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Sample records for high dose omeprazole

  1. Omeprazole

    MedlinePlus

    ... Omeprazole is in a class of medications called proton-pump inhibitors. It works by decreasing the amount ... watery stools stomach pain fever People who take proton pump inhibitors such as omeprazole may be more ...

  2. Cure of refractory duodenal ulcer and infection caused by Helicobacter pylori by high doses of omeprazole and amoxicillin in a homozygous CYP2C19 extensive metabolizer patient.

    PubMed

    Furuta, T; Takashima, M; Shirai, N; Xiao, F; Hanai, H; Ohashi, K; Ishizaki, T

    2000-06-01

    A 53-year old female patient with duodenal ulcer and Helicobacter pylori infection was treated three times with a proton pump inhibitor-based triple therapy, such as lansoprazole-clarithromycin-amoxicillin (INN, amoxicilline) and lansoprazole-minocycline-cefaclor. However, the H pylori infection was not cured. A culture test revealed that her infection was a clarithromycin-resistant but amoxicillin-sensitive strain of H pylori. Moreover, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis revealed that she was a homozygous extensive metabolizer of cytochrome P450 (CYP) 2C19 (wt/wt). The usual dose of the proton pump inhibitor was therefore assumed to be insufficient for her and then she was treated with a high dose of omeprazole (120 mg/day) and amoxicillin (2,250 mg/day) for 2 weeks. The H pylori infection and the ulcer lesion were then cured. One of the factors associated with success or failure of cure of H pylori infection by the proton pump inhibitor-based triple therapy appeared to be CYP2C19 genotype status. Dual treatment with a sufficient dose of a proton pump inhibitor plus amoxicillin could cure H pylori infection even after the failure to cure H pylori infection by a usual proton pump inhibitor-based triple therapy in patients with the wt/wt homozygous extensive metabolizer genotype of CYP2C19.

  3. Pharmacokinetics of intrarectal omeprazole in alpacas.

    PubMed

    Marmulak, T; Stanley, S; Kass, P H; Wiebe, V; McKemie, D; Pusterla, N

    2010-08-01

    The purpose of this study was to evaluate the pharmacokinetics of omeprazole in three different vehicles when administered rectally to six alpacas. Alpacas were given single doses of omeprazole (4 mg/kg) in a double-blinded, randomized cross-over design with a 1 week washout period. Omeprazole formulations consisted of (1) Treatment A: omeprazole paste mixed in surgical lubricant (2) Treatment B: omeprazole capsule contents in 8.4% sodium bicarbonate and (3) Treatment C: omeprazole capsule contents in surgical lubricant and 8.4% sodium bicarbonate solution. Plasma samples were drawn at 0, 5, 10, 15, 30, 45, 60, 90, 120, 180, 300 and 480 min. Omeprazole plasma concentrations were determined by high-pressure liquid chromatography-mass spectrometry. Pharmacokinetic results demonstrated median peak plasma concentrations (C(max)) of 7.35 (3.2-15.2), 7.30 (1.7-10.9) and 8.65 (1.8-19.3) ng/mL and median area under the concentration curve (AUC((0-180))) of 747 (237-1681) min x ng/mL, 552.9 (39-1063) min x ng/mL, and 972 (107-1841) min x ng/mL for treatments A, B and C, respectively. The median half-lives were similar between groups: 38, 50, and 53 min. As a result of the low measured omeprazole plasma concentrations, it is assumed that rectal absorption of omeprazole is poor in alpacas and not an effective route of administration. PMID:20646199

  4. Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle.

    PubMed

    Nazir, Shabnam; Iqbal, Zafar; Ahmad, Lateef; Shah, Yasar; Nasir, Fazli

    2015-03-01

    Omeprazole (OMP) is effective in the treatment of gastric hyperacidity and is metabolized by CYP2C19 and CYP3A4. These enzymes are modulated by estrogen and progesterone which regulate the menstrual cycle. The variations in the pharmacokinetics (PK) of many drugs like amphetamine, benzodiazepines and caffeine have been reported during menstrual cycle. In present study, the PK of the omeprazole and its metabolites was investigated during various phases of the menstrual cycle. A single oral dose, open-label, non-controlled, pharmacokinetic study of omeprazole was conducted in healthy young/premenopausal females (n = 16). The PK of omeprazole, 5-hydroxy-omeprazole and omeprazole sulphone was evaluated in three phases of menstrual cycle. The blood samples were analyzed using reversed-phase HPLC coupled with UV detector and the PK data were evaluated. The activities of CYP2C19 and CYP3A4 were determined as AUC(OH-OMP)/AUC(OMP) and AUC(OMP-SUL)/AUC(OMP), respectively. Omeprazole showed significantly (p < 0.05) higher [Formula: see text] and CL/F in follicular and menstrual phases, respectively. The [Formula: see text] of 5-hydroxy omeprazole was also significantly (p < 0.05) higher in follicular phase. The metabolic ratios (MR) of 5-hydroxy omeprazole and omeprazole sulphone were lower in follicular phase compared with the luteal phase. The present study suggests that high estrogen levels of follicular phase may result in increased absorption of omeprazole. The lower MR for 5-hydroxy omeprazole and omeprazole sulphone in follicular phase as compared to luteal phase suggests that metabolism of omeprazole is low in follicular phase as compared to luteal phase, which is progesterone-dominant phase. However, the clinical significance for these findings needs to be determined.

  5. [A relative bioavailability study of 2 oral formulations of omeprazole after their administration in repeated doses to healthy volunteers].

    PubMed

    Richards, J P; Gimeno, M; Moreland, T A; McEwen, J

    1999-04-01

    To determine the relative bioavailability of Ulceral (study formula) with respect to Losec (reference standard formula) and establish their bioequivalence daily doses of 20 mg of omeprazole were given during 5 consecutive days to 24 healthy volunteers. No significant differences were observed in the area under the curve (AUC0-t), a parameter directly related to the inhibition of acid secretion induced by omeprazole. The confidence interval of 90% for the difference between the two formulations for AUC0-t was within the interval of acceptance (0.80-1.25). The confidence interval for the difference between the two formulations for Cmax were also within the range of acceptance (0.70-1.43). In relation to the time for achieving (Cmax (tmax), the difference between the two formulations and the confidence interval of 95% for the tmax was 0.75 (-0.5-1.75) h indicating that no significant differences were observed between the two treatments. This study confirms the bioequivalence of Ulceral with the standard reference formulation as well as the tolerability of the two formulae. PMID:10349786

  6. Pharmacokinetic Comparison of Omeprazole Granule and Suspension Forms in Children: A Randomized, Parallel Pilot Trial.

    PubMed

    Karami, S; Dehghanzadeh, G; Haghighat, M; Mirzaei, R; Rahimi, H R

    2016-03-01

    Although, omeprazole is widely used for treatment of gastric acid-mediated disorders. However, its pharmacokinetic and chemical instability does not allow simple aqueous dosage form formulation synthesis for therapy of, especially child, these patients. The aim of this study was at first preparation of suspension dosage form omeprazole and second to compare the blood levels of 2 oral formulations/dosage forms of suspension & granule by high performance liquid chromatography (HPLC). The omeprazole suspension was prepared; in this regard omeprazole powder was added to 8.4% sodium bicarbonate to make final concentration 2 mg/ml omeprazole. After that a randomized, parallel pilot trial study was performed in 34 pediatric patients with acid peptic disorder who considered usage omeprazole. Selected patients were received suspension and granule, respectively. After oral administration, blood samples were collected and analyzed for omeprazole levels using validated HPLC method. The mean omeprazole blood concentration before usage the next dose, (trough level) were 0.12±0.08 µg/ml and 0.18±0.15 µg/ml for granule and suspension groups, respectively and mean blood level after dosing (C2 peak level) were 0.68±0.61 µg/ml and 0.86±0.76 µg/ml for granule and suspension groups, respectively. No significant changes were observed in comparison 2 dosage forms 2 h before (P=0.52) and after (P=0.56) the last dose. These results demonstrate that omeprazole suspension is a suitable substitute for granule in pediatrics. PMID:26398674

  7. Lansoprazole versus omeprazole for duodenal ulcer healing and prevention of relapse: a randomized, multicenter, double-masked trial.

    PubMed

    Dobrilla, G; Piazzi, L; Fiocca, R

    1999-08-01

    The aim of this randomized, multicenter, double-masked, parallel-group study was to compare the efficacy of lansoprazole with that of omeprazole monotherapy in duodenal ulcer healing and prevention of relapse. A total of 251 patients with duodenal ulcer were treated with either lansoprazole 30 mg/d (n = 167) or omeprazole 40 mg/d (n = 84). Patients with healed ulcers were then randomly allocated to 12 months of maintenance therapy with lansoprazole 15 mg/d (n = 74), lansoprazole 30 mg/d (n = 71), or omeprazole 20 mg/d (n = 73). Healing rates at 4 weeks (intent-to-treat analysis) were 93.9% (95% confidence interval [CI], 90.2% to 97.6%) with lansoprazole and 97.5% (95% CI, 93.7% to 100%) with omeprazole; there were no significant differences between groups. Endoscopic relapse rates after 6 months were 4.5% (95% CI, 0% to 10.6%) with lansoprazole 15 mg, 0% with lansoprazole 30 mg, and 6.3% (95% CI, 1.5% to 12.5%) with omeprazole 20 mg, compared with 3.3% (95% CI, 0% to 8.2%), 0%, and 3.5% (95% CI, 0% to 8.8%), respectively, at 12 months. Again, there were no significant differences between groups. The incidence of adverse events during acute treatment was 6.0% and 7.1% in the lansoprazole and omeprazole groups, respectively; during maintenance therapy, the incidences were 12.2% (lansoprazole 15 mg), 5.6% (lansoprazole 30 mg), and 11.0% (omeprazole 20 mg). Within treatment groups, pain was significantly ameliorated after the acute phase but not after maintenance therapy (P < 0.05); no differences were observed between groups. Gastrin values increased significantly after acute therapy (P < 0.05), persisted at these increased levels during maintenance therapy, and returned to normal after 6-month follow-up. Both lansoprazole and omeprazole were highly effective and well tolerated in the treatment of duodenal ulcer; relapse rates were similar for all doses studied. Thus no additional benefit is to be gained from using a proton-pump inhibitor at a dose > 15 mg

  8. High resolution magic angle spinning NMR as a tool for unveiling the molecular enantiorecognition of omeprazole by amylose-based chiral phase.

    PubMed

    Barreiro, Juliana Cristina; de Campos Lourenço, Tiago; Silva, Lorena Mara A; Venâncio, Tiago; Cass, Quezia Bezerra

    2014-03-21

    Polysaccharide-based chiral stationary phases (CSP) demonstrate great versatility and higher chiral selectivity for a variety of chiral compounds in multimodal elution modes (normal, reverse and polar organic). The main role of CSP phenyl carbamate based derivatives as chiral selectors is the formation of diastereoisomeric complexes by means of π-π interaction, dipole-dipole, hydrogen bonding and/or inclusion complex mechanisms. Nevertheless, the mechanism behind their enantioselectivity requires clarification. High resolution magic angle spinning nuclear magnetic resonance spectroscopy ((1)H HR/MAS NMR) has provided key information on the recognition process at the binding sites of the CSP surface. Herein we report the results obtained using omeprazole as a probe for these investigations.

  9. [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.

  10. The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects

    PubMed Central

    Palovaara, Sanna; Tybring, Gunnel; Laine, Kari

    2003-01-01

    Aims To study the effect of an oral contraceptive (OC) formulation containing ethinyloestradiol and levonorgestrel (LNG) (combination OC) or LNG alone on the CYP2C19-mediated hydroxylation of omeprazole in healthy females. Methods This was an open crossover study with three phases. In phase one, 10 healthy females received a single 40-mg dose of omeprazole. Thereafter the subjects received in a random order either 40 µg ethinyloestradiol and 75 µg LNG or 60 µg LNG alone once daily for 10 days. On day 10, 1 h after the last OC dose, subjects received a single 40-mg oral dose of omeprazole. The plasma concentrations of omeprazole, 5′-hydroxyomeprazole and omeprazole sulphone were determined for up to 8 h. Results The use of combination OC increased the area under the curve (AUC) of omeprazole by 38% [95% confidence interval (CI) − 3.8, 80; P = 0.040] and caused a 48% increase (95% CI 28, 68) in the AUC ratio of omeprazole/5-hydroxyomeprazole. LNG alone did not effect the 5′-hydroxylation of omeprazole. Neither of the OC preparations seemed to have an inhibitory effect on the formation of omeprazole sulphone by CYP3A4. Conclusions Oral contraceptives containing ethinyloestradiol but not those containing only LNG decrease CYP2C19 activity. PMID:12895199

  11. Relation between oesophageal acid exposure and healing of oesophagitis with omeprazole in patients with severe reflux oesophagitis.

    PubMed Central

    Holloway, R H; Dent, J; Narielvala, F; Mackinnon, A M

    1996-01-01

    BACKGROUND/AIMS--Reducing oesophageal acid exposure by suppressing acid secretion with omeprazole is highly effective in healing reflux oesophagitis. Some patients with severe oesophagitis, fail to heal and whether this results from inadequate acid suppression or other factors is unclear. The aim of this study, was to investigate the relation between oesophageal acid exposure and healing in patients with severe reflux oesophagitis treated with omeprazole. METHODS--Sixty one patients with grade 3 or 4 ulcerative oesophagitis were treated for eight weeks with omeprazole 20 mg every morning. Those patients unhealed at eight weeks were treated with 40 mg every morning for a further eight weeks. Endoscopy and 24 hour oesophageal pH monitoring were performed before treatment and at the end of each treatment phase while receiving treatment. RESULTS--Thirty per cent of patients failed to heal with the 20 mg dose. Unhealed patients had greater total 24 hour oesophageal acid exposure before treatment, and while receiving treatment also had greater acid exposure and a smaller reduction in acid exposure than did patients who healed. Forty seven per cent of the unhealed patients also failed to heal with the 40 mg dose. These patients had similar levels of acid exposure before treatment to those who healed, but had greater acid exposure while receiving treatment, particularly at night when supine. CONCLUSIONS--Patients with severe ulcerative oesophagitis who are refractory to omeprazole have greater oesophageal acid exposure while receiving treatment than responding patients. This is due to a reduced responsiveness to acid suppression, and is likely to be an important factor underlying the failure of the oesophagitis to heal. PMID:8707107

  12. Effect of intermittent administration of omeprazole on serum pepsinogens in duodenal ulcer patients and healthy volunteers.

    PubMed

    Biemond, I; Crobach, L F; Jansen, J B; Lamers, C B

    1990-04-01

    1. Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K(+)-APT-ase, was administered orally at a dose of 20 mg in the morning of 3 consecutive days, followed by a period of 4 days without medication, and this intermittent dosage regimen was continued for 4 weeks. 2. During intermittent administration of omeprazole to 10 patients with duodenal ulcer disease and 10 healthy volunteers concentrations of serum pepsinogen A and serum pepsinogen C were monitored by sensitive and specific radioimmunoassays to study whether the effect of this treatment on serum pepsinogens is different between patients and normal subjects and to evaluate whether serum pepsinogen levels can be used to assess compliance with therapy. 3. Administration of omeprazole for 3 days induced significant increases in pepsinogen A and pepsinogen C serum concentrations, which rapidly fell after stopping the omeprazole intake. The pattern of serum pepsinogens after stopping the drug was different for duodenal ulcer patients and normal subjects. Both pepsinogens were intra-individually related in both patients and healthy subjects when compared during the first and last 3-day course with omeprazole, but in duodenal ulcer patients both pepsinogens tended to be higher in the last treatment course, while the opposite was found in the normal subjects. 4. The present study confirms that serum pepsinogen concentrations are higher in duodenal ulcer patients than in normal subjects, but also shows for the first time that serum pepsinogens in the patients respond differently upon stimulation with omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2328194

  13. Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

    PubMed Central

    Daneshmend, T. K.; Hawkey, C. J.; Langman, M. J.; Logan, R. F.; Long, R. G.; Walt, R. P.

    1992-01-01

    OBJECTIVE--To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN--Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING--The medical wards of University and City Hospitals, Nottingham. SUBJECTS--1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES--Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS--Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS--Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena. PMID:1737157

  14. Stability of omeprazole in SyrSpend SF Alka (reconstituted).

    PubMed

    Whaley, Paul A; Voudrie, Mark A; Sorenson, Bridget

    2012-01-01

    Omeprazole is used in the treatment of dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, laryngopharyngeal reflux, and Zollinger-Ellison syndrome. Omeprazole is marketed by AstraZeneca under a number of names, most notably Prilosec and Losec, as well as being available from a number of generic manufacturers. Omeprazole is available in both tablet and capsule form, with varying strengths of each. The need for other administration options for those patients who cannot take tablets or capsules has led compounding pharmacies to seek other alternatives. One possible alternative is the use of a suspending agent to create an oral solution or suspension. In the past, this has been accomplished using a sodium bicarbonate solution as the vehicle. However, sodium bicarbonate/omeprazole combination imparts a bitter and unpleasant taste. SyrSpend SF Alka (reconstituted) is a vehicle for making a suspension which has a pleasant taste, thus increasing palpability and compliance. The objective of this study was to determine the stability of omeprazole in SyrSpend SF Alka (for reconstitution). The studied sample was compounded into a 2-mg/mL suspension and stored in a low-actinic plastic prescription bottle at temperatures between 2 degrees C and 8 degrees C. Six samples were assayed at each time point out to 92 days by a stability-indicating high-performance liquid chromatography method. The method was validated for its specificity through forced degradation studies. The shelf life of this product is at least 92 days, based on data collected when refrigerated and protected from light. PMID:23050328

  15. Effect of L-lactic acid on calcium absorption in rats fed omeprazole.

    PubMed

    Chonan, O; Takahashi, R; Yasui, H; Watanuki, M

    1998-06-01

    We examined the effect of L-lactic acid on calcium absorption in male Wistar rats made achlorhydric by dietary omeprazole, a proton pump inhibitor. The dietary omeprazole intake (0.03 g/100 g of diet) increased the gastric pH and decreased the apparent calcium absorption ratio. Dietary famotidine (0.03 g/100 g of diet), an H2-receptor antagonist, and lower doses of omeprazole (0.005 or 0.01 g/100 g of diet) did not affect the gastric pH or the calcium absorption. In a second experiment, dietary lactic acid (0.5, 1.0, or 2.5 g/100 g of diet) increased the intestinal calcium absorption dose dependently in rats fed omeprazole (0.03 g/100 g of diet). The gastric pH was significantly decreased only in the rats fed higher doses of lactic acid (1.0, or 2.5 g/100 g of diet). In a third experiment, a dietary sour milk beverage containing lactic acid (0.5 g/100 g of diet) increased the intestinal calcium absorption, but did not affect the gastric pH in rats fed omeprazole (0.03 g/100 g of diet). Although the significance of gastric acid in terms of overall calcium absorption is not known, under the present experimental conditions, the inhibition of gastric acid secretion by dietary omeprazole decreased the apparent calcium absorption, and the dietary lactic acid prevented the calcium absorption in rats fed omeprazole.

  16. High-performance liquid chromatographic separation of rolipram, bupivacaine and omeprazole using a tartardiamide-based stationary phase influence of flow rate and temperature on the enantioseparation.

    PubMed

    da Silva Junior, Ivanildo José; Sartor, João Paulo; Rosa, Paulo César Pires; de Veredas, Vinícius; Barreto Júnior, Amaro Gomes; Santana, Cesar Costapinto

    2007-08-24

    Chromatographic separation of the chiral drugs rolipram, bupivacaine and omeprazole on a tartardiamide-based stationary phase commercially named Kromasil CHI-TBB is shown in this work. The effect of temperature on the chromatographic separation of the chiral drugs using the Kromasil CHI-TBB stationary phase was determined quantitatively so as to contribute toward the design for the racemic mixtures of the named compound by using chiral columns. A decrease in the retention and selectivity factors was observed, when the column temperature increased. Van't Hoff plots provided the thermodynamic data. The variation of the thermodynamic parameters enthalpy and entropy are clearly negative meaning that the separation is enthalpy controlled.

  17. Omeprazole induces altered bile acid metabolism

    PubMed Central

    Shindo, K; Machida, M; Fukumura, M; Koide, K; Yamazaki, R

    1998-01-01

    Background—It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora. 
Aims—To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism. 
Methods—Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover on the tip and deconjugation was examined using thin layer chromatography. Fat malabsorption was detected by a triolein breath test. 
Results—In the bile acid breath test, expired breath samples from all patients and healthy volunteers showed significantly greater 14CO2 specific activity after omeprazole treatment (20 mg/day) than before treatment. Bacterial overgrowth was found in the jejunal fluid and gastric juice of both ulcer patients and healthy volunteers after omeprazole treatment. The following species were identified: Escherichia coli, Candida albicans, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, Eu parvum, and Corynebacterium granulosum. All of these species, except E coli and C albicans, deconjugate bile acids. There was a significant correlation between 14CO2 activity and gastric pH, both before and after omeprazole treatment in both groups. The triolein breath test revealed impaired fat absorption in both groups after omeprazole treatment. 
Conclusions—Both patients with gastric ulcer and healthy volunteers exhibited increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum and fat malabsorption after omeprazole treatment. The bacterial overgrowth consisted of both anaerobes and aerobes with deconjugation ability and was probably associated with an omeprazole induced shift to neutral pH in the gastric juice. 

 Keywords: omeprazole; bacterial overgrowth; deconjugation; bile acid breath

  18. Effects of omeprazole and aluminum hydroxide/magnesium hydroxide on riociguat absorption.

    PubMed

    Becker, Corina; Frey, Reiner; Unger, Sigrun; Artmeier-Brandt, Ulrike; Weimann, Gerrit; Mück, Wolfgang

    2016-03-01

    Riociguat, a soluble guanylate cyclase stimulator, is a novel therapy for the treatment of pulmonary hypertension. Riociguat bioavailability is reduced in neutral versus acidic conditions and therefore may be affected by concomitant use of medications that increase gastric pH. The effect of coadministration of the proton pump inhibitor omeprazole or the antacid AlOH/MgOH on the pharmacokinetics, safety, and tolerability of riociguat 2.5 mg was characterized in two open-label, randomized, crossover studies in healthy males. In study 1, subjects pretreated for 4 days with omeprazole 40 mg received cotreatment with omeprazole plus riociguat or riociguat alone (no pretreatment) on day 5 (n = 12). In study 2, subjects received cotreatment with 10 mL AlOH/MgOH plus riociguat or riociguat alone (n = 12). Pre- and cotreatment with omeprazole decreased riociguat bioavailability (mean decreases in area under the plasma concentration-time curve [AUC] and maximum concentration in plasma [C max] were 26% and 35%, respectively). Cotreatment with AlOH/MgOH resulted in greater decreases in riociguat bioavailability (mean decreases in AUC and C max were 34% and 56%, respectively). In both studies, most adverse events (AEs) were of mild intensity, and no serious AEs were reported. No additional safety signals were identified. Treatment with riociguat, with or without omeprazole or AlOH/MgOH, was well tolerated, with a good safety profile. Owing to the resulting increase of gastric pH, riociguat bioavailability is reduced by coadministration with AlOH/MgOH and, to a lesser extent, by coadministration with omeprazole. Thus, antacids should not be administered within an hour of receiving riociguat, but no dose adjustment is required for coadministration of proton pump inhibitors. PMID:27162626

  19. Chemical stability of extemporaneously compounded omeprazole formulations: a comparison of two methods of compounding.

    PubMed

    Garg, Sanjay; Svirskis, Darren; Al-Kabban, Majid; Farhan, Samer; Komeshi, Mohammed; Lee, Jacky; Liu, Quincy; Naidoo, Sacha; Kairuz, Therese

    2009-01-01

    Liquid preparations of omeprazole are compounded extemporaneously for patients who cannot tolerate or have difficulty with tablets or capsules, such as those with a nasogastric tube or jejunal or feeding tube, those with a swallowing disorder, and young children and the elderly. Recommendations for preparation of a liquid from the enteric-coated pellets of omeprazole capsules are available in the literature. The pellets are dissolved in a sodium bicarbonate solution; shaking is recommended to aid dissolution. Apparently some pharmacists crush the pellets to speed up the compounding process. The aim of this study was to investigate the chemical stability of omeprazole in extemporaneously compounded liquids prepared by the grinding and shaking methods. A high-performance liquid chromatographic method was developed for evaluation of chemical stability. Samples were stored at 2 deg C (refrigerated conditions) or 25 deg C/60% relative humidity and assayed for drug concentration at 0, 1, 2, 4, and 8 weeks. The method of preparation affected the chemical stability of omeprazole when stored at 25 deg C/60% relative humidity; it was stable for 4 weeks if prepared by the shaking method, but for only 1 week if prepared by the grinding method. For both methods, the suspension was stable for 8 weks if stored under refrigerated conditions. It is recommended that the shaking method be employed for extemporaneously compounded omeprazole suspensions, and that the prepared suspension be stored in the refrigerator. PMID:23966480

  20. Action of omeprazole (a benzimidazole derivative) on secretory responses to sham feeding and pentagastrin and upon serum gastrin and pancreatic polypeptide in duodenal ulcer patients.

    PubMed Central

    Konturek, S J; Kweicień, N; Obtułowicz, W; Kopp, B; Oleksy, J

    1984-01-01

    The effects of omeprazole, a benzimidazole derivative, have been determined on the secretory responses to modified sham feeding and pentagastrin, and upon serum gastrin and pancreatic polypeptide concentrations in duodenal ulcer patients. Intragastric administration of omeprazole in doses of 2 and 6 mumol/kg produced, respectively, about 50% and 90% reduction in acid outputs in responses to modified sham feeding and pentagastrin without affecting serum gastrin and pancreatic polypeptide response to modified sham feeding. PMID:6418621

  1. Inhibition of CYP2C19 and CYP3A4 by Omeprazole Metabolites and Their Contribution to Drug-Drug Interactions

    PubMed Central

    Shirasaka, Yoshiyuki; Sager, Jennifer E.; Lutz, Justin D.; Davis, Connie

    2013-01-01

    The aim of this study was to evaluate the contribution of metabolites to drug-drug interactions (DDI) using the inhibition of CYP2C19 and CYP3A4 by omeprazole and its metabolites as a model. Of the metabolites identified in vivo, 5-hydroxyomeprazole, 5′-O-desmethylomeprazole, omeprazole sulfone, and carboxyomeprazole had a metabolite to parent area under the plasma concentration–time curve (AUCm/AUCp) ratio ≥ 0.25 when either total or unbound concentrations were measured after a single 20-mg dose of omeprazole in a cocktail. All of the metabolites inhibited CYP2C19 and CYP3A4 reversibly. In addition omeprazole, omeprazole sulfone, and 5′-O-desmethylomeprazole were time dependent inhibitors (TDI) of CYP2C19, whereas omeprazole and 5′-O-desmethylomeprazole were found to be TDIs of CYP3A4. The in vitro inhibition constants and in vivo plasma concentrations were used to evaluate whether characterization of the metabolites affected DDI risk assessment. Identifying omeprazole as a TDI of both CYP2C19 and CYP3A4 was the most important factor in DDI risk assessment. Consideration of reversible inhibition by omeprazole and its metabolites would not identify DDI risk with CYP3A4, and with CYP2C19, reversible inhibition values would only identify DDI risk if the metabolites were included in the assessment. On the basis of inactivation data, CYP2C19 and CYP3A4 inhibition by omeprazole would be sufficient to identify risk, but metabolites were predicted to contribute 30–63% to the in vivo hepatic interactions. Therefore, consideration of metabolites may be important in quantitative predictions of in vivo DDIs. The results of this study show that, although metabolites contribute to in vivo DDIs, their relative abundance in circulation or logP values do not predict their contribution to in vivo DDI risk. PMID:23620487

  2. Efficacy of omeprazole paste in the prevention of gastric ulcers in 2 years old Thoroughbreds.

    PubMed

    Endo, Yoshiro; Tsuchiya, Takeru; Sato, Fumio; Murase, Harutaka; Omura, Takaya; Korosue, Kenji; Nambo, Yasuo; Ishimaru, Mutsuki; Wakui, Yasuhiro

    2012-08-01

    Prevalence of equine gastric ulcer syndrome in 85 young Thoroughbreds was investigated. The presence of gastric ulcers was confirmed in 27.1% (23/85) of the horses by endoscopic examination. Sixty-two horses without gastric ulcers were allocated randomly to either the treated group (31 horses) or sham-dosed control group (31 horses) in order to investigate the efficacy of omeprazole oral paste in the prevention of gastric ulcers. At the second endoscopic examination conducted after 28 days of administration, only 1 horse in the treated group developed gastric ulcers, while 12 horses developed gastric ulcers in the control group. Based on these data, the efficacy of omeprazole in prevention of equine gastric ulcers in young Thoroughbreds during the training period was confirmed.

  3. Preformulation Studies for Generic Omeprazole Magnesium Enteric Coated Tablets

    PubMed Central

    Migoha, C. O.; Kaale, E.; Kagashe, G.

    2015-01-01

    Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr's index), Hauser's ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr's index 17.5%, Hauser's ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350–2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation. PMID:25699270

  4. Severe adverse reactions caused by omeprazole: A case report

    PubMed Central

    Yu, Meiling; Qian, Jianghua; Guo, Daohua; Li, Li; Liu, Xiaolin

    2016-01-01

    A 61-year-old female patient was admitted to hospital following development of a whole-body rash for 10 days, diarrhea for 7 days, and unconsciousness and oliguria for 1 day. The patient had developed stomach discomfort following the oral administration of non-steroidal anti-inflammatory drugs, the exact nature of which was unknown, for the treatment of arthritic pain for >1 month. The patient was then prescribed omeprazole enteric-coated tablets (20 mg twice daily) for treatment of this symptom. However, the patient developed a whole-body rash 7 days after administering omeprazole, 10 days prior to admission. This symptom was followed by severe diarrhea with nausea and vomiting after 10 days, then shock. The shock occurred after administering omeprazole for 16 days. The patient developed a whole body rash 7 days after administering omeprazole, then 3 days later (after administering omeprazole for 10 days) severe diarrhea with nausea and vomiting occurred. The shock remained until administering omeprazole on the 16th day, with severe diarrhea with nausea and vomiting occurring 6 days later. The patient's condition did not improve following treatment for allergies, low blood pressure and oliguria in the Intensive Care Unit (ICU) department at Suzhou Municipal Hospital. For further diagnosis and treatment, the patient was admitted to the ICU department of The First Affiliated Hospital of Bengbu Medical College and was given a fluid infusion, antibiotics and phlegm-reducing treatment, a plasma infusion, blood filtration, and anti-diarrheal and anti-allergy treatment. The patient's vital signs were stable, with a normal temperature and hemogram results, and improved kidney function and deflorescence. Genetic screening revealed that the patient poorly metabolized omeprazole. Therefore, severe adverse reactions (allergic shock, rash and diarrhea) experienced by the patient were caused by the accumulation of omeprazole metabolites resulting from its slow metabolism in

  5. 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

  6. Therapeutic management of uncomplicated gastroesophageal reflux disease in france in 2005: Potential cost savings of omeprazole substitution

    PubMed Central

    Mouly, Stéphane; Charlemagne, Agnès; Lejeunne, Philippe; Fagnani, Francis

    2009-01-01

    Background: Proton pump inhibitors (PPIs) cost the French health care system >€1 billion in 2005, and ~50% of PPI prescriptions were for the treatment of gastroesophageal reflux disease (GERD). Objectives: This study aimed to describe the current use of PPIs for GERD, to estimate the total annual costs of treatment, and to evaluate the economic impact of the various possible substitutions among PPIs available for this indication in France. Methods: Data from a sample of patients aged ≥20 years who visited their general practitioner (GP) at least once in 2005 for uncomplicated, symptomatic GERD were retrieved from the Thales database (a group of 1200 representative GPs connected to a computerized network). Costs of the prescriptions presented for reimbursement and costs of those reimbursed by the French health care insurance system were analyzed. We then evaluated the economic consequences of replacing full-dose generic omeprazole (after substitution from brand-name omeprazole by the pharmacists) with other compounds that are indicated for mild symptoms at half dose (ie, lansoprazole 15 mg, pantoprazole 20 mg, rabeprazole 10 mg, and esomeprazole 20 mg). The results were adjusted to account for the proportions of patients who had full health care coverage and the treatment duration as reported in the database. Results are presented from the perspective of the French health care insurance system. Results: In 2005, a total of 122,571 patients (mean age, 55.7 years; 45.5% men; 13.8% with a history of at least 1 gastrointestinal disorder) met the inclusion criteria. Extrapolated to the French population, this sample corresponded to ≈5.7 million people (ie, 13% of the adult population who visited a GP during the year). PPIs were prescribed as first-line treatment for GERD in 84.1% of the consultations (14.3% in association with other antiulcer drugs). Omeprazole, as a proprietary or generic drug, was prescribed most often (78.9%) and at full dose (20 mg), while

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs.

    PubMed

    Mogi, Masayuki; Toda, Akiko; Iwasaki, Kazuhide; Kusumoto, Shogo; Takehara, Hiromi; Shimizu, Makiko; Murayama, Norie; Izumi, Hiroyuki; Utoh, Masahiro; Yamazaki, Hiroshi

    2012-01-01

    Small minipigs (Microminipig, registered as a novel variety of pig in Japan) were developed for use in non-clinical pharmacological/toxicological studies for new drug development. To assess the pharmacokinetics of selective substrates of human cytochrome P450s in Microminipigs, caffeine (human P450 1A2), warfarin (P450 2C9), omeprazole (P450 2C19), metoprolol (P450 2D6), and midazolam (P450 3A) were administered in combination, intravenously (0.20 mg kg(-1))( )or orally (1.0 mg kg(-1)). Plasma samples obtained, up to 24 hr after dosing, from four male and four female Microminipigs were analyzed by liquid chromatography tandem mass spectrometry to estimate typical pharmacokinetic parameters for each analyte. Bioavailabilities were approximately 80% for caffeine and warfarin, but less than 10% for omeprazole, metoprolol, and midazolam. No significant differences were noted, for the five probes, in area under the plasma concentration-time curve and peak plasma concentration values obtained from male and female Microminipigs. Clearance of caffeine, warfarin, omeprazole or midazolam in vivo, mediated mainly by cytochrome P450s 1A, 2C or 3A in Microminipigs, was similar to data reported for human. However, metoprolol metabolism, mediated by P450 2D enzymes in Microminipigs, was faster than reported for in vivo human kinetic parameters and in vitro in a human liver microsomal system. The results of this study suggest that the Microminipig is a suitable animal model for use in biological experiments for comparisons of pharmacokinetics of drugs in humans. The five-probes in combination used in this study demonstrate the disposition of typical P450 drugs in Microminipigs in vivo, with the aim of use in non-clinical pharmacological/toxicological studies. PMID:23208431

  13. 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.

  14. A phase 1 randomized study evaluating the effect of omeprazole on the pharmacokinetics of a novel 5-hydroxytryptamine receptor 4 agonist, revexepride (SSP-002358), in healthy adults

    PubMed Central

    Pierce, David; Corcoran, Mary; Velinova, Maria; Hossack, Stuart; Hoppenbrouwers, Mieke; Martin, Patrick

    2015-01-01

    Background About 30% of patients with gastroesophageal reflux disease continue to experience symptoms despite treatment with proton pump inhibitors. The 5-hydroxytryptamine 4 receptor agonist revexepride (SSP-002358) is a novel prokinetic that stimulates gastrointestinal motility, which has been suggested as a continued cause of symptoms in these patients. The aim of this study was to assess whether revexepride pharmacokinetics were affected by co-administration of omeprazole, in preparation for a proof-of-concept evaluation of revexepride added to proton pump inhibitor treatment. Methods In this phase 1, open-label, randomized, two-period crossover study, healthy adults aged 18–55 years were given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg. Pharmacokinetic parameters were assessed for up to 48 hours after administration of the investigational product. Adverse events, clinical chemistry and hematology parameters, electrocardiograms, and vital signs were monitored. Results In total, 42 participants were enrolled and 40 completed the study. The median age was 24 years (18–54 years), 55% were women and 93% were white. The pharmacokinetic parameters of revexepride were similar without or with omeprazole co-administration. The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) was 23.3 ng · h/mL (standard deviation [SD]: 6.33 ng · h/mL) versus 24.6 ng · h/mL (SD: 6.31 ng · h/mL), and maximum plasma concentrations (Cmax) were 3.89 ng/mL (SD: 1.30 ng/mL) and 4.12 ng/mL (SD: 1.29 ng/mL) in participants without and with omeprazole, respectively. For AUC0–∞ and Cmax, the 90% confidence intervals for the ratios of geometric least-squares means (with:without omeprazole) were fully contained within the pre-defined equivalence limits of 0.80–1.25. Mean apparent terminal phase half-life was 9.95 hours (SD: 2.06 hours) without omeprazole, and 11.0 hours (SD: 3.25 hours) with omeprazole. Conclusion

  15. Design, synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity.

    PubMed

    El-Nezhawy, Ahmed O H; Biuomy, Ayman R; Hassan, Fatma S; Ismaiel, Ayman K; Omar, Hany A

    2013-04-01

    A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-D-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation.

  16. 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

  17. 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

  18. Evergreening by whom? A review of secondary patents for omeprazole.

    PubMed

    Lloyd, Mike

    2013-11-01

    Evergreening, or the practice of technology developers to retain legal protection over valuable drugs beyond the normal patent term, is a well known practice by originators of successful drugs. Generic competitors also attempt similar strategies for commercial reasons. In this paper we look at secondary US and European patents in relation to the 'blockbuster' drug omeprazole (e.g., Prilosec® by AstraZeneca among other brands), with these secondary patents selected because they refer to the 'omeprazole' in either the title, abstract, Derwent Title or first claim. We find that 485 patents meet this criteria, with only 29% owned by the drugs originator (or known subsidiaries or predecessors). AstraZeneca was also the leading applicant by a number of measures, including grant ratio, number of patents filed, forward citation count, family member count and claim breadth.

  19. Effect of daily oral omeprazole on 24 hour intragastric acidity.

    PubMed Central

    Walt, R P; Gomes, M D; Wood, E C; Logan, L H; Pounder, R E

    1983-01-01

    Twenty four hour intragastric acidity was measured in nine patients with duodenal ulcer before and after one week of treatment with oral omeprazole 30 mg daily, a drug that inhibits gastric secretion by inhibition of parietal cell H+K+ adenosinetriphosphatase (ATPase). Omeprazole virtually eliminated intragastric acidity in all patients: the median 24 hour intragastric pH rose from 1.4 to 5.3 and the mean hourly hydrogen ion activity fell from 38.50 to 1.95 mmol(mEq)/1 (p less than 0.001). This inhibition of 24 hour intragastric acidity is more profound than that previously reported with either cimetidine 1 g daily or ranitidine 300 mg daily. PMID:6407676

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 21 CFR 520.1615 - Omeprazole.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... per pound (mg/lb) of body weight (4 milligrams per kilogram (mg/kg)) once daily for 4 weeks. For prevention of recurrence of gastric ulcers, 0.9 mg/lb of body weight (2 mg/kg) once daily for at least an... or 28 days. Each dose delivers at least 1 mg/kg of body weight. Horses over 1,200 lb body...

  5. 21 CFR 520.1615 - Omeprazole.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... veterinarian.” (d) Conditions of use in horses—(1) Amount—(i) For treatment of gastric ulcers, 1.8 milligrams... prevention of recurrence of gastric ulcers, 0.9 mg/lb of body weight (2 mg/kg) once daily for at least an additional 4 weeks. (ii) For prevention of gastric ulcers using the premarked syringe, one dose per day for...

  6. Effect of curing Helicobacter pylori infection on intragastric pH during treatment with omeprazole.

    PubMed Central

    Verdú, E F; Armstrong, D; Idström, J P; Labenz, J; Stolte, M; Dorta, G; Börsch, G; Blum, A L

    1995-01-01

    It has been shown that omeprazole treatment produces higher intragastric pH values in Helicobacter pylori positive subjects than in H pylori negative subjects. This study aimed to investigate the effect of curing H pylori on the intragastric pH in both the presence and absence of omeprazole therapy. Twenty four hour intragastric pH recordings were performed before and after a one week course of omeprazole (20 mg once daily) in 18 H pylori positive subjects and were repeated after the infection had been cured. In the absence of omeprazole, the total 24 hour pH values before cure did not differ from those afterwards. During omeprazole treatment the 24 hour pH values were much higher before (median (95% CI) 5.4: 4.3, 6.0), than after cure of infection (3.6: 2.1, 4.4; p < 0.001). The omeprazole induced fall in H+ activity before cure of H pylori did not, however, differ from that afterwards. It is concluded that the apparently greater antisecretory effect of omeprazole during H pylori infection may be a result of the production of acid neutralising compounds by the H pylori. Although a direct interaction between H pylori and omeprazole cannot be excluded, it seems unlikely. PMID:8537042

  7. Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone☆

    PubMed Central

    Yanagihara, Gabriela Rezende; de Paiva, Aline Goulart; Neto, Maurílio Pacheco; Torres, Larissa Helena; Shimano, Antônio Carlos; Louzada, Mário Jefferson Quirino; Annoni, Raquel; de Oliveira Penoni, Álvaro César

    2015-01-01

    Objectives Epidemiological studies have shown a relationship between long-term use of proton pump inhibitors and bone metabolism. However, this relationship has not yet become established. The aim of the present study was to analyze the mechanical properties and bone mineral density (BMD) of rats that were subjected to long-term omeprazole use. Methods Fifty Wistar rats weighing between 200 and 240 g were divided equally into five groups: OMP300 (omeprazole intake at a dose of 300 μmoL/kg/day); OMP200 (200 μmoL/kg/day); OMP40 (40 μmoL/kg/day); OMP10 (10 μmoL/kg/day); and Cont (control group; intake of dilution vehicle). The solutions were administered for 90 consecutive days. After the rats had been sacrificed, their BMD, the mechanical properties of the dissected femurs and their serum Ca++ levels were analyzed. Results The BMD of the OMP300 group was lower than that of the controls (p = 0.006). There was no difference on comparing the OMP200, OMP40 and OMP10 groups with the controls. The maximum strength and rigidity of the femur did not differ in the experimental groups in comparison with the controls. The OMP300 group had a statistically lower serum Ca++ concentration than that of the controls (p = 0.049), but the other groups did not show any difference in relation to the controls. Conclusion Daily intake of 300 μmoL/kg/day of omeprazole decreased the BMD of the femur, but without changes to the rigidity and strength of the femur in adult rats. PMID:26229922

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. In vivo and in vitro protective effects of omeprazole against neuropathic pain.

    PubMed

    Chanchal, Sanjay K; Mahajan, Umesh B; Siddharth, Sumit; Reddy, Navyya; Goyal, Sameer N; Patil, Prakash H; Bommanahalli, Basavaraj P; Kundu, Chanakya N; Patil, Chandragouda R; Ojha, Shreesh

    2016-01-01

    Apart from reducing the acid secretion, omeprazole inhibits activation of the nuclear factor-κB, release of inflammatory cytokines, and chemotaxis of neutrophils. These mechanisms prompted us to evaluate antineuropathic effect of omeprazole in the chronic constriction injury (CCI)-induced rat model of neuropathic pain and LPS mediated ROS-induced U-87 cells. Omeprazole at 50 mg/kg/day/oral for 14 days significantly reduced the intensity of neuropathic pain estimated as paw withdrawal latency, withdrawal pressure threshold and restored the motor nerve conduction velocity in the constricted nerve, when compared with respective groups. The histological findings revealed the protective effect of omeprazole against the CCI-induced damage. Omeprazole significantly decreased the levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) as compared to their respective control groups. It also reduced the oxidative stress by up regulating the SOD, catalase activity and decreasing MDA content. Similarly, in-vitro study, LPS mediated ROS-induced U-87 cells, omeprazole reduced the oxidative stress as well as the release of TNF-α, IL-1β and IL-6. Altogether, these results suggest that, neuroprotective effect of omeprazole is mediated through preventing release of proinflammatory cytokines, augmenting endogenous anti-oxidant defense system, and maintain the structural integrity of sciatic nerve from the CCI-induced structural damage and inflammatory changes. PMID:27435304

  16. In vivo and in vitro protective effects of omeprazole against neuropathic pain

    PubMed Central

    Chanchal, Sanjay K.; Mahajan, Umesh B.; Siddharth, Sumit; Reddy, Navyya; Goyal, Sameer N.; Patil, Prakash H.; Bommanahalli, Basavaraj P.; Kundu, Chanakya N.; Patil, Chandragouda R.; Ojha, Shreesh

    2016-01-01

    Apart from reducing the acid secretion, omeprazole inhibits activation of the nuclear factor-κB, release of inflammatory cytokines, and chemotaxis of neutrophils. These mechanisms prompted us to evaluate antineuropathic effect of omeprazole in the chronic constriction injury (CCI)-induced rat model of neuropathic pain and LPS mediated ROS-induced U-87 cells. Omeprazole at 50 mg/kg/day/oral for 14 days significantly reduced the intensity of neuropathic pain estimated as paw withdrawal latency, withdrawal pressure threshold and restored the motor nerve conduction velocity in the constricted nerve, when compared with respective groups. The histological findings revealed the protective effect of omeprazole against the CCI-induced damage. Omeprazole significantly decreased the levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) as compared to their respective control groups. It also reduced the oxidative stress by up regulating the SOD, catalase activity and decreasing MDA content. Similarly, in-vitro study, LPS mediated ROS-induced U-87 cells, omeprazole reduced the oxidative stress as well as the release of TNF-α, IL-1β and IL-6. Altogether, these results suggest that, neuroprotective effect of omeprazole is mediated through preventing release of proinflammatory cytokines, augmenting endogenous anti-oxidant defense system, and maintain the structural integrity of sciatic nerve from the CCI-induced structural damage and inflammatory changes. PMID:27435304

  17. 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

  18. 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.

  19. 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

  20. TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway.

    PubMed

    Pombo, Mónica; Lamé, Michael W; Walker, Naomi J; Huynh, Danh H; Tablin, Fern

    2015-05-19

    The role of the aryl hydrocarbon receptor (AhR) in hemostasis has recently gained increased attention. Here, we demonstrate, by qRT-PCR and western blot, that human platelets express both AhR mRNA and AhR protein. AhR protein levels increase in a dose dependent manner when incubated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole. Treatment of platelets with puromycin blocks increased AhR protein synthesis in the presence of AhR activators. Additionally, treatment of platelets with either activator results in phosphorylation of p38MAPK and cPLA2, two key signaling molecules in platelet activation pathways. Using the AhR competitive inhibitors alpha naphthoflavone and CH-223191, we show that phosphorylation of p38MAPK is AhR dependent. Further, inhibition of p38MAPK blocks downstream cPLA2 phosphorylation induced by TCDD or omeprazole. Treatment with AhR activators results in platelet priming, as demonstrated by increased platelet aggregation, which is inhibited by AhR antagonists. Our data support a model of the platelet AhR non-genomic pathway in which treatment with AhR activators results in increased expression of the AhR, phosphorylation of p38MAPK and cPLA2, leading to platelet priming in response to agonist. PMID:25797602

  1. Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats.

    PubMed

    Stancic-Rokotov, D; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Staresinic, M; Gjurasin, M; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Sikiric, P; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Kokic, N; Jagic, V; Boban-Blagaic, A

    2001-01-01

    Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions. PMID:11595454

  2. 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

  3. 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.

  4. 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.

  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. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

    PubMed Central

    Wang, Lianmei; Zhang, Hongbing; Li, Chunying; Yi, Yan; Liu, Jing; Zhao, Yong; Tian, Jingzhuo; Zhang, Yushi; Wei, Xiaolu; Gao, Yue; Liang, Aihua

    2016-01-01

    Aristolochia manshuriensis Kom (AMK) is a member of the Aristolochiaceae family and is a well-known cause of aristolochic acid (AA) nephropathy. In this study, we investigated the potential of omeprazole (OM) to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in human renal tubular epithelial cells (HKCs). HKCs with ectopic CYP 1A1 expression were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK-mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the coadministration of OM might be beneficial for reducing of AA-induced nephrotoxicity. PMID:27716846

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Nonsteroidal anti-inflammatory drugs: add an anti-ulcer drug for patients at high risk only. Always limit the dose and duration of treatment with NSAIDs.

    PubMed

    2011-09-01

    adverse effects while taking low-dose aspirin. After 48 weeks of treatment, pantoprazole was more effective than famotidine for the prevention of overt gastrointestinal bleeding. The symptomatic effects of PPIs and H2 antagonists may create a false sense of security, leading some patients to increase their NSAID use and resulting in a paradoxical increase in severe gastrointestinal effects. In practice, anti-ulcer drugs are not sufficiently effective to warrant their use by NSAID-treated adults who are not at high risk of severe gastrointestinal events. Misoprostol has proven efficacy in patients with risk factors for NSAID-induced severe gastroduodenal adverse effects, especially patients over 65 years of age, but it also has frequent adverse effects and necessitates 4 daily doses. Omeprazole is an alternative when the adverse effects or dosing frequency of misoprostol are unacceptable, provided patients are warned not to increase their NSAID consumption.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  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. Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

    PubMed

    Gan, Lu; Jiang, Xuemin; Mendonza, Anisha; Swan, Therese; Reynolds, Christine; Nguyen, Joanne; Pal, Parasar; Neelakantham, Srikanth; Dahlke, Marion; Langenickel, Thomas; Rajman, Iris; Akahori, Mizuki; Zhou, Wei; Rebello, Sam; Sunkara, Gangadhar

    2016-01-01

    LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions. PMID:27119576

  10. 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

  11. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms

    PubMed Central

    Anderson, Leticia; Venancio, Thiago M.; Nakaya, Helder I.; Miyasato, Patrícia A.; Rofatto, Henrique K.; Zerlotini, Adhemar; Nakano, Eliana; Oliveira, Guilherme; Verjovski-Almeida, Sergio

    2015-01-01

    Background Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis. Methodology We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay. Principal Findings We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect. Conclusions Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Do the omeprazole family compounds exert a protective effect against influenza-like illness?

    PubMed Central

    2014-01-01

    Background Infections by influenza viruses place a heavy burden on public health and economies worldwide. Although vaccines are the best weapons against influenza, antiviral drugs could offer an opportunity to alleviate the burden of influenza. Since omeprazole family compounds block the “proton pump”, we hypothesized that they could interfere with the mechanism of fusion of the virus envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism of influenza viruses. Methods A matched case-control study was performed in 2010-2011 in Italy. Cases were subjects aged over 18 years with a diagnosis of Influenza-like Illness (ILI); 254 case-control pairs were recruited. A multivariable conditional logistic regression analysis was used to assess the association between the prevention of ILI and the administration of omeprazole family compounds. The interaction between omeprazole family compounds and influenza vaccination was also examined. Results After control for potential confounders, subjects treated with omeprazole family compounds displayed a lower risk of catching ILI (ORadj = 0.29, 95% CI: 0.15-0.52). The risk of ILI in unvaccinated non-OFC users was about six times than that in vaccinated OFC users. Conclusions Although confirmation is necessary, these results suggest that omeprazole family compounds could be profitably used in the prevention of ILI. PMID:24889553

  18. Effective gastric acid suppression after oral administration of enteric-coated omeprazole granules.

    PubMed

    Mohiuddin, M A; Pursnani, K G; Katzka, D A; Gideon, R M; Castell, J A; Castell, D O

    1997-04-01

    Omeprazole is inactivated by exposure to gastric acid and is formulated as a gelatin capsule containing enteric-coated granules that release the drug in alkaline medium. In clinical situations where patients are unable to take the capsule orally, the optimum means of administration is uncertain. Eleven normal volunteers were given omeprazole 20 mg every day for one week before breakfast in random order as either a 20-mg capsule with water or free enteric-coated granules with either 8 oz of orange juice, 8 oz of water with 2 Alka-Seltzer antacid tablets (aspirin free), or 1 teaspoon of apple sauce. On day 7 of each regimen, an 8-hr intragastric pH study was performed following omeprazole 20 mg and standard breakfast. The median percentage of time of gastric acid pH > 4 after an omeprazole capsule was 68.5 (25-100); after granules with orange juice 59 (43-100); after granules in Alka-Seltzer solution 63 (31-100), and after granules in apple sauce 65 (30-99), with no significant differences (ANOVA). The time for the gastric pH to reach <4' after having been above was also similar for all four regimens (ANOVA). Omeprazole granules administered orally in a variety of ways achieve gastric acid suppression as effectively as the intact capsule. PMID:9125637

  19. Peak distortion in the column liquid chromatographic determination of omeprazole dissolved in borax buffer.

    PubMed

    Arvidsson, T; Collijn, E; Tivert, A M; Rosén, L

    1991-11-22

    Injection of a sample containing omeprazole dissolved in borax buffer (pH 9.2) into a reversed-phase liquid chromatographic system consisting of a mixture of acetonitrile and phosphate buffer (pH 7.6) as the mobile phase and a C18 surface-modified silica as the solid phase resulted under special conditions in split peaks of omeprazole. The degree of peak split and the retention time of omeprazole varied with the concentration of borax in the sample solution and the ionic strength of the mobile phase buffer as well as with the column used. Borax is eluted from the column in a broad zone starting from the void volume of the column. The retention is probably due to the presence of polyborate ions. The size of the zone varies with the concentration of borax in the sample injected. In the borax zone the pH is increased compared with the pH of the mobile phase, and when omeprazole (a weak acid) is co-eluting in the borax zone its retention is affected. In the front part and in the back part of the borax zone, pH gradients are formed, and these gradients can induce the peak splitting. When the dissolving medium is changed to a phosphate buffer or an ammonium buffer at pH 9 no peak distortion of omeprazole is observed.

  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. 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…

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

  9. 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.

  10. 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

  11. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE₂ induced pain model.

    PubMed

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D; da Silva, Carlos Antonio Trindade; Morisseau, Christophe; Hammock, Bruce D

    2015-12-15

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3mg/kg/day, p.o.) and OME (100mg/kg/day, p.o., 7 days)+TPPU (3mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE2 was monitored. While OME treatment by itself exhibited variable effects on PGE2 induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME+TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. PMID:26522832

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. '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.

  17. 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.

  18. Voltammetric Behavior and Determination of Trace Amounts of Omeprazole Using an Edge-plane Pyrolytic Graphite Electrode

    PubMed Central

    Shahrokhian, Saeed; Ghalkhani, Masoumeh; Bayat, Maryam; Ghorbani-Bidkorbeh, Fatemeh

    2015-01-01

    The voltammetric performance of edge-plane pyrolytic graphite (EPG) electrode via adsorptive stripping voltammetry was investigated for study of the electrochemical behavior of omeprazole (OMZ) in aqueous solution. The results revealed that the oxidation of OMZ is an irreversible pH-dependent process that proceeds with the transfer of one electron and one proton in an adsorption-controlled mechanism. The determination conditions, such as the pH values of the supporting electrolyte, accumulation time and scan rate were optimized. Simplicity, high reproducibility and low detection limit (3 nM) of the electrode response as well as wide linear range (0.01 to 4.0 µM) can be stated as significant features of this electrode. The EPG electrode was successfully applied for the determination of OMZ in pharmaceutical formulations and satisfactory results were obtained. PMID:25901153

  19. 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.

  20. 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

  1. Prediction of relative in vivo metabolite exposure from in vitro data using two model drugs: dextromethorphan and omeprazole.

    PubMed

    Lutz, Justin D; Isoherranen, Nina

    2012-01-01

    Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes, and be used as probes of drug-drug interactions or specific cytochrome P450 (P450) phenotypes. Thus, better understanding and prediction methods are needed to characterize metabolite exposures in vivo. This study aimed to test whether in vitro data could be used to predict and rationalize in vivo metabolite exposures using two model drugs and P450 probes: dextromethorphan and omeprazole with their primary metabolites dextrorphan, 5-hydroxyomeprazole (5OH-omeprazole), and omeprazole sulfone. Relative metabolite exposures were predicted using metabolite formation and elimination clearances. For dextrorphan, the formation clearances of dextrorphan glucuronide and 3-hydroxymorphinan from dextrorphan in human liver microsomes were used to predict metabolite (dextrorphan) clearance. For 5OH-omeprazole and omeprazole sulfone, the depletion rates of the metabolites in human hepatocytes were used to predict metabolite clearance. Dextrorphan/dextromethorphan in vivo metabolite/parent area under the plasma concentration versus time curve ratio (AUC(m)/AUC(p)) was overpredicted by 2.1-fold, whereas 5OH-omeprazole/omeprazole and omeprazole sulfone/omeprazole were predicted within 0.75- and 1.1-fold, respectively. The effect of inhibition or induction of the metabolite's formation and elimination on the AUC(m)/AUC(p) ratio was simulated. The simulations showed that unless metabolite clearance pathways are characterized, interpretation of the metabolic ratios is exceedingly difficult. This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data.

  2. 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.

  3. 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

  4. 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

  5. A study of the interaction between omeprazole and cyclosporine in renal transplant patients.

    PubMed Central

    Blohmé, I; Idström, J P; Andersson, T

    1993-01-01

    1. To determine any interaction between omeprazole and cyclosporine A (CsA) 10 male patients with 1-7 year renal transplants and stable renal function, participated in this randomised blind cross-over trial with omeprazole, 20 mg, and placebo treatment once daily for 2 consecutive weeks each. 2. Blood samples for measurement of trough concentrations of CsA were obtained twice a week during the 4 study weeks, and during the 2 weeks before and after the study. Unchanged CsA concentrations were measured by h.p.l.c. and using a monoclonal antibody r.i.a., and drug plus metabolites were measured by a polyclonal antibody f.p.i.a. In addition, one of the metabolites, M17, was assayed separately by h.p.l.c. 3. The mean whole blood trough CsA concentration during omeprazole treatment was 102 (95% confidence interval, 84-122) micrograms l-1 determined by h.p.l.c. and 81 (65-100) micrograms l-1 determined by r.i.a. Corresponding values during placebo treatment were 100 (79-127) micrograms l-1 and 95 (75-120) micrograms l-1. The ratios between omeprazole and placebo treatments were 1.01 (0.84-1.22) (h.p.l.c.) and 0.85 (0.67-1.08) (r.i.a.). Assuming that a change of < 30% in CsA blood concentrations is of no clinical significance, these results show that there was no clinically or statistically significant influence of omeprazole on CsA concentrations. Neither CsA concentrations determined by f.p.i.a. nor determination of M17 by h.p.l.c. indicated any effect of omeprazole on the metabolism of CsA. 4. It is concluded that omeprazole (20 mg daily) does not significantly interfere with CsA metabolism in stabilised renal transplant patients and may be used safely without extra monitoring of blood CsA concentrations. PMID:8443034

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. ``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).

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Monitoring the on-line titration of enantiomeric omeprazole employing continuous-flow capillary microcoil 1H NMR spectroscopy.

    PubMed

    Hentschel, Petra; Holtin, Karsten; Steinhauser, Lisa; Albert, Klaus

    2012-12-01

    The titration of the (S)-enantiomer of omeprazole with the (R)-enantiomer in chloroform-d(1) is monitored by continuous-flow capillary microcoil (1)H NMR spectroscopy employing a microcoil with a detection volume of 1.5 µl. The observed changes of the (1)H NMR chemical shifts indicate the formation of a heterochiral (R,S) dimer of omeprazole via its sulfinyl group and the NH group of the benzimidazole ring.

  5. 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

  6. 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.

  7. Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

    PubMed

    Sikiric, P; Seiwerth, S; Grabarevic, Z; Balen, I; Aralica, G; Gjurasin, M; Komericki, L; Perovic, D; Ziger, T; Anic, T; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Staresinic, M; Aralica, J; DiBiaggio, N; Simec, Z; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Sebecic, B; Ivasovic, Z; Boban-Blagaic, A; Sjekavica, I

    2001-01-01

    Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were

  8. 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.

  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. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

    PubMed

    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

  11. 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.

  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. Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria.

    PubMed Central

    Brand, S J; Stone, D

    1988-01-01

    Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells. Images PMID:2901431

  15. Instantaneous enteric nano-encapsulation of omeprazole: pharmaceutical and pharmacological evaluation.

    PubMed

    Bendas, Ehab R; Abdelbary, Aly A

    2014-07-01

    Recently, great attention has been paid to nanocapsules. The interest of these structures is due to their promising applications as drug delivery systems. The objective of this study was to develop novel enteric coating technique based on instantaneous encapsulation of the acid-labile drug, omeprazole in innovative enteric nanocapsules. Omeprazole enteric nanocapsules were formulated by varying the type and amount of the enteric polymer. The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE) values of the prepared enteric nanocapsules were determined. A full 2(1)×3(1) factorial design was used for planning and analysis of the experimental trials to select the optimized formulation. The highest desirability value was 0.7463 for formula E3 (containing 200mg hydroxypropyl methylcellulose phthalate (HPMCP)). The stability of omeprazole was reflected by the absence of the exothermal peak when the drug was encapsulated as detected by differential scanning calorimetry (DSC) thermograms. In vitro drug release study confirmed the USP specifications required to meet the key formulation characteristics of gastro-resistance. In vivo pharmacological assessment showed that the optimized nanocapsules were able to protect rat stomach against ulcer formation compared to the aqueous suspension of the drug which showed less significant protection.

  16. 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.

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

    PubMed

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

    2006-03-01

    The goal of the present study was to evaluate a calcium dose that was higher than the conventional dose for treatment of parturient paresis in cows. Thirty cows with parturient paresis received 1000 ml of 40 per cent calcium borogluconate solution supplemented with 6 per cent magnesium hypophosphite. Cows in group A received 200 ml of the solution intravenously over a 10-minute period, and the remaining 800 ml via a slow intravenous drip over a six-hour period. Cows in group B received 500 ml of the solution intravenously over a 20-minute period, and the remaining 500 ml via a slow intravenous drip over a six-hour period. Afterwards, the cows were monitored continuously and examined every hour for eight hours. Samples of blood were collected from all the cows before treatment and at 10, 20, 40, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes and 24, 48 and 72 hours after treatment. The concentrations of total calcium, ionised calcium, inorganic phosphorus and magnesium were determined. Cows that did not stand within 12 hours of treatment received one or more additional treatments. There was no significant difference in the recovery rate between the two groups. Of the 30 cows, 14 (47 per cent) rised after one treatment and 15 others (50 per cent) were cured after two or more treatments. One cow did not respond to repeated treatments and was euthanased four days after the start of treatment. The results of electrolyte analyses before treatment did not differ significantly between the two groups. In 27 (90 per cent) cows, the concentrations of calcium and inorganic phosphorus were lower than normal and in 3 (10 per cent) cows, only the concentration of inorganic phosphorus was lower than normal. The concentration of total calcium increased markedly ten minutes after the start of treatment in both groups, and at eight hours, the mean concentration of calcium was within the normal range. At 24 and 48 hours, the mean concentration of calcium was below normal, but at

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  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. 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.

  6. 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.

  7. 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

  8. 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

  9. [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

  10. [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.

  11. [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.

  12. 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).

  13. 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

  14. 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

  15. 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

  16. 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...

  17. 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

  18. 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.

  19. Comparative clinical evaluation on herbal formulation Pepsil, Safoof-e-Katira and Omeprazole in gastro esophageal reflux disease.

    PubMed

    Toseef, Muhammad Umar; Saeed, Aftab; Mohi-Ud-Din, Ejaz; Usmanghani, Khan; Nazar, Halima; Nawaz, Allah; Ahmad, Irshad; Siddiqui, Faheem Ahmed

    2015-05-01

    This study was conducted to evaluate the role of Unani herbal drugs Pepsil and Safoof-e-katira on the gastro esophageal reflux disease (GERD). This was multicentre randomized case control study conducted at Matab Hakeem Muhammad Noor-ud-din, Burewala; Aziz Muhammad din Medical and Surgical Centre, Burewala and Shifa-ul-mulk Memorial Hospital, Hamdard University Karachi. The patients were selected according to inclusion and exclusion criteria. In test group-1 the male female ratio was 40%, 60%; test group-2 was 42%, 58% and in control group was 44%, 56% respectively. The observed symptoms in the study were increased appetite (TG-1-95%, TG-2-95% and CG-89%), difficulty in swallowing (TG-1-93%, TG-2-96% and TC-94%), belching/burping (TG-1-97%, TG-2-97% and CG-95%), vomiting (TG-1-90%, TG-2-96% and CG-89%), heart burn (TG-1-100%, TG-2-100% and CG-98%), palpitation (TG-1-100%, TG-2-100% and CG-97%), epigastric pain (TG-1-97%, TG-2-97% and CG-90%), abdominal cramps (TG-1-97%, TG-2-98% and CG-95%), tenesmus (TG-1-100%, TG-2-100% and CG-97%), flatulence (TG-1-100%, TG-2-75% and CG-95%), wakeup during sleep (TG-1-94%, TG-2-87% and CG-94%). The p-value of the results of the symptoms was 0.000 except flatulence where the value was 0.001. The statistical results of the study prescribed that all the drugs studied (Pepsil, Safoof-e-katira and Omeprazole) are highly significant. The herbal coded drug Pepsil showed no side effects and unani herbal drug safoof-e-katira showed minimum result of 75% in the patients while Omeprazole resulted with some side effects. In the result it can be concluded that the herbal coded drug Pepsil is a potent herbal drug for gastro esophageal reflux disease. PMID:26004718

  20. 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

  1. 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.

  2. 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

  3. 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

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH-DOSE

  4. 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.

  5. 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)

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole

    PubMed Central

    Hansen, Bent-Are; Bruserud, Øyvind

    2016-01-01

    Hypomagnesemia can be caused by a wide range of diseases (e.g. gastrointestinal disorders, kidney diseases or endocrine disorders), but it can also be a side effect of several drugs. It can be asymptomatic or cause many different clinical symptoms, and the clinical manifestations mainly depend on the rate of development rather than the actual serum magnesium concentration. We here present a 40-year-old female patient with Torsade de pointes ventricular tachycardia and cardiac arrest caused by severe hypomagnesemia as an adverse effect of the proton pump inhibitor omeprazole. PMID:27471598

  2. Omeprazole does not Potentiate Acute Oxygen Toxicity in Fetal Human Pulmonary Microvascular Endothelial Cells Exposed to Hyperoxia

    PubMed Central

    Patel, Ananddeep; Zhang, Shaojie; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    Hyperoxia contributes to the pathogenesis of broncho-pulmonary dysplasia (BPD), which is a developmental lung disease of premature infants that is characterized by an interruption of lung alveolar and pulmonary vascular development. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Earlier we observed that OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury in adult mice and oxygen toxicity in adult human lung cells. However, our later studies in newborn mice demonstrated that OM potentiates hyperoxia-induced developmental lung injury. Whether OM exerts a similar toxicity in primary human fetal lung cells is unknown. Hence, we tested the hypothesis that OM potentiates hyperoxia-induced cytotoxicity and ROS generation in the human fetal lung derived primary human pulmonary microvascular endothelial cells (HPMEC). OM activated AhR as evident by a dose-dependent increase in cytochrome P450 (CYP) 1A1 mRNA levels in OM-treated cells. Furthermore, OM at a concentration of 100 μM (OM 100) increased NADP(H) quinone oxidoreductase 1 (NQO1) expression. Surprisingly, hyperoxia decreased rather than increase the NQO1 protein levels in OM 100-treated cells. Exposure to hyperoxia increased cytotoxicity and hydrogen peroxide (H2O2) levels. Interestingly, OM 100-treated cells exposed to air had increased H2O2 levels. However, hyperoxia did not further augment H2O2 levels in OM 100-treated cells. Additionally, hyperoxia-mediated oxygen toxicity was similar in both vehicle- and OM-treated cells. These findings contradict our hypothesis and support the hypothesis that OM does not potentiate acute hyperoxic injury in HPMEC in vitro. PMID:26779382

  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. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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. Alginate beads as a carrier for omeprazole/SBA-15 inclusion compound: A step towards the development of personalized paediatric dosage forms.

    PubMed

    Del Gaudio, Pasquale; De Cicco, Felicetta; Sansone, Francesca; Aquino, Rita Patrizia; Adami, Renata; Ricci, Maurizio; Giovagnoli, Stefano

    2015-11-20

    The treatment of gastro-esophageal reflux disease (GERD) shows several issues among paediatric patients. This work aims to the formulation of enteric alginate beads loaded with omeprazole (OME) allowing age- and weight-related personalized dosages in children. OME was entrapped in SBA-15 mesoporous compound, characterized and loaded into alginate beads by prilling at different OME and alginate concentrations. The beads resulted of homogeneous size, spherical morphology and very consistent in drug loading and distribution. Formulations demonstrated limited swelling and release (about 10%) in simulated gastric fluid (SGF) after 2h and a prolonged release in simulated intestinal fluid (SIF), till 6h, due to a mixed diffusion-case II transport mechanism. The beads were superior to the market product, which showed lower release in SGF but immediate dissolution in SIF. The high alginate beads uniformity and release properties make them a potential novel tool for a personalized treatment of GERD in children. PMID:26344303

  2. Enantioseparation of omeprazole--effect of different packing particle size on productivity.

    PubMed

    Enmark, Martin; Samuelsson, Jörgen; Forssén, Patrik; Fornstedt, Torgny

    2012-06-01

    Enantiomeric separation of omeprazole has been extensively studied regarding both product analysis and preparation using several different chiral stationary phases. In this study, the preparative chiral separation of omeprazole is optimized for productivity using three different columns packed with amylose tris (3,5-dimethyl phenyl carbamate) coated macroporous silica (5, 10 and 25 μm) with a maximum allowed pressure drop ranging from 50 to 400 bar. This pressure range both covers low pressure process systems (50-100 bar) and investigates the potential for allowing higher pressure limits in preparative applications in a future. The process optimization clearly show that the larger 25 μm packing material show higher productivity at low pressure drops whereas with increasing pressure drops the smaller packing materials have substantially higher productivity. Interestingly, at all pressure drops, the smaller packing material result in lower solvent consumption (L solvent/kg product); the higher the accepted pressure drop, the larger the gain in reduced solvent consumption. The experimental adsorption isotherms were not identical for the different packing material sizes; therefore all calculations were recalculated and reevaluated assuming identical adsorption isotherms (with the 10 μm isotherm as reference) which confirmed the trends regarding productivity and solvent consumption.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. [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)

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. [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

  18. 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

  19. 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.

  20. 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

  1. Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery.

    PubMed

    Khan, Sajjad; Trivedi, Vivek; Boateng, Joshua

    2016-03-16

    Buccal films were prepared from aqueous and ethanolic Metolose gels using the solvent casting approach (40°C). The hydration (PBS and simulated saliva), mucoadhesion, physical stability (20°C, 40°C), in vitro drug (omeprazole) dissolution (PBS and simulated saliva), ex vivo permeation (pig buccal mucosa) in the presence of simulated saliva, ex vivo bioadhesion and cell viability using MTT of films were investigated. Hydration and mucoadhesion results showed that swelling capacity and adhesion was higher in the presence of PBS than simulated saliva (SS) due to differences in ionic strength. Omeprazole was more stable at 20°C than 40°C whilst omeprazole release reached a plateau within 1h and faster in PBS than in SS. Fitting release data to kinetic models showed that Korsmeyer-Peppas equation best fit the dissolution data. Drug release in PBS was best described by zero order via non-Fickian diffusion but followed super case II transport in SS attributed to drug diffusion and polymer erosion. The amount of omeprazole permeating over 2h was 275 ug/cm(2) whilst the formulations and starting materials showed cell viability values greater than 95%, confirming their safety for potential use in paediatric buccal delivery. PMID:26802493

  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. 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.

  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. PMID:26457456

  8. 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

  9. 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.}.

  10. 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.

  11. 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.

  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. 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

  18. 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.

  19. 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.

  20. [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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  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. 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

  10. 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

  11. 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

  12. 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.

  13. 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...

  14. 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,...

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Micrometer size rod formed by secondary self assembly of omeprazole with α- and β-cyclodextrins

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Venkatesh, G.

    2015-02-01

    Self assembly of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) micro rods induced by omeprazole (OMP) were observed by SEM and TEM. OMP/CD inclusion complexes have formed the secondary self assembly micro meter size rod like structure. This structure was driven by the intermolecular hydrogen bonding as well as van der Waals forces. Both forces induced the ordered assembly and arrangement of OMP/CD inclusion complexes, whereas CD molecules acted as molecular bricks. The OMP/CD inclusion complexes primary assembled form individual nanorods and then secondary self aggregate nanorods were form a micro meter rod structure. The results indicate that inter-nanotubular hydrogen bonding plays a crucial role in the formation of the self assembled micro rods. The inclusion complexes were also characterized using FT-IR, DSC, powder XRD, 1H NMR, absorption, fluorescence, life time measurements and molecular modeling methods.

  20. Micrometer size rod formed by secondary self assembly of omeprazole with α- and β-cyclodextrins.

    PubMed

    Rajendiran, N; Venkatesh, G

    2015-02-25

    Self assembly of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) micro rods induced by omeprazole (OMP) were observed by SEM and TEM. OMP/CD inclusion complexes have formed the secondary self assembly micro meter size rod like structure. This structure was driven by the intermolecular hydrogen bonding as well as van der Waals forces. Both forces induced the ordered assembly and arrangement of OMP/CD inclusion complexes, whereas CD molecules acted as molecular bricks. The OMP/CD inclusion complexes primary assembled form individual nanorods and then secondary self aggregate nanorods were form a micro meter rod structure. The results indicate that inter-nanotubular hydrogen bonding plays a crucial role in the formation of the self assembled micro rods. The inclusion complexes were also characterized using FT-IR, DSC, powder XRD, (1)H NMR, absorption, fluorescence, life time measurements and molecular modeling methods.

  1. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture

    NASA Astrophysics Data System (ADS)

    Lotfy, Hayam M.; Hegazy, Maha A.; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-01

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits.

  2. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture.

    PubMed

    Lotfy, Hayam M; Hegazy, Maha A; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-15

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits. PMID:26322842

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. "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

  3. 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

  4. 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

  5. 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.

  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. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  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. PMID:23357598

  20. 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.

  1. 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).

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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).

  10. Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling.

    PubMed

    Sørensen, Amalie Møller; Hansen, Cecilie Hurup; Bonomo, Silvia; Olsen, Lars; Jørgensen, Flemming Steen; Weisser, Johan Juhl; Kretschmann, Andreas Christopher; Styrishave, Bjarne

    2016-08-01

    Enantiomers possess different pharmacokinetic and pharmacodynamic properties and this may not only influence the therapeutic effect of a drug but also its toxicological effects. In the present work we investigated the potential enantioselective endocrine disrupting effects of omeprazole (OME) and its two enantiomers on the human steroidogenesis using the H295R cell line. Differences in production of 16 steroid hormones were analyzed using LC-MS/MS. Additionally, to evaluate the differences in binding modes of these enantiomers, docking and molecular dynamics (MD) simulations of S-omeprazole (S-OME) and R-omeprazole (R-OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17α-hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed, indicating inhibition of CYP21A2 and CYP17A1. In both cases, the effect of R-OME was smaller compared to that of the S-OME and a certain degree of enantioselectivity of CYP17A1 and CYP21A2 was suggested. Docking indicated that the N-containing rings of OME possibly could interact with the iron atom of the heme for S-OME in CYP17A1 and S- and R-OME in CYP21A2. However, density functional theory calculations suggest that the direct N-Fe interaction is weak. The study demonstrates enantioselective differences in the endocrine disrupting potential of chiral drugs such as omeprazole. These findings may have potential implications for drug safety and drug design.

  11. 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.

  12. 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

  13. 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.

  14. [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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Looking for the interactions between omeprazole and amoxicillin in a disordered phase. An experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Russo, Marcos G.; Sancho, Matias I.; Silva, Lorena M. A.; Baldoni, Hector A.; Venancio, Tiago; Ellena, Javier; Narda, Griselda E.

    2016-03-01

    In this paper, co-grinding mixtures of omeprazole-amoxicillin trihydrate (CGM samples) and omeprazole-anhydrous amoxicillin (CGMa samples) at 3:7, 1:1 and 7:3 molar ratios, respectively, were studied with the aim of obtaining a co-amorphous system and determining the potential intermolecular interactions. These systems were fully characterized by differential scanning calorimetry (DSC), FT-infrared spectroscopy (FTIR), X-ray powder diffraction (PXRD), scanning electron microscopy (SEM) and solid state Nuclear Magnetic Resonance (ssNMR). The co-grinding process was not useful to get a co-amorphous system but it led to obtaining the 1:1 CGMa disordered phase. Moreover, in this system both FTIR and ssNMR analysis strongly suggest intermolecular interactions between the sulfoxide group of omeprazole and the primary amine of amoxicillin anhydrous. The solubility measurements were performed in simulated gastric fluid (SGF) to prove the effect of the co-grinding process. Complementarily, we carried out density functional theory calculations (DFT) followed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in order to shed some light on the principles that guide the possible formation of heterodimers at the molecular level, which are supported by spectroscopic experimental findings.

  20. Looking for the interactions between omeprazole and amoxicillin in a disordered phase. An experimental and theoretical study.

    PubMed

    Russo, Marcos G; Sancho, Matias I; Silva, Lorena M A; Baldoni, Hector A; Venancio, Tiago; Ellena, Javier; Narda, Griselda E

    2016-03-01

    In this paper, co-grinding mixtures of omeprazole-amoxicillin trihydrate (CGM samples) and omeprazole-anhydrous amoxicillin (CGMa samples) at 3:7, 1:1 and 7:3 molar ratios, respectively, were studied with the aim of obtaining a co-amorphous system and determining the potential intermolecular interactions. These systems were fully characterized by differential scanning calorimetry (DSC), FT-infrared spectroscopy (FTIR), X-ray powder diffraction (PXRD), scanning electron microscopy (SEM) and solid state Nuclear Magnetic Resonance (ssNMR). The co-grinding process was not useful to get a co-amorphous system but it led to obtaining the 1:1 CGMa disordered phase. Moreover, in this system both FTIR and ssNMR analysis strongly suggest intermolecular interactions between the sulfoxide group of omeprazole and the primary amine of amoxicillin anhydrous. The solubility measurements were performed in simulated gastric fluid (SGF) to prove the effect of the co-grinding process. Complementarily, we carried out density functional theory calculations (DFT) followed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in order to shed some light on the principles that guide the possible formation of heterodimers at the molecular level, which are supported by spectroscopic experimental findings. PMID:26654963

  1. 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...

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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 dosimeter, respectively. Results: Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). Conclusion: A safe 131I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers. PMID:27408884

  8. High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma.

    PubMed

    Kremens, B; Gruhn, B; Klingebiel, T; Hasan, C; Laws, H-J; Koscielniak, E; Hero, B; Selle, B; Niemeyer, C; Finckenstein, F G; Schulz, A; Wawer, A; Zintl, F; Graf, N

    2002-12-01

    Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. From April 1992 to December 1998, 23 evaluable patients received HDC within the German Cooperative Wilms Tumor Studies. Nineteen were given melphalan, etoposide and carboplatin (MEC); the others received different regimens. The dose of carboplatin was adjusted according to renal function. Indications for HDC were high-risk relapse in 20 patients, bone metastases in two patients and no response in one patient. Fourteen of 23 patients are alive after a median observation time of 41 months, 11 of 14 in continuous complete remission, three in CR after relapse post HDC. The estimated survival and event-free survival for these patients are 60.9% and 48.2%. Twelve children relapsed after HDC; nine of them died within 12 months and three are surviving from 20 to 33 months after relapse. The main toxicities were hematologic, mucositis and renal (tubular dysfunction; intermittent hemodialysis in one patient). There were no toxic deaths. About half of the children suffering from Wilms tumor with very unfavorable prognostic factors survive disease-free after HDC for over 3 years. Besides hematological toxicity, mucositis and infections, renal function is at risk during HDC. With dose adjustment on glomerular filtration rate, however, no permanent renal failure was observed. PMID:12476282

  9. High dose chemotherapy with stem cell support in the treatment of testicular cancer.

    PubMed

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-12-26

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  10. Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation.

    PubMed

    Shao, Lijian; Sun, Yan; Zhang, Zhonghui; Feng, Wei; Gao, Yongxing; Cai, Zailong; Wang, Zack Z; Look, A Thomas; Wu, Wen-Shu

    2010-06-10

    Bone marrow injury is a major adverse side effect of radiation and chemotherapy. Attempts to limit such damage are warranted, but their success requires a better understanding of how radiation and anticancer drugs harm the bone marrow. Here, we report one pivotal role of the BH3-only protein Puma in the radiosensitivity of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Puma deficiency in mice confers resistance to high-dose radiation in a hematopoietic cell-autonomous manner. Unexpectedly, loss of one Puma allele is sufficient to confer mice radioresistance. Interestingly, null mutation in Puma protects both primitive and differentiated hematopoietic cells from damage caused by low-dose radiation but selectively protects HSCs and HPCs against high-dose radiation, thereby accelerating hematopoietic regeneration. Consistent with these findings, Puma is required for radiation-induced apoptosis in HSCs and HPCs, and Puma is selectively induced by irradiation in primitive hematopoietic cells, and this induction is impaired in Puma-heterozygous cells. Together, our data indicate that selective targeting of p53 downstream apoptotic targets may represent a novel strategy to protecting HSCs and HPCs in patients undergoing intensive cancer radiotherapy and chemotherapy.

  11. High doses of gamma radiation suppress allergic effect induced by food lectin

    NASA Astrophysics Data System (ADS)

    Vaz, Antônio F. M.; Souza, Marthyna P.; Vieira, Leucio D.; Aguiar, Jaciana S.; Silva, Teresinha G.; Medeiros, Paloma L.; Melo, Ana M. M. A.; Silva-Lucca, Rosemeire A.; Santana, Lucimeire A.; Oliva, Maria L. V.; Perez, Katia R.; Cuccovia, Iolanda M.; Coelho, Luana C. B. B.; Correia, Maria T. S.

    2013-04-01

    One of the most promising areas for the development of functional foods lies in the development of effective methods to reduce or eliminate food allergenicity, but few reports have summarized information concerning the progress made with food irradiation. In this study, we investigated the relationship between allergenicity and molecular structure of a food allergen after gamma irradiation and evaluate the profile of the allergic response to irradiated allergens. Cramoll, a lectin isolated from a bean and used as a food allergen, was irradiated and the possible structural changes were accompanied by spectrofluorimetry, circular dichroism and microcalorimetry. Subsequently, sensitized animals subjected to intragastric administration of non-irradiated and irradiated Cramoll were treated for 7 days. Then, body weight, leukocytes, cytokine profiles and histological parameters were also determined. Cramoll showed complete inhibition of intrinsic activity after high radiation doses. Changes in fluorescence and CD spectra with a simultaneous collapse of the tertiary structure followed by a pronounced decrease of native secondary structure were observed after irradiation. After oral challenge, sensitized mice demonstrate an association between Cramoll intake, body weight loss, eosinophilia, lymphocytic infiltrate in the gut and Eotaxin secretion. Irradiation significantly reduces, according to the dose, the effects observed by non-irradiated food allergens. We confirm that high-dose radiation may render protein food allergens innocuous by irreversibly compromising their molecular structure.

  12. High dose chemotherapy with stem cell support in the treatment of testicular cancer

    PubMed Central

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-01-01

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  13. [Cytosine-arabinoside in high doses in refractory acute granulocytic leukemia. Apropos of 17 cases].

    PubMed

    Jouet, J P; Simon, M; Fenaux, P; Pollet, J P; Bauters, F

    1985-01-01

    A total of 17 patients, 6 female and 11 male (age range 13 to 56 years), received high dose Ara-C for treatment of refractory acute myelogenous leukemia. Ara-C was given at 3 g/m2 twice daily for 6 days as a 1 infusion. 1 patient (with induced acute leukemia) was treated directly, two after failure of a chemotherapy schedule containing the usual dose Ara-C, 12 for first relapse and 2 for subsequent relapse. Maximum follow up is 16 months. Beside hematological toxicity, systemic tolerance was good with no neurological of cutaneous effects. Despite preventive corticoid eyewash, ocular complications occurred in 6 cases, mild and resolvable in 5 of them. The immediate results were as follows: 3 deaths during induction (18%); 6 failures (35%); 8 complete remissions (CR) (47%). After primary chemo-resistance (two cases) failure was always noted. In 3 cases, after less than 12 infusions had been given, 2 failures and 1 very short CR were noted. In 2 patients, when doxorubicin was added to Ara-C, we observed 1 death during induction and 1 failure. Of the patients achieving CR 8 were treated by periodic courses with high dose Ara-C and 4 of them relapsed. The longest failure free duration was 11 months. Median survival duration of the 17 patients is 5 months. PMID:3862072

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

    PubMed

    Vuong, T; Devic, S; Podgorsak, E

    2007-11-01

    In the era of total mesorectal surgery, the issue of radiation toxicity is raised. A novel endocavitary brachytherapy technique was tested as a neoadjuvant treatment for patients with resectable rectal cancer. The objectives of the study were to evaluate the treatment-related toxicity and effects on local recurrence. A dose of 26 Gy was prescribed to the gross tumour volume and intramesorectal deposits seen on magnetic resonance imaging and given over four daily treatments, using the high dose rate delivery system followed by surgery 6-8 weeks later. The study included 93 T3, four T4 and three T2 tumours. Acute proctitis of grade 2 was observed in all patients, but one required transfusion. At a median follow-up time of 60 months, the 5-year actual local recurrence rate was 5%, disease-free survival was 65%, and overall survival was 70%. High dose rate endorectal brachytherapy seems to prevent local recurrence and has a favourable toxicity pattern compared with external beam radiotherapy. PMID:17714925

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

    PubMed

    Bauters, T; Vandenbroucke, J; Commeyne, S

    2015-12-01

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

  16. High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

    SciTech Connect

    Kim, Young Seok; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Choi, Eun Kyung

    2009-08-01

    Purpose: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. Methods and Materials: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). Results: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. Conclusion: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

  17. Radiation Dose Measurement for High-Intensity Laser Interactions with Solid Targets at SLAC

    SciTech Connect

    Liang, Taiee

    2015-09-25

    A systematic study of photon and neutron radiation doses generated in high-intensity laser-solid interactions is underway at SLAC National Accelerator Laboratory. We found that these laser-solid experiments are being performed using a 25 TW (up to 1 J in 40 fs) femtosecond pulsed Ti:sapphire laser at the Linac Coherent Light Source’s (LCLS) Matter in Extreme Conditions (MEC) facility. Additionally, radiation measurements were performed with passive and active detectors deployed at various locations inside and outside the target chamber. Results from radiation dose measurements for laser-solid experiments at SLAC MEC in 2014 with peak intensity between 1018 to 7.1x1019 W/cm2 are presented.

  18. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    NASA Astrophysics Data System (ADS)

    Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  19. A root cause analysis of the high occupational doses of industrial radiographers in Iran.

    PubMed

    Mianji, F; Hosseini Pooya, S M; Zakeri, F; Dashtipour, M R

    2016-03-01

    The Iran Nuclear Regulatory Authority has investigated overexposure cases in industrial radiography over a period of three years. Radiographers with thermoluminescence dosimeter (TLD) records of more than 4 mSv in any 2 month routine monitoring period were asked to fill in a questionnaire explaining their points of view of the reasons for such relatively high doses. The responses showed that more than 50% of the radiographers did not agree with their recorded TLD doses, although the majority of the alternative explanations were weak. The main causes of overexposures were found to be difficult working conditions and ignoring safety principles while accidents or device failures were a minor contribution. Also, there was poor correlation between the TLDs and direct reading dosimeters worn by the radiographers, indicating that personal monitoring instructions were not being implemented appropriately. PMID:26910013

  20. Erasure of a spinal memory trace of pain by a brief, high-dose opioid administration.

    PubMed

    Drdla-Schutting, Ruth; Benrath, Justus; Wunderbaldinger, Gabriele; Sandkühler, Jürgen

    2012-01-13

    Painful stimuli activate nociceptive C fibers and induce synaptic long-term potentiation (LTP) at their spinal terminals. LTP at C-fiber synapses represents a cellular model for pain amplification (hyperalgesia) and for a memory trace of pain. μ-Opioid receptor agonists exert a powerful but reversible depression at C-fiber synapses that renders the continuous application of low opioid doses the gold standard in pain therapy. We discovered that brief application of a high opioid dose reversed various forms of activity-dependent LTP at C-fiber synapses. Depotentiation involved Ca(2+)-dependent signaling and normalization of the phosphorylation state of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This also reversed hyperalgesia in behaving animals. Opioids thus not only temporarily dampen pain but may also erase a spinal memory trace of pain.

  1. A standard graphite calorimeter for dosimetry in brachytherapy with high dose rate 192Ir sources

    NASA Astrophysics Data System (ADS)

    Guerra, A. S.; Loreti, S.; Pimpinella, M.; Quini, M.; D'Arienzo, M.; Astefanoaei, I.; Caporali, C.; Bolzan, C.; Pagliari, M.

    2012-10-01

    Within the framework of the JRP06 European project ‘Increasing Cancer Treatment Efficacy Using 3D Brachytherapy’, a prototype of a graphite standard calorimeter for the measurement of the absorbed dose rate to water, \\dot {D}_w , for 192Ir sources used in high dose rate (HDR) brachytherapy has been developed at the Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI). The calorimeter was tested at the Sant'Andrea Hospital in Rome, where \\dot {D}_w measurements were performed in the quasi-adiabatic mode of operation using an 192Ir MicroSelectron® HDR V2 source. The \\dot {D}_w measurements showed a reproducibility of about 1%, while the combined standard uncertainty on the \\dot {D}_w value at the distance of 1 cm from the source was estimated as 1.4%, lower than the uncertainty of \\dot {D}_w determined from the reference air-kerma rate.

  2. Protection of mice from lethal influenza virus infection with high dose-short duration ribavirin aerosol.

    PubMed Central

    Wyde, P R; Wilson, S Z; Gilbert, B E; Smith, R H

    1986-01-01

    An aerosol generated from a reservoir containing 60 mg of ribavirin per ml given for 2 h twice daily for 4 days afforded the same high level of protection against lethal influenza virus infection of mice as a longer, conventional treatment schedule (20 mg/ml given for 11 h daily for 4 days). Incremental decreases in ribavirin concentration made while maintaining the 2-h intermittent schedule provided progressively less protection of mice. Mice exposed to the 60-mg/ml doses had significantly increased pulmonary and serum drug levels when compared with mice given 20 mg of drug per ml, these increases were transient, and no evidence of pulmonary intolerance was detected. These studies suggest that protective effects of ribavirin against influenza virus infection can be achieved without untoward effects if higher doses and shorter periods of administration are used. PMID:3813516

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

    PubMed

    Celis, Pilar; Rada, Gabriel

    2015-08-19

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

  4. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    SciTech Connect

    Hunt, W.A.; Joseph, J.A.; Rabin, B.M.

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  5. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

    SciTech Connect

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

    2013-03-01

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

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

    SciTech Connect

    Madu, Chika N. . E-mail: chikam@xrt.upenn.edu; Machuzak, Michael S.; Sterman, Daniel H.; Musani, Ali; Ahya, Vivek; McDonough, James; Metz, James M.

    2006-12-01

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

  7. Comparison between low-dose, high-sort and high-dose, low-sort semen on conception and calf sex ratio in Jersey heifers and cows.

    PubMed

    Lucena, J A; Kenyon, A G; Reynolds, J P; Moreno, J F; Lenz, R W; Carroll, D; Lehenbauer, T W; Champagne, J D; Aly, S S

    2014-03-01

    The objective of this clinical trial was to compare conception and newborn calf sex ratios among Jersey heifers and lactating cows inseminated with either standard sex-sorted semen (low-dose, high-sort; LDHS) containing 2.1 × 10(6) sorted sperm at 90% purity or high-dose, low-sort (HDLS) semen containing 10 × 10(6) sorted sperm at 75% purity. After a specified voluntary waiting period (VWP), female subjects, consisting of nulliparous heifers (VWP 10 mo of age) and lactating cows (VWP 50d in milk), received their first service and were systematically allocated to each treatment group in the order in which they presented for artificial insemination (AI). Females were bred to the same sire and type of sex-sorted semen for up to 2 additional services. Animals that were not pregnant after 3 breeding attempts were excluded. A total of 1,846 services were performed on 1,011 eligible females (LDHS; n=494, HDLS; n=517), which consisted of 516 nulliparous heifers and 495 lactating cows. Study groups were comparable with respect to the mean age at first AI for nulliparous heifers and the mean days in milk at first AI for parous cows. Insemination with HDLS semen did not result in a higher proportion of pregnancies per AI (P/AI) compared with LDHS semen for either nulliparous heifers (P/AI=43 vs. 38%) or parous cows (P/AI=47 vs. 43%). Insemination of nulliparous heifers using HDLS resulted in a lower proportion of newborn female calves compared with those bred to LDHS (76% vs. 87%). Similarly, lactating cows bred to HDLS gave birth to a lower proportion of newborn female calves compared with those bred to LDHS (79 vs. 90%). The odds ratio for a female calf to be born to an animal inseminated with HDLS compared with LDHS was 0.32 for nulliparous heifers and 0.19 for parous cows. Overall, the use of HDLS resulted in fewer females compared with LDHS, which may be explained by the lower concentration of X-bearing spermatozoa in HDLS compared with LDHS. PMID:24418279

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

    PubMed Central

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

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  9. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    SciTech Connect

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  10. Physics-aspects of dose accuracy in high dose rate (HDR) brachytherapy: source dosimetry, treatment planning, equipment performance and in vivo verification techniques

    PubMed Central

    Bradley, David; Nisbet, Andrew

    2012-01-01

    This study provides a review of recent publications on the physics-aspects of dosimetric accuracy in high dose rate (HDR) brachytherapy. The discussion of accuracy is primarily concerned with uncertainties, but methods to improve dose conformation to the prescribed intended dose distribution are also noted. The main aim of the paper is to review current practical techniques and methods employed for HDR brachytherapy dosimetry. This includes work on the determination of dose rate fields around brachytherapy sources, the capability of treatment planning systems, the performance of treatment units and methods to verify dose delivery. This work highlights the determinants of accuracy in HDR dosimetry and treatment delivery and presents a selection of papers, focusing on articles from the last five years, to reflect active areas of research and development. Apart from Monte Carlo modelling of source dosimetry, there is no clear consensus on the optimum techniques to be used to assure dosimetric accuracy through all the processes involved in HDR brachytherapy treatment. With the exception of the ESTRO mailed dosimetry service, there is little dosimetric audit activity reported in the literature, when compared with external beam radiotherapy verification. PMID:23349649

  11. Design and implementation of a film dosimetry audit tool for comparison of planned and delivered dose distributions in high dose rate (HDR) brachytherapy.

    PubMed

    Palmer, Antony L; Lee, Chris; Ratcliffe, Ailsa J; Bradley, David; Nisbet, Andrew

    2013-10-01

    A novel phantom is presented for 'full system' dosimetric audit comparing planned and delivered dose distributions in HDR gynaecological brachytherapy, using clinical treatment applicators. The brachytherapy applicator dosimetry test object consists of a near full-scatter water tank with applicator and film supports constructed of Solid Water, accommodating any typical cervix applicator. Film dosimeters are precisely held in four orthogonal planes bisecting the intrauterine tube, sampling dose distributions in the high risk clinical target volume, points A and B, bladder, rectum and sigmoid. The applicator position is fixed prior to CT scanning and through treatment planning and irradiation. The CT data is acquired with the applicator in a near clinical orientation to include applicator reconstruction in the system test. Gamma analysis is used to compare treatment planning system exported RTDose grid with measured multi-channel film dose maps. Results from two pilot audits are presented, using Ir-192 and Co-60 HDR sources, with a mean gamma passing rate of 98.6% using criteria of 3% local normalization and 3 mm distance to agreement (DTA). The mean DTA between prescribed dose and measured film dose at point A was 1.2 mm. The phantom was funded by IPEM and will be used for a UK national brachytherapy dosimetry audit.

  12. Low-dose, phase-contrast mammography with high signal-to-noise ratio

    PubMed Central

    Gromann, Lukas B.; Bequé, Dirk; Scherer, Kai; Willer, Konstantin; Birnbacher, Lorenz; Willner, Marian; Herzen, Julia; Grandl, Susanne; Hellerhoff, Karin; Sperl, Jonathan I.; Pfeiffer, Franz; Cozzini, Cristina

    2016-01-01

    Differential phase-contrast X-ray imaging using a Talbot-Lau interferometer has recently shown promising results for applications in medical imaging. However, reducing the applied radiation dose remains a major challenge. In this study, we consider the realization of a Talbot-Lau interferometer in a high Talbot order to increase the signal-to-noise ratio for low-dose applications. The quantitative performance of π and π/2 systems at high Talbot orders is analyzed through simulations, and the design energy and X-ray spectrum are optimized for mammography. It is found that operation even at very high Talbot orders is feasible and beneficial for image quality. As long as the X-ray spectrum is matched to the visibility spectrum, the SNR continuously increases with the Talbot order for π-systems. We find that the optimal X-ray spectra and design energies are almost independent of the Talbot order and that the overall imaging performance is robust against small variations in these parameters. Discontinuous spectra, such as that from molybdenum, are less robust because the characteristic lines may coincide with minima in the visibility spectra; however, they may offer slightly better performance. We verify this hypothesis by realizing a prototype system with a mean fringe visibility of above 40% at the seventh Talbot order. With this prototype, a proof-of-principle measurement of a freshly dissected breast at reasonable compression to 4 cm is conducted with a mean glandular dose of only 3 mGy but with a high SNR. PMID:26977347

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

    Ferritic/martensitic (F/M) steels are considered for core applications and pressure vessels in Generation IV reactors as well as first walls and blankets for fusion reactors. There are significant scientific data on testing and industrial experience in making this class of alloys worldwide. This experience makes F/M steels an attractive candidate. In this article, tensile behavior, fracture toughness and impact property, and creep behavior of the F/M steels under neutron irradiations to high doses with a focus on high Cr content (8 to 12) are reviewed. Tensile properties are very sensitive to irradiation temperature. Increase in yield and tensile strength (hardening) is accompanied with a loss of ductility and starts at very low doses under irradiation. The degradation of mechanical properties is most pronounced at <0.3 T M ( T M is melting temperature) and up to 10 dpa (displacement per atom). Ferritic/martensitic steels exhibit a high fracture toughness after irradiation at all temperatures even below 673 K (400 °C), except when tested at room temperature after irradiations below 673 K (400 °C), which shows a significant reduction in fracture toughness. Creep studies showed that for the range of expected stresses in a reactor environment, the stress exponent is expected to be approximately one and the steady state creep rate in the absence of swelling is usually better than austenitic stainless steels both in terms of the creep rate and the temperature sensitivity of creep. In short, F/M steels show excellent promise for high dose applications in nuclear reactors.

  14. Brain Magnetic Resonance Imaging After High-Dose Chemotherapy and Radiotherapy for Childhood Brain Tumors

    SciTech Connect

    Spreafico, Filippo Gandola, Lorenza; Marchiano, Alfonso; Simonetti, Fabio; Poggi, Geraldina; Adduci, Anna; Clerici, Carlo Alfredo; Luksch, Roberto; Biassoni, Veronica; Meazza, Cristina; Catania, Serena; Terenziani, Monica; Musumeci, Renato; Fossati-Bellani, Franca; Massimino, Maura

    2008-03-15

    Purpose: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. Methods and Materials: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Results: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T{sub 1}-weighted unevenly enhancing, and T{sub 2}-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74% {+-} 6% at 1 year and 57% {+-} 8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Conclusion: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-a-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.

  15. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    SciTech Connect

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

    2012-09-01

    Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

  16. 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

  17. A Dose-Volume Analysis of Magnetic Resonance Imaging-Aided High-Dose-Rate Image-Based Interstitial Brachytherapy for Uterine Cervical Cancer

    SciTech Connect

    Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

    2010-07-01

    Purpose: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Methods and Materials: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD{sub 2}). Results: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D{sub 2cc} of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Conclusions: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

  18. 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

  19. 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

  20. A generic high-dose rate {sup 192}Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism

    SciTech Connect

    Ballester, Facundo; Carlsson Tedgren, Åsa; Granero, Domingo; Haworth, Annette; Mourtada, Firas; Fonseca, Gabriel Paiva; Rivard, Mark J.; Siebert, Frank-André; Sloboda, Ron S.; and others

    2015-06-15

    Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) {sup 192}Ir source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR {sup 192}Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic {sup 192}Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra{sup ®} Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS{sup TM}]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201){sup 3} voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR {sup 192}Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by

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

    PubMed Central

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L.; Potthoff, Sebastian A.; Kelm, Malte; Schurgers, Leon J.; Westenfeld, Ralf

    2015-01-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

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

    PubMed

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L; Potthoff, Sebastian A; Kelm, Malte; Schurgers, Leon J; Westenfeld, Ralf

    2015-08-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  3. Prospective Clinical Trial of Bladder Filling and Three-Dimensional Dosimetry in High-Dose-Rate Vaginal Cuff Brachytherapy

    SciTech Connect

    Stewart, Alexandra J.; Cormack, Robert A.; Lee, Hang; Xiong Li; Hansen, Jorgen L.; O'Farrell, Desmond A.; Viswanathan, Akila N.

    2008-11-01

    Purpose: To investigate the effect of bladder filling on dosimetry and to determine the best bladder dosimetric parameter for vaginal cuff brachytherapy. Methods and Materials: In this prospective clinical trial, a total of 20 women underwent vaginal cylinder high-dose-rate brachytherapy. The bladder was full for Fraction 2 and empty for Fraction 3. Dose-volume histogram and dose-surface histogram values were generated for the bladder, rectum, and urethra. The midline maximal bladder point (MBP) and the midline maximal rectal point were recorded. Paired t tests, Pearson correlations, and regression analyses were performed. Results: The volume and surface area of the irradiated bladder were significantly smaller when the bladder was empty than when full. Of the several dose-volume histogram and dose-surface histogram parameters evaluated, the bladder maximal dose received by 2 cm{sup 3} of tissue, volume of bladder receiving {>=}50% of the dose, volume of bladder receiving {>=}70% of the dose, and surface area of bladder receiving {>=}50% of the dose significantly predicted for the difference between the empty vs. full filling state. The volume of bladder receiving {>=}70% of the dose and the maximal dose received by 2 cm{sup 3} of tissue correlated significantly with the MBP. Bladder filling did not alter the volume or surface area of the rectum irradiated. However, an empty bladder did result in the nearest point of bowel being significantly closer to the vaginal cylinder than when the bladder was full. Conclusions: Patients undergoing vaginal cuff brachytherapy treated with an empty bladder have a lower bladder dose than those treated with a full bladder. The MBP correlated well with the volumetric assessments of bladder dose and provided a noninvasive method for reporting the MBP dose using three-dimensional imaging. The MBP can therefore be used as a surrogate for complex dosimetry in the clinic.

  4. Monte Carlo dosimetric study of the Flexisource Co-60 high dose rate source

    PubMed Central

    Granero, Domingo; Perez-Calatayud, Jose; Ballester, Facundo

    2012-01-01

    Purpose Recently, a new HDR 60Co brachytherapy source, Flexisource Co-60, has been developed (Nucletron B.V. Veenendaal, The Netherlands). This study aims to obtain dosimetric data for this source for its use in clinical practice as required by AAPM and ESTRO. Material and methods Two Monte Carlo radiation transport codes were used: Penelope2008 and GEANT4. The source was centrally-positioned in a 100 cm radius water phantom. Absorbed dose and collisional kerma were obtained using 0.01 cm (close) and 0.1 cm (far) sized voxels to provide high-resolution dosimetry near (far from) the source. Dose rate distributions obtained with the two Monte Carlo codes were compared. Results and Discussion Simulations performed with those two radiation transport codes showed an agreement typically within 0.2% for r > 0.8 cm and up to 2% closer to the source. Detailed results of dose distributions are being made available. Conclusions Dosimetric data are provided for the new Flexisource Co-60 source. These data are meant to be used in treatment planning systems in clinical practice. PMID:23346138

  5. High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration

    PubMed Central

    Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung

    2016-01-01

    Purpose Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. Methods In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. Results The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Conclusions Increasing the dose of bevacizumab in refractory PED may be a possible treatment option. PMID:27478353

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

    SciTech Connect

    Scanderbeg, Daniel J.; Alksne, John F.; Lawson, Joshua D.; Murphy, Kevin T.

    2011-01-01

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

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

    PubMed

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

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm(3)to 23.3 cm(3)) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions. PMID:26378657

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  9. High dose rates obtained outside ISS in June 2015 during SEP event.

    PubMed

    Dachev, T P; Tomov, B T; Matviichuk, Yu N; Dimitrov, Pl G; Bankov, N G

    2016-06-01

    The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000µGyh(-1), while the inner radiation belt maximum dose was at the level of 2200µGyh(-1). If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84mGy after 6.5h, which is similar to the average absorbed dose inside ISS for 15days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA. PMID:27345205

  10. High dose rates obtained outside ISS in June 2015 during SEP event

    NASA Astrophysics Data System (ADS)

    Dachev, T. P.; Tomov, B. T.; Matviichuk, Yu. N.; Dimitrov, Pl. G.; Bankov, N. G.

    2016-06-01

    The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7 MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000 μGy h-1, while the inner radiation belt maximum dose was at the level of 2200 μGy h-1. If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84 mGy after 6.5 h, which is similar to the average absorbed dose inside ISS for 15 days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA.

  11. Endocrine function following high dose proton therapy for tumors of the upper clivus

    SciTech Connect

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  12. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-11-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.

  13. Histamine stimulates chloride secretion in omeprazole-inhibited frog gastric mucosa

    SciTech Connect

    McGreevy, J.; Barton, R.; Housinger, T.

    1986-03-05

    Omeprazole (OME) stops hydrogen ion (H) secretion in the histamine (HIST)-stimulated gastric mucosa while the chloride (Cl) which had accompanied the H continues to be pumped into the lumen. This finding suggests that the Cl pump is independent of the H/K ATP-ase driven H pump. To test this hypothesis, 16 Ussing-chambered frog mucosas were exposed to OME prior to HIST stimulation. If the Cl pump is independent, HIST should stimulate Cl secretion in the OME-inhibited mucosa. A 1 hr control (CON) interval preceded exposure to OME (10/sup -4/M) in the nutrient solution. Potential difference (PD), short-circuit current (Isc), resistance (R), H flux (J/sup H/) and Cl flux (J/sup Cl/ with /sup 36/Cl) were measured every 15 min. After 1 hr of OME exposure, HIST (10/sup -5/M) was added to the nutrient solution. The findings demonstrate that HIST stimulates Cl secretion in the OME-inhibited bullfrog gastric mucosa.

  14. 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

  15. SU-E-T-383: Can Stereotactic Body Radiotherapy Mimic the Dose Distribution of High-Dose-Rate Tandem and Ovoids/ring Brachytherapy?

    SciTech Connect

    Park, S; Demanes, J; Kamrava, M; Scanderbeg, D

    2014-06-01

    Purpose: To investigate whether stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) can mimic the dosimetry of tandem and ovoids/ring brachytherapy. Methods: We selected 5 patients treated with 3D-CT based high-dose rate (HDR) brachytherapy using 4 tandem and ovoid and 1 tandem and ring case. Manual optimization based on the Manchester system followed by graphical optimization (Nucletron Oncentra MasterPlan or Varian BrachyVision) was performed to deliver 6.0 Gy per fraction to a high-risk CTV while maintaining dose to organs at risk (OAR) below the ABS recommendations. For theoretical SBRT plans, CT images and OAR contours from the HDR plans were imported into Eclipse (Varian). The SBRT plan was created to mimic the heterogeneity of HDR plans by using a simultaneous integrated boost technique to match the V100, V150, and V200 isodose volumes from HDR. The OAR Dmax from HDR was used to define the OAR dose constraints for SBRT. Target coverage, dose spill-out, and OAR doses (D0.1cc, D1cc, and D2cc) between the HDR and SBRT plans were compared for significance using a two-tail paired ttest. Results: The mean isodose volumes for HDR vs. SBRT were 29.4 cc vs. 29.0 cc (V200, p = 0.674), 49.2 cc vs. 56.3 cc (V150, p = 0.017), 95.4 cc vs. 127.7 cc (V100, p = 0.001), and 271.9 cc vs. 581.6 cc (V50, p = 0.001). The D2cc to OAR for HDR vs. SBRT was 71.6% vs. 96.2% (bladder, p = 0.002), 69.2% vs. 101.7% (rectum, p = 0.0003), and 56.9% vs. 68.6% (sigmoid, p = 0.004). Conclusion: SBRT with VMAT can provide similar dose target coverage (V200), but dose spill-out and doses to OAR were statistically significantly higher than HDR. This study clearly demonstrated that brachytherapy can not be substituted with SBRT in gynecologic cervical cancer treatment.

  16. Hypersensitivity Reaction to High-Dose Methotrexate and Successful Rechallenge in a Pediatric Patient with Osteosarcoma

    PubMed Central

    Scott, Jeffrey R.; Ward, Deborah A.; Crews, Kristine R.; Panetta, John C.; Navid, Fariba

    2014-01-01

    Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted. PMID:23955991

  17. Interstitial injection in silicon after high-dose, low-energy arsenic implantation and annealing

    SciTech Connect

    Tsamis, C.; Skarlatos, D.; BenAssayag, G.; Claverie, A.; Lerch, W.; Valamontes, V.

    2005-11-14

    In this work, we investigate the interstitial injection into the silicon lattice due to high-dose, low-energy arsenic implantation. The approach consists in monitoring the diffusion of the arsenic profile as well as of the boron profile in buried {delta}-doped layers, when amounts of the as-implanted arsenic profile are removed by low-temperature wet silicon etching. The experimental results indicate that the contribution of the implantation damage to the transient enhanced diffusion of boron, and thus the interstitial injection, is not the main one. On the contrary, interstitial generation due to arsenic clustering seems to be more important for the present conditions.

  18. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation

    PubMed Central

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate. This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m2), and 4 doses of bortezomib (1.3 mg/m2). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients. There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83 ± 16.0 (14952 ± 5820) and 63 ± 36.0 (10321 ± 7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468–634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group. In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID:26844479

  19. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

    PubMed

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-02-01

    Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

  20. Global Gene Expression Responses to Low- or High-Dose Radiation in a Human Three-Dimensional Tissue Model

    PubMed Central

    Mezentsev, Alexandre; Amundson, Sally A.

    2011-01-01

    Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low-dose responses to better understand potential risks. Most such studies have used two-dimensional culture systems, which may not fully represent responses in three-dimensional tissues. To gain insight into low-dose responses in tissue, we have profiled global gene expression in EPI-200, a three-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 h after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low-LET protons. The most significant gene ontology groups among genes altered in expression were consistent with effects observed at the tissue level, where the low dose was associated with recovery and tissue repair, while the high dose resulted in loss of structural integrity and terminal differentiation. Network analysis of the significantly responding genes suggested that TP53 dominated the response to 2.5 Gy, while HNF4A, a novel transcription factor not previously associated with radiation response, was most prominent in the low-dose response. HNF4A protein levels and phosphorylation were found to increase in tissues and cells after low- but not high-dose irradiation. PMID:21486161

  1. High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea

    PubMed Central

    Graham, David Y.

    2016-01-01

    Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance. PMID:27413365

  2. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma.

    PubMed

    Kaufman, G P; Gertz, M A; Dispenzieri, A; Lacy, M Q; Buadi, F K; Dingli, D; Hayman, S R; Kapoor, P; Lust, J A; Russell, S; Go, R S; Hwa, Y L; Kyle, R A; Rajkumar, S V; Kumar, S K

    2016-03-01

    Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in situ hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years. PMID:26487275

  3. High-dose chemotherapy with autologous stem cell rescue in the outpatient setting.

    PubMed

    Dix, S P; Geller, R B

    2000-02-01

    Intensive outpatient care is rapidly becoming the primary mode of care for selected patients undergoing high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although the traditional inpatient model of care may still be necessary for high-risk patients, published data suggest that outpatient care is safe and feasible during or after administration of high-dose chemotherapy and autologous PBSC transplant. Blood and marrow transplant (BMT) centers have developed programs to provide more outpatient care under three basic models: an early discharge model, a delayed admission model, and a comprehensive, or total, outpatient model. This review will describe these models of care and address the elements necessary for the development of an outpatient BMT program, including patient selection, staff development, and patient and caregiver education. Available supportive care strategies to facilitate outpatient care will also be highlighted. Clinical outcome data and pharmacoeconomic analyses evaluating various outpatient BMT programs, as well as limited quality-of-life evaluations, will be reviewed.

  4. HLA-haploidentical blood or marrow transplantation with high-dose, post-transplantation cyclophosphamide.

    PubMed

    Fuchs, E J

    2015-06-01

    In the past, partially HLA-mismatched related donor, or HLA-haploidentical, blood or marrow transplantation (haploBMT), for hematologic malignancies has been complicated by unacceptably high incidences of graft rejection or GvHD resulting from intense bi-directional alloreactivity. Administration of high doses of cyclophosphamide early after haploBMT selectively kills proliferating, alloreactive T cells while sparing non-alloreactive T cells responsible for immune reconstitution and resistance to infection. In the clinic, haploBMT with high-dose, post-transplantation cyclophosphamide is associated with acceptably low incidences of fatal graft rejection, GvHD and non-relapse mortality, and provides an acceptable treatment option for hematologic malignancies patients lacking suitably HLA-matched donors. HaploBMT with PTCy is now being investigated as a treatment of hemoglobinopathy and as a method for inducing tolerance to solid organs transplanted from the same donor. Ongoing and future clinical trials will establish the hierarchy of donor preference for hematologic malignancy patients lacking an HLA-matched sibling.

  5. 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

  6. The Potential for Bayesian Compressive Sensing to Significantly Reduce Electron Dose in High Resolution STEM Images

    SciTech Connect

    Stevens, Andrew J.; Yang, Hao; Carin, Lawrence; Arslan, Ilke; Browning, Nigel D.

    2014-02-11

    The use of high resolution imaging methods in the scanning transmission electron microscope (STEM) is limited in many cases by the sensitivity of the sample to the beam and the onset of electron beam damage (for example in the study of organic systems, in tomography and during in-situ experiments). To demonstrate that alternative strategies for image acquisition can help alleviate this beam damage issue, here we apply compressive sensing via Bayesian dictionary learning to high resolution STEM images. These experiments successively reduce the number of pixels in the image (thereby reducing the overall dose while maintaining the high resolution information) and show promising results for reconstructing images from this reduced set of randomly collected measurements. We show that this approach is valid for both atomic resolution images and nanometer resolution studies, such as those that might be used in tomography datasets, by applying the method to images of strontium titanate and zeolites. As STEM images are acquired pixel by pixel while the beam is scanned over the surface of the sample, these post acquisition manipulations of the images can, in principle, be directly implemented as a low-dose acquisition method with no change in the electron optics or alignment of the microscope itself.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Although high-dose rifampicin holds promise for improving tuberculosis control by potentially shortening treatment duration, these effects attributed to eradication of persistent bacteria are unclear. The presence of persistent Mycobacterium tuberculosis was examined using resuscitation promoting factors (RPFs) in both in vitro hypoxia and in vivo murine tuberculosis models before and after treatment with incremental doses of rifampicin. Pharmacokinetic parameters and dose-dependent profile of rifampicin in the murine model were determined. The Cornell mouse model was used to test efficacy of high-dose rifampicin in combination with isoniazid and pyrazinamide and to measure relapse rate. There were large numbers of RPF-dependent persisters in vitro and in vivo. Stationary phase cultures were tolerant to rifampicin while higher concentrations of rifampicin eradicated plate count positive but not RPF-dependent persistent bacteria. In murine infection model, incremental doses of rifampicin exhibited a dose-dependent eradication of RPF-dependent persisters. Increasing the dose of rifampicin significantly reduced the risk of antibiotic resistance emergence. In Cornell model, mice treated with high-dose rifampicin regimen resulted in faster visceral clearance; organs were M. tuberculosis free 8 weeks post-treatment compared to 14 weeks with standard-dose rifampicin regimen. Organ sterility, plate count and RPF-dependent persister negative, was achieved. There was no disease relapse compared to the standard dose regimen (87.5%). High-dose rifampicin therapy results in eradication of RPF-dependent persisters, allowing shorter treatment duration without disease relapse. Optimizing rifampicin to its maximal efficacy with acceptable side-effect profiles will provide valuable information in human studies and can potentially improve current tuberculosis chemotherapy. PMID:26157437

  9. A Randomized, Double Blinded, Clinical Trial to Assess the Efficacy and Cost Effectiveness of Omeprazole Compared to Rabeprazole in the Maintenance Therapy of Patients With Gastroesophageal Reflux Disease

    PubMed Central

    Park, Jung Ho; Lee, Dong Ho; Sung, In Kyung

    2013-01-01

    Background/Aims The aim of this study was to evaluate the efficacy and cost efficiency of omeprazole 10 mg and rabeprazole 10 mg once daily for 24 weeks in the maintenance therapy. Methods This was a randomized, open-label study enrolling 279 patients with erosive esophagitis A or B (Los Angeles classification) and typical gastroesophageal reflux disease symptoms. Patients who showed complete endoscopic and symptomatic healing after 8 weeks of proton pump inhibitor treatment were randomly allocated to maintenance treatment with omeprazole 10 mg once daily or rabeprazole 10 mg once daily for 42 weeks. The primary efficacy endpoint was the proportion of patients with symptomatic remission at 42 weeks. Results At the end of 42 weeks of maintenance therapy, 96.4% of omeprazole and 95.1% of rabeprazole treated patients remained symptom free (P > 0.05). Two drugs were also comparable with regard to the severity and frequency of reflux symptoms during the maintenance phase (P > 0.05). By the cost-minimization analysis, the mean total costs per patient for remaining symptom-free for 6 months were 241,775 won for omeprazole and 287,115 won for rabeprazole, respectively. Conclusions Omeprazole 10 mg appeared to have similar efficacy in maintaining symptomatic remission as rabeprazole 10 mg, but was superior to rabeprazole 10 mg in terms of cost efficiency in the maintenance therapy of gastroesophageal reflux disease symptoms. PMID:23667753

  10. The relationship between repeat-dose toxicity and aromatic-ring class profile of high-boiling petroleum substances.

    PubMed

    Roth, Randy N; Simpson, Barry J; Nicolich, Mark J; Murray, F Jay; Gray, Thomas M

    2013-11-01

    A study was undertaken within the context of the U.S. EPA HPV Chemical Challenge Program to (1) characterize relationships between PAC content and repeat-dose toxicities of high-boiling petroleum substances (HBPS) and (2) develop statistical models that could be used to predict the repeat-dose toxicity of similar untested substances. The study evaluated 47 repeat-dose dermal toxicity and 157 chemical compositional studies. The four most sensitive endpoints of repeat-dose toxicity were platelet count, hemoglobin concentration, relative liver weight and thymus weight. Predictive models were developed for the dose-response relationships between the wt.% concentration of each of seven ring classes of aromatic compounds (the "ARC profile") and specific effects, with high correlations (r=0.91-0.94) between the observed and model-predicted data. The development of the mathematical models used to generate the results reported in this study is described by Nicolich et al. (2013). Model-generated dose-response curves permit the prediction of either the effect at a given dose or the dose that causes a given effect. The models generate values that are consistent with other standard measures. The models, using compositional data, can be used for predicting the repeat-dose toxicity of untested HBPS.

  11. Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.; Munck af Rosenschöld, Per; Oh, Jung Hun; Hunt, Margie; Kollmeier, Marisa; Happersett, Laura; Yorke, Ellen; Deasy, Joseph O.; Jackson, Andrew

    2014-02-01

    Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the

  12. SU-D-BRE-04: Evaluating the Dose Accuracy of a 2D Ion Chamber Array in High Dose Rate Pencil Beam Scanning Proton Beam

    SciTech Connect

    Perles, L; Mascia, A; Piskulich, F; Lepage, R; Zhang, Y; Giebeler, A; Dong, L

    2014-06-01

    Purpose: To evaluate the absolute dose accuracy of the PTW Octavius 729 XDR 2D ion chamber array at a high dose rate pencil beam scanning proton therapy facility. Methods: A set of 18 plans were created in our treatment planning system, each of which comprising a unique combination of field sizes (FS), length of spread out of Bragg peaks (SOBP) and depths. The parameters used were: FS of 5×5cm{sup 2}, 10×10cm{sup 2} and 15×15cm{sup 2}; flat SOBP of 5cm and 10cm; and isocenter depths of 10cm, 15cm and 20cm, which coincides with the center of the SOBP. The 2D array detector was positioned at the machine isocenter and the appropriate amount of solid water was used to match the planned depths of 10, 15 and 20 cm water equivalent depth. Subsequently, we measured the absolute dose at isocenter using a CC04 ion chamber in a 1D water tank. Both 2D array and CC04 were previously cross calibrated. We also collected the MU rates used by our proton machine from the log files. Results: The relative differences between the CC04 and the 2D array can be summarized into two groups, one with 5 cm SOBP and another with 10 cm SOBP. Plotting these datasets against FS shows that the 2D array response for high dose rate fields (FS of 5×5cm{sup 2} and 5cm SOBP) can be up to 2% lower. Similarly, plotting them against isocenter depths reveals the detector's response can be up to 2% lower for higher energy beams (about 200MeV nominal). The MU rate found in the machine log files for 5cm SOBP's were as high as twice the MU rate for the 10cm SOBP. Conclusion: The 2D array dose response showed a dose rate effect in scanning pencil beam delivery, which needs to be corrected to achieve a better dose accuracy.

  13. High-dose-rate interstitial brachytherapy for liver metastases: first study from India

    PubMed Central

    Thulkar, Sanjay; Sharma, Seema; Gandhi, Ajeet Kumar; Haresh, Kunhi Parambath; Gupta, Subhash; Rath, Goura Kisor; Julka, Pramod Kumar

    2013-01-01

    Purpose To study the safety and efficacy of high-dose-rate interstitial brachytherapy (HDRIBT) in patients with liver metastases (LM). Material and methods Between 2009 and 2011, 10 patients with 12 metastatic lesions in the liver were enrolled in this prospective trial. All patients had either refused surgery or found ineligible for surgery due to various factors. Under CT guidance, 16 gauze blind end stainless steel or rigid plastic brachytherapy needle was inserted in the center of lesion through the percutaneous route. Generally, a single interstitial brachytherapy (IBT) needle for lesions up to 3 cm and multiple needles for lesions more than 3 cm in diameter were inserted. Treatment was delivered with a single high-dose-rate (HDR) dose of 20 Gy prescribed to the target. The needles were removed immediately after the treatment. The endpoints of study were acute complications and local control of the disease. Results The median size of the lesion was 3.8 cm (2.7-7.0 cm). The average time for the entire IBT procedure was 65 minutes (50-105 minutes). Median follow up was 9 months (3-17 months). None of the patients had fatal complications. Minor complications like pain, nausea/vomiting, and asymptomatic pleural effusion were observed in 3, 2 and 1 patients, respectively. Local control rate at 12 months was 75%. The 1-year local progression free survival (LPFS) was 33%. Conclusion Although limited by small sample size, the results of our first study from India suggest that HDRIBT is a safe and effective non surgical option for LM. PMID:23878550

  14. [Effect of high dose pergolide mesilate on restless legs syndrome associated with Parkinson disease].

    PubMed

    Imamura, Akiko; Tsuboi, Yoshio; Tanaka, Miki; Obata, Toyoshi; Yamada, Tatsuo

    2007-04-01

    Restless legs syndrome (RLS) is one of the common nocturnal disturbance seen in Parkinson's disease (PD) patients. The prevalence of RLS with PD is greater than that of general populations; however, etiology of RLS in patients with PD is still controversial. We report a 63-year-old man with PD, who was admitted to our hospital with uncontrollable unpleasant feeling in both legs leading to sleep disturbance. At age 59, he experienced numbness and nocturnal myoclonus in his right foot. One year later, he developed resting tremor and bradykinesia in his right hand, and was diagnosed as PD. Levodopa was initiated with favorable response for his resting tremor and bradykinesia, however, his dysesthesia of the legs spread to both side and associated with an urge to move which occurs at rest and was ameliorated by walking. On admission, his parkinsonism was well controlled by 400 mg/ day of levodopa/benserazide. Polysomnography (PSG) revealed periodic limb movements in sleep (PLMS). Secondary RLS such as drug-induced, iron deficiency and uraemia, was excluded in this patient. Because levodopa did not improve his RLS, additional symptomatic RLS treatment was initiated. Oral dosage with 150 microg pergolide did not have any effect on his RLS symptoms. An increase up to 750 microg pergolide led to a marked reduction of symptoms. Repeated PSG showed significant reduction of PLMS and improved sleep efficacy. Usually, low dose of dopamine agonist is enough to treat RLS occurred in general populations. However, moderate to high dose of dopamine agonists were needed for our patient with RLS, indicating that pharmacological responses might be different between RLS in general and that associated with PD. It is important to consider that PD-related RLS can be treated with high dose dopamine agonist to obtain favorable management of nocturnal disturbances. PMID:17511286

  15. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  16. High-Dose-Rate Endobronchial Brachytherapy for Recurrent Airway Obstruction From Hyperplastic Granulation Tissue

    SciTech Connect

    Tendulkar, Rahul D. Fleming, Peter A.; Reddy, Chandana A.; Gildea, Thomas R.; Machuzak, Michael; Mehta, Atul C.

    2008-03-01

    Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV{sub 1}), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV{sub 1} improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively.

  17. Long-term results of high-dose methylprednisolone in aplastic anemia.

    PubMed

    López-Karpovitch, X; Gil-Rondero, C; Hurtado-Monroy, R

    1991-01-01

    Four males and two females, aged 13 to 57 years (median 22 years), with acquired severe aplastic anemia (AA) were treated with intravenous bolus of high doses of 6-methylprednisolone (MPL). Patients received MPL within a 30-day period at a dose of 20 mg/kg/day (3 days), 10 mg/kg/day (4 days), 5 mg/kg/day (4 days), 2 mg/kg/day (9 days), and 1 mg/kg/day (10 days). Within the first 3 months following MPL therapy, a response rate of 83%, assessed by means of increase in reticulocytes, neutrophils or platelets, was recorded in the group: two cases showed partial response and three improvement. The 3-month, and 1-, 2- and 3-year survival of the group was 67%, 50%, 33% and 33%, respectively. Neither the presence of reticulocytopenia or thrombocytopenia prior MPL therapy, nor age, gender, etiology of AA or time between diagnosis and initiation of MPL influenced survival. In contrast, neutrophil counts before MPL treatment had a strong prognostic value. Patients with less than 0.5 x 10(9)/L neutrophils had a median survival of 4.2 months (range 1.2 to 5.2 months) as compared to the 36.1 months median survival (range 12.1 to 36.8 months) of patients whose neutrophil counts were greater than 0.5 x 10(9)/L. Follow-up data suggest that the administration of androgens two months after MPL therapy did not modify survival. It is concluded that high-dose MPL is useful in the treatment of some patients with acquired severe AA, particularly in those with greater than 0.5 x 10(9)/L neutrophils who are not candidates for bone marrow transplantation.

  18. Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis.

    PubMed

    Durante-Mangoni, Emanuele; Andini, Roberto; Parrella, Antonio; Mattucci, Irene; Cavezza, Giusi; Senese, Alessandra; Trojaniello, Claudia; Caprioli, Roberta; Diana, Maria Veronica; Utili, Riccardo

    2016-07-01

    Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co-morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored.

  19. Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention

    PubMed Central

    Kreutz, Rolf P; Breall, Jeffrey A; Sinha, Anjan; von der Lohe, Elisabeth; Kovacs, Richard J; Flockhart, David A

    2016-01-01

    Background Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. Methods Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16–24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. Results Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16–24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37–2.8). Conclusion High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940). PMID:27350760

  20. Phase stability and microstructures of high entropy alloys ion irradiated to high doses

    NASA Astrophysics Data System (ADS)

    Xia, Songqin; Gao, Michael C.; Yang, Tengfei; Liaw, Peter K.; Zhang, Yong

    2016-11-01

    The microstructures of AlxCoCrFeNi (x = 0.1, 0.75 and 1.5 in molar ratio) high entropy alloys (HEAs) irradiated at room temperature with 3 MeV Au ions at the highest fluence of 105, 91, and 81 displacement per atom, respectively, were studied. Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analyses show that the initial microstructures and phase composition of all three alloys are retained after ion irradiation and no phase decomposition is observed. Furthermore, it is demonstrated that the disordered face-centered cubic (FCC) and disordered body-centered cubic (BCC) phases show much less defect cluster formation and structural damage than the NiAl-type ordered B2 phase. This effect is explained by higher entropy of mixing, higher defect formation/migration energies, substantially lower thermal conductivity, and higher atomic level stress in the disordered phases.

  1. Radiation tolerant fiber Bragg gratings for high temperature monitoring at MGy dose levels.

    PubMed

    Morana, A; Girard, S; Marin, E; Marcandella, C; Paillet, P; Périsse, J; Macé, J-R; Boukenter, A; Cannas, M; Ouerdane, Y

    2014-09-15

    We report a method for fabricating fiber Bragg gratings (FBG) resistant to very severe environments mixing high radiation doses (up to 3 MGy) and high temperatures (up to 230°C). Such FBGs have been written in two types of radiation resistant optical fibers (pure-silica and fluorine-doped cores) by exposures to a 800 nm femtosecond IR laser at power exceeding 500 mW and then subjected to a thermal annealing treatment of 15 min at 750°C. Under radiation, our study reveals that the radiation induced Bragg wavelength shift (BWS) at a 3 MGy dose is strongly reduced compared to responses of FBGs written with nonoptimized conditions. The BWS remains lower than 10 pm for temperatures of irradiation ranging from 25°C to 230°C without noticeable decrease of the FBG peak amplitude. For an applicative point of view, this radiation induced BWS corresponds to an additional error on the temperature measurements lower than 1.5°C, opening the way to the development of radiation-tolerant multi-point temperature sensors for nuclear industry. PMID:26466259

  2. Alcohol solutions of triphenyl-tetrazolium chloride as high-dose radiochromic dosimeters

    NASA Astrophysics Data System (ADS)

    Kovács, A.; Wojnárovits, L.; El-assy, N. B.; Afeefy, H. Y.; Al-Sheikhly, M.; Walker, M. L.; McLaughlin, W. L.

    1995-09-01

    The radiolytic reduction of colorless tetrazolium salts in aqueous solution to the highly colored formazan dye is a well-known acid-forming radiation chemical reaction. Radiochromic thin films and three-dimensional hydrocolloid gels have been used for imaging and mapping absorbed dose distributions. The high solubility of 2,3,5-triphenyl-tetrazolium chloride (TTC) in alcohols provides a useful liquid dosimeter (45 mM TTC in aerated ethanol) and shows a linear response of absorbance increase (λmax = 480 nm) with dose over the range 1-16 kGy. The linear molar absorption coefficient (ɛm) for the formazan at the absorption peak is 1.5 × 103 m2 mol-1, and the radiation chemical yield for the above solution is G (formazan) = 0.014 μmol J-1. The irradiation temperature coefficient is about 0.8 percent per degree Celsius rise in temperature over the temperature range 0-30 °C but is much larger between 30° and 60 °C. The unirradiated and irradiated solutions are stable over at least five days storage at normal laboratory temperature in the dark, but when stored in daylight at elevated temperature, the unirradiated solution in sealed amber glass ampoules undergoes slow photolytic dye formation, and the irradiated solution experiences initial fading and subsequent reversal (photochromism) when exposed to direct sunlight.

  3. Physiological and psychological effects of a high dose of alcohol in young men and women.

    PubMed

    Vinader-Caerols, Concepción; Monleón, Santiago; Parra, Andrés

    2014-01-01

    The objective of this study was to evaluate the effects of a high dose of alcohol on physiological and psychological parameters in young men and women with a previous history of alcohol consumption. Systolic and diastolic blood pressure, heart rate, state anxiety, attention, time estimation and manual dexterity were registered before (phase 1) and after (phase 2) intake of alcohol (38.4 g) or a non-alcoholic beverage. Trait anxiety was registered in phase 2 only. The results showed that acute consumption of a high dose of alcohol: i) improves attention in men (although the performance of alcohol consumers was not better than that of non-consumers); ii) blocks the systolic blood pressure habituation phenomenon (observed in controls) in women; and iii) blocks the improvement in manual dexterity (associated with experience in non-consumers) in both sexes. On the other hand, male consumers had a lower heart rate than non-consumers, independently of the phase, while female consumers had a higher state anxiety and performed worse in attention than controls, also independently of the phase. These results help to understand the extent of performance impairment of different tasks produced by risk alcohol consumption in young men and women.

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

    PubMed

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

    2016-09-01

    Associations between criminal activity and the use of psychotropic substances are well established. Flunitrazepam, specifically, has been suspected of triggering, per se, violent criminal behavior and severe memory disturbances in the form of anterograde amnesia. However, data from investigations of this relationship are scarce and have been primarily derived from forensic institutions, where there may be a reporting bias. This study was a qualitative exploration of high-dose benzodiazepine users' experiences of anterograde amnesia symptoms and their beliefs about their behavior during the phases of memory impairment in a nonforensic setting. Users subjectively reported experiencing symptoms of anterograde amnesia, especially after combining short-acting benzodiazepines with alcohol, but only rarely when using slow-onset, long-acting compounds. They perceived their experiences as unpleasurable, unpredictable, and embarrassing. Their awareness developed with time, triggered by descriptions of disinhibited and erratic behavior by others. Users described being victimized during phases of anterograde amnesia in addition to engaging in violent and criminal activities themselves. Although unable to recall, many participants believed that they had been able to make rational decisions while intoxicated with flunitrazepam, disregarding notions of diminished insight. In light of the varying terminology used for the phases of memory disturbance and these findings, we suggest that forensic experts additionally explore evaluees' beliefs about amnestic periods and their self-perceptions about their behaviors during these episodes, when evaluating high-dose benzodiazepine-dependent patients. PMID:27644866

  5. Can ultrasound and computed tomography replace high-dose urography in patients with impaired renal function?

    PubMed

    Webb, J A; Reznek, R H; White, F E; Cattell, W R; Fry, I K; Baker, L R

    1984-01-01

    Ninety-one patients with unexplained impaired renal function were investigated by high-dose urography, ultrasound and computed tomography (CT) without contrast. The aim was to evaluate the role of ultrasound and CT in renal failure, in particular their ability to define renal length and to show collecting system dilatation. In the majority of patients, renal length could be measured accurately by ultrasound. Measurements were less that those at urography because of the absence of magnification. Renal measurement by CT was not a sufficiently accurate indicator of renal length to be of clinical use. Both ultrasound and CT were sensitive detectors of collecting system dilatation: neither technique missed any case diagnosed by urography. However, in the presence of staghorn calculi or multiple cysts, neither ultrasound nor CT could exclude collecting system dilatation. CT was the only technique which demonstrated retroperitoneal nodes or fibrosis causing obstruction. It is proposed that the first investigation when renal function is impaired should be ultrasound, with plain films and renal tomograms to show calculi. CT should be reserved for those patients in whom ultrasound is not diagnostic or in whom ultrasound shows collecting system dilatation but does not demonstrate the cause. Using this scheme, ultrasound, plain radiography and CT would have demonstrated collecting system dilatation and, where appropriate, shown the cause of obstruction in 84 per cent of patients in this series. Only 16 per cent of patients would have required either high-dose urography or retrograde ureterograms.

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

    PubMed

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

    2014-06-01

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

  7. Dose-volume parameters and clinical outcome of CT-guided free-hand high-dose-rate interstitial brachytherapy for cervical cancer

    PubMed Central

    Wang, Yi; Ye, Wei-Jun; Du, Le-Hui; Li, Ai-Ju; Ren, Yu-Feng; Cao, Xin-Ping

    2012-01-01

    Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a better assessment of gross tumor volume (GTV) and the definition and delineation of target volume in cervix cancer. In this study, we investigated the feasibility of our novel computed tomography (CT)-guided free-hand high-dose-rate interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating the dosimetry and preliminary clinical outcome of this approach. Dose-volume histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO Working Group recommendations for image-based 3D treatment in cervical cancer. Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between March 2009 and June 2010 were studied. With a median of 5 (range, 4–7) implanted needles for each patient, the median dose of brachytherapy alone delivered to 90% of the target volume (D90) was 45 (range, 33–54) Gyα/β10 for high-risk clinical target volume (HR-CTV) and 30 (range, 20–36) Gyα/β10 for intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV covered by the prescribed dose (V100) of HR-CTV with brachytherapy alone was 81.9%–99.2% (median, 96.7%). With an additional dose of external beam radiotherapy (EBRT), the median D90 was 94 (range, 83–104) Gyα/β10 for HR-CTV and 77 (range, 70–87) Gyα/β10 for IR-CTV; the median dose delivered to 100% of the target volume (D100) was 75 (range, 66–84) Gyα/β10 for HR-CTV and 65 (range, 57–73) Gyα/β10 for IR-CTV. The minimum dose to the most irradiated 2 cc volume (D2cc) was 73–96 (median, 83) Gyα/β3 for the bladder, 64–98 (median, 73) Gyα/β3 for the rectum, and 52–69 (median, 61) Gyα/β3 for the sigmoid colon. After a median follow-up of 15 months (range, 3–24 months), two patients experienced local failure, and 1 showed internal iliac nodal metastasis. Despite the relatively small number of needles used, CT-guided HDRISBT for cervical cancer showed favorable

  8. Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer

    SciTech Connect

    Hepel, Jaroslaw T.; Syed, A.M. Nisar . E-mail: bvigil@memnet.org; Puthawala, Ajmel; Sharma, Anil; Frankel, Paul

    2005-08-01

    Background: A significant portion of head-and-neck cancer patients will develop persistent or recurrent disease after definitive treatment. Radiation therapy is often used as definitive therapy or as an adjunct to surgery. Recurrent cancer of the head and neck in the previously irradiated field is, thus, a common occurrence and poses a therapeutic challenge. Some studies have evaluated low-dose-rate (LDR) brachytherapy as a therapeutic option, including a large case series with long-term follow-up by our own institution. High-dose-rate (HDR) brachytherapy offers therapeutic advantages over LDR brachytherapy. This study evaluates the local control and outcomes of patients with previously irradiated recurrent head-and-neck cancer treated with HDR interstitial brachytherapy. Methods and Materials: Between 1997 and 2002, 30 patients who received prior radiation therapy for primary tumors of the head and neck were treated for biopsy-proven recurrent disease. All patients received previous radiation as definitive therapy alone or as adjunct to surgery. All patients were inoperable, refused surgery, or had gross residual disease after salvage surgery for their recurrent disease. Thirty-six sites on the 30 patients were implanted by application of high-dose-rate interstitial brachytherapy techniques with mean tumor dose of 34 Gy (18-48 Gy) in twice daily fractions of 300 to 400cGy per fraction. Results: At a minimum follow-up of 12 months, local tumor control was achieved in 69% of implanted sites. Disease-specific survival at 1 and 2 years was 54% and 45%, respectively. Overall survival at 1 and 2 years was 56% and 37%, respectively. Grade 3/4 late complications occurred in 16% of the patients. No fatal complications occurred. Conclusion: HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head-and-neck cancer. This study shows that comparable results are obtained by HDR brachytherapy with fewer late complications than

  9. Effect of high-dose irradiation on the optically stimulated luminescence of Al2O3:C

    NASA Technical Reports Server (NTRS)

    Yukihara, E. G.; Whitley, V. H.; McKeever, S. W. S.; Akselrod, A. E.; Akselrod, M. S.

    2004-01-01

    This paper examines the effect of high-dose irradiation on the optically stimulated luminescence (OSL) of Al2O3:C, principally on the shape of the OSL decay curve and on the OSL sensitivity. The effect of the degree of deep trap filling on the OSL was also studied by monitoring the sensitivity changes after doses of beta irradiation and after step-annealing of samples previously irradiated with high doses. The OSL response to dose shows a linear-supralinear-saturation behavior, with a decrease in the response for doses higher than those required for saturation. This behavior correlates with the sensitivity changes observed in the samples annealed only to 773 K, which show sensitization for doses up to 20-50 Gy and desensitization for higher doses. Data from the step-annealing study leads to the suggestion that the sensitization is caused by the filling of deep electron traps, which become thermally unstable at 1100-1200 K, whereas the desensitization is caused by the filling of deep hole traps, which become thermally unstable at 800-875 K, along with a concomitant decrease in the concentration of recombination centers (F+ -centers). Changes in the shape of the OSL decay curves are also observed at high doses, the decay becoming faster as the dose increases. These changes in the OSL decay curves are discussed in terms of multiple overlapping components, each characterized by different photoionization cross-sections. However, using numerical solutions of the rate equations for a simple model consisting of a main trap and a recombination center, it is shown that the kinetics of OSL process may also be partially responsible for the changes in the OSL curves at high doses in Al2O3:C. Finally, the implication of these results for the dosimetry of heavy charged particles is discussed. c2004 Elsevier Ltd. All rights reserved.

  10. Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial.

    PubMed

    Meesters, Michael I; Veerhoek, Dennis; de Lange, Fellery; de Vries, Jacob-Willem; de Jong, Jan R; Romijn, Johannes W A; Kelchtermans, Hilde; Huskens, Dana; van der Steeg, Robin; Thomas, Pepijn W A; Burtman, David T M; van Barneveld, Laurentius J M; Vonk, Alexander B A; Boer, Christa

    2016-08-01

    While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine-to-heparin dosing ratio group received less protamine (329 ± 95 vs 539 ± 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 ± 74 vs 196 ± 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 ± 40 % vs 6 ± 9 %; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95 % CI 500-830 ml vs 470 ml; 95 % CI 420-530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11 % vs 0 %; p=0.02) and platelet concentrate (21 % vs 6 %; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.

  11. Temperature response of two photographic films and TLDs suitable for patient dosimetry of high dose fluoroscopic procedures.

    PubMed

    Lien, W; Geise, R A

    1997-09-01

    When making direct measurements of skin entrance dose for patients undergoing interventional x-ray procedures the dosimeter may be placed near or in direct contact with the skin. The response of such dosimeters to heating during x-ray exposure must be known for accurate dosimetry. Two photographic films and MgB4O7 TLDs used for patient dose monitoring were exposed under different temperature conditions. Film dose response curves were obtained at room temperature and body temperature (22 degrees C and 38 degrees C). The TLD response at room and body temperature was also checked at 14 Gy. Dose response curves of FGP film show at most a 22+/-2% increase in predicted dose at 37 degrees C in the range of 0.3 to 2.8 Gy. LOC4 film showed less than a 2% difference in response between 22 and 37 degrees C over a range of 1 to 11 Gy. The TLDs showed less than a 2% difference at a dose of 14 Gy. Uncertainty in skin dose estimation is less than 2% using LOC4 film and MgB4O7 TLD arrays. Uncertainty in temperature during exposure of Kodak fine grain positive film may lead to errors in dose estimates of +/-11%. Arrays of TLDs and copy film are more suitable for measurements of high doses and are less sensitive to temperature changes during exposure than the fine grain film.

  12. Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

    SciTech Connect

    Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2010-11-01

    Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R{sup 2}, 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

  13. Scleromyxoedema: treatment of cutaneous and systemic manifestations with high-dose intravenous immunoglobulin.

    PubMed

    Kulczycki, A; Nelson, M; Eisen, A; Heffernan, M

    2003-12-01

    Scleromyxoedema is a rare disease characterized by cutaneous sclerosis, mucin deposition and paraproteinaemia. Internal disease is common, particularly musculoskeletal, gastrointestinal and central nervous system involvement. We report a series of three consecutive patients with scleromyxoedema treated with high-dose intravenous immunoglobulin (hdIVIg). Each of the three patients had relatively low levels of a highly basic IgG-lambda paraprotein, and each has demonstrated a sustained response of both their cutaneous and extracutaneous disease to hdIVIg. As all patients had perioral skin involvement and microstomia, one measure of cutaneous improvement was the increase in intraincisor distance. Extracutaneous manifestations of scleromyxoedema that improved included ureteral stricture, vocal strength and dysphagia.

  14. Secondary cancer-incidence risk estimates for external radiotherapy and high-dose-rate brachytherapy in cervical cancer: phantom study.

    PubMed

    Lee, Boram; Ahn, Sung Hwan; Kim, Hyeyoung; Son, Jaeman; Sung, Jiwon; Han, Youngyih; Huh, Seung Jae; Kim, Jin Sung; Kim, Dong Wook; Yoon, Myonggeun

    2016-01-01

    This study was designed to estimate radiation-induced secondary cancer risks from high-dose-rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out-of-field organs were measured at various loca-tions inside an anthropomorphic phantom. Brachytherapy-associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out-of-field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy-induced secondary cancer incidence dur-ing cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy-associated secondary

  15. Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators

    SciTech Connect

    Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

    2009-10-15

    Purpose: The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. Methods: In order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. Results: The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. Conclusions: The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate

  16. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

    PubMed Central

    Whitaker, May

    2016-01-01

    Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

  17. High Dose-Rate Intracavitary Brachytherapy for Cervical Carcinomas With Lower Vaginal Infiltration

    SciTech Connect

    Kazumoto, Tomoko Kato, Shingo; Tabushi, Katsuyoshi; Kutsutani-Nakamura, Yuzuru; Mizuno, Hideyuki; Takahashi, Michiko; Shiromizu, Kenji; Saito, Yoshihiro

    2007-11-15

    Purpose: This report presents the clinical applications of an automated treatment-planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for advanced uterine cervical cancer infiltrating the parametrium and the lower vagina. Methods and Materials: We adopted HDR-ICBT under optimized dose distribution for 22 cervical cancer patients with tumor infiltration of the lower half of the vagina. All patients had squamous cell carcinoma with International Federation of Gynecology and Obstetrics clinical stages IIB-IVA. After whole pelvic external beam irradiation with a median dose of 30.6 Gy, a conventional ICBT was applied as 'pear-shaped' isodose curve. Then 3-4 more sessions per week of this new method of ICBT were performed. With a simple determination of the treatment volume, the cervix-parametrium, and the lower vagina were covered automatically and simultaneously by this program, that was designated as 'utero-vaginal brachytherapy'. The mean follow-up period was 87.4 months (range, 51.8-147.9 months). Results: Isodose curve for this program was 'galaxy-shaped'. Five-year local-progression-free survival and overall survival rates were 90.7% and 81.8%, respectively. Among those patients with late complications higher than Grade 2 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity score, only one (4.5%) developed severe proctitis. Conclusions: Because of the favorable treatment outcomes, this treatment-planning program with a simplified target-volume based dosimetry was proposed for cervical cancer with lower vaginal infiltration.

  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. Dose-intensified CHOP with rituximab (R-Double-CHOP) followed by consolidation high-dose chemotherapies for patients with advanced diffuse large B-cell lymphoma.

    PubMed

    Kurita, Daisuke; Miura, Katsuhiro; Nakagawa, Masaru; Ohtake, Shimon; Sakagami, Masashi; Uchino, Yoshihito; Takahashi, Hiromichi; Kiso, Satomi; Hojo, Atsuko; Kodaira, Hitomi; Yagi, Mai; Hirabayashi, Yukio; Kobayashi, Yujin; Iriyama, Noriyoshi; Kobayashi, Sumiko; Hatta, Yoshihiro; Kura, Yoshimasa; Sugitani, Masahiko; Takei, Masami

    2015-06-01

    Even after the advent of rituximab, clinical outcomes of conventional immuno-chemotherapy for high-risk diffuse large B-cell lymphoma (DLBCL) remain unsatisfactory. We retrospectively evaluated the efficacy and safety of R-Double-CHOP (R-D-CHOP), consisting of rituximab (375 mg/m(2), day -2), cyclophosphamide (750 mg/m(2), day 1, 2), doxorubicin (50 mg/m(2), day 1, 2), vincristine [1.4 mg/m(2) (maximum 2.0 mg/body), day 1], and prednisolone (50 mg/m(2), day 1-5), followed by consolidation high-dose chemotherapy. This treatment was given to 51 de novo DLBCL patients with a median age of 54 (range 19-65), who were categorized as high/high-intermediate risk by the age-adjusted International Prognostic Index. Treatment was given every 3 weeks up to three courses. The overall response and the complete response rate for R-D-CHOP were 94 and 78 %, respectively. A total of 30 responders proceeded to high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT), whereas 16 received high-dose methotrexate (HD-MTX) alternatively. The 3-year overall survival and the event-free survival for all patients were 78 and 61 %, respectively. Major adverse events included hematological toxicities, but there were no treatment-related deaths during the observation period. We conclude that the R-D-CHOP regimen followed by HDC/ASCT or HD-MTX is a promising treatment option for younger patients with highly advanced DLBCL. PMID:25776837

  20. Dose-intensified CHOP with rituximab (R-Double-CHOP) followed by consolidation high-dose chemotherapies for patients with advanced diffuse large B-cell lymphoma.

    PubMed

    Kurita, Daisuke; Miura, Katsuhiro; Nakagawa, Masaru; Ohtake, Shimon; Sakagami, Masashi; Uchino, Yoshihito; Takahashi, Hiromichi; Kiso, Satomi; Hojo, Atsuko; Kodaira, Hitomi; Yagi, Mai; Hirabayashi, Yukio; Kobayashi, Yujin; Iriyama, Noriyoshi; Kobayashi, Sumiko; Hatta, Yoshihiro; Kura, Yoshimasa; Sugitani, Masahiko; Takei, Masami

    2015-06-01

    Even after the advent of rituximab, clinical outcomes of conventional immuno-chemotherapy for high-risk diffuse large B-cell lymphoma (DLBCL) remain unsatisfactory. We retrospectively evaluated the efficacy and safety of R-Double-CHOP (R-D-CHOP), consisting of rituximab (375 mg/m(2), day -2), cyclophosphamide (750 mg/m(2), day 1, 2), doxorubicin (50 mg/m(2), day 1, 2), vincristine [1.4 mg/m(2) (maximum 2.0 mg/body), day 1], and prednisolone (50 mg/m(2), day 1-5), followed by consolidation high-dose chemotherapy. This treatment was given to 51 de novo DLBCL patients with a median age of 54 (range 19-65), who were categorized as high/high-intermediate risk by the age-adjusted International Prognostic Index. Treatment was given every 3 weeks up to three courses. The overall response and the complete response rate for R-D-CHOP were 94 and 78 %, respectively. A total of 30 responders proceeded to high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT), whereas 16 received high-dose methotrexate (HD-MTX) alternatively. The 3-year overall survival and the event-free survival for all patients were 78 and 61 %, respectively. Major adverse events included hematological toxicities, but there were no treatment-related deaths during the observation period. We conclude that the R-D-CHOP regimen followed by HDC/ASCT or HD-MTX is a promising treatment option for younger patients with highly advanced DLBCL.

  1. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

    PubMed Central

    Chader, Driss; Cohen-Aubart, Fleur; Haroche, Julien; Fadlallah, Jehane; Claër, Laetitia; Musset, Lucile; Gorochov, Guy; Amoura, Zahir; Miyara, Makoto

    2015-01-01

    Background/Purpose A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE. Methods We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score. Results Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2. Conclusion IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE. PMID:26629828

  2. Development of dose delivery verification by PET imaging of photonuclear reactions following high energy photon therapy

    NASA Astrophysics Data System (ADS)

    Janek, S.; Svensson, R.; Jonsson, C.; Brahme, A.

    2006-11-01

    A method for dose delivery monitoring after high energy photon therapy has been investigated based on positron emission tomography (PET). The technique is based on the activation of body tissues by high energy bremsstrahlung beams, preferably with energies well above 20 MeV, resulting primarily in 11C and 15O but also 13N, all positron-emitting radionuclides produced by photoneutron reactions in the nuclei of 12C, 16O and 14N. A PMMA phantom and animal tissue, a frozen hind leg of a pig, were irradiated to 10 Gy and the induced positron activity distributions were measured off-line in a PET camera a couple of minutes after irradiation. The accelerator used was a Racetrack Microtron at the Karolinska University Hospital using 50 MV scanned photon beams. From photonuclear cross-section data integrated over the 50 MV photon fluence spectrum the predicted PET signal was calculated and compared with experimental measurements. Since measured PET images change with time post irradiation, as a result of the different decay times of the radionuclides, the signals from activated 12C, 16O and 14N within the irradiated volume could be separated from each other. Most information is obtained from the carbon and oxygen radionuclides which are the most abundant elements in soft tissue. The predicted and measured overall positron activities are almost equal (-3%) while the predicted activity originating from nitrogen is overestimated by almost a factor of two, possibly due to experimental noise. Based on the results obtained in this first feasibility study the great value of a combined radiotherapy-PET-CT unit is indicated in order to fully exploit the high activity signal from oxygen immediately after treatment and to avoid patient repositioning. With an RT-PET-CT unit a high signal could be collected even at a dose level of 2 Gy and the acquisition time for the PET could be reduced considerably. Real patient dose delivery verification by means of PET imaging seems to be

  3. Dose prediction accuracy of anisotropic analytical algorithm and pencil beam convolution algorithm beyond high density heterogeneity interface

    PubMed Central

    Rana, Suresh B.

    2013-01-01

    Purpose: It is well known that photon beam radiation therapy requires dose calculation algorithms. The objective of this study was to measure and assess the ability of pencil beam convolution (PBC) and anisotropic analytical algorithm (AAA) to predict doses beyond high density heterogeneity. Materials and Methods: An inhomogeneous phantom of five layers was created in Eclipse planning system (version 8.6.15). Each layer of phantom was assigned in terms of water (first or top), air (second), water (third), bone (fourth), and water (fifth or bottom) medium. Depth doses in water (bottom medium) were calculated for 100 monitor units (MUs) with 6 Megavoltage (MV) photon beam for different field sizes using AAA and PBC with heterogeneity correction. Combinations of solid water, Poly Vinyl Chloride (PVC), and Styrofoam were then manufactured to mimic phantoms and doses for 100 MUs were acquired with cylindrical ionization chamber at selected depths beyond high density heterogeneity interface. The measured and calculated depth doses were then compared. Results: AAA's values had better agreement with measurements at all measured depths. Dose overestimation by AAA (up to 5.3%) and by PBC (up to 6.7%) was found to be higher in proximity to the high-density heterogeneity interface, and the dose discrepancies were more pronounced for larger field sizes. The errors in dose estimation by AAA and PBC may be due to improper beam modeling of primary beam attenuation or lateral scatter contributions or combination of both in heterogeneous media that include low and high density materials. Conclusions: AAA is more accurate than PBC for dose calculations in treating deep-seated tumor beyond high-density heterogeneity interface. PMID:24455541

  4. Investigation of omeprazole and phenacetin first-pass metabolism in humans using a microscale bioreactor and pharmacokinetic models.

    PubMed

    Bricks, Thibault; Hamon, Jérémy; Fleury, Marie José; Jellali, Rachid; Merlier, Franck; Herpe, Yves Edouard; Seyer, Alexandre; Regimbeau, Jean-Marc; Bois, Frédéric; Leclerc, Eric

    2015-07-01

    A new in vitro microfluidic platform (integrated insert dynamic microfluidic platform, IIDMP) allowing the co-culture of intestinal Caco-2 TC7 cells and of human primary hepatocytes was used to test the absorption and first-pass metabolism of two drugs: phenacetin and omeprazole. The metabolism of these drugs by CYP1A2, CYP2C19 and CYP3A4 was evaluated by the calculation of bioavailabilities and of intrinsic clearances using a pharmacokinetic (PK) model. To demonstrate the usefulness of the device and of the PK model, predictions were compared with in vitro and in vivo results from the literature. Based on the IIDMP experiments, hepatic in vivo clearances of phenacetin and omeprazole in the IIDMP were predicted to be 3.10 ± 0.36 and 1.46 ± 0.25 ml/min/kg body weight, respectively. This appeared lower than the in vivo observed data with values ranging between 11.9-19.6 and 5.8-7.5 ml/min/kg body weight, respectively. Then the calculated hepatic and intestinal clearances led to predicting an oral bioavailability of 0.85 and 0.77 for phenacetin and omeprazole versus 0.92 and 0.78 using separate data from the simple monoculture of Caco-2 TC7 cells and hepatocytes in Petri dishes. When compared with the in vivo data, the results of oral bioavailability were overestimated (0.37 and 0.71, respectively). The feasibility of co-culture in a device allowing the integration of intestinal absorption, intestinal metabolism and hepatic metabolism in a single model was demonstrated. Nevertheless, further experiments with other drugs are needed to extend knowledge of the device to predict oral bioavailability and intestinal first-pass metabolism.

  5. Anesthetic and pathological changes following high doses of ketamine and xylazine in Sprague Dawley rats

    PubMed Central

    GIROUX, Marie-Chantal; HÉLIE, Pierre; BURNS, Patrick; VACHON, Pascal

    2015-01-01

    The main objective of this study was to compare the effects of ketamine and xylazine in aging rats when coadministered intraperitoneally at high anesthetic doses. Three groups (n=6 rats/group) consisting of rats at 3, 6 and 12 months of age were used. During anesthesia, animals were monitored for heart rate, respiratory frequency, blood oxygen saturation, and rectal temperature. The corneal and paw withdrawal reflex were also examined during anesthesia. During anesthesia, withdrawal and corneal reflexes were absent for progressively longer durations with increasing age. Significant decreases in cardiac and respiratory frequency and, blood oxygen saturation occurred for the 6- and 12-month-old animals. Respiratory frequency and blood oxygen saturation returned to normal at the end of the anesthesia; however, the significant decrease in cardiac frequency persisted in the 6- and 12-month-old animals. Rectal temperature was decreased significantly only in the 3-month-old animals. Pulmonary edema and effusion occurred in 50% of the 12-month-old animals. In conclusion, if ketamine-xylazine are used for anesthesia, the doses should be optimized for the age of the subjects prior to initiation of the research project. PMID:25818316

  6. [Infection control in neutropenia induced by high-dose cytarabine chemotherapy].

    PubMed

    Miyazaki, Masayuki; Senzaki, Kouji; Kiyoi, Hitoshi; Kohno, Shigekatu; Noda, Yukihiro; Nabeshima, Toshitaka

    2004-11-01

    A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully used as a postremission consolidation therapy for acute myeloid leukemia (AML). Although this chemotherapy has been estimated to cause severe myelosuppression, there has been no report about infection risk relating to HDAC chemotherapy. The purpose of this retrospective study is to evaluate the infection risk in AML patients treated with HDAC (n = 18) compared to those treated with standard-dose Ara-C (SDAC, n = 18). The mean duration of severe neutropenia (neutrophils < 500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively, indicating a significant prolongation in the HDAC group (p < 0.05). The frequency of febrile neutropenia in the HDAC group tended to increase compared to that in the SDAC group (p = 0.093). The average days of usage of quinolone antimicrobial prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the HDAC group were significantly longer than those of the SDAC group (quinolone; p < 0.01, aminoglycoside; p < 0.05). The frequency of Streptococcus infection isolated from pharyngeal mucus in the HDAC group was significantly higher than that in the SDAC group (100% versus 75%; p < 0.05). These results suggest that HDAC chemotherapy increased the infection risk compared to SDAC, and especially patients who received HDAC need a further prevention plan against gram-positive bacteria.

  7. Definitive high-dose radiotherapy with concurrent chemotherapy for locally advanced rectal cancer

    PubMed Central

    Kim, Min-Jeong; Kim, Eun Seok; Yeo, Seung-Gu

    2016-01-01

    Abstract Background: Standard management for locally advanced rectal cancer (LARC) involves preoperative chemoradiotherapy (CRT) and radical surgery. However, this level of treatment may be unnecessary for a subgroup of LARC patients. Previous reports have shown that approximately 20% of LARC patients experience a complete tumor response to preoperative CRT. Post-CRT nonoperative management of these patients may prevent morbidities associated with radical surgery. To our knowledge, this case report firstly presents the favorable long-term outcomes of a LARC patient who underwent definitive aim CRT. Methods: The patient was 73 years’ old, and staging workups revealed T3N2bM0 rectal adenocarcinoma. He agreed to receive CRT, but refused surgery. A radiotherapy (RT) dose of 64.8 Gy was prescribed, which was higher than conventional (50.4 Gy) preoperative aim RT. The regimen of concurrent chemotherapy was the same as that used in preoperative aim CRT: 2 cycles of 5-fluorouracil and leucovorin. Results: Three months after CRT completion, a complete tumor response was identified clinically. Colonoscopic biopsy after 1 year showed no tumor cells. This patient is alive after 4 years with no evidence of recurrence or severe toxicity. Conclusion: The long-term outcomes of this case indicate the feasibility of definitive high-dose RT with concurrent chemotherapy for LARC. PMID:27749573

  8. Four-Dimensional Positron Emission Tomography: Implications for Dose Painting of High-Uptake Regions

    SciTech Connect

    Aristophanous, Michalis; Killoran, Joseph H.; Chen, Aileen B.; Berbeco, Ross I.

    2011-07-01

    Purpose: To investigate the behavior of tumor subvolumes of high [18F]-fluorodeoxyglucose (FDG) uptake as seen on clinical four-dimensional (4D) FDG-positron emission tomography (PET) scans. Methods and Materials: Four-dimensional FDG-PET/computed tomography scans from 13 patients taken before radiotherapy were available. The analysis was focused on regions of high uptake that are potential dose-painting targets. A total of 17 lesions (primary tumors and lymph nodes) were analyzed. On each one of the five phases of the 4D scan a classification algorithm was applied to obtain the region of highest uptake and segment the tumor volume. We looked at the behavior of both the high-uptake subvolume, called 'Boost,' and the segmented tumor volume, called 'Target.' We measured several quantities that characterize the Target and Boost volumes and quantified correlations between them. Results: The behavior of the Target could not always predict the behavior of the Boost. The shape deformation of the Boost regions was on average 133% higher than that of the Target. The gross to internal target volume expansion was on average 27.4% for the Target and 64% for the Boost, a statistically significant difference (p < 0.05). Finally, the inhale-to-exhale phase (20%) had the highest shape deformation for the Boost regions. Conclusions: A complex relationship between the measured quantities for the Boost and Target volumes is revealed. The results suggest that in cases in which advanced therapy techniques such as dose painting are being used, a close examination of the 4D PET scan should be performed.

  9. High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

    SciTech Connect

    Kaprealian, Tania; Weinberg, Vivian; Speight, Joycelyn L.; Gottschalk, Alexander R.; Roach, Mack; Shinohara, Katsuto; Hsu, I.-Chow

    2012-01-01

    Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

  10. Intermittent High-Dose Ethanol Exposure Increases Ethanol Preference in Rats

    PubMed Central

    Peris, Joanna; Rhodes, Nathaniel; McCullough, Brian; Aramini, Richard; Zharikova, Alevtina

    2015-01-01

    Objective: Alcohol use disorders have both high social and economic costs and are among the leading causes of preventable death in the United States. Understanding the factors that contribute to escalation of alcohol intake is important in developing effective treatments for this problem. This study further characterizes the effects of limited intermittent exposure to high levels of alcohol on the preference for alcohol consumption over other incentives. Method: Fourteen male, Sprague-Dawley rats were trained to consume ethanol in a gelatin vehicle. They were then given free access to both ethanol gelatin and plain gelatin during daily choice periods interspersed with nonchoice periods (only plain gelatin access). After baseline ethanol preference was established, half of the rats were given eight injections of 3 g/kg ethanol during nonchoice periods (spread out over about 2 months), and the other half received saline injections. Ethanol preference was measured during subsequent choice periods. Results: Intermittent ethanol injections increased ethanol preference from 21% (SEM = 2.3%) of their total gelatin consumption during the first choice period to 46.8% (SEM = 3.4%) during the third choice period. The saline-treated rats had no significant change in ethanol preference. In addition, the ethanol-treated rats exhibited higher ethanol intake than saline-treated rats when ethanol gelatin was the only choice available. Conclusions: The results indicate that intermittent exposure to sedative doses of ethanol leads to an increased ethanol preference in rats. This suggests that occasional high-dose alcohol exposure could be an important contributor to the development of enhanced ethanol intake, which may affect the incidence of chronic alcoholism. PMID:25486406

  11. [Omeprazole/amoxicillin: improved eradication of Helicobacter pylori in smokers because of N-acetylcysteine].

    PubMed

    Zala, G; Flury, R; Wüst, J; Meyenberger, C; Ammann, R; Wirth, H P

    1994-08-01

    Colonization of Helicobacter pylori (HP) beneath the protective film of gastric mucus enables the organism to survive in the hostile environment of the gastric mucosa. N-acetylcysteine (NAC), a sulfhydryl compound with potent mucolytic activity, induces a reduction of gastric barrier mucus thickness of about 75% and reduces mucus viscoelasticity. We therefore tested the hypothesis whether better eradication results could be achieved by addition of NAC to omeprazole/amoxicillin (OME/AMOX). 34 HP positive outpatients with endoscopically documented recurrent duodenal ulcer were included in an ongoing, prospective, randomized trial. Exclusion criteria were: alcoholism, previous gastric surgery, or intake of antibiotics, OME, bismuth salts, corticosteroids or NSAIDs within 4 weeks before study entry. Patients currently smoking > 10 cigarettes/day were classified as smokers. HP infection was confirmed by histology (3 biopsy specimens from gastric antrum and 2 from gastric body; H&E, Giemsa) and at least positive rapid urease test or culture. All 34 patients underwent ulcer therapy with OME (20 mg per day) for 20 days (d 1-20). Group A: in 17 patients (5 females, 12 males, mean age 46 [29-74] years; 8 smokers, 9 nonsmokers) the subsequent eradication therapy, consisting of oral OME (40 mg bid) and AMOX solute (750 mg tid) for 10 days, was combined with NAC solute (2 x 600 mg bid (d 21-30). Group B: 17 patients (2 females, 15 males, mean age 39 [19-70] years; 11 smokers, 6 nonsmokers) underwent eradication therapy without NAC (d 21-30). Control endoscopy was done after a minimal interval of 30 days from the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8091167

  12. [Omeprazole/amoxicillin: improved eradication of Helicobacter pylori in smokers because of N-acetylcysteine].

    PubMed

    Zala, G; Flury, R; Wüst, J; Meyenberger, C; Ammann, R; Wirth, H P

    1994-08-01

    Colonization of Helicobacter pylori (HP) beneath the protective film of gastric mucus enables the organism to survive in the hostile environment of the gastric mucosa. N-acetylcysteine (NAC), a sulfhydryl compound with potent mucolytic activity, induces a reduction of gastric barrier mucus thickness of about 75% and reduces mucus viscoelasticity. We therefore tested the hypothesis whether better eradication results could be achieved by addition of NAC to omeprazole/amoxicillin (OME/AMOX). 34 HP positive outpatients with endoscopically documented recurrent duodenal ulcer were included in an ongoing, prospective, randomized trial. Exclusion criteria were: alcoholism, previous gastric surgery, or intake of antibiotics, OME, bismuth salts, corticosteroids or NSAIDs within 4 weeks before study entry. Patients currently smoking > 10 cigarettes/day were classified as smokers. HP infection was confirmed by histology (3 biopsy specimens from gastric antrum and 2 from gastric body; H&E, Giemsa) and at least positive rapid urease test or culture. All 34 patients underwent ulcer therapy with OME (20 mg per day) for 20 days (d 1-20). Group A: in 17 patients (5 females, 12 males, mean age 46 [29-74] years; 8 smokers, 9 nonsmokers) the subsequent eradication therapy, consisting of oral OME (40 mg bid) and AMOX solute (750 mg tid) for 10 days, was combined with NAC solute (2 x 600 mg bid (d 21-30). Group B: 17 patients (2 females, 15 males, mean age 39 [19-70] years; 11 smokers, 6 nonsmokers) underwent eradication therapy without NAC (d 21-30). Control endoscopy was done after a minimal interval of 30 days from the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Formulation, characterisation and stabilisation of buccal films for paediatric drug delivery of omeprazole.

    PubMed

    Khan, Sajjad; Boateng, Joshua S; Mitchell, John; Trivedi, Vivek

    2015-08-01

    This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0-1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation.

  14. Interstitial high-dose-rate brachytherapy in locally advanced and recurrent vulvar cancer

    PubMed Central

    Białas, Brygida; Fijałkowski, Marek; Wojcieszek, Piotr; Szlag, Marta; Cholewka, Agnieszka; Ślęczka, Maciej; Kołosza, Zofia

    2016-01-01

    Purpose The aim of the study was to report our experience with high-dose-rate interstitial brachytherapy (HDR-ISBT) in locally advanced and recurrent vulvar cancer. Material and methods Between 2004 and 2014, fourteen women with locally advanced or recurrent vulvar cancer were treated using HDR-ISBT in our Centre. High-dose-rate interstitial brachytherapy was performed as a separate treatment or in combination with external beam radiotherapy (EBRT) (given prior to brachytherapy). Results Patients were divided into: group I (n = 6) with locally advanced tumors, stages III-IVA after an incisional biopsy only, and group II (n = 8) with recurrent vulvar cancer after previous radical surgery. In group I, median follow up was 12 months (range 7-18 months); 1-year overall survival (OS) was 83%. Transient arrest of cancer growth or tumor regression was noticed in all patients but 4/6 developed relapse. Median time to failure was 6.3 months (range 3-11 months). The 1-year progression-free survival (PFS) was 33%. In group II, median follow up was 28 months (range 13-90 months). The 1-year and 3-year OS was 100% and 80%, respectively. The arrest of cancer growth or tumor regression was achieved in all patients. In 4/8 patients neither clinical nor histological symptoms of relapse were observed but 4/8 women experienced relapse. Median time to failure was 31 months (range 13-76 months). The 1-year and 3-year PFS was 100% and 62.5%, respectively. Two patients (14.3%) in group II had severe late toxicity (G3). Conclusions High-dose-rate interstitial brachytherapy is a well-tolerated treatment option in selected patients with advanced or recurrent vulvar cancer. It is a safe and effective treatment modality for advanced and recurrent vulvar cancer, yielding good local control with acceptable late treatment related side effects. In our study, patients with recurrent vulvar cancer had better results in HDR-ISBT treatment, probably because of the smaller tumor volume. This

  15. Direction-Modulated Brachytherapy for High-Dose-Rate Treatment of Cervical Cancer. I: Theoretical Design

    SciTech Connect

    Han, Dae Yup; Webster, Matthew J.; Scanderbeg, Daniel J.; Yashar, Catheryn; Choi, Dongju; Song, Bongyong; Devic, Slobodan; Ravi, Ananth; Song, William Y.

    2014-07-01

    Purpose: To demonstrate that utilization of the direction-modulated brachytherapy (DMBT) concept can significantly improve treatment plan quality in the setting of high-dose-rate (HDR) brachytherapy for cervical cancer. Methods and Materials: The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter, grooved along a nonmagnetic tungsten-alloy rod (ρ = 18.0 g/cm{sup 3}), enclosed in Delrin tubing (polyoxymethylene, ρ = 1.41 g/cm{sup 3}), with a total thickness of 6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic {sup 192}Ir dose distributions. An in-house-developed inverse planning platform, geared with simulated annealing and constrained-gradient optimization algorithms, was used to replan 15 patient cases (total 75 plans) treated with a conventional tandem and ovoids (T and O) applicator. Prescription dose was 6 Gy. For replanning, we replaced the conventional tandem with that of the new DMBT tandem for optimization but left the ovoids in place and kept the dwell positions as originally planned. All DMBT plans were normalized to match the high-risk clinical target volume V100 coverage of the T and O plans. Results: In general there were marked improvements in plan quality for the DMBT plans. On average, D2cc for the bladder, rectum, and sigmoid were reduced by 0.59 ± 0.87 Gy (8.5% ± 28.7%), 0.48 ± 0.55 Gy (21.1% ± 27.2%), and 0.10 ± 0.38 Gy (40.6% ± 214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%), 2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical target volume D90 was similar, with 6.55 ± 0.96 Gy and 6.59 ± 1.06 Gy for T and O and DMBT, respectively. Conclusions: Application of the DMBT concept to cervical cancer allowed for improved organ at risk sparing while achieving similar target coverage on a sizeable patient population, as intended, by maximally utilizing the anatomic information contained in 3-dimensional

  16. The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation.

    PubMed

    Sikiric, P; Separovic, J; Anic, T; Buljat, G; Mikus, D; Seiwerth, S; Grabarevic, Z; Stancic-Rokotov, D; Pigac, B; Hanzevacki, M; Marovic, A; Rucman, R; Petek, M; Zoricic, I; Ziger, T; Aralica, G; Konjevoda, P; Prkacin, I; Gjurasin, M; Miklic, P; Artukovic, B; Tisljar, M; Bratulic, M; Mise, S; Rotkvic, I

    1999-12-01

    A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1 x 1 x 0.25 cm; V = 0.25 mL) with the same quantities of BPC 157 (10 ng x mL(-1), 10 microg x mL(-1), 50 microg x kg(-1)) or reference agents (cimetidine: 10, 100, 500 mg x mL(-1); ranitidine: 2.5, 25, 250 mg x mL(-1); famotidine: 10, 50, 100 mg x mL(-1); omeprazole: 10, 50, 100 mg x mL(-1); sucralfate: 1, 5, 10 mg x mL(-1) were implanted subcutaneously in the lumbar region. The sponges were removed after 3 or 7 d, fixed in formalin, and processed for histologic and histochemical evaluation and morphometry assessment. Compared with the control values, the number of newly formed endothelial spaces inside newly formed granulation tissue was markedly increased in all animals treated with BPC 157, cimetidine, ranitidine, famotidine, sucralfate and omeprazole, a consistent finding noted after either 3 or 7 d. Compared with control values, markedly more granulation tissue was noted in the rats in the groups of animals treated with BPC 157 (50 microg) and in the rats treated with sucralfate in all dosages used, euthanized after 3 d. In all groups treated with H2-blockers however, similar values to those of controls were noted. Thus, it could be concluded that an evident angiogenic property was consistently noted for the novel pentadecapeptide BPC 157, H2-blockers (cimetidine, famotidine and ranitidine) and omeprazole, besides the well known angiogenic effect of sucralfate. Furthermore, unlike H2-blockers and omeprazole

  17. Nephrotoxicity as a Dose-Limiting Factor in a High-Dose Cisplatin-Based Chemoradiotherapy Regimen for Head and Neck Carcinomas

    PubMed Central

    Hoek, Jantien; Bloemendal, Karen M.; van der Velden, Lilly-Ann A.; van Diessen, Judi N.A.; van Werkhoven, Erik; Klop, Willem M.C.; Tesselaar, Margot E.T.

    2016-01-01

    Purpose: Loco-regional control and organ preservation are significantly improved with concomitant cisplatin/radiotherapy and are compromised with less than 5% grade 3 nephrotoxicity (creatinine clearance 15–29 mL/min). However, although clinically important, in none of the randomized trials is grade 2 nephrotoxicity (defined as creatinine clearance 59–30 mL/min) mentioned. In this study, we assessed nephrotoxicity in daily practice among patients treated with high-dose cisplatin (100 mg/m2 on days 1, 22, and 43), concurrently with chemoradiotherapy (CCRT) and the impact on treatment modifications. Methods: 208 patients with advanced-stage malignancies of the head and neck region were evaluated. All patients were treated with high-dose cisplatin CCRT. The main outcome parameters were nephrotoxicity (defined as creatinine clearance grade 2 or more) and cumulative doses of cisplatin and radiation. Results: 133 patients (64%) completed all pre-planned courses of cisplatin. Nephrotoxicity was the main reason to discontinue the chemotherapy. Grade 3 nephrotoxicity was seen in 16 patients (8%) while grade 2 nephrotoxicity was seen in 53 patients (25%). Thirty six patients (17%) could not complete the pre-planned chemotherapy due to nephrotoxicity. Conclusions: In head and neck cancer patients, nephrotoxicity grade 2 is under-reported but is the major factor for discontinuing cisplatin during CCRT. PMID:26891330

  18. Computational Modeling of Cellular Effects Post-Irradiation with Low- and High-Let Particles and Different Absorbed Doses

    PubMed Central

    Tavares, Adriana Alexandre S.; Tavares, João Manuel R. S.

    2013-01-01

    The use of computational methods to improve the understanding of biological responses to various types of radiation is an approach where multiple parameters can be modelled and a variety of data is generated. This study compares cellular effects modelled for low absorbed doses against high absorbed doses. The authors hypothesized that low and high absorbed doses would contribute to cell killing via different mechanisms, potentially impacting on targeted tumour radiotherapy