peng,2 Xiaogang Li1 1Department of Neurology, 2Department of Neurosurgery, The Affiliated Hospital of Luzhou Medical College, Luzhou, People’s Republic of China Objective: Vortioxetine is a novel antidepressant approved for the treatment of major depressive disorder by the US Food and Drug Administration in September 2013. This meta-analysis assessed the efficacy and safety of different doses of vortioxetine for generalized anxiety disorder of adults.Methods: PubMed, Cochrane Library, PsycINFO, and Clinical Trials databases were searched from 2000 through 2015. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were searched to identify additional studies. The search was limited to individual randomized controlled trials (RCTs, and there was no language restriction. Four RCTs met the selection criteria. These studies included 1,843 adult patients. Results were expressed as odds ratios (ORs and 95% confidence intervals (CIs. The data were pooled with a random-effects or fixed-effects model.Results: The results showed that multiple doses (2.5, 5, and 10 mg/d of vortioxetine did not significantly improve the generalized anxiety disorder symptoms compared to placebo (OR=1.16, 95% CI=0.84–1.60, Z=0.89, P=0.38; OR=1.41, 95% CI=0.82–2.41, Z=1.25, P=0.21; OR=1.05, 95% CI=0.76–1.46, Z=0.32, P=0.75, respectively. We measured the efficacy of 2.5 mg/d vortioxetine compared to 10 mg/d, and no significant differences were observed. The common adverse effects included nausea and headache. With increased dose, nausea was found to be more frequent in the vortioxetine (5 and 10 mg/d group (OR=2.99, 95% CI=1.31–6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85–4.25, Z=4.85, P<0.00001, respectively, but no significant differences were observed for headache.Conclusion: The results showed no significant improvement in the treatment of generalized anxiety disorder for vortioxetine compared to placebo

  18. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

    International Nuclear Information System (INIS)

    Lips, Irene M; Dehnad, Homan; Gils, Carla H van; Boeken Kruger, Arto E; Heide, Uulke A van der; Vulpen, Marco van

    2008-01-01

    We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used

  19. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

    Directory of Open Access Journals (Sweden)

    Boeken Kruger Arto E

    2008-05-01

    Full Text Available Abstract We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment and weekly during treatment (acute toxicity were scored using the Common Toxicity Criteria (CTC. The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU complaints and 2% experienced grade 2 gastrointestinal (GI complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4. In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

  20. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...... and at the end of each day. Both treatments were effective immediately after the first dose and during the subsequent multiple-dose phase. There were no statistically significant differences between ketorolac and Ketogan. The results show that 10-mg doses of ketorolac in intramuscular injections followed by 10......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...

  1. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit

    2015-01-01

    antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated...... on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. MAIN RESULTS AND THE ROLE OF CHANCE: The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid...... were seen between groups. LIMITATIONS, REASONS FOR CAUTION: The number of patients included is limited and conclusions need to be verified in a larger RCT. WIDER IMPLICATIONS OF THE FINDINGS: Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH...

  2. Levels of daily light doses under changed day-night cycles regulate temporal segregation of photosynthesis and N2 Fixation in the cyanobacterium Trichodesmium erythraeum IMS101.

    Science.gov (United States)

    Cai, Xiaoni; Gao, Kunshan

    2015-01-01

    While the diazotrophic cyanobacterium Trichodesmium is known to display inverse diurnal performances of photosynthesis and N2 fixation, such a phenomenon has not been well documented under different day-night (L-D) cycles and different levels of light dose exposed to the cells. Here, we show differences in growth, N2 fixation and photosynthetic carbon fixation as well as photochemical performances of Trichodesmium IMS101 grown under 12L:12D, 8L:16D and 16L:8D L-D cycles at 70 μmol photons m-2 s-1 PAR (LL) and 350 μmol photons m-2 s-1 PAR (HL). The specific growth rate was the highest under LL and the lowest under HL under 16L:8D, and it increased under LL and decreased under HL with increased levels of daytime light doses exposed under the different light regimes, respectively. N2 fixation and photosynthetic carbon fixation were affected differentially by changes in the day-night regimes, with the former increasing directly under LL with increased daytime light doses and decreased under HL over growth-saturating light levels. Temporal segregation of N2 fixation from photosynthetic carbon fixation was evidenced under all day-night regimes, showing a time lag between the peak in N2 fixation and dip in carbon fixation. Elongation of light period led to higher N2 fixation rate under LL than under HL, while shortening the light exposure to 8 h delayed the N2 fixation peaking time (at the end of light period) and extended it to night period. Photosynthetic carbon fixation rates and transfer of light photons were always higher under HL than LL, regardless of the day-night cycles. Conclusively, diel performance of N2 fixation possesses functional plasticity, which was regulated by levels of light energy supplies either via changing light levels or length of light exposure.

  3. Method of examination of blood microcirculation in skin by multiple using of an identical dose of radioactive Xe/sup 133/ gas

    Energy Technology Data Exchange (ETDEWEB)

    Lewandowski, J.; Bogdanowski, T.; Brzezinska-Wcislo, L. (Slaska Akademia Medyczna, Katowice (Poland))

    1981-01-01

    The introduced method of Xe/sup 133/ gas application on epidermis serves to the investigation of microcirculation of blood within skin. It consists in a single use a dose of radioactive gas which is injected under the plastic membrane adhering to the skin surface. Our method of gaseous Xe/sup 133/ contact with epidermis enabling the multiple utilization of once applied dose to further examination is described.

  4. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

    Science.gov (United States)

    Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

    2018-02-01

    Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

  5. Evaluation of multiple low doses of copper oxide wire particles compared with levamisole for control of Haemonchus contortus in lambs.

    Science.gov (United States)

    Burke, J M; Miller, J E

    2006-06-30

    High levels of anthelmintic resistance in gastrointestinal nematodes (GIN) of small ruminants have created the need for alternative approaches to parasite control. Copper oxide wire particles (COWP; 2g) have proven effective in decreasing GIN infection in lambs. However, the risk of copper toxicity has limited the usefulness of this approach. Recently, smaller doses (0.5 and 1g) have proven effective in GIN control, reducing the risk of toxicity. The objective of this study was to examine the effectiveness and risk of toxicity using multiple small doses of COWP for GIN control in lambs between weaning and market weight. Dorper crossbred ram lambs were orally administered levamisole (Levasol, 8.0mg/kg; n=8), 0.5g (n=9), or 1g COWP (n=9) at weaning (Day 0; 118+/-2 days of age; late May 2005) and again at 6-week intervals for a total of four treatments. A pooled fecal culture determined that Haemonchus contortus was the predominant gastrointestinal parasite at weaning. Lambs grazed bermudagrass pastures and were supplemented with up to 500g corn/soybean meal and free choice trace mineralized salt. Fecal egg counts (FEC), packed cell volume (PCV), and plasma aspartate aminotransferase (AST) activity were determined every 14 days and lambs weighed every 28 days. GIN infection reached a peak at Day 42 (high FEC, low PCV). COWP effectively reduced FEC on Days 0 and 42 compared with the previous week, but did not reduce FEC on Days 84 and 126 (treatment by time interaction, Pcopper in the liver on Day 155 were greater in COWP-treated lambs (Pcopper toxicity.

  6. Variation in water disappearance, daily dose, and synovial fluid concentrations of tylvalosin and 3-O-acetyltylosin in commerical pigs during five day water medication with tylvalosin under field conditions.

    Science.gov (United States)

    Canning, P; Bates, J; Skoland, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Gauger, P; Ramirez, A; Karriker, L

    2018-03-23

    Tylvalosin (TVN) is a water soluble macrolide used in swine production to treat enteric, respiratory, and arthritic pathogens. There is limited data on its distribution to synovial fluid beyond gavage studies, which do not represent field conditions. This study measured water disappearance, TVN concentration in the medicated water, daily dose, and concentrations of TVN and 3-O-acetyltylosin (3AT) in the synovial fluid and plasma of treated pigs over the administration period. The study emphasized understanding variation in tissue TVN concentrations within the context of a field setting. Sixty finisher pigs were housed individually with individual waterers. Six pigs were randomly allocated to the following time points for sample collection: 0, 48, 60, 72, 84, 96, 102, 108, 114, and 120 hr on medication. TVN was administered daily in the water for 5 days. Water disappearance and medicated water concentration were measured daily. At each time point, six pigs were euthanized and plasma and synovial fluid were collected for analysis. Median TVN synovial fluid concentrations ranged between <1 ng/ml (hour 0) to 3.6 ng/ml (hour 84). There was substantial variation between individual pigs for water disappearance (mean 4.36L and range 0-7.84). Median TVN water concentration was 59 ppm (range 38-75 ppm). © 2018 John Wiley & Sons Ltd.

  7. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    Science.gov (United States)

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

  8. [Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis].

    Science.gov (United States)

    Rossiev, V A; Makarov, S V; Aleksandrova, I Ia; Dolgikh, G T; Lipshina, S R; Stukalova, T A; Trushina, O A; Fedorova, E Iu; Lipina, L N; Sivak, V F; Korenev, P P; Murashov, B F

    2002-01-01

    To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

  9. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

    Science.gov (United States)

    Nath, Sayantan; Ghosh, Sankar Kumar; Choudhury, Yashmin

    A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg -1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg -1 bw daily) and metformin (50mgkg -1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Use of and reasons for using multiple other tobacco products in daily and nondaily smokers: Associations with cigarette consumption and nicotine dependence.

    Science.gov (United States)

    Dunbar, Michael S; Shadel, William G; Tucker, Joan S; Edelen, Maria O

    2016-11-01

    Use of other tobacco products (OTPs) among smokers is increasing. Little is known about types of OTP used and the reasons for use, and how OTP use and reasons for use correlate with smoking patterns and nicotine dependence in daily and nondaily smokers. This paper addresses these gaps in the literature. 656 daily smokers and 203 nondaily smokers provided information on their use of different OTPs (hookah, e-cigarettes, chew/snuff, snus, cigars, dissolvables), and reasons for using OTPs (e.g., "to cut down on smoking"), as well as their cigarette consumption and nicotine dependence. Logistic regression models assessed the association of smoking status with OTP use (ever and current) and reasons for use. Within each smoking group, separate logistic regression models examined the associations of OTP use and reasons for use with cigarette consumption and nicotine dependence. Compared to daily smokers, nondaily smokers were more likely to use hookah and cigars, less likely to use dissolvables, and less likely to endorse using OTPs to reduce their smoking. Among non-daily smokers, nicotine dependence was associated with a higher likelihood of current OTP use (OR=1.04 [95% CI 1.01-1.07]; p<0.05), whereas cigarette consumption was not. Results suggest OTP use in nondaily smokers does not correlate with less frequent smoking, but may correlate with higher nicotine dependence. Use of combustible OTPs among nondaily smokers may offset any potential benefits achieved through less frequent cigarette consumption. Providers should explicitly address OTP use when discussing cigarette cessation and reduction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Ocular Pharmacokinetics of Dorzolamide and Brinzolamide After Single and Multiple Topical Dosing: Implications for Effects on Ocular Blood FlowS⃞

    Science.gov (United States)

    Kadam, Rajendra S.; Jadhav, Gajanan; Ogidigben, Miller

    2011-01-01

    Ophthalmic carbonic anhydrase inhibitors have been shown to improve retinal and optic nerve blood flow. However, the relative tissue distributions of commercially available carbonic anhydrase inhibitors to the optic nerve are not known. The objective of this study was to compare the ocular pharmacokinetics and tissue distribution profiles of dorzolamide and brinzolamide after single and multiple topical applications. Pigmented rabbits were treated with single or multiple topical administrations of 30 μl of Trusopt (dorzolamide hydrochloride ophthalmic solution, 2%) to one eye and 30 μl of Azopt (brinzolamide ophthalmic suspension, 1%) to the other eye. Rabbits were euthanized at 10 predetermined time intervals over a period of 24 h, and ocular tissues and plasma samples were collected. For multiple dosing, rabbits were dosed twice per day with an 8-h interval between two doses, groups of rabbits were euthanized at 7, 14, and 21 days at 1 h after the last dose, and ocular tissues and plasma samples were collected. Drug levels in tissue samples were measured using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters (Cmax, Tmax, and AUC0–24) were estimated by noncompartmental analysis. After a single dose, dorzolamide delivery (AUC0–24) to the aqueous humor, anterior sclera, posterior sclera, anterior retina, posterior retina, anterior vitreous, and optic nerve was 2-, 7-, 2.6-, 1.4-, 1.9-, 1.2-, and 9-fold higher than those of brinzolamide. Cmax was 2- to 5-fold higher for dorzolamide than that of brinzolamide in all of the ocular tissue. After multiple dosing, dorzolamide levels in the aqueous humor, sclera, retina, vitreous humor, and optic nerve were higher than those of brinzolamide, but statistical significance was achieved only with aqueous humor, vitreous humor, and optic nerve. Dorzolamide levels in the aqueous humor, anterior vitreous, posterior vitreous, and optic nerve were 1.4- to 3.2-, 2.4- to 2.7-, 2.2- to 4.5-, and 2.4- to

  13. Cost-effectiveness of insulin pumps compared with multiple daily injections both provided with structured education for adults with type 1 diabetes: a health economic analysis of the Relative Effectiveness of Pumps over Structured Education (REPOSE) randomised controlled trial.

    Science.gov (United States)

    Pollard, Daniel John; Brennan, Alan; Dixon, Simon; Waugh, Norman; Elliott, Jackie; Heller, Simon; Lee, Ellen; Campbell, Michael; Basarir, Hasan; White, David

    2018-04-07

    To assess the long-term cost-effectiveness of insulin pumps and Dose Adjustment for Normal Eating (pumps+DAFNE) compared with multiple daily insulin injections and DAFNE (MDI+DAFNE) for adults with type 1 diabetes mellitus (T1DM) in the UK. We undertook a cost-utility analysis using the Sheffield Type 1 Diabetes Policy Model and data from the Relative Effectiveness of Pumps over Structured Education (REPOSE) trial to estimate the lifetime incidence of diabetic complications, intervention-based resource use and associated effects on costs and quality-adjusted life years (QALYs). All economic analyses took a National Health Service and personal social services perspective and discounted costs and QALYs at 3.5% per annum. A probabilistic sensitivity analysis was performed on the base case. Further uncertainties in the cost of pumps and the evidence used to inform the model were explored using scenario analyses. Eight diabetes centres in England and Scotland. Adults with T1DM who were eligible to receive a structured education course and did not have a strong clinical indication or a preference for a pump. Pumps+DAFNE. MDI+DAFNE. Incremental costs, incremental QALYs gained and incremental cost-effectiveness ratios (ICERs). Compared with MDI+DAFNE, pumps+DAFNE was associated with an incremental discounted lifetime cost of +£18 853 (95% CI £6175 to £31 645) and a gain in discounted lifetime QALYs of +0.13 (95% CI -0.70 to +0.96). The base case mean ICER was £142 195 per QALY gained. The probability of pump+DAFNE being cost-effective using a cost-effectiveness threshold of £20 000 per QALY gained was 14.0%. All scenario and subgroup analyses examined indicated that the ICER was unlikely to fall below £30 000 per QALY gained. Our analysis of the REPOSE data suggests that routine use of pumps in adults without an immediate clinical need for a pump, as identified by National Institute for Health and Care Excellence, would not be cost-effective. ISRCTN61215213

  14. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  15. Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses

    NARCIS (Netherlands)

    van Hoogstraten, H. J.; Wolfhagen, F. H.; van de Meeberg, P. C.; Kuiper, H.; Nix, G. A.; Becx, M. C.; Hoek, A. C.; van Houte, D. P.; Rijk, M. C.; Salemans, J. M.; Scherpenisse, J.; Schrijver, M.; Smit, A. M.; Spoelstra, P.; Stadhouders, P. H.; Tan, T. G.; Hop, W. C.; ten Kate, F. J.; vanBerge-Henegouwen, G. P.; Schalm, S. W.; van Buuren, H. R.

    1998-01-01

    Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration. A 2-year multicentre randomised controlled

  16. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    Science.gov (United States)

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

  17. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A.; Oturai, D B; Sørensen, P S

    2015-01-01

    BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate...... the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. METHODS: A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference...... population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. RESULTS: Osteopenia was present in 38...

  18. Daily Nutritional Dose Supplementation with Antioxidant Nutrients and Phytochemicals Improves DNA and LDL Stability: A Double-Blind, Randomized, and Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    You Jin Kim

    2013-12-01

    Full Text Available Reactive oxygen species are important risk factors for age-related diseases, but they also act as signaling factors for endogenous antioxidative defense. The hypothesis that a multi-micronutrient supplement with nutritional doses of antioxidant nutrients and phytochemicals (MP may provide protection against oxidative damage and maintain the endogenous antioxidant defense capacity was assessed in subjects with a habitually low intake of fruits and vegetables. In a randomized, placebo-controlled, and parallel designed trial, 89 eligible subjects were assigned to either placebo or MP for eight weeks. Eighty subjects have completed the protocol and included for the analysis. MP treatment was superior at increasing serum folate (p < 0.0001 and resistance to DNA damage (p = 0.006, tail intensity; p = 0.030, tail moment by comet assay, and LDL oxidation (p = 0.009 compared with the placebo. Moreover, the endogenous oxidative defense capacity was not weakened after MP supplementation, as determined by the levels of glutathione peroxidase (p = 0.442, catalase (p = 0.686, and superoxide dismutase (p = 0.804. The serum folate level was negatively correlated with DNA damage (r = −0.376, p = 0.001 for tail density; r = −0.329, p = 0.003 for tail moment, but no correlation was found with LDL oxidation (r = −0.123, p = 0.275. These results suggest that MP use in healthy subjects with habitually low dietary fruit and vegetable intake may be beneficial in providing resistance to oxidative damage to DNA and LDL without suppressing the endogenous defense mechanisms.

  19. Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

    International Nuclear Information System (INIS)

    Levegrün, Sabine; Pöttgen, Christoph; Wittig, Andrea; Lübcke, Wolfgang; Abu Jawad, Jehad; Stuschke, Martin

    2013-01-01

    Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N mets ) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV mets ) and of the individual metastasis planning target volume (PTV ind met ) were 8.7 ± 8.9 cm 3 (range, 1.3-35.5 cm 3 ) and 2.5 ± 4.5 cm 3 (range, 0.19-24.7 cm 3 ), respectively. Dose distributions in PTV mets and PTV ind met were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N mets was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV mets amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV ind met were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV mets (CN = 0.737 for PTV mets ≤4.32 cm 3 vs CN = 0.848 for PTV mets >4.32 cm 3 , P=.006), in contrast to N mets . The achieved dose conformity to PTV mets , assessed by both CN and PITV, was in all investigated volume strata

  20. GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice.

    Science.gov (United States)

    Wang, Z; Gleichmann, H

    1998-01-01

    In mice, diabetes can be induced by multiple low doses of streptozotocin (MLD-STZ), i.e., 40 mg/kg body wt on each of 5 consecutive days. In this model, diabetes develops only when STZ induces both beta-cell toxicity and T-cell-dependent immune reactions. The target molecule(s) of MLD-STZ-induced beta-cell toxicity are not known, however. In this study, we report that GLUT2 is a target molecule for MLD-STZ toxicity. Ex vivo, a gradual decrement of both GLUT2 protein and mRNA expression was found in pancreatic islets isolated from MLD-STZ-treated C57BL/6 male mice, whereas mRNA expression of beta-actin, glucokinase, and proinsulin remained unaffected. Significant reduction of both GLUT2 protein and mRNA expression was first noted 1 day after the third STZ injection, clearly preceding the onset of hyperglycemia. The extent of reduction increased with the number of STZ injections administered and increased over time, after the last, i.e., fifth, STZ injection. The STZ-induced reduction of GLUT2 protein and mRNA was not due to an essential loss of beta-cells, because ex vivo, not only the total RNA yield and protein content in isolated islets, but also proinsulin mRNA expression, failed to differ significantly in the differently treated groups. Furthermore, islets isolated from MLD-STZ-treated donors responded to the nonglucose secretagogue arginine in a pattern similar to that of solvent-treated donors. Interestingly, the MLD-STZ-induced reduction of both GLUT2 protein and mRNA was prevented by preinjecting mice with 5-thio-D-glucose before each STZ injection. Apparently, GLUT2 is a crucial target molecule of MLD-STZ toxicity, and this toxicity seems to precede the immune reactions against beta-cells.

  1. Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

    NARCIS (Netherlands)

    van der Linden, F.A.H.; Kragt, J.J.; van Bon, M.; Klein, M.; Thompson, A.J.; van der Ploeg, H.M.; Polman, C.H.; Uitdehaag, B.M.J.

    2008-01-01

    Background: The use of self-report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self-assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis (MS), data collection might be

  2. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

    Science.gov (United States)

    Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

    2018-03-01

    Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

  3. Development of a flattening filter free multiple source model for use as an independent, Monte Carlo, dose calculation, quality assurance tool for clinical trials.

    Science.gov (United States)

    Faught, Austin M; Davidson, Scott E; Popple, Richard; Kry, Stephen F; Etzel, Carol; Ibbott, Geoffrey S; Followill, David S

    2017-09-01

    The Imaging and Radiation Oncology Core-Houston (IROC-H) Quality Assurance Center (formerly the Radiological Physics Center) has reported varying levels of compliance from their anthropomorphic phantom auditing program. IROC-H studies have suggested that one source of disagreement between institution submitted calculated doses and measurement is the accuracy of the institution's treatment planning system dose calculations and heterogeneity corrections used. In order to audit this step of the radiation therapy treatment process, an independent dose calculation tool is needed. Monte Carlo multiple source models for Varian flattening filter free (FFF) 6 MV and FFF 10 MV therapeutic x-ray beams were commissioned based on central axis depth dose data from a 10 × 10 cm 2 field size and dose profiles for a 40 × 40 cm 2 field size. The models were validated against open-field measurements in a water tank for field sizes ranging from 3 × 3 cm 2 to 40 × 40 cm 2 . The models were then benchmarked against IROC-H's anthropomorphic head and neck phantom and lung phantom measurements. Validation results, assessed with a ±2%/2 mm gamma criterion, showed average agreement of 99.9% and 99.0% for central axis depth dose data for FFF 6 MV and FFF 10 MV models, respectively. Dose profile agreement using the same evaluation technique averaged 97.8% and 97.9% for the respective models. Phantom benchmarking comparisons were evaluated with a ±3%/2 mm gamma criterion, and agreement averaged 90.1% and 90.8% for the respective models. Multiple source models for Varian FFF 6 MV and FFF 10 MV beams have been developed, validated, and benchmarked for inclusion in an independent dose calculation quality assurance tool for use in clinical trial audits. © 2017 American Association of Physicists in Medicine.

  4. A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

    Science.gov (United States)

    Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

    2017-06-01

    Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Estimation of lung tissue doses following exposure to low-LET radiation in the Canadian study of cancer following multiple fluoroscopies

    International Nuclear Information System (INIS)

    Howe, G.R.; Yaffe, M.

    1992-02-01

    Lung tissue doses from exposure to external low-LET radiation have been estimated for each year between 1930 and 1960 for 92,707 tuberculosis patients first treated in Canadian institutions between 1930 and 1952. Many of these patients received multiple chest fluoroscopies together with treatment by artificial pneumothorax, and thus accumulated doses up to 15.7 grays. The estimated doses have been used in a statistical analysis of lung cancer mortality between 1950 and 1987 occurring among 64,698 patients known to be alive at the start of 1950, and followed by linkage to the Canadian national mortality data base. There were substantial variations in the total cumulative lung tissue dose received by the cohort, with 2,490 individuals having doses in excess of 1.7 grays. A total of 1,156 lung cancer deaths was observed in the cohort, and these have been used to estimate relative risks. The most appropriate risk model appears to be a simple linear relative risk function, with an excess relative risk coefficient of 0.089 for an absorbed dose of 1 gray. This contrasts with estimates of relative risk based on the atomic bomb survivors study, for which the excess relative risk coefficient for males 20 years after the first exposure is estimated to be 0.64. The difference is statistically significant. It is postulated that fractionation and dose rate effectiveness factors may account for some of the discrepancy. (Modified author abstract) (14 refs., 20 tabs.)

  6. A longitudinal qualitative study examining the factors impacting on the ability of persons with T1DM to assimilate the Dose Adjustment for Normal Eating (DAFNE principles into daily living and how these factors change over time

    Directory of Open Access Journals (Sweden)

    White Florence

    2011-08-01

    Full Text Available Abstract Background The literature reveals that structured education programmes, such as DAFNE, result in many positive outcomes for people with Type 1 diabetes including a decrease in HbA1c levels and reductions in hypoglycaemia. While there is evidence that some of these outcomes are maintained we do not know at present what factors are most important over time. The study aim was to identify the key factors impacting on persons with Type 1 diabetes ability to assimilate the Dose Adjustment For Normal Eating (DAFNE DAFNE principles into their daily lives and how these factors change over time. Methods This is a longitudinal descriptive qualitative study. Interviews were undertaken with 40 participants who had attended DAFNE in one of 5 study sites across the Island of Ireland, at 6 weeks, 6 and 12 months after completion of the programme. The interviews lasted from 30 to 60 minutes and were transcribed verbatim. Data were analysed in three ways, a within time analysis, a cross sectional analysis for each participant and a thematic analysis which focused on examining changes over time Results Four themes that influenced participants' ability to assimilate DAFNE into their daily lives over time were identified. These were: embedded knowledge, continued responsive support, enduring motivation and being empowered. Support at the 6 month period was found to be crucial to continued motivation. Conclusions Understanding the factors that influence people's ability to assimilate DAFNE principles over time into their daily lives can help health professionals give focused responsive support that helps people with diabetes become more empowered. Understanding that continued support matters, particularly around 6 months, is important as health professionals can influence good management by providing appropriate support and enhancing motivation. Trial registration ISRCTN79759174

  7. A longitudinal qualitative study examining the factors impacting on the ability of persons with T1DM to assimilate the Dose Adjustment For Normal Eating (DAFNE) principles into daily living and how these factors change over time

    LENUS (Irish Health Repository)

    Casey, Dympna

    2011-08-30

    Abstract Background The literature reveals that structured education programmes, such as DAFNE, result in many positive outcomes for people with Type 1 diabetes including a decrease in HbA1c levels and reductions in hypoglycaemia. While there is evidence that some of these outcomes are maintained we do not know at present what factors are most important over time. The study aim was to identify the key factors impacting on persons with Type 1 diabetes ability to assimilate the Dose Adjustment For Normal Eating (DAFNE) DAFNE principles into their daily lives and how these factors change over time. Methods This is a longitudinal descriptive qualitative study. Interviews were undertaken with 40 participants who had attended DAFNE in one of 5 study sites across the Island of Ireland, at 6 weeks, 6 and 12 months after completion of the programme. The interviews lasted from 30 to 60 minutes and were transcribed verbatim. Data were analysed in three ways, a within time analysis, a cross sectional analysis for each participant and a thematic analysis which focused on examining changes over time Results Four themes that influenced participants\\' ability to assimilate DAFNE into their daily lives over time were identified. These were: embedded knowledge, continued responsive support, enduring motivation and being empowered. Support at the 6 month period was found to be crucial to continued motivation. Conclusions Understanding the factors that influence people\\'s ability to assimilate DAFNE principles over time into their daily lives can help health professionals give focused responsive support that helps people with diabetes become more empowered. Understanding that continued support matters, particularly around 6 months, is important as health professionals can influence good management by providing appropriate support and enhancing motivation. Trial registration ISRCTN79759174

  8. Effect of Equal Daily Doses Achieved by Different Power Densities of Low-Level Laser Therapy at 635 nm on Open Skin Wound Healing in Normal and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Róbert Kilík

    2014-01-01

    Full Text Available Background and Objective. Despite the fact that the molecular mechanism of low-level laser therapy (LLLT is not yet known, the exploitation of phototherapy in clinical medicine and surgery is of great interest. The present study investigates the effects of LLLT on open skin wound healing in normal and diabetic rats. Materials and Methods. Four round full-thickness skin wounds on dorsum were performed in male adult nondiabetic (n=24 and diabetic (n=24 Sprague–Dawley rats. AlGaInP (635 nm, wavelength; 5 J/cm2, daily dose was used to deliver power densities of 1, 5, and 15 mW/cm2 three times daily until euthanasia. Results. PMNL infiltration was lower in the irradiated groups (15 mW/cm2. The synthesis and organisation of collagen fibres were consecutively enhanced in the 5 mW/cm2 and 15 mW/cm2 groups compared to the others in nondiabetic rats. In the diabetic group the only significant difference was recorded in the ratio PMNL/Ma at 15 mW/cm2. A significant difference in the number of newly formed capillaries in the irradiated group (5, 15 mW/cm2 was recorded on day six after injury compared to the control group. Conclusion. LLLT confers a protective effect against excessive inflammatory tissue response; it stimulates neovascularization and the early formation of collagen fibres.

  9. Switch from a ZDV/3TC-based regimen to a completely once daily (QD regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT

    Directory of Open Access Journals (Sweden)

    Arasteh K

    2009-05-01

    Full Text Available Abstract Objectives To assess the efficacy and safety of a treatment switch from a twice-daily (BID regimen containing zidovudine (ZDV and lamivudine (3TC plus a third agent to a once daily (QD regimen containing the fixed-dose combination of tenofovir DF/emtricitabine (TDF/FTC, Truvada® plus a divergent third QD agent in HIV-1 infected patients. Methods Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA 50 cells/μl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. Results During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs. At week 48, plasma HIV-1 RNA was p Conclusions Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

  10. Radiation in daily life

    International Nuclear Information System (INIS)

    Mora Rodriguez, P.

    1999-01-01

    The medical community benefits on a daily basis from the ionizing radiations used in the diagnosis and treatment of disease. The doses received in the medical field are only a small fraction of the total radiation received in a year. This bibliographic review has several objectives. The first one is to present the different components of natural radiation (background radiation). Secondly, it will introduce many consumer products that contain radioactive sources and expose our bodies. Third, arguments to diminish the radiation phobia will be presented and finally an easy to understand dosimetric magnitude will be introduced for the physician, the technologist and the patient. (author) [es

  11. Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

    Science.gov (United States)

    Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

    2018-03-01

    There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other

  12. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high).......A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  13. Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica.

    Science.gov (United States)

    Okkerse, Pieter; Hay, Justin L; Versage, Eve; Tang, Yongqiang; Galluppi, Gerald; Ravina, Bernard; Verma, Ajay; Williams, Leslie; Aycardi, Ernesto; Groeneveld, Geert Jan

    2016-07-01

    BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study were to evaluate the pharmacokinetic and safety profiles and to determine the effects on pain of ascending doses of intravenous injections of BG00010 in patients with sciatica. This was a randomized, blinded, placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ). Safety and efficacy assessments were used as endpoints. The BG00010 concentration-time data indicated relatively low inter-patient variability and there was a dose-dependent (not dose-proportional) increase in serum exposure from 150 to 1200 μg kg(-1) . The effective half-life was between 40 and 60 h. The most frequently occurring adverse events (AEs) reported by patients receiving BG00010 were headache (67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in greater pain reduction than placebo or lower dose regimens, although a clear dose-response relationship was not seen. The pharmacokinetic profile of BG00010 was characterized by low intra-patient variability. These data from a small sample suggest that BG00010 may have a benefit for patients with sciatica. © 2016 The British Pharmacological Society.

  14. The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation.

    Science.gov (United States)

    Osmonov, Daniar K; Jünemann, Klaus P; Bannowsky, Andreas

    2017-07-01

    Radical prostatectomy (RP) is the most common definitive invasive treatment option for localized prostate cancer. Although the different surgical procedures-open RP, laparoscopic RP, and robot-assisted laparoscopic RP-do not differ significantly for the results of postoperative erectile dysfunction (ED) and continence, the fear of losing erectile function (EF) is often an important factor for preoperatively sexually active men when deciding for or against a procedure. To review the available literature on rehabilitation of EF after RP and to evaluate the value of the "Kiel concept" against different strategies of phosphodiesterase type 5 inhibitor (PDE5i) low-dose treatments. A review of the available literature up to January 2017 was undertaken using the key terms postsurgical ED, penile rehabilitation," PDE5i rehabilitation, and PDE5i daily dose treatment. As a main outcome measure we chose reviewed different concepts on the rehabilitation of EF after RP, taking into account the clinical background of the Kiel concept. The different therapeutic concepts for rehabilitation of EF after nerve-sparing RP are surprising. The most frequently applied method is application of different PDE5is. Despite different studies on efficacy, the issue of an optimal concept remains unresolved. The reason for this, among others, can be found in the difficulty of comparing different studies, which can vary with respect to the degree of nerve sparing, postoperative preservation of nocturnal erections, concomitant morbidity, and the number and experience of surgeons. In 86% of patients, the Kiel concept has been shown to support rehabilitation of EF after nerve-sparing RP with some form of therapeutic method. The Kiel concept is one therapeutic option among other comparable therapeutic options. Osmonov DK, Jünemann KP, Bannowsky A. The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and

  15. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

  16. A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

    Science.gov (United States)

    Buck, David; Subramanyam, Rajeev; Varughese, Anna

    2016-01-01

    The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

    Hansen, Per Boye; Penkowa, Milena

    2017-01-01

    show for the first time that bismuth significantly reduces grade 2 stomatitis, febrile neutropenia and infections caused by melphalan in multiple myeloma, where adverse effects also were significantly linked to gender. In lymphoma patients, bismuth significantly reduces diarrhoea relative to placebo......PURPOSE: High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey...

  18. Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

    Science.gov (United States)

    Jamaludin, A; Mohamad, M; Navaratnam, V; Yeoh, P Y; Wernsdorfer, W H

    1990-09-01

    A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

  19. The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.

    Science.gov (United States)

    Görgens, Christian; Guddat, Sven; Bosse, Christina; Geyer, Hans; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

    2017-05-10

    Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis.

    Science.gov (United States)

    Olsson, A; Oturai, D B; Sørensen, P S; Oturai, P S; Oturai, A B

    2015-10-01

    Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. Osteopenia was present in 38% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both lumbar and femoral BMD. Reduced BMD was prevalent in patients with MS. GC treatment appears not to be the primary underlying cause of secondary osteoporosis in MS patients. © The Author(s), 2015.

  1. Thermally assisted OSL application for equivalent dose estimation; comparison of multiple equivalent dose values as well as saturation levels determined by luminescence and ESR techniques for a sedimentary sample collected from a fault gouge

    Energy Technology Data Exchange (ETDEWEB)

    Şahiner, Eren, E-mail: sahiner@ankara.edu.tr; Meriç, Niyazi, E-mail: meric@ankara.edu.tr; Polymeris, George S., E-mail: gspolymeris@ankara.edu.tr

    2017-02-01

    Highlights: • Multiple equivalent dose estimations were carried out. • Additive ESR and regenerative luminescence were applied. • Preliminary SAR results employing TA-OSL signal were discussed. • Saturation levels of ESR and luminescence were investigated. • IRSL{sub 175} and SAR TA-OSL stand as very promising for large doses. - Abstract: Equivalent dose estimation (D{sub e}) constitutes the most important part of either trap-charge dating techniques or dosimetry applications. In the present work, multiple, independent equivalent dose estimation approaches were adopted, using both luminescence and ESR techniques; two different minerals were studied, namely quartz as well as feldspathic polymineral samples. The work is divided into three independent parts, depending on the type of signal employed. Firstly, different D{sub e} estimation approaches were carried out on both polymineral and contaminated quartz, using single aliquot regenerative dose protocols employing conventional OSL and IRSL signals, acquired at different temperatures. Secondly, ESR equivalent dose estimations using the additive dose procedure both at room temperature and at 90 K were discussed. Lastly, for the first time in the literature, a single aliquot regenerative protocol employing a thermally assisted OSL signal originating from Very Deep Traps was applied for natural minerals. Rejection criteria such as recycling and recovery ratios are also presented. The SAR protocol, whenever applied, provided with compatible D{sub e} estimations with great accuracy, independent on either the type of mineral or the stimulation temperature. Low temperature ESR signals resulting from Al and Ti centers indicate very large D{sub e} values due to bleaching in-ability, associated with large uncertainty values. Additionally, dose saturation of different approaches was investigated. For the signal arising from Very Deep Traps in quartz saturation is extended almost by one order of magnitude. It is

  2. Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

    Directory of Open Access Journals (Sweden)

    Thompson Alan J

    2008-02-01

    Full Text Available Abstract Background The use of self-report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self-assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis (MS, data collection might be problematic. In these situations, information obtained from proxy respondents (e.g. partners may replace self-ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient-proxy agreement on possible changes in disease impact of MS. Methods Fifty-six MS patients and their partners completed the Multiple Sclerosis Impact Scale (MSIS-29 at baseline and follow-up, two years later. Patient-proxy agreement was assessed at both time points by calculating intraclass correlation coefficients (ICCs, exact and global agreement and the mean directional differences between groups. Agreement of change over time was assessed by calculating ICCs between change scores. In parallel, global ratings of both patients and proxy respondents of the extent to which the patient had improved or deteriorated over the past two years were collected to validate possible changes on the MSIS-29. Results At both time points, agreement on the physical scale was higher than agreement on the psychological scale (ICCs at baseline were 0.81 for the physical scale and 0.72 for the psychological scale; at follow-up, the ICC values were 0.86 and 0.65 respectively. At follow-up, statistically significant mean differences between patients and proxies were noted for the physical scale (-4.8 ± 12.7, p = 0.006 and the psychological scale (-8.9 ± 18.8, p = 0.001. Agreement between change scores on the MSIS-29 was fair (ICC Conclusion Proxy respondents could act as a reliable source of information in cross-sectional studies. Moreover, results suggested that agreement on change over time might be better for proxy respondents compared to

  3. Multiple daily injection of insulin regimen for a 10-month-old infant with type 1 diabetes mellitus and diabetic ketoacidosis

    Directory of Open Access Journals (Sweden)

    Ji Hyun Park

    2016-06-01

    Full Text Available The incidence of type 1 diabetes is increasing worldwide, and the greatest increase has been observed in very young children under 4 years of age. A case of infantile diabetic ketoacidosis in a 10-month-old male infant was encountered by these authors. The infant's fasting glucose level was 490 mg/dL, his PH was 7.13, his pCO2 was 15 mmHg, and his bicarbonate level was 5.0 mmol/L. The glycosylated hemoglobin level had increased to 9.4%. Ketonuria and glucosuria were detected in the urinalysis. The fasting C-peptide and insulin levels had decreased. The infant was positive for anti-insulin and antiglutamic acid decarboxylase antibodies. Immediately after the infant's admission, fluid therapy and intravenous insulin infusion therapy were started. On the second day of the infant's hospitalization and after fluid therapy, he recovered from his lethargic condition, and his general condition improved. Feeding was started on the third day, and he was fed a formula 5 to 7 times a day and ate rice, vegetables, and lean meat. Due to the frequent feeding, the frequency of rapid-acting insulin injection was increased from 3 times before feeding to 5 times, adjusted according to the feeding frequency. The total dose of insulin that was injected was 0.8–1.1 IU/kg/day, and the infant was discharged on the 12th day of his hospitalization. The case is presented herein with a brief review of the relevant literature.

  4. Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

    Directory of Open Access Journals (Sweden)

    Kristen Ashley eHorner

    2011-05-01

    Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

  5. Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice.

    Science.gov (United States)

    Zecca, C; Digesu, G A; Robshaw, P; Puccini, F; Khullar, V; Tubaro, A; Gobbi, C

    2014-03-01

    Posterior tibial nerve stimulation (PTNS) is an effective treatment option for lower urinary tract symptoms (LUTS) in multiple sclerosis (MS) patients. Patients with MS and LUTS unresponsive to medical treatment received PTNS for 12 weeks after saline urodynamics to evaluate the prevalence of motor, sensory and combined responses during PTNS and to determine whether the type of response can predict treatment outcome. LUTS were also assessed using a 3-day bladder diary, patient perception of bladder condition (PPBC) questionnaire, patient perception of intensity of urgency scale (PPIUS), Kings Health QOL questionnaire (KHQ) and Overactive Bladder Questionnaire (OAB-q) before and after treatment. Patients were considered as "responders" if they reported an improvement >50% in their LUTS according to the PPBC. Sensory, motor and combined sensory/motor responses were compared between responders and non-responders. Eighty-three patients were included. 61% (51/83) of patients were responders. Sensory, motor and combined sensory/motor responses were found in 64% (53/83), 6% (5/83) and 30% (25/83) of patients respectively. A sensory response alone, or in combination with a motor response, was better associated with a successful outcome than the presence of a motor response alone (P = 0.001). A sensory response, either alone or in combination with a motor response, is more frequent and seems to be better associated with a successful outcome of PTNS than motor response alone. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  6. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

    Science.gov (United States)

    Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

    2017-09-01

    Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. TLD-300 detectors for separate measurement of total and gamma absorbed dose distributions of single, multiple, and moving-field neutron treatments

    International Nuclear Information System (INIS)

    Rassow, J.

    1984-01-01

    Fast neutron therapy requirements, because of the poor depth dose characteristic of present therapeutical sources, are at least as complex in treatment plans as photon therapy. The physical part of the treatment planning is very important; however, it is much more complicated than for photons or electrons owing to the need for: Separation of total and gamma absorbed dose distributions (Dsub(T) and Dsub(G)); and more stringent tissue-equivalence conditions of phantoms than in photon therapy. Therefore, methods of clinical dosimetry for the separate determination of total and gamma absorbed dose distributions in irregularly shaped (inhomogeneous) phantoms are needed. A method using TLD-300 (CaF 2 :Tm) detectors is described, which is able to give an approximate solution of the above-mentioned dosimetric requirements. The two independent doses, Dsub(T) and Dsub(G), can be calculated by an on-line computer analysis of the digitalized glow curve of TLD-300 detectors, irradiated with d(14)+Be neutrons of the cyclotron isocentric neutron therapy facility CIRCE in Essen. Results are presented for depth and lateral absorbed dose distributions (Dsub(T) and Dsub(G)) for fixed neutron beams of different field sizes compared with measurements by standard procedures (TE-TE ionization chamber, GM counter) in an A-150 phantom. The TLD-300 results for multiple and moving-field treatments (with and without wedge filters) in a patient simulating irregularly shaped (inhomogeneous) phantoms, are shown together with computer calculations of these dose distributions. The probable causes for some systematic deviations are discussed, which lead to open problems for further investigations owing to features of the detector material and the evaluation method, but mainly to differences in the composition of phantom materials used for the calculations (standard dose distributions) and TLD-300 measurements. (author)

  8. A randomized, non-inferiority study comparing efficacy and safety of a single dose of pegfilgrastim versus daily filgrastim in pediatric patients after autologous peripheral blood stem cell transplant.

    Directory of Open Access Journals (Sweden)

    Simone Cesaro

    Full Text Available PURPOSE: To assess the non-inferiority of pegfilgrastim versus filgrastim in speeding the recovery of polymorphonuclear cells (PMN in pediatric patients who underwent autologous peripheral blood stem cell transplant (PBSCT. METHODS: The sample size of this randomized, multicenter, phase III study, was calculated assuming that a single dose of pegfilgrastim of 100 ug/kg was not inferior to 9 doses of filgrastim of 5 ug/kg/day. Randomization was performed by a computer-generated list and stored by sequentially numbered sealed envelopes. RESULTS: Sixty-one patients, with a median age of 11.5 years, were recruited: 29 in the filgrastim arm and 32 in the pegfilgrastim arm. Twenty percent were affected by lymphoma/leukaemia and eighty percent by solid tumors. The mean time to PMN engraftment was 10.48 days (standard deviation [SD] 1.57 and 10.44 days (SD 2.44 in the filgrastim and pegfilgrastim arms, respectively. Having fixed a non-inferiority margin Delta of 3, the primary endpoint of non-inferiority was reached. No differences were observed for other secondary endpoints: platelet engraftment, mean time to platelet recovery (28 days vs. 33 days, fever of unknown origin (79% vs. 78%, proven infection (34% vs. 28%, mucositis (76% vs. 59%. After a median follow-up of 2.3 years (95% C.I.: 1.5, 3.3, 20 deaths were observed due to disease progression. CONCLUSIONS: We conclude that pegfilgrastim was not inferior to daily filgrastim in pediatric patients who underwent PBSCT. EU CLINICAL TRIAL REGISTER NUMBER: 2007-001430-14.

  9. Dose evaluation using multiple-aliquot quartz OSL: Test of methods and a new protocol for improved accuracy and precision

    DEFF Research Database (Denmark)

    Jain, M.; Bøtter-Jensen, L.; Singhvi, A.K.

    2003-01-01

    -dose-dependent sensitivity changes during the pre-heat, and fundamental variability in the shapes of quartz OSL (blue-green or blue-light stimulated luminescence) decay forms. A new protocol using a combination of 'elevated temperature IR cleaning' (ETIR) and 'component-specific dose normalisation' (CSDN) has been developed....... CSDN accounts for variability in the OSL decay forms and absorbs such sensitivity changes. A combination of ETIR and CSDN protocol increased palaeodose precision from +/-100% to +/-4% in quartz separates from the fluvially transported sands in the Thar desert. A comparison with palaeodose estimates...

  10. Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

    Science.gov (United States)

    Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

    2016-12-01

    While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in

  11. Optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system

    International Nuclear Information System (INIS)

    Shen, L.; Levine, S.H.; Catchen, G.L.

    1987-01-01

    This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration

  12. A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor.

    Science.gov (United States)

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Sonnichsen, Daryl

    2012-07-01

    Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects. A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7. No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea. Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing.

  13. Evaluation of the effect of multiple doses of lansoprazole on the pharmacokinetics and safety of ponatinib in healthy subjects.

    Science.gov (United States)

    Narasimhan, Narayana I; Dorer, David J; Davis, Jeffrey; Turner, Christopher D; Sonnichsen, Daryl

    2014-10-01

    In vitro studies have demonstrated that the aqueous solubility of the tyrosine kinase inhibitor ponatinib decreases as pH increases. The primary aim of this study was to assess the effects of the gastric proton pump inhibitor lansoprazole on the pharmacokinetics of ponatinib. The single-dose safety profile of ponatinib with and without coadministration of lansoprazole was also characterized. This was a phase I, open-label, non-randomized, two-period crossover study in 20 healthy subjects aged 18-55 years. Subjects received a single oral dose of ponatinib 45 mg alone on day 1, an oral dose of lansoprazole 60 mg on day 14, and ponatinib 45 mg plus lansoprazole 60 mg on day 15. Lansoprazole coadministration resulted in a 1-h increase in the time to maximum plasma concentration (t max) of ponatinib (6 vs. 5 h post-dose; P lansoprazole versus ponatinib alone (40.67 vs. 53.96 ng/mL). Importantly, lansoprazole did not decrease the overall ponatinib systemic exposure as assessed by the ponatinib area under the plasma concentration-time curve from time zero to infinity (AUC∞ 1,153 ng·h/mL for lansoprazole + ponatinib vs. 1,222 ng·h/mL for ponatinib alone). The safety profile was considered acceptable when ponatinib was administered alone or with lansoprazole. Although coadministration of lansoprazole led to a modest, albeit statistically significant, reduction in ponatinib C max, overall systemic exposure to ponatinib did not change. The findings suggest that no dose adjustment is necessary when ponatinib is administered with drugs that increase gastric pH.

  14. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a combin......-mg doses of oral ketorolac are as effective as Ketogan for the treatment of pain following orthopaedic surgery. Ketorolac appears to be better tolerated than Ketogan since significantly fewer patients reported adverse events (P = 0.004) when taking ketorolac.......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...... combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...

  15. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  16. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S

    2014-01-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment

  17. Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience.

    Science.gov (United States)

    Cerchione, Claudio; Nappi, Davide; Pareto, Anna E; Romano, Alessandra; Martinelli, Vincenzo; Picardi, Marco; Pane, Fabrizio; Catalano, Lucio

    2018-04-01

    Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.

  18. Utility of the sore throat pain model in a multiple-dose assessment of the acute analgesic flurbiprofen: a randomized controlled study.

    Science.gov (United States)

    Schachtel, Bernard; Aspley, Sue; Shephard, Adrian; Shea, Timothy; Smith, Gary; Schachtel, Emily

    2014-07-03

    The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Adults (n=198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n=101) or matching placebo lozenges (n=97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (Pflurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all Pflurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010.

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

    International Nuclear Information System (INIS)

    Wu, Q; Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N

    2015-01-01

    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

  20. 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.

  1. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    Science.gov (United States)

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

  2. ß-cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice

    DEFF Research Database (Denmark)

    Börjesson, A; Rønn, S G; Karlsen, A E

    2011-01-01

    We investigated the impact of ß-cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic......RNA in islet cells and secretion of IL-1Ra into culture medium. MLDSTZ treatment caused gradual hyperglycemia both in the wt mice and in the transgenic mice with the latter tending to be more sensitive. In vitro experiments on wt and transgenic islets did not reveal any differences in sensitivity to damaging...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Background: Infections are life-threatening complications in patients undergoing high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious pathogens is essential to make a safe outpatient setting. Methods: We conducted a retrospective study of 208 patients treated with HDT...... related mortality was similar between the groups. Conclusion: The frequency of isolated pathogens, positive blood cultures, and the diversity of pathogens were higher in MM patients as compared to NHL patients. However, this did not translate into higher transplantation-related mortality, probably because....... The population included non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received prophylactic antibacterial treatment. Results: Pathogens were isolated from 44% of all patients. MM patients more frequently had multiple pathogens in blood cultures (38% versus 25%). Transplantation...

  4. A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults.

    Science.gov (United States)

    Paniz, Clovis; Bertinato, Juliano Felix; Lucena, Maylla Rodrigues; De Carli, Eduardo; Amorim, Patrícia Mendonça da Silva; Gomes, Guilherme Wataru; Palchetti, Cecília Zanin; Figueiredo, Maria Stella; Pfeiffer, Christine M; Fazili, Zia; Green, Ralph; Guerra-Shinohara, Elvira Maria

    2017-09-01

    Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown. Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase ( DHFR ), methylenetetrahydrofolate reductase ( MTHFR ), interferon γ ( IFNG ), tumor necrosis factor α ( TNFA ), and interleukin 8 ( IL8 ) genes; and concentrations of serum inflammatory markers. Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m 2 ) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells. Results: Serum folate concentrations increased by ∼5-fold after the intervention ( P 1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number ( P < 0.001) and cytotoxicity ( P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d ( P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d ( P = 0.001 for both). Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp. © 2017 American Society for Nutrition.

  5. Dose-Dependent Effects of Multiple Acute Cocaine Injections on Maternal Behavior and Aggression in Sprague-Dawley Rats

    OpenAIRE

    Johns, Josephine M.; Nelson, Christina J.; Meter, Kathleen E.; Lubin, Deborah A.; Couch, C. Destine; Ayers, Andy; Walker, Cheryl H.

    1998-01-01

    Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3), postpartum day 6 (PPD 6) and postpartum day 10 (PPD 10). Dams were observed 30 min following injections for maternal behavior (MB) towar...

  6. Mammalian Toxicity of Munition Compounds. Phase II. Effects of Multiple Doses. Part III. 2,6-Dinitrotoluene

    Science.gov (United States)

    1976-07-01

    and the neuromuscular effects in these dogs were not due to hypocalcemia . The lowest serum calcium concen- tration in these dogs was 4.2 meq/liter...motor end plate might produce a local hypocalcemia . Such a mechanism is purely speculative. Qualitatively and quantitavely, most of the effects of 2,6...I ýNw,- -MIM I/ MIDWEST RESEARCH INS14ITUTE H0q .3L I LU -_ MAMMALIAN TOXICITY OF MUNITIONS COMPOUlNDSPHASE II: EFFECTS OF MiULTIPLE DOSES C* •PART

  7. The impact of extended release exenatide as adjuvant therapy on hemoglobin A1C, weight, and total daily dose of insulin in patients with type 2 diabetes mellitus using U-500 insulin.

    Science.gov (United States)

    Farwig, Phillip A; Zielinski, Angela J; Accursi, Mallory L; Burant, Christopher J

    2017-12-01

    To evaluate the efficacy and safety of adjuvant exenatide extended release (ER) therapy in patients treated with regular U-500 insulin. In this retrospective chart review at an ambulatory care center in the Midwest, 18 patients with type 2 diabetes being treated with regular U-500 insulin and adjuvant exenatide ER were identified. These patients were evaluated for outcomes following the addition of exenatide ER. The primary outcome was change in HbA 1C from baseline to 3, 6, and 12months. Secondary outcomes included change in weight, total daily dose (TDD) of insulin, and hypoglycemia. Repeated measures ANOVA was performed to assess the differences in mean scores over four time periods. A total of 18 of 50 patients met inclusion criteria with sufficient data to be included in analysis. HbA 1C showed non-significant findings from baseline to 12months (8.08% vs. 8.23%; p=0.75). A non-significant, modest weight loss occurred (146.4kgvs. 144.2kg; -2.2kg; p=0.31). A significant decrease in TDD of insulin was observed (378 units vs. 326 units; p1). There was a trend towards hypoglycemia from baseline to month 3 post addition of exenatide ER (0.33 events vs. 1.33 events; p=0.055). In patients treated with regular U-500 insulin, adjuvant exenatide ER therapy showed no significant improvement in HbA 1C , but did show modest weight loss as well as decreased insulin requirements to achieve a HbA 1C that was comparable to baseline. Published by Elsevier B.V.

  8. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.

    Science.gov (United States)

    Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin

    2011-05-01

    Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.

  9. Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2017-01-01

    The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

  10. Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Overgaard, Jens; Alsner, Jan

    2005-01-01

    cell lines after various ionizing radiation (IR) schemes in order to provide information on potential targets for prevention and to suggest candidate genes for SNP association studies aimed at predicting individual risk of radiation-induced morbidity. PATIENTS AND METHODS: Thirty different human......BACKGROUND AND PURPOSE: Transcriptional profiling of fibroblasts derived from breast cancer patients might improve our understanding of subcutaneous radiation-induced fibrosis. The aim of this study was to get a comprehensive overview of the changes in gene expression in subcutaneous fibroblast...... fibroblast cell lines were included in the study, and two different radiation schemes; single dose experiments with 3.5 Gy or fractionated with 3 x 3.5 Gy. Expression analyses were performed on unexposed and exposed cells after different time points. The IR response was analyzed using the statistical method...

  11. Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

    Science.gov (United States)

    Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

    2017-04-01

    A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

  12. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

    Science.gov (United States)

    Christensen, Steven; Paluch, Ed; Jayawardena, Shyamalie; Daniels, Stephen; Meeves, Suzanne

    2017-05-01

    Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P ibuprofen IR/ER, respectively (P ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses. © 2016, The American College of Clinical Pharmacology.

  13. Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

    Science.gov (United States)

    Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

    2005-07-01

    We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

  14. Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides

    International Nuclear Information System (INIS)

    Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

    2005-01-01

    We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (μg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r = 0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r = 0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA

  15. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial.

    Science.gov (United States)

    Younes, Anas; Berdeja, Jesus G; Patel, Manish R; Flinn, Ian; Gerecitano, John F; Neelapu, Sattva S; Kelly, Kevin R; Copeland, Amanda R; Akins, Amy; Clancy, Myles S; Gong, Lucy; Wang, Jing; Ma, Anna; Viner, Jaye L; Oki, Yasuhiro

    2016-05-01

    Treatment options for patients with relapsed or refractory lymphoma and multiple myeloma are limited. CUDC-907 is an oral, first-in-class, small molecule that is designed to inhibit both histone deacetylase (HDAC) and PI3K enzymes, which are members of common oncogenic pathways in haematological malignancies. We aimed to assess overall safety and preliminary activity in this dose-escalation study of CUDC-907 monotherapy in patients with relapsed or refractory lymphoma and multiple myeloma. This open-label, first-in-man, phase 1 trial recruited adult patients (aged ≥18 years) with lymphoma or multiple myeloma who were refractory to or had relapsed after two or more previous regimens, from four US cancer centres. CUDC-907 was orally administered in a standard 3 + 3 dose-escalation design at four different dosing schedules, to which participants were sequentially assigned as follows: once daily, intermittently (twice or three times weekly; simultaneous enrolment), and daily for 5 days followed by a 2-day break (5/2), in 21-day cycles. Dosing started at 30 mg for the once-daily schedule and 60 mg for other schedules, escalating in 30 mg increments. Patients continued to receive CUDC-907 until disease progression or until other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose, assessed in patients who received at least 66% of cycle 1 doses without modification and those who had a dose-limiting toxicity (DLT) in cycle 1 irrespective of dose modification. We assessed safety in all patients who received at least one dose of study drug. This ongoing trial is registered at ClinicalTrials.gov, number NCT01742988. Between Jan 23, 2013, and July 27, 2015, we enrolled 44 patients, of whom ten were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to three-times-weekly (MTD 150 mg), and seven to the 5/2 dosing schedule (MTD 60 mg). 37

  16. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

    Science.gov (United States)

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

    2016-12-24

    Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

  17. Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD and Multiple Approaches for Selection of Chemical Point of Departure (PoD.

    Directory of Open Access Journals (Sweden)

    A Francina Webster

    Full Text Available Many regulatory agencies are exploring ways to integrate toxicogenomic data into their chemical risk assessments. The major challenge lies in determining how to distill the complex data produced by high-content, multi-dose gene expression studies into quantitative information. It has been proposed that benchmark dose (BMD values derived from toxicogenomics data be used as point of departure (PoD values in chemical risk assessments. However, there is limited information regarding which genomics platforms are most suitable and how to select appropriate PoD values. In this study, we compared BMD values modeled from RNA sequencing-, microarray-, and qPCR-derived gene expression data from a single study, and explored multiple approaches for selecting a single PoD from these data. The strategies evaluated include several that do not require prior mechanistic knowledge of the compound for selection of the PoD, thus providing approaches for assessing data-poor chemicals. We used RNA extracted from the livers of female mice exposed to non-carcinogenic (0, 2 mg/kg/day, mkd and carcinogenic (4, 8 mkd doses of furan for 21 days. We show that transcriptional BMD values were consistent across technologies and highly predictive of the two-year cancer bioassay-based PoD. We also demonstrate that filtering data based on statistically significant changes in gene expression prior to BMD modeling creates more conservative BMD values. Taken together, this case study on mice exposed to furan demonstrates that high-content toxicogenomics studies produce robust data for BMD modelling that are minimally affected by inter-technology variability and highly predictive of cancer-based PoD doses.

  18. Development of 99mTc imaging method using multiple imaging plates for reduction of patient's dose

    International Nuclear Information System (INIS)

    Ito, Shigeki; Nishizawa, Kunihide; Ariga, Eiji; Saze, Takuya

    2008-01-01

    A system for taking static thyroid 99m Tc images was devised by using multiple imaging plates (IPs) and a low energy high resolution collimator. Sensitivity was represented by using lower detection limits (LDL). The sensitivity and resolution of IP systems using a collimator and 9 IPs were determined by using a 20 ml thyroid phantom, and compared with the sensitivity of gamma cameras. The sensitivity of the IP systems increased in proportion to the number of IPs. The sensitivity and resolution of a probe using 9 IPs and a high resolution collimator were equivalent to or superior to the gamma camera for taking static thyroid 99m Tc images. IP systems can be applied clinically as static nuclear imaging devices as same as a gamma camera. (author)

  19. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  20. Analgesic efficacy of lysine clonixinate plus tramadol versus tramadol in multiple doses following impacted third molar surgery.

    Science.gov (United States)

    Perez-Urizar, J; Martínez-Rider, R; Torres-Roque, I; Garrocho-Rangel, A; Pozos-Guillen, A

    2014-03-01

    This study compared the analgesic and anti-inflammatory efficacy, trismus control, and tolerability of the combination of lysine clonixinate and tramadol (LCT) versus tramadol (T) alone after surgical removal of impacted mandibular third molars. This study was a double-blind, randomized clinical trial, including two study groups of 20 patients each, who exhibited acute pain subsequent to surgical extraction of two mandibular third molars. Pain intensity was quantified over a 96-h period using a visual analogue scale and a 5-point verbal rating scale. Secondary indicators of analgesic and anti-inflammatory efficacy, trismus control, and tolerability were determined. Patients administered LCT exhibited better therapeutic effects that those administered T. Fifty percent of patients in the LCT group rated this therapy as 'excellent analgesia' compared with only 10% in the T group. The onset of the analgesic effect of LCT was significantly faster, without any therapeutic failures. There were no significant differences between the groups with regard to anti-inflammatory effect or trismus. The results of this study suggest that the postsurgical analgesic efficacy of LCT in combination (LC 125 mg + T 25 mg) is superior to that obtained with T alone, administered at the standard dose of 50 mg, for up to 96 h after the extraction of both impacted mandibular third molars. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  1. Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

    International Nuclear Information System (INIS)

    Breeman, Wout A. P.; Jong, Marion de; Bernard, Bert F.; Bakker, Willem H.; Rolleman, Edgar J.; Kwekkeboom, Kik J.; Visser, Theo J.; Krenning, Eric P.

    1997-01-01

    In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin[reg]) is usually discontinued 24-48 h before and after injection with the radioligand 111 In-pentetreotide ([ 111 In-DTPA o ]octreotide) (Octreoscan[reg]) because octreotide competes with radioligand for the same receptors. However, Doerr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 μg) of 111 In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111 In-pentetreotide. Administration of 100 μg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111 In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration

  2. Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

    Directory of Open Access Journals (Sweden)

    Seyed Amir Dadkhahi

    2017-05-01

    Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

  3. Sustainability Instruction in High Doses: Results From Incorporation of Multiple InTeGrate Modules Into an Environmental Science Class

    Science.gov (United States)

    Rademacher, L. K.

    2017-12-01

    The Interdisciplinary Teaching about Earth for a Sustainable Future (InTeGrate) community has developed extensive courses and modules designed for broad adoption into geoscience classrooms in diverse environments. I participated in a three-semester research project designed to test the efficacy of incorporating "high doses" (minimum 3 modules or 18 class periods) of InTeGrate materials into a course, in my case, an introductory environmental science class. InTeGrate materials were developed by groups of instructors from a range of institutions across the US. These materials include an emphasis on systems thinking, interdisciplinary approaches, and sustainability, and those themes are woven throughout the modules. The three semesters included a control in which no InTeGrate materials were used, a pilot in which InTeGrate materials were tested, and a treatment semesters in which tested materials were modified as needed and fully implemented into the course. Data were collected each semester on student attitudes using the InTeGrate Attitudinal Instrument (pre and post), a subset of Geoscience Literacy Exam questions (pre and post), and a series of assessments and essay exam questions (post only). Although results suggest that learning gains were mixed, changes in attitudes pre- and post-instruction were substantial. Changes in attitudes regarding the importance of sustainable employers, the frequency of self-reported individual sustainable actions, and motivation level for creating a sustainable society were observed in the control and treatment semesters, with the treatment semester showing the greatest gains. Importantly, one of the biggest differences between the control and treatment semesters is the reported impact that the course had on influencing students' sustainable behaviors. The treatment semester course impacted students' sustainable behaviors far more than the control semester.

  4. Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.

    Science.gov (United States)

    Van Sanden, Suzy; Ito, Tetsuro; Diels, Joris; Vogel, Martin; Belch, Andrew; Oriol, Albert

    2018-03-01

    Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations. The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies. The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; p  = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p  < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; p  = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p  = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%). The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma. This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these

  5. Palliative radiation therapy for multiple myeloma

    International Nuclear Information System (INIS)

    Minowa, Yasushi; Sasai, Keisuke; Ishigaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

    1996-01-01

    Radiation therapy is a useful palliative modality for refractory lesions of multiple myeloma. It has been reported that total doses of 10 to 20 Gy are usually adequate to obtain some degree of pain relief. However, there are many patients who need additional doses to obtain sufficient pain relief. In this study. we retrospectively analyzed the records of patients with multiple myeloma irradiated at our department, in an attempt to develop an effective treatment policy for this disease. Twenty-nine patients with 53 lesions were treated between 1968 and 1993. Total irradiation