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Sample records for administered high doses

  1. Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements.

    PubMed

    Heying, Emily K; Hovel, Elizabeth; Tanumihardjo, Sherry A

    2015-10-01

    A proposed intervention for newborn infants in countries with suspected vitamin A (VA) deficiency is to administer 50,000 IU retinyl palmitate at birth to reduce mortality risk. However, no studies have investigated birth weight effects. In this study, low birth weight (LBW; <1 kg, n = 18) and healthy birth weight (HBW) piglets (>1.5 kg, n = 18) from VA-depleted sows were dosed with 25,000 or 50,000 IU retinyl palmitate (26.2 or 52.4 µmol retinol equivalents) at birth to compare VA reserves. Blood was collected at varying times (n = 3-5/time/dose), and piglets were killed at 12 or 24 h for blood, liver, kidneys, spleen, lungs, adrenal gland, and intestinal contents. HBW piglets had significantly higher birth, death, and organ weights than LBW (P < 0.0001 for all). HBW and LBW piglets, which received VA, had higher liver and kidney VA concentrations (0.18 ± 0.09, 0.24 ± 0.10 µmol/g liver and 13.4 ± 4.1, 14.2 ± 4.5 nmol/g kidney, respectively) than controls (n = 10) (0.051 ± 0.01 µmol/g liver and 1.01 ± 0.43 nmol/g kidney) (P = 0.0061 and < 0.0001, respectively). Total liver (9.75 ± 5.16 µmol) and kidney retinol (204 ± 79.1 nmol) were higher in HBW than LBW piglets (P < 0.0001). Extrahepatic tissues, except lung, had higher VA concentration than controls (P < 0.0001). Serum retinol and ester concentrations were higher in treated than control piglets (P = 0.0028, P < 0.0001, respectively), and significantly changed during the times sampled (P = 0.022, P = 0.011, respectively). Peak serum retinyl ester concentrations, which occurred at 3 h, were higher in piglets that received 50,000 IU (4.2 ± 4.4 µmol/L) than 25,000 IU (2.7 ± 2.3 µmol/L) (P = 0.031). Regardless of dose amount, HBW piglets stored more supplemental VA than LBW piglets when administered at birth. PMID:25681469

  2. Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements

    PubMed Central

    Heying, Emily K; Hovel, Elizabeth

    2015-01-01

    A proposed intervention for newborn infants in countries with suspected vitamin A (VA) deficiency is to administer 50,000 IU retinyl palmitate at birth to reduce mortality risk. However, no studies have investigated birth weight effects. In this study, low birth weight (LBW; <1 kg, n = 18) and healthy birth weight (HBW) piglets (>1.5 kg, n = 18) from VA-depleted sows were dosed with 25,000 or 50,000 IU retinyl palmitate (26.2 or 52.4 µmol retinol equivalents) at birth to compare VA reserves. Blood was collected at varying times (n = 3–5/time/dose), and piglets were killed at 12 or 24 h for blood, liver, kidneys, spleen, lungs, adrenal gland, and intestinal contents. HBW piglets had significantly higher birth, death, and organ weights than LBW (P < 0.0001 for all). HBW and LBW piglets, which received VA, had higher liver and kidney VA concentrations (0.18 ± 0.09, 0.24 ± 0.10 µmol/g liver and 13.4 ± 4.1, 14.2 ± 4.5 nmol/g kidney, respectively) than controls (n = 10) (0.051 ± 0.01 µmol/g liver and 1.01 ± 0.43 nmol/g kidney) (P = 0.0061 and < 0.0001, respectively). Total liver (9.75 ± 5.16 µmol) and kidney retinol (204 ± 79.1 nmol) were higher in HBW than LBW piglets (P < 0.0001). Extrahepatic tissues, except lung, had higher VA concentration than controls (P < 0.0001). Serum retinol and ester concentrations were higher in treated than control piglets (P = 0.0028, P < 0.0001, respectively), and significantly changed during the times sampled (P = 0.022, P = 0.011, respectively). Peak serum retinyl ester concentrations, which occurred at 3 h, were higher in piglets that received 50,000 IU (4.2 ± 4.4 µmol/L) than 25,000 IU (2.7 ± 2.3 µmol/L) (P = 0.031). Regardless of dose amount, HBW piglets stored more supplemental VA than LBW piglets when administered at birth. PMID:25681469

  3. Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial.

    PubMed

    Pizzuti, Laura; Barba, Maddalena; Giannarelli, Diana; Sergi, Domenico; Botti, Claudio; Marchetti, Paolo; Anzà, Michele; Maugeri-Saccà, Marcello; Natoli, Clara; Di Filippo, Simona; Catenaro, Teresa; Tomao, Federica; Amodio, Antonella; Carpano, Silvia; Perracchio, Letizia; Mottolese, Marcella; Di Lauro, Luigi; Sanguineti, Giuseppe; Di Benedetto, Anna; Giordano, Antonio; Vici, Patrizia

    2016-11-01

    To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  4. Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial.

    PubMed

    Pizzuti, Laura; Barba, Maddalena; Giannarelli, Diana; Sergi, Domenico; Botti, Claudio; Marchetti, Paolo; Anzà, Michele; Maugeri-Saccà, Marcello; Natoli, Clara; Di Filippo, Simona; Catenaro, Teresa; Tomao, Federica; Amodio, Antonella; Carpano, Silvia; Perracchio, Letizia; Mottolese, Marcella; Di Lauro, Luigi; Sanguineti, Giuseppe; Di Benedetto, Anna; Giordano, Antonio; Vici, Patrizia

    2016-11-01

    To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27187274

  5. The effect of a single high dose of PGF2α administered to dairy cattle 3.5 days after ovulation on luteal function, morphology, and follicular dynamics.

    PubMed

    Cuervo-Arango, J; García-Roselló, E; García-Muñoz, A; Valldecabres-Torres, X; Martínez-Ros, P; González-Bulnes, A

    2011-12-01

    A single treatment with PGF2α is assumed to have no luteolytic effect on cows with corpora lutea < 5 days old. The objective of this study was to determine the effect of a single high dose of PGF2α administered to dairy cattle on the morphology and function of the early CL. The study followed a crossover design with a treatment cycle in which 50 mg of dinoprost were administered 3.5 days postovulation and a control untreated cycle. Ultrasound examination and blood samples were performed during the two consecutive cycles. Corpus luteum (CL) diameter, progesterone concentration, and follicular dynamics characteristics were compared between control and treated cycles. Two of nine cows (22%) developed full luteolysis. The remaining seven cows (78%) had partial luteolysis with a decrease (P < 0.05) in progesterone concentration and CL diameter for two and 12 days post-treatment, respectively. The interovulatory interval of treated cycles (19.7 ± 2.4 days) was not different (P > 0.05) from that of controls (23.8 ± 0.9 days). The transient reduction in progesterone of cows with partial luteolysis had no effect on the proportion of cows with two or three follicular waves, follicle growth rate, or preovulatory diameter (P > 0.05). Two cows developed ovarian cystic degeneration during the PGF2α-induced cycle. In conclusion, the treatment of cows with a high dose of PGF2α 3.5 days postovulation induced some degree of luteolysis in all treated cows. This resulted in partial luteolysis in 78% of treated animals and in full luteolysis in the remaining 22%.

  6. Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife

    PubMed Central

    Fukuda, Shoichi; Seo, Yuji; Shiomi, Hiroya; Yamada, Yuji; Ogata, Toshiyuki; Morimoto, Masahiro; Konishi, Koji; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2014-01-01

    The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm3 for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm3 (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted. PMID:24957754

  7. Blood methanol concentrations in one-year-old infants administered graded doses of aspartame.

    PubMed

    Stegink, L D; Brummel, M C; Filer, L J; Baker, G L

    1983-08-01

    Blood methanol concentrations were measured in 24 1-year-old infants administered aspartame, a dipeptide methyl ester sweetener. The doses studied included a dose projected to be the 99th percentile of daily ingestion for adults (34 mg/kg body weight), a very high use dose (50 mg/kg body weight) and a dose considered to be in the abuse range (100 mg/kg body weight). Blood methanol values in infants were compared to values observed previously in adults administered equivalent doses of aspartame. Methanol concentrations were below the level of detection (0.35 mg/dl) in the blood of 10 infants administered aspartame at 34 mg/kg body weight, but were significantly elevated (P less than or equal to 0.05) after ingestion of aspartame at 50 and 100 mg/kg body weight. At the latter doses, mean peak blood methanol concentrations and the area under the blood methanol concentration-time curve increased in proportion to dose. Mean (+/- SEM) peak blood methanol concentration was 0.30 +/- 0.10 mg/100 ml at a 50 mg/kg body weight aspartame dose (n = 6) and 1.02 +/- 0.28 mg/ml at the 100 mg/kg body weight dose (n = 8). Blood methanol values in infants were similar to those observed in normal adults.

  8. Does administering iodine in radiological procedures increase patient doses?

    SciTech Connect

    He, Wenjun; Yao, Hai; Huda, Walter; Mah, Eugene

    2014-11-01

    Purpose: The authors investigated the changes in the pattern of energy deposition in tissue equivalent phantoms following the introduction of iodinated contrast media. Methods: The phantom consisted of a small “contrast sphere,” filled with water or iodinated contrast, located at the center of a 28 cm diameter water sphere. Monte Carlo simulations were performed using MCNP5 codes, validated by simulating irradiations with analytical solutions. Monoenergetic x-rays ranging from 35 to 150 keV were used to simulate exposures to spheres containing contrast agent with iodine concentrations ranging from 1 to 100 mg/ml. Relative values of energy imparted to the contrast sphere, as well as to the whole phantom, were calculated. Changes in patterns of energy deposition around the contrast sphere were also investigated. Results: Small contrast spheres can increase local absorbed dose by a factor of 13, but the corresponding increase in total energy absorbed was negligible (<1%). The highest localized dose increases were found to occur at incident photon energies of about 60 keV. For a concentration of about 10 mg/ml, typical of clinical practice, localized absorbed doses were generally increased by about a factor of two. At this concentration of 10 mg/ml, the maximum increase in total energy deposition in the phantom was only 6%. These simulations demonstrated that increases in contrast sphere doses were offset by corresponding dose reductions at distal and posterior locations. Conclusions: Adding iodine can result in values of localized absorbed dose increasing by more than an order of magnitude, but the total energy deposition is generally very modest (i.e., <10%). Their data show that adding iodine primarily changes the pattern of energy deposition in the irradiated region, rather than increasing patient doses per se.

  9. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    PubMed

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions. PMID:26056878

  10. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    PubMed

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

  11. Brain-Cocaine Concentrations Determine the Dose Self-Administered by Rats on a Novel Behaviorally Dependent Dosing Schedule

    PubMed Central

    Zimmer, Benjamin A; Dobrin, Carson V; Roberts, David C S

    2011-01-01

    A novel behaviorally dependent dosing (BDD) schedule was used to examine the relationship between doses of cocaine self-administered by rats and brain drug levels within a session. The BDD schedule used a hold-down response to activate a syringe pump. The length of time the lever was held down determined the duration that the syringe pump was activated. In the first experiment, rats self-administered cocaine for daily 3 h sessions and brain levels of cocaine were modeled using well-established parameters. Although analysis revealed that rats self-administered doses within a predicted range, one extremely large dose was consistently observed at the beginning of each session when brain levels of cocaine were low. In the second experiment, we introduced a range of timeout periods (10–25 min) in order to produce variability in brain-cocaine concentrations. Animals self-administered larger doses immediately following each timeout period and the dose size was inversely correlated with the length of the timeout. These results show that the dose of cocaine that rats self-administer within a session is inversely related to the amount of drug on board. PMID:21849981

  12. Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

    SciTech Connect

    Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-10-01

    Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethal dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the systemic

  13. Semi-micro column high-performance liquid chromatography with UV detection for quantification of aspirin and salicylic acid and its application to patients' sera administered with low-dose enteric-coated aspirin.

    PubMed

    Ohwaki, Yuichi; Yamane, Tomoko; Ishimatsu, Takashi; Wada, Mitsuhiro; Nakashima, Kenichiro

    2007-03-01

    A simultaneous determination of aspirin (ASA) and its metabolite, salicylic acid (SA), in human serum by a semi-micro column HPLC-UV was developed. A relatively small size of serum sample (100 microL) containing ASA and SA was cleaned up by a simple solid phase extraction. A good separation of ASA and SA could be achieved within 25 min using a semi-micro ODS column with an eluent of MeOH/0.7 mm phosphoric acid solution (pH 2.5) = 50:50 (v/v). The calibration curves for ASA and SA showed good linearity (r = 0.999) with the detection limits 114 and 38 ng/mL at a signal-to-noise ratio of 3, respectively. ASA and SA in patients' sera administered with low-dose enteric-coated aspirin were determined, and the concentration ranges obtained for ASA and SA were 1.2-2.2 and 0.5-57.3 microg/mL, respectively. PMID:17221906

  14. Semi-micro column high-performance liquid chromatography with UV detection for quantification of aspirin and salicylic acid and its application to patients' sera administered with low-dose enteric-coated aspirin.

    PubMed

    Ohwaki, Yuichi; Yamane, Tomoko; Ishimatsu, Takashi; Wada, Mitsuhiro; Nakashima, Kenichiro

    2007-03-01

    A simultaneous determination of aspirin (ASA) and its metabolite, salicylic acid (SA), in human serum by a semi-micro column HPLC-UV was developed. A relatively small size of serum sample (100 microL) containing ASA and SA was cleaned up by a simple solid phase extraction. A good separation of ASA and SA could be achieved within 25 min using a semi-micro ODS column with an eluent of MeOH/0.7 mm phosphoric acid solution (pH 2.5) = 50:50 (v/v). The calibration curves for ASA and SA showed good linearity (r = 0.999) with the detection limits 114 and 38 ng/mL at a signal-to-noise ratio of 3, respectively. ASA and SA in patients' sera administered with low-dose enteric-coated aspirin were determined, and the concentration ranges obtained for ASA and SA were 1.2-2.2 and 0.5-57.3 microg/mL, respectively.

  15. Dose and elasticity of demand for self-administered cocaine in rats.

    PubMed

    Kearns, David N; Silberberg, Alan

    2016-04-01

    The present experiment tested whether the elasticity of demand for self-administered cocaine in rats is dose-dependent. Subjects lever pressed for three different doses of intravenous cocaine - 0.11, 0.33, and 1.0 mg/kg/infusion - on a demand procedure where the number of lever presses required per infusion increased within a session. The main finding was that demand for the 0.11 mg/kg dose was more elastic than it was for the two larger doses. There was no difference in demand elasticity between the 0.33 and 1.0 mg/kg doses. These results parallel findings previously reported in monkeys. The present study also demonstrated that a within-session procedure can be used to generate reliable demand curves. PMID:26866971

  16. Justification of administered dose level in brain perfusion imaging with 99mTc-HMPAO

    NASA Astrophysics Data System (ADS)

    Stefanoyiannis, A. P.; Gerogiannis, I.; Geronikola-Trapali, X.; Armeniakos, I.; Prentakis, A.; Soultanis, S.; Chatziioannou, S. N.

    2011-09-01

    Brain perfusion imaging by means of 99mTc-HMPAO is widely used in the diagnosis of Alzheimer's disease. The administered dose range recommended by the manufacturer and reported in bibliography is rather wide (~ 9.5 - 27 mCi), necessitating further quantitative analysis. In the framework of this study, a quantitative evaluation of the radiopharmaceutical performance for different values of administered dose was carried out, based on image quality indicators. Evaluation of image quality was based on wavelet-generated contrast, noise, and contrast-to-noise ratio indicators, denoted as CI, NI and CNR respectively. Subsequently, a generic image quality index was correlated with the administered dose, to produce an overall performance indicator (denoted as PI). Application of appropriate statistical tests (analysis of variance for normal and Kruskal-Wallis test for non-normal distributions) showed that there is a statistically significant difference in CI (p < 0.01), NI (p < 0.001) and CNR (p < 0.05), but not in PI (p > 0.05) values. Application of Tukey test for CI and NI normal distributions demonstrated that CI (10 mCi) = CI (20 mCi) < CI (15 mCi) and NI (10 mCi) > NI (20 mCi), while NI (15 mCi) could not be characterised. Finally, application of non-parametric multiple comparisons showed that CNR (20 mCi) < CNR (10 mCi), while CNR (15 mCi) could not be characterised. Consequently, brain perfusion imaging, by means of 99mTc-HMPAO utilising an administered dose of 20 mCi, results in improved image quality on the basis of the estimated indicators. Additionally, this image quality improvement is sufficient to justify the increased patient radiation burden.

  17. Plasma and erythrocyte concentrations of free amino acids in adult humans administered abuse doses of aspartame.

    PubMed

    Stegink, L D; Filer, L J; Baker, G L

    1981-02-01

    Plasma and erythrocyte concentrations of amino acids were measured in 18 fasting adult subjects (9 male, 9 female) administered abuse doses of aspartame (100, 150, and 200 mg/kg body weight) dissolved in 500 ml orange juice. Six subjects were studied at each dose. Plasma aspartate concentrations increased significantly (p less than or equal to 0.05) over baseline values after ingestion of each dose. However, the increase was small in each case, and maximal levels observed were below those noted postprandially in formula-fed infants. No significant changes (p greater than 0.05) were noted in erythrocyte glutamate, or erythrocyte aspartate concentrations after any dose. Plasma phenylalanine concentrations increased significantly over fasting concentrations (p less than 0.01) from 15 min to 6 h after each dose, and the increase was proportional to dose. Mean (+/- SD) peak plasma phenylalanine concentrations were 20.3 +/- 2.03, 35.1 +/- 11.3, and 48.7 +/- 15.5 mumol/dl, respectively, after aspartame doses of 100, 150, and 200 mg/kg. Erythrocyte phenylalanine concentrations showed similar changes. Although these phenylalanine concentrations are considerably above the normal postprandial range (12 +/- 3 mumol/dl), they are below values associated with toxic findings. These data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame.

  18. Dose Ranging, Expanded Acute Toxicity and Safety Pharmacology Studies for Intravenously Administered Functionalized Graphene Nanoparticle Formulations

    PubMed Central

    Kanakia, Shruti; Toussaint, Jimmy; Chowdhury, Sayan Mullick; Tembulkar, Tanuf; Lee, Stephen; Jiang, Ya-Ping; Lin, Richard Z.; Shroyer, Kenneth R.; Moore, William; Sitharaman, Balaji

    2014-01-01

    Graphene nanoparticles dispersions show immense potential as multifunctional agents for in vivo biomedical applications. Herein, we follow regulatory guidelines for pharmaceuticals that recommend safety pharmacology assessment at least 10 – 100 times higher than the projected therapeutic dose, and present comprehensive single dose response, expanded acute toxicology, toxicokinetics, and respiratory/cardiovascular safety pharmacology results for intravenously administered dextran-coated graphene oxide nanoplatelet (GNP-Dex) formulations to rats at doses between 1–500 mg/kg. Our results indicate that the maximum tolerable dose (MTD) of GNP-Dex is between 50 mg/kg ≤ MTD < 125 mg/kg, blood half-life < 30 minutes, and majority of nanoparticles excreted within 24 hours through feces. Histopathology changes were noted at ≥ 250 mg/kg in the heart, liver, lung, spleen, and kidney; we found no changes in the brain and no GNP-Dex related effects in the cardiovascular parameters or hematological factors (blood, lipid, and metabolic panels) at doses < 125 mg/kg. The results open avenues for pivotal preclinical single and repeat dose safety studies following good laboratory practices (GLP) as required by regulatory agencies for investigational new drug (IND) application. PMID:24854092

  19. [High dose rate brachytherapy].

    PubMed

    Aisen, S; Carvalho, H A; Chavantes, M C; Esteves, S C; Haddad, C M; Permonian, A C; Taier, M do C; Marinheiro, R C; Feriancic, C V

    1992-01-01

    The high dose rate brachytherapy uses a single source os 192Ir with 10Ci of nominal activity in a remote afterloading machine. This technique allows an outpatient treatment, without the inconveniences of the conventional low dose rate brachytherapy such as use of general anesthesia, rhachianesthesia, prolonged immobilization, and personal exposition to radiation. The radiotherapy department is now studying 5 basic treatment schemes concerning carcinomas of the uterine cervix, endometrium, lung, esophagus and central nervous system tumors. With the Micro Selectron HDR, 257 treatment sessions were done in 90 patients. Mostly were treated with weekly fractions, receiving a total of three to four treatments each. No complications were observed neither during nor after the procedure. Doses, fraction and ideal associations still have to be studied, so that a higher therapeutic ratio can be reached.

  20. Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame.

    PubMed

    Stegink, L D; Brummel, M C; McMartin, K; Martin-Amat, G; Filer, L J; Baker, G L; Tephly, T R

    1981-02-01

    Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body weight) and three doses considered to be in the abuse range (100, 150, and 200 mg/kg body weight). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (p less than or equal to 0 .001) after ingestion of each abuse dose, with the mean peak blood methanol concentrations and the areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (+/- SD) peak blood methanol concentrations were 1.27 +/- 0.48 mg/dl at the 100 mg/kg dose, 2.14 +/- 0.35 mg/dl at the 150 mg/kg dose, and 2.58 +/- 0.78 mg/dl at the 200 mg/kg dose. Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in the 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicate that the toxic effects of methanol are due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. Similarly, no differences were noted in ophthalmologic examinations carried out before and after aspartame loading.

  1. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    SciTech Connect

    Sinha, Neeharika; Cifter, Gizem; Sajo, Erno; Kumar, Rajiv; Sridhar, Srinivas; Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike; Ngwa, Wilfred

    2015-02-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application with

  2. BIOCHANIN A SHOWS NO EFFECT ON SKELETAL SYSTEM IN OVARIECTOMIZED RATS, WHEN ADMINISTERED IN MODERATE DOSE.

    PubMed

    Kaczmarczyk-Sedlak, Ilona; Zych, Maria; Wojnar, Weronika; Ozimina-Kamińska, Ewa; Dudek, Sławomir; Chadała, Natalia; Kachel, Agnieszka

    2015-01-01

    Biochanin A is a naturally occurring isoflavone. Its main sources are clover species such as Trifolium pretense, Trifolium subterraneum or Trifolium incarnatum. Phytoestrogens, including isoflavones, are plant-derived substances, which exhibit estrogen-like properties, thus they may be used as an alternative for hormonal replacement therapies and prevent postmenopausal osteoporosis. Therefore, the aim of the presented study, was to investigate the effect of biochanin A on chemistry and mechanical properties of skeletal system in rats with ovariectomy-induced osteoporosis. The animals were divided into 4 groups--(I) sham-operated rats, (II) ovariectomized rats, (III) ovariectomized rats receiving estradiol at a dose of 0.2 mg/kg p.o., which were a positive control, and (IV) ovariectomized rats receiving biochanin A at a dose of 5 mg/kg p.o. for four weeks. The administered dose of biochanin A is considered as moderate for human, which can be received in the dietary supplements, and was established using ten-fold conversion rate resulting from faster metabolism in rats. Obtained results showed that ovariectomy induced harmful changes in bone tissue, causing worsening in both chemistry and mechanical parameters in bones. Administration of biochanin A to ovariectomized rats did not affect any changes in bone tissue in comparison to the bones of untreated ovariectomized rats. There was neither improvement nor deterioration noted in chemical composition and mechanical properties in all analyzed bones. Basing on the results, it could be concluded, that biochanin A administered in a moderate dose shows no influence on bone tissue of rats with ovariectomy-induced osteoporosis.

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

    SciTech Connect

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

    1994-06-15

    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 [times] three fractions/48 h or 5 Gy/fractions [times] 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.

  4. [Dose-dependent effects of intracisternally administered insulin on rat's behavior and glucose level].

    PubMed

    Shestakova, S A; Stepanov, I I; Eliseeva, A P; Shatik, S V; Fedorova, N V; Klimenko, V M

    2007-03-01

    Rat behavior in the open field and elevated plus-maze as well as glycaemia level were analyzed in rats after intracisternal administration of 2.5, 25, 50 and 200 ng of insulin. Dose-dependent changes were found in both behavioral tests: insulin in low doses (2.5 and 25 ng) increased probability of locomotion and investigative activity in open field, while insulin in high doses (50 and 200 ng) did not alter locomotor activity and showed tendency to weakening of the investigative behavior (especially in the dose of 50 ng). Significant decrease of rat anxiety level during the first 5 minutes of testing was found after administration of 2.5 and 200 ng of insulin and during the next 5 minutes after administration of 2.5 and 25 ng of insulin in elevated plus-maze. The glucose level in rats was increased in 1-2 hours after insulin administration, though glycaemia level did not exceed normal values. Thus revealed alterations of behavior are supposed to be the result of direct insulin influence on central mechanisms of activation and/or suppression of underlying behavioral characteristics of animals. PMID:17598469

  5. Liver regeneration in rats administered high levels of carbohydrates.

    PubMed

    Gershbein, L L

    1976-01-01

    Partially hepatectomized male rats were administered high levels of carbohydrates by drinker, in a casein-cellulose synthetic medium and in a commercial meal over a period of 10 days after surgery and the amount of liver regenerating or the increment ascertained; representative hepatic glycogen changes were also followed. Of the carbohydrate solutions, 5% levulose, 5% levulose+5% glucose and 10% sucrose increased the extent of liver regeneration as was also the case with the synthetic diet suplemented with 30 and 60% glucose, 30 and 60% levulose, 30% levulose+30% glucose, 30% each of galactose and the arabinoglactan, Stractan and 60% each of sucrose, honey and unsulphured molasses. The liver increments and glycogen contents were in the control range for animals fed the synthetic diet containing 30% each of lactose, sorbitol, corn starch and raffinose pentahydrate, 5% ascorbic acid and 15% L-arabinose but the liver glycogen was depressed with 30% xylose, a diet which was poorly tolerated; 15% mannitol caused a decrease inthe increment. The incorporation of several sugars into the commercial rat meal, including xylose (11%), raffinose (15%), L-arabinose (8%), D-arabinose (5%), L-sorbose (17%), galactosamine (0.20%) and galactono-gamma-lactone (10%), led to little change over the control increments. In intact rats fed the synthetic diet containing 30% each of glucose, lactose, galactose, sucrose and levulose for an interval of 10 days, the wet and dry liver--body weight ratios were significantly elevated only with the last two sugars but liver glycogen was increased in each instance.

  6. Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy.

    PubMed

    Wang, Xin; Poenisch, Falk; Sahoo, Narayan; Zhu, Ronald X; Lii, MingFwu; Gillin, Michael T; Li, Jing; Grosshans, David

    2016-01-01

    This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 μSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure. PMID:27685136

  7. Safety and pharmacokinetics of multiple doses of aclidinium bromide administered twice daily in healthy volunteers.

    PubMed

    Lasseter, K; Dilzer, S; Jansat, J M; Garcia Gil, E; Caracta, C F; Ortiz, S

    2012-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction and increased cholinergic tone. The global initiative for chronic obstructive lung disease (GOLD) guidelines recommend long-acting anticholinergics for COPD maintenance treatment. Aclidinium bromide is a novel, long-acting muscarinic antagonist developed for the treatment of COPD. A phase I, randomized, single-blind, multiple-dose clinical trial was conducted to assess the safety and pharmacokinetics (PK) of multiple doses of twice-daily (BID) aclidinium in healthy subjects. Thirty healthy male and female subjects received aclidinium 200 μg, 400 μg, 800 μg, or placebo twice daily for 7 days. Subjects were randomized to 1 of 3 cohorts and 10 subjects in each cohort were randomized (8:2) to either aclidinium or placebo groups. Safety was assessed via adverse events (AEs), laboratory evaluations, vital signs, and ECGs. Plasma samples were obtained at multiple time points throughout the study and analyzed for aclidinium and its inactive acid and alcohol metabolites using a fully validated method of liquid chromatography coupled with tandem mass spectrometry. A total of 9 treatment-emergent AEs were reported (1, placebo; 3, aclidinium 400 μg; 5, aclidinium 800 μg), all of which were mild in severity. No serious AEs were reported. There were no clinically meaningful changes in laboratory parameters or vital signs. PK parameters on Day 7 following BID dosing of aclidinium showed that steady state was achieved for aclidinium and its metabolites. On Days 1 and 7, maximum plasma concentrations (Cmax) of aclidinium were generally observed at the first PK time point (5 min postdose) and rapidly declined, with plasma concentrations generally less than 10% of Cmax by 6 h postdose in all aclidinium groups. Mean effective t(½) after the evening dose on Day 7 ranged from 4.6 to 7.0 h for aclidinium 400 μg and 800 μg, similar to the terminal t(½) observed on Day 1 (4.5-5.9 h

  8. Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose

    PubMed Central

    2013-01-01

    Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that

  9. What you think is not what they get: significant discrepancies between prescribed and administered doses of tube feeding.

    PubMed

    van den Broek, Paulina W J H; Rasmussen-Conrad, Ellen L; Naber, Anton H J; Wanten, Geert J A

    2009-01-01

    Enteral tube feeding remains an indispensible strategy to treat disease-related malnutrition. In the present study we evaluated in clinical practice whether prescribed feeding volumes correspond with administered quantities and we highlight possible causes for discrepancies. During a 4-month observation period data from all patients fully depending on tube feeding (1.5-2.5 litres/d) were collected in a Dutch 900-bed academic hospital. The range for administered feeds to be adequate was set at 100 +/- 10% of the prescribed dose. Fifty-five patients (mean age 57 (SD 30) years) were included. Tube feeding was given continuously via pump (n 37) or drip (n 3), in portions (n 14) or by combined modes (n 1). Administered tube feeding amounts were significantly lower than prescribed in 40% of all patients (P < or = 0.001). The mean ratio of administered v. prescribed energy was 87 (SD 21) % (all modes), 85 (SD 24) % (pump), 94 (SD 12) % (portions) and 88.3 (SD 18.1) % (drip), respectively. The mean energy deficit amounted to 1089 kJ/d (range -7955 to +795). Only on intensive care unit wards did feeding administration meet the set goal. Feeding interruptions because of diagnostic or therapeutic procedures were the main reason for decreased intakes. Our findings show that many patients relying on tube feeding do not meet their nutritional goals during hospital stay. This problem can be addressed by adapting feeding schedules and the use of formulations with a higher energy density.

  10. High dose rate brachytherapy for oral cancer

    PubMed Central

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

    2013-01-01

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

  11. Fixed-dose combination ezetimibe+atorvastatin lowers LDL-C equivalent to co-administered components in randomized trials: use of a dose-response model.

    PubMed

    Bays, Harold E; Chen, Erluo; Tomassini, Joanne E; McPeters, Gail; Polis, Adam B; Triscari, Joseph

    2015-04-01

    Co-administration of ezetimibe with atorvastatin is a generally well-tolerated treatment option that reduces LDL-C levels and improves other lipids with greater efficacy than doubling the atorvastatin dose. The objective of the study was to demonstrate the equivalent lipid-modifying efficacy of fixed-dose combination (FDC) ezetimibe/atorvastatin compared with the component agents co-administered individually in support of regulatory filing. Two randomized, 6-week, double-blind cross-over trials compared the lipid-modifying efficacy of ezetimibe/atorvastatin 10/20 mg (n = 353) or 10/40 mg (n = 280) vs. separate co-administration of ezetimibe 10 mg plus atorvastatin 20 mg (n = 346) or 40 mg (n = 280), respectively, in hypercholesterolemic patients. Percent changes from baseline in LDL-C (primary endpoint) and other lipids (secondary endpoints) were assessed by analysis of covariance; triglycerides were evaluated by longitudinal-data analysis. Expected differences between FDC and the corresponding co-administered doses were predicted from a dose-response relationship model; sample size was estimated given the expected difference and equivalence margins (±4%). LDL-C-lowering equivalence was based on 97.5% expanded confidence intervals (CI) for the difference contained within the margins; equivalence margins for other lipids were not prespecified. Ezetimibe/atorvastatin FDC 10/20 mg was equivalent to co-administered ezetimibe+atorvastatin 20 mg in reducing LDL-C levels (54.0% vs. 53.8%) as was FDC 10/40 mg and ezetimibe+atorvastatin 40 mg (58.9% vs. 58.7%), as predicted by the model. Changes in other lipids were consistent with equivalence (97.5% expanded CIs <±3%, included 0); triglyceride changes varied more. All treatments were generally well tolerated. Hypercholesterolemic patients administered ezetimibe/atorvastatin 10/20 and 10/40 mg FDC had equivalent LDL-C lowering. This FDC formulation proved to be an efficacious and generally well

  12. Chick development and high dose of bendiocarb.

    PubMed

    Petrovova, Eva; Sedmera, David; Luptakova, Lenka; Mazensky, David; Danko, Jan

    2012-01-01

    Developmental data of carbamate pesticides are scarce although they generally possess low toxicity for vertebrates. The aim of the study was to investigate the toxicity of bendiocarb to liver and central nervous system of chick embryos. Bendiocarb (1600 μg/egg) was administered to the embryo through membrana papyracea on embryonic day 3 and 10. In the liver and central nervous system we observed no macroscopic or microscopic changes. These organs were also investigated for caspase activity in regard to application of bendiocarb and no differences in the caspase immunopositivity were observed in comparison with the control. The embryolethality after bendiocarb respective dose was high (94 %) on the embryonic day 3, though following results indicated no toxicity to investigated organs and no increase in the number of apoptotic cells in survived chick embryos on both the early (day 3 of incubation) and the later (day 10 of incubation) developmental stage. PMID:22540656

  13. Histopathology of myocardium of copper-deficient rats administered a toxic dose a cocaine

    SciTech Connect

    Burns, W.; Bielenberg, U.; Seung, S.K.; Reddy, P.P.; Dulin, A.M.; Smith, J.C. )

    1989-02-15

    The present study examined the effects of a single dose of cocaine (Coc) on cardiac ultrastructure in rats fed copper sufficient (Cus) compared to copper deficient (CuD) diets. Weanling males were fed either CuS (n-13) or CuD (n-12) for 7 wk. Ten in each group, (paired for Cu status), were injected (ip) with Coc-HCl (80-90mg/kg bw) 5 served as controls. Rats which survived for >15 min, (CuD 40% CuS (80%) controls), were killed and tissues obtained for histology and Cu analysis. Lower Cu concentrations in heart, liver and serum confirmed the CuD. The hearts were examined by light (Lm) and transmission electron microscopy. Myocardial foci showed necrosis, fibrosis, and inflammation in all given Coc but were more severe in the CuD group. CuS controls (no Coc) showed no similar lesions. Ultrastructural observations supported Lm findings. There was an apparent increase in number of mitochondria (Mito) of variable sizes and shapes. Foci of molding Mito and some with crystalline configuration of cristae were also observed. This was most pronounced in the CuD rats given Coc but absent in CuS animals (no Coc). The data support previous findings of myocardial lesionsin CuD rats the effect of Coc in exacerbation these lesions requires further elucidation.

  14. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

    EPA Science Inventory

    DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
    Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

  15. PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    PubMed

    Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

    2015-09-01

    Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species. PMID:26352950

  16. PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    PubMed

    Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

    2015-09-01

    Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

  17. The effects of acutely administered low dose sarin on cognitive behaviour and the electroencephalogram in the common marmoset.

    PubMed

    Pearce, P C; Crofts, H S; Muggleton, N G; Ridout, D; Scott, E A

    1999-01-01

    Previous studies have suggested that administration of a clinically sign-free dose of sarin to non-human primates gives rise to subtle changes in brain electrical activity as measured by electroencephalography (EEG) several months following exposure. The functional significances of such changes are unclear. The present study monitored EEG by using implantable radiotelemetry, and also assessed the performance of complex behavioural tasks, in non-human primates for up to 15 months following exposure to a low dose of sarin. Baselines of EEG and behaviour were shown to be stable over several months in control animals. The doses of sarin administered caused erythrocyte cholinesterase inhibitions of 36.4% to 67.1%. Overall, no significant changes in EEG patterns were observed although there were increases in beta 2 amplitude which approached significance (p=0.07). No deleterious effects on performance were seen on the touchscreen mediated discrimination tasks presented from the Cambridge Neuropsychological Test Automated Battery (CANTAB). This study illustrates the validity of the approach employed and makes an important contribution to the investigation of the long-term effects of organophosphorous compounds.

  18. Short- and long-term hormonal effects of a single dose of 50 mg tamoxifen administered to normal males.

    PubMed

    Fauser, B C; Dony, J M; Doesburg, W H; Thomas, C M; Rolland, R

    1984-01-01

    To five potentially fertile males, a single dose of 50 mg tamoxifen was administered orally to explore the short- and long-term hormonal effects on the hypothalamic-pituitary-gonadal axis. Blood specimens were obtained through an integrated sampling technique for the first two hours after the intake of the drug. Then, samples were taken daily throughout one week, and twice weekly for the next two weeks. Hormone measurements of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and oestradiol were obtained by specific RIA. All the subjects showed different response patterns. No general characteristic of the hormonal changes in the investigated group could be given. A consistent correlation between the within-individual levels of gonadotrophin and sex steroid changes could not be observed. It is concluded, within the limits of the used experimental design, that in healthy males a single administration of tamoxifen does not result in consistent changes in serum levels of either gonadotrophins or sex steroid hormones.

  19. Relative Bioavailability of a Single Dose of Belimumab Administered Subcutaneously by Prefilled Syringe or Autoinjector in Healthy Subjects

    PubMed Central

    Murtaugh, Thomas; Gilbert, Jane; Barton, Matthew E.; Fire, Joseph; Groark, James; Fox, Norma Lynn; Roth, David; Gordon, David

    2015-01-01

    Abstract Intravenous belimumab is approved for the treatment of systemic lupus erythematosus; subcutaneous self‐administration would enable greater patient access. This study assessed relative bioavailability, tolerability, and safety of 1 subcutaneous dose of self‐administered belimumab by healthy subjects using a single‐use autoinjector or prefilled syringe. Subjects (randomized 1:1:1:1) self‐administered belimumab 200 mg subcutaneously (abdomen or thigh) by prefilled syringe or autoinjector. Pharmacokinetics, adverse events (AEs), injection‐site pain, and administration errors were recorded. Of 81 subjects, 5 experienced administration errors and were excluded from pharmacokinetic analyses. Mean serum belimumab concentration profiles were similar for both devices, with a weak trend toward higher concentrations for thigh injection compared with abdominal injections. Maximum observed serum concentration was slightly higher with the autoinjector (27.0 vs 25.3 µg/mL) and area under the concentration–time curve slightly lower (701 vs 735 day · μg/mL), compared with the prefilled syringe. Incidence of AEs was 51% (41 of 81 subjects; headache was most common), with no serious or severe AEs. Median injection‐site pain scores were low (0 after 1 hour). Device handling was reported as acceptable by ≥95% of autoinjector users and ≥90% of prefilled syringe users for each characteristic assessed. These results support the use of either device for belimumab subcutaneous administration. PMID:27163500

  20. Population based evaluation of a multi-parametric steroid profiling on administered endogenous steroids in single low dose.

    PubMed

    Van Renterghem, Pieter; Van Eenoo, Peter; Delbeke, Frans T

    2010-12-12

    Steroid profiling provides valuable information to detect doping with endogenous steroids. Apart from the traditionally monitored steroids, minor metabolites can play an important role to increase the specificity and efficiency of current detection methods. The applicability of several minor steroid metabolites was tested on administration studies with low doses of oral testosterone (T), T gel, dihydrotestosterone (DHT) gel and oral dehydroepiandrosterone (DHEA). The collected data for all monitored parameters were evaluated with the respective population based reference ranges. Besides the traditional markers T/E, T and DHT, minor metabolites 4-OH-Adion and 6α-OH-Adion were found as most sensitive metabolites to detect oral T administration. The most sensitive metabolites for the detection of DHEA were identified as 16α-OH-DHEA and 7β-OH-DHEA but longest detection up to three days (after oral administration of 50 mg) was obtained with non-specific 5β-steroids and its ratios. Steroids applied as a gel had longer effects on the metabolism but were generally not detectable with universal decision criteria. It can be concluded that population based reference ranges show limited overall performance in detecting misuse of small doses of natural androgens. Although some minor metabolites provide additional information for the oral testosterone and DHEA formulations, the topical administered steroids could not be detected for all volunteers using universal reference limits. Application of other population based threshold limits did not lead to longer detection times. PMID:20688095

  1. The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine.

    PubMed

    Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

    2015-01-01

    This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

  2. The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine

    PubMed Central

    Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

    2015-01-01

    This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12–13 year-old girls who were vaccinated at the age of 9–10 with 2 doses of qHPV (0–6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99–100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88–98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93–99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4–1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses. PMID:25714044

  3. Specific accumulation of orally administered redox nanotherapeutics in the inflamed colon reducing inflammation with dose-response efficacy.

    PubMed

    Vong, Long Binh; Mo, John; Abrahamsson, Bertil; Nagasaki, Yukio

    2015-07-28

    Although current medications for ulcerative colitis (UC) are effective to some extent, there are still some limitation of their use due to the non-specific distribution, drug metabolism in the gastrointestinal tract, and severe adverse effects. In our previous studies, we developed oral redox nanoparticles (RNP(O)) that specifically accumulated and scavenged overproduced reactive oxygen species (ROS) in an inflamed colon. However, the mechanism leading to specific accumulation of RNP(O) in an inflamed colon is still unclear. In this study, we investigated the cellular uptake of RNP(O) into ROS-treated epithelial colonic cells in vitro, and compared to the untreated cells, found a significantly increased uptake in ROS-treated cells. In vivo, we discovered that orally administered RNP(O) were not internalized into the cells of a normal colon. A significant amount of disintegrated RNP(O) was detected in the cells of an inflamed colon of dextran sodium sulfate (DSS)-induced colitis mice, resulting in scavenging of ROS and suppression of inflammation with low adverse effects. Furthermore, we confirmed a significant reduction of disease activity and a robust dose response efficacy following RNP(O) treatment in acute DSS-induced colitis mice, outperforming the positive control 5-aminosalicylic acid. Oral administration of RNP(O) is a promising approach to develop a new therapy for UC disease. PMID:25998050

  4. Efficacy of ketoprofen administered in drinking water at a low dose for the treatment of porcine respiratory disease complex.

    PubMed

    Salichs, M; Sabaté, D; Homedes, J

    2013-09-01

    The purpose of this study was to evaluate the efficacy of an oral solution of ketoprofen administered in drinking water at a lower dose as a complement to antimicrobial therapy in a mild outbreak of porcine respiratory disease complex. The study was performed with 120 pigs with rectal temperature between 39.9 and 41°C and at least 1 sign indicating porcine respiratory disease complex (dyspnea, cough, nasal discharge, or depression). Animals were randomly allocated in 2 groups (treated and control group). Animals in both groups received etiological therapy with doxycycline at 10 mg · kg(-1) in drinking water for 5 d. The animals in the treated group also received 1.5 mg · kg(-1) of ketoprofen during the first 3 d. The reduction in rectal temperature in the treated group was significantly greater during the days of ketoprofen administration and up to 1 d after the end of treatment (P < 0.05). The percentage of dyspneic animals was significantly less (P < 0.05) in the treated group from d 2 to 5 of the study. Also, a significant improvement regarding depression and cough was seen in the animals of the treated group. No statistically significant (P > 0.05) differences were evidenced in productive variables. In conclusion, oral treatment with ketoprofen at 1.5 mg · kg(-1) in combination with antimicrobial therapy was found to be a clinically effective approach in outbreaks of mild porcine respiratory disease complex.

  5. Safety and immunogenicity of two doses of quadrivalent meningococcal conjugate vaccine or one dose of meningococcal group C conjugate vaccine, both administered concomitantly with routine immunization to 12- to 18-month-old children

    PubMed Central

    Noya, Francisco; McCormack, Deirdre; Reynolds, Donna L; Neame, Dion; Oster, Philipp

    2014-01-01

    OBJECTIVES: To describe the immunogenicity and safety of a two-dose series of a quadrivalent meningococcal (serogroups A, C, Y and W) polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-D) administered to toddlers. METHODS: Children were randomly assigned (1:1) at study entry to receive MenACYW-D at 12 and 18 months of age (group 1; n=61) or meningococcal serogroup C conjugate vaccine (MCC) at 12 months of age (group 2; n=62). All received routine childhood immunizations. A, C, Y and W antibody titres were measured in group 1 before and one month after the 18-month MenACYW-D vaccination and were measured in group 2 at one and seven months post-MCC vaccination. Antibodies elicited by diphtheria and tetanus toxoids, and acellular pertussis vaccine adsorbed combined with inactivated poliomyelitis vaccine and Haemophilus influenzae b conjugate (DTaP-IPV-Hib) vaccine coadministered at the 18-month vaccination were measured one month later. Safety data were collected. RESULTS: At 19 months of age, ≥96% in group 1 achieved protective titres for the four meningococcal serogroups after dose 2; 67% in group 2 exhibited protective titres against serogroup C 28 days after MCC vaccination at 12 months of age, declining to 27% seven months later. DTaP-IPV-Hib elicited high antibody concentrations/titres in groups 1 and 2, consistent with historical values. The safety profiles after each dose generated no unexpected safety signals; no serious adverse events were related to vaccination. DISCUSSION: A two-dose series of MenACYW-D given concomitantly with a DTaP-IPV-Hib booster dose at 18 months of age demonstrated a good immunogenicity and safety profile. A two-dose series of MenACYW-D can be used as an alternative to one dose of MCC and provides protection against additional serogroups (NCT ID: NCT01359449). PMID:25285126

  6. Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination

    PubMed Central

    Romanowski, Barbara; Schwarz, Tino F; Ferguson, Linda M; Ferguson, Murdo; Peters, Klaus; Dionne, Marc; Schulze, Karin; Ramjattan, Brian; Hillemanns, Peter; Behre, Ulrich; Suryakiran, Pemmaraju; Thomas, Florence; Struyf, Frank

    2014-01-01

    This randomized, partially-blind study (ClinicalTrials.gov registration number NCT00541970) evaluated the immunogenicity and safety of 2-dose (2D) schedules of the HPV-16/18 AS04-adjuvanted vaccine. Results to month (M) 24 have been reported previously and we now report data to M48 focusing on the licensed vaccine formulation (20 μg each of HPV-16 and -18 antigens) administered at M0,6 compared with the standard 3-dose (3D) schedule (M0,1,6). Healthy females (age stratified: 9–14, 15–19, 20–25 years) were randomized to receive 2D at M0,6 (n = 240) or 3D at M0,1,6 (n = 239). In the according-to-protocol immunogenicity cohort, all initially seronegative subjects seroconverted for HPV-16 and -18 antibodies and remained seropositive up to M48. For both HPV-16 and -18, geometric mean antibody titer (GMT) ratios (3D schedule in women aged 15–25 years divided by 2D schedule in girls aged 9–14 years) at M36 and M48 were close to 1, as they were at M7 when non-inferiority was demonstrated. The kinetics of HPV-16, -18, -31, and -45 antibody responses were similar for both groups and HPV-16 and -18 GMTs were substantially higher than natural infection titers. The vaccine had a clinically acceptable safety profile in both groups. In summary, antibody responses to a 2D M0,6 schedule of the licensed vaccine formulation in girls aged 9–14 years appeared comparable to the standard 3D schedule in women aged 15–25 years up to 4 years after first vaccination. A 2D schedule could facilitate implementation of HPV vaccination programs and improve vaccine coverage and series completion rates. PMID:24576907

  7. The pharmacokinetics of a single oral or rectal dose of concurrently administered isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas maximus).

    PubMed

    P Brock, A; Isaza, R; Egelund, E F; Hunter, R P; Peloquin, C A

    2014-10-01

    Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in captive Asian elephants (Elephas maximus). Treatment for tuberculosis in elephants utilizes multidrug protocols combining isoniazid, rifampin, pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30 mg/kg was administered orally to six Asian elephants, and rectally to five elephants using a cross-over design. Blood samples were collected serially over 24 h. Pyrazinamide and ethambutol concentrations were determined using validated gas chromatography assays. Isoniazid and rifampin concentrations were determined using validated high-performance liquid chromatography assays. Rectal isoniazid produced an earlier Tmax compared with oral administration. Oral isoniazid resulted in a comparatively lower Cmax , but higher AUC values compared with rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and AUC values compared with rectal pyrazinamide. Results of this study indicate that currently recommended therapeutic monitoring sample collection times for rectal isoniazid and oral rifampin do not provide an accurate assessment of exposure for these drugs. This study demonstrates notable individual variability, indicating that dosing of these medications requires individual monitoring and provides additional information to guide the clinician when treating elephants.

  8. The pharmacokinetics of a single oral or rectal dose of concurrently administered isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas maximus).

    PubMed

    P Brock, A; Isaza, R; Egelund, E F; Hunter, R P; Peloquin, C A

    2014-10-01

    Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in captive Asian elephants (Elephas maximus). Treatment for tuberculosis in elephants utilizes multidrug protocols combining isoniazid, rifampin, pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30 mg/kg was administered orally to six Asian elephants, and rectally to five elephants using a cross-over design. Blood samples were collected serially over 24 h. Pyrazinamide and ethambutol concentrations were determined using validated gas chromatography assays. Isoniazid and rifampin concentrations were determined using validated high-performance liquid chromatography assays. Rectal isoniazid produced an earlier Tmax compared with oral administration. Oral isoniazid resulted in a comparatively lower Cmax , but higher AUC values compared with rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and AUC values compared with rectal pyrazinamide. Results of this study indicate that currently recommended therapeutic monitoring sample collection times for rectal isoniazid and oral rifampin do not provide an accurate assessment of exposure for these drugs. This study demonstrates notable individual variability, indicating that dosing of these medications requires individual monitoring and provides additional information to guide the clinician when treating elephants. PMID:24684601

  9. Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice.

    PubMed

    Yokohira, Masanao; Arnold, Lora L; Pennington, Karen L; Suzuki, Shugo; Kakiuchi-Kiyota, Satoko; Herbin-Davis, Karen; Thomas, David J; Cohen, Samuel M

    2011-06-01

    The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, female As3mt knockout (KO) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite administration on the urothelium are dose dependent. Female wild-type C57BL/6 mice and As3mt KO mice were divided into five groups (n = 7) with free access to drinking water containing 0, 1, 10, 25, or 50 ppm arsenic as arsenite for 4 weeks. At sacrifice, urinary bladders of both As3mt KO and wild-type mice showed hyperplasia by light microscopy; however, the hyperplasia was more severe in the As3mt KO mice. Intracytoplasmic granules were detected in the urothelium of As3mt KO and wild-type mice at arsenic doses ≥ 10 ppm but were more numerous, more extensive, and larger in the KO mice. A no effect level for urothelial effects was identified at 1 ppm arsenic in the wild-type and As3mt KO mice. In As3mt KO mice, livers showed mild acute inflammation and kidneys showed hydronephrosis. The present study shows a dose-response for the effects of orally administered arsenite on the bladder urothelium of wild-type and As3mt KO mice, with greater effects in the KO strain but with a no effect level of 1 ppm for both.

  10. Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation

    PubMed Central

    McCaffrey, Katherine A.; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H.; Patisaul, Heather B.

    2013-01-01

    Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000 mg/kg bw/day BPA through daily, noninvasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50 mg/kg/day can alter sex specific hypothalamic morphology in the rat. PMID:23500335

  11. Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation.

    PubMed

    Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Kumar, Rajiv; Ngwa, Wilfred

    2015-09-21

    Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV

  12. Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation

    PubMed Central

    Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Kumar, Rajiv; Ngwa, Wilfred

    2016-01-01

    Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo–generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to

  13. Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation

    NASA Astrophysics Data System (ADS)

    Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Kumar, Rajiv; Ngwa, Wilfred

    2015-09-01

    Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV

  14. The effect of administered dose of lipid-based formulations on the in vitro and in vivo performance of cinnarizine as a model poorly water-soluble drug.

    PubMed

    Lee, Kathy Wai Yu; Porter, Christopher J H; Boyd, Ben J

    2013-02-01

    The influence of varying the amount of lipid co-administered with the drug on drug solubilisation and absorption is poorly understood. In the current study, the effect of lipid dose on the in vitro drug distribution is compared with the in vivo absorption of cinnarizine (CZ) when formulated using long-chain triacylglyceride (LCT) and medium-chain triacylglycerides (MCT). At a fixed drug-lipid ratio, in the closed in vitro model, the drug concentrations in the aqueous phase increased and decreased for MCT and LCT, respectively, with increasing lipid dose. However, in vivo, the oral bioavailability (F%) of CZ was independent of the quantity of lipid administered for both MCT and LCT, but was higher for LCT (32.1 ± 2.3%) than for MCT (16.6 ± 2.3%). Increasing the quantity of lipid relative to the dose of CZ resulted in an increase in the oral F% when the lipid mass was increased from 125 to 250 mg, but was no greater at 500 mg lipid dose. The results confirm the limitations of the in vitro model but positively indicate that the use of the rat as a pre-clinical model for studying the bioavailability of poorly water-soluble drugs is not compromised by the mass of formulation administered. PMID:23242691

  15. Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery.

    PubMed Central

    Martin, C; Mallet, M N; Sastre, B; Viviand, X; Martin, A; De Micco, P; Gouin, F

    1995-01-01

    The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin. In both groups, the initial dose was administered again after 2 h. Blood samples were collected to determine peak and trough antibiotic levels. Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03). Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively. In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens. In most of the tissues investigated, increased the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in

  16. Hypocholesterolaemic effect of rat-administered oral doses of the isolated 7S globulins from cowpeas and adzuki beans.

    PubMed

    Ferreira, Ederlan S; Amaral, Ana Lucia S; Demonte, Aureluce; Zanelli, Cleslei F; Capraro, Jessica; Duranti, Marcello; Neves, Valdir A

    2015-01-01

    The role of seed proteins, especially soyabean 7S globulins, in controlling dyslipidaemia is widely acknowledged. Amino acid sequence homology among the proteins of this family could reflect similar biological functions in other species. The aim of the present study was to unveil a hypolipidaemic effect of the 7S globulins from cowpeas (7S-C) and adzuki beans (7S-A), administered orally to rats fed a hypercholesterolaemic (HC; high cholesterol and TAG) diet for 28 d. A total of forty-five rats were divided into five groups (nine rats per group): (1) standard (STD) diet; (2) HC diet; (3) HC diet + 7S-C (300 mg/kg per d); (4) HC diet + 7S-A (300 mg/kg per d); and (5) HC diet + simvastatin (SVT; 50 mg/kg per d), as a control. Significant decreases in food intake and final body weight of rats receiving HC + 7S-C and HC + 7S-A diets compared with groups fed the HC and STD diets were observed. Significant decreases in serum total and non-HDL-cholesterol of 7S-C, 7S-A and SVT groups were also observed. HDL-cholesterol levels increased in the 7S-C, 7S-A and SVT groups, while hepatic cholesterol and TAG concentrations were significantly lower than in the HC diet group for the 7S-C-supplemented group only. Faecal excretions of fat and cholesterol in HC diet groups were considerably higher in animals consuming the 7S globulins. The results show that cowpea and adzuki bean 7S globulins promote cholesterol-decreasing effects in hypercholesterolaemic rats even at low dosages, as already observed for other legume seed storage proteins of this family. This main effect is discussed in relation to the possible mechanisms of action. PMID:26090103

  17. Behavioral toxicity and physiological changes from repeated exposure to fluorene administered orally or intraperitoneally to adult male Wistar rats: A dose-response study.

    PubMed

    Peiffer, Julie; Grova, Nathalie; Hidalgo, Sophie; Salquèbre, Guillaume; Rychen, Guido; Bisson, Jean-François; Appenzeller, Brice M R; Schroeder, Henri

    2016-03-01

    Fluorene is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in the environment by reason of its high volatility. Demonstrated to be a neurotoxicant through inhalation, it was also identified as a contributive PAH to food contamination. Since no data are available on its oral neurotoxicity, the purpose of the present study was to assess the behavioral and physiological toxicity of repeated oral administration of fluorene to adult Wistar male rats. Animals were daily treated with fluorene at 1, 10 or 100mg/kg/day for 28 consecutive days. Administration was intraperitoneal (i.p.) or oral (p.o.) to evaluate the influence of the route of exposure on fluorene toxicity. Following this period of treatment, animals in both groups were subjected to similar cognitive evaluations, namely anxiety (elevated-plus maze), locomotor activity (open-field) and learning and memory abilities (eight-arm maze and avoidance test of an aversive light stimulus), as well as physiological measurements. The behavioral testing occurred from the 28th to the 60th day of the experiment during which fluorene treatment continued uninterrupted. At the end of this period, the concentration levels of fluorene and of three of its monohydroxylated metabolites in blood and brain were determined using a GC-MS/MS method. The results demonstrated a reduction in rat anxiety level at the lowest doses administered (1 and 10mg/kg/day) regardless of the treatment route, whereas locomotor activity and learning abilities remained unchanged. Moreover, a less significant weight gain was noticed in animals i.p.- and p.o.-treated with 100mg/kg/day during the 28-day period of treatment, which, upon comparison with the three other groups, induced a body weight gap that was maintained throughout the experiment. Significant increases in relative liver weight were also observed in a dose-dependent manner in orally treated rats and only in animal treated i.p. with 100mg/kg/day. According to the dose, higher

  18. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia

    PubMed Central

    Byrd, John C.; Lin, Thomas S.; Dalton, James T.; Wu, Di; Phelps, Mitch A.; Fischer, Beth; Moran, Mollie; Blum, Kristie A.; Rovin, Brad; Brooker-McEldowney, Michelle; Broering, Sarah; Schaaf, Larry J.; Johnson, Amy J.; Lucas, David M.; Heerema, Nyla A.; Lozanski, Gerard; Young, Donn C.; Suarez, Jose-Ramon; Colevas, A. Dimitrios; Grever, Michael R.

    2007-01-01

    Despite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200 × 109/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases. PMID:17003373

  19. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia.

    PubMed

    Byrd, John C; Lin, Thomas S; Dalton, James T; Wu, Di; Phelps, Mitch A; Fischer, Beth; Moran, Mollie; Blum, Kristie A; Rovin, Brad; Brooker-McEldowney, Michelle; Broering, Sarah; Schaaf, Larry J; Johnson, Amy J; Lucas, David M; Heerema, Nyla A; Lozanski, Gerard; Young, Donn C; Suarez, Jose-Ramon; Colevas, A Dimitrios; Grever, Michael R

    2007-01-15

    Despite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200x10(9)/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases.

  20. XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind, placebo-controlled, dose-escalating study

    PubMed Central

    Deloche, Catherine; Lopez-Lazaro, Luis; Mouz, Sébastien; Perino, Julien; Abadie, Claire; Combette, Jean-Marc

    2014-01-01

    The aim of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of the JNK inhibitor XG-102 in a randomized, double blind, placebo controlled, sequential ascending dose parallel group Phase 1 Study. Three groups of male subjects received as randomly assigned ascending single XG-102 doses (10, 40, and 80 μg/kg; 6 subjects per dose) or placebo (2 subjects per dose) as an intravenous (IV) infusion over 60 min. Safety and tolerability were assessed by physical examination, vital signs, electrocardiography, eye examination, clinical laboratory tests and adverse events (AEs). PK was analyzed using noncompartmental methods. All reported AEs were mild to moderate and neither their number nor their distribution by System Organ Class suggest a dose relationship. Only headache and fatigue were considered probably or possibly study drug related. Headache frequency was similar for active and placebo, consequently this was not considered to be drug related but probably to study conditions. The other examinations did not show clinically relevant deviations or trends suggesting a XG-102 relationship. Geometric mean half-life was similar among doses, ranging from 0.36 to 0.65 h. Geometric mean XG-102 AUC0–last increased more than linearly with dose, 90% confidence intervals (CIs) did not overlap for the two highest doses. Geometric mean dose normalized Cmax values suggest a more than linear increase with dose but 90% CIs overlap. It may be concluded that XG-102 single IV doses of 10–80 μg/kg administered over 1 h to healthy male subjects were safe and well tolerated. PMID:25505576

  1. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

    PubMed Central

    Garcia, Maristela Magnavita Oliveira; Varela, Carolina Garcez; Silva, Patricia Fontes; Lima, Paulo Roberto Passos; Góes, Paulo Meira; Rodrigues, Marilia Galeffi; Silva, Maria de Lourdes Lima Souza e; Ladeia, Ana Marice Teixeira; Guimarães, Armênio Costa; Correia, Luis Claudio Lemos

    2016-01-01

    Background The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms. PMID:27142792

  2. The margin of safety of a single application of transdermal fentanyl solution when administered at multiples of the therapeutic dose to laboratory dogs.

    PubMed

    Savides, M C; Pohland, R C; Wilkie, D A; Abbott, J A; Newbound, G C; Freise, K J; Clark, T P

    2012-08-01

    Previous studies have demonstrated that a single, topical application of a novel, long-acting transdermal fentanyl solution provides analgesic fentanyl concentrations for at least 4 days. The objective of this study was to describe the margin of safety following application at multiples of the therapeutic dose. Twenty-four laboratory dogs were administered a single placebo or 1×, 3×, or 5× multiple of the dose of 2.6 mg/kg (50 μL/kg) to the ventral abdominal skin and observed for 14 days. Plasma fentanyl concentrations increased in proportion to dose. Adverse reactions in the 1× group were transient and included a low prevalence (≤ 33%) of mild sedation, reduced food intake, modest weight loss, and minimal reductions in heart rate and rectal temperature. Moderate to severe sedation emerged in the 3× and 5× groups, which was associated with a dose-limiting reduction in food and water intake, necessitating maintenance fluid replacement for the first 2 days following application. Also observed in the higher-dose groups were an increased prevalence of abnormal stools and transient lens opacities. All abnormal health observations were completely resolved prior to necropsy on day 14, and there were no histological abnormalities identified. These data support the safe use of the 1× dose and describe the outcome of an overdose of up to 5× dose in the absence of opioid reversal.

  3. Estimating the intake of abused methamphetamines using experimenter-administered deuterium labeled R-methamphetamine: selection of the R-methamphetamine dose.

    PubMed

    Li, Linghui; Lopez, Juan Carlos; Galloway, Gantt P; Baggott, Matthew J; Everhart, Tom; Mendelson, John

    2010-08-01

    All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, the quantity of illicit drug ingested is related to the severity of addiction. Unfortunately, there are no objective methods to estimate intake for most addictive drugs. Using experimenter-administered doses of deuterium-labeled R-methamphetamine (R-[-]-MA-d3), we have developed a method to estimate the amount of abused methamphetamine intake in addicts enrolled in clinical trials. This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of single oral doses of R-MA in healthy adults to select a dose of R-MA-d3 to be used as a biomarker for estimation the amount of methamphetamine abuse. This was a five-session randomized, double-blind, placebo-controlled, balanced crossover study in eight subjects. Oral R-(-)-MA was dosed at 0 mg, 1 mg, 2.5 mg, 5 mg, or 10 mg; bioavailability was estimated by slow intravenous dosing (30 minutes) of 2.5 mg R-(-)-MA-d3 given with the 2.5 mg R-(-)-MA oral dose condition. Pharmacokinetic and pharmacodynamic measures were obtained. No serious adverse events occurred during the study and all doses of R-MA were well tolerated. Linear pharmacokinetics was observed within our oral dose range of 1 to 10 mg. Complete bioavailability and pharmacologic inactivity were found for all oral doses. These characteristics indicate the advantage of using a small oral R-(-)-MA-d3 dose as a biomarker to estimate exposure to abused methamphetamine. Based on these results, 5 mg R-(-)-MA-d3 has been selected as the biomarker dose in future studies. Preliminary findings from our study indicate that experimenter-administered oral R-(-)-MA-d3 may allow estimation of abused methamphetamine intake and exposure. Knowledge of the quantity of methamphetamine intake may allow better estimation of disease severity and treatment efficacy. Experience gained from this study also can be applied to the management of other drug dependence problems such as

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

    SciTech Connect

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

    1985-02-01

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

  5. Retinal risks of high-dose ornithine supplements: a review.

    PubMed

    Hayasaka, Seiji; Kodama, Tatsuo; Ohira, Akihiro

    2011-09-01

    We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH(3) detoxification in the hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 μmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 μmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 μmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH(3) detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine. PMID:21767450

  6. NTP toxicity report of reproductive dose range-finding study of Genistein (CAS No. 446-72-0) administered in feed to Sprague-Dawley rats.

    PubMed

    Delclos, K B; Newbold, Retha

    2007-11-01

    Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. A series of short-term studies with genistein was conducted with two goals: 1) to obtain data necessary to establish dose levels for subsequent multigeneration reproductive and chronic toxicity studies and 2) to evaluate the effects of genistein on endpoints outside the reproductive tract. The data generated from these studies have been reported previously in the peer-reviewed literature or in technical reports (Appendix C). In addition, selected data from these studies were analyzed and discussed in the National Toxicology Program's Report of the Endocrine Disruptors Low-Dose Peer Review (NTP, 2001). The present report focuses on the reproductive and general toxicology endpoints evaluated. Data obtained in separate evaluations of behavioral, neuroanatomical, neurochemical, and immunological endpoints, as well as the assessment of serum genistein levels, are also discussed to put in better perspective the selection of doses for the multigenerational and chronic studies. Genistein was administered in an irradiated soy- and alfalfa-free diet (Purina 5K96) at exposure concentrations of 0, 5, 25, 100, 250, 625, or 1,250 ppm to 10 vaginal plug-positive, female Sprague-Dawley rats starting on gestation day 7 and continuing throughout pregnancy. These dietary exposure concentrations resulted in ingested doses of approximately 0.3, 1.7, 6.4, 16, 38, and 72 mg genistein/kg body weight to dams in the 5, 25, 100, 250, 625, and 1,250 ppm groups, respectively. Dietary exposure of the dams continued through lactation, during which time ingested doses were approximately 0.6, 3.5, 14, 37, 84, and 167 mg/kg per day. Pups from five litters, culled to eight per litter with an equal sex distribution on postnatal day (PND) 2

  7. High-dose tocopherol acetate therapy in epidermolysis bullosa siblings of the Cockayne-Touraine type.

    PubMed

    Shirakata, Y; Shiraishi, S; Sayama, K; Shinmori, H; Miki, Y

    1993-11-01

    We have employed a successful therapy for epidermolysis bullosa with high-dose oral tocopherol acetate. Two siblings with dominant dystrophic epidermolysis bullosa of the Cockayne-Touraine type were reported. Both siblings suffered from tense blisters and erosions healing with scars and transient milia on the extremities. Electron microscopic study of the blisters revealed a cleavage beneath the lamina densa in both siblings. High-dose oral tocopherol acetate therapy was administered to them with satisfactory clinical reduction of the blister formation.

  8. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

    PubMed

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Furukawa, Souhei; Kakimoto, Naoya; Shimizutani, Kimishige; Inoue, Toshihiko

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n = 341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer.

  9. Rat hepatocarcinogenesis induced by N-nitrosodiethylamine and N-nitrosomorpholine continuously administered at low doses. From basophilic areas of hepatocytes to hepatocellular tumors.

    PubMed Central

    Cortinovis, C.; Klimek, F.; Nogueira, E.

    1991-01-01

    The development of hepatocellular tumors was investigated with histological, histochemical, and morphometrical methods in male Sprague-Dawley rats continuously administered N-nitrosodiethylamine (DEN) or N-nitrosomorpholine (NNM) in the drinking water at low doses (0.5 mg DEN/100 ml; 1 mg NNM/100 ml). Groups of control, DEN-, and NNM-treated rats were investigated at 5-week intervals. Similar results were obtained in DEN- and NNM-treated rats. Two types of areas composed of basophilic or glycogenotic hepatocytes were observed preceding the appearance of hepatocellular adenomas and carcinomas. Besides their cytologic differences, the basophilic and glycogenotic areas induced displayed distinct histochemical features. Both types of areas were detected simultaneously and increased in parallel with time to a similar incidence, but basophilic areas reached larger sizes than the glycogenotic ones. Furthermore, each type of area, which clustered around and along efferent veins, was differently linked to tumorigenesis. Basophilic areas frequently developed into basophilic adenomas and trabecular carcinomas through a characteristic sequence. Early basophilic areas consisted of hepatocytes with lamellar cytoplasmic hyperbasophilia and exhibited the normal laminar liver structure. With time, an increasing number of basophilic areas also contained hepatocytes with powdered diffuse hyperbasophilia, which frequently were arranged in thick trabeculae, showed abundant mitotic figures, and invaded efferent veins. Neither such signs of malignancy nor conversion into basophilic areas or tumors could be established for areas of clear and acidophilic glycogenotic hepatocytes. However, a few small glycogenotic adenomas probably developed from glycogenotic areas. Our data thus underline the central role of basophilic areas for hepatocarcinogenesis. Moreover, taking into account the data from other experiments, it seems likely that although glycogenotic areas may be associated with the

  10. Thyroid carcinoma after radioiodide therapy for hyperthyroidism. Analysis based on age, latency, and administered dose of I-/sup 131/

    SciTech Connect

    Spencer, R.P.; Chapman, C.N.; Rao, H.

    1983-05-01

    Twenty-five reports in the medical literature of thyroid carcinomas which were detected after radioiodide therapy for hyperthyroidism were reviewed. These cases did not show a usual characteristic of radiation-associated tumors, namely a long latency period. That is, in 8/25 the latency period was under five years, and the mean latency was only 7.3 years. Further, there was no relationship between latency and age at treatment, or between latency and the dose of radioiodide employed. In 15/25 of the cases, there were known thyroid nodules. Three of the patients had thyroiditis (which itself has a correlation with thyroid carcinoma), and one individual had prior head and neck external radiation. There was no substantiating evidence that radioiodide treatment for hyperthyroidism was the cause of these thyroid carcinomas.

  11. The effects of midazolam and butorphanol, administered alone or combined, on the dose and quality of anaesthetic induction with alfaxalone in goats.

    PubMed

    Dzikiti, T Brighton; Zeiler, Gareth E; Dzikiti, Loveness N; Garcia, Eva R

    2014-01-01

    Goats are rarely anaesthetised; consequently, scant information is available on the efficacy of anaesthetic drugs in this species. Alfaxalone is a relatively new anaesthetic agent, of which the efficacy in goats has not yet been studied. In this study, the sedative and alfaxalone sparing effects of midazolam and butorphanol, administered alone or concomitantly, in goats were assessed. Eight clinically healthy goats, four does and four wethers, were enlisted in a randomised crossover manner to receive intramuscular sedative treatments consisting of saline 0.05 mL/kg, or midazolam 0.30 mg/kg, or butorphanol 0.10 mg/kg, or a combination of midazolam 0.30 mg/kg with butorphanol 0.10 mg/kg before intravenous induction of general anaesthesia with alfaxalone. Following induction, the goats were immediately intubated and the quality of anaesthesia and basic physiological cardiorespiratory and blood-gas parameters were assessed until the goats had recovered from anaesthesia. The degree of sedation, quality of induction and recovery were scored. When compared with saline (3.00 mg/kg), midazolam,administered alone or with butorphanol, caused a statistically significant increased level of sedation and a reduction in the amount of alfaxalone required for induction (2.00 mg/kg and 1.70 mg/kg, respectively). Butorphanol alone (2.30 mg/kg) did not cause significant changes in level of sedation or alfaxalone-induction dose. During induction and recovery, the goats were calm following all treatments, including the control group. Cardiorespiratory and blood-gas parameters were maintained within clinically acceptable limits. The present study showed that midazolam, administered alone or combined with butorphanol, produces a degree of sedation that significantly reduces the dose of alfaxalone required for induction of general anaesthesia in goats, without causing any major adverse cardiorespiratory effects. PMID:25686277

  12. [Changes in the rat liver after exposure to high doses of bromex].

    PubMed

    Krustev, L; Kaloianova-Simeonova, F

    1982-01-01

    Experiments were carried out with male albino rats treated with the phosphorous-organic compound--bromex. The pesticide was perorally administered to one of the experimental groups--a single dose of 1/2 LD50. The same quantity bromex was administered to the other experimental group after a previous 20-day treatment with the same preparation but with a dose of 1/20 LD50. The changes, not particularly well manifested, progressing the organelles of the liver cells were followed up. The changes were established (in mitochondria, endoplasmatic reticulum, lysozoymes and some other organelles) to be better manifested in the group under a single effect of bromex. In this case they are interpreted as manifestation of one initial alterative process. In the group with the 20-day low doses, followed up by one high dose, the changes were gradual, lighter and considered a manifestation of a sort of adaptation or a form of subcellular liver regeneration. PMID:7178067

  13. Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

    PubMed Central

    2013-01-01

    Background This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320–400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively. Results Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively

  14. The combination of trastuzumab and pertuzumab administered at approved doses may delay development of trastuzumab resistance by additively enhancing antibody-dependent cell-mediated cytotoxicity

    PubMed Central

    Tóth, Gábor; Szöőr, Árpád; Simon, László; Yarden, Yosef; Szöllősi, János; Vereb, György

    2016-01-01

    ABSTRACT Although the recently concluded CLEOPATRA trial showed clinical benefits of combining trastuzumab and pertuzumab for treating HER2-positive metastatic breast cancer, trastuzumab monotherapy is still the mainstay in adjuvant settings. Since trastuzumab resistance occurs in over half of these cancers, we examined the mechanisms by which treatment of intrinsically trastuzumab-resistant and -sensitive tumors can benefit from the combination of these antibodies. F(ab′)2 of both trastuzumab and pertuzumab were generated and validated in order to separately analyze antibody-dependent cell-mediated cytotoxicity (ADCC)-based and direct biological effects of the antibodies. Compared to monotherapy, combination of the two antibodies at clinically permitted doses enhanced the recruitment of natural killer cells responsible for ADCC, and significantly delayed the outgrowth of xenografts from intrinsically trastuzumab-resistant JIMT-1 cells. Antibody dose-response curves of in vitro ADCC showed that antibody-mediated killing can be saturated, and the two antibodies exert an additive effect at sub-saturation doses. Thus, the additive effect in vivo indicates that therapeutic tissue levels likely do not saturate ADCC. Additionally, isobole studies with the in vitro trastuzumab-sensitive BT-474 cells showed that the direct biological effect of combined treatment is additive, and surpasses the maximum effect of either monotherapy. Our results suggest the combined therapy is expected to give results that are superior to monotherapy, whatever the type of HER2-positive tumor may be. The combination of both antibodies at maximum clinically approved doses should thus be administered to patients to recruit maximum ADCC and cause maximum direct biological growth inhibition. PMID:27380003

  15. A Simple Low-dose X-ray CT Simulation from High-dose Scan

    PubMed Central

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong

    2015-01-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements. PMID:26543245

  16. High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study.

    PubMed Central

    Jonkhoff, A. R.; Plaizier, M. A.; Ossenkoppele, G. J.; Teule, G. J.; Huijgens, P. C.

    1995-01-01

    Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia. Images Figure 2 PMID:8519674

  17. Immune reactivity after high-dose irradiation

    SciTech Connect

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-03-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient.

  18. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

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

    2014-01-01

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

  19. Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

    PubMed

    Hannoun-Lévi, J-M; Peiffert, D

    2014-10-01

    Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations.

  20. Resource utilization. High dose rate versus low dose rate brachytherapy for gynecologic cancer.

    PubMed

    Bastin, K; Buchler, D; Stitt, J; Shanahan, T; Pola, Y; Paliwal, B; Kinsella, T

    1993-06-01

    A comparative analysis of anesthesia use, perioperative morbidity and mortality, capital, and treatment cost of high dose rate versus low dose rate intracavitary brachytherapy for gynecologic malignancy is presented. To assess current anesthesia utilization, application location, and high dose rate afterloader availability for gynecologic brachytherapy in private and academic practices, a nine-question survey was sent to 150 radiotherapy centers in the United States, of which 95 (63%) responded. Of these 95 respondents, 95% used low dose rate brachytherapy, and 18% possessed high dose rate capability. General anesthesia was used in 95% of programs for tandem + ovoid and in 31% for ovoids-only placement. Differences among private and academic practice respondents were minimal. In our institution, a cost comparison for low dose rate therapy (two applications with 3 hospital days per application, operating and recovery room use, spinal anesthesia, radiotherapy) versus high dose rate treatment (five outpatient departmental applications, intravenous anesthesia without an anesthesiologist, radiotherapy) revealed a 244% higher overall charge for low dose rate treatment, primarily due to hospital and operating room expenses. In addition to its ability to save thousands of dollars per intracavitary patient, high dose rate therapy generated a "cost-shift," increasing radiotherapy departmental billings by 438%. More importantly, perioperative morbidity and mortality in our experience of 500+ high dose rate applications compared favorably with recently reported data using low dose rate intracavitary treatment. Capital investment, maintenance requirements, and depreciation costs for high dose rate capability are reviewed. Application of the defined "revenue-cost ratio" formula demonstrates the importance of high application numbers and consistent reimbursement for parity in high dose rate operation. Logically, inadequate third-party reimbursement (e.g., Medicare) reduces high

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

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

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

  2. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose.

    PubMed

    Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Guan, Peipei; Tan, Yanan; Lian, Ruyue; Qi, Jianping; Wu, Wei

    2012-06-01

    Oral delivery of protein or polypeptide drugs remains a challenge due to gastric and enzymatic degradation as well as poor permeation across the intestinal epithelia. In this study, liposomes containing bile salts were developed as a new oral insulin delivery system. The primary goal was to investigate the effect of cholate type, particle size and dosage of the liposomes on the hypoglycemic activity and oral bioavailability. Liposomes containing sodium glycocholate (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a reversed-phase evaporation method. After oral administration, all liposomes elicited a certain degree of hypoglycemic effect in parallel with an increase in blood insulin level. The highest oral bioavailability of approximately 8.5% and 11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed slower and sustained action over a period of over 20 h with peak time around 8-12h. SGC-liposomes showed higher oral bioavailability than liposomes containing STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent with the highest at 150 nm or 400 nm and was proportionally correlated to the administered dose. The results supported the hypothesis of insulin absorption as intact liposomes.

  3. High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.

    PubMed

    Nguyen, M A; Staubach, P; Tamai, I; Langguth, P

    2015-02-20

    Naringin is considered the major causative ingredient of the inhibition of intestinal drug uptake by grapefruit juice. Moreover, it is contained in highly dosed nutraceuticals available on the market. A controlled, open, randomized, crossover study was performed in 10 healthy volunteers to investigate the effect of high-dose naringin on the bioavailability of talinolol, a substrate of intestinal organic anion-transporting polypeptide (OATP)-mediated uptake. Following 6-day supplementation with 3 capsules of 350 mg naringin daily, 100mg talinolol were administered orally with 3 capsules of the same dietary supplement (1050 mg naringin) on the seventh day. This test treatment was compared to 100mg talinolol only (control). The results showed that short-term high-dose naringin supplementation did not significantly affect talinolol pharmacokinetics. Geometric mean ratios of test versus control ranged between 0.90 and 0.98 for talinolol c(max), AUC(0-48 h), AUC(0-∞), t(1/2) and A(e(0-48 h)). The high dose may provoke inhibition of the efflux transporter P-glycoprotein (P-gp) which counteracts the uptake inhibition. As disintegration and dissolution processes are required for the solid dosage form, dissolved naringin may arrive at the site of interaction after talinolol is already absorbed. In conclusion, the effect of nutraceuticals on drug pharmacokinetics can deviate from that observed when administered as food component due to the different dose and dosage form.

  4. Immunotherapy with low-dose recombinant interleukin 2 after high-dose chemotherapy and autologous stem cell transplantation in neuroblastoma.

    PubMed

    Pession, A; Prete, A; Locatelli, F; Pierinelli, S; Pession, A L; Maccario, R; Magrini, E; De Bernardi, B; Paolucci, P; Paolucci, G

    1998-08-01

    The purpose of this study was to evaluate in a phase I-II trial whether low doses of recombinant human interleukin 2 (rHuIL-2) over a prolonged period of time are safe and effective in eradicating or controlling minimal residual disease in children with neuroblastoma given high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). From January 1992 to July 1996, 17 consecutive patients, with either stage IV or relapsed neuroblastoma, were enrolled. Patients received rHuIL-2 after a median time interval (min-max) of 105 days (56-153) after HDCT and ASCT. The protocol consisted of 2 'priming' courses of rHuIL-2 at escalating doses administered intravenously at 72-h intervals, followed by 'maintenance' with 11 monthly and six bimonthly boosting 5-day courses administered subcutaneously on an outpatient basis. At April 1997, 7 out of the 17 patients had completed the treatment schedule, four had discontinued treatment because of toxicity and four because of relapse; the remaining two patients are still on treatment, having completed 15 courses. Expansion of T lymphocytes, together with an increase in both natural killer cells and in activated T lymphocytes was evidenced. After a median (min-max) follow-up time of 30 (16-64) months, 12 out of 17 patients are alive and well. Two patients relapsed and died 14 and 35 months after transplant. Three patients are alive after having relapsed at 41, 21 and 13 months. The actuarial 2-year event-free survival and overall survival are 67% and 92% respectively. Intermittent administration of low doses of rHuIL-2 given for a long period of time is well tolerated and seems capable of controlling minimal residual disease after HDCT and ASCT in children with high-risk neuroblastoma.

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

    PubMed Central

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

    2012-01-01

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

  6. "Effects of recombinant human erythropoietin high mimicking abuse doses on oxidative stress processes in rats".

    PubMed

    Bianchi, Sara; Fusi, Jonathan; Franzoni, Ferdinando; Giovannini, Luca; Galetta, Fabio; Mannari, Claudio; Guidotti, Emanuele; Tocchini, Leonardo; Santoro, Gino

    2016-08-01

    Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n=36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30μg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F2α, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NOX were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses. PMID:27470373

  7. Dose characterization in the near-source region for two high dose rate brachytherapy sources.

    PubMed

    Wang, Ruqing; Li, X Allen

    2002-08-01

    High dose rate (HDR) 192Ir sources are currently used in intravascular brachytherapy (IVB) for the peripheral arterial system. This poses a demand on evaluating accurate dose parameters in the near-source region for such sources. The purpose of this work is to calculate the dose parameters for the old VariSource HDR 192Ir source and the new microSelectron HDR 192Ir source, using Monte Carlo electron and photon transport simulation. The two-dimensional (2D) dose rate distributions and the air kerma strengths for the two HDR sources were calculated by EGSnrc and EGS4 Monte Carlo codes. Based on these data, the dose parameters proposed in the AAPM TG-60 protocol were derived. The dose rate constants obtained are 13.119+/-0.028 cGy h(-1) U(-1) for the old VariSource source, and 22.751+/-0.031 cGy h(-1) U(-1) for the new microSelectron source at the reference point (r0 = 2 mm, theta = pi/2). The 2D dose rate distributions, the radial dose functions, and the anisotropy functions presented for the two sources cover radial distances ranging from 0.5 to 10 mm. In the near-source region on the transverse plane, the dose effects of the charged particle nonequilibrium and the beta-particle dose contribution were studied. It is found that at radial distances ranging from 0.5 to 2 mm, these effects increase the calculated dose rates by up to 29% for the old VariSource source, and by up to 12% for the new microSelectron source, which, in turn, change values of the radial dose function and the anisotropy function. The present dose parameters, which account for the charged particle nonequilibrium and the beta particle contribution, may be used for accurate IVB dose calculation. PMID:12201413

  8. Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats

    PubMed Central

    Ingberg, Edvin; Theodorsson, Elvar; Theodorsson, Annette; Ström, Jakob O.

    2016-01-01

    The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct. PMID:26839007

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

    PubMed

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

    2013-08-29

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

  10. In-phantom neutron dose distribution for bladder cancer cases treated with high-energy photons

    NASA Astrophysics Data System (ADS)

    Khaled, N. E.; Attalla, E. M.; Ammar, H.; Khalil, W.

    2011-06-01

    This work presents an estimation of the neutron dose distribution for common bladder cancer cases treated with high-energy photons of 15 MV therapy accelerators. Neutron doses were measured in an Alderson phantom, using TLD 700 and 600 thermoluminescence dosimeters, resembling bladder cancer cases treated with high-energy photons from 15 MV LINAC and having a treatment plan using the four-field pelvic box technique. Thermal neutron dose distribution in the target area and the surrounding tissue was estimated. The sensitivity of all detectors for both gamma and neutrons was estimated and used for correction of the TL reading. TLD detectors were irradiated with a Co60 gamma standard source and thermal neutrons at the irradiation facility of the National Institute for Standards (NIS). The TL to dose conversion factor was estimated in terms of both Co60 neutron equivalent dose and thermal neutron dose. The dose distribution of photo-neutrons throughout each target was estimated and presented in three-dimensional charts and isodose curves. The distribution was found to be non-isotropic through the target. It varied from a minimum of 0.23 mSv/h to a maximum of 2.07 mSv/h at 6 cm off-axis. The mean neutron dose equivalent was found to be 0.63 mSv/h, which agrees with other published literature. The estimated average neutron equivalent to the bladder per administered therapeutic dose was found to be 0.39 mSv Gy-1, which is also in good agreement with published literature. As a consequence of a complete therapeutic treatment of 50 Gy high-energy photons at 15 MV, the total thermal neutron equivalent dose to the abdomen was found to be about 0.012 Sv.

  11. High-Dose-Rate 192Ir Brachytherapy Dose Verification: A Phantom Study

    PubMed Central

    Nikoofar, Alireza; Hoseinpour, Zohreh; Rabi Mahdavi, Seied; Hasanzadeh, Hadi; Rezaei Tavirani, Mostafa

    2015-01-01

    Background: The high-dose-rate (HDR) brachytherapy might be an effective tool for palliation of dysphagia. Because of some concerns about adverse effects due to absorbed radiation dose, it is important to estimate absorbed dose in risky organs during this treatment. Objectives: This study aimed to measure the absorbed dose in the parotid, thyroid, and submandibular gland, eye, trachea, spinal cord, and manubrium of sternum in brachytherapy in an anthropomorphic phantom. Materials and Methods: To measure radiation dose, eye, parotid, thyroid, and submandibular gland, spine, and sternum, an anthropomorphic phantom was considered with applicators to set thermoluminescence dosimeters (TLDs). A specific target volume of about 23 cm3 in the upper thoracic esophagus was considered as target, and phantom planned computed tomography (CT) for HDR brachytherapy, then with a micro-Selectron HDR (192Ir) remote after-loading unit. Results: Absorbed doses were measured with calibrated TLDs and were expressed in centi-Gray (cGy). In regions far from target (≥ 16 cm) such as submandibular, parotid and thyroid glands, mean measured dose ranged from 1.65 to 5.5 cGy. In closer regions (≤ 16 cm), the absorbed dose might be as high as 113 cGy. Conclusions: Our study showed similar depth and surface doses; in closer regions, the surface and depth doses differed significantly due to the role of primary radiation that had imposed a high-dose gradient and difference between the plan and measurement, which was more severe because of simplifications in tissue inhomogeneity, considered in TPS relative to phantom. PMID:26413250

  12. High-resolution low-dose scanning transmission electron microscopy

    PubMed Central

    Buban, James P.; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D.; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM. PMID:19915208

  13. High-resolution low-dose scanning transmission electron microscopy.

    PubMed

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  14. Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Chun, S. Y.; Reginatto, M.; Hajnal, F.

    1995-01-01

    The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neo-plastic transformation as function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical application.

  15. Calculation of Dose, Dose Equivalent, and Relative Biological Effectiveness for High Charge and Energy Ion Beams

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Reginatto, M.; Hajnal, F.; Chun, S. Y.

    1995-01-01

    The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H1OT1/2 cell survival and neoplastic transformation as a function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical applications.

  16. Postoperative High-Dose-Rate Brachytherapy in the Prevention of Keloids

    SciTech Connect

    Veen, Ronald E. Kal, Henk B.

    2007-11-15

    Background: The aim of this study is to show the efficiency of keloidectomy and postoperative interstitial high-dose-rate (HDR) brachytherapy in the prevention of keloids. Methods and Materials: Between 1998 and 2004, 35 patients with 54 keloids were treated postoperatively with HDR brachytherapy. The first HDR dose was applied within 6 hours after surgery, and two additional HDR doses were administered on the next day with a six-hour interval. The majority of patients received 6 Gy as the first dose postsurgery and two fractions of 4 Gy (38 keloids) on the next day. Seven keloids were treated postoperatively with three fractions of 6 Gy. The biologically effective dose (BED), derived from the linear quadratic concept, was applied to calculate the BED for the various radiation regimens. The keloid recurrence rates at specific BED values were compared with those derived for other fractionation schemes in the literature. Results: Four recurrences/nonsatisfactory results out of nine treated keloids were observed after treatments with 1 x 4 Gy + 2 x 3 Gy. Only one recurrence out of 38 was found after 1 x 6 Gy + 2 x 4 Gy and none after 3 x 6 Gy. Better cosmetic results were found at the higher-dose schemes. Conclusion: The results of this study prove the effectiveness of HDR brachytherapy after keloidectomy provided that the total HDR dose is sufficient. Currently our scheme is 3 x 6 Gy.

  17. Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic tolerance to a subsequent high-dose methamphetamine binge.

    PubMed

    O'Neil, Meghan L; Kuczenski, Ronald; Segal, David S; Cho, Arthur K; Lacan, Goran; Melega, William P

    2006-11-01

    A major feature of human methamphetamine (METH) abuse is the gradual dose escalation that precedes high-dose exposure. The period of escalating doses (EDs) is likely associated with development of tolerance to aspects of METH's pharmacologic and toxic effects but the relative contributions of pharmacokinetic and pharmacodynamic factors have not been well defined. In our prior studies in rats, we showed that pretreatment with an ED-METH regimen (0.1-4.0 mg/kg over 14 days) attenuated the toxicity of a subsequently administered high-dose METH binge (4 x 6 mg/kg at 2 h interval) that itself produced behavioral stereotypy, increases in core temperature, and decreases in DA system phenotypic markers in caudate-putamen (CP). Using those ED-METH and binge protocols in the present studies, pharmacokinetic and pharmacodynamic parameters that may have contributed to the apparent neuroprotection afforded by ED-METH were assessed. The ED-METH regimen itself reduced [(3)H]WIN35,428 (WIN) binding to the dopamine transporter (DAT) by 15% in CP, but did not affect DA content. During the METH binge, ED-METH pretreated animals showed attenuated increases in core temperature while concurrent microdialysis studies in CP showed a reduced DA response despite unaltered extracellular levels of METH. At 1 h after the binge, concentrations of METH and its metabolite amphetamine in brain and plasma were unaffected by the ED-METH. The results show that ED-METH pretreatment produces reductions in DAT binding and the DA response during a subsequent METH binge by altering pharmacodynamic and not pharmacokinetic parameters.

  18. Efficacy of a single high oxfendazole dose against gastrointestinal nematodes in naturally infected pigs.

    PubMed

    Alvarez, Luis; Saumell, Carlos; Fusé, Luis; Moreno, Laura; Ceballos, Laura; Domingue, Gilbert; Donadeu, Meritxell; Dungu, Baptiste; Lanusse, Carlos

    2013-05-01

    The goal of the current experiment was to assess the clinical efficacy of oxfendazole (OFZ) administered as a single oral dose (30 mg/kg) to pigs naturally parasitized with Ascaris suum, Oesophagostomum spp., Metastrongylus spp. and Trichuris suis. Thirty-six local ecotype piglets were divided into three independent experiments, named I, II and III (n=12 each), respectively. Each experiment involved two different groups (n=6): Untreated Control and OFZ treated. Animals were naturally parasitized with A. suum (Experiments I, II and III), Oesophagostomum spp. (Experiments I and II), T. suis (Experiments II and III) and Metastrongylus spp. (Experiment I). Pigs in the treated group received OFZ (Synanthic(®), Merial Ltd., 9.06% suspension) orally at 30 mg/kg dose. At five (5) days post-treatment, animals were sacrificed and the clinical efficacy of the OFZ treatment was established following the currently available WAAVP guidelines for a controlled efficacy test. None of the animals involved in this experiment showed any adverse events during the study. OFZ treatment given as a single 30 mg/kg oral dose showed a 100% efficacy against all the nematode parasites present in the three experiments. In conclusion, under the current experimental conditions, OFZ orally administered to naturally parasitized piglets at a single dose of 30 mg/kg was safe and highly efficacious (100%) against adult stages of A. suum, Oesophagostomum spp., T. suis and Metastrongylus spp. PMID:23357598

  19. Efficacy of a single high oxfendazole dose against gastrointestinal nematodes in naturally infected pigs.

    PubMed

    Alvarez, Luis; Saumell, Carlos; Fusé, Luis; Moreno, Laura; Ceballos, Laura; Domingue, Gilbert; Donadeu, Meritxell; Dungu, Baptiste; Lanusse, Carlos

    2013-05-01

    The goal of the current experiment was to assess the clinical efficacy of oxfendazole (OFZ) administered as a single oral dose (30 mg/kg) to pigs naturally parasitized with Ascaris suum, Oesophagostomum spp., Metastrongylus spp. and Trichuris suis. Thirty-six local ecotype piglets were divided into three independent experiments, named I, II and III (n=12 each), respectively. Each experiment involved two different groups (n=6): Untreated Control and OFZ treated. Animals were naturally parasitized with A. suum (Experiments I, II and III), Oesophagostomum spp. (Experiments I and II), T. suis (Experiments II and III) and Metastrongylus spp. (Experiment I). Pigs in the treated group received OFZ (Synanthic(®), Merial Ltd., 9.06% suspension) orally at 30 mg/kg dose. At five (5) days post-treatment, animals were sacrificed and the clinical efficacy of the OFZ treatment was established following the currently available WAAVP guidelines for a controlled efficacy test. None of the animals involved in this experiment showed any adverse events during the study. OFZ treatment given as a single 30 mg/kg oral dose showed a 100% efficacy against all the nematode parasites present in the three experiments. In conclusion, under the current experimental conditions, OFZ orally administered to naturally parasitized piglets at a single dose of 30 mg/kg was safe and highly efficacious (100%) against adult stages of A. suum, Oesophagostomum spp., T. suis and Metastrongylus spp.

  20. High-dose MVCT image guidance for stereotactic body radiation therapy

    SciTech Connect

    Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.; Chao, Edward; Lucas, Dan; Flynn, Ryan T.; Miften, Moyed

    2012-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a

  1. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INSULIN. Animal models have shown high-dose insulin to be superior to calcium salts, glucagon, epinephrine, and vasopressin in terms of survival. Currently, there are no published controlled clinical trials in humans, but a review of case reports and case series supports the use of high-dose insulin as an initial therapy. HIGH-DOSE INSULIN TREATMENT PROTOCOLS. When first introduced, insulin doses were cautiously initiated at 0.5 U/kg bolus followed by a 0.5-1 U/kg/h continuous infusion due to concern for hypoglycemia and electrolyte imbalances. With increasing clinical experience and the publication of animal studies, high-dose insulin dosing recommendations have been increased to 1 U/kg insulin bolus followed by a 1-10 U/kg/h continuous infusion. Although the optimal regimen is still to be determined, bolus doses up to 10 U/kg and continuous infusions as high as 22 U/kg/h have been administered with good outcomes and minimal adverse events. ADVERSE EFFECTS OF HIGH-DOSE INSULIN. The major anticipated adverse events associated with high-dose insulin are hypoglycemia and hypokalemia. Glucose concentrations must be monitored regularly and supplementation of glucose will likely be required throughout therapy and for up to 24 h after discontinuation of high-dose insulin. The change in serum potassium concentrations reflects a shifting of potassium from the extracellular to intracellular space rather than a decrease in total body stores. CONCLUSIONS. While more clinical data are needed, animal studies and human case reports demonstrate that high-dose insulin (1-10 U/kg/hour) is a superior treatment in terms of safety and survival in both beta-blocker and calcium-channel blocker poisoning. High-dose insulin should be considered initial therapy in these poisonings. PMID:21563902

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

    PubMed

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

    2015-10-01

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

  3. [Ototoxicity following the administration of high doses of cisplatin in children with malignant neoplasms].

    PubMed

    Stura, M; Perin, G P; Dini, G; Dallorso, S; Squazzini, G; Tacchino, A; Tarantino, V; De Bernardi, B

    1985-01-01

    CDDP is an antitumor agent which has shown effectiveness in a variety of pediatric and adult solid tumors. Main toxic effects of CDDP involve kidney, bone marrow and ear functions. Recently, CDDP has been used at "high doses" (200 mg/sq m, compared with 90-100 mg/sq m used previously) on the basis of its dose dependent antitumor activity. Ear toxicity might be higher with the "high doses" schedule, and this could be of much importance for younger patients, due the irreversibility of the lesion induced by the drug on the ear structure. In this study, the Authors have prospectively evaluated the ear function in children undergoing treatment with "high doses" CDDP and have compared it with that determined by the drug administered at "traditional" doses. Between september 1984 and march 1985, ten children aged 3-10 years, affected by tumors either resistant to first line therapy or at relapse, were treated with CDDP, 200 mg/sq m divided in five daily doses (days 2-6) (Vincristine, 2 mg/sq m and Cyclophosphamide, 600 mg/sq m, were given on day 1). Six out of ten children had been previously treated with CDDP at "traditional" doses. Acoustic function has been evaluated with tonal audiometry performed before therapy, 2 and 15 days after each cycle of therapy. A deficit was scored mild for levels between 15 and 30 dB, medium for levels between 30 and 60 dB, severe for levels greater than 60 dB. The Audiometry performed in six children who had previously been treated with CDDP at "traditional doses" demonstrated a deficit limited at 8000 Hz in five of them.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Effect of aspartame and protein, administered in phenylalanine-equivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man.

    PubMed

    Møller, S E

    1991-05-01

    Six human males each received 0.56 g phenylalanine (Phe) in the form of 1.0 g aspartame or 12.2 g bovine albumin in 200 ml water or water alone. Venous blood samples collected before consumption and during the following 4 hr were assayed for plasma levels of large, neutral amino acids (LNAA), aspartate, insulin and glucose. The area under the curve for plasma Phe was 40% greater, although not significant, after aspartame compared with albumin intake. The indicated increased clearance rate of plasma Phe after albumin may be caused by the significant increase of insulin, on which aspartame had no effect. There was a significant main effect of aspartame for plasma tyrosine but not for tryptophan, valine, isoleucine or leucine. Plasma aspartate was significantly increased at 0.25 hr after the aspartame intake. The percentage Phe/LNAA decreased slightly in response to albumin but increased 55% after aspartame and remained significantly increased for 2 hr. Tyrosine/LNAA increased and tryptophan/LNAA decreased modestly after aspartame intake. The study showed that the intake of aspartame in a not unrealistically high dose produced a marked and persistent increase of the availability of Phe to the brain, which was not observed after protein intake. The study indicated, furthermore, that Phe was cleared faster from the plasma after consumption of protein compared with aspartame.

  5. High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma

    PubMed Central

    Seo, Min-Seok; Kim, Ja-Kyung

    2015-01-01

    We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma. PMID:26256994

  6. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  7. Pharmacokinetics and buccal mucosal concentrations of a 15 milligram per kilogram of body weight total dose of liposomal amphotericin B administered as a single dose (15 mg/kg), weekly dose (7.5 mg/kg), or daily dose (1 mg/kg) in peripheral stem cell transplant patients.

    PubMed

    Gubbins, Paul O; Amsden, Jarrett R; McConnell, Scott A; Anaissie, Elias J

    2009-09-01

    The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 microg/ml for the first 7 days and >0.220 microg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 microg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB. PMID:19546359

  8. Pharmacokinetics and Buccal Mucosal Concentrations of a 15 Milligram per Kilogram of Body Weight Total Dose of Liposomal Amphotericin B Administered as a Single Dose (15 mg/kg), Weekly Dose (7.5 mg/kg), or Daily Dose (1 mg/kg) in Peripheral Stem Cell Transplant Patients▿

    PubMed Central

    Gubbins, Paul O.; Amsden, Jarrett R.; McConnell, Scott A.; Anaissie, Elias J.

    2009-01-01

    The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 μg/ml for the first 7 days and >0.220 μg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 μg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB. PMID:19546359

  9. Pharmacokinetics and buccal mucosal concentrations of a 15 milligram per kilogram of body weight total dose of liposomal amphotericin B administered as a single dose (15 mg/kg), weekly dose (7.5 mg/kg), or daily dose (1 mg/kg) in peripheral stem cell transplant patients.

    PubMed

    Gubbins, Paul O; Amsden, Jarrett R; McConnell, Scott A; Anaissie, Elias J

    2009-09-01

    The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 microg/ml for the first 7 days and >0.220 microg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 microg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB.

  10. Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

    NASA Astrophysics Data System (ADS)

    Armpilia, C.; Dale, R. G.; Sandilos, P.; Vlachos, L.

    2006-09-01

    This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BEDeq) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component.

  11. Interaction of 2-Gy Equivalent Dose and Margin Status in Perioperative High-Dose-Rate Brachytherapy

    SciTech Connect

    Martinez-Monge, Rafael; Cambeiro, Mauricio; Moreno, Marta; Gaztanaga, Miren; San Julian, Mikel; Alcalde, Juan; Jurado, Matias

    2011-03-15

    Purpose: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clinica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions: Two-gray equivalent doses {>=}70 Gy may compensate the effect of close margins {>=}1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses {<=}50 Gy with PHDRB alone.

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  13. Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies

    PubMed Central

    Puzanov, Igor; LoRusso, Patricia M.; Cohen, Roger B.; Morris, John C.; Olowokure, Olugbenga O.; Yin, Jian Y.; Doroumian, Séverine; Shen, Liji; Olszanski, Anthony J.

    2015-01-01

    Taxane–gemcitabine combinations have demonstrated antitumor activity. This phase I study (NCT01001221) aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus gemcitabine and to assess the preliminary efficacy of this combination. The patients included had metastatic or unresectable solid tumors and had exhausted standard treatment. Cohorts of three to six patients received cabazitaxel (15–20 mg/m2) before (part 1a) or after (part 1b) gemcitabine (700–1000 mg/m2) on Day 1 and gemcitabine alone on Day 8. Prophylactic growth factors were not allowed in cycle 1. In part 1a (n=12), five patients received 20 mg/m2 cabazitaxel plus 1000 mg/m2 gemcitabine (20/1000), five received 15/900, two received 15/700. In part 1b, all six patients received the lowest dose (700/15). At all doses, two or more patients experienced a DLT, regardless of administration sequence, including febrile neutropenia (n=4), grade 4 neutropenia (n=2), grade 4 thrombocytopenia (n=2), and grade 3 aspartate transaminase increase (n=1). The MTD was not established as all cohorts exceeded the MTD by definition. All patients experienced an adverse event; the most frequent all-grade nonhematologic events were fatigue (66.7%), decreased appetite (50.0%), and diarrhea (44.4%). The most frequent grade 3–4 hematologic abnormalities were neutropenia (83.3%), leukopenia (77.8%), and lymphopenia (72.2%). Toxicity was sequence-independent but appeared worse with gemcitabine followed by cabazitaxel. Durable partial responses were observed in three patients (prostate cancer, appendiceal cancer, and melanoma). The unacceptable DLTs with cabazitaxel plus gemcitabine, at doses reduced more than 25% from single-agent doses, preclude further investigation. PMID:26020806

  14. High or low dose radioiodine ablation of thyroid remnants?

    PubMed

    Creutzig, H

    1987-01-01

    The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose 131I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiated pT2-3NoMo thyroid cancer were studied. The uptake was 5%-10% at 24 h. Ten patients received 100 mCi, the others 30 mCi 131I. Three months later all patients received a therapeutic dose of 150 mCi 131I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%-10%. Ten patients received 300 mCi and ten 30 mCi 131I as ablation dose. Three months later all received 300 mCi 131I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24 h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, N X M1 patients the ablation was effective in seven out of ten cases in both groups. If "effective" ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in N X M1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3569338

  15. High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse.

    PubMed

    Leelahavanichkul, Asada; Somparn, Poorichaya; Bootprapan, Tanabodee; Tu, Hongbin; Tangtanatakul, Pattarin; Nuengjumnong, Ratchanok; Worasilchai, Navaporn; Tiranathanagul, Khajohn; Eiam-ong, Somchai; Levine, Mark; Chinampon, Ariya; Srisawat, Nattachai

    2015-08-01

    Amphotericin B (Ampho B) isa fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically.W e tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression inpatients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with < 11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage,liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans. PMID:25994956

  16. Assessments for High Dose Radionuclide Therapy Treatment Planning

    SciTech Connect

    Fisher, Darrell R.

    2003-10-01

    Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.

  17. Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F{sub 1} mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide

    SciTech Connect

    Tareke, Eden; Twaddle, Nathan C.; McDaniel, L. Patrice; Churchwell, Mona I.; Young, John F.; Doerge, Daniel R. . E-mail: daniel.doerge@fda.hhs.gov

    2006-11-15

    Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells and carcinogenic in rodents. AA is also formed in many commonly consumed starchy foods during cooking. Our previous toxicokinetic investigations of AA and its important genotoxic metabolite, glycidamide (GA), in rodents showed that AA is highly bioavailable from oral routes of administration, is widely distributed to tissues and that the dietary route, in particular, favors metabolism to GA. Measurements of DNA adducts in many tissues supported the hypothesis that AA is carcinogenic in rodent bioassays through metabolism to GA. The current investigation describes the development and validation of methodology for measuring hemoglobin (Hb) adducts with AA and GA in the same rodents previously used for toxicokinetic and DNA adduct measurements. The goal was to investigate possible relationships between these circulating biomarkers of exposure and serum toxicokinetic parameters for AA and GA and tissue GA-DNA adducts in rodents from both single and repeated dosing with AA. Significant correlations were observed between GA-Hb and liver GA-DNA adducts for either single or multiple dosing regimens with AA. Using available GA-Hb adduct data, empirical and allometric relationships permitted estimation of liver DNA adducts in humans in the range of 0.06-0.3 adducts/10{sup 8} nucleotides. This approach may prove useful in extrapolating human cancer risks from findings in rodent bioassays.

  18. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor

    PubMed Central

    Sung, Ki Woong; Lim, Do Hoon; Yi, Eun Sang; Choi, Young Bae; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Ji Hye; Suh, Yeon-Lim; Joung, Yoo Sook; Shin, Hyung Jin

    2016-01-01

    Purpose We prospectively evaluated the effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in improving the survival of patients with atypical teratoid/rhabdoid tumors while reducing the risks of late adverse effects from radiotherapy (RT). Materials and Methods For young children (< 3 years old), tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. RT was deferred until after 3 years of age unless the tumor showed relapse or progression. For older patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6 Gy) was administered either after two cycles of induction chemotherapy or after surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. Results A total of 13 patients (five young and eight older) were enrolled from November 2004 to June 2012. Eight patients, including all five young patients, had metastatic disease at diagnosis. Six patients (four young and two older) experienced progression before initiation of RT, and seven were able to proceed to HDCT/auto-SCT without progression during induction treatment. Three of six patients who experienced progression during induction treatment underwent HDCT/auto-SCT as salvage treatment. All five young patients died from disease progression. However, four of the eight older patients remain progression-freewith a median follow-up period of 64 months (range, 39 to 108 months). Treatment-related late toxicities were acceptable. Conclusion The required dose of craniospinal RT might be reduced in older patients if the intensity of chemotherapy is increased. However, early administration of RT should be considered to prevent early progression in young patients. PMID:27034140

  19. Japanese consensus guidelines for pediatric nuclear medicine. Part 1: Pediatric radiopharmaceutical administered doses (JSNM pediatric dosage card). Part 2: Technical considerations for pediatric nuclear medicine imaging procedures.

    PubMed

    Koizumi, Kiyoshi; Masaki, Hidekazu; Matsuda, Hiroshi; Uchiyama, Mayuki; Okuno, Mitsuo; Oguma, Eiji; Onuma, Hiroshi; Kanegawa, Kimio; Kanaya, Shinichi; Kamiyama, Hiroshi; Karasawa, Kensuke; Kitamura, Masayuki; Kida, Tetsuo; Kono, Tatsuo; Kondo, Chisato; Sasaki, Masayuki; Terada, Hitoshi; Nakanishi, Atsushi; Hashimoto, Teisuke; Hataya, Hiroshi; Hamano, Shin-ichiro; Hirono, Keishi; Fujita, Yukihiko; Hoshino, Ken; Yano, Masayuki; Watanabe, Seiichi

    2014-06-01

    The Japanese Society of Nuclear Medicine has recently published the consensus guidelines for pediatric nuclear medicine. This article is the English version of the guidelines. Part 1 proposes the dose optimization in pediatric nuclear medicine studies. Part 2 comprehensively discusses imaging techniques for the appropriate conduct of pediatric nuclear medicine procedures, considering the characteristics of imaging in children.

  20. Synthesis and dose interval dependent hepatotoxicity evaluation of intravenously administered polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticle on Wistar rats.

    PubMed

    Rajan, Balan; Sathish, Shanmugam; Balakumar, Subramanian; Devaki, Thiruvengadam

    2015-03-01

    Superparamagnetic iron oxide nanoparticles are being used in medical imaging, drug delivery, cancer therapy, and so on. However, there is a direct need to identify any nanotoxicity associated with these nanoparticles. However uncommon, drug-induced liver injury (DILI) is a major health concern that challenges pharmaceutical industry and drug regulatory agencies alike. In this study we have synthesized and evaluated the dose interval dependent hepatotoxicity of polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticles (PUSPIOs). To assess the hepatotoxicity of intravenously injected PUSPIOs, alterations in basic clinical parameters, hematological parameters, hemolysis assay, serum levels of liver marker enzymes, serum and liver lipid peroxidation (LPO) levels, enzymatic antioxidant levels, and finally histology of liver, kidney, spleen, lung, brain, and heart tissues were studied in control and experimental Wistar rat groups over a 30-day period. The results of our study showed a significant increase in the aspartate transaminase (AST) enzyme activity at a dose of 10mg/kg b.w. PUSPIOs twice a week. Besides, alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) enzyme activity showed a slender increase when compared with control experimental groups. A significant increase in the serum and liver LPO levels at a dose of 10mg/kg b.w. PUSPIOs twice a week was also observed. Histological analyses of liver, kidney, spleen, lung, brain and heart tissue samples showed no obvious uncharacteristic changes. In conclusion, PUSPIOs were found to posses excellent biocompatibility and Wistar rats showed much better drug tolerance to the dose of 10mg/kg b.w. per week than the dose of 10mg/kg b.w. twice a week for the period of 30 days.

  1. Synthesis and dose interval dependent hepatotoxicity evaluation of intravenously administered polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticle on Wistar rats.

    PubMed

    Rajan, Balan; Sathish, Shanmugam; Balakumar, Subramanian; Devaki, Thiruvengadam

    2015-03-01

    Superparamagnetic iron oxide nanoparticles are being used in medical imaging, drug delivery, cancer therapy, and so on. However, there is a direct need to identify any nanotoxicity associated with these nanoparticles. However uncommon, drug-induced liver injury (DILI) is a major health concern that challenges pharmaceutical industry and drug regulatory agencies alike. In this study we have synthesized and evaluated the dose interval dependent hepatotoxicity of polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticles (PUSPIOs). To assess the hepatotoxicity of intravenously injected PUSPIOs, alterations in basic clinical parameters, hematological parameters, hemolysis assay, serum levels of liver marker enzymes, serum and liver lipid peroxidation (LPO) levels, enzymatic antioxidant levels, and finally histology of liver, kidney, spleen, lung, brain, and heart tissues were studied in control and experimental Wistar rat groups over a 30-day period. The results of our study showed a significant increase in the aspartate transaminase (AST) enzyme activity at a dose of 10mg/kg b.w. PUSPIOs twice a week. Besides, alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) enzyme activity showed a slender increase when compared with control experimental groups. A significant increase in the serum and liver LPO levels at a dose of 10mg/kg b.w. PUSPIOs twice a week was also observed. Histological analyses of liver, kidney, spleen, lung, brain and heart tissue samples showed no obvious uncharacteristic changes. In conclusion, PUSPIOs were found to posses excellent biocompatibility and Wistar rats showed much better drug tolerance to the dose of 10mg/kg b.w. per week than the dose of 10mg/kg b.w. twice a week for the period of 30 days. PMID:25721486

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

    PubMed Central

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

    2013-01-01

    Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

  3. Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain

    PubMed Central

    Leppert, Wojciech; Kowalski, Grzegorz

    2015-01-01

    Background Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB]) in cancer patients with severe neuropathic pain. However, high doses of TB of 140 µg/h are rarely used. Patients and methods Three cancer patients with severe neuropathic Numeric Rating Scale (NRS) pain scores of 8–10 who were successfully treated with high doses of TB up to 140 µg/h along with other opioids and adjuvant analgesics. Results TB was administered for a long period of follow-up (9 months to 4 years, including 34–261 days of treatment with the dose of 140 µg/h), which allowed achievement of satisfactory analgesia (NRS 3–5) and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 µg/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment. Conclusion TB at doses of up to 140 µg/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients’ quality of life. Clinical studies may explore higher than maximal 140 µg/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. PMID:26675083

  4. Spectroscopic gamma camera for use in high dose environments

    NASA Astrophysics Data System (ADS)

    Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Kometani, Yutaka; Suzuki, Yasuhiko; Umegaki, Kikuo

    2016-06-01

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  5. Population pharmacokinetics of mefloquine, administered as a fixed-dose combination of artesunate-mefloquine in Indian patients for the treatment of acute uncomplicated Plasmodium falciparum malaria

    PubMed Central

    2014-01-01

    Background Fixed-dose combinations of artemisinin combination therapy are strongly recommended to facilitate drug administration and compliance. New fixed-dose combinations must nevertheless be evaluated in relevant populations in terms of efficacy and pharmacokinetics. Methods A single-arm, open-label, clinical trial was performed in Indian patients with acute uncomplicated Plasmodium falciparum malaria to investigate the efficacy and the pharmacokinetics of mefloquine when combined with artesunate in a fixed-dose combination (400/200 mg of mefloquine base/artesunate). The pharmacokinetic analysis was performed using a population approach. Results Seventy-seven patients were included in the study. Mefloquine pharmacokinetics obeys a two-compartment model with first-order absorption and elimination. Mean parameter estimates (% inter-individual variability) were as follows: 0.16 h-1 (75%) for the absorption rate constant, 1.13 L/h (30%) for the apparent plasma clearance, 271 L (21%) for the apparent central distribution volume, 344 L (54%) for the apparent peripheral distribution volume, and 1.43 L/h for the apparent distribution clearance. These values were consistent with the pharmacokinetic results described in Thai patients. No significant covariate was found for clearance. Body weight explained the inter-individual variability of the apparent central and peripheral distribution volumes. The PCR-adjusted efficacy of the treatment was 100%. Conclusions The lack of significant covariate explaining the inter-individual variability of mefloquine clearance, combined with the excellent efficacy, supports the use of the standard 200/400 mg of artesunate-mefloquine fixed-dose combination in Indian patients with uncomplicated P. falciparum malaria. Trial Registration Clinical Trial Registration: ISRCTN70618692 PMID:24886117

  6. Bispectral EEG index monitoring of high-dose nitrous oxide and low-dose sevoflurane sedation.

    PubMed Central

    Hall, David L.; Weaver, Joel; Ganzberg, Steven; Rashid, Robert; Wilson, Stephen

    2002-01-01

    This single-blind controlled clinical study characterized the effects of 30-70% nitrous oxide (N2O) and 0.2-0.8% sevoflurane conscious sedation on quantitative electroencephalographic (EEG) readings of 22 healthy dental students as measured by the bispectral index (BIS). The study verified the 2 previously published BIS/N2O investigations showing no correlation between N2O dosage up to 70% and BIS. Observer's Assessment of Alertness and Sedation scores (OAA/S), however, correlated well with increasing doses of N2O from approximately 35 to 70%. A near linear dose-response relationship was established between OAA/S and end tidal (ET) sevoflurane concentrations of 0.4-0.7%. Only at the highest level of end tidal sevoflurane recorded, 0.7%, was statistically significant BIS depression seen. Subjects evaluated the acceptability of the sedative effect of the 2 gases, showing a slight preference for N2O. Comparable partial anterograde amnesia and sedation (OAA/S) were produced by both agents in administered concentrations of 40-70% N2O and 0.6-0.8% sevoflurane. Female subjects exhibited better memory and significantly less amnesia than males. No statistically significant changes occurred in any of the monitored vital signs. EMG readings demonstrated a statistically significant difference from control values only at the highest, 0.7%, ET concentration of sevoflurane. BIS does not appear useful for evaluating the level of nitrous oxide sedation in the dental setting but may have some value in assessing depth of sedation at deeper levels of sevoflurane sedation. Images Figure 1 Figure 2 PMID:15384293

  7. Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity.

    PubMed

    McKee, Richard H; Nicolich, Mark; Roy, Timothy; White, Russell; Daughtrey, Wayne C

    2014-01-01

    Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general.

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

    SciTech Connect

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

    2014-02-15

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about −3%. When the source was positioned at the skin surface, dose differences were smaller than −1% for {sup 60}Co and {sup 192}Ir, yet −3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were −7% for {sup 60}Co, −0.6% for {sup 192}Ir, and −2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For

  9. Monte Carlo Study of Radiation Dose Enhancement by Gadolinium in Megavoltage and High Dose Rate Radiotherapy

    PubMed Central

    Zhang, Daniel G.; Feygelman, Vladimir; Moros, Eduardo G.; Latifi, Kujtim; Zhang, Geoffrey G.

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed. PMID:25275550

  10. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    PubMed

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

  11. Ocular toxicity following high dose chemotherapy and autologous transplant.

    PubMed

    Rubin, P; Hulette, C; Khawly, J A; Elkordy, M; Hussein, A; Vredenburgh, J J; Jaffe, G J; Peters, W P

    1996-07-01

    A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful. PMID:8832031

  12. Hepatotoxicity of High Oral Dose (-)-Epigallocatechin-3-Gallate in Mice

    PubMed Central

    Lambert, Joshua D.; Kennett, Mary J.; Sang, Shengmin; Reuhl, Kenneth R.; Ju, Jihyeung; Yang, Chung S.

    2009-01-01

    The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been studied for chronic disease preventive effects, and is marketed as part of many dietary supplements. However, case reports have associated the use of green tea-based supplements with liver toxicity. We studied the hepatotoxic effects of high dose EGCG in male CF-1 mice. A single dose of EGCG (1500 mg/kg, i.g.) increased plasma alanine aminotransferase (ALT) by 138-fold and reduced survival by 85%. Once-daily dosing with EGCG increased hepatotoxic response. Plasma ALT levels were increased 184-fold following two once-daily doses of 750 mg/kg, i.g. EGCG. Moderate to severe hepatic necrosis was observed following treatment with EGCG. EGCG hepatotoxicity was associated with oxidative stress including increased hepatic lipid peroxidation (5-fold increase), plasma 8-isoprostane (9.5-fold increase) and increased hepatic metallothionein and γ-histone 2AX protein expression. EGCG also increased plasma interleukin-6 and monocyte chemoattractant protein 1. Our results indicate that higher bolus doses of EGCG are hepatotoxic to mice. Further studies on the dose-dependent hepatotoxic effects of EGCG and the underlying mechanisms are important given the increasing use of green tea dietary supplements, which may deliver much higher plasma and tissue concentrations of EGCG than tea beverages. PMID:19883714

  13. Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study

    PubMed Central

    Romanowski, Barbara; Schwarz, Tino F; Ferguson, Linda; Peters, Klaus; Dionne, Marc; Behre, Ulrich; Schulze, Karin; Hillemanns, Peter; Suryakiran, Pemmaraju; Thomas, Florence; Struyf, Frank

    2016-01-01

    In this randomized, partially-blind study (clinicaltrials.gov; NCT00541970), the licensed formulation of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (20 μg each of HPV-16/18 antigens) was found highly immunogenic up to 4 y after first vaccination, whether administered as a 2-dose (2D) schedule in girls 9–14 y or 3-dose (3D) schedule in women 15–25 y. This end-of-study analysis extends immunogenicity and safety data until Month (M) 60, and presents antibody persistence predictions estimated by piecewise and modified power law models. Healthy females (age stratified: 9–14, 15–19, 20–25 y) were randomized to receive 2D at M0,6 (N = 240 ) or 3D at M0,1,6 (N = 239). Here, results are reported for girls 9–14 y (2D) and women 15–25 y (3D). Seropositivity rates, geometric mean titers (by enzyme-linked immunosorbent assay) and geometric mean titer ratios (GMRs; 3D/2D; post-hoc exploratory analysis) were calculated. All subjects seronegative pre-vaccination in the according-to-protocol immunogenicity cohort were seropositive for anti-HPV-16 and −18 at M60. Antibody responses elicited by the 2D and 3D schedules were comparable at M60, with GMRs close to 1 (anti-HPV-16: 1.13 [95% confidence interval: 0.82–1.54]; anti-HPV-18: 1.06 [0.74–1.51]). Statistical modeling predicted that in 95% of subjects, antibodies induced by 2D and 3D schedules could persist above natural infection levels for ≥ 21 y post-vaccination. The vaccine had a clinically acceptable safety profile in both groups. In conclusion, a 2D M0,6 schedule of the HPV-16/18 AS04-adjuvanted vaccine was immunogenic for up to 5 y in 9–14 y-old girls. Statistical modeling predicted that 2D-induced antibodies could persist for longer than 20 y. PMID:26176261

  14. Finnish spectrolite as high-dose gamma detector

    NASA Astrophysics Data System (ADS)

    Antonio, Patrícia L.; Caldas, Linda V. E.

    2015-11-01

    A natural material called spectrolite, from Finland, was studied in this work. The purpose was to test it in gamma radiation beams to verify its performance as a high-dose detector. From this material, pellets were manufactured with two different concentrations of Teflon and spectrolite, and their responses were verified using two luminescent techniques: thermoluminescence (TL) and optically stimulated luminescence (OSL). The TL and OSL signals were evaluated by means of characterization tests of the material response, after exposure to a nominal absorbed dose interval of 5 Gy to 10 kGy. The results obtained, for both concentrations, showed a good performance of this material in beams of high-dose gamma radiation. Both techniques were utilized in order to investigate the properties of the spectrolite+Teflon samples for different applications.

  15. Dosimetric characteristics of jasper samples for high dose dosimetry.

    PubMed

    Teixeira, Maria Inês; Caldas, Linda V E

    2012-07-01

    Different colored jasper samples from Brazilian mines were powdered and mixed with teflon (composites jasper-teflonTM). This paper describes a preliminary study of a thermoluminescent method (TL) to verify the possibility of their use as high dose dosimeters or irradiation indicators in industrial areas. The jasper samples were exposed to different radiation doses, using the gamma-cell 220 system (60Co) of IPEN. The TL emission curves of samples presented two peaks at 130 °C and 190 °C. Calibration curves were obtained for the jasper samples between 50 Gy and 20 kGy. All five types of jasper samples showed their usefulness as irradiation indicators and as high-dose dosimeters.

  16. Efficiency of oxfendazole administered as a single dose or in a controlled release capsule against benzimidazole-resistant haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis.

    PubMed

    Le Jambre, L F; Prichard, P K; Hennessy, D R; Laby, R H

    1981-11-01

    Laboratory strains of Haemonchus contortus and Ostertagia circumcincta selected for thiabendazole resistance were found to have a strong side resistance to a single dose of oxfendazole. The LD50 and LD95 in mg of drug per host liveweight were respectively 4.28 and 18.46 mg/kg for H contortus and 3.61 and 11.20 mg/kg for O circumcincta. A field strain of Trichostrongylus colubriformis that had not been selected with thiabendazole for seven years also had a strong side resistance to oxfendazole with approximately 50 per cent of its population resistant to the recommended dose rate of 5 mg/kg. Prolonged administration of oxfendazole by intraruminal controlled release capsules was found to be effective against both susceptible and resistant strains of the above parasites. The first observed effect of oxfendazole, from controlled release capsules, on resistant worms was a decrease in the percentage of eggs developing to third stage larvae. This was followed by a decrease in egg count and in worm numbers.

  17. Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib

    PubMed Central

    Olshen, Adam; Tang, Min; Cortes, Jorge; Gonen, Mithat; Hughes, Timothy; Branford, Susan; Quintás-Cardama, Alfonso; Michor, Franziska

    2014-01-01

    Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors – such as dasatinib and nilotinib – have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite eliciting similar clinical responses, the molecular effects of these agents on different subpopulations of leukemic cells remain incompletely understood. Furthermore, the consequences of using high-dose imatinib therapy have not been investigated in detail. Here we utilized clinical data from patients treated with dasatinib, nilotinib, or high-dose imatinib, together with a statistical data analysis and mathematical modeling approach, to investigate the molecular treatment response of leukemic cells to these agents. We found that these drugs elicit very similar responses if administered front-line. However, patients display significantly different kinetics when treated second-line, both in terms of differences between front-line and second-line treatment for the same drug, and among agents when used as second-line. We then utilized a mathematical framework describing the behavior of four differentiation levels of leukemic cells during therapy to predict the treatment response kinetics for the different cohorts of patients. The dynamics of BCR-ABL1 clearance observed in our study suggest that the use of standard or high-dose imatinib or a second-generation tyrosine kinase inhibitor such as nilotinib or dasatinib elicits similar responses when administered as front-line therapy for patients with chronic myeloid leukemia in chronic phase. PMID:25216683

  18. High-dose-rate prostate brachytherapy inverse planning on dose-volume criteria by simulated annealing

    NASA Astrophysics Data System (ADS)

    Deist, T. M.; Gorissen, B. L.

    2016-02-01

    High-dose-rate brachytherapy is a tumor treatment method where a highly radioactive source is brought in close proximity to the tumor. In this paper we develop a simulated annealing algorithm to optimize the dwell times at preselected dwell positions to maximize tumor coverage under dose-volume constraints on the organs at risk. Compared to existing algorithms, our algorithm has advantages in terms of speed and objective value and does not require an expensive general purpose solver. Its success mainly depends on exploiting the efficiency of matrix multiplication and a careful selection of the neighboring states. In this paper we outline its details and make an in-depth comparison with existing methods using real patient data.

  19. High-dose-rate prostate brachytherapy inverse planning on dose-volume criteria by simulated annealing.

    PubMed

    Deist, T M; Gorissen, B L

    2016-02-01

    High-dose-rate brachytherapy is a tumor treatment method where a highly radioactive source is brought in close proximity to the tumor. In this paper we develop a simulated annealing algorithm to optimize the dwell times at preselected dwell positions to maximize tumor coverage under dose-volume constraints on the organs at risk. Compared to existing algorithms, our algorithm has advantages in terms of speed and objective value and does not require an expensive general purpose solver. Its success mainly depends on exploiting the efficiency of matrix multiplication and a careful selection of the neighboring states. In this paper we outline its details and make an in-depth comparison with existing methods using real patient data. PMID:26760757

  20. Low-dose high-resolution CT of lung parenchyma

    SciTech Connect

    Zwirewich, C.V.; Mayo, J.R.; Mueller, N.L. )

    1991-08-01

    To evaluate the efficacy of low-dose high-resolution computed tomography (HRCT) in the assessment of lung parenchyma, three observers reviewed the scans of 31 patients. The 1.5-mm-collimation, 2-second, 120-kVp scans were obtained at 20 and 200 mA at selected identical levels in the chest. The observers evaluated the visualization of normal pulmonary anatomy, various parenchymal abnormalities and their distribution, and artifacts. The low-dose and conventional scans were equivalent in the evaluation of vessels, lobar and segmental bronchi, and anatomy of secondary pulmonary lobules, and in characterizing the extent and distribution of reticulation, honeycomb cysts, and thickened interlobular septa. The low-dose technique failed to demonstrate ground-glass opacity in two of 10 cases (20%) and emphysema in one of nine cases (11%), in which they were evident but subtle on the high-dose scans. These differences were not statistically significant. Linear streak artifact was more prominent on images acquired with the low-dose technique, but the two techniques were judged equally diagnostic in 97% of cases. The authors conclude that HRCT images acquired at 20 mA yield anatomic information equivalent to that obtained with 200-mA scans in the majority of patients, without significant loss of spatial resolution or image degradation due to linear streak artifact.

  1. High performance liquid chromatographic determination of some co-administered anticancer drugs in pharmaceutical preparations and in spiked human plasma.

    PubMed

    Fahmy, Ossama T; Korany, Mohamed A; Maher, Hadir M

    2004-03-10

    Two HPLC methods are introduced in this paper for the simultaneous determination of doxorubicin hydrochloride (DOX) and 5-fluorouracil (5-FU), combination I, and of cytarabine (CYT) and etoposide (ETO), combination II, as co-administered drugs. In both combinations, a [250 mm x 4.6 mm C-18 column is used. The mobile phase for combination I consists of a mixture of acetonitrile and 0.05 M disodium hydrogenphosphate (50:50, v/v) containing 0.1% sodium laurylsulfate (SLS) adjusted to pH 3.7 at a flow rate 1 ml/min, with UV detection at 260 nm and ambient temperature. For combination II, the mobile phase consists of a mixture of 0.02 M sodium dihydrogenphosphate aqueous solution adjusted to pH 6.0 (with 0.2 M orthophosphoric acid or sodium hydroxide) and acetonitrile in a ratio of (7:3) at a flow rate 1 ml/min, with UV detection at 254 nm and ambient temperature. The methods also permitted the determination of methyl hydroxybenzoate (MHB) which is used as a preservative in DOX vials, combination I, and of benzyl alcohol (BZA) preservative in ETO vials, combination II. The proposed HPLC methods were successfully applied to the determination of the investigated drugs, of the two combinations, both in injection solutions and spiked human plasma samples with high precision and accuracy. Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are presented in the text.

  2. Effect of steroid and high-dose immunoglobulin therapy on opsoclonus-myoclonus syndrome occurring in neuroblastoma.

    PubMed

    Veneselli, E; Conte, M; Biancheri, R; Acquaviva, A; De Bernardi, B

    1998-01-01

    The authors describe a case of an 8-month-old boy with opsoclonus-myoclonus syndrome (OMS) and coincident unresectable neuroblastoma (NB). He achieved a complete remission for NB after 6 courses of standard-dose chemotherapy without significant neurological improvement despite the use of steroids and high-dose immunoglobulin (HIG), administered separately. Only the combined treatment withthese two drugs induced a complete disappearance of neurological symptoms. On the basis of this experience, the authors suggest the association of steroids plus HIG for the treatment of OMS in patients not responsive to conventional first line therapy with steroids.

  3. Efficacy and safety of ipratropium bromide/salbutamol sulphate administered in a hydrofluoroalkane metered-dose inhaler for the treatment of COPD

    PubMed Central

    Bhattacharya, Amal; Bhargava, Salil; Singh, Virendra; Talwar, Deepak; Whig, Jagdeep; Rebello, Juliet; Purandare, Shrinivas; Gogtay, Jaideep

    2016-01-01

    Background The use of chlorofluorocarbons (CFCs) has contributed to the depletion of the stratospheric ozone layer resulting in serious health concerns. Ipratropium bromide/salbutamol sulphate CFC-pressurized metered-dose inhalers (IB/SAL-CFC pMDI) have been in widespread use for many years without any apparent ill consequences. This combination has now been reformulated using the hydrofluoroalkane (HFA) propellant. This study sought to establish the clinical noninferiority of a new HFA-containing IB/SAL pMDI to the conventional IB/SAL-CFC pMDI in subjects with mild/moderate COPD. Methods This was a randomized, double-blind, parallel-group, multicenter study in two consecutive periods: a 14-day run-in period followed by a 85-day treatment period. Eligible mild-to-moderate stable COPD subjects aged 40−75 years were enrolled into the study and entered the run-in period during which subjects withdrew all the bronchodilators, except for salbutamol as rescue medication. Subjects were randomized to 85 days treatment with either IB/SAL-HFA or IB/SAL-CFC, 20 μg qid. Results Of the 290 randomized patients, 249 completed the study. The primary efficacy variable was the change in forced expiratory volume in one second from predose to 60 minutes after dosing on day 85. At the end of the treatment period, the adjusted mean change in forced expiratory volume in one second at 60 minutes was 123 mL in the IB/SAL-HFA pMDI group and 115 mL in the IB/SAL-CFC pMDI group. Because the lower limit of the 95% confidence interval for the between-group difference (−62 mL) was well within the noninferiority margin (−100 mL), the HFA formulation was deemed clinically noninferior to the CFC formulation. This finding was supported by secondary efficacy assessments. Both formulations of IB/SAL were well tolerated during the prolonged multiple dosing. Conclusion It is concluded that IB/SAL-HFA pMDI provides effective bronchodilation of similar degree to that achieved with IB/SAL-CFC p

  4. Effects of two human chorionic gonadotropin doses administered to the ovarian states during the in vitro fertilization and embryo transfer program

    PubMed Central

    MA, MINGXING; WANG, JIALIN; XU, LIJUN; ZHANG, QINXI; DU, BOTAO; JIANG, XIAOYING; SHI, QINGLI; ZHOU, LILI; LI, BAOXIN; SAITO, HIDEKAZU; KURACHI, HIROHISA

    2015-01-01

    The aim of the present study was to examine the effects of the human chorionic gonadotropin (hCG) dose on the pulsatility indices (PI) of the intraovarian artery on the day of follicle aspiration and the oocyte quality, intrafollicular oxidative stress and luteinization. PI was also measured on the day of hCG administration. A total of 15 patients were undergoing the in vitro fertilization and embryo transfer (IVF-ET) program. To estimate whether there was any difference between the intraovarian artery blood flow and oocyte development of the same patients treated with 5,000 or 10,000 IU hCG, the intraovarian artery blood flow was measured by transvaginal color ultrasonography pulsed wave Doppler, and the follicular fluids and the granulosa cells were collected at follicle aspiration. There were statistically significant differences between the same patients undergoing the two different hCG-dose treatments in which the first protocol included 10,000 IU and the second protocol included 5,000 IU hCG treatment. These differences were apparent in the PI of intraovarian artery blood flow on the day of follicle aspiration (P=0.0023), in the incidence of apoptosis in cumulus (ApoC) and mural (ApoM) granulosa cells (ApoC, P=0.0077; ApoM, P=0.0128), in the total oocytes retrieved (P=0.0342) and in the follicle fluid progesterone concentration (P=0.0044). There were no significant differences between the two protocols in the PI of intraovarian artery blood flow on the day of hCG administration (P=0.4326), serum steroid on the day of follicle aspiration [serum P, P>0.9999; serum estradiol (E2), P=0.8589], follicle fluid E2 concentration (P=0.8939), mature oocyte rate (P=0.3743) and total mature oocytes retrieved (P=0.2026). In conclusion, the dose of hCG administration can significantly affect the intraovarian artery blood flow and the development of follicles and oocytes in an IVF-ET program. PMID:26075075

  5. Radiation Dose Testing on Juno High Voltage Cables

    NASA Technical Reports Server (NTRS)

    Green, Nelson W.; Kirkham, Harold; Kim, Wousik; McAlpine, Bill

    2008-01-01

    The Juno mission to Jupiter will have a highly elliptical orbit taking the spacecraft through the radiation belts surrounding the planet. During these passes through the radiation belts, the spacecraft will be subject to high doses of radiation from energetic electrons and protons with energies ranging from 10 keV to 1 GeV. While shielding within the spacecraft main body will reduce the total absorbed dose to much of the spacecraft electronics, instruments and cables on the outside of the spacecraft will receive much higher levels of absorbed dose. In order to estimate the amount of degradation to two such cables, testing has been performed on two coaxial cables intended to provide high voltages to three of the instruments on Juno. Both cables were placed in a vacuum of 5x10(exp -6) torr and cooled to -50(deg)C prior to exposure to the radiation sources. Measurements of the coaxial capacitance per unit length and partial discharge noise floor indicate that increasing levels of radiation make measurable but acceptably small changes to the F EP Teflon utilized in the construction of these cables. In addition to the radiation dose testing, observations were made on the internal electrostatic charging characteristics of these cables and multiple discharges were recorded.

  6. Radiation Dose Testing on Juno High Voltage Cables

    NASA Technical Reports Server (NTRS)

    Green, Nelson W.; Kirkham, Harold; Kim, Wousik; McAlpine, Bill

    2008-01-01

    The Juno mission to Jupiter will have a highly elliptical orbit taking the spacecraft through the radiation belts surrounding the planet. During these passes through the radiation belts, the spacecraft will be subject to high doses of radiation from energetic electrons and protons with energies ranging from 10 keV to 1 GeV. While shielding within the spacecraft main body will reduce the total absorbed dose to much of the spacecraft electronics, instruments and cables on the outside of the spacecraft will receive much higher levels of absorbed dose. In order to estimate the amount of degradation to two such cables, testing has been performed on two coaxial cables intended to provide high voltages to three of the instruments on Juno. Both cables were placed in a vacuum of 5x10-6 torr and cooled to -50 C prior to exposure to the radiation sources. Measurements of the coaxial capacitance per unit length and partial discharge noise floor indicate that increasing levels of radiation make measurable but acceptably small changes to the F EP Teflon utilized in the construction of these cables. In addition to the radiation dose testing, observations were made on the internal electrostatic charging characteristics of these cables and multiple discharges were recorded.

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

    PubMed

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

    1980-05-01

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

  8. High dose calibrations at the pacific northwest laboratory

    NASA Astrophysics Data System (ADS)

    McDonald, J. C.; Fox, R. A.

    1989-04-01

    he need is increasing for both high radiation exposures and calibration measurements that provide traceability of such exposures to national standards. The applications of high exposures include: electronic component damage studies, sterilization of medical products and food irradiation. Accurate high exposure measurements are difficult to obtain and cannot, in general, be carried out with a single dose measurement system or technique because of the wide range of doses and the variety of materials involved. This paper describes the dosimetric measurement and calibration techniques used at the Pacific Northwest Laboratory (PNL) that make use of radiochromic dye films, thermoluminescence dosimeters (TLDs), ionization chambers and calorimetric dosimeters. The methods used to demonstrate the consistency of PNL calibrations with national standards will also be discussed.

  9. Hardening electronic devices against very high total dose radiation environments

    NASA Technical Reports Server (NTRS)

    Buchanan, B.; Shedd, W.; Roosild, S.; Dolan, R.

    1972-01-01

    The possibilities and limitations of hardening silicon semiconductor devices to the high neutron and gamma radiation levels and greater than 10 to the eighth power rads required for the NERVA nuclear engine development are discussed. A comparison is made of the high dose neutron and gamma hardening potential of bipolar, metal insulator semiconductors and junction field effect transistors. Experimental data is presented on device degradation for the high neutron and gamma doses. Previous data and comparisons indicate that the JFET is much more immune to the combined neutron displacement and gamma ionizing effects than other transistor types. Experimental evidence is also presented which indicates that p channel MOS devices may be able to meet the requirements.

  10. Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium

    NASA Astrophysics Data System (ADS)

    Paiva Fonseca, Gabriel; Carlsson Tedgren, Åsa; Reniers, Brigitte; Nilsson, Josef; Persson, Maria; Yoriyaz, Hélio; Verhaegen, Frank

    2015-06-01

    Dose calculation in high dose rate brachytherapy with 192Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (Dm,m) and dose-to-water-in-medium (Dw,m). The relation between Dm,m and Dw,m for 192Ir is the main goal of this study, in particular the dependence of Dw,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: Dm,m, Dw,m (LCT), mean photon energy and photon fluence. Dw,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between Dm,m and Dw,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between Dw,m (SCT) and Dw,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between Dm,m and Dw,m (SCT) mainly depend on tissue type, differences between Dm,m and Dw,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources.

  11. Developmental toxicity of clarified slurry oil, syntower bottoms, and distillate aromatic extract administered as a single oral dose to pregnant rats

    SciTech Connect

    Feuston, M.H.; Mackerer, C.R.

    1996-09-01

    Clarified slurry oil (CSO), syntower bottoms (STB), and distillate aromatic extract (DAE) are refinery streams produced by processing crude oil. Available data indicate that some refinery streams are developmentally toxic by the dermal route of exposure. However, there is no conclusive evidence for their being teratogenic. The present studies were designed to further explore the suspected teratogenic potency of refinery streams while at the same time limiting embryolethality. In general, evidence of maternal toxicity (i.e., decreased body weight gain, decreased thymus weight) was observed at doses greater than or equal to 500 mg/kg. For each refinery stream tested, the incidence of resorption was greatest on GD 11. A common pattern of fetal malformations was observed for all of the refinery streams tested and included cleft palate, diaphragmatic hernia, and paw and tail defects. The incidence and type of malformation observed were influenced by the gestation day of exposure. The incidence and type of malformation observed were influenced by the gestation day of exposure. The incidences of external and skeletal malformations were greatest on GD 11 and 12 for fetuses exposed to CSO; on GD 13 and 14, the incidence of malformation was comparable for CSO- and STB-exposed fetuses. The incidence of visceral anomalies was greatest on GD 11-13 for fetuses exposed to CSO and STB; on Gestation D 14, the incidence was comparable for each of the refinery streams tested. In general, the ability to produce adverse effects on development was greatest for CSO and least for DAE. Effects produced by STB were comparable to or less severe than those observed for CSO. 24 refs., 11 tabs.

  12. [Two cases of long-term home parenteral nutrition in which increased doses of intravenous selenium were administered and the serum and hair selenium concentration was measured].

    PubMed

    Washizawa, Naohiro; Kozono, Koki; Naganuma, Hirokazu; Kimura, Yuki; Sato, Yukihiko; Sakai, Masahiro; Chino, Kenichi; Shimoda, Masato; Suzuki, Takashi; Oshima, Yoko; Kaneko, Hiromasa

    2013-12-01

    Care should be taken regarding the intravenous administration of selenium (Se), an essential element, which is known to be associated with toxemia. The concentration of Se in the serum and hair of 2 patients (patient A and B) with short bowel syndrome, undergoing long-term home parenteral nutrition (HPN), was measured. As nutritional management, commercial total parenteral nutrition infusion was used without restricting oral intake. The patients received sodium selenite (Na2O3Se x 5H2O), a hospital preparation, at the Toho University Omori Medical Center. The dosage was gradually increased from 40 microg/ week to 120 micog/week over 17 months, and the Se concentration in serum and hair was measured bimonthly using inductively coupled plasma mass spectrometry (ICP-MS). The serum concentration of Se increased from 2.0 to 5.3 microg/dL and from 9.0 to 9.7 microg/dL in the case of patient A and B, respectively; however, it did not reach the average value that was observed in healthy volunteers (11.8 microg/dL). In contrast, the concentration of Se in hair gradually approached the reference value (reference range, 405-784 ppb at color correction criteria range 217-520 ppb) in the case of patient A (change from 189 to 278 ppb) and B (change from 291 to 200 ppb). Therefore, we were able to safely manage these cases without any deficiency and poisoning symptoms, by gradually increasing the administration doses.

  13. Orally administered grass pollen.

    PubMed

    Taudorf, E; Weeke, B

    1983-11-01

    In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.

  14. [Treatment of parturient paresis with high-dose calcium].

    PubMed

    Braun, U; Jehle, W; Siegwart, N; Bleul, U; Hässig, M

    2006-03-01

    72 hours it was again within the normal range. The concentration of inorganic phosphorus increased slowly in both groups, although it was not within the normal range at eight hours. In both groups, it achieved normal values at 24, 48 and 72 hours. The mean electrolyte concentrations did not differ significantly at any measuring point between cows that stood within eight hours of treatment and those that did not. Our results indicate that increasing the dose of calcium administered does not improve the recovery rate of cows with parturient paresis.

  15. THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS

    EPA Science Inventory

    THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS.

    Abstract:

    The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...

  16. Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.

    PubMed

    Ship, J A; Fox, P C; Michalek, J E; Cummins, M J; Richards, A B

    1999-08-01

    The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events. PMID:10476942

  17. High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer

    PubMed Central

    Alwers, Elizabeth; Cifuentes, Javier; Bobadilla, Ivan; Torres, Felipe; Arbelaez, Juan; Gaitan, Armando; Cortes, Helber; Acevedo, Yenny; Quintero, Paulo; Vasquez, Jaider

    2015-01-01

    Purpose High-dose-rate (HDR) brachytherapy has been accepted as an effective and safe method to treat prostate cancer. The aim of this study was to describe acute toxicity following HDR brachytherapy to the prostate, and to examine the association between dosimetric parameters and urinary toxicity in low-risk prostate cancer patients. Material and methods Patients with low-risk prostate cancer were given HDR brachytherapy as monotherapy in two 12.5 Gy fractions. Planning objectives for the planning target volume (PTV) were V100% ≥ 90% and V150% ≤ 35%. Planning objectives for organs at risk were V75% ≤ 1 cc for the bladder, rectum and perineum, and V125% ≤ 1 cc for the urethra. Toxicity was assessed three months after treatment using the Common Terminology Criteria for Adverse Events. Results Seventy-three patients were included in the analysis. Thirty-three patients (45%) reported having any type of toxicity in the three months following HDR brachytherapy. Most toxicity cases (26%) were grade 1 urinary toxicity. Mean coverage index was 0.89 and mean V100 was 88.85. Doses administered to the urethra were associated with urinary toxicity. Patients who received more than 111.3% of the prescribed dose in 1 cc of the urethra were four times more likely to have urinary toxicity compared to patients receiving less than 111.3% (OR = 4.71, 95% CI: 1.43-15.6; p = 0.011). Conclusions High-dose-rate brachytherapy administered as monotherapy for prostate cancer proved to be a safe alternative treatment for patients with low-risk prostate cancer. Urinary toxicity was associated with the dose administered to 1 cc and 0.1 cc of the urethra and was remarkably inferior to the reported toxicity in similar studies. PMID:25829931

  18. High-dose secondary calibration laboratory accreditation program

    SciTech Connect

    Humphreys, J.C.

    1993-12-31

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

  19. Effect of Sodium Arsenite Dose Administered in the Drinking Water on the Urinary Bladder Epithelium of Female Arsenic (+3 oxidation state) Methyltransferase Knockout Mice

    EPA Science Inventory

    The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, we evaluated whether the As3mt null genotype in mice modified cytotoxic and proli...

  20. PLUTONIUM/HIGH-LEVEL VITRIFIED WASTE BDBE DOSE CALCULATION

    SciTech Connect

    J.A. Ziegler

    2000-11-20

    The purpose of this calculation is to provide a dose consequence analysis of high-level waste (HLW) consisting of plutonium immobilized in vitrified HLW to be handled at the proposed Monitored Geologic Repository at Yucca Mountain for a beyond design basis event (BDBE) under expected conditions using best estimate values for each calculation parameter. In addition to the dose calculation, a plutonium respirable particle size for dose calculation use is derived. The current concept for this waste form is plutonium disks enclosed in cans immobilized in canisters of vitrified HLW (i.e., glass). The plutonium inventory at risk used for this calculation is selected from Plutonium Immobilization Project Input for Yucca Mountain Total Systems Performance Assessment (Shaw 1999). The BDBE examined in this calculation is a nonmechanistic initiating event and the sequence of events that follow to cause a radiological release. This analysis will provide the radiological releases and dose consequences for a postulated BDBE. Results may be considered in other analyses to determine or modify the safety classification and quality assurance level of repository structures, systems, and components. This calculation uses best available technical information because the BDBE frequency is very low (i.e., less than 1.0E-6 events/year) and is not required for License Application for the Monitored Geologic Repository. The results of this calculation will not be used as part of a licensing or design basis.

  1. High dose rate (HDR) brachytherapy quality assurance: a practical guide

    PubMed Central

    Wilkinson, DA

    2006-01-01

    The widespread adoption of high dose rate brachytherapy with its inherent dangers necessitates adoption of appropriate quality assurance measures to minimize risks to both patients and medical staff. This paper is aimed at assisting someone who is establishing a new program or revising one already in place into adhere to the recently issued Nuclear Regulatory Commission (USA) regulations and the guidelines from the American Association of Physicists in Medicine. PMID:21614233

  2. High-dose versus low-dose valproate for the treatment of juvenile myoclonic epilepsy: Going from low to high.

    PubMed

    Hernández-Vanegas, Laura E; Jara-Prado, Aurelio; Ochoa, Adriana; Rodríguez Y Rodríguez, Nayelli; Durón, Reyna M; Crail-Meléndez, Daniel; Alonso, Ma Elisa; Delgado-Escueta, Antonio V; Martínez-Juárez, Iris E

    2016-08-01

    Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy accounting for 3-12% of adult cases of epilepsy. Valproate has proven to be the first-choice drug in JME for controlling the most common seizure types: myoclonic, absence, and generalized tonic-clonic (GTC). In this retrospective study, we analyzed seizure outcome in patients with JME using valproate monotherapy for a minimum period of one year. Low valproate dose was considered to be 1000mg/day or lower, while serum levels were considered to be low if they were at or below 50mcg/dl. One hundred three patients met the inclusion criteria. Fifty-six patients (54.4%) were female. The current average age was 28.4±7.4years, while the age of epilepsy onset was 13.6±2.9years. Most patients corresponded to the subsyndrome of classic JME. Forty-six (44.7%) patients were free from all seizure types, and 76 (73.7%) patients were free from GTC seizures. No significant difference was found in seizure freedom among patients using a low dose of valproate versus a high dose (p=0.535) or among patients with low blood levels versus high blood levels (p=0.69). In patients with JME, it seems appropriate to use low doses of valproate (500mg to 1000mg) for initial treatment and then to determine if freedom from seizures was attained. PMID:27300146

  3. SU-E-T-315: The Change of Optically Stimulated Luminescent Dosimeters (OSLDs) Sensitivity by Accumulated Dose and High Dose

    SciTech Connect

    Han, S; Jung, H; Kim, M; Ji, Y; Kim, K; Choi, S; Park, S; Yoo, H; Yi, C

    2014-06-01

    Purpose: The objective of this study is to evaluate radiation sensitivity of optical stimulated luminance dosimeters (OSLDs) by accumulated dose and high dose. Methods: This study was carried out in Co-60 unit (Theratron 780, AECL, and Canada) and used InLight MicroStar reader (Landauer, Inc., Glenwood, IL) for reading. We annealed for 30 min using optical annealing system which contained fluorescent lamps (Osram lumilux, 24 W, 280 ∼780 nm). To evaluate change of OSLDs sensitivity by repeated irradiation, the dosimeters were repeatedly irradiated with 1 Gy. And whenever a repeated irradiation, we evaluated OSLDs sensitivity. To evaluate OSLDs sensitivity after accumulated dose with 5 Gy, We irradiated dose accumulatively (from 1 Gy to 5 Gy) without annealing. And OSLDs was also irradiated with 15, 20, 30 Gy to certify change of OSLDs sensitivity after high dose irradiation. After annealing them, they were irradiated with 1Gy, repeatedly. Results: The OSLDs sensitivity increased up to 3% during irradiating seven times and decreased continuously above 8 times. That dropped by about 0.35 Gy per an irradiation. Finally, after 30 times irradiation, OSLDs sensitivity decreased by about 7%. For accumulated dose from 1 Gy to 5 Gy, OSLDs sensitivity about 1 Gy increased until 4.4% after second times accumulated dose compared with before that. OSLDs sensitivity about 1 Gy decreased by 1.6% in five times irradiation. When OSLDs were irradiated ten times with 1Gy after irradiating high dose (10, 15, 20 Gy), OSLDs sensitivity decreased until 6%, 9%, 12% compared with it before high dose irradiation, respectively. Conclusion: This study certified OSLDs sensitivity by accumulated dose and high dose. When irradiated with 1Gy, repeatedly, OSLDs sensitivity decreased linearly and the reduction rate of OSLDs sensitivity after high dose irradiation had dependence on irradiated dose.

  4. Multidisciplinary therapy including high-dose chemotherapy followed by peripheral blood stem cell transplantation for invasive thymoma.

    PubMed

    Iwasaki, Yoshinobu; Ohsugi, Shuji; Takemura, Yoshizumi; Nagata, Kazuhiro; Harada, Hidehiko; Nakagawa, Masao

    2002-12-01

    We describe two patients with invasive thymomas who responded to high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) combined with surgery and radiotherapy. The first patient was a 42-year-old man admitted to the hospital with chest pain, and the second patient was a 45-year-old man admitted with myasthenia gravis. Both patients had nonresectable thymomas (stage IVa) because of invasion of the aorta, pulmonary artery, or both, and dissemination to the pericardium. They initially received two cycles of chemotherapy consisting of adriamycin (40 mg/m(2), day 1), cisplatin (50 mg/m(2), day 1), vincristine (0.6 mg/m(2), day 3), and cyclophosphamide (700 mg/m(2), day 4) at 3-week intervals. Four weeks later, they were administered high-dose etoposide (300 mg/m(2), days 1 to 5) followed by granulocyte colony-stimulating factor (G-CSF) [50 micro g/m(2)/d] subcutaneously to mobilize stem cells into the blood. After two additional cycles of adriamycin, cisplatin, vincristine, and cyclophosphamide (ADOC), the patients received high-dose ifosfamide (1.5 g/m(2), days 1 to 4), carboplatin (400 mg/m(2), days 3 to 5), and etoposide (200 mg/m(2), days 1 to 5) followed by PBSCT. They were administered G-CSF (50 micro g/m(2)/d) after PBSCT, with subsequent rapid recovery of neutrophil and platelet level. The tumors shrank remarkably, and could be excised completely in both patients. Postoperatively, 50 Gy of irradiation was administered. Disease-free status has been maintained for 5 years in the first patient and 2 years in the second patient. Our findings suggest that high-dose ifosfamide, carboplatin, and etoposide followed by PBSCT in combination with an ADOC regimen, surgery, and radiotherapy is very effective and well tolerated in patients with advanced nonresectable thymoma.

  5. High-dose neutron irradiation performance of dielectric mirrors

    DOE PAGES

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation-tolerance: alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of 1 and 4 dpa at 458 10K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa results in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to 1 dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopymore » (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects which increases size with irradiation dose. The typical size of each defect was 8 nm in 1 dpa and 42 nm in 4 dpa specimens. Buckling type delamination of the interface between the substrate and first layer was typically observed in both 1 and 4 dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high resolution scanning-TEM mode using energy dispersive spectroscopy. A significant interdiffusion between the film layers was observed in Al2O3/SiO2 mirror, though less evident in HfO2/SiO2 system. Lastly, the ultimate goal of this work is the provide insight into the radiation-induced failure mechanisms of these mirrors.« less

  6. High-dose neutron irradiation performance of dielectric mirrors

    SciTech Connect

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation-tolerance: alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of 1 and 4 dpa at 458 10K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa results in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to 1 dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopy (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects which increases size with irradiation dose. The typical size of each defect was 8 nm in 1 dpa and 42 nm in 4 dpa specimens. Buckling type delamination of the interface between the substrate and first layer was typically observed in both 1 and 4 dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high resolution scanning-TEM mode using energy dispersive spectroscopy. A significant interdiffusion between the film layers was observed in Al2O3/SiO2 mirror, though less evident in HfO2/SiO2 system. Lastly, the ultimate goal of this work is the provide insight into the radiation-induced failure mechanisms of these mirrors.

  7. Evaluation of High Performance Converters Under Low Dose Rate Total Ionizing Dose (TID) Testing for NASA Programs

    NASA Technical Reports Server (NTRS)

    Sharma, Ashok K.; Sahu, Kusum

    1998-01-01

    This paper reports the results of low dose rate (0.01-0.18 rads(Si)/sec) total ionizing dose (TID) tests performed on several types of high performance converters. The parts used in this evaluation represented devices such as a high speed flash converter, a 16-bit ADC and a voltage-to-frequency converter.

  8. Germanium implanted with high dose oxygen and its optical properties

    NASA Astrophysics Data System (ADS)

    Zhang, Qi-Chu; Kelly, J. C.; Kenny, M. J.

    1990-05-01

    Single crystal n-type Ge samples are implanted with 1 × 10 17 to 1.5 × 10 18 cm -2 oxygen ions at 45 keV. Infrared and Rutherford backscattering measurements indicate that germanium dioxide is formed. The atomic ratio of oxygen to germanium is near the GeO 2 stoichiometric value of 2.0 from the surface down to a depth of 550 Å for germanium samples implanted to 1.5 × 10 18 cm -2. The excess oxygen is redistributed during the implantation. The results of optical reflectivity measurements indicate that the reflectivity of germanium in the 0.2-1.4 μm wavelength region is greatly reduced after high dose oxygen ion implantation. The reflectivity value at about 0.7 μm is near zero for germanium implanted to a dose of 1.5 × 10 18 cm -2.

  9. Effective Dose of Ramosetron for Prophylaxis of Postoperative Nausea and Vomiting in High-Risk Patients

    PubMed Central

    Lee, Seongheon; Jeong, Sinho; Kim, Joungmin; Jeong, Seongwook

    2015-01-01

    Background. Postoperative nausea and vomiting (PONV) are common adverse events with an incidence of up to 80% in high-risk patients. Ramosetron, a selective 5-HT3 receptor antagonist, is widely used to prevent PONV. The purpose of this study was to evaluate the effective dose of ramosetron for the prevention of PONV in high-risk patients. Methods. Fifty-one patients were randomly allocated to 3 groups and were administered ramosetron 0.3 mg (group A), 0.45 mg (group B), or 0.6 mg (group C), at the end of their surgery. The episodes of PONV were assessed 1, 6, 24, and 48 hours after the injection and all the adverse events were observed. Results. The complete response rate in the postoperative period 6–24 hours after the anesthesia was higher in group C than in group A: 93% versus 44%. Group C's experience score of Rhodes index was lower than group A's: 0.81 ± 2.56 versus 3.94 ± 5.25. No adverse drug reaction could be observed in all groups. Conclusions. The effective dose of ramosetron to be injected for the near-complete prophylaxis of PONV 6 to 24 hours after surgery in high-risk patients is a 0.6 mg bolus injection at the end of the surgery. PMID:26258145

  10. Pharmacokinetics and Safety of FV-100, a Novel Oral Anti-Herpes Zoster Nucleoside Analogue, Administered in Single and Multiple Doses to Healthy Young Adult and Elderly Adult Volunteers▿

    PubMed Central

    Pentikis, Helen S.; Matson, Mark; Atiee, George; Boehlecke, Brian; Hutchins, Jeff T.; Patti, Joseph M.; Henson, Geoffrey W.; Morris, Amy

    2011-01-01

    FV-100 is the prodrug of the highly potent anti-varicella zoster virus bicyclic nucleoside analogue CF-1743. To characterize the pharmacokinetics and safety of oral FV-100, 3 randomized, double-blind, placebo-controlled clinical trials were conducted: (i) a single-ascending-dose study in 32 healthy subjects aged 18 to 55 years (100-, 200-, 400-, and 800-mg doses) with an evaluation of the food effect in the 400-mg group; (ii) a multiple-ascending-dose study in 48 subjects aged 18 to 55 years (100 mg once daily [QD], 200 mg QD, 400 mg QD, 400 mg twice a day, and 800 mg QD for 7 days); and (iii) a 2-part study in subjects aged 65 years and older with a single 400-mg dose in 15 subjects and a 400-mg QD dosing regimen for 7 days in 12 subjects. FV-100 was rapidly and extensively converted to CF-1743, the concentration of which remained above that required to reduce viral activity by 50% for the 24-hour dosing period. Renal excretion of CF-1743 was very low. A high-fat meal reduced exposure to CF-1743; a low-fat meal did not. Pharmacokinetic parameters for the elderly subjects were comparable to those for the younger subjects. FV-100 was well tolerated by all subjects. The pharmacokinetic and safety profiles of FV-100 support its continued investigation for the treatment of herpes zoster and prevention of postherpetic neuralgia with once-daily dosing and without dose modifications for elderly or renally impaired patients. PMID:21444712

  11. High-dose versus low-dose antivenom in the treatment of poisonous snake bites: A systematic review

    PubMed Central

    Das, Rashmi Ranjan; Sankar, Jhuma; Dev, Nishanth

    2015-01-01

    Though snake antivenom (SAV) is the mainstay of therapy for poisonous snake bites, there is no universally accepted standard regimen regarding the optimum dose (low vs. high). We therefore, undertook this systematic review to address this important research question. We searched all the published literature through the major electronic databases till August 2014. Randomized clinical trials (RCTs) were included. Eligible trials compared low versus high dose SAV in poisonous snake bite. The review has been registered at PROSPERO (Registration number: CRD42014009700). Of 36 citations retrieved, a total of 5 RCTs (n = 473) were included in the final analyses. Three trials were open-label, 4 conducted in Indian sub-continent and 1 in Brazil. The doses of SAV varied in the high dose group from 40 ml to 550 ml, and in the low dose group from 20 ml to 220 ml. There was no significant difference between the two groups for any of the outcomes except duration of hospital stay, which was lower in the low dose group. The GRADE evidence generated was of “very low quality.” Low-dose SAV is equivalent or may be superior to high-dose SAV in management of poisonous snake bite. Low dose is also highly cost-effective as compared to the high dose. But the GRADE evidence generated was of “very low quality” as most were open label trials. Further trials are needed to make definitive recommendations regarding the dose and these should also include children <9 years of age. PMID:26195860

  12. Tolerance of high doses of amphotericin B by infusion of a liposomal formulation in children with cancer.

    PubMed

    Emminger, W; Graninger, W; Emminger-Schmidmeier, W; Zoubek, A; Pillwein, K; Susani, M; Wasserer, A; Gadner, H

    1994-01-01

    Conventional amphotericin B (Amph-B) is the drug of choice for treating systemic fungal infections. Recently, a new formulation has become available, encapsulated in liposomes (Amph-lip). This new form of administration was developed in order to lower the acute side effects and to offer the possibility of administering high doses of amphotericin B. Experience with Amph-lip is limited, especially in children. We treated four children with documented systemic fungal infections with Amph-lip and administered it empirically to 12 children. Fifteen of these 16 children were severely granulocytopenic oncologic patients. One 3-month-old baby suffered from systemic candidiasis. Amph-lip was preferred to conventional Amph-B in children with organ dysfunction developing as a consequence of conventional chemotherapy or bone marrow transplantation, after failure of conventional Amph-B to improve a fungal infection, and after adverse drug reactions had occurred. The daily doses of Amph-lip ranged from 1 to 6 mg/kg (median 3 mg/kg), the cumulative doses from 13 to 311 mg/kg (median 75 mg/kg). Acute adverse reactions or organ function abnormalities attributable to Amph-lip did not occur in 402 administrations. Amph-lip has proven to be well tolerated by children in terms of acute toxicity and in the long term. Although large cumulative doses were given, organ function abnormalities attributable to Amph-lip doses were not detected in any of ten long-term survivors over a median observation time of 36 months (range 30-44 months). Amph-lip appears to be a promising alternative antifungal treatment, especially for patients with impaired organ function, when high doses of amphotericin B are necessary. PMID:8110875

  13. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351

  14. On carbon nitride synthesis at high-dose ion implantation

    NASA Astrophysics Data System (ADS)

    Romanovsky, E. A.; Bespalova, O. V.; Borisov, A. M.; Goryaga, N. G.; Kulikauskas, V. S.; Sukharev, V. G.; Zatekin, V. V.

    1998-04-01

    Rutherford backscattering spectrometry was used for the study of high dose 35 keV nitrogen ions implantation into graphites and glassy carbon. Quantitative data on depth profiles and its dependencies on irradiation fluence and ion beam density were obtained. The stationary dome-shaped depth profile with maximum nitrogen concentration 22-27 at.% and half-width more than twice exceeding projected range of ions is reached at fluence Φ ˜10 18 cm -2. The dependence of the maximum concentration in the profile on ion current density was studied. The largest concentration was obtained at reduced ion current density.

  15. Cation disorder in high-dose, neutron-irradiated spinel

    SciTech Connect

    Sickafus, K.E.; Larson, A.C.; Yu, N.

    1995-04-01

    The objective of this effort is to determine whether MgAl{sub 2}O{sub 4} spinel is a suitable ceramic for fusion applications. The crystal structures of MgAl{sub 2}O{sub 4} spinel single crystals irradiated to high neutron fluences [>5{times}10{sup 26} n/m{sup 2} (E{sub n}>0.1 MeV)] were examined by neutron diffraction. Crystal structure refinement of the highese dose sample indicated that the average scattering strength of the tetrahedral crystal sites decreased by {approx}20% while increasing by {approx}8% on octahedral sites.

  16. The susceptibility of TaOx-based memristors to high dose rate ionizing radiation and total ionizing dose

    DOE PAGES

    McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; Mickel, Patrick R.; Hanson, Donald J.; McDonald, Joseph K.; Hughart, David Russell; Marinella, Matthew J.

    2014-11-11

    This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaOx) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×107 rad(Si)/s to 4.7 ×108 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×108 rad(Si)/s. This is the first dose rate study on any type of memristive memory technology. Inmore » addition to assessing the tolerance of TaOx memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

  17. On-label and off-label use of high-dose influenza vaccine in the United States, 2010–2012

    PubMed Central

    McGrath, Leah J; Brookhart, M Alan

    2015-01-01

    High-dose inactivated, influenza vaccine was licensed by the FDA in December 2009 for adults aged 65 y and older. The ACIP did not issue or state a preference for a specific vaccine in the elderly population. The extent of its on-label and off-label use is unknown. Using the MarketScan Commercial Claims and Encounters and the Medicare Supplemental database, we identified individuals who received the high-dose influenza vaccine or the standard, seasonal trivalent influenza vaccine between January 1, 2010 and December 31, 2012. For people aged ≥65 y, we used multivariable regression to assess the association between patient and provider level variables and high-dose influenza vaccine versus standard influenza vaccine. We characterized all off-label high-dose vaccine administered to people younger than 65 y of age, and investigated whether sicker patients were targeted for off-label use by examining the association between various comorbid conditions and receipt of the high-dose vaccine among adults aged 18–64. Among patients aged ≥65 y who received an influenza vaccine, 18.4% received the high-dose vaccine. Uptake was minimal in 2010, but 25% and 32% of influenza shots were the high-dose formulation in 2011 and 2012, respectively. Almost 27,000 seniors received a second high-dose vaccine with a median of 368 d (IQR: 350–387 days) between doses. Older age, family practice physicians, and having PPO insurance were positively associated with receiving high-dose vaccine. There were 36,624 off-label high-dose vaccines administered. Half of the patients receiving off-label doses were aged 50–64. Adults aged 18–64 y receiving high-dose vaccine were more likely to have chronic comorbidities than people receiving standard influenza vaccine; however, there was not one specific illness that seemed to be targeted by physicians. In the first 3 y since licensure, use of the high-dose vaccine among seniors has been limited. The safety of this vaccine should be

  18. Phase I study of high-dose continuous intravenous infusion of VP-16 in combination with high-dose melphalan followed by autologous bone marrow transplantation in children with stage IV neuroblastoma.

    PubMed

    Valteau-Couanet, D; Vassal, G; Pondarré, C; Bonnay, M; Benhamou, E; Couanet, D; Plantaz, D; Hartmann, O

    1996-04-01

    The purpose of the study was to determine the maximum tolerated dose of continuous infusion of high-dose VP-16 in combination with high-dose melphalan (HDM) for conditioning before autologous bone marrow transplantation (ABMT). Thirteen children (median age 27 months) with stage IV neuroblastoma were treated with high-dose VP-16 and HDM followed by ABMT as consolidation treatment. All had previously received conventional chemotherapy with a mean number of six drugs. Surgery of the primary tumor had been performed in 12/13. We performed a dose-escalating study of VP-16 from 1800 mg/m2/72 h with 300 mg/m2/72 h dose increments according to toxicity. VP-16 was administered as a 72-h i.v. infusion. Melphalan (140 mg/m2/day) was administered once as an i.v. push. VP-16 pharmacokinetics were analyzed in 12 patients. Five children received 1800 mg/m2/72 h of VP-16, five received 2100 mg/m2/72 h and three, 2400 mg/m2/72 h. The mean duration of granulocytopenia (< 0.5 x 10(9)/1) was 24 days and thrombocytopenia (< 50 x 10(9)/1) was 36 days. No major infectious complications occurred. Gastrointestinal (GI) toxicity was the dose-limiting toxicity. Five severe manifestations of GI toxicity in three patients led us to consider 2400 mg/m2/72 h as the MTD. The mean VP-16 clearance rate was 17.3 ml/min/m2 with continuous infusion. A mean steady-state plasma concentration of 24.2 micrograms/ml (s.d. = 2) and 28.3 micrograms/ml (s.d. = 1.9) was achieved at the 1800 mg/ml and 2100 mg/m2 dose levels, respectively, GI toxicity is dose limiting when VP-16 at 2400 mg/m2/72 h, is associated with HDM. When given as a continuous i.v. infusion, at 2100 mg/m2/72 h, VP-16 associated with HDM is well tolerated before ABMT in young heavily pre-treated children.

  19. Anti-angiogenic effect of high doses of ascorbic acid

    PubMed Central

    Mikirova, Nina A; Ichim, Thomas E; Riordan, Neil H

    2008-01-01

    Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA. PMID:18789157

  20. High Dose-Rate Versus Low Dose-Rate Brachytherapy for Lip Cancer

    SciTech Connect

    Ghadjar, Pirus; Bojaxhiu, Beat; Simcock, Mathew; Terribilini, Dario; Isaak, Bernhard; Gut, Philipp; Wolfensberger, Patrick; Broemme, Jens O.; Geretschlaeger, Andreas; Behrensmeier, Frank; Pica, Alessia; Aebersold, Daniel M.

    2012-07-15

    Purpose: To analyze the outcome after low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy for lip cancer. Methods and Materials: One hundred and three patients with newly diagnosed squamous cell carcinoma of the lip were treated between March 1985 and June 2009 either by HDR (n = 33) or LDR brachytherapy (n = 70). Sixty-eight patients received brachytherapy alone, and 35 received tumor excision followed by brachytherapy because of positive resection margins. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events 3.0. Results: Median follow-up was 3.1 years (range, 0.3-23 years). Clinical and pathological variables did not differ significantly between groups. At 5 years, local recurrence-free survival, regional recurrence-free survival, and overall survival rates were 93%, 90%, and 77%. There was no significant difference for these endpoints when HDR was compared with LDR brachytherapy. Forty-two of 103 patients (41%) experienced acute Grade 2 and 57 of 103 patients (55%) experienced acute Grade 3 toxicity. Late Grade 1 toxicity was experienced by 34 of 103 patients (33%), and 5 of 103 patients (5%) experienced late Grade 2 toxicity; no Grade 3 late toxicity was observed. Acute and late toxicity rates were not significantly different between HDR and LDR brachytherapy. Conclusions: As treatment for lip cancer, HDR and LDR brachytherapy have comparable locoregional control and acute and late toxicity rates. HDR brachytherapy for lip cancer seems to be an effective treatment with acceptable toxicity.

  1. Dopaminergic responses to self-administered cocaine in Rhesus monkeys do not sensitize following high cumulative intake.

    PubMed

    Bradberry, Charles W; Rubino, Susan R

    2006-05-01

    Sensitization of mesolimbic dopamine (DA) systems by administration of psychostimulants has been observed repeatedly in rodents. This phenomenon has been incorporated into theories of neurobiological adaptation underlying addiction, and is believed to be a mechanism whereby drug-associated cues acquire the ability to control behaviour via a conditioned release of DA. However, we have previously demonstrated in nonhuman primates that drug cues that cause cocaine seeking do not promote a conditioned increase in DA release of sufficient endurance to be measured in 2-min samples. In addition, imaging studies in humans and nonhuman primates that have been chronically exposed to psychostimulants have not demonstrated an increase in DA release upon psychostimulant challenge. Here we report that following 32 weeks of self-administration by rhesus monkeys, no increase over time in the DA response to self-administered cocaine was observed in any striatal subregion or individual animal. These results are consistent with clinical imaging studies showing a lack of DA sensitization, and might provide a mechanism to explain our previous observation that the rodent and primate differ in neurochemical response to drug-associated cues. PMID:16817880

  2. High-Dose Atomoxetine Treatment of ADHD in Youths with Limited Response to Standard Doses

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Michelson, David; Newcorn, Jeffrey H.; Weiss, Margaret D.; Busner, Joan; Moore, Rodney J.; Ruff, Dustin D.; Ramsey, Janet; Dickson, Ruth; Turgay, Atilla; Saylor, Keith E.; Luber, Stephen; Vaughan, Brigette; Allen, Albert J.

    2007-01-01

    Objective: To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD). Method: Two randomized, double-blind trials of atomoxetine nonresponders ages 6 to 16 years were conducted comparing continued treatment with same-dose atomoxetine to treatment using greater than…

  3. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    SciTech Connect

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A.

    2012-08-15

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  4. Correlation of Point B and Lymph Node Dose in 3D-Planned High-Dose-Rate Cervical Cancer Brachytherapy

    SciTech Connect

    Lee, Larissa J.; Sadow, Cheryl A.; Russell, Anthony; Viswanathan, Akila N.

    2009-11-01

    Purpose: To compare high dose rate (HDR) point B to pelvic lymph node dose using three-dimensional-planned brachytherapy for cervical cancer. Methods and Materials: Patients with FIGO Stage IB-IIIB cervical cancer received 70 tandem HDR applications using CT-based treatment planning. The obturator, external, and internal iliac lymph nodes (LN) were contoured. Per fraction (PF) and combined fraction (CF) right (R), left (L), and bilateral (Bil) nodal doses were analyzed. Point B dose was compared with LN dose-volume histogram (DVH) parameters by paired t test and Pearson correlation coefficients. Results: Mean PF and CF doses to point B were R 1.40 Gy +- 0.14 (CF: 7 Gy), L 1.43 +- 0.15 (CF: 7.15 Gy), and Bil 1.41 +- 0.15 (CF: 7.05 Gy). The correlation coefficients between point B and the D100, D90, D50, D2cc, D1cc, and D0.1cc LN were all less than 0.7. Only the D2cc to the obturator and the D0.1cc to the external iliac nodes were not significantly different from the point B dose. Significant differences between R and L nodal DVHs were seen, likely related to tandem deviation from irregular tumor anatomy. Conclusions: With HDR brachytherapy for cervical cancer, per fraction nodal dose approximates a dose equivalent to teletherapy. Point B is a poor surrogate for dose to specific nodal groups. Three-dimensional defined nodal contours during brachytherapy provide a more accurate reflection of delivered dose and should be part of comprehensive planning of the total dose to the pelvic nodes, particularly when there is evidence of pathologic involvement.

  5. Mosquitoes Inoculate High Doses of West Nile Virus as They Probe and Feed on Live Hosts

    PubMed Central

    Styer, Linda M; Kent, Kim A; Albright, Rebecca G; Bennett, Corey J; Kramer, Laura D; Bernard, Kristen A

    2007-01-01

    West Nile virus (WNV) is transmitted to vertebrate hosts by mosquitoes as they take a blood meal. The amount of WNV inoculated by mosquitoes as they feed on a live host is not known. Previous estimates of the amount of WNV inoculated by mosquitoes (101.2–104.3 PFU) were based on in vitro assays that do not allow mosquitoes to probe or feed naturally. Here, we developed an in vivo assay to determine the amount of WNV inoculated by mosquitoes as they probe and feed on peripheral tissues of a mouse or chick. Using our assay, we recovered approximately one-third of a known amount of virus inoculated into mouse tissues. Accounting for unrecovered virus, mean and median doses of WNV inoculated by four mosquito species were 104.3 PFU and 105.0 PFU for Culex tarsalis, 105.9 PFU and 106.1 PFU for Cx. pipiens, 104.7 PFU and 104.7 PFU for Aedes japonicus, and 103.6 PFU and 103.4 PFU for Ae. triseriatus. In a direct comparison, in vivo estimates of the viral dose inoculated by Cx. tarsalis were approximately 600 times greater than estimates obtained by an in vitro capillary tube transmission assay. Virus did not disperse rapidly, as >99% of the virus was recovered from the section fed or probed upon by the mosquito. Furthermore, 76% (22/29) of mosquitoes inoculated a small amount of virus (∼102 PFU) directly into the blood while feeding. Direct introduction of virus into the blood may alter viral tropism, lead to earlier development of viremia, and cause low rates of infection in co-feeding mosquitoes. Our data demonstrate that mosquitoes inoculate high doses of WNV extravascularly and low doses intravascularly while probing and feeding on a live host. Accurate estimates of the viral dose inoculated by mosquitoes are critical in order to administer appropriate inoculation doses to animals in vaccine, host competence, and pathogenesis studies. PMID:17941708

  6. Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism.

    PubMed

    Turello, Rita; Rentsch, Katharina; Di Paolo, Ermindo; Popovic, Maja Beck

    2008-01-01

    We report the case of an 11-year-old female treated for mediastinal T-cell lymphoma who presented renal failure following the second cycle of high-dose methotrexate (HDMTX). Because of life threatening plasma methotrexate (MTX) levels, carboxypeptidase G2 (CPDG2) was administered resulting in a dramatic decrease within 1 hr. The patient recovered from renal failure and no other side effects were observed. Homozygosity for the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism diagnosed by molecular genetic analysis was the only explanation for this toxicity. PMID:17387702

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

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

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

  8. Shelf-stable food through high dose irradiation

    NASA Astrophysics Data System (ADS)

    Plaček, V.; Svobodová, V.; Bartoníček, B.; Rosmus, J.; Čamra, M.

    2004-09-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75°C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30°C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Řež 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  9. High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: the ZEBRAS study.

    PubMed

    Goff, Donald C; McEvoy, Joseph P; Citrome, Leslie; Mech, Arnold W; Bustillo, Juan R; Gil, Roberto; Buckley, Peter; Manschreck, Theo C; Achtyes, Eric D; Macklin, Eric A

    2013-08-01

    Uncontrolled studies have suggested that increasing the dose of ziprasidone above the standard maximum daily dose of 160 mg may be more effective for some patients with schizophrenia. To test this hypothesis, we conducted an 8-week, placebo-controlled, fixed-dose escalation trial comparing ziprasidone 160 versus 320 mg/d in individuals with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks. Of 75 randomized patients, 42 completed the study. Serum ziprasidone concentrations increased significantly in the high-dose group compared with the standard-dose group at week 4 but did not differ between groups at week 8. Both treatment groups exhibited significant symptomatic improvement. Response did not differ between treatment groups; however, in the high-dose group, higher ziprasidone serum concentrations were associated with better response at a trend level. Higher ziprasidone concentrations were also associated with reductions in diastolic blood pressure and, at a trend level, with more prominent negative symptoms and greater QTc prolongation. In summary, increasing the ziprasidone dose to 320 mg/d did not produce a sustained elevation in serum concentrations or symptomatic improvement compared with a standard ziprasidone dose of 160 mg/d.

  10. Paclitaxel with mitoxantrone with or without 5-fluorouracil and high-dose leucovorin in the treatment of metastatic breast cancer.

    PubMed

    Greco, F A; Hainsworth, J D

    1997-10-01

    Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. We added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, 5-fluorouracil, and high-dose leucovorin. Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous infusion on day 1; mitoxantrone 10 mg/m2 by intravenous bolus on day 1; 5-fluorouracil 350 mg/m2 by intravenous bolus on days 1, 2, and 3; and leucovorin 300 mg intravenous over 30 to 60 minutes, immediately preceding 5-fluorouracil on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients. Of 45 assessable patients, 23 (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. There were four treatment-related deaths, two sepsis, one congestive heart failure, and one sepsis and congestive heart failure, the last two after a large cumulative anthracycline dose. This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although how its activity compares with that of other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than had been anticipated based on previous results with the mitoxantrone/5-fluorouracil/high-dose leucovorin regimen or with single-agent paclitaxel administered at this dose and schedule. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with

  11. Escalating dose methamphetamine pretreatment alters the behavioral and neurochemical profiles associated with exposure to a high-dose methamphetamine binge.

    PubMed

    Segal, David S; Kuczenski, Ronald; O'Neil, Meghan L; Melega, William P; Cho, Arthur K

    2003-10-01

    The neurotoxic effects of methamphetamine (METH) have been characterized primarily from the study of high-dose binge regimens in rodents. However, this drug administration paradigm does not include a potentially important feature of stimulant abuse in humans, that is, the gradual escalation of stimulant doses that frequently occurs prior to high-dose exposure. We have argued that pretreatment with escalating doses (EDs) might significantly alter the neurotoxic profile produced by a single high-dose binge. In the present study, we tested this hypothesis by pretreating rats with saline or gradually increasing doses of METH (0.1-4.0 mg/kg over 14 days), prior to an acute METH binge (4 x 6 mg/kg at 2 h intervals). These animals, whose behavior was continuously monitored throughout drug treatment, were then killed 3 days later for determination of caudate-putamen dopamine (DA) content, levels of [(3)H]WIN 35,428 binding to the DA transporter, and levels of [(3)H]dihydrotetrabenazine ([(3)H]DTBZ) binding to the vesicular monoamine transporter. ED pretreatment markedly attenuated the stereotypy response, as well as the hyperthermia and indices of sympathetic activation associated with the acute binge. In addition, ED pretreatment prevented the decline in [(3)H]WIN 35,428 binding, and significantly diminished the decrease in DA levels, but did not affect the decrease in [(3)H]DTBZ binding associated with the acute binge. We suggest that further study of the effects produced by a regimen which includes a gradual escalation of doses prior to high-dose METH binge exposure could more accurately identify the neurochemical and behavioral changes relevant to those that occur as a consequence of high-dose METH abuse in humans.

  12. Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

    PubMed

    Shin, Y S; Lee, S W; Park, K; Chung, W S; Kim, S W; Hyun, J S; Moon, D G; Yang, S-K; Ryu, J K; Yang, D Y; Moon, K H; Min, K S; Park, J K

    2015-01-01

    To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner. PMID:25471318

  13. Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

    PubMed

    Shin, Y S; Lee, S W; Park, K; Chung, W S; Kim, S W; Hyun, J S; Moon, D G; Yang, S-K; Ryu, J K; Yang, D Y; Moon, K H; Min, K S; Park, J K

    2015-01-01

    To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner.

  14. High Doses of Fish Oil Might Help Healing After Heart Attack

    MedlinePlus

    ... gov/news/fullstory_160178.html High Doses of Fish Oil Might Help Healing After Heart Attack Study ... Heart attack patients who took high doses of fish oil supplements for six months showed improved heart ...

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

    PubMed

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

    2013-05-22

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

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

    PubMed

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

    2013-01-01

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3-5 days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease. PMID:23704441

  17. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    NASA Technical Reports Server (NTRS)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  18. Improving Low-Dose Blood-Brain Barrier Permeability Quantification Using Sparse High-Dose Induced Prior for Patlak Model

    PubMed Central

    Fang, Ruogu; Karlsson, Kolbeinn; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Blood-brain-barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis. PMID:24200529

  19. Absorbed dose simulations in near-surface regions using high dose rate Iridium-192 sources applied for brachytherapy

    NASA Astrophysics Data System (ADS)

    Moura, E. S.; Zeituni, C. A.; Sakuraba, R. K.; Gonçalves, V. D.; Cruz, J. C.; Júnior, D. K.; Souza, C. D.; Rostelato, M. E. C. M.

    2014-02-01

    Brachytherapy treatment with Iridium-192 high dose rate (HDR) sources is widely used for various tumours and it could be developed in many anatomic regions. Iridium-192 sources are inserted inside or close to the region that will be treated. Usually, the treatment is performed in prostate, gynaecological, lung, breast and oral cavity regions for a better clinical dose coverage compared with other techniques, such as, high energy photons and Cobalt-60 machines. This work will evaluate absorbed dose distributions in near-surface regions around Ir-192 HDR sources. Near-surface dose measurements are a complex task, due to the contribution of beta particles in the near-surface regions. These dose distributions should be useful for non-tumour treatments, such as keloids, and other non-intracavitary technique. For the absorbed dose distribution simulations the Monte Carlo code PENELOPE with the general code penEasy was used. Ir-192 source geometry and a Polymethylmethacrylate (PMMA) tube, for beta particles shield were modelled to yield the percentage depth dose (PDD) on a cubic water phantom. Absorbed dose simulations were realized at the central axis to yield the Ir-192 dose fall-off along central axis. The results showed that more than 99.2% of the absorbed doses (relative to the surface) are deposited in 5 cm depth but with slower rate at higher distances. Near-surface treatments with Ir-192 HDR sources yields achievable measurements and with proper clinical technique and accessories should apply as an alternative for treatment of lesions where only beta sources were used.

  20. Bortezomib salvage followed by a phase I/II study of bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma

    PubMed Central

    Nishihori, Taiga; Alekshun, Todd J.; Shain, Kenneth; Sullivan, Daniel M.; Baz, Rachid; Perez, Lia; Pidala, Joseph; Kharfan-Dabaja, Mohamed A.; Ochoa-Bayona, Jose L; Fernandez, Hugo F; Yarde, Danielle N.; Oliveira, Vasco; Fulp, William; Han, Gang; Kim, Jongphil; Chen, Dung-Tsa; Raychaudhuri, Jyoti; Dalton, William; Anasetti, Claudio; Alsina, Melissa

    2014-01-01

    Summary We conducted a phase 1/2 study of bortezomib administered in combination with high-dose melphalan followed by tandem autologous transplants in patients with primary resistant multiple myeloma. Thirty patients received 2 cycles of salvage bortezomib followed by stem cell mobilization with G-CSF and harvest. Melphalan 100 mg/m2/day on two consecutive days was administered, immediately followed by one dose of bortezomib (dose escalation) and stem cell infusion. The median beta 2-microglobulin was 4.35 mg/L (range: 1.8 - 11.4); albumin was 3.7 g/dL (range: 3.1 - 4.9); high-risk karyotypes were noted in 45% of patients. The maximum planned dose of bortezomib at 1.3 mg/m2 was well tolerated and a formal maximum tolerated dose was not determined. The peak of best overall response (≥PR) and complete response rates after tandem transplants were 84% and 36%, respectively. With a median follow-up of 48 months, the median progression-free survival was 15 (95% CI: 11 - 21) months and the median overall survival was 35 (95% CI: 22 - 43) months. Correlative studies demonstrated decreased expression of FANCD1 (P=0.0072) and FANCF (P=0.0458) mRNA following bortezomib treatment. Bortezomib combined with high-dose melphalan is a well tolerated conditioning with some activity in patients with resistant myeloma. PMID:22449149

  1. Effects of Parent-Administered, Home-Based, High-Probability Request Sequences on Compliance by Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Humm, Stephen P.; Blampied, Neville M.; Liberty, Kathleen A.

    2005-01-01

    In the high-probability request sequence (high-p) procedure, a requester presents a rapid sequence of requests a child is known to be likely to comply with, followed by a request to perform a response for which there is a low probability of compliance (low-p request). To extend previous research from institutional and research settings to home…

  2. Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer

    PubMed Central

    Hohaus, S; Funk, L; Martin, S; Schlenk, R F; Abdallah, A; Hahn, U; Egerer, G; Goldschmidt, H; Schneeweiß, A; Fersis, N; Kaul, S; Wallwiener, D; Bastert, G; Haas, R

    1999-01-01

    and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours. © 1999 Cancer Research Campaign PMID:10188897

  3. Pellicle Life-Testing for High Exposure Dose Applications

    NASA Astrophysics Data System (ADS)

    Schurz, Dan L.; Flack, Warren W.

    2002-12-01

    There are an increasing number of microlithography applications such as advanced packaging, nanotechnology and thin film head production that require the use of thick photoresist materials. The exposure dose requirements for these applications dramatically increase as the photoresist thickness increases. For example, some positive acting novolak photoresists require exposures in excess of 5000 mJoules/cm2 for 100 μm thick films. When a single reticle is used to pattern many wafers, a significant amount of light and heat energy is transferred from the lithography tool illumination source to the pellicle protecting the reticle image. In high volume production environments, a pellicle can be subjected to accumulated dosages exceeding 500 kJoules/cm2 within a matter of weeks. Because thick photoresist applications benefit from using 1X broadband steppers with high wafer plane irradiance, life-testing results were reviewed for broadband pellicles designed for maximum transmission at g, h and i-line wavelengths of Hg. Historically, pellicle lifetime testing was typically carried out only to approximately 500 kJoules/cm2 . While this test limit may have been sufficient for thin photoresist applications used in semiconductor applications, longer lifetime studies are required to determine pellicle durability for thick photoresist applications. In this study, life testing was performed on multiple pellicle films designed for broadband illumination, including nitrocellulose, cellulose acetate, cellulose ester and fluoropolymer films. Spectroscopic transmission at g, h and i-line was first measured on unexposed pellicles. The pellicles were attached to test reticles and exposed to high-energy doses on an Ultratech broadband stepper, accumulating up to 3000 kJoules/cm2 . Transmission was periodically re-measured and the pellicle films were visually inspected for color change and any apparent physical damage. Results were compared to the expected optical properties for each

  4. 'In vivo' Dose Measurements in High-Dose-Rate Brachytherapy Treatments for Cervical Cancer: A Project Proposal

    SciTech Connect

    Reynoso Mejia, C. A.; Buenfil Burgos, A. E.; Ruiz Trejo, C.; Mota Garcia, A.; Trejo Duran, E.; Rodriguez Ponce, M.; Gamboa de Buen, I.

    2010-12-07

    The aim of this thesis project is to compare doses calculated from the treatment planning system using computed tomography images, with those measured 'in vivo' by using thermoluminescent dosimeters placed at different regions of the rectum and bladder of a patient during high-dose-rate intracavitary brachytherapy treatment of uterine cervical carcinoma. The experimental dosimeters characterisation and calibration have concluded and the protocol to carry out the 'in vivo' measurements has been established. In this work, the calibration curves of two types of thermoluminescent dosimeters (rods and chips) are presented, and the proposed protocol to measure the 'in vivo' dose is fully described.

  5. Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience

    PubMed Central

    LY, K. INA; CREW, LAURA L.; GRAHAM, CARRIE A.; MRUGALA, MACIEJ M.

    2016-01-01

    Rituximab (RTX) improves the outcome in patients with systemic diffuse large B-cell lymphoma (DLBCL), but its benefit in primary central nervous system lymphoma (PCNSL) is unclear. In the present study, a single-institution retrospective analysis was performed for 12 patients with newly diagnosed PCNSL treated with combined high-dose methotrexate (HD-MTX) and RTX. MTX was administered biweekly at 8 g/m2/dose until a complete response (CR) was achieved or for a maximum of eight doses. RTX was provided for a total of eight weekly doses at 375 mg/m2/dose. Following a median of 11 cycles of MTX, the radiographic overall response rate was 91% and the CR rate was 58%. A CR was achieved after a median 6 cycles of MTX. The median progression-free survival time was 22 months and the median overall survival time has not yet been attained. These results compare favorably to single-agent HD-MTX and suggest a role for immunochemotherapy in the treatment of PCNSL. PMID:27123138

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

    PubMed Central

    Nama, Nassr; Menon, Kusum; Iliriani, Klevis; Pojsupap, Supichaya; Sampson, Margaret; O’Hearn, Katie; Zhou, Linghong (Linda); McIntyre, Lauralyn; Fergusson, Dean

    2016-01-01

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

  7. SU-E-T-636: Investigation of Dose Variation in High Dose Radiation Brachytherapy

    SciTech Connect

    Hyvarinen, M; Leventouri, T; Casey, C; Long, S; Pella, S; Dumitru, N; Herrera, R

    2014-06-15

    Purpose: The purpose of this study is to revise most of the HDR types of treatments with their applicators and their localization challenges. Since every millimeter of misplacement counts the study will look into the necessity of increasing the immobilization for several types of applicators Methods: The study took over 136 plans generated by the treatment planning system (TPS) looking into the applicator's placement in regard to the organs at risk (OR) and simulated the three possible displacements at the hottest dose point on the critical organ for several accessories to evaluate the variation of the delivered dose at the point due to the displacement. Results: Significant dose variation was obtained for the Contura, Savi, MLM and Prostate applicators. Conclusion: This study data indicates that an improvement of the immobilization devices for HDR is absolutely necessary. Better applicator fixation devices are required too. Developing new immobilization devices for all the applicators is recommended. Florida Atlantic University may provide Travel reimbursements.

  8. Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years.

    PubMed

    Black, Steven; Friedland, Leonard R; Schuind, Anne; Howe, Barbara

    2006-08-28

    Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.

  9. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    NASA Technical Reports Server (NTRS)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  10. High-dose beclometasone dipropionate/formoterol fumarate in fixed-dose combination for the treatment of asthma.

    PubMed

    Corradi, Massimo; Spinola, Monica; Petruzzelli, Stefano; Kuna, Piotr

    2016-10-01

    The high-strength formulation of extrafine beclometasone dipropionate/formoterol fumarate (BDP/Form) 200/6 µg has been developed to step up inhaled corticosteroid treatment, without increasing the dose of the bronchodilator, in patients who are not controlled with previous therapies. Two clinical studies have evaluated efficacy of high-strength BDP/Form as compared with another high-dose fixed combination and BDP monotherapy. Overall, data show that BDP/Form 200/6 μg improves lung function and has beneficial effects on symptoms, use of rescue medication and asthma control, with an acceptable safety profile comparable with that of high-dose fluticasone propionate/salmeterol. Therefore, BDP/Form 200/6 μg could be considered as an effective and safe treatment for patients with asthma who are not adequately controlled with high doses of inhaled corticosteroid monotherapy or medium doses of inhaled corticosteroid/long-acting β2-agonist combinations. PMID:27340255

  11. A Convenient Method for Measuring Blood Ascorbate Concentrations in Patients Receiving High-Dose Intravenous Ascorbate

    PubMed Central

    Ma, Yan; Sullivan, Garrett G; Schrick, Elizabeth; Choi, In-Young; He, Zhuoya; Lierman, JoAnn; Lee, Phil; Drisko, Jeanne A; Chen, Qi

    2013-01-01

    Objective A simple method of using fingerstick blood glucose monitors (FSBG) to estimate blood ascorbate values after high-dose intravenous (IV) ascorbate infusion is evaluated as a substitution for HPLC measurement. Methods In 33 participants, readings from FSBG were taken before and after IV ascorbate infusions at various time points, with the post-infusion FSBG readings subtracted by the baseline glucose readings. The results of the subtractions (AAFSBG) were correlated with ascorbate concentrations detected by HPLC (AAHPLC). Results A linear regression was found between ascorbate concentrations detected by the fingersitck method (AAFSBG) and by HPLC (AAHPLC). The linear correlations were identical in healthy subjects, diabetic subjects and cancer patients. ANOVA analysis obtained an AAFSBG/AAHPLC ratio of 0.90, with 90% confidence interval of (0.69, 1.20). The corrections of AAFSBG improved similarity to AAHPLC, but did not significantly differ from the un-corrected values. Conclusion The FSBG method can be used as an approximate estimation of high blood ascorbate concentration after IV ascorbate (>50 mg/dL, or 2.8 mM) without correction. However this measurement is not accurate in detecting lower or baseline blood ascorbate. It is also important to highlight that in regard to glucose monitoring, FSBG readings will be erroneously elevated following intravenous ascorbate use and insulin should not be administered to patients based on these readings. PMID:23885992

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

    The aim of this study was evaluate the effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats. Bilateral ovariectomy was performed on 14 rats weighing 250 g. Thirty days later, vaginal smears were collected verifying the menopause status by anoestrus cytology. Rats were divided randomly into groups: experimental rats (n = 9) received 1 mg tibolone/day orally and control rats (n = 6) received placebo (carboxymethylcellulose). After 150 days, all rats were sedated and euthanized by cervical displacement. The vagina was removed, fixed in 10% buffered formalin, sampled and processed for paraffin embedding. Histological sections were stained with haematoxylin and eosin, picrosirius red, periodic acid Schiff (PAS) and PAS-diastase, and Weigert's resorcin–fuchsin. Cell proliferation was analysed by immunohistochemistry to detect Ki67. Histomorphometric analyses were performed for epithelial thickness, per cent area of collagen fibres and blood vessels, mast cells and Ki67-positive nuclei per mm of basal membrane. Means and standard error of means were calculated, and data were compared using the Mann–Whitney test, with significance level at P < 0.05. In the vagina, epithelial thickness, number of Ki67-positive nuclei per mm of basal membrane, number of vessels and number of mast cells were significantly higher in the tibolone group when compared with the control group. Furthermore, the content of glycogen and glycoproteins in the vaginal epithelium was modified by tibolone. Tibolone administered in high dose and for a long period has a trophic effect, reversing vaginal atrophy, and has no dysplastic or neoplastic effect in the vagina of ovariectomized rats. PMID:21518049

  14. Pharmacodynamics of tandem high-dose melphalan with peripheral blood stem cell transplantation in children with neuroblastoma and medulloblastoma.

    PubMed

    Vassal, G; Tranchand, B; Valteau-Couanet, D; Mahé, C; Couanet, D; Schoeppfer, C; Grill, J; Kalifa, C; Hill, C; Ardiet, C; Hartmann, O

    2001-03-01

    Repeated high-dose (HD) chemotherapy with peripheral blood stem cell (PBSC) transplantation is a new modality aimed at increasing both the dose and its intensity in the treatment of chemosensitive tumours. The aim of this study was to evaluate the tolerance, pharmacokinetics (PK) and pharmacodynamics (PD) of HD single-agent melphalan administered over two consecutive courses (C1 and C2) in children. Twenty-one patients (10 girls) with a median age of 4.1 years (range 8 months-14 years) were entered into this study. Five had metastatic neuroblastoma (NB) and 16 a cerebral primitive neuroectodermal tumour (PNET). Melphalan was given at a dose of 100 mg/m(2) every 21 days. PBSCs were infused at a median number of 2.98 x 10(6) CD34(+) cells/kg. Forty courses, ie 21 C1 and 19 C2, were administered. Both courses were well tolerated. The median duration of ANC < 500/microl was 7 and 6 days after C1 and C2, respectively. Platelet recovery (not mandatory to continue the HD strategy) was achieved in 52% of courses. GI toxicity was mild to moderate. The melphalan AUC ranged from 177 to 475 microg small middle dotmin/ml (no difference between C1 and C2). Prolonged neutropenia was associated with a young age (P < 0.001) and a low amount of CFU-GM (P = 0.002). A long time to platelet recovery was associated with a high AUC (P = 0.004) and a young age (P = 0.02). Grade 1 or 2 GI toxicity was associated with a high AUC (P = 0.015). Partial remission was observed in 11/14 patients with measurable cerebral PNET. In conclusion, tandem HD melphalan is feasible and safe in children, and achieved a high response rate in cerebral PNET. The observed PK-PD relationships may help us design PK-guided outpatient treatment.

  15. Cation disorder in high dose neutron irradiated spinel

    SciTech Connect

    Sickafus, K.E.; Larson, A.C.; Yu, N.; Nastasi, M.; Hollenberg, G.W.; Garner, F.A.; Bradt, R.C.

    1994-06-01

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

  16. Suitability of laser stimulated TLD arrays as patient dose monitors in high dose x-ray imaging.

    PubMed

    Geise, R A; Schueler, B A; Lien, W; Jones, S C

    1997-10-01

    Skin entrance doses of patients undergoing interventional x-ray procedures are capable of causing skin damage and should be monitored routinely. Single TLD chips are not suitable because the location of maximum skin exposure cannot be predicted. Most photographic films are too sensitive at diagnostic x-ray energies for dosimetry, exhibit temporal changes in response, and require special packaging by the user. We have investigated the suitability of laser heated MgB4O7 TLDs in a polyimide binder in the range of 0.2-20 Gy. These are available in radioluscent arrays up to 30 x 30 cm for direct measurement of patient skin dose. Dose response was compared with a calibrated ion chamber dosimeter. Exposures were made at 60, 90, and 120 kVp, at low (fluoroscopy) and high (DSA) dose rates, and at different beam incidence angles. Longitudinal reproducibility and response to temperature changes during exposure were also checked. The dose response is linear below approximately 6 Gy where the slope starts to increase 2% per Gy. Errors were less than +/- 2% over a 0-80 degrees range of beam incidence angles; less than +/- 3% for both dose rate variations and kVp differences between 70 and 120 kVp. The response was unaffected by temperature changes between 20 and 37 degrees C. Reproducibility is current +/- 7%. MgB4O7 TLD arrays are suitable for patient dosimetry in high dose fluoroscopy procedures if appropriate calibrations are used. Uncertainty in skin dose measurement is less than 10%, which is substantially better than film dosimetry. PMID:9350720

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

    PubMed

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

    2014-09-01

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

  18. Molecular Mechanisms Linking High Dose Medroxyprogesterone with HIV-1 Risk

    PubMed Central

    Irvin, Susan C.; Herold, Betsy C.

    2015-01-01

    Background Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Methods Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Results Treatment of VK2/E6E7 cells with high doses (>15μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. Conclusion We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml) MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo. PMID:25798593

  19. Conventional High-Dose-Rate Brachytherapy With Concomitant Complementary IMRT Boost: A Novel Approach for Improving Cervical Tumor Dose Coverage

    SciTech Connect

    Duan, Jun; Kim, Robert Y. Elassal, Shaaban; Lin Huiyi; Shen Sui

    2008-07-01

    Purpose: To investigate the feasibility of combining conventional high-dose-rate (HDR) brachytherapy with a concomitant complementary intensity-modulated radiotherapy (IMRT) boost for improved target coverage in cervical cancers. Methods and Materials: Six patients with cervical cancer underwent conventional HDR (C-HDR) treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired with a CT/MRI-compatible applicator in place. The clinical target volumes (CTVs), defined as the gross target volume with a 3-mm margin and the uterus, were delineated on the CT scans, along with the organs at risk (OARs). The IMRT plans were optimized to generate dose distributions complementing those of C-HDR to cover the CTV while maintaining low doses to the OARs (IMRT-HDR). For comparison, dwell-weight optimized HDR (O-HDR) plans were also generated to cover the CTV and spare the OARs. The three treatment techniques (C-HDR, O-HDR, and IMRT-HDR) were compared. The percentage of volume receiving 95% of the prescription dose (V{sub 95}) was used to evaluate dose coverage to the CTV, and the minimal doses in the 2.0-cm{sup 3} volume receiving the greatest dose were calculated to compare the doses to the OARs. Results: The C-HDR technique provided very poor CTV coverage in 5 cases (V{sub 95} <62%). Although O-HDR provided excellent gross tumor volume coverage (V{sub 95} {>=}96.9%), it resulted in unacceptably high doses to the OARs in all 6 cases and unsatisfactory coverage to the whole CTV in 3 cases. IMRT-HDR not only yielded substantially improved CTV coverage (average V{sub 95} = 95.3%), but also kept the doses to the bladder and rectum reasonably low. Conclusion: Compared with C-HDR and O-HDR, concomitant IMRT boost complementary to C-HDR not only provided excellent CTV coverage, but also maintained reasonably low doses to the OARs.

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

    PubMed

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

    1988-03-01

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

  1. Extrapolation of the dna fragment-size distribution after high-dose irradiation to predict effects at low doses

    NASA Technical Reports Server (NTRS)

    Ponomarev, A. L.; Cucinotta, F. A.; Sachs, R. K.; Brenner, D. J.; Peterson, L. E.

    2001-01-01

    The patterns of DSBs induced in the genome are different for sparsely and densely ionizing radiations: In the former case, the patterns are well described by a random-breakage model; in the latter, a more sophisticated tool is needed. We used a Monte Carlo algorithm with a random-walk geometry of chromatin, and a track structure defined by the radial distribution of energy deposition from an incident ion, to fit the PFGE data for fragment-size distribution after high-dose irradiation. These fits determined the unknown parameters of the model, enabling the extrapolation of data for high-dose irradiation to the low doses that are relevant for NASA space radiation research. The randomly-located-clusters formalism was used to speed the simulations. It was shown that only one adjustable parameter, Q, the track efficiency parameter, was necessary to predict DNA fragment sizes for wide ranges of doses. This parameter was determined for a variety of radiations and LETs and was used to predict the DSB patterns at the HPRT locus of the human X chromosome after low-dose irradiation. It was found that high-LET radiation would be more likely than low-LET radiation to induce additional DSBs within the HPRT gene if this gene already contained one DSB.

  2. Low-dose glimepiride with sitagliptin improves glycemic control without dose-dependency in patients with type 2 diabetes inadequately controlled on high-dose glimepiride.

    PubMed

    Umayahara, Rieko; Yonemoto, Takako; Kyou, Chika; Morishita, Kae; Ogawa, Tatsuo; Taguchi, Yoshitaka; Inoue, Tatsuhide

    2014-01-01

    This randomized, prospective study was conducted in 76 subjects to assess whether low-dose (0.5-2 mg/day) glimepiride, in combination therapy with sitagliptin, improves glycemic control in a dose-dependent manner in Japanese patients with type 2 diabetes. Eligible subjects had been treated with glimepiride at doses of 3-6 mg/day for at least 3 months and had a HbA1c level of ≥6.9%. Subjects were randomly assigned to three treatment groups of reduced doses of glimepiride (0.5 mg/day, 1 mg/day, or 2 mg/day) in addition to sitagliptin for 24 weeks. The primary efficacy analysis evaluated the change in HbA1c from baseline to week 24. Secondary efficacy endpoints included the changes in fasting plasma glucose, insulin secretion capacity, and β-cell function. Safety endpoints included hypoglycemia and any adverse event. Despite dose reduction of glimepiride, combination therapy with sitagliptin induced significant improvements in HbA1c levels (-0.8%, p < 0.001). Insulin secretion parameters (CPI, SUIT) also increased significantly. There were no significant differences between groups in changes from baseline HbA1c, insulin secretion capacity, and β-cell function (proinsulin/insulin) at 24 weeks of combination therapy. Multivariate analysis showed that baseline HbA1c was the only predictor for efficacy of combination therapy with sitagliptin and low-dose glimeripide. No changes in body weight were noted and no symptomatic hypoglycemia was documented. These findings indicate that combination therapy with sitagliptin and low-dose glimepiride (0.5 mg/day) is both effective for glycemic control and safe in Japanese patients with type 2 diabetes inadequately controlled with high-dose glimepiride. PMID:25168659

  3. Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.

    PubMed

    Vinnikov, Volodymyr A; Maznyk, Nataliya A

    2013-04-01

    The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed.

  4. High doses of highly pathogenic avian influenza virus in chicken meat are required to infect ferrets

    PubMed Central

    2014-01-01

    High pathogenicity avian influenza viruses (HPAIV) have caused fatal infections in mammals through consumption of infected bird carcasses or meat, but scarce information exists on the dose of virus required and the diversity of HPAIV subtypes involved. Ferrets were exposed to different HPAIV (H5 and H7 subtypes) through consumption of infected chicken meat. The dose of virus needed to infect ferrets through consumption was much higher than via respiratory exposure and varied with the virus strain. In addition, H5N1 HPAIV produced higher titers in the meat of infected chickens and more easily infected ferrets than the H7N3 or H7N7 HPAIV. PMID:24894438

  5. Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report

    PubMed Central

    Jackevicius, Cynthia A.; Ton, Mannhu N.

    2009-01-01

    This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic valve replacement was prescribed high-dose ketoconazole and hydrocortisone for the treatment of prostate cancer. Despite lowering the warfarin dosage by 35% during the start of high dose ketoconazole, an additional dose reduction was required subsequently when the INR rose from 2.62 to 3.82 within nine days. After a total dose reduction of 43%, the INR returned to therapeutic range within two weeks. The Naranjo probability scale revealed a probable adverse reaction of increased anticoagulant effect associated with high dose ketoconazole. Due to the inhibition of warfarin metabolism by ketoconazole, patients taking high dose ketoconazole concomitantly with warfarin may need their warfarin dosage reduced by more than is currently recommended, as well as receive more frequent INR monitoring to avoid over anticoagulation. PMID:20029646

  6. Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.

    PubMed

    Meesat, Ridthee; Belmouaddine, Hakim; Allard, Jean-François; Tanguay-Renaud, Catherine; Lemay, Rosalie; Brastaviceanu, Tiberius; Tremblay, Luc; Paquette, Benoit; Wagner, J Richard; Jay-Gerin, Jean-Paul; Lepage, Martin; Huels, Michael A; Houde, Daniel

    2012-09-18

    Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits. PMID:22927378

  7. Discussion on the usefulness of dose dynamic multi-leaf collimator-based plan to overcome dose limit of spinal cord in high-dose radiotherapy

    NASA Astrophysics Data System (ADS)

    Kim, E. C.; Cho, J. H.; Park, C. S.; Kim, D. H.; Choi, C. W.

    2014-03-01

    In this study, the conventional plan was compared with the plan that was based on a dose dynamic multi-leaf collimator (MLC), and a dose dynamic MLC was used to evaluate its usefulness. Then, this study examined if it was possible to perform a high-dose radiation therapy by adjusting the dose limit of the spinal cord when the dose dynamic MLC-based plan was used. First of all, linear accelerator was used to compare the conventional plan with the dose dynamic MLC-based plan. Then, the study was conducted in two methods in order to examine the proper range of the shield for the spinal cord when the dose dynamic MLC was used to adjust the dose of the spinal cord. In the first method, X-omat film was used to perform film dosimetry. In the second method, radiation treatment planning (RTP) system was used to find out the proper range among 0, 3, 6, and 9 mm. When film scan was performed in the each range, respectively, from the spinal cord and under the same conditions, it was confirmed to be appropriate to use the range of 3 mm. When the RTP system was used to perform planning in the shield range of each range, respectively, from the spinal cord, dose-volume histogram (DVH) was a slight difference could be found in the region from 25% to 35%. On the contrary, no radiation exposure was found in the region of 35% or higher for all of the each range. Consequently, if MLC is selected in consideration of the planning target volume (PTV), the most proper value can be obtained by selecting the range of 3 mm. Next, the DVH was compared to examine the relationship in PTV when the each range was used for planning. All of the ranges showed the same pattern up to the point of 90%. However, the results were different in the region of higher than 90% because the dose was low for the spinal cord, and a relatively useful dose was used for PTV when the range was 3 mm.

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

    NASA Astrophysics Data System (ADS)

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

    2008-08-01

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

  9. Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

    NASA Astrophysics Data System (ADS)

    Pervez, Nadeem

    Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

  10. High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

    PubMed Central

    O'Brien, Susan; Schiller, Gary; Lister, John; Damon, Lloyd; Goldberg, Stuart; Aulitzky, Walter; Ben-Yehuda, Dina; Stock, Wendy; Coutre, Steven; Douer, Dan; Heffner, Leonard T.; Larson, Melissa; Seiter, Karen; Smith, Scott; Assouline, Sarit; Kuriakose, Philip; Maness, Lori; Nagler, Arnon; Rowe, Jacob; Schaich, Markus; Shpilberg, Ofer; Yee, Karen; Schmieder, Guenter; Silverman, Jeffrey A.; Thomas, Deborah; Deitcher, Steven R.; Kantarjian, Hagop

    2013-01-01

    Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR. PMID:23169518

  11. Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease.

    PubMed

    Darlington, Andrew; Tello-Montoliu, Antonio; Rollini, Fabiana; Ueno, Masafumi; Ferreiro, José Luis; Patel, Ronakkumar; Desai, Bhaloo; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2014-02-01

    Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.

  12. Intermediate-dose versus high-dose prophylaxis for severe hemophilia: comparing outcome and costs since the 1970s

    PubMed Central

    Steen Carlsson, Katarina; Petrini, Pia; Holmström, Margareta; Ljung, Rolf; van den Berg, H. Marijke; Berntorp, Erik

    2013-01-01

    Prophylactic treatment in severe hemophilia is very effective but is limited by cost issues. The implementation of 2 different prophylactic regimens in The Netherlands and Sweden since the 1970s may be considered a natural experiment. We compared the costs and outcomes of Dutch intermediate- and Swedish high-dose prophylactic regimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970 and 1994, using prospective standardized outcome assessment and retrospective collection of cost data. Seventy-eight Dutch and 50 Swedish patients, median age 24 years (range, 14-37 years), were included. Intermediate-dose prophylaxis used less factor concentrate (median: Netherlands, 2100 IU/kg per year [interquartile range (IQR), 1400-2900 IU/kg per year] vs Sweden, 4000 IU/kg per year [IQR, 3000-4900 IU/kg per year]); (P < .01). Clinical outcome was slightly inferior for the intermediate-dose regimen (P < .01) for 5-year bleeding (median, 1.3 [IQR, 0.8-2.7] vs 0 [IQR, 0.0-2.0] joint bleeds/y) and joint health (Haemophilia Joint Health Score >10 of 144 points in 46% vs 11% of participants), although social participation and quality of life were similar. Annual total costs were 66% higher for high-dose prophylaxis (mean, 180 [95% confidence interval, 163 - 196] × US$1000 for Dutch vs 298 [95% confidence interval, 271-325]) × US$1000 for Swedish patients; (P < .01). At group level, the incremental benefits of high-dose prophylaxis appear limited. At the patient level, prophylaxis should be tailored individually, and many patients may do well receiving lower doses of concentrate without compromising safety. PMID:23777770

  13. Intermediate-dose versus high-dose prophylaxis for severe hemophilia: comparing outcome and costs since the 1970s.

    PubMed

    Fischer, Kathelijn; Steen Carlsson, Katarina; Petrini, Pia; Holmström, Margareta; Ljung, Rolf; van den Berg, H Marijke; Berntorp, Erik

    2013-08-15

    Prophylactic treatment in severe hemophilia is very effective but is limited by cost issues. The implementation of 2 different prophylactic regimens in The Netherlands and Sweden since the 1970s may be considered a natural experiment. We compared the costs and outcomes of Dutch intermediate- and Swedish high-dose prophylactic regimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970 and 1994, using prospective standardized outcome assessment and retrospective collection of cost data. Seventy-eight Dutch and 50 Swedish patients, median age 24 years (range, 14-37 years), were included. Intermediate-dose prophylaxis used less factor concentrate (median: Netherlands, 2100 IU/kg per year [interquartile range (IQR), 1400-2900 IU/kg per year] vs Sweden, 4000 IU/kg per year [IQR, 3000-4900 IU/kg per year]); (P < .01). Clinical outcome was slightly inferior for the intermediate-dose regimen (P < .01) for 5-year bleeding (median, 1.3 [IQR, 0.8-2.7] vs 0 [IQR, 0.0-2.0] joint bleeds/y) and joint health (Haemophilia Joint Health Score >10 of 144 points in 46% vs 11% of participants), although social participation and quality of life were similar. Annual total costs were 66% higher for high-dose prophylaxis (mean, 180 [95% confidence interval, 163 - 196] × US$1000 for Dutch vs 298 [95% confidence interval, 271-325]) × US$1000 for Swedish patients; (P < .01). At group level, the incremental benefits of high-dose prophylaxis appear limited. At the patient level, prophylaxis should be tailored individually, and many patients may do well receiving lower doses of concentrate without compromising safety.

  14. Effect of conjoint administration of tamoxifen and high-dose radiation on the development of mammary carcinoma

    SciTech Connect

    Kantorowitz, D.A. ); Thompson, H.J. ); Furmanski, P. )

    1993-04-30

    Tamoxifen is currently advocated for post-menopausal breast cancer patients receiving definitive irradiation after limited surgery. The purpose of this study was to assess in an experimental model for breast cancer whether the efficacy of irradiation is altered by conjoint administration of tamoxifen. To this end, rats with small tumors induced by 1-methyl-1-nitrosourea (MNU) were treated with tamoxifen, radiation, or a combination of the two modalities. Female Sprague Dawley rats were injected i.p. with 50 mg MNU/kg body weight at 50 days of age. At 64 days post carcinogen, the majority of the rats had at least one palpable mammary tumor. At that time radiation with or without tamoxifen treatment was initiated and given 5 days per week for 5 weeks. Radiation dose was 4500 cGy delivered as 25, 180 cGy fractions. Tamoxifen, 500 mg/kg body weight, was administered subcutaneously each day during the irradiation interval. The study was terminated 28 weeks after carcinogen treatment. High dose radiation alone induced a reduction in the size of existing tumors, but resulted in a significant increase in the number of tumors that were detected. Treatment with tamoxifen alone also caused a reduction in tumor volume, but had no effect on final incidence or number of mammary tumors. Combined modality treatment resulted in a significant reduction in the volume of existing tumors and suppressed the enhanced occurrence of additional tumors observed when only radiation alone was administered. The findings of this study indicate that in the context of fractionated, high dose radiation treatment of established mammary cancers, tamoxifen may reduce the likelihood of subsequent tumor development and by so doing prove a helpful simultaneous conjoint adjuvant treatment to post-operative irradiation. 35 refs., 1 fig., 2 tabs.

  15. SU-C-12A-05: Radiation Dose in High-Pitch Pediatric Cardiac CTA: Correlation Between Lung Dose and CTDIvol, DLP, and Size Specific Dose Estimates (SSDE)

    SciTech Connect

    Wang, J; Kino, A; Newman, B; Chan, F

    2014-06-01

    Purpose: To investigate the radiation dose for pediatric high pitch cardiac CTA Methods: A total of 14 cases were included in this study, with mean age of 6.2 years (ranges from 2 months to 15 years). Cardiac CTA was performed using a dual-source CT system (Definition Flash, Siemens). Tube voltage (70, 80 and 100kV) was chosen based on patient weight. All patients were scanned using a high-pitch spiral mode (pitch ranges from 2.5 to 3) with tube current modulation technique (CareDose4D, Siemens). For each case, the three dimensional dose distributions were calculated using a Monte Carlo software package (IMPACT-MC, CT Image GmbH). Scanning parameters of each exam, including tube voltage, tube current, beamshaping filters, beam collimation, were defined in the Monte Carlo calculation. Tube current profile along projection angles was obtained from projection data of each tube, which included data within the over-scanning range along z direction. The volume of lungs was segmented out with CT images (3DSlicer). Lung doses of all patients were calculated and compared with CTDIvol, DLP, and SSDE. Results: The average (range) of CTDIvol, DLP and SSDE of all patients was 1.19 mGy (0.58 to 3.12mGy), 31.54 mGy*cm (12.56 to 99 mGy*cm), 2.26 mGy (1.19 to 6.24 mGy), respectively. Radiation dose to the lungs ranged from 0.83 to 4.18 mGy. Lung doses correlated with CTDIvol, DLP and SSDE with correlation coefficients(k) at 0.98, 0.93, and 0.99. However, for the cases with CTDIvol less than 1mGy, only SSDE preserved a strong correlation with lung doses (k=0.83), while much weaker correlations were found for CTDIvol (k=0.29) and DLP (k=-0.47). Conclusion: Lung doses to pediatric patients during Cardiac CTA were estimated. SSDE showed the most robust correlation with lung doses in contrast to CTDIvol and DLP.

  16. An Absorbed-Dose/Dose-Rate Dependence for the Alanine-EPR Dosimetry System and Its Implications in High-Dose Ionizing Radiation Metrology

    PubMed Central

    Desrosiers, M. F.; Puhl, J. M.; Cooper, S. L.

    2008-01-01

    NIST developed the alanine dosimetry system in the early 1990s to replace radiochromic dye film dosimeters. Later in the decade the alanine system was firmly established as a transfer service for high-dose radiation dosimetry and an integral part of the internal calibration scheme supporting these services. Over the course of the last decade, routine monitoring of the system revealed a small but significant observation that, after examination, led to the characterization of a previously unknown absorbed-dose-dependent, dose-rate effect for the alanine system. Though the potential impact of this effect is anticipated to be extremely limited for NIST’s customer-based transfer dosimetry service, much greater implications may be realized for international measurement comparisons between National Measurement Institutes. PMID:27096113

  17. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies

    PubMed Central

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6–35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3–17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6–35 months and 3–17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158. PMID:26176592

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

    SciTech Connect

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

    2013-01-14

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

  19. Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion.

    PubMed

    Salgado, R; Pereiro, N; López-Doval, S; Lafuente, A

    2015-09-01

    Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release. PMID:26032630

  20. Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion.

    PubMed

    Salgado, R; Pereiro, N; López-Doval, S; Lafuente, A

    2015-09-01

    Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release.

  1. Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

  2. Acute toxicity of high doses of the glycoalkaloids, alpha-solanine and alpha-chaconine, in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Schrøder, Malene; Stewart, Derek; Meyer, Otto; Conner, Sean; Davies, Howard; Poulsen, Morten

    2008-09-24

    Sprouted, stressed, or spoiled potato tubers have reportedly led to human acute intoxication, coma, and death when consumed in high amounts. These effects have been attributed to glycoalkaloids (GAs), primarily alpha-solanine and alpha-chaconine, naturally present in all potatoes. The level of GAs in potato tubers has previously been shown to increase substantially as a result of improper handling and postharvest storage. A short-term study was performed to investigate the dose-response profile of alpha-solanine and alpha-chaconine alone or in combination, administered daily by oral gavage to Syrian Golden hamsters. Daily doses of 100 mg of alpha-solanine [kg body weight (BW)] (-1) induced death in two of four hamsters within 4 days, when administered by gavage to female Syrian hamsters. Doses of 100 mg of alpha-chaconine alone or alpha-solanine and alpha-chaconine combined in a ratio of 1:2.5, in doses of 75 or 100 mg (kg BW) (-1), induced death in one of four hamsters within the same period. Animals dosed with alpha-solanine alone or in combination with alpha-chaconine suffered from fluid-filled and dilated small intestines. The GA administration had no effect on acetyl cholinesterase (AChE) or butyryl cholinesterase (BuChE) activity in plasma or brain. Liquid chromatography-mass spectrometry-based metabolomics showed that there was a specific accumulation of alpha-chaconine in the liver tissues. In addition, metabolomics gave direct evidence of glycolytic metabolism of the GA with the beta 1, beta 2, and gamma-GAs detected in the urine and, to a lesser extent, the feces. Doses from 75 mg (kg BW) (-1) of alpha-chaconine, alpha-solanine, or the two compounds combined were potentially lethal within 4-5 days in the Syrian Golden hamster. However, the cause of death in these studies could not be established. No synergistic effects of alpha-solanine combined with alpha-chaconine were evident.

  3. HDRMC, an accelerated Monte Carlo dose calculator for high dose rate brachytherapy with CT-compatible applicators

    SciTech Connect

    Chibani, Omar C-M Ma, Charlie

    2014-05-15

    Purpose: To present a new accelerated Monte Carlo code for CT-based dose calculations in high dose rate (HDR) brachytherapy. The new code (HDRMC) accounts for both tissue and nontissue heterogeneities (applicator and contrast medium). Methods: HDRMC uses a fast ray-tracing technique and detailed physics algorithms to transport photons through a 3D mesh of voxels representing the patient anatomy with applicator and contrast medium included. A precalculated phase space file for the{sup 192}Ir source is used as source term. HDRM is calibrated to calculated absolute dose for real plans. A postprocessing technique is used to include the exact density and composition of nontissue heterogeneities in the 3D phantom. Dwell positions and angular orientations of the source are reconstructed using data from the treatment planning system (TPS). Structure contours are also imported from the TPS to recalculate dose-volume histograms. Results: HDRMC was first benchmarked against the MCNP5 code for a single source in homogenous water and for a loaded gynecologic applicator in water. The accuracy of the voxel-based applicator model used in HDRMC was also verified by comparing 3D dose distributions and dose-volume parameters obtained using 1-mm{sup 3} versus 2-mm{sup 3} phantom resolutions. HDRMC can calculate the 3D dose distribution for a typical HDR cervix case with 2-mm resolution in 5 min on a single CPU. Examples of heterogeneity effects for two clinical cases (cervix and esophagus) were demonstrated using HDRMC. The neglect of tissue heterogeneity for the esophageal case leads to the overestimate of CTV D90, CTV D100, and spinal cord maximum dose by 3.2%, 3.9%, and 3.6%, respectively. Conclusions: A fast Monte Carlo code for CT-based dose calculations which does not require a prebuilt applicator model is developed for those HDR brachytherapy treatments that use CT-compatible applicators. Tissue and nontissue heterogeneities should be taken into account in modern HDR

  4. Targeted Lung Delivery of Nasally Administered Aerosols

    PubMed Central

    Tian, Geng; Hindle, Michael; Longest, P. Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. PMID:24932058

  5. Use of high-dose epinephrine and sodium bicarbonate during neonatal resuscitation: is there proven benefit?

    PubMed

    Wyckoff, Myra H; Perlman, Jeffrey M

    2006-03-01

    For adults and pediatric age patients, high-dose intravenous epinephrine was recommended if standard-dose epinephrine failed to achieve return of spontaneous circulation. More recent trials suggest that high-dose epinephrine is not beneficial and may result in increased harm. There are no randomized clinical studies of high-dose versus standard-dose intravenous epinephrine in neonates. Routine use of high-dose epinephrine during neonatal resuscitation cannot be recommended. Although sodium bicarbonate has been used during neonatal resuscitation, the only randomized controlled trial of its use during brief neonatal resuscitation showed no benefit. Sodium bicarbonate infusion during neonatal cardiopulmonary resuscitation (CPR) has several known and potential side effects. The use of sodium bicarbonate infusion should be discouraged during brief CPR. Whether sodium bicarbonate is beneficial for infants who require prolonged CPR despite adequate ventilation is unknown.

  6. PLUTONIUM/HIGH LEVEL VITRIFIED WASTE - DBE OFFSITE DOSE CALCULATION

    SciTech Connect

    S. O. Bader

    1999-09-20

    The purpose of this calculation is to provide a bounding dose consequence analysis of the immobilized plutonium (can-in-canister) waste form to be handled at the Monitored Geologic Repository (MGR) at Yucca Mountain. The current concept for the Plutonium Can-in-Canister waste form is provided in Attachment III. A typical design basis event (DBE) defines a scenario that generally includes an initiating event and the sequences of events that follow. This analysis will provide (1) radiological releases and dose consequences for a postulated, bounding DBE and (2) design-related assumptions on which the calculated dose consequences are based. This analysis is part of the safety design basis for the repository. Results will be used in other analyses to determine or modify the safety classification and quality assurance level of repository structures, systems, and components (SSCs). The Quality Assurance (QA) program applies to this calculation. The work reported in this document is part of the analysis of MGR DBEs and is performed using AP-3.12Q, Calculations. The work done for this analysis was evaluated according to QAP-2-0, Control of Activities. This evaluation determined that such activities are subject to DOE/RW/0333PY Quality Assurance Requirements and Description (DOE 1998), requirements. This calculation is quality affecting because the results may be used to support analyses of repository SSCs per QAP-2-3, Classification of Permanent Items.

  7. Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

    SciTech Connect

    Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J.; Zheng, Suqing; Huang, Jeffrey T.-J.; Honda, Tadashi; Dinkova-Kostova, Albena T.

    2015-09-25

    The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC{sub 0–24h} was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the k{sub el} was 0.068 h{sup −1}. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. - Highlights: • TBE-31 is a cysteine targeting compound with a reversible covalent mode of action. • After a single oral dose, the blood concentration of TBE-31 exhibits two peaks. • Oral TBE-31 is a potent activator of Nrf2-dependent enzymes in

  8. Malaria-Infected Mice Live Until At Least Day 30 After A New Artemisinin-Derived Thioacetal Thiocarbonate Combined with Mefloquine Are Administered Together In A Single, Low, Oral Dose

    PubMed Central

    Jacobine, Alexander M.; Mazzone, Jennifer R.; Slack, Rachel D.; Tripathi, Abhai K.; Sullivan, David J.; Posner, Gary H.

    2012-01-01

    In only three steps and in 21–67% overall yields from the natural trioxane artemisinin, a series of 21 new trioxane C-10 thioacetals was prepared. Upon receiving a single oral dose of only 6 mg/kg of the monomeric trioxane 12c combined with 18 mg/kg of mefloquine hydrochloride, Plasmodium berghei-infected mice survived on average 29.8 days after infection. Two of the four mice in this group had no parasites detectable in their blood on day 30 after infection and they behaved normally and appeared healthy. One of the mice had 11% blood parasitemia on day 30, and one mouse in this group died on day 29. Of high medicinal importance, the efficacy of this ACT chemotherapy is much better than (almost double) the efficacy under the same conditions using as a positive control the popular trioxane drug artemether plus mefloquine hydrochloride (average survival time of only 16.5 days). PMID:22891714

  9. A computer simulation method for low-dose CT images by use of real high-dose images: a phantom study.

    PubMed

    Takenaga, Tomomi; Katsuragawa, Shigehiko; Goto, Makoto; Hatemura, Masahiro; Uchiyama, Yoshikazu; Shiraishi, Junji

    2016-01-01

    Practical simulations of low-dose CT images have a possibility of being helpful means for optimization of the CT exposure dose. Because current methods reported by several researchers are limited to specific vendor platforms and generally rely on raw sinogram data that are difficult to access, we have developed a new computerized scheme for producing simulated low-dose CT images from real high-dose images without use of raw sinogram data or of a particular phantom. Our computerized scheme for low-dose CT simulation was based on the addition of a simulated noise image to a real high-dose CT image reconstructed by the filtered back-projection algorithm. First, a sinogram was generated from the forward projection of a high-dose CT image. Then, an additional noise sinogram resulting from use of a reduced exposure dose was estimated from a predetermined noise model. Finally, a noise CT image was reconstructed with a predetermined filter and was added to the real high-dose CT image to create a simulated low-dose CT image. The noise power spectrum and modulation transfer function of the simulated low-dose images were very close to those of the real low-dose images. In order to confirm the feasibility of our method, we applied this method to clinical cases which were examined with the high dose initially and then followed with a low-dose CT. In conclusion, our proposed method could simulate the low-dose CT images from their real high-dose images with sufficient accuracy and could be used for determining the optimal dose setting for various clinical CT examinations.

  10. Dose-Rate Dependence of High-Dose Health Effects in Humans from Photon Radiation with Application to Radiological Terrorism

    SciTech Connect

    Strom, Daniel J.

    2005-01-14

    In 1981, as part of a symposium entitled ''The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack,'' Lushbaugh, H?bner, and Fry published a paper examining ''radiation tolerance'' of various human health endpoints as a function of dose rate. This paper may not have received the notice it warrants. The health endpoints examined by Lushbaugh et al. were the lethal dose that will kill 50% of people within 60 days of exposure without medical care (LD50/60); severe bone marrow damage in healthy men; severe bone marrow damage in leukemia patients; temporary sterility (azoospermia); reduced male fertility; and late effects such as cancer. Their analysis was grounded in extensive clinical experience and anchored to a few selected data points, and based on the 1968 dose-rate dependence theory of J.L. Bateman. The Lushbaugh et al. paper did not give predictive equations for the relationships, although they were implied in the text, and the relationships were presented in a non-intuitive way. This work derives the parameters needed in Bateman's equation for each health endpoint, tabulates the results, and plots them in a more conventional manner on logarithmic scales. The results give a quantitative indication of how the human organism can tolerate more radiation dose when it is delivered at lower dose rates. For example, the LD50/60 increases from about 3 grays (300 rads) when given at very high dose rates to over 10 grays (1,000 rads) when given at much lower dose rates over periods of several months. The latter figure is borne out by the case of an individual who survived for at least 19 years after receiving doses in the range of 9 to 17 grays (900-1700 rads) over 106 days. The Lushbaugh et al. work shows the importance of sheltering when confronted with long-term exposure to radiological contamination such as would be expected from a radiological dispersion event, reactor accident, or ground-level nuclear explosion.

  11. Concomitant 5-fluorouracil infusion and high-dose radiation for stage III non-small cell lung cancer

    SciTech Connect

    Lokich, J.; Chaffey, J.; Neptune, W. )

    1989-09-01

    Thirty patients with Stage III non-small cell lung cancer were entered on a trial to evaluate the feasibility of combined radiation and concomitant 5-fluorouracil infusion. Patients had received prior debulking surgery (nine), induction chemotherapy (16), or no therapy (five). Radiation employed standard fractionation (180-200 rad/day) administered to a median cumulative dose of 5500 rad (range, 4500-6200 rad). 5-Fluorouracil was infused 24 hours per day throughout the period of radiation at a dose of 300 mg/m2/day for a median of 42 days (range, 28-56 days). Radiation complications included pneumonitis three of 30 (10%) and esophagitis (27%). Chemotherapy complications included stomatitis, two of 27 (7%), and hand-foot syndrome, three of 30 (10%). Treatment interruptions were necessary in six of 30 (20%) and four of 30 required parenteral nutrition. At a median follow-up of 12 months 26/30 (87%) maintained local control and eight had distant metastases (three of whom presented with Stage IV disease). 5-Fluorouracil delivered continuously throughout standard fractionation radiation to high cumulative doses is feasible and practical. Comparative clinical trials of the various combined radiation and chemotherapy schedules employed are in order. One additional clinical observation was the identification of six of 30 (20%) with brain metastases at presentation or after 12 months, all of whom had adenocarcinoma histologic subtype.

  12. Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma

    SciTech Connect

    Fayed, Alaa; Mutch, David G.; Rader, Janet S.; Gibb, Randall K. |; Powell, Matthew A. |; Wright, Jason D.; El Naqa, Issam; Zoberi, Imran |; Grigsby, Perry W. |||. E-mail: pgrigsby@wustl.edu

    2007-02-01

    Purpose: To compare the outcomes for endometrial carcinoma patients treated with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. Methods and Materials: This study included 1,179 patients divided into LDR (1,004) and HDR groups (175). Patients with International Federation of Gynecology and Obstetrics (FIGO) surgical Stages I-III were included. All patients were treated with postoperative irradiation. In the LDR group, the postoperative dose applied to the vaginal cuff was 60-70 Gy surface doses to the vaginal mucosa. The HDR brachytherapy prescription was 6 fractions of 2 Gy each to a depth of 0.5 cm from the surface of the vaginal mucosa. Overall survival, disease-free survival, local control, and complications were endpoints. Results: For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the LDR group were 70%, 69%, and 81%, respectively. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the HDR group were 68%, 62%, and 78%, respectively. There were no significant differences in early or late Grade III and IV complications in the HDR or LDR groups. Conclusion: Survival outcomes, pelvic tumor control, and Grade III and IV complications were not significantly different in the LDR brachytherapy group compared with the HDR group.

  13. Ceramic Matrix Composites Performances Under High Gamma Radiation Doses

    NASA Astrophysics Data System (ADS)

    Cemmi, A.; Baccaro, S.; Fiore, S.; Gislon, P.; Serra, E.; Fassina, S.; Ferrari, E.; Ghisolfi, E.

    2014-06-01

    Ceramic matrix composites reinforced by continuous ceramic fibers (CMCs) represent a class of advanced materials developed for applications in automotive, aerospace, nuclear fusion reactors and in other specific systems for harsh environments. In the present work, the silicon carbide/silicon carbide (SiCf/SiC) composites, manufactured by Chemical Vapour Infiltration process at FN S.p.A. plant, have been evaluated in term of gamma radiation hardness at three different absorbed doses (up to around 3MGy). Samples behavior has been investigated before and after irradiation by means of mechanical tests (flexural strength) and by surface and structural analyses (X-ray diffraction, SEM, FTIR-ATR, EPR).

  14. Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

    PubMed Central

    Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J.; Zheng, Suqing; Huang, Jeffrey T.-J.; Honda, Tadashi; Dinkova-Kostova, Albena T.

    2015-01-01

    The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC0–24h was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the kel was 0.068 h−1. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. PMID:26265043

  15. TLD efficiency of 7LiF for doses deposited by high-LET particles

    NASA Technical Reports Server (NTRS)

    Benton, E. R.; Frank, A. L.; Benton, E. V.

    2000-01-01

    The efficiency of 7 LiF TLDs (TLD-700) in registering dose from high-LET (> or = 10 keV/micrometers) charged particles (relative to 137Cs gamma rays) has been measured for a number of accelerated heavy ions at various particle accelerator facilities. These measured efficiency values have been compared with similar results obtained from the open literature and a dose efficiency function has been fitted to the combined data set. While it was found that the dose efficiency is not only a function of LET, but also of the charge of the incident particle, the fitted function can be used to correct the undermeasured value of dose from exposures made in mixed radiation fields where LET information is available. This LET-dependent dose efficiency function is used in our laboratory in determining total absorbed dose and dose equivalent from combined TLD and CR-39 plastic nuclear track detector measurements.

  16. Hyperhaploid and tetraploid sperm detected in men who ingested ultra-high doses of diazepam

    SciTech Connect

    Baumgartner, A. |; Adler, I.D.; Schmid, T.E.

    1997-10-01

    Diazepam is widely administered as a sedative, muscle relaxant and anxiolytic drug. Five young non-smoking men who were hospitalized after their suicide attempt using diazepam, {approximately}1-7 mg/kg (oral intake), provided semen samples 40-50 days and {approximately}100 days after exposure to assess drug effects on meiotic cells and to evaluate persistence. Five healthy men served as local clinical controls. A multicolor FISH assay was applied to detect aneuploidy for chromosome X, Y, and 21 in sperm. Sex ratios were not significantly different from 1:1 among 133,143 cells analyzed. The 40-day samples showed an increase in several sperm aneuploidy groups: disomy 21 (1.5 fold, p=0.04); disomy X (2.7 fold, p=0.0006), and XY aneuploidy (1.6 folk, p=0 0.017). The results for {approximately}100 days after exposure were similar to controls suggesting that hyperhaploidy effects may not persist. Phase contrast microscopy was used to identify flagellated tetraploid sperm, i.e., X-X-Y-Y-21-21-21-21. Tetraploid sperm were found among 8 semen samples provided by five patients (1.4 {+-} 1.2 per 10,000 cells; >80,000 cells) while none were detected among >50,000 cells from healthy men. Our findings are consistent with the possible aneuploidy-inducing effect of diazepam during male meiosis but further studies are needed before these results can be extrapolated to therapeutic dosing because suicide patients are a highly exposed cohort and other confounding factors (alcohol, drugs, antidotes) cannot be ruled out.

  17. Effect of high doses of gamma radiation on the functional characteristics of amniotic membrane

    NASA Astrophysics Data System (ADS)

    Singh, Rita; Purohit, Sumita; Chacharkar, M. P.

    2007-06-01

    The effect of different doses of gamma radiation viz. 25, 36 and 50 kGy on the chemical and functional characteristics of the amniotic membrane was studied. The change in the chemical structure of amniotic membranes at high doses of gamma irradiation was evaluated by means of Infrared (IR) Spectroscopy. The degradation of amnion on irradiation with gamma rays could produce a relative variation in IR absorption troughs. This kind of variation was absent in the samples irradiated to doses of 25, 36 and 50 kGy indicating no qualitative change in the material property of amnion. No significant differences in the water absorption capacity and water vapour transmission rate of amniotic membranes irradiated to different doses were observed. Impermeability of the amniotic membranes to different microorganisms was also not affected at high doses of gamma radiation. Gamma irradiation at doses of 25-50 kGy did not evoke undesirable changes in the functional properties of the amniotic membrane.

  18. TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses

    PubMed Central

    Zheng, Xiao-Hui; Nie, Xin; Liu, Hai-Ying; Fang, Yi-Ming; Zhao, Yong; Xia, Li-Xin

    2016-01-01

    TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended “side-effect” of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy. PMID:27221067

  19. Plasma Doping - Enabling Technology for High Dose Logic and Memory Applications

    SciTech Connect

    Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

    2008-11-03

    As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

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

    PubMed Central

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

    1988-01-01

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

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

    PubMed

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

    2010-01-01

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

  2. Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation

    PubMed Central

    Bang, Hyun Soon; Choi, Moo Hyun; Kim, Cha Soon; Choi, Seung Jin

    2016-01-01

    Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID:27006382

  3. Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

    NASA Astrophysics Data System (ADS)

    Fournier, P.; Crosbie, J. C.; Cornelius, I.; Berkvens, P.; Donzelli, M.; Clavel, A. H.; Rosenfeld, A. B.; Petasecca, M.; Lerch, M. L. F.; Bräuer-Krisch, E.

    2016-07-01

    Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.

  4. Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates.

    PubMed

    Fournier, P; Crosbie, J C; Cornelius, I; Berkvens, P; Donzelli, M; Clavel, A H; Rosenfeld, A B; Petasecca, M; Lerch, M L F; Bräuer-Krisch, E

    2016-07-21

    Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency's TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called 'current ramping' method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials. PMID:27366861

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

    PubMed

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

    2013-04-01

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

  6. Design and validation of a self-administered test to assess bullying (bull-M) in high school Mexicans: a pilot study

    PubMed Central

    2013-01-01

    Background Bullying (Bull) is a public health problem worldwide, and Mexico is not exempt. However, its epidemiology and early detection in our country is limited, in part, by the lack of validated tests to ensure the respondents’ anonymity. The aim of this study was to validate a self-administered test (Bull-M) for assessing Bull among high-school Mexicans. Methods Experts and school teachers from highly violent areas of Ciudad Juarez (Chihuahua, México), reported common Bull behaviors. Then, a 10-item test was developed based on twelve of these behaviors; the students’ and peers’ participation in Bull acts and in some somatic consequences in Bull victims with a 5-point Likert frequency scale. Validation criteria were: content (CV, judges); reliability [Cronbach’s alpha (CA), test-retest (spearman correlation, rs)]; construct [principal component (PCA), confirmatory factor (CFA), goodness-of-fit (GF) analysis]; and convergent (Bull-M vs. Bull-S test) validity. Results Bull-M showed good reliability (CA = 0.75, rs = 0.91; p < 0.001). Two factors were identified (PCA) and confirmed (CFA): “bullying me (victim)” and “bullying others (aggressor)”. GF indices were: Root mean square error of approximation (0.031), GF index (0.97), and normalized fit index (0.92). Bull-M was as good as Bull-S for measuring Bull prevalence. Conclusions Bull-M has a good reliability and convergent validity and a bi-modal factor structure for detecting Bull victims and aggressors; however, its external validity and sensitivity should be analyzed on a wider and different population. PMID:23577755

  7. [High-dose buprenorphine for outpatient palliative pain therapy].

    PubMed

    Gastmeier, K; Freye, E

    2009-04-01

    The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care. PMID:19066981

  8. [High-dose buprenorphine for outpatient palliative pain therapy].

    PubMed

    Gastmeier, K; Freye, E

    2009-04-01

    The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care.

  9. [Biochemical modulation of 5-fluorouracil by high-dose leucovorin].

    PubMed

    Aiba, K

    1988-03-01

    The biochemical modulation of 5-fluorouracil (FU) by using it in combination with leucovorin (LV) is reviewed. One of the mechanisms of action of FU is inhibition of thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate required for DNA repair and synthesis. In the presence of 5, 10-methylene tetrahydrofolate, 5-fluoro-deoxyuridine monophosphate (FdUMP), which is an active nucleotide of FU, forms a ternary complex with TS, resulting in enzyme inhibition. The rationale for the use of LV with FU is to increase of formation and stability of catalytically inactive ternary complexes. In clinical trials, the dose schedules of 500 mg/m2 iv bolus or 500 mg/m2 continuously iv infusion is frequently used in order to obtain an ideal plasma concentration of active LV metabolites. Preliminary clinical trials using the combination of FU and LV appear to be capable of increasing of the clinical activity of FU for colorectal and breast cancers. Several randomized studies have supported the increase in response rates seen in the uncontrolled trials but additional studies are required to demonstrate a positive impact on the survival of treated patients.

  10. Dose rate dependence of the PTW 60019 microDiamond detector in high dose-per-pulse pulsed beams

    NASA Astrophysics Data System (ADS)

    Brualla-González, Luis; Gómez, Faustino; Pombar, Miguel; Pardo-Montero, Juan

    2016-01-01

    Recombination effects can affect the detectors used for the dosimetry of radiotherapy fields. They are important when using ionization chambers, especially in liquid-filled ionization chambers, and should be corrected for. The introduction of flattening-filter-free accelerators increases the typical dose-per-pulse used in radiotherapy beams, which leads to more important recombination effects. Diamond detectors provide a good solution for the dosimetry and quality assurance of small radiotherapy fields, due to their low energy dependence and small volume. The group of Università di Roma Tor Vergata has developed a synthetic diamond detector, which is commercialized by PTW as microDiamond detector type 60019. In this work we present an experimental characterization of the collection efficiency of the microDiamond detector, focusing on high dose-per-pulse FFF beams. The collection efficiency decreases with dose-per-pulse, down to 0.978 at 2.2 mGy/pulse, following a Fowler-Attix-like curve. On the other hand, we have found no significant dependence of the collection efficiency on the pulse repetition frequency (or pulse period).

  11. High dose of tigecycline for extremely resistant Gram-negative pneumonia: yes, we can

    PubMed Central

    2014-01-01

    Few antimicrobials are currently active to treat infections caused by extremely resistant Gram-negative bacilli (ERGNB), which represent a serious global public health concern. Tigecycline, which covers the majority of these ERGNB (with the exception of Pseudomonas aeruginosa), is not currently approved for hospital-acquired pneumonia, and several meta-analyses have suggested an increased risk of death in patients receiving this antibiotic. Other studies suggest that the use of high-dose tigecycline may represent an alternative in daily practice. De Pascale and colleagues report that the clinical cure rate in patients with ventilator-associated pneumonia is significantly higher with a high dose of tigecycline than with the conventional dose, although mortality was unaffected. This high dose is safe; no patients required discontinuation or dose reduction. PMID:25043402

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

    PubMed Central

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

    2014-01-01

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

  13. Childhood mortality after a high dose of vitamin A in a high risk population.

    PubMed Central

    Daulaire, N. M.; Starbuck, E. S.; Houston, R. M.; Church, M. S.; Stukel, T. A.; Pandey, M. R.

    1992-01-01

    OBJECTIVES--To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme. DESIGN--Opportunistic controlled trial. SETTING--Jumla district, Nepal. SUBJECTS--All children aged under 5 years; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation. MAIN OUTCOME MEASURES--Mortality and cause of death in the five months after supplementation. RESULTS--Risk of death for children aged 1-59 months in supplemented communities was 26% lower (relative risk 0.74, 95% confidence interval 0.55 to 0.99) than in unsupplemented communities. The reduction in mortality was greatest among children aged 6-11 months: death rate (deaths/1000 child years at risk) was 133.8 in supplemented children and 260.8 in unsupplemented children (relative risk 0.51, 0.30 to 0.89). The death rate from diarrhoea was also reduced (63.5 supplemented v 97.5 unsupplemented; relative risk 0.65, 0.44 to 0.95). The extra cost per death averted was about $11. CONCLUSION--The results support a role for Vitamin A in increasing child survival. The supplementation programme was readily integrated with the ongoing community health programme at little extra cost. PMID:1739794

  14. Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

    EPA Science Inventory

    Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

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

    PubMed Central

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

    2012-01-01

    Summary People with spinal cord injury (SCI) lose bone and muscle integrity after their injury. Early doses of stress, applied through electrically induced muscle contractions, preserved bone density at high-risk sites. Appropriately prescribed stress early after the injury may be an important consideration to prevent bone loss after SCI. Introduction Skeletal muscle force can deliver high compressive loads to bones of people with spinal cord injury (SCI). The effective osteogenic dose of load for the distal femur, a chief site of fracture, is unknown. The purpose of this study is to compare three doses of bone compressive loads at the distal femur in individuals with complete SCI who receive a novel stand training intervention. Methods Seven participants performed unilateral quadriceps stimulation in supported stance [150% body weight (BW) compressive load—“High Dose” while opposite leg received 40% BW—“Low Dose”]. Five participants stood passively without applying quadriceps electrical stimulation to either leg (40% BW load—“Low Dose”). Fifteen participants performed no standing (0% BW load—“Untrained”) and 14 individuals without SCI provided normative data. Participants underwent bone mineral density (BMD) assessment between one and six times over a 3-year training protocol. Results BMD for the High Dose group significantly exceeded BMD for both the Low Dose and the Untrained groups (p<0.05). No significant difference existed between the Low Dose and Untrained groups (p>0.05), indicating that BMD for participants performing passive stance did not differ from individuals who performed no standing. High-resolution CT imaging of one High Dose participant revealed 86% higher BMD and 67% higher trabecular width in the High Dose limb. Conclusion Over 3 years of training, 150% BW compressive load in upright stance significantly attenuated BMD decline when compared to passive standing or to no standing. High-resolution CT indicated that

  16. Toxico-kinetics, recovery, and metabolism of napropamide in goats following a single high-dose oral administration.

    PubMed

    Pahari, A K; Majumdar, S; Mandal, T K; Chakraborty, A K; Bhattacharyya, A; Chowdhury, A

    2001-04-01

    Toxicokinetic behavior, recovery and metabolism of napropamide (a pre-emergent herbicide) and its effect on Cytochrome P(450) of liver microsomal pellet were studied following a single high-dose oral administration of 2.5 g kg(-1) and continuous (7 days) oral administration of 500 mg kg(-1) in black Bengal goat. Napropamide was detected in blood at 15 min and the maximum quantity was recovered at 3 h after administration. The absorption rate constant (Ka) value was low indicating poor absorption from the gastrointestinal tract. High elimination half-life (t(1/2) beta) and low body clearance (Cl(B)) values coupled with higher transfer of compound from tissue to central compartment (K(21)) suggest that napropamide persisted in the blood for a long time, i.e., after 72 h of oral administration. The recovery percentage of napropamide, including metabolites, from goats varied from 75.94 to 80.08 and excretion of the parent compound through feces varied from 18.86 to 21.59%, indicating that a major portion of the orally administered napropamide was absorbed from the gastrointestinal tract of goat. Napropamide significantly increased the Cytochrome P(450) content of liver microsomal pellet. The recovery of metabolites from feces, urine, and tissues ranged from 4.2--6.2, 40.81--49.42, and 2.7--11.6%, respectively, during a 4--7 day period. The material balance of napropamide (including metabolites) following a single high-dose oral administration at 2.5 g kg(-1) during 4--7 days after dosing was found to be in the range of 75--80%. PMID:11308331

  17. Sputtering of HOPG under high-dose ion irradiation

    NASA Astrophysics Data System (ADS)

    Borisov, A. M.; Mashkova, E. S.; Nemov, A. S.; Virgiliev, Yu. S.

    2007-03-01

    The dependences of sputtering yield Y of highly oriented pyrolytic graphite under high fluences (1018-1019 ion/cm2) 30 keV N2+ irradiation at ion incidence angles from θ = 0 (normal incidence) to θ = 80° at room temperature (RT) and T = 400 °C have been measured to trace the radiation damage influence on angular behavior of sputtering yield. A difference has been found between angular dependences of sputtering yields at RT, when the irradiation leads to a high degree of disorder, and at temperatures, larger than the temperature Ta responsible for annealing the radiation damage at continuous ion bombardment.

  18. Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

    SciTech Connect

    Zapatero, Almudena; Garcia-Vicente, Feliciano; Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile; Fernandez, Inmaculada; Rabadan, Mariano

    2011-12-01

    Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

  19. Thermoluminescence glow-curve characteristics of LiF phosphors at high doses of gamma radiation

    NASA Astrophysics Data System (ADS)

    Benny, P. G.; Khader, S. A.; Sarma, K. S. S.

    2013-05-01

    High doses of ionising radiation are becoming increasingly common for radiation-processing applications of various medical, agricultural and polymer products using gamma and electron beams. The objective of this work was to study thermoluminescence (TL) glow-curve characteristics of commonly used commercial LiF TL phosphors at high doses of radiation with a view to use them in dosimetry of radiation-processing applications. The TL properties of TLD 100 and 700 phosphors, procured from the Thermo-Scientific (previously Harshaw) company, have been studied in the dose range of 1-60 kGy. The shift in glow peaks was observed in this dose range. Integral TL responses of TLD 100 and TLD 700 were found to decrease as a linear function of dose in the range of 5-50 kGy. The paper describes initial results related to the glow-curve characteristics of these phosphors.

  20. The OVLT initiates the fall in arterial pressure evoked by high dose lipopolysaccharide: Evidence that dichotomous, dose-related mechanisms mediate endotoxic hypotension

    PubMed Central

    Feleder, Carlos; Yilmaz, M. Sertac; Peng, Jianya; Göktalay, Gökhan; Millington, William R.

    2015-01-01

    This study tested the hypothesis that lipopolysaccharide (LPS) lowers arterial pressure through two different mechanisms depending on the dose. Previously, we found that a low hypotensive dose of LPS (1 mg/kg) lowers arterial pressure by activating vagus nerve afferents. Here we report that hypotension evoked by high dose LPS (15 mg/kg) can be prevented by injecting lidocaine into the OVLT but not by vagotomy or inactivation of the NTS. The hypotension produced by both LPS doses was correlated with elevated extracellular norepinephrine concentrations in the POA and prevented by blocking alpha-adrenergic receptors. Thus, initiation of endotoxic hypotension is dose-related, mechanistically. PMID:26198924

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

    PubMed

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

    2012-09-07

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

  2. High-Dose Sirolimus And Immune Selective Pentostatin Plus Cyclophosphamide Conditioning Yields Stable Mixed Chimerism and Insufficient Graft-Versus-Tumor Responses

    PubMed Central

    Mossoba, Miriam E.; Halverson, David C.; Kurlander, Roger; Schuver, Bazetta Blacklock; Carpenter, Ashley; Hansen, Brenna; Steinberg, Seth M.; Ali, Syed Abbas; Tageja, Nishant; Hakim, Frances T.; Gea-Banacloche, Juan; Sportes, Claude; Hardy, Nancy M.; Hickstein, Dennis D.; Pavletic, Steven Z.; Khuu, Hanh; Sabatini, Marianna; Stroncek, David; Levine, Bruce L.; June, Carl H.; Mariotti, Jacopo; Rixe, Olivier; Fojo, Antonio Tito; Bishop, Michael R.; Gress, Ronald. E.; Fowler, Daniel H.

    2015-01-01

    PURPOSE We hypothesized that lymphoid-selective host conditioning and subsequent adoptive transfer of sirolimus-resistant allogeneic T cells (T-Rapa), when combined with high-dose sirolimus drug therapy in vivo, would safely achieve anti-tumor effects while avoiding GVHD. EXPERIMENTAL DESIGN Patients (n=10) with metastatic renal cell carcinoma (RCC) were accrued because this disease is relatively refractory to high-dose conditioning yet may respond to high-dose sirolimus. A 21-day outpatient regimen of weekly pentostatin (P; 4 mg/m2/dose) combined with daily, dose-adjusted cyclophosphamide (C; ≤ 200 mg/day) was designed to deplete and suppress host T cells. After PC conditioning, patients received matched sibling, T cell-replete peripheral blood stem cell allografts and high-dose sirolimus (serum trough target, 20–30 ng/ml). To augment graft-versus-tumor (GVT) effects, multiple T-Rapa donor lymphocyte infusions (DLI) were administered (days 0, 14, and 45 post-transplant) and sirolimus was discontinued early (day 60 post-transplant). RESULTS PC conditioning depleted host T cells without neutropenia or infection and facilitated donor engraftment (10/10 cases). High-dose sirolimus therapy inhibited multiple T-Rapa DLI, as evidenced by stable mixed donor/host chimerism. No anti-tumor responses were detected by RECIST criteria and no significant classical acute GVHD was observed. CONCLUSIONS Immune-selective PC conditioning represents a new approach to safely achieve alloengraftment without neutropenia. However, allogeneic T cells generated ex vivo in sirolimus are not resistant to the tolerance-inducing effects of in vivo sirolimus drug therapy, thereby cautioning against use of this intervention in patients with refractory cancer. PMID:26071480

  3. Effects of high-dose and multiple-dose gonadotropin stimulation on mouse oocyte quality as assessed by preimplantation development following in vitro fertilization.

    PubMed

    Edgar, D H; Whalley, K M; Mills, J A

    1987-10-01

    The effects of increasing the level of ovarian stimulation on preimplantation embryonic development were assessed using a mouse in vitro fertilization system. When F1 hybrid (C57BL/6 X CBA/Ca) mice received a single injection of 5 IU pregnant mare's serum gonadotropin (PMSG) followed 60 hr later by 5 IU human chorionic gonadotropin (hCG) approximately 50% of the resultant postovulatory oocytes developed to the blastocyst stage following in vitro fertilization. Increasing the single dose of PMSG to 10 or 15 IU resulted in significant reductions in the frequency of development to the blastocyst stage. When one or two additional doses of 5 IU PMSG were administered 24 and 48 hr after an initial injection of 5 IU, lower frequencies of oocytes with the potential for full preimplantation development were again observed. This reduction in gamete quality was significantly greater when the final dose of PMSG was administered only 12 hr prior to hCG. The results suggest that excessive gonadotropin stimulation may compromise the quality of the preimplantation embryos obtained following in vitro fertilization and that the timing of gonadotropin administration may also be critical.

  4. An Alternative to the Use of High-Dose Estrogens for Postcoital Contraception.

    ERIC Educational Resources Information Center

    Schilling, Lee H.

    1979-01-01

    Research is reported on the use of ethinyl estradiol and norgestrel for contraception after intercourse. This treatment is offered as an alternative to high doses of estrogen and appears to be successful in preventing unwanted pregnancies. (JMF)

  5. Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment

    PubMed Central

    Oinuma, K; Harada, Y; Nawata, Y; Takabayashi, K; Abe, I; Kamikawa, K; Moriya, H

    2001-01-01

    OBJECTIVES—To investigate the actual time of onset of osteonecrosis (ON) after high dose corticosteroid treatment in systemic lupus erythematosus (SLE).
METHODS—72 patients with active SLE, who received high dose corticosteroid for the first time, for the development of ON at hips and knees were monitored by magnetic resonance imaging for at least 12 months.
RESULTS—ON lesions were detected in 32/72 patients (44%) between one and five months (3.1 months on average) after starting high dose corticosteroid treatment. No osteonecrotic lesion was newly detected from the sixth month of treatment until the end of the follow up period.
CONCLUSION—The findings suggested that the actual time of onset of ON in SLE is within the first month of high dose corticosteroid treatment.

 PMID:11709458

  6. High-Dose Ketamine Sedation of an Agitated Patient During Air Medical Transport.

    PubMed

    Reicher, David

    2016-01-01

    We report a case in which a high-dose ketamine infusion was used to sedate an agitated patient for air medical transport, avoiding the risks of general anesthesia and causing no exacerbation of psychiatric symptoms. PMID:27021674

  7. SU-E-J-93: Parametrisation of Dose to the Mucosa of the Anterior Rectal Wall in Transrectal Ultrasound Guided High-Dose-Rate Brachytherapy of the Prostate

    SciTech Connect

    Aitkenhead, A; Hamlett, L; Wood, D; Choudhury, A

    2014-06-01

    Purpose: In high-dose-rate (HDR) brachytherapy of the prostate, radiation is delivered from a number of radioactive sources which are inserted via catheter into the target volume. The rectal mucosa also receives dose during the treatment, which may lead to late toxicity effects. To allow possible links between rectal dose and toxicity to be investigated, suitable methods of parametrising the rectal dose are needed. Methods: During treatment of a series of 95 patients, anatomy and catheter locations were monitored by transrectal ultrasound, and target volume positions were contoured on the ultrasound scan by the therapist. The anterior rectal mucosal wall was identified by contouring the transrectal ultrasound balloon within the ultrasound scan. Source positions and dwell times, along with the dose delivered to the patient were computed using the Oncentra Prostate treatment planning system (TPS). Data for the series of patients were exported from the TPS in Dicom format, and a series of parametrisation methods were developed in a Matlab environment to assess the rectal dose. Results: Contours of the anterior rectal mucosa were voxelised within Matlab to allow the dose to the rectal mucosa to be analysed directly from the 3D dose grid. Dose parametrisations based on dose-surface (DSH) and dose-line (DLH) histograms were obtained. Both lateral and longitudinal extents of the mucosal dose were parametrised using dose-line histograms in the relevant directions. Conclusion: We have developed a series of dose parametrisations for quantifying the dose to the rectal mucosa during HDR prostate brachytherapy which are suitable for future studies investigating potential associations between mucosal dose and late toxicity effects. The geometry of the transrectal probe standardises the rectal anatomy, making this treatment technique particularly suited to studies of this nature.

  8. Oral high-dose medroxyprogesterone acetate (MPA) treatment: cortisol/MPA serum profiles in relation to breast cancer regression.

    PubMed

    Mahlke, M; Grill, H J; Knapstein, P; Wiegand, U; Pollow, K

    1985-01-01

    Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed.

  9. Neuropsychological and biochemical investigations in heterozygotes for phenylketonuria during ingestion of high dose aspartame (a sweetener containing phenylalanine).

    PubMed

    Trefz, F; de Sonneville, L; Matthis, P; Benninger, C; Lanz-Englert, B; Bickel, H

    1994-04-01

    Aspartame, a high intensity sweetener, is used extensively worldwide in over 5,000 products. Upon ingestion, aspartame is completely metabolized to two amino acids and methanol (approximately 50% phenylalanine, 40% aspartic acid, and 10% methanol). The effects of aspartame on cognitive function, electroencephalograms (EEGs) and biochemical parameters were evaluated in 48 adult (21 men, 27 women) heterozygotes for phenylketonuria (PKUH), PKUH subjects whose carrier status had been proven by DNA analysis ingested aspartame (either 15 or 45 mg/kg/day) and placebo for 12 weeks on each treatment using a randomized, double-blind, placebo-controlled, crossover study. A computerized battery of neuropsychological tests was administered at baseline weeks -2 and -1, and during treatment at weeks 6, 12, 18, and 24. Samples for plasma amino acids and urinary organic acids were also collected during these visits. EEGs were evaluated by conventional and spectral analysis at baseline week -1 and treatment weeks 12 and 24. The results of the neuropsychological tests demonstrated that aspartame had no effect on cognitive function. Plasma phenylalanine significantly increased, within the normal range for PKUH, at 1 and 3 h following the morning dose of aspartame in the group receiving the 45 mg/kg per day dose only. There were no significant differences in the conventional or spectral EEG analyses, urinary organic acid concentrations, and adverse experiences when aspartame was compared with placebo. This study reaffirms the safety of aspartame in PKUH and refutes the speculation that aspartame affects cognitive performance, EEGs, and urinary organic acids.

  10. The immunogenicity and safety of a single 0.5 mL dose of virosomal subunit influenza vaccine administered to unprimed children aged ≥6 to <36 months: data from a randomized, Phase III study.

    PubMed

    Esposito, Susanna; Marchisio, Paola; Montinaro, Valentina; Bianchini, Sonia; Weverling, Gerrit Jan; Pariani, Elena; Amendola, Antonella; Fabiano, Valentina; Pivetti, Valentina; Zanetti, Alessandro; Zuccotti, Gian Vincenzo

    2012-11-19

    This study evaluated the immunogenicity, safety and tolerability of a single 0.5 mL dose of the seasonal virosomal subunit influenza vaccine (Inflexal V, Crucell, Switzerland) in 205 healthy, unprimed children aged at least 6 to <36 months, evaluated at four weeks post-vaccination and seven months from baseline. Of the enrolled children, 102 received one single 0.5 mL dose and 103 received the standard two 0.25 mL doses given four weeks apart. Both treatments evoked an immune response that satisfied the EMA/CHMP criteria for yearly vaccine licensing for all three vaccine strains. Exploratory analyses revealed no differences between the groups at four weeks post-vaccination. Furthermore, immunogenicity was maintained seven months after the first vaccination after both the 0.5 mL and standard two 0.25 mL doses. Adverse events were comparable between groups and were as expected according to the safety profile of the vaccine; overall, the vaccine was well tolerated. Our results show that a single 0.5 mL dose effectively and safely provided long-term immunogenicity to all three influenza strains in unprimed children aged at least 6 to <36 months.

  11. Absolute dose measurements by means of a small cylindrical ionization chamber for very high dose per pulse high energy electron beams

    SciTech Connect

    Karaj, E.; Righi, S.; Di Martino, F.

    2007-03-15

    Very high dose per pulse (3-13 cGy/pulse) high energy electron beams are currently produced by special linear accelerators (linac) dedicated to Intra Operative Radiation Therapy (IORT). The electron beams produced by such linacs are collimated by special Perspex applicators of various size and cylindrically shaped. The biggest problems from the dosimetric point of view are caused by the high dose-per-pulse values and the use of inclined applicators. In this work measurements of absolute dose for the inclined applicators were done by using a small cylindrical ionization chamber, type CC01 (Wellhofer), a parallel plane ionization chamber type Markus (PTW 23343) and radiochromic films type EBT. We show a method which allows calculating the quality correction factors for CC01 chamber with an uncertainty of 1% and the absolute dose value for the inclined applicators using CC01 with an uncertainty of 3.1% for electron beams of energy of 6 and 7 MeV produced by the linac dedicated to IORT Novac7.

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

    PubMed Central

    Pellizzon, Antônio Cássio Assis

    2016-01-01

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

  13. Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis

    SciTech Connect

    Lee, Percy; Eppinga, Wietse; Lagerwaard, Frank; Cloughesy, Timothy; Slotman, Benjamin; Nghiemphu, Phioanh L.; Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John; Selch, Michael T.; Steinberg, Michael; Kang, Jung Julie

    2013-07-15

    Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

  14. Absorption of orally administered amphotericin B lozenges.

    PubMed

    Ching, M S; Raymond, K; Bury, R W; Mashford, M L; Morgan, D J

    1983-07-01

    The systemic absorption of amphotericin B, administered as a 10 mg lozenge, was investigated in 14 patients with malignancies, who received three or four doses daily during chronic administration. The mean plasma amphotericin B concentration, measured 3 h after the morning dose on from 1-20 occasions over a 1-80 day period, ranged among subjects from 46 +/- 13 ng/ml (s.d., n = 20) to 136 +/- 25 ng/ml (n = 19). Using the previously reported intravenous clearance of the drug, the fraction of the dose absorbed was estimated at 8.3-9.9%. This is considerably greater than that estimated from earlier reports (0.2-0.9%), which used much higher oral doses (2-10 g/day). PMID:6882617

  15. The radiation dosimetry of intrathecally administered radionuclides

    SciTech Connect

    Stabin, M.G.; Evans, J.F.

    1999-01-01

    The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energy deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.

  16. Dose Control System in the Optima XE Single Wafer High Energy Ion Implanter

    SciTech Connect

    Satoh, Shu; Yoon, Jongyoon; David, Jonathan

    2011-01-07

    Photoresist outgassing can significantly compromise accurate dosimetry of high energy implants. High energy implant even at a modest beam current produces high beam powers which create significantly worse outgassing than low and medium energy implants and the outgassing continues throughout the implant due to the low dose in typical high energy implant recipes. In the previous generation of high energy implanters, dose correction by monitoring of process chamber pressure during photoresist outgassing has been used. However, as applications diversify and requirements change, the need arises for a more versatile photoresist correction system to match the versatility of a single wafer high energy ion implanter. We have successfully developed a new dosimetry system for the Optima XE single wafer high energy ion implanter which does not require any form of compensation due to the implant conditions. This paper describes the principles and performance of this new dose system.

  17. High doses of cobalt induce optic and auditory neuropathy.

    PubMed

    Apostoli, Pietro; Catalani, Simona; Zaghini, Anna; Mariotti, Andrea; Poliani, Pietro Luigi; Vielmi, Valentina; Semeraro, Francesco; Duse, Sarah; Porzionato, Andrea; Macchi, Veronica; Padovani, Alessandro; Rizzetti, Maria Cristina; De Caro, Raffaele

    2013-09-01

    The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.

  18. Elastic stability of high dose neutron irradiated spinel

    SciTech Connect

    Li, Z.; Chan, S.K.; Garner, F.A.

    1995-04-01

    The objective of this effort is to identify ceramic materials that are suitable for fusion reactor applications. Elastic constants (C{sub 11}, C{sub 12}, and C{sub 44}) of spinel (MgAl{sub 2}O{sub 4}) single crystals irradiated to very high neutron fluences have geen measured by an ultrasonic technique. Although results of a neutron diffraction study show that cation occupation sites are significantly changed in the irradiated samples, no measurable differences occurred in their elastic properties. In order to understand such behavior, the elastic properties of a variety of materials with either normal or inverse spinel structures were studied. The cation valence and cation distribution appear to have little influence on the elastic properties of spinel materials.

  19. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

    PubMed

    Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

    2010-04-19

    This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.

  20. Successful treatment of persistent MRSA bacteremia using high-dose daptomycin combined with rifampicin.

    PubMed

    Hagiya, Hideharu; Terasaka, Tomohiro; Kimura, Kosuke; Satou, Asuka; Asano, Kikuko; Waseda, Koichi; Hanayama, Yoshihisa; Otsuka, Fumio

    2014-01-01

    We herein report a case of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that was successfully treated with combination therapy consisting of high-dose daptomycin (DAP, 10 mg/kg) and rifampicin. The patient's condition was complicated with multiple infectious foci, including an iliopsoas abscess and epidural abscess, as well as discitis and spondylitis at the cervical, thoracic and lumbar levels. Monotherapy treatments with vancomycin, linezolid and usual-dose DAP were all ineffective. It has been shown that usual-dose DAP administration may result in the emergence of a resistant strain and treatment failure. We would like to emphasize the importance of high-dose DAP therapy for MRSA bacteremia, a condition with a potentially high mortality rate. PMID:25224207

  1. High and low dose radiation effects on mammary adenocarcinoma cells – an epigenetic connection

    PubMed Central

    Luzhna, Lidia; Filkowski, Jody; Kovalchuk, Olga

    2016-01-01

    The successful treatment of cancer, including breast cancer, depends largely on radiation therapy and proper diagnostics. The effect of ionizing radiation on cells and tissues depends on the radiation dose and energy level, but there is insufficient evidence concerning how tumor cells respond to the low and high doses of radiation that are often used in medical diagnostic and treatment modalities. The purpose of this study was to investigate radiation-induced gene expression changes in the MCF-7 breast adenocarcinoma cell line. Using microarray technology tools, we were able to screen the differential gene expressions profiles between various radiation doses applied to MCF-7 cells. Here, we report the substantial alteration in the expression level of genes after high-dose treatment. In contrast, no dramatic gene expression alterations were noticed after the application of low and medium doses of radiation. In response to a high radiation dose, MCF-7 cells exhibited down-regulation of biological pathways such as cell cycle, DNA replication, and DNA repair and activation of the p53 pathway. Similar dose-dependent responses were seen on the epigenetic level, which was tested by a microRNA expression analysis. MicroRNA analysis showed dose-dependent radiation-induced microRNA expression alterations that were associated with cell cycle arrest and cell death. An increased rate of apoptosis was determined by an Annexin V assay. The results of this study showed that high doses of radiation affect gene expression genetically and epigenetically, leading to alterations in cell cycle, DNA replication, and apoptosis. PMID:27226982

  2. A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy.

    PubMed

    Rivard, Mark J; Melhus, Christopher S; Zinkin, Heather D; Stapleford, Liza J; Evans, Krista E; Wazer, David E; Odlozilíková, Anna

    2005-09-01

    While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.

  3. Neutron spectra and dose equivalents calculated in tissue for high-energy radiation therapy

    SciTech Connect

    Kry, Stephen F.; Howell, Rebecca M.; Salehpour, Mohammad; Followill, David S.

    2009-04-15

    Neutrons are by-products of high-energy radiation therapy and a source of dose to normal tissues. Thus, the presence of neutrons increases a patient's risk of radiation-induced secondary cancer. Although neutrons have been thoroughly studied in air, little research has been focused on neutrons at depths in the patient where radiosensitive structures may exist, resulting in wide variations in neutron dose equivalents between studies. In this study, we characterized properties of neutrons produced during high-energy radiation therapy as a function of their depth in tissue and for different field sizes and different source-to-surface distances (SSD). We used a previously developed Monte Carlo model of an accelerator operated at 18 MV to calculate the neutron fluences, energy spectra, quality factors, and dose equivalents in air and in tissue at depths ranging from 0.1 to 25 cm. In conjunction with the sharply decreasing dose equivalent with increased depth in tissue, the authors found that the neutron energy spectrum changed drastically as a function of depth in tissue. The neutron fluence decreased gradually as the depth increased, while the average neutron energy decreased sharply with increasing depth until a depth of approximately 7.5 cm in tissue, after which it remained nearly constant. There was minimal variation in the quality factor as a function of depth. At a given depth in tissue, the neutron dose equivalent increased slightly with increasing field size and decreasing SSD; however, the percentage depth-dose equivalent curve remained constant outside the primary photon field. Because the neutron dose equivalent, fluence, and energy spectrum changed substantially with depth in tissue, we concluded that when the neutron dose equivalent is being determined at a depth within a patient, the spectrum and quality factor used should be appropriate for depth rather than for in-air conditions. Alternately, an appropriate percent depth-dose equivalent curve should be

  4. Acute high dose exposure to benzene in shipyard workers

    SciTech Connect

    Midzenski, M.A.; McDiarmid, M.A.; Rothman, N.; Kolodner, K. )

    1992-01-01

    Fifteen degassers were acutely exposed over several days to high concentrations (> 60 ppm) of benzene during removal of residual fuel (degassing) from shipboard fuel tanks. Medical surveillance evaluation mandated by the Occupational Safety and Health Administration's (OSHA) Benzene Standard initially revealed 11 workers (73%) reporting neurotoxic symptoms while degassing. Workers with more than 2 days (16 hours) of acute exposure were significantly more likely to report dizziness and nausea than those with 2 or fewer days of acute exposure. Repeated laboratory analyses performed over a 4-month period after the acute exposure revealed at least one hematologic abnormality consistent with benzene exposure in 9 (60%) of these degassers. One year later, 6 workers (40%) had persistent abnormalities; an additional worker with normal hematologic parameters at the time of our initial evaluation subsequently developed an abnormality consistent with benzene exposure. Numerous large granular lymphocytes were observed on 6 (40%) of the peripheral blood smears. Despite these laboratory findings, there were no significant associations between the presence of hematologic abnormalities and either the number of hours of acute benzene exposure or the duration of employment as a degasser. Volatilization of benzene from the residual fuel was the suspected source of benzene in the headspace of tanks. Confined space exposure to petroleum products may be exposing workers to benzene at levels above the OSHA Short-Term Exposure Limit (STEL). This situation warrants further study.

  5. X-ray storage performance of KCl:Eu2+ with high cumulated dose

    NASA Astrophysics Data System (ADS)

    Hansel, Rachael A.; Xiao, Zhiyan; Zhang, Lei; Li, H. Harold

    2014-05-01

    The effects of high cumulative radiation dose on the luminescence properties of KCl:Eu2+ are investigated. Pellet samples of KCl:Eu2+ were given doses of up to 200 kGy at the Louisiana State University Synchrotron facility. After synchrotron irradiation, samples were optically bleached and given a clinical dose of 2 Gy from a 6 MV medical linear accelerator. Optical properties were evaluated using photostimulated luminescence (PSL), photoluminescence (PL), and temperature-dependent PSL measurements. For a cumulated dose of up to 5-10 kGy, the PSL emission intensity increased by 15% compared to the PSL signal with no radiation history. For doses higher than 10 kGy, the PSL emission intensity retained at least 70% of the original intensity. Spatial correlation of the charge storage centers increased for doses up to 5 kGy and then decreased for higher cumulative doses. Emission band at 975 nm was attributed to transitions of Eu1+. PL spectra showed an intense peak centered at 420 nm for all cumulative doses. The results of this work show that KCl:Eu2+ storage phosphors are excellent reusable materials for radiation therapy dosimetry.

  6. PLUTONIUM/HIGH-LEVEL VITRIFIED WASTE BDBE DOSE CALCULATION

    SciTech Connect

    D.C. Richardson

    2003-03-19

    In accordance with the Nuclear Waste Policy Amendments Act of 1987, Yucca Mountain was designated as the site to be investigated as a potential repository for the disposal of high-level radioactive waste. The Yucca Mountain site is an undeveloped area located on the southwestern edge of the Nevada Test Site (NTS), about 100 miles northwest of Las Vegas. The site currently lacks rail service or an existing right-of-way. If the Yucca Mountain site is found suitable for the repository, rail service is desirable to the Office of Civilian Waste Management (OCRWM) Program because of the potential of rail transportation to reduce costs and to reduce the number of shipments relative to highway transportation. A Preliminary Rail Access Study evaluated 13 potential rail spur options. Alternative routes within the major options were also developed. Each of these options was then evaluated for potential land use conflicts and access to regional rail carriers. Three potential routes having few land use conflicts and having access to regional carriers were recommended for further investigation. Figure 1-1 shows these three routes. The Jean route is estimated to be about 120 miles long, the Carlin route to be about 365 miles long, and Caliente route to be about 365 miles long. The remaining ten routes continue to be monitored and should any of the present conflicts change, a re-evaluation of that route will be made. Complete details of the evaluation of the 13 routes can be found in the previous study. The DOE has not identified any preferred route and recognizes that the transportation issues need a full and open treatment under the National Environmental Policy Act. The issue of transportation will be included in public hearings to support development of the Environmental Impact Statement (EIS) proceedings for either the Monitored Retrievable Storage Facility or the Yucca Mountain Project or both.

  7. Multicentre randomised trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial).

    PubMed Central

    Halliday, H L; Tarnow-Mordi, W O; Corcoran, J D; Patterson, C C

    1993-01-01

    A randomised trial was conducted in 82 centres using the porcine surfactant extract, Curosurf, to compare two regimens of multiple doses to treat infants with respiratory distress syndrome and arterial to alveolar oxygen tension ratio < 0.22. Infants were randomly allocated to a low dosage group (100 mg/kg initially, with two further doses at 12 and 24 hours to a maximum cumulative total of 300 mg/kg; n = 1069) or a high dosage group (200 mg/kg initially with up to four further doses of 100 mg/kg to a maximum cumulative total of 600 mg/kg; n = 1099). There was no difference between those allocated low and high dosage in the rates of death or oxygen dependency at 28 days (51.1% v 50.8%; difference -0.3%, 95% confidence interval (CI) -4.6% to 3.9%), death before discharge (25.0% v 23.5%; difference -1.5%, 95% CI -5.1% to 2.2%), and death or oxygen dependency at the expected date of delivery (32.2% v 31.0%; difference -1.2%, 95% CI -5.2% to 2.7%). For 14 predefined secondary measures of clinical outcome there were no significant differences between the groups but the comparison of duration of supplemental oxygen > 40% did attain significance; 48.4% of babies in the low dose group needed > 40% oxygen after three days compared with 42.6% of those in the high dose group. The total amount of surfactant administered in the low dose regimen (mean 242 mg phospholipid/kg) was probably enough to replace the entire pulmonary surfactant pool. Adopting the low dose regimen would lead to considerable cost savings, with no clinically significant loss in efficacy. PMID:8215564

  8. 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

    PubMed Central

    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

  9. Gene interaction network analysis suggests differences between high and low doses of acetaminophen

    SciTech Connect

    Toyoshiba, Hiroyoshi . E-mail: toyoshiba.hiroyoshi@nies.go.jp; Sone, Hideko; Yamanaka, Takeharu; Parham, Frederick M.; Irwin, Richard D.; Boorman, Gary A.; Portier, Christopher J.

    2006-09-15

    Bayesian networks for quantifying linkages between genes were applied to detect differences in gene expression interaction networks between multiple doses of acetaminophen at multiple time points. Seventeen (17) genes were selected from the gene expression profiles from livers of rats orally exposed to 50, 150 and 1500 mg/kg acetaminophen (APAP) at 6, 24 and 48 h after exposure using a variety of statistical and bioinformatics approaches. The selected genes are related to three biological categories: apoptosis, oxidative stress and other. Gene interaction networks between all 17 genes were identified for the nine dose-time observation points by the TAO-Gen algorithm. Using k-means clustering analysis, the estimated nine networks could be clustered into two consensus networks, the first consisting of the low and middle dose groups, and the second consisting of the high dose. The analysis suggests that the networks could be segregated by doses and were consistent in structure over time of observation within grouped doses. The consensus networks were quantified to calculate the probability distribution for the strength of the linkage between genes connected in the networks. The quantifying analysis showed that, at lower doses, the genes related to the oxidative stress signaling pathway did not interact with the apoptosis-related genes. In contrast, the high-dose network demonstrated significant interactions between the oxidative stress genes and the apoptosis genes and also demonstrated a different network between genes in the oxidative stress pathway. The approaches shown here could provide predictive information to understand high- versus low-dose mechanisms of toxicity.

  10. High-dose chemotherapy: is it standard management for any common solid tumor?

    PubMed

    MacNeil, M; Eisenhauer, E A

    1999-10-01

    High-dose chemotherapy with stem-cell support had as its basis the observation of dose-response relationships for many chemotherapeutic agents in laboratory models. The rationale to explore high-dose treatment in the clinic was further enhanced by several retrospective reviews in the 1980s which suggested delivered dose intensity of treatment was an important determinant of patient outcome. The availability of hematopoietic growth factors and technologic advances in the efficiency of stem-cell collection and administration have made the evaluation of exploring high-dose therapy safe and feasible. However, real questions remain regarding the apparently superior results of this treatment in the management of solid tumors. This paper reviews the results of high-dose chemotherapy in breast, ovarian and small cell lung cancers. Firstly the evidence for a dose-response relationship to chemotherapeutic agents in the 'standard' dosage range is examined. Secondly results of non-randomized and, where available, randomized trials of high-dose chemotherapy (HDCT) with stem-cell support are summarized and finally conclusions regarding the weight of the evidence for use of HDCT as 'standard' treatment are given. In none of these tumors is there sufficient evidence from randomized trials to consider HDCT a standard to be offered to all patients with a given stage of disease. The apparent benefit of HDCT seen in phase II trials could well be explained by such phenomena as stage shifts and patient selection. Many randomized trials in ovary and breast cancer are either ongoing or presented only as abstracts so final results must be awaited to quantify the benefit, if any of HDCT. It is acknowledged, however, that some practitioners already utilize this treatment. We speculate about the differences in philosophical approaches to cancer treatment which might contribute to early acceptance of novel therapies in the absence of adequate randomized data.

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

    PubMed

    Teixeira, Maria Inês; Melo, Adeilson P; Ferraz, Gilberto M; Caldas, Linda V E

    2010-01-01

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

  12. A high-dose dosimeter-based polyvinyl chloride dyed with malachite green

    NASA Astrophysics Data System (ADS)

    Kattan, M.; Daher, Y.; Alkassiri, H.

    2007-07-01

    Polyvinyl chloride (PVC) film dyed with malachite green was studied for high-dose radiation dosimetry using visible spectrophotometry. A linear relationship between the relative absorbance and the absorbed dose at the wavelength 628 nm in the range of 0-125 kGy was found. The effect of dose rate, irradiation temperature, film thickness and dye intensity were found not to influence the response. The effects of shelf life and the post-irradiation storage in darkness and indirect daylight conditions on dosimetry performance were discussed.

  13. Electron paramagnetic resonance radiation dose assessment in fingernails of the victim exposed to high dose as result of an accident.

    PubMed

    Romanyukha, Alexander; Trompier, François; Reyes, Ricardo A; Christensen, Doran M; Iddins, Carol J; Sugarman, Stephen L

    2014-11-01

    In this paper, we report results of radiation dose measurements in fingernails of a worker who sustained a radiation injury to his right thumb while using 130 kVp X-ray for nondestructive testing. Clinically estimated absorbed dose was about 20-25 Gy. Electron paramagnetic resonance (EPR) dose assessment was independently carried out by two laboratories, the Naval Dosimetry Center (NDC) and French Institut de Radioprotection et de Sûreté Nucléaire (IRSN). The laboratories used different equipments and protocols to estimate doses in the same fingernail samples. NDC used an X-band transportable EPR spectrometer, e-scan produced by Bruker BioSpin, and a universal dose calibration curve. In contrast, IRSN used a more sensitive Q-band stationary spectrometer (EMXplus) with a new approach for the dose assessment (dose saturation method), derived by additional dose irradiation to known doses. The protocol used by NDC is significantly faster than that used by IRSN, nondestructive, and could be done in field conditions, but it is probably less accurate and requires more sample for the measurements. The IRSN protocol, on the other hand, potentially is more accurate and requires very small amount of sample but requires more time and labor. In both EPR laboratories, the intense radiation-induced signal was measured in the accidentally irradiated fingernails and the resulting dose assessments were different. The dose on the fingernails from the right thumb was estimated as 14 ± 3 Gy at NDC and as 19 ± 6 Gy at IRSN. Both EPR dose assessments are given in terms of tissue kerma. This paper discusses the experience gained by using EPR for dose assessment in fingernails with a stationary spectrometer versus a portable one, the reasons for the observed discrepancies in dose, and potential advantages and disadvantages of each approach for EPR measurements in fingernails.

  14. High-dose therapy with auto-SCT is feasible in high-risk cardiac amyloidosis.

    PubMed

    Kongtim, P; Qazilbash, M H; Shah, J J; Hamdi, A; Shah, N; Bashir, Q; Wang, M; Champlin, R; Manasanch, E E; Weber, D; Orlowski, R Z; Parmar, S

    2015-05-01

    Cardiac involvement in light-chain amyloidosis (AL) predicts poor prognosis and is associated with higher TRM and morbidity during high-dose therapy and auto-SCT (HDT-ASCT). We studied the outcomes of 30 patients with cardiac amyloidosis undergoing HDT-ASCT at our center between January 1998 and March 2012. The median age of the patients was 53 years (range, 36-74) with a median follow-up of 35 months (range, 0.4-97 months). Twenty-seven patients (90%) had more than one organ involved besides the heart with 37% with cardiac stage ⩾3. Melphalan-based conditioning regimen (140-200 mg/m(2)) was used for HDT-ASCT. One-year TRM is 10%. Three-year OS and EFS from HDT-ASCT was 83% and 56.8%, respectively. Cumulative incidence of relapse at 3 years was 38.5%. Negative factors affecting survival included age >60 years, lack of novel induction therapy and BM plasmacytosis >10%. We conclude that HDT-ASCT is well tolerated in patients with high-risk cardiac amyloidosis and can lead to improved overall outcomes.

  15. Determination of Appropriate Weight-Based Cutoffs for Empiric Cefazolin Dosing Using Data from a Phase 1 Pharmacokinetics and Safety Study of Cefazolin Administered for Surgical Prophylaxis in Pediatric Patients Aged 10 to 12 Years

    PubMed Central

    Schmitz, Michael L.; Blumer, Jeffrey L.; Cetnarowski, Wes

    2015-01-01

    Despite over 40 years of worldwide usage, relatively few data have been published on the pharmacokinetics of cefazolin in pediatric surgical patients. The primary objectives of this study were to examine the pharmacokinetics and safety of cefazolin in children 10 to 12 years of age (inclusive) receiving 1 or 2 g of cefazolin, based on body weight. This multiple-center, open-label study enrolled pediatric patients electively scheduled for surgical procedures who required cefazolin as part of their routine clinical management. Patients weighing ≥25 to <50 kg received a 1-g dose, and patients weighing ≥50 to ≤85 kg received a 2-g dose. Postdose pharmacokinetic and safety assessments were conducted following drug administration. Cefazolin concentration-time data were analyzed by using both noncompartmental and population pharmacokinetics methods. Monte Carlo simulations were performed to identify appropriate weight-based cutoffs for the dosing of children aged 10 to 17 years of age. Twelve patients were enrolled in this study and provided the requisite pharmacokinetic data. In general, cefazolin was well tolerated. The mean cefazolin terminal elimination half-life, clearance, and area under the concentration-time curve from time zero to infinity in this population were 1.95 h, 0.804 ml/min/kg, and 607 mg · h/liter, respectively. Patients weighing 50 to 60 kg exhibited elevated cefazolin exposures. Observed pharmacokinetic parameters and simulation results indicated that a weight-based cutoff of 60 kg is predicted to provide cefazolin exposure consistent with that observed in normal, healthy adults at recommended doses for surgical prophylaxis. (This study has been registered at ClinicalTrials.gov under registration no. NCT01904357.) PMID:25941220

  16. The susceptibility of TaOx-based memristors to high dose rate ionizing radiation and total ionizing dose

    SciTech Connect

    McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; Mickel, Patrick R.; Hanson, Donald J.; McDonald, Joseph K.; Hughart, David Russell; Marinella, Matthew J.

    2014-11-11

    This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaOx) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×107 rad(Si)/s to 4.7 ×108 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×108 rad(Si)/s. This is the first dose rate study on any type of memristive memory technology. In addition to assessing the tolerance of TaOx memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.

  17. Assessment of simulated high-dose partial-body irradiation by PCC-R assay

    PubMed Central

    Romero, Ivonne; García, Omar; Lamadrid, Ana I.; Gregoire, Eric; González, Jorge E.; Morales, Wilfredo; Martin, Cécile; Barquinero, Joan-Francesc; Voisin, Philippe

    2013-01-01

    The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0–20 Gy, with 60Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10–90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth's u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D0 value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10–20 Gy, and the initial fraction of irradiated cells in the interval from 10–90%. PMID:23596200

  18. Assessment of simulated high-dose partial-body irradiation by PCC-R assay.

    PubMed

    Romero, Ivonne; García, Omar; Lamadrid, Ana I; Gregoire, Eric; González, Jorge E; Morales, Wilfredo; Martin, Cécile; Barquinero, Joan-Francesc; Voisin, Philippe

    2013-09-01

    The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0-20 Gy, with ⁶⁰Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10-90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth's u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D₀ value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10-20 Gy, and the initial fraction of irradiated cells in the interval from 10-90%.

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

    PubMed Central

    Day, Troy; Read, Andrew F.

    2016-01-01

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

  20. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  1. Safety of recombinant activated factor VII (rFVIIa) in patients with congenital haemophilia with inhibitors: overall rFVIIa exposure and intervals following high (>240 μg kg⁻¹) rFVIIa doses across clinical trials and registries.

    PubMed

    Shapiro, A D; Neufeld, E J; Blanchette, V; Salaj, P; Gut, R Z; Cooper, D L

    2014-01-01

    Recombinant activated factor VII (rFVIIa) is indicated for treatment of bleeding in congenital haemophilia with inhibitors (CHwI) using 90 μg kg(-1) every 2-3 h (EU and US) or a single 270 μg kg(-1) dose (EU only) with ~90% efficacy reported for both regimens. Dosing of rFVIIa varies, and home treatment makes assessment of frequency of doses >90 μg kg(-1), the intervals before additional treatment, and the risk for thromboembolic events (TEs) more difficult. This post hoc analysis assessed the safety and distribution of rFVIIa dosing in CHwI and the impact of >240 μg kg(-1) dosing on subsequent bypassing agent (BPA) dosing interval and frequency. Data regarding on-demand or prophylactic rFVIIa dosing, TE incidence and subsequent BPA dosing after high rFVIIa doses were compiled from multiple sources incorporating safety surveillance. A total of 61 734 rFVIIa doses were reported in 481 patients treated for 3947 bleeds and for 43 135 prophylaxis days. Over half (52%) exceeded 120 μg kg(-1), 37% exceeded 160 μg kg(-1) and 15% exceeded 240 μg kg(-1). Subsequent doses of BPA(s) were administered after 38% of initial and 49% of any rFVIIa dose >240 μg kg(-1), and were most frequently administered ≥24 h after initial (40%) or any (53%) doses >240 μg kg(-1). No TEs were reported. The findings of this analysis show that rFVIIa doses >90 μg kg(-1) are utilized for 'real-world' treatment of children and adults. When additional BPA was administered following an rFVIIa dose >240 μg kg(-1), reported intervals were prolonged, often ≥24 h. No safety issues were identified in the 61,734 doses analysed.

  2. Application of TL dosemeters for dose distribution measurements at high temperatures in nuclear reactors.

    PubMed

    Osvay, M; Deme, S

    2006-01-01

    Al2O3:Mg,Y ceramic thermoluminescence dosemeters were developed at the Institute of Isotopes for high dose applications at room temperatures. The glow curve of Al2O3:Mg,Y exhibits two peaks--one at 250 degrees C (I) and another peak at approximately 400 degrees C (II). In order to extend the application of these dosemeters to high temperatures, the effect of irradiation temperature was investigated using temperature controlled heating system during high dose irradiation at various temperatures (20-100 degrees C). The new calibration and measuring method has been successfully applied for dose mapping within the hermetic zone of the Paks Nuclear Power Plant even at high temperature parts of blocks.

  3. High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

    SciTech Connect

    Zhang, Qibin; Matzke, Melissa M.; Schepmoes, Athena A.; Moore, Ronald J.; Webb-Robertson, Bobbie-Jo M.; Hu, Zeping; Monroe, Matthew E.; Qian, Weijun; Smith, Richard D.; Morgan, William F.

    2014-03-18

    It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome – the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

  4. Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

    PubMed Central

    Jackson, James; McCollum, Betsy; Ognibene, Judy; Diaz, Francisco J.; de Leon, Jose

    2015-01-01

    Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published. Case 1 received VPA for seizures and schizophrenia and had >50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t = −9.6; df = 6.3, p < 0.001) during the VPA concentrate therapy, possibly due to autoinduction in that formulation. Case 2 had VPA for schizoaffective psychosis with 10 VPA concentrations during an 8-week admission. To maintain a VPA level ≥50 μg/mL, VPA doses increased from 1500 to 4000 mg/day. Case 3 had tuberous sclerosis and epilepsy and was followed up for >4 years with 137 VPA concentrations. To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p < 0.001) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time. PMID:26000191

  5. Monitor units are not predictive of neutron dose for high-energy IMRT

    PubMed Central

    2012-01-01

    Background Due to the substantial increase in beam-on time of high energy intensity-modulated radiotherapy (>10 MV) techniques to deliver the same target dose compared to conventional treatment techniques, an increased dose of scatter radiation, including neutrons, is delivered to the patient. As a consequence, an increase in second malignancies may be expected in the future with the application of intensity-modulated radiotherapy. It is commonly assumed that the neutron dose equivalent scales with the number of monitor units. Methods Measurements of neutron dose equivalent were performed for an open and an intensity-modulated field at four positions: inside and outside of the treatment field at 0.2 cm and 15 cm depth, respectively. Results It was shown that the neutron dose equivalent, which a patient receives during an intensity-modulated radiotherapy treatment, does not scale with the ratio of applied monitor units relative to an open field irradiation. Outside the treatment volume at larger depth 35% less neutron dose equivalent is delivered than expected. Conclusions The predicted increase of second cancer induction rates from intensity-modulated treatment techniques can be overestimated when the neutron dose is simply scaled with monitor units. PMID:22883384

  6. Dose Contribution from High Level Waste Uranium and Plutonium. Revision 1

    SciTech Connect

    Chandler, M.C.; Gray, P.L.; d`Entremont, P.D.; Marra, J.E.; Monahon, T.M.

    1994-10-07

    Radiological source terms for safety analyses traditionally have been curie lists of radionuclides. Converting the source term to dose values allows each radionuclide to be evaluated for its impact on dose, which is the purpose of the source term. This report is one in a series of reports establishing source terms for High Level Waste (HLW) by evaluating the dose impact of each radionuclide. These reports will be used in establishing the source terms to be used in HLW Safety Analysis Reports. The purpose of this report is to document the bounding element dose impact of uranium and plutonium in HLW. This technique (use of dose rather than curies) demonstrates vividly the relative importance of these nuclides in accident analyses. A large amount of available data permitted dose values to be established for uranium and plutonium; therefore, these two elements were evaluated independent of other nuclides. Solubility and adsorption data, available for these elements, allow bounding conditions to be established for their contribution to dose for various HLW processes.

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

    PubMed Central

    2012-01-01

    Background The growing use of imaging procedures in medicine has raised concerns about exposure to low-dose ionising radiation (LDIR). While the disastrous effects of high dose ionising radiation (HDIR) is well documented, the detrimental effects of LDIR is not well understood and has been a topic of much debate. Since little is known about the effects of LDIR, various kinds of wet-lab and computational analyses are required to advance knowledge in this domain. In this paper we carry out an “upside-down pyramid” form of systems biology analysis of microarray data. We characterised the global genomic response following 10 cGy (low dose) and 100 cGy (high dose) doses of X-ray ionising radiation at four time points by analysing the topology of gene coexpression networks. This study includes a rich experimental design and state-of-the-art computational systems biology methods of analysis to study the differences in the transcriptional response of skin cells exposed to low and high doses of radiation. Results Using this method we found important genes that have been linked to immune response, cell survival and apoptosis. Furthermore, we also were able to identify genes such as BRCA1, ABCA1, TNFRSF1B, MLLT11 that have been associated with various types of cancers. We were also able to detect many genes known to be associated with various medical conditions. Conclusions Our method of applying network topological differences can aid in identifying the differences among similar (eg: radiation effect) yet very different biological conditions (eg: different dose and time) to generate testable hypotheses. This is the first study where a network level analysis was performed across two different radiation doses at various time points, thereby illustrating changes in the cellular response over time. PMID:22594378

  8. Comparison of Two High-Dose Magnesium Infusion Regimens in the Treatment of Status Asthmaticus

    PubMed Central

    Vaiyani, Danish

    2016-01-01

    OBJECTIVES: To determine the feasibility and safety of a simplified high-dose magnesium sulfate infusion (sHDMI) for the treatment of status asthmaticus. METHODS: We retrospectively compared 2 different high-dose magnesium sulfate infusion regimens, as adjunctive treatment in status asthmatics, using data that were preciously collected. The initial high-dose, prolonged magnesium infusion (HDMI) regimen consisted of a loading dose of 75 mg/kg (weight ≤ 30 kg) or 50 mg/kg (weight > 30 kg) over a period of 30 to 45 minutes followed by a continuous infusion of 40 mg/kg/hr for an additional 4 hours. This was compared to the sHDMI regimen that consisted of 50 mg/kg/hr for 5 hours. No loading dose was given to the patients in the sHDMI arm. Obese patients were dosed by using ideal body weight. Physiologic parameters (i.e., heart rate, blood pressure, respiratory rate, oxygen saturation) and serum magnesium (SrMg) concentrations were monitored during administration of magnesium sulfate. RESULTS: Nineteen patients receiving the initial HDMI regimen were compared with 10 patients who received the sHDMI regimen. There was no significant difference in SrMg concentrations or physiologic parameters between the 2 dose regimens. CONCLUSIONS: The HDMI and sHDMI regimens both produced SrMg concentrations that are associated with bronchodilation. The safety profile was also similar for the 2 regimens. The unambiguity of sHDMI has the potential to reduce medication errors that are associated with calculation of the loading dose, product preparation, and ultimate administration. PMID:27453701

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

    PubMed

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

    2014-05-01

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

  10. Stage I and II Stress Incontinence (SIC): High dosed vitamin D may improve effects of local estriol

    PubMed Central

    Schulte-Uebbing, Claus; Schlett, Siegfried; Craiut, Doru; Bumbu, Gheorghe

    2016-01-01

    Abstract After the age of 55 almost every third woman suffers from conditions of the incapability to retain urine when the intra-abdominal pressure is raised by different causes. So called stress incontinence. It’ s caused by a predisposition in the family, weakness of the tissue, physical strain, deficiency in the metabolism, especially an increasing local estrogen deficiency and a local and systemic vitamin D deficiency. Patients: We evaluated the data of 60 meno- and postmenopausal female patients with a stress incontinence (SIC). All had a SIC in spite of a former local estriol treatment with a treatment of OeKolp® forte (= 0.5 mg estriol/ov), 3 times a week, for 6 weeks and in spite of a regular pelvic floor exercise for 6 weeks in the morning and in the evening, according to the protocol. Thirty were in stage I SIC and 30 were in stage II SIC. Method: We evaluated vitamin-D-levels in serum of our 60 postmenopausal women. Only 20% of this group had good vitamin D-levels. The medical intervention combined estriol (0.5 mg) together with high dosed vitamin D (12.500 I.U.) locally 3 times a week for a period of 6 weeks. The patients also had the instruction to continue their daily exercises in pelvic floor (morning and evening, due to their protocol). After six weeks of treatment the vitamin D level in serum was defined and correlated to the patients condition (symptomatic of stress incontinence, protocol of micturitions, Pad-test). Results: About one-third of women from our test assigned to be now capable of retaining urine. More than one-third of our patients cleared a profit of treatment. They reported mimimum regression about 25% of volume of incontinence. Therefore more than 2-third of our women being incapable of retaining urine improved their body conditions by using a combination of locally administered etriol and high dosed vitamin D. Conclusion: Stress incontinence (being incapable of retaining urine when the intra-abdominal pressure arises

  11. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications.

    PubMed

    Shwetha, Bondel; Ravikumar, Manickam; Supe, Sanjay S; Sathiyan, Saminathan; Lokesh, Vishwanath; Keshava, Subbarao L

    2012-01-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  12. Bladder–Rectum Spacer Balloon in High-Dose-Rate Brachytherapy in Cervix Carcinoma

    SciTech Connect

    Rai, Bhavana; Patel, Firuza D.; Chakraborty, Santam; Sharma, Suresh C.; Kapoor, Rakesh; Aprem, Abi Santhosh

    2013-04-01

    Purpose: To compare bladder and rectum doses with the use of a bladder–rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. Methods and Materials: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm{sup 3}, 1-cm{sup 3}, 2-cm{sup 3}, 5-cm{sup 3}, and 10-cm{sup 3} volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. Results: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, 5 cm{sup 3}, and 10 cm{sup 3} and ICRU bladder point. Statistically significant dose reductions to 0.1-cm{sup 3}, 1-cm{sup 3}, and 2-cm{sup 3} volumes for rectum were observed with the BRSB. No significant differences in 5-cm{sup 3} and 10-cm{sup 3} volumes and ICRU rectum point were observed. Conclusion: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of

  13. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

    PubMed Central

    Sweetenham, J. W.; McKendrick, J. J.; Jones, D. H.; Whitehouse, J. M.; Williams, C. J.

    1990-01-01

    Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered. PMID:2155645

  14. A Monte Carlo Study for Photoneutron Dose Estimations around the High-Energy Linacs

    PubMed Central

    Mohammadi, N; Miri-Hakimabad, S H; Rafat-Motavalli, L

    2014-01-01

    Background: High-energy linear accelerator (linac) is a valuable tool and the most commonly used device for external beam radiation treatments in cancer patients. In the linac head, high-energy photons with energies above the threshold of (γ,n) interaction produce photoneutrons. These photoneutrons deliver the extra dose to the patients undergoing radiation treatment and increase the risk of secondary cancer. Objective: In this study, a simplified model of the linac head was simulated and photoneutron dose equivalent was calculated at the isocenter and maze in the sphere detector. In addition, the absorbed and equivalent dose of photoneutron were estimated in the some organs of the phantom. Methods: The simulations were made using the Monte Carlo code. The ICRP reference adult male voxel phantom was used as the human body model for dosimetry calculations. Results: The results of dose calculations at the isocenter and maze showed that photoneutron dose decreases as the function of distance from the isocenter and increases with increasing the distance from the entrance maze. Conclusion: It is concluded that the simplified model of linac head is a useful and reliable method in dosimetry calculations. Calculations illustrated that the photoneutron dose is not negligible and duo to its harmful biological effects on body, it should be considered in the treatment plans. PMID:25599059

  15. Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis

    PubMed Central

    2012-01-01

    Background Many studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs. Methods Subjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27). Results An initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group). Conclusion Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis. PMID:22455511

  16. Losartan/hydrochlorothiazide combination therapy surpasses high-dose angiotensin receptor blocker in the reduction of morning home blood pressure in patients with morning hypertension.

    PubMed

    Hanayama, Yoshihisa; Uchida, Haruhito Adam; Nakamura, Yoshio; Makino, Hirofumi

    2012-01-01

    Angiotensin receptor blockers (ARBs) are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP) in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs). Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n = 26) or high-dose ARB (n = 22) in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p < 0.05, respectively). The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively). However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure. PMID:23254579

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

    PubMed

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

    2006-12-21

    The correction for charge recombination was determined for different plane-parallel ionization chambers exposed to clinical electron beams with low and high dose per pulse, respectively. The electron energy was nearly the same (about 7 and 9 MeV) for any of the beams used. Boag's two-voltage analysis (TVA) was used to determine the correction for ion losses, k(s), relevant to each chamber considered. The presence of free electrons in the air of the chamber cavity was accounted for in determining k(s) by TVA. The determination of k(s) was made on the basis of the models for ion recombination proposed in past years by Boag, Hochhäuser and Balk to account for the presence of free electrons. The absorbed dose measurements in both low-dose-per-pulse (less than 0.3 mGy per pulse) and high-dose-per-pulse (20-120 mGy per pulse range) electron beams were compared with ferrous sulphate chemical dosimetry, a method independent of the dose per pulse. The results of the comparison support the conclusion that one of the models is more adequate to correct for ion recombination, even in high-dose-per-pulse conditions, provided that the fraction of free electrons is properly assessed. In this respect the drift velocity and the time constant for attachment of electrons in the air of the chamber cavity are rather critical parameters because of their dependence on chamber dimensions and operational conditions. Finally, a determination of the factor k(s) was also made by zero extrapolation of the 1/Q versus 1/V saturation curves, leading to the conclusion that this method does not provide consistent results in high-dose-per-pulse beams. PMID:17148826

  18. Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally disintegrating tablet administered with or without water in healthy subjects: an open-label, randomized, single-dose, 3-period crossover study.

    PubMed

    Swan, Suzanne K; Alcorn, Harry; Rodgers, Anthony; Hustad, Carolyn M; Ramsey, Karen E; Woll, Susan; Skobieranda, Franck

    2006-02-01

    This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg rizatriptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P < .001). ODTc had a slightly, but not statistically significantly, greater geometric mean AUC(0-1h) compared with rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting. PMID:16432269

  19. High doses of aspartame have no effects on sensorimotor function or learning and memory in rats.

    PubMed

    Tilson, H A; Hong, J S; Sobotka, T J

    1991-01-01

    Acute or repeated (14 days) intragastric administration of L-d-aspartyl-L-phenylalanine methyl ester (aspartame) suspended in saline and Tween-80 in doses of up to 1,000 mg/kg had no significant effect in male Fischer-344 rats on routine measures of sensorimotor function, including spontaneous motor activity, acoustic startle reflex and prepulse inhibition. Other experiments found that aspartame (500 or 1,000 mg/kg) had no significant effect on acquisition of passive or active avoidance or a spatial, reference memory task in the Morris water maze. A series of separate studies found that aspartame had no effects in rats fasted 24 hours prior to testing, or if it was suspended in carboxymethylcellulose or administered by the intraperitoneal route. Under the conditions of these experiments, large doses of aspartame have no significant neurobiological effects in adult rats as measured by procedures known to be sensitive to the neurobiological effects of neurotoxicants, including convulsants, organochlorine insecticides and heavy metals.

  20. Short-term, high-dose administration of corticosterone by injection facilitates trace eyeblink conditioning in young male rats.

    PubMed

    Wentworth-Eidsaune, Christine L; Hennessy, Michael B; Claflin, Dragana I

    2016-02-01

    Glucocorticoids released as part of the physiological response to stress are known to affect cognitive function, presumably via effects on the hippocampus. Trace classical eyeblink conditioning is an associative learning task which depends on the hippocampus and has been used to examine the development of learning processes in young mammals. Previously, we demonstrated deficits in trace eyeblink conditioning associated with postnatal administration of the glucocorticoid corticosterone by creating a sustained elevation with methods such as subcutaneous timed-release pellets and osmotic mini-pumps which were active over several days. In the present study, we examined the effects of an oscillating pattern of corticosterone elevation on subsequent trace eyeblink conditioning. Twice daily corticosterone injections (high, low, or vehicle) were administered over a 3-day period, starting at postnatal day 15. Then, on postnatal day 28, animals underwent trace classical eyeblink conditioning to examine the possible influence of earlier corticosterone elevations on the development of learning and memory. Eyeblink conditioning was affected by corticosterone treatments, but only for males, and only very early in acquisition; Males receiving the high dose of corticosterone exhibited facilitation of learning relative to controls. These data demonstrate that oscillating corticosterone elevations produce opposite effects on this associative learning task than do sustained elevations.

  1. Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin.

    PubMed

    Li, Xian-Wei; Liu, Yan; Hao, Wei; Yang, Jie-Ren

    2014-05-01

    Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)(-1)·d(-1)) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22(phox), p47(phox), NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22(phox), p47(phox), NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

  2. High-dose glucocorticoid aggravates TBI-associated corticosteroid insufficiency by inducing hypothalamic neuronal apoptosis.

    PubMed

    Zhu, Hui; Zhao, Zilong; Zhou, Yuan; Chen, Xin; Li, Ying; Liu, Xiao; Lu, Hujie; Zhang, Yanjun; Zhang, Jianning

    2013-12-01

    Emerging experimental and clinical data suggest that severe illness, such as traumatic brain injury (TBI), can induce critical illness-related corticosteroid insufficiency (CIRCI). However, underlying mechanisms of this TBI-associated CIRCI remain poorly understood. We hypothesized that dexamethasone (DXM), a synthetic glucocorticoid, which was widely used to treat TBI, induces hypothalamic neuronal apoptosis to aggravate CIRCI. To test this hypothesis, we have evaluated the dose effect of DXM (1 or 10mg/kg) on the development of acute CIRCI in rats with fluid percussion injury-induced TBI and on cultured rat hypothalamic neurons in vitro (DXM, 10(-5)-10(-8)mol/L). Corticosterone Increase Index was recorded as the marker for CIRCI. In addition, MTT and TUNEL assays were used to measure the viability and apoptosis of hypothalamic neurons in primary culture. Moreover, high-resolution hopping probe ion conductance microscopy (HPICM) was used to monitor the DXM-induced morphological changes in neurons. The incidence of acute CIRCI was significantly higher in the high-dose DXM group on post-injury day 7. Cellular viability was significantly decreased from 12h to 24h after the treatment with a high-dose of DXM. A significantly increase in TUNEL positive cells were detected in cultured cells treated with a high-dose of DXM after 18h. Neurites of hypothalamic neuron were dramatically thinner and the numbers of dendritic beadings increased in neurons treated with the high dose of DXM for 12h. In conclusion, high-dose DXM induced hypothalamic neurons to undergo apoptosis in vivo and in vitro, which may aggravate TBI-associated CIRCI.

  3. Dose response of multiple parameters for calyculin A-induced premature chromosome condensation in human peripheral blood lymphocytes exposed to high doses of cobalt-60 gamma-rays.

    PubMed

    Lu, Xue; Zhao, Hua; Feng, Jiang-Bin; Zhao, Xiao-Tao; Chen, De-Qing; Liu, Qing-Jie

    2016-09-01

    Many studies have investigated exposure biomarkers for high dose radiation. However, no systematic study on which biomarkers can be used in dose estimation through premature chromosome condensation (PCC) analysis has been conducted. The present study aims to screen the high-dose radiation exposure indicator in calyculin A-induced PCC. The dose response of multiple biological endpoints, including G2/A-PCC (G2/M and M/A-PCC) index, PCC ring (PCC-R), ratio of the longest/shortest length (L/L ratio), and length and width ratio of the longest chromosome (L/B ratio), were investigated in calyculin A-induced G2/A-PCC spreads in human peripheral blood lymphocytes exposed to 0-20Gy (dose-rate of 1Gy/min) cobalt-60 gamma-rays. The G2/A-PCC index was decreased with enhanced absorbed doses of 4-20Gy gamma-rays. The G2/A PCC-R at 0-12Gy gamma-rays conformed to Poisson distribution. Three types of PCC-R were scored according to their shape and their solidity or hollowness. The frequencies of hollow PCC-R and PCC-R including or excluding solid ring in G2/A-PCC spreads were enhanced with increased doses. The length and width of the longest chromosome, as well as the length of the shortest chromosome in each G2/M-PCC or M/A-PCC spread, were measured. All L/L or L/B ratios in G2/M-PCC or M/A-PCC spread increased with enhanced doses. A blind test with two new irradiated doses was conducted to validate which biomarker could be used in dose estimation. Results showed that hollow PCC-R and PCC-R including solid ring can be utilized for accurate dose estimation, and that hollow PCC-R was optimal for practical application.

  4. High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency

    PubMed Central

    Zaleski, Amanda; Panza, Gregory; Swales, Heather; Arora, Pankaj; Newton-Cheh, Christopher; Wang, Thomas; Thompson, Paul D.; Taylor, Beth

    2015-01-01

    Introduction. Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD). However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension. Methods. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP), carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation. Results. There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (all p > 0.202). High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p = 0.047) and 4.0 ± 1.5 mmHg (p = 0.02), respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p = 0.425). Conclusion. High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity. Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier: NCT01240512). PMID:26451070

  5. Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer

    SciTech Connect

    Bayley, Andrew; Rosewall, Tara; Craig, Tim; Bristow, Rob; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2010-06-01

    Purpose: To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). Methods and Materials: A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladder walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. Results: A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. Conclusion: These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.

  6. Pharmacokinetics and Pharmacodynamics of High-Dose Human Regular U-500 Insulin Versus Human Regular U-100 Insulin in Healthy Obese Subjects

    PubMed Central

    de la Peña, Amparo; Riddle, Matthew; Morrow, Linda A.; Jiang, Honghua H.; Linnebjerg, Helle; Scott, Adam; Win, Khin M.; Hompesch, Marcus; Mace, Kenneth F.; Jacobson, Jennie G.; Jackson, Jeffrey A.

    2011-01-01

    OBJECTIVE Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL). RESEARCH DESIGN AND METHODS This was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects. RESULTS Both overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC0-t’]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tRmax50, tRlast) were prolonged for U-500R versus U-100R at both doses (P < 0.05). CONCLUSIONS Overall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes. PMID:21994429

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    High-dose baclofen is a promising treatment for alcohol use disorder, with a specific action on craving. A more general action on craving in other addictive disorders has been suggested based on the hypothesis of a common neurobiological pathway in addictions. We report the case of a woman with both alcohol use disorder and bulimia nervosa. There was a positive response to high-dose baclofen on alcohol craving, but no response on food craving. The case illustrates that craving could be differentially responsive to anti-craving drugs. PMID:26457456

  9. Nebuhaler or nebulizer for high dose bronchodilator therapy in chronic bronchitis: a comparison.

    PubMed

    Allen, M B; Pugh, J; Wilson, R S

    1988-10-01

    We have compared the clinical efficacy of high dose terbutaline sulphate (10 mg four times daily) delivered by either a Nebuhaler or jet nebulizer in 13 patients with chronic bronchitis in a 2-week, open, crossover study. Both treatment regimens improved run-in symptom scores but no significant changes were recorded in peak flow and spirometry. Side-effects were more common with the Nebuhaler and more patients preferred the nebulizer. However, the Nebuhaler is an alternative therapeutic option for delivery of high doses of bronchodilators in patients with chronic bronchitis. PMID:3076792

  10. Low or High Fractionation Dose {beta}-Radiotherapy for Pterygium? A Randomized Clinical Trial

    SciTech Connect

    Viani, Gustavo Arruda; De Fendi, Ligia Issa; Fonseca, Ellen Carrara; Stefano, Eduardo Jose

    2012-02-01

    Purpose: Postoperative adjuvant treatment using {beta}-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. Methods: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90 eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. Results: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. Conclusions: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy{sub 10.}.

  11. Image-Guided Stereotactic Radiosurgery Using a Specially Designed High-Dose-Rate Linac

    SciTech Connect

    Bayouth, John E. . E-mail: john-bayouth@uiowa.edu; Kaiser, Heather S.; Smith, Mark C.; Pennington, Edward C.; Anderson, Kathleen M. C.; Ryken, Timothy C.; Buatti, John M.

    2007-07-01

    Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed.

  12. Delayed activation of human microglial cells by high dose ionizing radiation.

    PubMed

    Chen, Hongxin; Chong, Zhao Zhong; De Toledo, Sonia M; Azzam, Edouard I; Elkabes, Stella; Souayah, Nizar

    2016-09-01

    Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia. PMID:27265419

  13. SU-F-BRF-11: Dose Rearrangement in High Dose Locally Advanced Lung Patients Based On Perfusion Imaging

    SciTech Connect

    Matrosic, C; Jarema, D; Kong, F; McShan, D; Stenmark, M; Owen, D; Ten Haken, R; Matuszak, M

    2014-06-15

    Purpose: The use of mean lung dose (MLD) limits allows individualization of lung patient tumor doses at safe levels. However, MLD does not account for local lung function differences between patients, leading to toxicity variability at the same MLD. We investigated dose rearrangement to minimize dose to functional lung, as measured by perfusion SPECT, while maintaining target coverage and conventional MLD limits. Methods: Retrospective plans were optimized for 15 locally advanced NSCLC patients enrolled in a prospective imaging trial. A priority-based optimization system was used. The baseline priorities were (1) meet OAR dose constraints, (2) maximize target gEUD, and (3) minimize physical MLD. As a final step, normal tissue doses were minimized. To determine the benefit of rearranging dose using perfusion SPECT, plans were reoptimized to minimize functional lung gEUD as the 4th priority. Results: When only minimizing physical MLD, the functional lung gEUD was 10.8+/−5.0 Gy (4.3–19.8 Gy). Only 3/15 cases showed a decrease in functional lung gEUD of ≥4% when rearranging dose to minimize functional gEUD in the cost function (10.5+/−5.0 Gy range 4.3−19.7). Although OAR constraints were respected, the dose rearrangement resulted in ≥10% increases in gEUD to an OAR in 4/15 cases. Only slight reductions in functional lung gEUD were noted when omitting the minimization of physical MLD, suggesting that constraining the target gEUD minimizes the potential to redistribute dose. Conclusion: Prioritydriven optimization permits the generation of plans that respect traditional OAR limits and target coverage, but with the ability to rearrange dose based on functional imaging. The latter appears to be limited due to the decreased solution space when constraining target coverage. Since dose rearrangement may increase dose to other OARs, it is also worthwhile to investigate global biomarkers of lung toxicity to further individualize treatment in this population

  14. Relative Efficiency of TLD-100 to High Linear Energy Transfer Radiation: Correction to Astronaut Absorbed Dose

    NASA Technical Reports Server (NTRS)

    Badhwar, G. D.; Cash, B. L.; Semones, E. J.; Yasuda, H.; Fujitaka, K.

    1999-01-01

    Response of thermoluminescent detectors (TLD-100) to high linear energy transfer (LET) particles has been studied using helium, carbon, silicon, and iron ions from the Heavy Ion Medical Accelerator at Chiba (Japan), iron ions from the Brookhaven National Laboratory (NY) Alternate Gradient Synchrotron, and 53, 134, 185, and 232 MeV protons from the Loma Linda accelerator. Using the measured relative (to 137Cs) dose efficiency, and measured LET spectra from a tissue equivalent proportional counter (TEPC) on 20 Space Shuttle flights, and 7 Mir flights, the underestimation of absorbed dose by these detectors has been evaluated. The dose underestimation is between 15-20% depending upon the flight inclination and shielding location. This has been confirmed by direct correlation of measured dose by TEPC and TLD-100 at a low shielded location in the Shuttle mid-deck. A comparison of efficiency- LET data with a compilation of similar data from TLD-700, shows that shapes of the two curves are nearly identical, but that the TLD-100 curve is systematically lower by about 13%, and is the major cause of dose underestimation. These results strongly suggest that TLDs used for crew dose estimation be regularly calibrated using heavy ions.

  15. The effect of additional high dose carbon implantation on the tribological properties of titanium implanted steel

    NASA Astrophysics Data System (ADS)

    Hayashi, Kazunori; Sasaki, Jun; Ichiko, Osami; Hashiguchi, Yoshihiro

    1996-08-01

    The tribological properties and the structural changes of hardened steel implanted with titanium followed by carbon were investigated as a function of additional carbon dose. The dose of Ti was 5×10 17 Ti cm -2 and the additional C doses were 0, 4×10 17, 8×10 17 and 1.2×10 18 C cm -2. After Ti implantation, the steel surface transformed to a FeTiC ternary amorphous phase. Additional implantation of carbon to a dose of 4×10 17 C cm -2 produced fine TiC precipitates dispersed in the ternary amorphous matrix. When the additional C dose exceeded 8×10 17 C cm -2, very fine graphite precipitates appeared in the ternary amorphous phase. The steel surface with very fine graphite precipitates exhibited superior tribological properties. The benefits provided by additional high dose carbon implantation are considered as follows: strengthening of the amorphous phase, thickening of the modified layer, dispersion strengthening of the implanted layer by very fine graphite precipitates and lubrication effect by graphite particles. Comparing the friction properties of Ti+C implanted steel with that of C implanted steel, the role of Ti implantation is to reduce the friction of the surface during sliding and the role of C implantation is to increase the lifetime of the surface against wear.

  16. EPR and UV spectroscopic study of table sugar as a high-dose dosimeter

    NASA Astrophysics Data System (ADS)

    Yordanov, N. D.; Gancheva, V.; Georgieva, E.

    2002-10-01

    The possibilities for the estimation of the absorbed dose for high-energy radiation with a new self-calibrated dosimeter containing table sugar as a radiation-sensitive material and Mn 2+/MgO as an internal standard by the method of electron paramagnetic resonance (EPR) is reported. The dose response of this dosimeter is represented as the ratio between the EPR signal intensities of sugar and Mn 2+ versus absorbed dose. Because the EPR spectra of both substances are simultaneously recorded, the influence of some related instrumental setting parameters were investigated. UV spectral studies on water solutions of irradiated solid sugar were also performed. In all solutions of irradiated sugar samples a band at 267 nm was recorded as linearly increasing intensity with the absorbed dose. The minimum detectable dose using the UV spectrum of water solutions of irradiated sugar is 100 Gy. Combination of EPR and UV spectral data is possible to use for independent internal or international calibration and control of dose estimations.

  17. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

    SciTech Connect

    Barkati, Maroie; Williams, Scott G.; Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat; Dyk, Sylvia van; See, Andrew; Duchesne, Gillian M.

    2012-04-01

    Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

  18. In vivo real-time dosimetric verification in high dose rate prostate brachytherapy

    SciTech Connect

    Seymour, Erin L.; Downes, Simon J.; Fogarty, Gerald B.; Izard, Michael A.; Metcalfe, Peter

    2011-08-15

    Purpose: To evaluate the performance of a diode array in the routine verification of planned dose to points inside the rectum from prostate high dose rate (HDR) brachytherapy using a real-time planning system. Methods: A dosimetric study involving 28 patients was undertaken where measured doses received during treatment were compared to those calculated by the treatment planning system (TPS). After the ultrasound imaging required for treatment planning had been recorded, the ultrasound probe was replaced with a geometric replica that contained an 8 mm diameter cylindrical cavity in which a PTW diode array type 9112 was placed. The replica probe was then positioned inside the rectum with the individual diode positions determined using fluoroscopy. Dose was then recorded during the patients' treatment and compared to associated coordinates in the planning system. Results: Factors influencing diode response and experimental uncertainty were initially investigated to estimate the overall uncertainty involved in dose measurements, which was determined to be {+-}10%. Data was acquired for 28 patients' first fractions, 11 patients' second fractions, and 13 patients' third fractions with collection dependent upon circumstances. Deviations between the diode measurements and predicted values ranged from -42% to +35% with 71% of measurements experiencing less than a 10% deviation from the predicted values. If the {+-}10% measurement uncertainty was combined with a tolerated dose discrepancy of {+-}10% then over 95% of the diode results exhibited agreement with the calculated data to within {+-}20%. It must also be noted that when large dose discrepancies were apparent they did not necessarily occur for all five diodes in the one measurement. Conclusions: This technique provided a method that could be utilized to detect gross errors in dose delivery of a real-time prostate HDR plan. Limitations in the detection system used must be well understood if meaningful results are to

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

    SciTech Connect

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

    1985-09-01

    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.

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

    PubMed

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

    2010-10-01

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

  1. [High-dose chemotherapy with stem cell support for solid tumors in adults].

    PubMed

    Rodenhuis, S; de Vries, E G

    1999-04-01

    High-dose chemotherapy for advanced solid malignancies has been the subject of many clinical studies. The replacement of autologous bone marrow transplantation by peripheral blood haematopoietic progenitor cell transplantation and other advances in supportive care have led to a considerable reduction of therapy-related mortality and morbidity. In certain rare disorders, such as germ cell tumours or pediatric sarcomas in adults, high-dose therapy is currently considered the therapeutic standard. It is likely that a subgroup of patients with high-risk or disseminated breast cancer can also benefit in terms of survival from this treatment modality, but final proof from randomized studies remains to be generated. On theoretical grounds, high-dose chemotherapy could also be effective in small cell lung cancer and ovarian cancer, and randomized studies to answer this question are in progress. Many investigators concur that high-dose chemotherapy often leads to dramatic cytoreduction in solid tumours, but only rarely achieves cure. Novel therapeutic modalities are required to control the residual microscopic disease.

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

    SciTech Connect

    Sharma, Renu; Jursinic, Paul A.

    2013-07-15

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

  3. Differences in clinical disease and immune response of pigs challenged with a high-dose versus low-dose inoculum of porcine reproductive and respiratory syndrome virus.

    PubMed

    Loving, Crystal L; Brockmeier, Susan L; Vincent, Amy L; Lager, Kelly M; Sacco, Randy E

    2008-09-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be an economically important infectious disease of swine. Mechanisms governing activation of the innate immune response to PRRSV remain to be elucidated. Virulence differences observed between PRRSV isolates have been attributed to replication ability in vivo, though immunogenic differences likely contribute to virulence also. The current study utilized a single PRRSV isolate given at two different challenge doses to investigate the effect of viral replication and load on immune responses, including type I interferon activation. Body temperature, viral load, antibody levels, cellular infiltration into pulmonary tissue, and the interferon response were measured in animals receiving either a low (10(2) CCID(50)) or high (10(6) CCID(50)) dose of inoculum to understand the role of challenge dose in acute immune responses. Initial PRRSV dose did not correlate with serum levels of PRRSV vRNA or antibody titers during the acute stage of infection (days 2-12 PI), but did have an effect on the immune response and mortality. Type I interferon responses, measured by transcriptional changes in IFN-beta, IFN-alpha, Mx, and PKR, were uniquely different when assessed relative to viral dose or cell type, but no overall trend existed to discern responses based on challenge dose. Serum IFN-gamma levels correlated with serum viral RNA load at day 19 PI. Overall, between days 2 and 12 PI, serum vRNA load was not significantly different between pigs challenged with a low or high dose of PRRSV. Animals receiving high-dose inoculum were viremic longer and eventually succumbed to respiratory disease. IFN-gamma may play a role in PRRSV pathogenesis, as serum levels increased significantly in pigs challenged with the high dose of PRRSV.

  4. Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

    PubMed

    Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

    2016-01-01

    To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

  5. Systemic treatment with high dose of flunixin-meglumine is able to block ovulation in mares by inducing hemorrhage and luteinisation of follicles.

    PubMed

    Cuervo-Arango, J; Domingo-Ortiz, R

    2011-03-01

    Prostaglandins play an obligatory role during the process of ovulation in mammals. Ovulation can be blocked by intrafollicular administration of non-steroidal anti-inflammatory drugs (NSAIDs) in several domestic species including the mare as well as by systemic administration of these drugs in women. In the mare, the effect of systemic NSAIDs treatment on ovulation has not been critically studied. The objectives of this study were: a) to determine whether high dose of flunixin-meglumine (FM) administered systemically to mares during the periovulatory period was able to block ovulation; and b) to study the follicular ultrasound characteristics of FM treated mares. Six mares were used in the study during two consecutive estrous cycles. Each mare received 2 mg FM/kg i.v. twice a day starting at the time of treatment with hCG when the follicle reached a diameter of ≥ 32 mm and continuing until ovulation. During the consecutive control cycle (CON) the mares received the same dose of hCG but were not administered FM. During the FM cycles five of six mares failed to ovulate and collapse the preovulatory follicle; but echoic specks were observed within the follicles, which continued to grow until a mean diameter of 55 mm. Eventually, the follicular contents were organised and luteinised. All CON mares ovulated normally. In conclusion, when mares were treated with FM, they had a higher incidence of ovulatory failure and development of luteinised unruptured follicles (83%, P = 0.015) compared with untreated mares.

  6. Not too little, not too much-just right! (Better ways to give high dose melphalan).

    PubMed

    Shaw, P J; Nath, C E; Lazarus, H M

    2014-12-01

    Of the 13 286 autologous haematopoietic cell transplant procedures reported in the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high-dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience with high-dose melphalan, and its continuing central role as cytoreductive therapy for large numbers of patients with myeloma, the pharmacodynamics and pharmacogenomics of melphalan are still in their infancy. The addition of protectant agents such as amifostine and palifermin allows dose escalation to 280 mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose-limiting. Although combination with additional alkylating agents is feasible, the additional TRM may not be justified when so many post-consolidation therapies are available for myeloma patients. Current research should optimise the delivery of this single-agent chemotherapy. This includes the use of newer formulations and real-time PKs. These strategies may allow a safe and effective platform for adding synergistic novel therapies and provide a window of lymphodepletion for the addition of immunotherapies.

  7. Effect of particle size in the TL response of natural quartz sensitized with high gamma dose

    NASA Astrophysics Data System (ADS)

    Carvalho, A. B., Jr.; Guzzo, P. L.; Sullasi, H. L.; Khoury, H. J.

    2010-11-01

    The aim of this study is to investigate the effect of particle size in the thermoluminescence (TL) response of natural quartz sensitized with high gamma dose. For this, fragments of a single crystal taken from the Solonópole district (Brazil) were crushed and classified into ten size fractions ranging from 38 μm to 5 mm. Aliquots of each size fraction were sensitized with 25 kGy of gamma dose of 60Co and heat-treated in a muffle furnace at 400oC. The non-sensitized samples were exposed to test doses between 50 Gy and 5 kGy and the sensitized samples were exposed to a unique test dose equal to 50 mGy. For non-sensitized samples, the TL peak near 325 °C increases with the particle size decreasing. However, in the case of sensitized samples, the TL output near 280 °C increases with the increasing of particle size up to mean grain size equal to 308 μm. Above 308 μm, an abrupt reduction in the TL intensity was noticed. These effects are discussed in relation to the specific surface area and the different interaction of high gamma doses with fine and coarse particles of quartz.

  8. Study protocol: safety correction of high dose antipsychotic polypharmacy in Japan

    PubMed Central

    2014-01-01

    Background In Japan, combination therapy with high doses of antipsychotic drugs is common, but as a consequence, many patients with schizophrenia report extrapyramidal and autonomic nervous system side effects. To resolve this, we proposed a method of safety correction of high dose antipsychotic polypharmacy (the SCAP method), in which the initial total dose of all antipsychotic drugs is calculated and converted to a chlorpromazine equivalent (expressed as milligrams of chlorpromazine, mg CP). The doses of low-potency antipsychotic drugs are then reduced by ≤ 25 mg CP/week, and the doses of high-potency antipsychotics are decreased at a rate of ≤50 mg CP/week. Although a randomized, case-controlled comparative study has demonstrated the safety of this method, the number of participants was relatively small and its results required further validation. In this study of the SCAP method, we aimed to substantially increase the number of participants. Methods/design The participants were in- or outpatients treated with two or more antipsychotics at doses of 500–1,500 mg CP/day. Consenting participants were randomized into control and dose reduction groups. In the control group, patients continued with their normal regimen for 3 months without a dose change before undergoing the SCAP protocol. The dose reduction group followed the SCAP strategy over 3–6 months with a subsequent 3-month follow-up period. Outcome measures were measured at baseline and then at 3-month intervals, and included clinical symptoms measured on the Manchester scale, the extent of extrapyramidal and autonomic side effects, and quality of life using the Euro QOL scale. We also measured blood drug concentrations and drug efficacy-associated biochemical parameters. The Brief Assessment of Cognition in Schizophrenia, Japanese version, was also undertaken in centers where it was available. Discussion The safety and efficacy of the SCAP method required further validation in a large

  9. Calibrating the High Density Magnetic Port within Tissue Expanders to Achieve more Accurate Dose Calculations for Postmastectomy Patients with Immediate Breast Reconstruction

    NASA Astrophysics Data System (ADS)

    Jones, Jasmine; Zhang, Rui; Heins, David; Castle, Katherine

    In postmastectomy radiotherapy, an increasing number of patients have tissue expanders inserted subpectorally when receiving immediate breast reconstruction. These tissue expanders are composed of silicone and are inflated with saline through an internal metallic port; this serves the purpose of stretching the muscle and skin tissue over time, in order to house a permanent implant. The issue with administering radiation therapy in the presence of a tissue expander is that the port's magnetic core can potentially perturb the dose delivered to the Planning Target Volume, causing significant artifacts in CT images. Several studies have explored this problem, and suggest that density corrections must be accounted for in treatment planning. However, very few studies accurately calibrated commercial TP systems for the high density material used in the port, and no studies employed fusion imaging to yield a more accurate contour of the port in treatment planning. We compared depth dose values in the water phantom between measurement and TPS calculations, and we were able to overcome some of the inhomogeneities presented by the image artifact by fusing the KVCT and MVCT images of the tissue expander together, resulting in a more precise comparison of dose calculations at discrete locations. We expect this method to be pivotal in the quantification of dose distribution in the PTV. Research funded by the LS-AMP Award.

  10. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria

    PubMed Central

    2014-01-01

    Introduction The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses. Methods We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated. Results Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure. Conclusions TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria. PMID:24887101

  11. Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy

    PubMed Central

    Kayvan Jafari, Sabah; Nezafat Firizi, Maryam; Abbaspour, Ali Reza; Ghafoori Gharib, Fahime; Ghobadi, Yusef; Gholizadeh, Samira

    2016-01-01

    Objective In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. Methods Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and 17β-estradiol, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. Results We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and 17β-estradiol levels, and a reduced frequency of macrophages and uNK cells. Conclusion Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes. PMID:27104153

  12. Efficacy of high-dose methylprednisolone pulse therapy in the treatment of enterovirus 71 encephalitis.

    PubMed

    Zhang, Guangyou; Wang, Jiwen; Yao, Guo; Shi, Baohai

    2016-07-01

    To investigate the efficacy of high-dose methylprednisolone pulse therapy in the treatment of Enterovirus 71 (EV71) encephalitis. To determine whether high-dose methylprednisolone pulse therapy should be used, 80 cases of pediatric patients with EV71 encephalitis were randomly divided into steroid pulse therapy group and non-steroid pulse therapy group and their clinical information was compared using statistic analysis. There was no statistical difference in the duration of fever, duration of nervous system involvement, duration of hospital stay, blood pressure, and cure rates between the two groups (p>0.05). The heart rate, respiratory rate, white blood cell counts and blood glucose of the steroid pulse therapy group were significantly higher than those of the non-steroid pulse therapy group (p<0.05). High-dose steroid pulse therapy to treat EV71 encephalitis can't shorten the course or improve the prognosis of the disease. In contrast, it has side effects and might aggravate disease condition or interfere with disease diagnosis. Our study suggested that there is no beneficial effect to use high-dose steroid pulse therapy for the treatment of EV71 encephalitis. PMID:27592493

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

    PubMed

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

    2014-08-01

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

  14. HUMAN ACTIVITIES THAT MAY LEAD TO HIGH INHALED INTAKE DOSES IN CHILDREN AGED 6-13

    EPA Science Inventory

    The paper focuses on possible activities of children aged 6-13 that may make them susceptible to high hourly intake doses of ozone (O3) air pollution. Data from an O3 exposure modeling exercise indicates that a relatively few hours can account for a significant amount of the t...

  15. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  16. Calorimetry of electron beams and the calibration of dosimeters at high doses

    NASA Astrophysics Data System (ADS)

    Humphreys, J. C.; McLaughlin, W. L.

    Graphite or metal calorimeters are used to make absolute dosimetric measurements of high-energy electron beams. These calibrated beams are then used to calibrate several types of dosimeters for high-dose applications such as medical-product sterilization, polymer modification, food processing, or electronic-device hardness testing. The electron beams are produced either as continuous high-power beams at approximately 4.5 MeV by d.c. type accelerators or in the energy range of approximately 8 to 50 MeV using pulsed microwave linear accelerators (linacs). The continuous beams are generally magnetically scanned to produce a broad, uniform radiation environment for the processing of materials of extended lateral dimensions. The higher-energy pulsed beams may also be scanned for processing applications or may be used in an unscanned, tightly-focused mode to produce maximum absorbed dose rates such as may be required for electronic-device radiation hardness testing. The calorimeters are used over an absorbed dose range of 10 2 to 10 4 Gy. Intercomparison studies are reported between National Institute of Standards and Technology (NIST) and UK National Physical Laboratory (NPL) graphite disk calorimeters at high doses, using the NPL 10-MeV linac, and agreement was found within 1.5%. It was also shown that the electron-beam responses of radiochromic film dosimeters and alanine pellet dosimeters can be accurately calibrated by comparison with calorimeter readings.

  17. Vulnerability of OFDR-based distributed sensors to high γ-ray doses.

    PubMed

    Rizzolo, S; Boukenter, A; Marin, E; Cannas, M; Perisse, J; Bauer, S; Mace, J-R; Ouerdane, Y; Girard, S

    2015-07-27

    Vulnerability of Optical Frequency Domain Reflectometry (OFDR) based sensors to high γ-ray doses (up to 10 MGy) is evaluated with a specific issue of a radiation-hardened temperature and strain monitoring system for nuclear industry. For this, we characterize the main radiation effects that are expected to degrade the sensor performances in such applicative domain: the radiation-induced attenuation (RIA), the possible evolution with the dose of the Rayleigh scattering phenomenon as well as its dependence on temperature and strain. This preliminary investigation is done after the irradiation and for five different optical fiber types covering the range from radiation-hardened fibers to highly radiation sensitive ones. Our results show that at these high dose levels the scattering mechanism at the basis of the used technique for the monitoring is unaffected (changes below 5%), authorizing acceptable precision on the temperature or strain measurements. RIA has to be considered as it limits the sensing range. From our vulnerability study, the OFDR sensors appear as promising candidates for nuclear industry even at doses as high as 10 MGy.

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

    PubMed

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

    2014-05-01

    CCD/CMOS cameras, loaded on a robot system, are generally used as the eye of the robot and monitoring unit. A major problem that arises when dealing with images provided by CCD/CMOS cameras under severe accident situations of a nuclear power plant is the presence of speckles owing to the high dose-rate gamma irradiation fields. To use a CCD/CMOS camera as a monitoring unit in a high radiation area, the legibility of the camera image in such intense gamma-radiation fields should therefore be defined. In this paper, the authors describe the monitoring index as a figure of merit of the camera's legibleness under a high dose-rate gamma ray irradiation environment. From a low dose-rate (10 Gy h) to a high dose-rate (200 Gy h) level, the legible performances of the cameras owing to the speckles are evaluated. The numbers of speckles generated by gamma ray irradiation in the camera image are calculated by an image processing technique. The legibility of the sensor indicator (thermo/hygrometer) owing to the number of speckles is also presented. PMID:24667385

  19. Spurious thyroid cancer metastasis: saliva contamination artifact in high dose iodine-131 metastases survey

    SciTech Connect

    Park, H.M.; Tarver, R.D.; Schauwecker, D.S.; Burt, R.

    1986-05-01

    The use of high dose /sup 131/I for workup of thyroid cancer patients increases the chance of contamination artifact which may mimic metastases. Two elderly male patients with follicular carcinoma of the thyroid had salivary contamination artifacts on metastatic survey scans. These patients received a 1 and 10 mCi dose of /sup 131/I, respectively. The artifacts were recognized only retrospectively when follow-up scans were obtained and compared. The characteristics of contamination artifacts and several methods to confirm these are discussed.

  20. Antagonistic effect of rifampin on the efficacy of high-dose levofloxacin in staphylococcal experimental foreign-body infection.

    PubMed

    Murillo, O; Pachón, M E; Euba, G; Verdaguer, R; Tubau, F; Cabellos, C; Cabo, J; Gudiol, F; Ariza, J

    2008-10-01

    Since levofloxacin at high doses was more active than levofloxacin at conventional doses and was the best therapy alone in a rat model of staphylococcal foreign-body infection, in this study we tested how these differences affect the activities of their respective combinations with rifampin in vitro and in vivo. In vitro studies were performed in the log and stationary phases. By using this model, rifampin at 25 mg/kg of body weight/12 h, levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, levofloxacin at 50 mg/kg/day, levofloxacin at 50 mg/kg/day plus rifampin, or a control treatment was administered for 7 days; and therapy with for levofloxacin at 100 mg/kg/day alone and rifampin alone was prolonged to 14 days. We screened for the appearance of resistant strains. Killing curves in the log phase showed a clear antagonism with levofloxacin at concentrations >or=2x MIC and rifampin and tended to occur in the stationary phase. At the end of 7 days of therapy, levofloxacin at 100 mg/kg/day was the best treatment and decreased the bacterial counts from tissue cage fluid (P < 0.05 compared with the results for groups except those receiving rifampin alone). At the end of 14 days of therapy with levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, and the control treatment, the bacterial counts on the coverslips were 2.24 (P < 0.05 compared with the results with the combined therapy), 3.36, and 5.4 log CFU/ml, respectively. No rifampin or levofloxacin resistance was detected in any group except that receiving rifampin alone. In conclusion, high-dose levofloxacin was the best treatment and no resistant strains appeared; the addition of rifampin showed an antagonistic effect. The efficacy of the rifampin-levofloxacin combination is not significantly improved by the dosage of levofloxacin.

  1. A Comprehensive Analysis of Cardiac Dose in Balloon-Based High-Dose-Rate Brachytherapy for Left-Sided Breast Cancer

    SciTech Connect

    Valakh, Vladimir; Kim, Yongbok; Werts, E. Day; Trombetta, Mark G.

    2012-04-01

    Purpose: To investigate radiation dose to the heart in 60 patients with left-sided breast cancer who were treated with balloon-based high-dose-rate brachytherapy using MammoSite or Contura applicators. Methods and Materials: We studied 60 consecutive women with breast cancer who were treated with 34 Gy in 10 twice-daily fractions using MammoSite (n = 37) or Contura (n = 23) applicators. The whole heart and the left and right ventricles were retrospectively delineated, and dose-volume histograms were analyzed. Multiple dosimetrics were reported, such as mean dose (D{sub mean}); relative volume receiving 1.7, 5, 10, and 20 Gy (V1.7, V5, V10, and V20, respectively); dose to 1 cc (D{sub 1cc}); and maximum point dose (D{sub max}). Biologic metrics, biologically effective dose and generalized equivalent uniform dose were computed. The impact of lumpectomy cavity location on cardiac dose was investigated. Results: The average {+-} standard deviation of D{sub mean} was 2.45 {+-} 0.94 Gy (range, 0.56-4.68) and 3.29 {+-} 1.28 Gy (range, 0.77-6.35) for the heart and the ventricles, respectively. The average whole heart V5 and V10 values were 10.2% and 1.3%, respectively, and the heart D{sub max} was >20 Gy in 7 of 60 (11.7%) patients and >25 Gy in 3 of 60 (5%) patients. No cardiac tissue received {>=}30 Gy. The V1.7, V5, V10, V20, and D{sub mean} values were all higher for the ventricles than for the whole heart. For balloons located in the upper inner quadrant of the breast, the average whole heart D{sub mean} was highest. The D{sub mean}, biologically effective dose, and generalized equivalent uniform dose values for heart and ventricles decreased with increasing minimal distance from the surface of the balloon. Conclusions: On the basis of these comprehensive cardiac dosimetric data, we recommend that cardiac dose be routinely reported and kept as low as possible in balloon-based high-dose-rate brachytherapy treatment planning for patients with left-sided breast cancer so

  2. Temozolomide-Associated Bronchiolitis Obliterans Organizing Pneumonia Successfully Treated with High-Dose Corticosteroid

    PubMed Central

    Kim, Tae-Ok; Kang, Hyun-Wook; Chi, Su-Young; Ban, Hee-Jung; Kwon, Yong-Soo; Kim, Kyu-Sik; Kim, Yu-Il; Lim, Sung-Chul; Kim, Young-Chul

    2012-01-01

    Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patient's clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically. PMID:22468112

  3. Dyed acrylic-acid grafted polypropylene films for high-dose radiation dosimetry

    NASA Astrophysics Data System (ADS)

    Abdel-Fattah, A. A.; Said, F. I. A.; Ebraheem, S.; El-Kelany, M.; El Miligy, A. A.

    1999-03-01

    Gamma radiation-induced polymerization of acrylic acid (AAc) onto polypropylene (PP) film has been carried out under nitrogen atmosphere. The grafted film of PP-g-PAAc was allowed to react with solutions of two ionic dyes, namely malachite green (MALG) or methylene green (METG). The investigations show that these new dosimeter films of PPMALG and PPMETG may be useful for high-dose gamma radiation applications. The useful absorbed dose range of the dyed films extends up to about 400 kGy, with a minimum useful dose of about 5 kGy. The radiation-induced colour bleaching has been analyzed with visible spectrophotometry, either at the maximum of the absorption band peaking at 601 nm (for PPMETG) or that peaking at 623 nm for (PPMALG). The effects of relative humidity during irradiation, shelf-life and post-irradiation storage in dark and indirect daylight conditions on dosimeters performance are discussed.

  4. Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk

    PubMed Central

    Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

    2015-01-01

    Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

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

    PubMed Central

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

    2016-01-01

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

  6. Sleep is more sensitive to high doses of caffeine in the middle years of life.

    PubMed

    Robillard, Rébecca; Bouchard, Maude; Cartier, Annick; Nicolau, Laurence; Carrier, Julie

    2015-06-01

    During the middle years of life, sleep becomes more fragile and its sensitivity to psychostimulants may increase. This study evaluated the effects of 200 mg and 400 mg of caffeine on sleep in young and middle-aged adults. The sleep of 22 young (23.5 ± 1.9 years) and 24 middle-aged (51.7 ± 11.5 years) adults was recorded using polysomnography in two conditions (placebo and caffeine) in a double-blind cross-over design. Compared to placebo, caffeine increased sleep latency, shortened total sleep duration and reduced sleep efficiency. At the higher dose, these effects were more pronounced in middle-aged than in young adults. Furthermore, the higher dose of caffeine increased absolute stage 1 sleep in young adults, whereas it decreased absolute stage 2 sleep in middle-aged adults. Caffeine also induced dose-dependent increases in relative stage 1 sleep and reductions in absolute and relative slow wave sleep and absolute rapid eye movement sleep in both age groups. There was no dose- or age-related modulation of the effects of caffeine on quantified electroencephalographic measures. These results indicate that, compared to young adults, middle-aged adults are generally more sensitive to the effects of a high dose of caffeine on sleep quantity and quality.

  7. Amorphous and crystalline optical materials used as instruments for high gamma radiation doses estimations

    NASA Astrophysics Data System (ADS)

    Ioan, M.-R.

    2016-06-01

    Nuclear radiation induce some changes to the structure of exposed materials. The main effect of ionizing radiation when interacting with optical materials is the occurrence of color centers, which are quantitatively proportional to the up-taken doses. In this paper, a relation between browning effect magnitude and dose values was found. Using this relation, the estimation of a gamma radiation dose can be done. By using two types of laser wavelengths (532 nm and 633 nm), the optical powers transmitted thru glass samples irradiated to different doses between 0 and 59.1 kGy, were measured and the associated optical browning densities were determined. The use of laser light gives the opportunity of using its particularities: monochromaticity, directionality and coherence. Polarized light was also used for enhancing measurements quality. These preliminary results bring the opportunity of using glasses as detectors for the estimation of the dose in a certain point in space and for certain energy, especially in particles accelerators experiments, where the occurred nuclear reactions are involving the presence of high gamma rays fields.

  8. A favorable risk-benefit analysis of high dose thyroid for treatment of bipolar disorders with regard to osteoporosis.

    PubMed

    Kelly, Tammas

    2014-09-01

    High dose thyroid hormone has been in use since the 1930s for the treatment of affective disorders. Despite numerous papers showing benefit, the lack of negative trials and its inclusion in multiple treatment guidelines, high dose thyroid has yet to find wide spread use. The major objection to the use of high dose thyroid is the myth that it causes osteoporosis. This paper reviews the literature surrounding the use of high dose thyroid, both in endocrinology and in psychiatry. High dose thyroid does not appear to be a significant risk factor for osteoporosis while other widely employed psychiatric medications do pose a risk. Psychiatrists are uniquely qualified to do the risk-benefit analyses of high dose thyroid for the treatment of the bipolar I, bipolar II and bipolar NOS. Other specialties do not have the requisite knowledge of the risks of alterative medications or of the mortality and morbidity of the bipolar disorders to do a full risk benefit analysis.

  9. Factors for Predicting Rectal Dose of High-Dose-Rate Intracavitary Brachytherapy After Pelvic Irradiation in Patients With Cervical Cancer: A Retrospective Study With Radiography-Based Dosimetry

    SciTech Connect

    Huang Engyen; Wang Chongjong; Lan Jenhong; Chen Huichun; Fang Fumin; Hsu, H.-C.; Huang Yujie; Wang Changyu; Wang Yuming

    2010-02-01

    Purpose: To evaluate the predictive factors for rectal dose of the first fraction of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. Methods and Materials: From March 1993 through February 2008, 946 patients undergoing pelvic irradiation and HDR-ICBT were analyzed. Examination under anesthesia (EUA) at the first implantation of the applicator was usually performed in the early period. Rectal point was determined radiographically according to the 38th Report of the International Commission of Radiation Units and Measurements (ICRU). The ICRU rectal dose (PRD) as a percentage of point A dose was calculated; multiple linear regression models were used to predict PRD. Results: Factors influencing successful rectal dose calculation were EUA (p < 0.001) and absence of diabetes (p = 0.047). Age (p < 0.001), body weight (p = 0.002), diabetes (p = 0.020), and EUA (p < 0.001) were independent factors for the PRD. The predictive equation derived from the regression model was PRD (%) = 57.002 + 0.443 x age (years) - 0.257 x body weight (kg) + 6.028 x diabetes (no: 0; yes: 1) - 8.325 x EUA (no: 0; yes: 1) Conclusion: Rectal dose at the first fraction of HDR-ICBT is positively influenced by age and diabetes, and negatively correlated with EUA and body weight. A small fraction size at point A may be considered in patients with a potentially high rectal dose to reduce the biologically effective dose if the ICRU rectal dose has not been immediately obtained in the first fraction of HDR-ICBT.

  10. Pharmacodynamic Target Attainment for Various Ceftazidime Dosing Schemes in High-Flux Hemodialysis

    PubMed Central

    Loo, Angela S.; Neely, Michael; Anderson, Evan J.; Ghossein, Cybele; McLaughlin, Milena M.

    2013-01-01

    Ceftazidime is a broad-spectrum cephalosporin with high-level activity against a variety of Gram-negative pathogens, including Pseudomonas aeruginosa. Improved outcomes are associated with cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%TMIC) of >45 to 70% of the dosing interval. Optimal dosing to achieve a 90% probability of target attainment (PTA) in patients receiving high-flux hemodialysis (HFHD) is unknown. We used existing data from six anephric adults receiving hemodialysis to construct a population model with the Pmetrics package for R. From the final model's joint probability density, we simulated the PTA for various ceftazidime dosing regimens, HFHD schedules, and organism MICs. For HFHD every 48 h and 1 g of ceftazidime given posthemodialysis, the PTA exceeds 90% for all isolates with MICs of ≤8 μg/ml, assuming a goal of 70%TMIC. For 72-h dialysis intervals, postdialysis dosing of 1 g is adequate for achievement of the 70%TMIC goal only for organisms with MICs of ≤4 μg/ml, while 2 g is adequate for organisms with MICs of ≤8 μg/ml. A dose of 500 mg once daily, regardless of HFHD schedule, has a 90% PTA for organisms with MICs of ≤16 μg/ml, while 1 g once daily may achieve 100% PTA even for resistant organisms with a MIC of 32 μg/ml. Therefore, to ensure maximal ceftazidime activity, once-daily dosing of 500 mg to 1 g ceftazidime in patients receiving HFHD may be preferable for critically ill patients when MIC data are unavailable and for more resistant organisms with ceftazidime MICs of 16 to 32 μg/ml. PMID:24018264

  11. Dose-volume histogram parameters of high-dose-rate brachytherapy for Stage I-II cervical cancer (≤4cm) arising from a small-sized uterus treated with a point A dose-reduced plan.

    PubMed

    Nakagawa, Akiko; Ohno, Tatsuya; Noda, Shin-ei; Kubo, Nobuteru; Kuwako, Keiko; Saitoh, Jun-Ichi; Nakano, Takashi

    2014-07-01

    We investigated the rectal dose-sparing effect and tumor control of a point A dose-reduced plan in patients with Stage I-II cervical cancer (≤4 cm) arising from a small-sized uterus. Between October 2008 and August 2011, 19 patients with Stage I-II cervical cancer (≤4 cm) were treated with external beam radiotherapy (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated with brachytherapy with standard loading of source-dwell positions and a fraction dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a small uterus close to the rectum or small intestine were treated with brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy as the dose constraint ('point A dose-reduced plan') instead of the 6-Gy plan at point A ('tentative 6-Gy plan'). The total doses from EBRT and brachytherapy were added up and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2, respectively. With a median follow-up period of 35 months, three patients developed Grade-1 late rectal complications and no patients developed local recurrence. Our preliminary results suggested that CT-guided brachytherapy using an individualized point A dose-reduced plan might be useful for reducing late rectal complications while maintaining primary tumor control.

  12. Is Heparin Effective for the Controlled Delivery of High-Dose Bone Morphogenetic Protein-2?

    PubMed

    Kim, Ri Youn; Lee, Beomseok; Park, Si-Nae; Ko, Jae-Hyung; Kim, In Sook; Hwang, Soon Jung

    2016-05-01

    Sustained release of bone morphogenetic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low-dose BMP-2. However, its effect with high-dose BMP-2 is still unclear and should be clarified considering the clinical use of a high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of a heparin-conjugated collagen sponge (HCS) with high-dose BMP-2 delivery by investigating in vivo initial osteogenic regulation and bone healing over 12 weeks in comparison with that of an absorbable collagen sponge (ACS). The in vitro BMP-2 release profile in the HCS exhibited a lower burst followed by a sustained release of BMP-2, whereas that of the ACS showed an initial burst phase only. As a result of a lower burst, the HCS-BMP group showed higher expression of bone-forming/resorbing markers and enhanced activation of osteoclasts than the ACS-BMP group within the scaffold of defect after 7 days, which is presumed to be because of retention of relatively higher amounts of BMP-2. However, the surrounding calvariae were less resorbed in the HCS-BMP group, compared with the aggressive resorptive response in the ACS-BMP group. Microcomputed tomography and histology revealed that HCS-BMP guided more effective bone regeneration of central defect over time inducing minor ossification at the defect exterior, whereas ACS-BMP exhibited excessive ossification at the defect exterior. These results showed that HCS-mediated BMP-2 delivery at a high dose has advantages over ACS, including less early resorption of surrounding bone tissue and higher efficacy in compact bone regeneration over a longer period, highlighting a clinical feasibility of this technology. PMID:27098389

  13. Magnetic Resonance Lymphography-Guided Selective High-Dose Lymph Node Irradiation in Prostate Cancer

    SciTech Connect

    Meijer, Hanneke J.M.; Debats, Oscar A.; Kunze-Busch, Martina; Kollenburg, Peter van; Leer, Jan Willem; Witjes, J. Alfred; Kaanders, Johannes H.A.M.; Barentsz, Jelle O.; Lin, Emile N.J.Th. van

    2012-01-01

    Purpose: To demonstrate the feasibility of magnetic resonance lymphography (MRL) -guided delineation of a boost volume and an elective target volume for pelvic lymph node irradiation in patients with prostate cancer. The feasibility of irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes in conjunction with irradiation of the prostate using intensity-modulated radiotherapy (IMRT) was also investigated. Methods and Materials: In 4 prostate cancer patients with a high risk of lymph node involvement but no enlarged lymph nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis. These lymph nodes were identified and delineated on a radiotherapy planning CT to create a boost volume. Based on the location of the MRL-positive lymph nodes, the standard elective pelvic target volume was individualized. An IMRT plan with a simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes, and 72 Gy to the prostate. Results: All MRL-positive lymph nodes could be identified on the planning CT. This information could be used to delineate a boost volume and to individualize the pelvic target volume for elective irradiation. IMRT planning delivered highly acceptable radiotherapy plans with regard to the prescribed dose levels and the dose to the organs at risk (OARs). Conclusion: MRL can be used to select patients with limited lymph node involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and an elective pelvic target volume for selective high-dose lymph node irradiation with IMRT is feasible. Whether this approach will result in improved outcome for these patients needs to be investigated in further clinical studies.

  14. Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients

    PubMed Central

    2013-01-01

    Background Glucocorticoids commonly cause drug-induced diabetes. This association is well recognized but available evidence does not answer clinically relevant issues in subjects without diabetes. Methods Thirty-five individuals without diabetes with a recent diagnosis of acute lymphoblastic leukemia or non-Hodgkin’s lymphoma on high-dose glucocorticoid therapy were studied. Close systematic monitoring of fasting and postprandial glycemia and fasting insulin determinations, HOMA-insulin resistance and HOMA β-cell function were performed. The primary objective was to define the incidence of secondary diabetes in patients treated with high-dose glucocorticoids. Secondary objectives were to specify the intensity, the moment it appears and the evolution of hyperglycemia, in addition to the risk factors, mechanisms and impact of continuous and cyclical glucocorticoids on the development of hyperglycemia. Results Mean age of patients was 38.4 ± 18.7 years. The incidence of diabetes was 40.6% and was found after the first week; half the time it occurred between the second and fourth. Two-thirds spontaneously normalized by eight weeks. Continuous glucocorticoid administration had a higher incidence of fasting hyperglycemia (P = 0.003). Mean peak insulin levels were significantly higher in cases of diabetes. Conclusions High-dose prednisone for 2 to 3 months produced an elevated incidence of diabetes, usually with mild hyperglycemia occurring between the second and fourth week, normalizing spontaneously in all cases. Hyperglycemia was more frequent with continuous doses and occurred in cases with increased insulin resistance. The clinical and therapeutic characteristics of our participants, who were otherwise healthy, could represent the clinical setting of many patients with illness from other medical areas that might require high doses of GC for six to twelve weeks. PMID:23557386

  15. Pharmacokinetic properties of single-dose primaquine in Papua New Guinean children: feasibility of abbreviated high-dose regimens for radical cure of vivax malaria.

    PubMed

    Moore, Brioni R; Salman, Sam; Benjamin, John; Page-Sharp, Madhu; Robinson, Leanne J; Waita, Elizabeth; Batty, Kevin T; Siba, Peter; Mueller, Ivo; Davis, Timothy M E; Betuela, Inoni

    2014-01-01

    Since conventional 14-day primaquine (PMQ) radical cure of vivax malaria is associated with poor compliance, and as total dose, not therapy duration, determines efficacy, a preliminary pharmacokinetic study of two doses (0.5 and 1.0 mg/kg of body weight) was conducted in 28 healthy glucose-6-phosphate dehydrogenase-normal Papua New Guinean children, aged 5 to 12 years, to facilitate development of abbreviated high-dose regimens. Dosing was with food and was directly observed, and venous blood samples were drawn during a 168-h postdose period. Detailed safety monitoring was performed for hepatorenal function and hemoglobin and methemoglobin concentrations. Plasma concentrations of PMQ and its metabolite carboxyprimaquine (CPMQ) were determined by liquid chromatography-mass spectrometry and analyzed using population pharmacokinetic methods. The derived models were used in simulations. Both single-dose regimens were well tolerated with no changes in safety parameters. The mean PMQ central volume of distribution and clearance relative to bioavailability (200 liters/70 kg and 24.6 liters/h/70 kg) were within published ranges for adults. The median predicted maximal concentrations (Cmax) for both PMQ and CPMQ after the last dose of a 1.0 mg/kg 7-day PMQ regimen were approximately double those at the end of 14 days of 0.5 mg/kg daily, while a regimen of 1.0 mg/kg twice daily resulted in a 2.38 and 3.33 times higher Cmax for PMQ and CPMQ, respectively. All predicted median Cmax concentrations were within ranges for adult high-dose studies that also showed acceptable safety and tolerability. The present pharmacokinetic data, the first for PMQ in children, show that further studies of abbreviated high-dose regimens are feasible in this age group. PMID:24189254

  16. Precipitate behavior in self-ion irradiated stainless steels at high doses

    NASA Astrophysics Data System (ADS)

    Jiao, Z.; Was, G. S.

    2014-06-01

    To study radiation-induced precipitation at high doses, solution annealed 304L SS and cold worked 316 SS were irradiated to 46 and 260 dpa at 380 °C using 5 MeV Fe++ and the radiation-induced precipitates were examined using atom probe tomography. Ni/Si-rich clusters were observed in all examined conditions. G-phase precipitates were observed in 316 SS at 46 dpa but only appeared in 304L SS at 260 dpa. Using the neutron irradiation to 46 dpa at 320 °C as a reference, the temperature shift for cold worked 316 SS appeared to be smaller than that of solution annealed 304L SS, probably due to the high density of dislocations, which served as defect sinks and mitigated the effect of high dose rate.

  17. Analgesic efficacy of orally administered buprenorphine in rats.

    PubMed

    Martin, L B; Thompson, A C; Martin, T; Kristal, M B

    2001-02-01

    The analgesic effect of orally administered buprenorphine was compared with that induced by a standard therapeutic injected dose (0.05 mg/kg of body weight, s.c.) in male Long-Evans rats. Analgesia was assessed by measuring pain threshold, using the hot-water tail-flick assay before and after administration of buprenorphine. The results suggest that a commonly used formula for oral buprenorphine in flavored gelatin, at a dose of 0.5 mg/kg, does not increase pain threshold in rats. Instead, oral buprenorphine doses of 5 and 10 mg/kg were necessary to induce significant increases in pain threshold. However, these doses had to be administered by orogastric infusion because the rats would not voluntarily eat flavored gelatin containing this much buprenorphine. The depth of analgesia induced by these infused doses was comparable to that induced by the clinically effective s.c. treatment (0.05 mg/kg).

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

    PubMed

    Oretti, Rossana

    2015-10-01

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

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

    PubMed Central

    2010-01-01

    Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel®) every four weeks. All patients were German nationals and Caucasian. When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH) levels were successfully reduced (in three patients GH <2.5 ng/ml was achieved). Insulin-like growth factor 1 levels were normalized in three patients and decreased in two patients. One patient failed to show a biochemical response to lanreotide therapy or pegvisomant therapy. Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. Conclusions These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat. PMID:20211008

  20. SU-E-T-244: Motion Control Challenges in High Dose Rate Brachytherapy

    SciTech Connect

    Hyvarinen, M; Leventouri, T; Pella, S; Dumitru, N

    2014-06-01

    Purpose: High dose rate (HDR) brachytherapy dose distribution is highly localized and has a very sharp fall-off. Thus the one of the most important part of the treatment is the localization and immobilization of the applicator from the implantation to the setup verification to the treatment delivery. The smallest motions of the patient can induce a small rotation, tilt, or translational movement of the applicator that can convert into miss of a significant part of the tumor or to over irradiating a nearby critical organ.The purpose of this study is to revise most of the HDR types of treatments with their applicators and their localization challenges. Since every millimeter of misplacement counts the study will look into the necessity of increasing the immobilization for several types of applicators. Methods: The study took over 136 plans generated by the treatment planning system (TPS) looking into the applicator placement in regard to the organs at risk (OR) and simulated the three possible displacements at the hottest dose point on the critical organ for several accessories to evaluate the variation of the delivered dose at the point due to the displacement. Results: Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment. Conclusion: This study data indicates that an improvement of the immobilization devices for HDR is absolutely necessary. Better applicator fixation devices are required too. Developing new immobilization devices for all the applicators is recommended.

  1. Comparison of low- and high-dose recombinant activated factor VII for postcardiac surgical bleeding

    PubMed Central

    Habib, Aly Makram

    2016-01-01

    Aim of the Study: A retrospective observational study to compare safety and efficacy of high and low doses of recombinant activated factor VIIa (rFVIIa) in severe postcardiac surgical bleeding. Patients and Methods: From 2004 to 2014, all patients who received rFVIIa for bleeding after cardiac surgery were included and arranged in two groups; Group 1: Low dose (40–50 mcg/kg) (n = 98) and Group 2: High dose (90–120 mcg/kg) (n = 156). Results: There was no significant difference in demographic and surgical characteristics of both groups on admission to Cardiac Surgical Intensive Care Unit (CSICU). There was no significant difference between the two groups regarding the reduction in chest tube bleeding in the first 6 h or the transfusion requirement in the 24 h after admission to CSICU. A total of 15 patients (5.9%) had thromboembolic adverse events. (Seven (7.1%) patients in Group 1 compared to 8 (5.1%) patients in Group 2, P = 0.58). There were no significant differences in all-cause mortality at 30 days (2% in Group 1 vs. 3.2% in Group 2, P = 0.6) and at hospital discharge between the two study groups (6.1% in Group 1 vs. 8.3% in Group 2, P = 0.5), respectively. There was no significant difference between the two groups regarding the need for re-exploration, days on mechanical ventilation, CSICU, or hospital stay. Conclusion: In this report, Low-dose rFVIIa showed equivalent efficacy and safety to high-dose rFVIIa. Further prospective randomized studies are needed to confirm these findings. PMID:27688624

  2. Combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C (HibMenC) or serogroup C and Y-tetanus toxoid conjugate (and HibMenCY) vaccines are well-tolerated and immunogenic when administered according to the 2,3,4 months schedule with a fourth dose at 12-18 months of age.

    PubMed

    Habermehl, Pirmin; Leroux-Roels, Geert; Sänger, Roland; Mächler, Gudrun; Boutriau, Dominique

    2010-08-01

    Combined HibMenCY and HibMenC conjugate vaccines may facilitate inclusion of vaccination against MenC and MenY into routine vaccination schedules, without additional injections. Immunogenicity and reactogenicity of vaccination with three different formulations of a novel HibMenCY-conjugate vaccine, or a HibMenC-conjugate vaccine was assessed. Infants were randomized to receive either Hib(2.5 µg)-MenC(5 µg)-MenY(5 µg)-TT, Hib(5 µg)-MenC(10 µg)-MenY(10 µg)-TT, Hib(5 µg)-MenC(5 µg)-MenY(5 µg)-TT or Hib(5 µg)-MenC(5 µg)-TT vaccines co-administered with DTPa-HBV-IPV at 2-3-4 months of age. Controls received licensed conjugate MenC-CRM197 vaccine co-administered with DTPa-HBV-IPV/Hib. A fourth dose was administered to a subset of children at age 12-18 months. Anti-PRP concentrations and meningococcal bactericidal (rSBA-MenC/Y) titres were measured prior to and one month post third and fourth vaccination dose. Solicited local, general symptoms and unsolicited adverse events were recorded for 7 and 30 days after each vaccination, respectively. Post dose 3, all subjects had anti-PRP antibody levels ≥ 0.15 µg/ml and rSBA-MenC ≥ 1:8. 97.0%-98.6% of HibMenCY recipients had rSBA-MenY ≥ 1:8. Pre-dose-4, 95.6%-100% of HibMenCY and HibMenC recipients had anti-PRP ≥ 0.15 µg/ml and 90.7%-97.6% recipients had rSBA-MenC titres ≥ 1:8. In HibMenCY groups, 78.6%-86.7% had persisting rSBA-MenY ≥ 1:8. The post-dose-4 response was robust after all vaccines with all subjects having anti-PRP ≥ 1 µg/ml and 92.3%-100% rSBA-MenC ≥ 1:128. All HibMenCY recipients had rSBA-MenY ≥ 1:128. Vaccination with the novel Hib-meningococcal vaccines had a safety profile similar to control. HibMenCY and HibMenC conjugate vaccine formulations given at 2-3-4 months of age with a fourth dose in the second year of life were immunogenic and had a comparable safety profile to licensed vaccines. (study 792014 and 100381;www.clinicaltrial.govID:NCT00129116)

  3. Dosimetric comparison of Acuros™ BV with AAPM TG43 dose calculation formalism in breast interstitial high-dose-rate brachytherapy with the use of metal catheters

    PubMed Central

    Nagarajan, Vivekanandan; Reddy K, Sathyanarayana; Karunanidhi, Gunaseelan; Singhavajala, Vivekanandam

    2015-01-01

    Purpose Radiotherapy for breast cancer includes different techniques and methods. The purpose of this study is to compare dosimetric calculations using TG-43 dose formalism and Varian Acuros™ BV (GBBS) dose calculation algorithm for interstitial implant of breast using metal catheters in high-dose-rate (HDR) brachytherapy, using 192Ir. Material and methods Twenty patients who were considered for breast conservative surgery (BCS), underwent lumpectomy and axillary dissection. These patients received perioperative interstitial HDR brachytherapy as upfront boost using rigid metal implants. Whole breast irradiation was delivered TG-43 after a gap of two weeks. Standard brachytherapy dose calculation was done by dosimetry. This does not take into account tissue heterogeneity, attenuation and scatter in the metal applicator, and effects of patient boundary. Acuros™ BV is a Grid Based Boltzmann Solver code (GBBS), which takes into consideration all the above, was used to compute dosimetry and the two systems were compared. Results Comparison of GBBS and TG-43 formalism on interstitial metal catheters shows difference in dose prescribed to CTV and other OARs. While the estimated dose to CTV was only marginally different with the two systems, there is a significant difference in estimated doses of starting from 4 to 53% in the mean value of all parameters analyzed. Conclusions TG-43 algorithm seems to significantly overestimate the dose to various volumes of interest; GBBS based dose calculation algorithm has impact on CTV, heart, ipsilateral lung, heart, contralateral breast, skin, and ribs of the ipsilateral breast side; the prescription changes occurred due to effect of metal catheters, inhomogeneities, and scatter conditions. PMID:26622230

  4. The prognostic impact of peripheral blood progenitor cell dose following high-dose therapy and autologous stem cell transplant for hematologic malignancies.

    PubMed

    Sauter, Craig S; Giralt, Sergio

    2015-06-01

    High-dose chemotherapy (HDT) followed by autologous peripheral blood progenitor cell transplant (PBPCT) has become a standard intervention in certain clinical settings of hematologic malignancies, particularly multiple myeloma and relapsed/refractory lymphoma. While the minimal required PBPCs infused, as defined by number of CD34 + cells, has been relatively well delineated for adequate hematopoietic recovery post-HDT, optimal PBPC dose has not been clearly defined. This is particularly relevant in the context of retrospective data suggesting improved survival outcomes with increased PBPC doses. The potential confounding of these data as they relate to disease risk is discussed within this review. Additionally, other retrospective data have suggested that enhanced quantitative lymphocyte subset reconstitution post-HDT-PBPCT may confer progression-free and overall survival advantage. These reported series herein reviewed may inform discussion of future, prospective clinical trials with the intent of defining optimal autologous PBPC dose following HDT, especially as it may relate to metrics beyond hematopoietic recovery.

  5. Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer

    PubMed Central

    Hansen, Jorgen L.; Bhagwat, Mandar S.; O'Farrell, Desmond A.; Friesen, Scott; Harris, Thomas C.; Damato, Antonio L.; Cormack, Robert A.; Martin, Neil E.; Devlin, Phillip M.

    2016-01-01

    Purpose In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA) and the initial clinical experience in high-dose-rate (HDR) brachytherapy treatment of esophageal cancer, using this applicator. Material and methods Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT) images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient's response to the treatment were elaborated as well. Results The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction) was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. Conclusions The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can lead to improved

  6. Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer

    PubMed Central

    Hansen, Jorgen L.; Bhagwat, Mandar S.; O'Farrell, Desmond A.; Friesen, Scott; Harris, Thomas C.; Damato, Antonio L.; Cormack, Robert A.; Martin, Neil E.; Devlin, Phillip M.

    2016-01-01

    Purpose In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA) and the initial clinical experience in high-dose-rate (HDR) brachytherapy treatment of esophageal cancer, using this applicator. Material and methods Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT) images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient's response to the treatment were elaborated as well. Results The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction) was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. Conclusions The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can lead to improved

  7. [Successful collection of peripheral blood stem cells mobilized by high-dose etoposide for patients with chemotherapy-resistant and/or poor prognostic testicular cancer].

    PubMed

    Nakagawa, S; Sugimoto, K; Mikami, K; Watanabe, H; Sonoda, Y; Kuzuyama, Y; Abe, T; Fujii, H

    1994-04-01

    Clinical effects of peripheral blood stem cell autotransplantation (PBSCT) after ultra high-dose chemotherapy were evaluated in patients with chemotherapy-resistant and/or poor prognostic testicular cancer. Four patients with testicular cancer, who had high-risk malignancy, were treated with high-dose etoposide (500 mg/m2 x 4 days) in order to collect peripheral blood stem cells. After the administration of high-dose etoposide, rG-CSF (250 micrograms/body) was administered from nadir state. Blood mononuclear cells were collected using a Fenwall CS-3000 blood cell separator. Fractions enriched for stem cells were obtained by discontinuous Percoll gradient centrifugation and were stored in liquid nitrogen using patient's sera and DMSO. The mean number of peripheral blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one apheresis was 22.3 x 10(5)/kg body weight. In addition, CFU-GM more than 2.0 x 10(5)/kg body weight could be collected in each apheresis, which was though to be sufficient dosis to perform PBSCT in safe, based upon our previous studies. All the patients were treated by a combination of cisplatin (20 mg/m2 x 5 days), etoposide (100 mg/m2 x 5 days) and bleomycin (15 mg x 3 days). Three patients responded to BEP therapy and obtained a CR, however, remaining 1 patient failed to achieve CR, who was later treated by ultrahigh-dose chemotherapy including carboplatin (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and cyclophosphamide (50 mg/kg x 2 days) followed by PBSCT. He responded to this therapy and obtained a CR for 10 months. The results suggested the method was promising for patients with chemotherapy-resistant and/or poor prognostic testicular cancer.

  8. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma

    PubMed Central

    Veal, Gareth J.; Errington, Julie; Rowbotham, Sophie E.; Illingworth, Nicola A.; Malik, Ghada; Cole, Michael; Daly, Ann K.; Pearson, Andrew D.J.; Boddy, Alan V.

    2012-01-01

    Purpose To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cisRA disposition in high-risk neuroblastoma patients. Experimental Design 13cisRA (160mg/m2 or 5.33mg/kg/day) was administered to 103 patients ≤21 years and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. 71 patients were recruited to a dose adjustment group, targeting a 13-cisRA Cmax of 2μM, with dose increases of 25-50% implemented for patients with Cmax values <2μM. A population pharmacokinetic model was applied and polymorphisms in relevant cytochrome P450 genes analyzed. Results 13-cisRA Cmax values ranged from 0.42–11.2μM, with 34/103 (33%) patients failing to achieve a Cmax >2μM. Dose increases carried out in 20 patients in the dose adjustment study group led to concentrations >2μM in 18 patients (90%). 8/11 (73%) patients <12kg, receiving a dose of 5.33mg/kg, failed to achieve a Cmax ≥2μM. Significantly lower Cmax values were observed for patients treated with 5.33mg/kg versus 160mg/m2 (1.9±1.2 versus 3.1±2.0μM; mean±SD; P=0.023). Cmax was higher in patients who swallowed 13-cisRA capsules as compared to receiving the drug extracted from capsules (4.0±2.2 versus 2.6±1.8μM; P=0.0012). The target Cmax was achieved by 93% (25/27) versus 55% (42/76) of patients in these two groups respectively. No clear relationships were found between genetic variants and 13-cisRA pharmacokinetic parameters. Conclusions Dosing regimen and method of administration have a marked influence on 13-cisRA plasma concentrations. Body weight-based dosing should not be implemented for children <12kg and pharmacological data support higher doses for children unable to swallow 13-cisRA capsules. PMID:23087409

  9. TLD skin dose measurements and acute and late effects after lumpectomy and high-dose-rate brachytherapy only for early breast cancer

    SciTech Connect

    Perera, Francisco . E-mail: francisco.perera@lrcc.on.ca; Chisela, Frank; Stitt, Larry; Engel, Jay; Venkatesan, Varagur

    2005-08-01

    Purpose: This report examines the relationships between measured skin doses and the acute and late skin and soft tissue changes in a pilot study of lumpectomy and high-dose-rate brachytherapy only for breast cancer. Methods and Materials: Thirty-seven of 39 women enrolled in this pilot study of high-dose-rate brachytherapy (37.2 Gy in 10 fractions b.i.d.) each had thermoluminescent dosimetry (TLD) at 5 points on the skin of the breast overlying the implant volume. Skin changes at TLD dose points and fibrosis at the lumpectomy site were documented every 6 to 12 months posttreatment using a standardized physician-rated cosmesis questionnaire. The relationships between TLD dose and acute skin reaction, pigmentation, or telangiectasia at 5 years were analyzed using the GEE algorithm and the GENMOD procedure in the SAS statistical package. Fisher's exact test was used to determine whether there were any significant associations between acute skin reaction and late pigmentation or telangiectasia or between the volumes encompassed by various isodoses and fibrosis or fat necrosis. Results: The median TLD dose per fraction (185 dose points) multiplied by 10 was 9.2 Gy. In all 37 patients, acute skin reaction Grade 1 or higher was observed at 5.9% (6 of 102) of dose points receiving 10 Gy or less vs. 44.6% (37 of 83) of dose points receiving more than 10 Gy (p < 0.0001). In 25 patients at 60 months, 1.5% telangiectasia was seen at dose points receiving 10 Gy or less (1 of 69) vs. 18% (10 of 56) telangiectasia at dose points receiving more than 10 Gy (p 0.004). Grade 1 or more pigmentation developed at 1.5% (1 of 69) of dose points receiving less than 10 Gy vs. 25% (14 of 56) of dose points receiving more than 10 Gy (p < 0.001). A Grade 1 or more acute skin reaction was also significantly associated with development of Grade 1 or more pigmentation or telangiectasia at 60 months. This association was most significant for acute reaction and telangiectasia directly over the

  10. Photonuclear dose calculations for high-energy photon beams from Siemens and Varian linacs.

    PubMed

    Chibani, Omar; Ma, Chang-Ming Charlie

    2003-08-01

    The dose from photon-induced nuclear particles (neutrons, protons, and alpha particles) generated by high-energy photon beams from medical linacs is investigated. Monte Carlo calculations using the MCNPX code are performed for three different photon beams from two different machines: Siemens 18 MV, Varian 15 MV, and Varian 18 MV. The linac head components are simulated in detail. The dose distributions from photons, neutrons, protons, and alpha particles are calculated in a tissue-equivalent phantom. Neutrons are generated in both the linac head and the phantom. This study includes (a) field size effects, (b) off-axis dose profiles, (c) neutron contribution from the linac head, (d) dose contribution from capture gamma rays, (e) phantom heterogeneity effects, and (f) effects of primary electron energy shift. Results are presented in terms of absolute dose distributions and also in terms of DER (dose equivalent ratio). The DER is the maximum dose from the particle (neutron, proton, or alpha) divided by the maximum photon dose, multiplied by the particle quality factor and the modulation scaling factor. The total DER including neutrons, protons, and alphas is about 0.66 cSv/Gy for the Siemens 18 MV beam (10 cm x 10 cm). The neutron DER decreases with decreasing field size while the proton (or alpha) DER does not vary significantly except for the 1 cm x 1 cm field. Both Varian beams (15 and 18 MV) produce more neutrons, protons, and alphas particles than the Siemens 18 MV beam. This is mainly due to their higher primary electron energies: 15 and 18.3 MeV, respectively, vs 14 MeV for the Siemens 18 MV beam. For all beams, neutrons contribute more than 75% of the total DER, except for the 1 cm x 1 cm field (approximately 50%). The total DER is 1.52 and 2.86 cSv/Gy for the 15 and 18 MV Varian beams (10 cm x 10 cm), respectively. Media with relatively high-Z elements like bone may increase the dose from heavy charged particles by a factor 4. The total DER is sensitive to

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

    PubMed

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

    2015-01-01

    Maternal folic acid supplementation had a positive effect on preventing neural tube defects (NTDs), but its effects in infant asthma remained unclear. A hospital-based case-control study was conducted with outpatients between March 2010 and March 2011 including 150 onset infant asthma cases and 212 controls, together with a meta-analysis involving 14,438 participants, was performed. The association between maternal folic acid supplementation and the risk of infant asthma was not significant either in the meta-analysis (OR = 1.06, 95% CI =0.99-1.14) or in the case-control study (OR = 0.72, 95% CI =0.37-1.39). However, quantitative analysis of the supplementation dose demonstrated that the risk of infant asthma significantly increased for the infants whose mother were with high-dose supplementation (>72,000 µg•d; OR = 3.16, 95% CI =1.15-8.71) after adjusting for confounding factors in the case-control study. Meanwhile, the risk of infant asthma significantly decreased for the infants whose mother were with low-dose supplementation (<36,000 µg•d; OR = 0.36, 95% CI =0.17-0.77). A high dose of folic acid supplementation for mother during pregnancy was associated with an increased risk of infant asthma, whereas supplementation with a relatively low-dose was associated with a decreased risk of infant asthma. These findings should be further investigated in a large population.

  12. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.; Kasap, S. O.

    2014-02-01

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm3+) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm3+-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm3+-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm2+ to Sm3+ reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm2+ to Sm3+ reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

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

    PubMed Central

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

    2016-01-01

    Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies. PMID:27162802

  14. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    SciTech Connect

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C. Kasap, S. O.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.

    2014-02-14

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm{sup 3+}) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm{sup 3+}-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm{sup 3+}-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm{sup 2+} to Sm{sup 3+} reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm{sup 2+} to Sm{sup 3+} reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  15. Dose response of multiple parameters for calyculin A-induced premature chromosome condensation in human peripheral blood lymphocytes exposed to high doses of cobalt-60 gamma-rays.

    PubMed

    Lu, Xue; Zhao, Hua; Feng, Jiang-Bin; Zhao, Xiao-Tao; Chen, De-Qing; Liu, Qing-Jie

    2016-09-01

    Many studies have investigated exposure biomarkers for high dose radiation. However, no systematic study on which biomarkers can be used in dose estimation through premature chromosome condensation (PCC) analysis has been conducted. The present study aims to screen the high-dose radiation exposure indicator in calyculin A-induced PCC. The dose response of multiple biological endpoints, including G2/A-PCC (G2/M and M/A-PCC) index, PCC ring (PCC-R), ratio of the longest/shortest length (L/L ratio), and length and width ratio of the longest chromosome (L/B ratio), were investigated in calyculin A-induced G2/A-PCC spreads in human peripheral blood lymphocytes exposed to 0-20Gy (dose-rate of 1Gy/min) cobalt-60 gamma-rays. The G2/A-PCC index was decreased with enhanced absorbed doses of 4-20Gy gamma-rays. The G2/A PCC-R at 0-12Gy gamma-rays conformed to Poisson distribution. Three types of PCC-R were scored according to their shape and their solidity or hollowness. The frequencies of hollow PCC-R and PCC-R including or excluding solid ring in G2/A-PCC spreads were enhanced with increased doses. The length and width of the longest chromosome, as well as the length of the shortest chromosome in each G2/M-PCC or M/A-PCC spread, were measured. All L/L or L/B ratios in G2/M-PCC or M/A-PCC spread increased with enhanced doses. A blind test with two new irradiated doses was conducted to validate which biomarker could be used in dose estimation. Results showed that hollow PCC-R and PCC-R including solid ring can be utilized for accurate dose estimation, and that hollow PCC-R was optimal for practical application. PMID:27542714

  16. The Use of Very High-Doses of Baclofen for the Treatment of Alcohol-Dependence: A Case Series

    PubMed Central

    de Beaurepaire, Renaud

    2014-01-01

    Baclofen, particularly high-dose baclofen, has recently emerged as a treatment of major interest for alcohol-dependence. However, baclofen has many potentially dangerous side effects, and the maximal dose of baclofen that may be used is a matter of discussion. Here, the author analyses the medical charts of the last 100 patients seen in his clinic, 17 of whom have been taking a very high dose of baclofen, which is to say, more than 300 mg/day. The analysis of the charts shows that the very high-doses baclofen were justified in almost all the cases. Side effects are analyzed. PMID:25346700

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

    PubMed

    Palmer, Antony; Mzenda, Bongile

    2009-12-21

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

  18. Effect of high-energy X-ray doses on bone elastic properties and residual strains.

    PubMed

    Singhal, A; Deymier-Black, Alix C; Almer, J D; Dunand, D C

    2011-11-01

    Bone X-ray irradiation occurs during medical treatments, sterilization of allografts, space travel and in vitro studies. High doses are known to affect the post-yield properties of bone, but their effect on the bone elastic properties is unclear. The effect of such doses on the mineral-organic interface has also not been adequately addressed. Here, the evolution of elastic properties and residual strains with increasing synchrotron X-ray dose (5-3880 kGy) is examined on bovine cortical bone. It is found that these doses affect neither the degree of nanometer-level load transfer between the hydroxyapatite (HAP) platelets and the collagen up to stresses of -60 MPa nor the microscopic modulus of collagen fibrils (both measured by synchrotron X-ray scattering during repeated in situ loading and unloading). However, the residual elastic strains in the HAP phase decrease markedly with increased irradiation, indicating damage at the HAP-collagen interface. The HAP residual strain also decreases after repeated loading/unloading cycles. These observations can be explained by temporary de-bonding at the HAP/collagen interface (thus reducing the residual strain), followed by rapid re-bonding (so that load transfer capability is not affected).

  19. Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy

    SciTech Connect

    Schaake-Koning, C.S.; Schuster-Uitterhoeve, L.; Hart, G.; Gonzalez, D.G.

    1983-07-01

    A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with >65 Gy, the two year local control was 35%. If treated with <65 Gy the one year local control was less than or equal to 40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was <100 cm/sup 2/, the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis was found.

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

    PubMed Central

    Anwer, Faiz; Yun, Seongseok; Nair, Anju; Ahmad, Yusuf; Krishnadashan, Ravitharan; Deeg, H. Joachim

    2015-01-01

    Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D) immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag. PMID:26180646

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

    PubMed

    Anwer, Faiz; Yun, Seongseok; Nair, Anju; Ahmad, Yusuf; Krishnadashan, Ravitharan; Deeg, H Joachim

    2015-01-01

    Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D) immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag. PMID:26180646

  2. Ultrastructural changes in the parenchymal liver cells of rats treated with high doses of rifampicin.

    PubMed Central

    Piriou, A.; Maissiat, R.; Jacqueson, A.; Warnet, J. M.; Claude, J. R.

    1987-01-01

    Ultrastructural study of hepatic parenchyma was carried out in female Wistar rats after they had received high doses (400 mg X kg-1) of rifampicin for 1, 2, 4, 6 and 8 days. Morphological changes in the endoplasmic reticulum, Golgi apparatus and mitochondria were observed as early as day 1 of intoxication. These changes corroborate the biochemical data available regarding RFP-induced fatty liver. Images Fig. 1 Fig. 2 Fig. 3 & 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:3580280

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

    PubMed

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

    2016-01-01

    Microalgae possess higher photosynthetic efficiency and accumulate more neutral lipids when supplied with high-dose CO2. However, the nature of lipid accumulation under conditions of elevated CO2 has not been fully elucidated so far. We now revealed that the enhanced lipid accumulation of Chlorella in high-dose CO2 was as efficient as under heterotrophic conditions and this may be attributed to the driving of enlarged carbon source. Both photoautotrophic and heterotrophic cultures were established by using Chlorella sorokiniana CS-1. A series of changes in the carbon fixation, lipid accumulation, energy conversion, and carbon-lipid conversion under high-dose CO2 (1-10%) treatment were characterized subsequently. The daily carbon fixation rate of C. sorokiniana LS-2 in 10% CO2 aeration was significantly increased compared with air CO2. Correspondingly, double oil content (28%) was observed in 10% CO2 aeration, close to 32.3% produced under heterotrophic conditions. In addition, with 10% CO2 aeration, the overall energy yield (Ψ) in Chlorella reached 12.4 from 7.3% (with air aeration) because of the enhanced daily carbon fixation rates. This treatment also improved the energetic lipid yield (Ylipid/Es) with 4.7-fold, tending to the heterotrophic parameters. More significantly, 2.2 times of carbon-lipid conversion efficiency (ηClipid/Ctotal, 42.4%) was observed in 10% CO2 aeration, towards to 53.7% in heterotrophic cultures, suggesting that more fixed carbon might flow into lipid synthesis under both 10% CO2 aeration and heterotrophic conditions. Taken together, all our evidence showed that 10% CO2 may push photoautotrophic Chlorella to display heterotrophic-like efficiency at least in lipid production. It might bring us an efficient model of lipid production based on microalgal cells with high-dose CO2, which is essential to sustain biodiesel production at large scales. PMID:26712624

  4. Low-dose insulin infusions in diabetic patients with high insulin requirements.

    PubMed

    Dandona, P; Foster, M; Healey, F; Greenbury, E; Beckett, A G

    1978-08-01

    Six patients with high insulin requirements (range 120-3000 units daily) have been infused with much smaller doses (range 50-63 units daily) of insulin intravenously. All six maintained adequate glucose homoestasis on this regimen. It is suggested that subcutaneous tissue at the site of injection may alter insulin or impair its absorption. Insulin resistance in some patients may be due to these mechanisms.

  5. Phase-Diverse Coherent Diffractive Imaging: High Sensitivity with Low Dose

    NASA Astrophysics Data System (ADS)

    Putkunz, Corey T.; Clark, Jesse N.; Vine, David J.; Williams, Garth J.; Pfeifer, Mark A.; Balaur, Eugeniu; McNulty, Ian; Nugent, Keith A.; Peele, Andrew G.

    2011-01-01

    This Letter demonstrates that coherent diffractive imaging (CDI), in combination with phase-diversity methods, provides reliable and artefact free high-resolution images. Here, using x rays, experimental results show a threefold improvement in the available image contrast. Furthermore, in conditions requiring low imaging dose, it is demonstrated that phase-diverse CDI provides a factor of 2 improvement in comparison to previous CDI techniques.

  6. High-dose therapy and innovative approaches to treatment of multiple myeloma.

    PubMed

    Barlogie, B

    2001-04-01

    High-dose therapy in multiple myeloma (MM) appears to be superior in terms of event-free survival and overall survival compared with conventional therapy. Melphalan-based high-dose therapy increases complete remission rates from 5% to 50% and extends event-free survival beyond 3 years and overall survival beyond 6 years. Critical disease features associated with durable complete remission, event-free survival, and overall survival include the absence of chromosome 13 deletion, low beta(2)-microglobulin, and low C-reactive protein levels. Data on 1,000 patients enrolled in tandem high-dose trials show that chromosome 13 deletion is an important prognostic feature. The timely application of a second cycle of high-dose therapy extends event-free survival and overall survival markedly in MM patients with low beta(2)-microglobulin levels. Long-term results of the total therapy trial indicate that patients who do not have chromosome 13 deletions and present with low C-reactive protein and beta(2)-microglobulin levels have longer complete remissions than patients lacking these prognostic factors. Thalidomide shows clear evidence of antitumor activity possibly because of its antiangiogenic activity. Magnetic resonance imaging (MRI) indicates that bone marrow lesions become smaller or disappear while patients receive dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation chemotherapy and that patients who have a compete remission after diagnostic MRI have a superior event-free and overall survival than those who still have persistent MRI lesions. Prospective trials are underway to evaluate the effectiveness of consolidation therapy (total therapy II).

  7. False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

    PubMed

    Tenore, Peter L

    2012-01-01

    In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

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

    PubMed

    Asadi-Pooya, Ali A

    2015-04-01

    Most experts agree that folic acid supplementation is a key preconception intervention, particularly in women with epilepsy who take anti-epileptic drugs (AEDs). Primary prevention of neural tube defect through folic acid supplementation results in reduction of risk in an otherwise healthy population. The current folic acid supplementation recommendation is that all women of childbearing potential be supplemented with at least 0.4 mg of folic acid daily prior to conception and during pregnancy. It is recommended that all women with epilepsy and of childbearing potential be supplemented with folic acid daily prior to conception and during pregnancy. However, considering the potential significant drug-drug interactions between high doses of folic acid and some AEDs in patients with epilepsy and also with the emerging evidence from animal studies that high levels of folic acid throughout gestation may have adverse effects on fetal brain development, it is not suggested to advocate high dose folic acid supplementation in women with epilepsy until more information is available about its appropriate, safe and optimal dosing. PMID:25891927

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

    PubMed

    Asadi-Pooya, Ali A

    2015-04-01

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

  10. [Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

    PubMed

    Sugimoto, K; Nakagawa, S; Mikami, K; Watanabe, H; Sonoda, Y; Abe, T; Fujii, H

    1994-02-01

    This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

  11. Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

    NASA Astrophysics Data System (ADS)

    Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

    2015-05-01

    The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

  12. High-Dose 131I-Tositumomab (Anti-CD20) Radioimmunotherapy for Non-Hodgkin's Lymphoma: Adjusting Radiation Absorbed Dose to Actual Organ Volumes

    SciTech Connect

    Rajendran, Joseph G.; Fisher, Darrell R.; Gopal, A K.; Durack, L. D.; Press, O. W.; Eary, Janet F.

    2004-06-01

    Radioimmunotherapy (RIT) using 131I-tositumomab has been used successfully to treat relapsed or refractory B-cell non-Hodgin's lymphoma (NHL). Our approach to treatment planning has been to determine limits on radiation absorbed close to critical nonhematopoietic organs. This study demonstrates the feasibility of using CT to adjust for actual organ volumes in calculating organ-specific absorbed dose estimates. Methods: Records of 84 patients who underwent biodistribution studies after a trace-labeled infusion of 131I-tositumomab for RIT (January 1990 and April 2003) were reviewed. Serial planar -camera images and whole-body Nal probe counts were obtained to estimate 131I-antibody source-organ residence times as recommended by the MIRD Committee. The source-organ residence times for standard man or woman were adjusted by the ratio of the MIRD phantom organ mass to the CT-derived organ mass. Results: The mean radiation absorbed doses (in mGy/MBq) for our data using the MIRD model were lungs= 1.67; liver= 1.03; kidneys= 1.08; spleen= 2.67; and whole body= 0.3; and for CT volume-adjusted organ volumes (in mGy/MBq) were lungs= 1.30; liver= 0.92; kidneys= 0.76; spleen= 1.40; and whole body= 0.22. We determined the following correlation coefficients between the 2 methods for the various organs; lungs, 0.49; (P= 0.0001); liver, 0.64 (P= 0.004); kidneys, 0.45 (P= 0.0001), for the residence times. For therapy, patients received mean 131I administered activities of 19.2 GBq (520 mCi) after adjustment for CT-derived organ mass compared with 16.0 GBq (433 mCi) that would otherwise have been given had therapy been based only using standard MIRD organ volumes--a statistically significant difference (P= 0.0001). Conclusion: We observed large variations in organ masses among our patients. Our treatments were planned to deliver the maximally tolerated radiation dose to the dose-limiting normal organ. This work provides a simplified method for calculating patient-specific radiation

  13. An absolute dose determination of helical tomotherapy accelerator, TomoTherapy High-Art II

    SciTech Connect

    Bailat, Claude J.; Buchillier, Thierry; Pachoud, Marc; Moeckli, Raphaeel; Bochud, Francois O.

    2009-09-15

    Purpose: A helical tomotherapy accelerator presents a dosimetric challenge because, to this day, there is no internationally accepted protocol for the determination of the absolute dose. Because of this reality, we investigated the different alternatives for characterizing and measuring the absolute dose of such an accelerator. We tested several dosimetric techniques with various metrological traceabilities as well as using a number of phantoms in static and helical modes. Methods: Firstly, the relationship between the reading of ionization chambers and the absorbed dose is dependent on the beam quality value of the photon beam. For high energy photons, the beam quality is specified by the tissue phantom ratio (TPR{sub 20,10}) and it is therefore necessary to know the TPR{sub 20,10} to calculate the dose delivered by a given accelerator. This parameter is obtained through the ratio of the absorbed dose at 20 and 10 cm depths in water and was measured in the particular conditions of the tomotherapy accelerator. Afterward, measurements were performed using the ionization chamber (model A1SL) delivered as a reference instrument by the vendor. This chamber is traceable in absorbed dose to water in a Co-60 beam to a water calorimeter of the American metrology institute (NIST). Similarly, in Switzerland, each radiotherapy department is directly traceable to the Swiss metrology institute (METAS) in absorbed dose to water based on a water calorimeter. For our research, this traceability was obtained by using an ionization chamber traceable to METAS (model NE 2611A), which is the secondary standard of our institute. Furthermore, in order to have another fully independent measurement method, we determined the dose using alanine dosimeters provided by and traceable to the British metrology institute (NPL); they are calibrated in absorbed dose to water using a graphite calorimeter. And finally, we wanted to take into account the type of chamber routinely used in clinical

  14. High dose grass pollen tablets used for hyposensitization in hay fever patients. A one-year double blind placebo-controlled study.

    PubMed

    Mosbech, H; Dreborg, S; Madsen, F; Ohlsson, H; Stahl Skov, P; Taudorf, E; Weeke, B

    1987-08-01

    Previous, placebo-controlled clinical trials with oral hyposensitization in grass pollinosis have been disappointing. Since the results possibly could be explained by too low doses of ingested allergens, the present study was initiated to evaluate the effect of high doses of allergens. Forty-two adults with symptoms in the grass pollen season and with grass pollen sensitivity demonstrated by skin prick test and conjunctival provocation test were included. Enterosoluble tablets were administered daily for 1 year. Twenty-two patients, who completed the study, received placebo and 17 mixed grass pollen allergens from rye grass, timothy grass, cultivated rye and velvet grass. Evaluated either by self-assessment or by symptom and medicine score before and after treatment, the group receiving pollens did not improve clinically compared the controls. During the study, conjunctival sensitivity decreased equally in the two groups, and changes in specific IgE, allergen-induced histamine release from blood cells and skin prick test were insignificant and with no difference between groups. Five patients, who received pollen allergens, had episodes of urticaria or angioedema, and a further three patients on the same treatment had slight gastrointestinal side effects. In conclusion, enterosoluble grass pollen allergens in contrast to birch pollens did not have any therapeutic effect, even in doses more than 4,000 times higher than those used for subcutaneous hypersensitization. The reason may be degradation of allergens before the immune system is reached.

  15. Calculating drug doses.

    PubMed

    2016-09-01

    Numeracy and calculation are key skills for nurses. As nurses are directly accountable for ensuring medicines are prescribed, dispensed and administered safely, they must be able to understand and calculate drug doses. PMID:27615351

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

    SciTech Connect

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-08-01

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

  17. High-dose regions versus likelihood of cure after prostate brachytherapy

    SciTech Connect

    Wallner, Kent . E-mail: kent.wallner@med.va.gov; Merrick, Gregory; Sutlief, Steven; True, Laurence; Butler, Wayne

    2005-05-01

    Purpose: To analyze the effect of high-dose regions on biochemical cancer control rates after prostate brachytherapy. Methods and Materials: Patients with 1997 American Joint Committee on Cancer clinical Stage T1c-T2a prostate carcinoma (Gleason grade 5-6, prostate-specific antigen level 4-10 ng/mL) were randomized to implantation with {sup 125}I (144 Gy) vs. {sup 103}Pd (125 Gy, National Institute of Standards and Technology 1999). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. Of the 313 patients entered in the protocol, 270 were included in this analysis. The {sup 125}I source strength ranged from 0.4 to 0.89 mCi (median, 0.55 mCi), and the {sup 103}Pd source strength ranged from 1.3 to 1.6 mCi (median, 1.5 mCi). CT was performed within 4 h after implantation. The dosimetric parameters analyzed included the percentage of the postimplant prostate volume covered by the 100%, 150%, 200%, and 300% prescription dose (V{sub 100}, V{sub 150}, V{sub 200}, and V{sub 300}, respectively). The median time to the last follow-up for patients without failure was 2.7 years. Freedom from biochemical failure was defined as a serum prostate-specific antigen level of {<=}0.5 ng/mL at last follow-up. Patients were censored at last follow-up if their serum prostate-specific antigen level was still decreasing. Results: The mean V{sub 100}, V{sub 150}, V{sub 200}, and V{sub 300} value was 90% ({+-}8%), 63% ({+-}14), 35% ({+-}13%), and 14% ({+-}7%), respectively. Patients with a V{sub 100} of {>=}90% had a 3-year freedom from biochemical failure rate of 96% vs. 87% for those with a V{sub 100} of <90% (p = 0.0029). Overall, patients with more high-dose regions had a greater chance of biochemical control. However, when only patients with a V{sub 100} of {>=}90% were analyzed, no relationship was found between higher dose regions and the likelihood of cancer control. This lack of effect on biochemical control was apparent for both

  18. NEONATAL LOW- AND HIGH-DOSE EXPOSURE TO ESTRADIOL BENZOATE IN THE MALE RAT: I. EFFECTS ON THE PROSTATE GLAND

    EPA Science Inventory

    Neonatal Low- And High-Dose Exposure To Estradiol Benzoate In The Male Rat: 1. Effects On The Prostate Gland. Oliver Putz, Christian B. Schwartz, Steve Kim, Gerald A. LeBlanc Ralph L. Cooper, Gail S. Prins

    ABSTRACT
    Brief exposure of rats to high doses of natural estro...

  19. Efficacy of intravenously administered ibandronate in postmenopausal Korean women with insufficient response to orally administered bisphosphonates.

    PubMed

    Bae, Sung Jin; Kim, Beom-Jun; Lim, Kyeong Hye; Lee, Seung Hun; Kim, Hong Kyu; Kim, Ghi Su; Koh, Jung-Min

    2012-09-01

    We investigated rates of insufficient and over-responsiveness to orally administered bisphosphonates in postmenopausal women, and tested the efficacy of intravenous ibandronate in patients with insufficient response to orally administered bisphosphonates. Postmenopausal women were treated with either alendronate (70 mg/week; n = 88) or risedronate (35 mg/week; n = 84) for 1 year, and their response to orally administered bisphosphonates was assessed using serum C-telopeptide (CTX) levels. Insufficient responders were changed to once-quarterly intravenous ibandronate 3 mg injection (n = 13) or maintained on orally administered bisphosphonates (n = 19), according to patients' preference, for an additional 1 year. There was no significant difference in baseline characteristics between two orally administered bisphosphonate groups except the bone mineral density values at the lumbar spine. Insufficient rate was higher in the risedronate group (19.0 %) than in the alendronate group (8.0 %), using the premenopausal serum CTX median as a cut-off (P = 0.043). The over-response rate among the alendronate group (59.1 %) was significantly higher than that in the risedronate group (38.1 %), based on a serum CTX cut-off value of 0.100 ng/ml (P = 0.006). Intravenous ibandronate suppressed serum CTX levels to a significantly greater degree at 7 days after the second dosing (0.191 ± 0.110 ng/mL; P < 0.001) and 3 months after the fourth dosing (0.274 ± 0.159 ng/mL; P = 0.004) among insufficient responders, compared with post-oral/pre-intravenous levels (0.450 ± 0.134 ng/mL). Rates of insufficient and over-responsiveness to orally administered bisphosphonates were considerable, and a change to intravenous bisphosphonates may be considered in patients showing an insufficient response to orally administered bisphosphonates.

  20. High-Dose Fluoride Impairs the Properties of Human Embryonic Stem Cells via JNK Signaling

    PubMed Central

    Fu, Xin; Xie, Fang-Nan; Dong, Ping; Li, Qiu-Chen; Yu, Guang-Yan; Xiao, Ran

    2016-01-01

    Fluoride is a ubiquitous natural substance that is often used in dental products to prevent dental caries. The biphasic actions of fluoride imply that excessive systemic exposure to fluoride can cause harmful effects on embryonic development in both animal models and humans. However, insufficient information is available on the effects of fluoride on human embryonic stem cells (hESCs), which is a novel in vitro humanized model for analyzing the embryotoxicities of chemical compounds. Therefore, we investigated the effects of sodium fluoride (NaF) on the proliferation, differentiation and viability of H9 hESCs. For the first time, we showed that 1 mM NaF did not significantly affect the proliferation of hESCs but did disturb the gene expression patterns of hESCs during embryoid body (EB) differentiation. Higher doses of NaF (2 mM and above) markedly decreased the viability and proliferation of hESCs. The mode and underlying mechanism of high-dose NaF-induced cell death were further investigated by assessing the sub-cellular morphology, mitochondrial membrane potential (MMP), caspase activities, cellular reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs). High-dose NaF caused the death of hESCs via apoptosis in a caspase-mediated but ROS-independent pathway, coupled with an increase in the phospho-c-Jun N-terminal kinase (p-JNK) levels. Pretreatment with a p-JNK-specific inhibitor (SP600125) could effectively protect hESCs from NaF-induced cell death in a concentration- and time-dependent manner. These findings suggest that NaF might interfere with early human embryogenesis by disturbing the specification of the three germ layers as well as osteogenic lineage commitment and that high-dose NaF could cause apoptosis through a JNK-dependent pathway in hESCs. PMID:26859149

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

    PubMed

    Lundvig, Ditte M S; Pennings, Sebastiaan W C; Brouwer, Katrien M; Mtaya-Mlangwa, Matilda; Mugonzibwa, Emeria; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-08-15

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between epidermal keratinocytes and dermal fibroblasts are essential. We previously demonstrated that curcumin increased reactive oxygen species (ROS) formation and apoptosis in dermal fibroblasts, which could be prevented by pre-induction of the cytoprotective enzyme heme oxygenase (HO)-1. To better understand the effects of curcumin on wound repair, we now assessed the effects of high doses of curcumin on the survival of HaCaT keratinocytes and the role of the HO system. We exposed HaCaT keratinocytes to curcumin in the presence or absence of the HO-1 inducers heme (FePP) and cobalt protoporphyrin (CoPP). We then assessed cell survival, ROS formation, and caspase activation. Curcumin induced caspase-dependent apoptosis in HaCaT keratinocytes via a ROS-dependent mechanism. Both FePP and CoPP induced HO-1 expression, but only FePP protected against curcumin-induced ROS formation and caspase-mediated apoptosis. In the presence of curcumin, FePP but not CoPP induced the expression of the iron scavenger ferritin. Together, our data show that the induction of ferritin, but not HO, protects HaCaT keratinocytes against cytotoxic doses of curcumin. The differential response of fibroblasts and keratinocytes to high curcumin doses may provide the basis for improving curcumin-based wound healing therapies. PMID:26071936

  2. Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia.

    PubMed

    Maschio, Marta; Marchesi, Francesco; Dispenza, Sabrina; Dinapoli, Loredana; Sperati, Francesca; Petreri, Gianluca; Gumenyuk, Svitlana; Dessanti, Maria Laura; Zarabla, Alessia; Cantelmi, Tonino; Mengarelli, Andrea

    2016-04-01

    Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (≥3 g/m(2) die), 4 with standard dose (100 mg/m(2) die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6 months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.

  3. Efficacy of a High-Dose in Addition to Daily Low-Dose Vitamin A in Children Suffering from Severe Acute Malnutrition with Other Illnesses

    PubMed Central

    Sattar, Samima; Ahmed, Tahmeed; Rasul, Choudhury Habibur; Saha, Debasish; Salam, Mohammed Abdus; Hossain, Md Iqbal

    2012-01-01

    Background Efficacy of high-dose vitamin A (VA) in children suffering from severe acute malnutrition (SAM) has recently been questioned. This study compared the efficacy of a single high-dose (200,000 IU) in addition to daily low-dose (5000 IU) VA in the management of children suffering from SAM with diarrhea and/or acute lower respiratory tract infection (ALRI). Methods In a randomized, double-blind, controlled clinical trial in icddr,b, Bangladesh during 2005–07, children aged 6–59 months with weight-for-height <−3 Z-score and/or bipedal edema (SAM) received either a high-dose VA or placebo on admission day. Both the groups received 5,000 IU/day VA in a multivitamins drop for 15 days and other standard treatment which is similar to WHO guidelines. Results A total 260 children (130 in each group) were enrolled. All had diarrhea, 54% had concomitant ALRI, 50% had edema, 48.5% were girl with a mean±SD age of 16±10 months. None had clinical signs of VA deficiency. Mean±SD baseline serum retinol was 13.15±9.28 µg/dl, retinol binding protein was 1.27±0.95 mg/dl, and pre-albumin was 7.97±3.96 mg/dl. Median (inter quartile range) of C-reactive protein was 7.8 (2.1, 22.2) mg/L. Children of the two groups did not differ in any baseline characteristic. Over the 15 days treatment period resolution of diarrhea, ALRI, edema, anthropometric changes, and biochemical indicators of VA were similar between the groups. The high-dose VA supplementation in children with SAM did not show any adverse event. Conclusions Efficacy of daily low-dose VA compared to an additional single high-dose was not observed to be better in the management of children suffering from SAM with other acute illnesses. A single high-dose VA may be given especially where the children with SAM may leave the hospital/treatment center early. Trial Registration ClinicalTrials.gov NCT00388921 PMID:22479361

  4. High-Dose Hook Effect in 17-Hydroxyprogesterone Assay in a Patient with 21-Hydroxylase Deficiency

    PubMed Central

    Parlak, Mesut; Ellidağ, Hamit Yaşar; Türkkahraman, Doğa

    2015-01-01

    Congenital adrenal hyperplasia (CAH) describes a group of disorders characterized by enzyme defects in adrenal steroidogenesis. 21-hydroxylase deficiency (21-OHD) is the most commonly encountered form. The analysis of steroids in pediatric cases requires high-sensitivity assays. A 14-year-old Syrian girl was referred for evaluation of short stature, amenorrhea, and hirsutism. On physical examination, breast development was Tanner stage 1. She had a phallic clitoris with a single urogenital orifice. Laboratory findings revealed primary adrenal deficiency with high androgen levels and low levels of 17-hydroxyprogesterone (17-OHP), (<0.05 ng/mL) and estrogen. This unexpected result led to suspicion of a high-dose hook effect. The measurement was repeated after 1/10 dilution of serum, and a high level of 17-OHP (115.4 ng/mL) was detected with the same test-enzyme-linked immunosorbent assay (ELISA). Simple virilizing form of CAH (21-OHD) was suspected and confirmed with genetic analysis. After initiation of glucocorticoid therapy, breast development was noted along with a decrease in testosterone level and an increase in estrogen level. To our knowledge, this is the first case report of hook effect for 17-OHP immunoassay in a patient with 21-OHD. High-dose hook effect should be suspected in patients with CAH when the test results are incompatible with one another. Additionally, this case demonstrates that a high testosterone level can block aromatase activity and consequently also estrogen production and breast development. PMID:26777045

  5. Comparison of Gavage, Water Bottle, and a High-Moisture Diet Bolus as Dosing Methods for Quantitative D-xylose Administration to B6D2F1 (Mus musculus) Mice

    NASA Technical Reports Server (NTRS)

    Zimmer, J. Paul; Lewis, Sherry M.; Moyer, Jerry L.

    1993-01-01

    Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.

  6. High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand

    PubMed Central

    Nantajit, Danupon; Saengsuda, Sureerat; NaNakorn, Pattama; Saengsuda, Yuthana

    2015-01-01

    Objective(s): The aim of this study was to determine whether high-dose radioactive iodine (Na131I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. Methods: A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects’ willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dos