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Sample records for high dose omeprazole

  1. Omeprazole

    MedlinePlus

    ... heartburn and possible injury of the esophagus (the tube between the throat and stomach). Prescription omeprazole is ... capsules can both be given through a feeding tube. If you have a feeding tube, ask your ...

  2. Optimal dose of oral omeprazole for maximal 24 hour decrease of intragastric acidity.

    PubMed Central

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

    1984-01-01

    In a series of 59 experiments in nine duodenal ulcer patients, 24 hour intragastric acidity was measured before, during, and after treatment with daily oral omeprazole. Omeprazole 10, 20, and 30 mg/day for one week caused a 37, 90, and 97% decrease of 24 hour intragastric acidity, respectively. No further decrease of acidity was observed when the dose of omeprazole was doubled to 60 mg/day, or after a second week of treatment with 30 mg/day. One week after stopping treatment with omeprazole (14 doses) there was a significant 26% decrease of 24 hour intragastric acidity, with full recovery seven weeks later. Fasting plasma gastrin concentration was significantly raised during treatment with all doses of omeprazole. Omeprazole 30 mg/day is the optimal dose for a maximal decrease of 24 hour intragastric acidity in duodenal ulcer patients. PMID:6469081

  3. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

    PubMed Central

    Park, Gab-jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    Purpose A microdose drug–drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (Cmax) and area under the curve to the last measurement (AUCt) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16 (micro) and 0.15 (regular) for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

  4. Metabolism of omeprazole after two oral doses in children 1 to 9 months old.

    PubMed

    Hoyo-Vadillo, Carlos; Venturelli, Caterina R; González, Hector; Romero, Elba; Cervantes, Roberto; Mata, Norberto; Ortiz, Ana Carolina; Rincón, Victor; Zarate, Flora; Sosa, Cristina; Ramírez-Mayans, Jaime

    2005-01-01

    Proton pump inhibitors (PPIs) have been used recently for gastrointestinal esophageal reflux disease (GERD) in children older than one year with good results. However, the pharmacokinetics of PPIs have not been studied in children less than two years old. The aim of our study was to evaluate the frequency of the main phenotypes of the metabolizing enzymes CYP2C19 and CYP3A4 in Mexican infants. Our results indicate no significant difference between the 0.5 and the 1.5 mg/kg doses. The percentage of CYP2C19-poor metabolizers was 17% in babies below 4 months and was not detected in children above 3 months. When a combined CYP2C19- and CYP3A4- phenotype was estimated, omeprazole levels were significantly higher in poor metabolizers than in extended metabolizers. The percentage of ultra-extensive metabolizers in children older than 3 months were 20% and 33% for CYP2C19 and CYP3A4 respectively, compared to only 6% and 9% respectively, in babies between 1 and 3 months old. In general children, under 4 months had higher omeprazole levels and an immature metabolism. Studies in children older than 2 years old have showed similar pharmacokinetics to adults. For children between 1 month old and up to 9 months, we suggest the use of the 0.5 mg/kg dose, since it prevents accumulation in poor metabolizers, caution is recommended to identify ultra-fast metabolizers, but this would require new studies.

  5. High resolution mass spectrometry to investigate omeprazole and venlafaxine metabolites in wastewater.

    PubMed

    Boix, Clara; Ibáñez, María; Bagnati, Renzo; Zuccato, Ettore; Sancho, Juan V; Hernández, Félix; Castiglioni, Sara

    2016-01-25

    This study reports an investigation of omeprazole and venlafaxine parent substances and metabolites in Italian municipal influent wastewaters (IWWs). These pharmaceuticals were selected because they are widely consumed in Italy, but are poorly detected in waste and surface water. The aim of the study was to identify the most relevant pharmaceuticals metabolites in wastewater in order to improve the prioritization step and choose priority pollutants for environmental monitoring campaigns. This was done by investigating omeprazole, venlafaxine and their main metabolites in 30 IWWs from ten Italian cities and by comparing results with information from pharmacokinetic studies. Analysis was performed by solid phase extraction (SPE) and high-performance liquid chromatography (HPLC) coupled to high resolution mass spectrometry (HRMS). We searched for 23 omeprazole and four venlafaxine metabolites using data-dependent and MS/MS methods. Parent omeprazole was never present in the samples. Six omeprazole metabolites were found in IWWs. Venlafaxine and two metabolites were present in all the samples. The metabolic profiles in Italian IWW agreed with results in IWW from Spain and with urinary excretion profiles from pharmacokinetic studies. Comparing results from different sources was useful to improve the identification of pharmaceuticals metabolites in environmental samples and to focus the attention of future studies on the most relevant compounds.

  6. 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.

  7. 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.

  8. Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach

    PubMed Central

    Kaguelidou, Florentia; Alberti, Corinne; Biran, Valerie; Bourdon, Olivier; Farnoux, Caroline; Zohar, Sarah; Jacqz-Aigrain, Evelyne

    2016-01-01

    Objective Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker. Design Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%). Setting Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France. Patients Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth. Intervention Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day. Main outcome measures Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation. Results Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3–99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24). Conclusions Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux

  9. Animal pharmacodynamics of omeprazole. A survey of its pharmacological properties in vivo.

    PubMed

    Larsson, H; Mattson, H; Sundell, G; Carlsson, E

    1985-01-01

    In the present paper, a collection of experimental data is presented describing the pharmacological profile of omeprazole mainly in dogs and rats. Omeprazole potently inhibited gastric acid secretion in different experimental models. In the dog, for instance, omeprazole was 2-7 times more potent than cimetidine, depending on the route of administration, and in the rat the difference was even greater. Omeprazole was equally potent against different types of stimulation, whereas cimetidine was not, indicating differences in their mechanisms of action. In the dog, the duration of the antisecretory effect was long and lasted for 3-4 days after a single maximal dose of omeprazole. The inhibitory effect after repeated, daily administration of submaximal doses therefore gradually increased and attained a steady-state level after five doses. Treatment up to one year with very high oral doses did not affect the duration of effect. During long-term treatment with high doses of omeprazole a 10-fold increase in meal-stimulated plasma gastrin levels was recorded. This was probably due to a nearly complete inhibition of acid secretion over 24 hours during the study. The gastrin values returned to control levels within eight days after the end of the treatment. Omeprazole was rapidly absorbed (peak plasma levels were reached within one hour) and the elimination half-life was approximately one hour. In the dog, the gastric antisecretory effect was related to the total dose and the area under the plasma concentration curve, whereas the peak level or the shape of the curve was of minor importance. Omeprazole, given orally to rats, dose-dependently prevented experimentally induced gastric lesions. Neither inhibition of acid secretion, stimulation of gastric bicarbonate secretion nor interference with the synthesis of endogenous prostaglandins seems to be of any great importance for the gastric protective effect of omeprazole. Omeprazole seems to be very specific in its gastric acid

  10. 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.

  11. Giardial triosephosphate isomerase as possible target of the cytotoxic effect of omeprazole in Giardia lamblia.

    PubMed

    Reyes-Vivas, Horacio; de la Mora-de la Mora, Ignacio; Castillo-Villanueva, Adriana; Yépez-Mulia, Lilian; Hernández-Alcántara, Gloria; Figueroa-Salazar, Rosalia; García-Torres, Itzhel; Gómez-Manzo, Saúl; Méndez, Sara T; Vanoye-Carlo, América; Marcial-Quino, Jaime; Torres-Arroyo, Angélica; Oria-Hernández, Jesús; Gutiérrez-Castrellón, Pedro; Enríquez-Flores, Sergio; López-Velázquez, Gabriel

    2014-12-01

    Giardiasis is highly prevalent in the developing world, and treatment failures with the standard drugs are common. This work deals with the proposal of omeprazole as a novel antigiardial drug, focusing on a giardial glycolytic enzyme used to follow the cytotoxic effect at the molecular level. We used recombinant technology and enzyme inactivation to demonstrate the capacity of omeprazole to inactivate giardial triosephosphate isomerase, with no adverse effects on its human counterpart. To establish the specific target in the enzyme, we used single mutants of every cysteine residue in triosephosphate isomerase. The effect on cellular triosephosphate isomerase was evaluated by following the remnant enzyme activity on trophozoites treated with omeprazole. The interaction of omeprazole with giardial proteins was analyzed by fluorescence spectroscopy. The susceptibility to omeprazole of drug-susceptible and drug-resistant strains of Giardia lamblia was evaluated to demonstrate its potential as a novel antigiardial drug. Our results demonstrate that omeprazole inhibits giardial triosephosphate isomerase in a species-specific manner through interaction with cysteine at position 222. Omeprazole enters the cytoplasmic compartment of the trophozoites and inhibits cellular triosephosphate isomerase activity in a dose-dependent manner. Such inhibition takes place concomitantly with the cytotoxic effect caused by omeprazole on trophozoites. G. lamblia triosephosphate isomerase (GlTIM) is a cytoplasmic protein which can help analyses of how omeprazole works against the proteins of this parasite and in the effort to understand its mechanism of cytotoxicity. Our results demonstrate the mechanism of giardial triosephosphate isomerase inhibition by omeprazole and show that this drug is effective in vitro against drug-resistant and drug-susceptible strains of G. lamblia.

  12. Giardial Triosephosphate Isomerase as Possible Target of the Cytotoxic Effect of Omeprazole in Giardia lamblia

    PubMed Central

    Reyes-Vivas, Horacio; de la Mora-de la Mora, Ignacio; Castillo-Villanueva, Adriana; Yépez-Mulia, Lilian; Hernández-Alcántara, Gloria; Figueroa-Salazar, Rosalia; García-Torres, Itzhel; Gómez-Manzo, Saúl; Méndez, Sara T.; Vanoye-Carlo, América; Marcial-Quino, Jaime; Torres-Arroyo, Angélica; Oria-Hernández, Jesús; Gutiérrez-Castrellón, Pedro; Enríquez-Flores, Sergio

    2014-01-01

    Giardiasis is highly prevalent in the developing world, and treatment failures with the standard drugs are common. This work deals with the proposal of omeprazole as a novel antigiardial drug, focusing on a giardial glycolytic enzyme used to follow the cytotoxic effect at the molecular level. We used recombinant technology and enzyme inactivation to demonstrate the capacity of omeprazole to inactivate giardial triosephosphate isomerase, with no adverse effects on its human counterpart. To establish the specific target in the enzyme, we used single mutants of every cysteine residue in triosephosphate isomerase. The effect on cellular triosephosphate isomerase was evaluated by following the remnant enzyme activity on trophozoites treated with omeprazole. The interaction of omeprazole with giardial proteins was analyzed by fluorescence spectroscopy. The susceptibility to omeprazole of drug-susceptible and drug-resistant strains of Giardia lamblia was evaluated to demonstrate its potential as a novel antigiardial drug. Our results demonstrate that omeprazole inhibits giardial triosephosphate isomerase in a species-specific manner through interaction with cysteine at position 222. Omeprazole enters the cytoplasmic compartment of the trophozoites and inhibits cellular triosephosphate isomerase activity in a dose-dependent manner. Such inhibition takes place concomitantly with the cytotoxic effect caused by omeprazole on trophozoites. G. lamblia triosephosphate isomerase (GlTIM) is a cytoplasmic protein which can help analyses of how omeprazole works against the proteins of this parasite and in the effort to understand its mechanism of cytotoxicity. Our results demonstrate the mechanism of giardial triosephosphate isomerase inhibition by omeprazole and show that this drug is effective in vitro against drug-resistant and drug-susceptible strains of G. lamblia. PMID:25223993

  13. Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.

    PubMed Central

    Borody, T J; Andrews, P; Fracchia, G; Brandl, S; Shortis, N P; Bae, H

    1995-01-01

    Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (>95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with

  14. [Helicobacter pylori eradication therapy with omeprazole and amoxicillin: current status].

    PubMed

    Bayerdörffer, E; Miehlke, S; Mannes, G A

    1994-11-01

    Combined therapy with the proton pump inhibitor omeprazole and amoxicillin has become an important alternative in the treatment of ulcer disease associated with Helicobacter pylori infection. Due to the high efficacy in eradicating H.pylori, missing resistance of H.pylori against amoxicillin and high tolerability and digestibility this regimen may be recommended for widespread routine use. In a randomized, double-blind multicenter trial an H.pylori eradication rate of over 90% has been achieved for the first time by dual therapy using a daily omeprazole dose of 120 mg (3x40 mg) in combination with 3 x 750 mg amoxicillin for 14 days, which is comparable with classical triple therapy containing bismuth and two antibiotics. On the basis of an "intention-to-treat-analysis" dual therapy of omeprazole 3x40 mg + 3x750 mg amoxicillin is considered at present to be the most effective regimen for the treatment of H.pylori-associated diseases.

  15. Duodenal bacterial overgrowth during treatment in outpatients with omeprazole.

    PubMed Central

    Fried, M; Siegrist, H; Frei, R; Froehlich, F; Duroux, P; Thorens, J; Blum, A; Bille, J; Gonvers, J J; Gyr, K

    1994-01-01

    The extent of duodenal bacterial overgrowth during the pronounced inhibition of acid secretion that occurs with omeprazole treatment is unknown. The bacterial content of duodenal juice of patients treated with omeprazole was therefore examined in a controlled prospective study. Duodenal juice was obtained under sterile conditions during diagnostic upper endoscopy. Aspirates were plated quantitatively for anaerobic and aerobic organisms. Twenty five outpatients with peptic ulcer disease were investigated after a 5.7 (0.5) weeks (mean (SEM)) treatment course with 20 mg (nine patients) or 40 mg (16 patients). The control group consisted of 15 outpatients referred for diagnostic endoscopy without prior antisecretory treatment. No patient in the control group had duodenal bacterial overgrowth. In the omeprazole group bacterial overgrowth (> or = 10(5) cfu/ml) was found in 14 (56%) patients (p = 0.0003). The number of bacteria (log10) in duodenal juice in patients treated with omeprazole was distinctly higher (median 5.7; range < 2-8.7) when compared with the control group (median < 2; range < 2-5.0; p = 0.0004). As well as orally derived bacteria, faecal type bacteria were found in seven of 14 and anaerobic bacteria in three of 14 patients. Bacterial overgrowth was similar with the two doses of omeprazole. These results indicate that duodenal bacterial overgrowth of both oral and faecal type bacteria occurs often in ambulatory patients treated with omeprazole. Further studies are needed to determine the clinical significance of these findings, particularly in high risk groups during long term treatment with omeprazole. PMID:8307444

  16. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    PubMed

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

  17. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    PubMed Central

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative. PMID:8566861

  18. Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole

    PubMed Central

    2014-01-01

    Background Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Methods Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. Results 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). Conclusions In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. Trial registration ClinicalTrial.gov: NCT01136317 PMID:25027286

  19. Investigating the presence of omeprazole in waters by liquid chromatography coupled to low and high resolution mass spectrometry: degradation experiments.

    PubMed

    Boix, C; Ibáñez, M; Sancho, J V; Niessen, W M A; Hernández, F

    2013-10-01

    Omeprazole is one of the most consumed pharmaceuticals around the world. However, this compound is scarcely detected in urban wastewater and surface water. The absence of this pharmaceutical in the aquatic ecosystem might be due to its degradation in wastewater treatment plants, as well as in receiving water. In this work, different laboratory-controlled degradation experiments have been carried out on surface water in order to elucidate generated omeprazole transformation products (TPs). Surface water spiked with omeprazole was subjected to hydrolysis, photo-degradation under both sunlight and ultraviolet radiation and chlorination. Analyses by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF MS) permitted identification of up to 17 omeprazole TPs. In a subsequent step, the TPs identified were sought in surface water and urban wastewater by LC-QTOF MS and by LC coupled to tandem mass spectrometry with triple quadrupole. The parent omeprazole was not detected in any of the samples, but four TPs were found in several water samples. The most frequently detected compound was OTP 5 (omeprazole sulfide), which might be a reasonable candidate to be included in monitoring programs rather than the parent omeprazole.

  20. Effect of various salts on the stability of lansoprazole, omeprazole, and pantoprazole as determined by high-performance liquid chromatography.

    PubMed

    Ekpe, A; Jacobsen, T

    1999-09-01

    A fast and reproducible reverse-phase high-performance liquid chromatography (HPLC) assay method has been developed for the simultaneous quantitation of omeprazole, lansoprazole, and pantoprazole. The three compounds were monitored at 280 nm using Zorbax Eclipse XDB C8 (5 microns, 150 cm x 4.6 mm i.d.) and a mobile phase consisting of 700:300 phosphate buffer:acetonitrile with the pH adjusted to 7.0 with phosphoric acid. The method was used to study the effect of pH and various salts on the stability of the three compounds. The pH rate profile curve showed that pantoprazole was the most stable compound and lansoprazole the least stable. The stabilities of the compounds in salt solutions were found to be in the following order: phosphate buffer < trisodium citrate < citrate buffer < or = acetate buffer < citric acid < or = monosodium citrate < or = calcium carbonate < sodium bicarbonate < sodium chloride < water. The rate of degradation had a direct relationship with the H+ and salt concentration.

  1. A Validated High-Throughput Fluorometric Method for Determination of Omeprazole in Quality Control Laboratory via Charge Transfer Sensitized Fluorescence.

    PubMed

    Mahmoud, Ashraf M; Ahmed, Sameh A

    2016-03-01

    A high-throughput 96-microwell plate fluorometric method was developed and validated to determine omeprazole (OMZ) in its dosage forms. The method was based on the charge-transfer (CT) sensitized fluorescence reaction of OMZ with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ). This fluorescence reaction provided a new approach for simple, sensitive and selective determinations of OMZ in pharmaceutical preparations. In the present method, the fluorescence reaction was carried out in 96-microwell plates as reaction vessels in order to increase the automation of the methodology and the efficiency of its use in quality control laboratories. All factors affecting the fluorescence reaction were carefully studied and the conditions were optimized. The stoichiometry of the fluorescence reaction between OMZ and DDQ was determined and the reaction mechanism was suggested. Under the optimum conditions, the linear range was 100-6000 ng/ml with the lowest LOD of 33 ng/ml. Analytical performance of the proposed assay, in terms of accuracy and precision, was statistically validated and the results were satisfactory; RSD was <2.6 % and the accuracy was 98.6-101.6 %. The method was successfully applied to the analysis of OMZ in its dosage forms; the recovery values were 98.26-99.60 ± 0.95-2.22 %. The developed methodology may provide a safer, automated and economic tool for the analysis of OMZ in quality control laboratories.

  2. Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection

    PubMed Central

    Jeppesen, P; Staun, M; Tjellesen, L; Mortensen, P

    1998-01-01

    Background—H2 receptor blockers and proton pump inhibitors reduce intestinal output in patients with short bowel syndrome. 
Aims—To evaluate the effect of intravenous omeprazole and ranitidine on water, electrolyte, macronutrient, and energy absorption in patients with intestinal resection. 
Methods—Thirteen patients with a faecal weight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowel length of 100cm were studied. Omeprazole 40 mg twice daily or ranitidine 150mg twice daily were administered for five days in a randomised, double blind, crossover design followed by a three day control period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had no influence on the results. 
Results—Omeprazole increased median intestinal wet weight absorption compared with no treatment and ranitidine (p<0.03). The effect of ranitidine was not significant. Four patients with faecal volumes below 2.6 kg/day did not respond to omeprazole; in two absorption increased by 0.5-1 kg/day; and in five absorption increased by 1−2 kg/day. Absorption of sodium, calcium, magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged. Four high responders continued on omeprazole for 12-15 months, but none could be weaned from parenteral nutrition. 
Conclusion—Omeprazole increased water absorption in patients with faecal output above 2.50 kg/day. The effect varied significantly and was greater in patients with a high output, but did not allow parenteral nutrition to be discontinued. Absorption of energy, macronutrients, electrolytes, and divalent cations was not improved. The effect of ranitidine was not significant, possibly because the dose was too low. 

 Keywords: short bowel syndrome; human; diarrhoea; ranitidine; omeprazole PMID:9824602

  3. Pharmacokinetic evaluation of omeprazole suspension following oral administration in rats: effect of neutralization of gastric acid.

    PubMed

    Watanabe, K; Matsuka, N; Furuno, K; Eto, K; Kawasaki, H; Gomita, Y

    1996-08-01

    In order to evaluate a clinical use of omeprazole suspension, we examined the pharmacokinetics of omeprazole after oral administration in rats. Although the administration of omeprazole suspension buffered by NaHCO3 solution did not produce a significant increase in the area under the concentration-time curve (AUC) value compared with non-buffered group, the administration of NaHCO3 buffer immediately after dosing of omeprazole suspension buffered by NaHCO3 caused a significant increase in the AUC value. These results suggest that the NaHCO3 treatment following the administration of omeprazole buffered suspension effectively decreased the degradation of the compound by gastric acid. Therefore, the successive administration of NaHCO3 solution after the omeprazole dosing seems to be a simple and useful method for the administration to patients who cannot receive tablets.

  4. Zegerid--immediate-release omeprazole.

    PubMed

    2005-04-11

    The FDA has approved marketing of Zegerid powder for oral suspension (Santarus), an immediate-release formulation of the proton-pump inhibitor (PPI) omeprazole (Prilosec, and others). All other oral PPIs are delayed-release, enteric-coated formulations designed to prevent degradation of the drug by gastric acid. Each 20- or 40-mg packet of Zegerid contains 1680 mg sodium bicarbonate, which protects the drug from gastric acid degradation. A dose of Zegerid contains 460 mg of sodium, which may be excessive for some patients. Zegerid is the first oral PPI to be approved by the FDA for reduction of risk of upper GI bleeding in critically ill patients. The drug may be useful for patients who are unable to swallow and have nasogastric (NG) tubes in place. Zegerid cost $70.00 for 14 days' treatment, compared to less than $10 for 14 tablets of Prilosec OTC.

  5. Sensitive quantification of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry.

    PubMed

    Hofmann, Ute; Schwab, Matthias; Treiber, Gerd; Klotz, Ulrich

    2006-02-02

    A sensitive method was developed for the simultaneous determination of omeprazole and its major metabolites 5-hydroxyomeprazole and omeprazole sulfone in human plasma by HPLC-electrospray mass spectrometry. Following liquid-liquid extraction HPLC separation was achieved on a ProntoSil AQ, C18 column using a gradient with 10 mM ammonium acetate in water (pH 7.25) and acetonitrile. The mass spectrometer was operated in the selected ion monitoring mode using the respective MH(+) ions, m/z 346 for omeprazole, m/z 362 for 5-hydroxy-omeprazole and omeprazol-sulfone and m/z 300 for the internal standard (2-{[(3,5-dimethylpyridine-2-yl)methyl]thio}-1H-benzimidazole-5-yl)methanol. The limit of quantification (LOQ) achieved with this method was 5 ng/ml for 5-hydroxyomeprazole and 10 ng/ml for omeprazole and omeprazole-sulfone using 0.25 ml of plasma. Intra- and inter-assay variability was below 11% over the whole concentration range from 5 to 250 ng/ml for 5-hydroxyomeprazol and from 10 to 750 ng/ml for omeprazole and omeprazole-sulfone. The method was successfully applied to the determination of pharmacokinetic parameters of esomeprazole and the two major metabolites after a single dose and under steady state conditions.

  6. Stability of omeprazole in an extemporaneously prepared oral liquid.

    PubMed

    Quercia, R A; Fan, C; Liu, X; Chow, M S

    1997-08-15

    The stability of omeprazole 2 mg/mL. in an extemporaneously prepared oral liquid was studied. The contents of five 20-mg omeprazole capsules were mixed with 50 mL of 8.4% sodium bicarbonate solution in a Luer-Lok syringe. Three vials of this liquid were prepared for storage at 24, 5, and -20 degrees C. A 3-mL. sample of each was taken initially and on days 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, 26, and 30 and assayed by high-performance liquid chromatography. The liquids stored at 5 degrees C and at -20 degrees C did not change color during the study period, but the color of the liquid stored at 24 degrees C changed from white to brown. There were no significant changes in the omeprazole concentrations of the liquids stored at 5 and -20 degrees C during the study period, but the omeprazole concentration of the liquid stored at 24 degrees C was < 90% of the initial concentration on day 18. Omeprazole 2 mg/mL in an oral liquid compounded extemporaneously from capsules and sodium bicarbonate injection was stable for up to 14 days at 24 degrees C and for up to 30 days at 5 and -20 degrees C.

  7. [Behavior of acid secretion under the long-term daily administration of omeprazol].

    PubMed

    Dammann, H G; Müller, P; Seitz, H K; Simon, B

    1983-06-18

    The effect of the substituted benzimidazole omeprazole on acid secretion after repeated administration to healthy volunteers has been studied. During repeated dosage of 30 mg once daily inhibition of basal and pentagastrin-stimulated acid output was increased from 30% after the first dose to about 60% after dose 4. The extent of inhibition did not further increase between day 5 and day 10. In four volunteers acid secretion returned to predose levels within 5 days after drug withdrawal. The 24-hour gastric acidity was reduced by about 72% and 82% after 9-day pretreatment with 30 mg and 60 mg omeprazole respectively. The antisecretory effect of omeprazole was independent of peak plasma concentrations. Omeprazole given once daily therefore possesses a long-lasting effect on gastric acid secretion, i.e. for more than 24 hours. This effect appears to be fully reversible since control levels of acid output are reached within 5 days.

  8. Acid Inhibitory Effect of a Combination of Omeprazole and Sodium Bicarbonate (CDFR0209) Compared With Delayed-Release Omeprazole 40 mg Alone in Healthy Adult Male Subjects.

    PubMed

    Kim, Kyu-Nam; Yang, Sung-Won; Kim, Hyunil; Kwak, Seong Shin; Kim, Young-Sang; Cho, Doo-Yeoun

    2017-01-23

    CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state.

  9. Omeprazole pharmacodynamics and gastric acid suppression in critically ill pediatric transplant patients.

    PubMed

    Olsen, K M; Bergman, K L; Kaufman, S S; Rebuck, J A; Collier, D S

    2001-07-01

    OBJECTIVE: To characterize the pharmacodynamics and pharmacokinetics of omeprazole suspension in critically ill pediatric liver/intestinal transplant patients. DESIGN: Open-label pharmacodynamic and pharmacokinetic study. SETTING: Pediatric intensive care unit of an academic medical center. PATIENTS: Eleven pediatric liver and/or intestinal transplant patients. INTERVENTIONS: Extemporaneously prepared 0.5 mg/kg omeprazole suspension every 12 hrs via nasogastric tube before sequential measurements of omeprazole serum concentration and gastric pH monitoring. Gastric pH was monitored continuously for 48 hrs and plasma omeprazole concentrations were determined upon first and multiple dosing. MEASUREMENTS AND MAIN RESULTS: Mean onset of action of omeprazole in a sodium bicarbonate vehicle was 62 +/- 82 mins (range, 2-226 mins). Subjects <4 yrs of age exhibited a more variable onset of omeprazole action (range, 3-226 mins) when compared with older subjects (onset of action, 2-40 min). Omeprazole maximum concentration and area under the concentration-time curve for the dosage interval were significantly greater upon multiple dosing when compared with the first dose. Mean baseline gastric pH in this study population was 1.0 +/- 0.8. Gastric pH remained >4.0 for 78.8% +/- 18.9% of the first dosage interval and 97.8% +/- 5.4% of multiple dosage intervals regardless of age when administered twice daily as a suspension. CONCLUSION: These results support the use of omeprazole administered twice daily as a suspension to maintain gastric pH of >4.0 and to achieve maximal pharmacodynamic effect in pediatric liver and/or intestinal transplant patients.

  10. Normal and polar-organic-phase high-performance liquid chromatographic enantioresolution of omeprazole, rabeprazole, lansoprazole and pantoprazole using monochloro-methylated cellulose-based chiral stationary phase and determination of dexrabeprazole.

    PubMed

    Dixit, Shuchi; Dubey, Rituraj; Bhushan, Ravi

    2014-01-01

    Enantioresolution of four anti-ulcer drugs (chiral sulfoxides), namely, omeprazole, rabeprazole, lansoprazole and pantoprazole, was carried out by high-performance liquid chromatography using a polysaccharide-based chiral stationary phase consisting of monochloromethylated cellulose (Lux cellulose-2) under normal and polar-organic-phase conditions with ultraviolet detection at 285 nm. The method was validated for linearity, accuracy, precision, robustness and limit of detection. The optimized enantioresolution method was compared for both the elution modes. The optimized method was further utilized to check the enantiomeric purity of dexrabeprazole.

  11. Reversible renal failure after treatment with omeprazole.

    PubMed

    Post, A T; Voorhorst, G; Zanen, A L

    2000-08-01

    Omeprazole is a proton pump inhibitor widely used in the treatment of gastro-esophageal reflux disease and peptic ulcer disease. In a 73-year-old man we describe renal failure due to acute interstitial nephritis after use of omeprazol during 4 months. Unexpected renal failure without signs of hydronephrosis should always provoke awareness of drug reaction, omeprazole being one of the possible drugs.

  12. Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus).

    PubMed

    Uehara, Shotaro; Inoue, Takashi; Utoh, Masahiro; Toda, Akiko; Shimizu, Makiko; Uno, Yasuhiro; Sasaki, Erika; Yamazaki, Hiroshi

    2016-01-01

    1. Pharmacokinetics of human cytochrome P450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) composite, after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg(-1), respectively, to four male common marmosets were investigated. 2. The plasma concentrations of caffeine and warfarin decreased slowly in a monophasic manner but those of omeprazole, metoprolol and midazolam decreased extensively after intravenous and oral administrations, in a manner that approximated those as reported for pharmacokinetics in humans. 3. Bioavailabilities were ∼100% for caffeine and warfarin, but <25% for omeprazole and metoprolol. Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system. 4. These results suggest that common marmosets, despite their rapid clearance of some human P450 probe substrates, could be an experimental model for humans and that marmoset P450s have functional characteristics that differ from those of human and/or cynomolgus monkey P450s in some aspects, indicating their importance in modeling in P450-dependent drug metabolism studies in marmosets and of further studies.

  13. Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis.

    PubMed

    Novotna, Aneta; Dvorak, Zdenek

    2014-01-01

    Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S-omeprazole were much stronger as compared to those of R-omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations.

  14. Suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole.

    PubMed

    Ajmera, Akash V; Shastri, Ghanshyam S; Gajera, Mithil J; Judge, Thomas A

    2012-05-01

    Iron deficiency anemia is commonly encountered in outpatient practice. Gastric acid is one of the important factors for optimum absorption of iron. Proton pump inhibitors are very commonly prescribed medications. One of the debated effects of proton pump inhibitors is on oral iron absorption. Their effect on absorption of oral iron supplementation in iron-deficient patients has not been studied. At the Cooper Hematology Outpatient office, we reviewed charts of iron-deficient anemic patients who were on omeprazole for the last 4 years. Fifty patients having no apparent ongoing blood loss, having other causes of anemia especially that of chronic diseases ruled out, and on omeprazole while starting ferrous sulfate therapy for iron deficiency were selected for chart review. The iron-study results at the start of oral ferrous sulfate therapy and at 3 months follow-up were compared to evaluate the response of ferrous sulfate. The mean hemoglobin change was 0.8 ± 1.2 g/L. The mean change in ferrtin values was 10.2 ± 7.8 μg/L. Only 16% of the patients had a normal response to hemoglobin levels (rise of >2 g/dL), and only 40% had a normal response to ferritin levels (rise of >20 μg/dL). The average age of patients having a suboptimal response to both hemoglobin and ferritin was significantly higher compared with that of the patients with an optimal response. Omeprazole and possibly all proton pump inhibitors decrease the absorption of oral iron supplementation. Iron-deficient patients taking proton pump inhibitors may have to be treated with high dose iron therapy for a longer duration or with intravenous iron therapy.

  15. 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.

  16. Solid solution hardening of molecular crystals: tautomeric polymorphs of omeprazole.

    PubMed

    Mishra, Manish Kumar; Ramamurty, Upadrasta; Desiraju, Gautam R

    2015-02-11

    In the context of processing of molecular solids, especially pharmaceuticals, hardness is an important property that often determines the manufacturing steps employed. Through nanoindentation studies on a series of omeprazole polymorphs, in which the proportions of the 5- and 6-methoxy tautomers vary systematically, we demonstrate that solid-solution strengthening can be effectively employed to engineer the hardness of organic solids. High hardness can be attained by increasing lattice resistance to shear sliding of molecular layers during plastic deformation.

  17. [Hopes of high dose-rate radiotherapy].

    PubMed

    Fouillade, Charles; Favaudon, Vincent; Vozenin, Marie-Catherine; Romeo, Paul-Henri; Bourhis, Jean; Verrelle, Pierre; Devauchelle, Patrick; Patriarca, Annalisa; Heinrich, Sophie; Mazal, Alejandro; Dutreix, Marie

    2017-03-07

    In this review, we present the synthesis of the newly acquired knowledge concerning high dose-rate irradiations and the hopes that these new radiotherapy modalities give rise to. The results were presented at a recent symposium on the subject.

  18. Omeprazole impairs the absorption of mycophenolate mofetil but not of enteric-coated mycophenolate sodium in healthy volunteers.

    PubMed

    Kees, M G; Steinke, T; Moritz, S; Rupprecht, K; Paulus, E M; Kees, F; Bucher, M; Faerber, L

    2012-08-01

    In 2 crossover studies, 12 healthy volunteers (6 male/6 female) received a single oral dose of mycophenolate mofetil (MMF) 1000 mg or an equimolar dose of enteric-coated mycophenolate sodium (EC-MPS) 720 mg fasting with and without coadministered omeprazole 20 mg bid. The plasma concentrations of mycophenolic acid (MPA) and of the inactive metabolite mycophenolic acid glucuronide (MPA-G) were measured by high-performance liquid chromatography (HPLC). In addition, dissolution of MMF 500 mg or EC-MPS 360 mg tablets was determined using an USP paddle apparatus in aqueous buffer of pH 1 to 7. The bioavailability of MPA following administration of MMF or EC-MPS was similar except for the time to peak concentration, which was longer in the EC-MPS group. Concomitant treatment with omeprazole lowered significantly C(max) and AUC(12h) of MPA following administration of MMF. The pharmacokinetics of EC-MPS was not affected. Dissolution of MMF in aqueous buffer decreased dramatically at pH above 4.5. The EC-MPS tablet was stable up to pH 5. Above, EC-MPS was quantitatively disintegrated and MPS quantitatively dissolved. There is strong evidence that impaired absorption of MMF with concomitant proton pump inhibitors is due to incomplete dissolution of MMF in the stomach at elevated pH.

  19. Omeprazole inhibits H+ secretion by Amphiuma jejunum.

    PubMed

    White, J F

    1985-02-01

    The effect on HCO3- absorption of the substituted benzimidazole omeprazole, an inhibitor of active H+-K+ exchange, was examined in in vitro Amphiuma jejunum. HCO-3 absorption was measured using titration in short-circuited intestinal segments bathed in a Cl--free (SO2-(4)-based) medium (pH 7.40). At 1 mM omeprazole lowered the short-circuit current (Isc) and the absorptive flux of HCO3- from mucosa to serosa by about 40% over 1 h. When the serosal medium was maintained at pH 5.0, additions of omeprazole beginning at 0.1 mM caused proportional reductions of the Isc. Omeprazole also reduced intracellular potassium activity (aiK) from 74 to 59 mM and lowered the luminal membrane potential (psi m) slightly over 30 min when this was measured with double-barreled, K+-sensitive microelectrodes. After 30 min aiK and psi m tended to spontaneously revert toward control values. Galactose added to the mucosal medium (to 20 mM) stimulated the Isc equally in omeprazole-treated tissues and paired untreated control tissues. These results support the view that a fraction of the absorptive HCO3- flux (so-called) is driven by an active luminal exchange of H+ for K+.

  20. 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.

  1. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study.

    PubMed Central

    Thorens, J; Froehlich, F; Schwizer, W; Saraga, E; Bille, J; Gyr, K; Duroux, P; Nicolet, M; Pignatelli, B; Blum, A L; Gonvers, J J; Fried, M

    1996-01-01

    -nitroso compounds. The clinical significance of these findings needs to be assessed in studies with long-term treatment with omeprazole, in particular in patients belonging to high risk groups such as HIV infected and intensive care units patients. PMID:8881809

  2. Cervix cancer brachytherapy: high dose rate.

    PubMed

    Miglierini, P; Malhaire, J-P; Goasduff, G; Miranda, O; Pradier, O

    2014-10-01

    Cervical cancer, although less common in industrialized countries, is the fourth most common cancer affecting women worldwide and the fourth leading cause of cancer death. In developing countries, these cancers are often discovered at a later stage in the form of locally advanced tumour with a poor prognosis. Depending on the stage of the disease, treatment is mainly based on a chemoradiotherapy followed by uterovaginal brachytherapy ending by a potential remaining tumour surgery or in principle for some teams. The role of irradiation is crucial to ensure a better local control. It has been shown that the more the delivered dose is important, the better the local results are. In order to preserve the maximum of organs at risk and to allow this dose escalation, brachytherapy (intracavitary and/or interstitial) has been progressively introduced. Its evolution and its progressive improvement have led to the development of high dose rate brachytherapy, the advantages of which are especially based on the possibility of outpatient treatment while maintaining the effectiveness of other brachytherapy forms (i.e., low dose rate or pulsed dose rate). Numerous innovations have also been completed in the field of imaging, leading to a progress in treatment planning systems by switching from two-dimensional form to a three-dimensional one. Image-guided brachytherapy allows more precise target volume delineation as well as an optimized dosimetry permitting a better coverage of target volumes.

  3. Inhibitory potency of twice-a-day omeprazole on gastric acidity is enhanced by eradication of H. pylori in duodenal ulcer patients.

    PubMed

    Thomson, A B R; Keelan, M; Lastiwka, R; Appelman-Eszczuk, S; Zuk, L; Drozdowski, L; Prentice, A; Sinclair, P

    2003-10-01

    The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1alpha, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H+ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H+ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.

  4. High dose Nutrizym 22 in cystic fibrosis.

    PubMed

    Shah, A; Dinwiddie, R; Madge, S; Prescott, P; Hudson, G

    1993-09-01

    New high dose pancreatic enzyme preparations could be potentially helpful to cystic fibrosis (CF) patients. The purpose of this study was to compare the efficacy of the new high dose pancreatic enzyme preparation, Nutrizym 22 with the standard preparation Nutrizym GR. Twenty-five CF children (aged 7-16 years) entered the study and 22 completed it; 3 did not, due to non-compliance. All were taking Nutrizym GR for at least 2 weeks before entering the study. A randomised double blind, crossover method using standard Nutrizym GR or double strength Nutrizym 22 capsules was carried out over two consecutive 14-day periods. Crossover analyses of variance showed no statistically significant differences in actual weight gain, appetite, abdominal pain, stool consistency or faecal fat during the prestudy and study periods. It is concluded that half the capsule numbers of the high strength preparation are just as effective as the standard capsule dosage.

  5. The effect of omeprazole pre-treatment on rafts formed by reflux suppressant tablets containing alginate.

    PubMed

    Dettmar, P W; Little, S L; Baxter, T

    2005-01-01

    Alginate-based reflux suppressant preparations provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study investigated whether reduced acidity in the stomach brought about by omeprazole pre-treatment affected the formation and gastric residence time of alginate rafts. It was a balanced, cross-over study in 12 healthy non-patient volunteers following a single dose of two indium-111-labelled alginate tablets in the presence or absence of 3 days' pre-treatment with omeprazole. Raft formation and gastric residence, in the presence of a technetium-99m-labelled meal, were assessed by gamma scintigraphy for 3 h after alginate tablet administration. The relative raft-forming ability of alginate tablets after omeprazole compared with alginate tablets alone was 0.950 with 95% confidence intervals of 0.882 and 1.018. Pre-treatment and co-administration with omeprazole has no significant effect on the raft-forming ability of alginate tablets.

  6. High-dose neutron detector project update

    SciTech Connect

    Menlove, Howard Olsen; Henzlova, Daniela

    2016-08-10

    These are the slides for a progress review meeting by the sponsor. This is an update on the high-dose neutron detector project. In summary, improvements in both boron coating and signal amplification have been achieved; improved boron coating materials and procedures have increased efficiency by ~ 30-40% without the corresponding increase in the detector plate area; low dead-time via thin cell design (~ 4 mm gas gaps) and fast amplifiers; prototype PDT 8” pod has been received and testing is in progress; significant improvements in efficiency and stability have been verified; use commercial PDT 10B design and fabrication to obtain a faster path from the research to practical high-dose neutron detector.

  7. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats.

    PubMed

    Patlolla, Jagan M R; Zhang, Yuting; Li, Qian; Steele, Vernon E; Rao, Chinthalapally V

    2012-01-01

    Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers and gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis induction in human colon cancer cells. Five-week-old male F344 rats were fed a control or experimental diet containing two doses of omeprazole (200 and 400 ppm). After one week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for two weeks). Rats continued on experimental diets for seven more weeks before being sacrificed. Colons were histopathologically evaluated for ACF. Human colon cancer HCT-116 and HCA-7 cells treated with omeprazole were evaluated for different markers associated with proliferation and apoptotic markers using Western blot technique. Rats fed with 200 and 400 ppm of omeprazole significantly suppressed total colonic ACF formation (~30%, P<0.001) and showed significant suppression of multi-crypt foci (~30-50%, P<0.05-0.001). Omeprazole produced significant dose-response effects on inhibition of multi-crypt foci (≥4). Omeprazole treatment in human colon cancer cell lines HCT-116 and HCA-7 cells resulted in induction of p21waf1/cip1 and decreased the expression of anti-apoptotic proteins Bcl-2, Bcl-XL and survivin in a dose-dependent manner. Anticancer properties observed in colon cancer cell lines suggest that omeprazole may induce key signaling molecules of antiproliferation and inhibition of anti-apoptotic proteins.

  8. Review of immediate-release omeprazole for the treatment of gastric acid-related disorders.

    PubMed

    Castell, Donald

    2005-11-01

    Immediate-release omeprazole (Zegerid, Santarus) is the first immediate-release oral proton pump inhibitor to reach the market. As a powder formulation for oral suspension, it is indicated for the treatment of gastroesophageal reflux disease, erosive oesophagitis, duodenal ulcer and gastric ulcer, and is the only proton pump inhibitor approved for the reduction of risk of upper gastrointestinal bleeding in critically ill patients. Administration of immediate-release omeprazole at bedtime results in a rapid and sustained elevation of gastric pH, and seems to provide better night time control of gastric acidity than that observed with conventional morning dosing of delayed-release proton pump inhibitors. The immediate-release formulation may provide a good treatment option for patients who require flexible dosing, quick onset of action and nocturnal gastric acid control.

  9. Optical fibres for high radiation dose environments

    NASA Astrophysics Data System (ADS)

    Henschel, H.; Kohn, O.; Schmidt, H. U.; Bawirzanski, E.; Landers, A.

    1994-06-01

    A variety of modern single mode (SM) and graded index (GI) fibres as well as a new pure silica multimode step index (MMSI) fibre with high OH content were irradiated at a Co-60 gamma ray source with a dose rate of approximately = 1.5Gy/s up to a total dose of 10(exp 6)Gy. The radiation-induced loss of all fibres was measured continuously during and after irradiation at discrete wavelengths (approximately = 850, approximately = 1070, approximately = 1300, approximately = 1550nm). With one SM fibre type also the 'breaking stress' before and after irradiation was determined. Radiation-induced losses of approximately less than 5dB/50m (at approximately = 1300nm) were found with some of the SM fibres, whereas the MMSI fibre showed a final induced loss of only 0.5dB/50m at 1070nm wavelength. The breaking stress of the SM fibre increased by about 10%.

  10. Omeprazole Blocks STAT6 Binding to the Eotaxin-3 Promoter in Eosinophilic Esophagitis Cells

    PubMed Central

    Zhang, Xi; Cheng, Edaire; Huo, Xiaofang; Yu, Chunhua; Zhang, Qiuyang; Pham, Thai H.; Wang, David H.; Spechler, Stuart J.; Souza, Rhonda F.

    2012-01-01

    Background Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD) nevertheless can respond to proton pump inhibitors (PPIs), which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE). The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells. Methods/Findings Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter. Conclusions/Significance PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion. PMID:23185525

  11. Using omeprazole to link the components of the post-prandial alkaline tide in the spiny dogfish, Squalus acanthias.

    PubMed

    Wood, Chris M; Schultz, Aaron G; Munger, R Stephen; Walsh, Patrick J

    2009-03-01

    After a meal, dogfish exhibit a metabolic alkalosis in the bloodstream and a marked excretion of basic equivalents across the gills to the external seawater. We used the H(+), K(+)-ATPase pump inhibitor omeprazole to determine whether these post-prandial alkaline tide events were linked to secretion of H(+) (accompanied by Cl(-)) in the stomach. Sharks were fitted with indwelling stomach tubes for pretreatment with omeprazole (five doses of 5 mg omeprazole per kilogram over 48 h) or comparable volumes of vehicle (saline containing 2% DMSO) and for sampling of gastric chyme. Fish were then fed an involuntary meal by means of the stomach tube consisting of minced flatfish muscle (2% of body mass) suspended in saline (4% of body mass total volume). Omeprazole pre-treatment delayed the post-prandial acidification of the gastric chyme, slowed the rise in Cl(-) concentration of the chyme and altered the patterns of other ions, indicating inhibition of H(+) and accompanying Cl(-) secretion. Omeprazole also greatly attenuated the rise in arterial pH and bicarbonate concentrations and reduced the net excretion of basic equivalents to the water by 56% over 48 h. Arterial blood CO(2) pressure (Pa(CO(2))) and plasma ions were not substantially altered. These results indicate that elevated gastric H(+) secretion (as HCl) in the digestive process is the major cause of the systemic metabolic alkalosis and the accompanying rise in base excretion across the gills that constitute the alkaline tide in the dogfish.

  12. Pyrexia, anaemia and acute renal failure secondary to omeprazole.

    PubMed Central

    Landray, M. J.; Ringrose, T.; Ferner, R. E.; Arnold, I. R.

    1998-01-01

    We present the case of a 77-year-old woman who initially presented with pyrexia of unknown origin, anaemia and mild renal impairment. When her omeprazole was stopped she improved rapidly. When omeprazole was re-started she developed fever and acute renal failure, which again settled quickly on discontinuation of omeprazole. This case demonstrates how drugs can cause severe multisystem disorders that may appear to be infective or inflammatory. Images Figure PMID:9799915

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

    PubMed

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

    2015-10-01

    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.

  14. [OMEPRAZOL VS RANITIDINE IN UPPER DIGESTIVE BLEEDING

    PubMed

    Regis R, Regina; Bisso A, Aland; Rebaza, Segundo

    1999-01-01

    Pectic ulcer is the most frequent cause of gastrointestinal bleeding. The homeostatic mechanism of bleeding, and coagulation, does not happen with values of pH less than 5,0. Therefore neutralization of gastric acidity (pH more than 5,0) is a recourse of control, improve the evolution and healing of peptic ulcer and to avoid a new bleeding. The aim of this study was to compare the results of treatment with omeprazole and ranitidine, in 57 patients admitted at emergency room of the Hospital Central de la Polic a Nacional del Per with endoscopic diagnosis of peptic ulcer, using Forrest classification. Patients received omeprazole 40 mg in bolus IV, followed by continuos infusion of 8 mg/hour for 72 hours (group A) or ranitidine 50 mg IV each 8 hours for 72 hours (group B). A new endoscopy was made 72 hours after admission demostrated a succesful therapy in both group. Bleeding stopped in 26/27 patients in group A (96,2%) and in 23/30 patients in group B (76,6%) (p<0,05). The results of this study show that the omeprazole IV is more effective than ranitidine IV in the control of UGB because of peptic ulcer and provides a faster healing.

  15. High-dose gallium imaging in lymphoma

    SciTech Connect

    Anderson, K.C.; Leonard, R.C.; Canellos, G.P.; Skarin, A.T.; Kaplan, W.D.

    1983-08-01

    The role of gallium-67 imaging in the management of patients with lymphoma, traditionally assessed using low tracer doses and the rectilinear scanner, was assessed when using larger doses (7 to 10 mCi) and a triple-peak Anger camera. Gallium scan results in 51 patients with non-Hodgkin's lymphoma and 21 patients with Hodgkin's disease were compared with simultaneous radiologic, clinical, and histopathologic reports. Subsequent disease course was also evaluated in light of radionuclide findings. Sensitivity and specificity of the scans were 0.90 or greater for both non-Hodgkin's lymphoma and Hodgkin's disease, and overall accuracy by site was 96 percent. Although there are insufficient numbers of pretreatment scans to allow any conclusions, our data suggest that newer approaches to gallium scanning in treated patients are (1) highly specific in all lymphomas and most sensitive in high-grade non-Hodgkin's lymphoma and Hodgkin's disease; (2) valuable in assessing the mediastinum in both non-Hodgkin's lymphoma and Hodgkin's disease; and (3) helpful adjuncts to computed tomographic scanning and ultrasonography in assessing abdominal node disease.

  16. 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.

  17. Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05.

    PubMed

    2004-01-01

    Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers. Acitreltrade mark is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders. Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8-week period. In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

  18. Pharmacokinetics and bioequivalence testing of five commercial formulations of omeprazole in the horse.

    PubMed

    Sykes, B W; Underwood, C; Greer, R; McGowan, C M; Mills, P C

    2016-02-01

    Omeprazole is widely used in the treatment of equine gastric ulcer syndrome. To date, little is known about the relative pharmacokinetics of the different formulations making comparisons between products difficult. The objectives of the study were to investigate the relative pharmacokinetics of five commercially available formulations of omeprazole in the horse and to test for bioequivalence of four of the formulations using one of the formulations as a reference standard. Twelve mature Thoroughbred horses were fasted for 16 h then administered 2 g of each formulation in a cross-over design. Serial blood samples were collected and plasma omeprazole concentration was determined by ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS). No significant differences were present between three of the formulations and the reference formulation, while the fourth formulation had a lower Cmax and longer Tmax than the reference formulation. Bioequivalence against the reference formulation could not be demonstrated for any of the formulations tested. The findings of the study suggested that the method of protection utilised by different formulations of omeprazole (enteric-coated granules vs. buffering) does not significantly alter the pharmacokinetics of the drug. Further work to establish bioequivalence is needed before direct comparisons can be drawn between different formulations.

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

    PubMed

    Hannoun-Lévi, J-M; Peiffert, D

    2014-10-01

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

  20. Highly sensitive LC-MS/MS methods for the determination of seven human CYP450 activities using small oral doses of probe-drugs in human.

    PubMed

    Grangeon, Alexia; Gravel, Sophie; Gaudette, Fleur; Turgeon, Jacques; Michaud, Veronique

    2017-01-01

    Cocktails composed of several Cytochrome P450 (CYP450)-selective probe drugs have been shown of value to characterize in vivo drug-metabolism activities. Our objective was to develop and validate highly sensitive and selective LC-MS/MS assays allowing the determination of seven major human CYP450 isoenzyme activities following administration of low oral doses of a modified CYP450 probe-drug cocktail in patients. The seven-drug cocktail was composed of caffeine, bupropion, tolbutamide, omeprazole, dextromethorphan, midazolam (all administered concomitantly) and chlorzoxazone (administered separately) to phenotype for CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5 and 2E1, respectively. Serial plasma and urine samples were collected over an 8h period. The probe-drugs and their respective metabolites were measured in both human plasma and urine, except for omeprazole (plasma only) and chlorzoxazone (urine only). Samples were analyzed by high performance liquid chromatography with heated electrospray ionization tandem mass spectrometry (HPLC-HESI-MS/MS) using a Phenomenex Luna PFP (2) analytical column (3μm PFP(2) 150×3mm) for chromatographic separation. Optimal detection was achieved based on 3 different analytical methods; (1) isocratic elution with a mobile phase consisting of acetonitrile and water both fortified with 0.01% formic acid for the analysis of bupropion, tolbutamide, chlorzoxazone and their respective metabolites; (2) isocratic elution with a mobile phase composed of acetonitrile and ammonium formate (pH 3; 10mM) for omeprazole, dextromethorphan, midazolam and their metabolites; (3) for caffeine and paraxanthine, gradient elution using acetonitrile and 0.01% formic acid in water was used. All calibration functions were linear for all probe drugs and metabolites in both matrices over wide analytical ranges. The main advantages of our methods are the use of specific probe drugs available in most countries, the administration of small doses of probe drugs, small

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

    SciTech Connect

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

    2011-01-01

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

  2. ELDRS Characterization for a Very High Dose Mission

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  3. High Dose versus Low Dose Intravenous Pantoprazole in Bleeding Peptic Ulcer: A Randomized Clinical Trial

    PubMed Central

    Masjedizadeh, Abdol Rahim; Hajiani, Eskandar; Alavinejad, Pezhman; Hashemi, Seyed Jalal; Shayesteh, Ali Akbar; Jamshidian, Noordin

    2014-01-01

    BACKGROUND The appropriate dose of proton pump inhibitors for treatment of patients with upper (GI) bleeding remains controversial. This study compares high-dose versus low-dose intravenous proton pump inhibitor (PPI) infusion for prevention of GI bleeding complications. METHODS A total of 166 patients with bleeding peptic ulcers underwent therapeutic endoscopy using concomitant therapy by argon plasma coagulation (APC) and diluted epinephrine injection. Patients were randomly divided into two groups: high-dose pantoprazole (80 mg bolus, 8 mg per hour) and low-dose pantoprazole (40 mg bolus, 4 mg per hour) infused for three days. Initial outcomes were rebleeding, need for surgery, hemoglobin drop more than two units, and hospitalization for more than five days. Secondary outcome included mortality rate. RESULTS Overall, 166 patients (83 patients per group) enrolled in the study. The average age of patients in the high-dose group was 59.5±15.6 years and 52.3±13.3 years in the low-dose group (p=0.58). Males comprised 69.7% of patients. In the high-dose group, the mean number of units of transfused blood was 3.3±1.71 and in the low-dose group, it was 2.82±1.73 (p=0.50). There were 36 (43.37%) patients in the high-dose group and 40 (48.19%) in the low-dose group who were hospitalized for more than 5 days (p=0.53). Rebleeding was observed in 27 (32.53%) patients in the high-dose group and in 21 (25.30%) in the low-dose group (p=0.30). There were no significant differences observed in drop in hemoglobin of more than two units (p=0.15), mortality (p=0.99) and surgery (p=0.75) between the two groups. CONCLUSION For controlling peptic ulcer bleeding, there is no difference between high dose and low dose pantoprazole infusion. PMID:25093061

  4. High-dose photoirradiation of esophageal cancer.

    PubMed Central

    Thomas, R J; Abbott, M; Bhathal, P S; St John, D J; Morstyn, G

    1987-01-01

    Fifteen patients with locally advanced esophageal cancer were treated with phototherapy. Each patient had dysphagia and weight loss before therapy and could not be operated on because of the extent of the tumor or poor performance status. Patients received a photosensitizer (hematoporphyrin derivative) 72 hours before phototherapy and were then treated by light delivered by an argon pumped dye laser or gold metal vapor laser at powers up to 2.2 W and doses of 337 J/cm2. Fourteen patients received 24 treatments. The results were all patients achieved a tumor response. The depth of response depended on the dose and dose rate of radiation. There were four of 24 local complications (mediastinitis 3, bronchoesophageal fistula 1). These occurred in patients treated with a power of greater than 1.5 W. There were two complete pathologic remissions in patients with locally advanced cancer. In conclusion, phototherapy is an effective alternative to other forms of palliation and potentially may be an alternative to surgery in selected cases of locally advanced esophageal cancer. Images Fig. 1. Fig. 2.,Fig. 3.,Fig. 4. Fig. 6. PMID:3606245

  5. 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

  6. Effect of gastric pH on erlotinib pharmacokinetics in healthy individuals: omeprazole and ranitidine.

    PubMed

    Kletzl, Heidemarie; Giraudon, Mylene; Ducray, Patricia Sanwald; Abt, Markus; Hamilton, Marta; Lum, Bert L

    2015-06-01

    The aim of this study was to evaluate the effect of coadministration of acid-reducing agents on the pharmacokinetic exposure of orally administered epidermal growth factor receptor inhibitor erlotinib, a drug that displays pH-dependent solubility. Two studies were conducted, the first with the proton pump inhibitor omeprazole and the second with the H2-receptor antagonist ranitidine. Twenty-four healthy male and female volunteers were enrolled in each study. Erlotinib was administered as a single oral 150 mg dose on day 1. After the washout a subsequent study period evaluated 150 mg erlotinib administered with the acid-reducing agent. Omeprazole (40 mg once daily) was given on days 11-14, concomitantly with erlotinib on day 15, and for two additional days (days 16-17). In the ranitidine study, on day 13, participants were randomized to either concomitant dosing (treatment B) or staggered administration (treatment C) of erlotinib and ranitidine and crossed over to the other treatment starting on day 27. For treatment B, ranitidine (300 mg once daily) was administered in the morning for 5 days, 2 h before erlotinib. For treatment C, ranitidine was administered as a divided dose (150 mg twice daily) for 5 days, with erlotinib given 10 h after the previous evening dose and 2 h before the next ranitidine morning dose. Plasma samples were obtained for determination of the concentrations of erlotinib and its metabolite OSI-420, following each erlotinib dose. All participants were monitored for safety and tolerability. The geometric mean ratios of AUC0-∞ and Cmax for erlotinib and AUC0-last and Cmax for OSI-420 were substantially decreased when erlotinib was dosed with omeprazole. The estimated mean ratio (90% confidence interval) for erlotinib was 0.54 (0.49-0.59) for AUC0-∞ and 0.39 (0.32-0.48) for Cmax. For OSI-420, the estimated mean ratio was 0.42 (0.37-0.48) for AUC0-last and 0.31 (0.24-0.41) for Cmax. AUC0-∞ and Cmax for erlotinib were substantially decreased

  7. 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.

  8. Dose dependence of interface traps in gate oxides at high levels of total dose

    SciTech Connect

    Baze, M.P.; Plaag, R.E.; Johnston, A.H. )

    1989-12-01

    Interface traps in gate oxides were found to saturate at high total dose levels. An empirical model was developed to describe the nonlinear dependence and saturation characteristics. Three different processes were studied including CMOS/SOS, hardened bulk CMOS and unhardened bulk CMOS using several combinations of dose rate and bias. An evaluation was made of the model's accuracy in extrapolating the effect of interface traps to very high doses. A possible application of the model in characterizing devices for space environments is discussed along with implications for a physical model of radiation induced interface trap buildup.

  9. 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.

  10. 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.

  11. Purpura and dermal thinning associated with high dose inhaled corticosteroids.

    PubMed Central

    Capewell, S; Reynolds, S; Shuttleworth, D; Edwards, C; Finlay, A Y

    1990-01-01

    OBJECTIVE--To assess the effect of high dose inhaled corticosteroids on skin. DESIGN--Cross sectional study of patients receiving treatment for chest diseases. SETTING--Outpatient chest clinic in a teaching hospital. PATIENTS--68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES--Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS--Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION--Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids. PMID:2372620

  12. Trazodone and Omeprazole Interaction causing Frequent Second-Degree Mobitz Type 1 Atrioventricular (AV) Block (Wenckebach Phenomenon) and Syncope: A Case Report and Literature Review

    PubMed Central

    Akinseye, Oluwaseun A.; Alfishawy, Mostafa; Radparvar, Farshid; Bakshi, Sanjiv

    2015-01-01

    Patient: Male, 54 Final Diagnosis: Trazodone and omeprazole interaction causing second-degree Mobitz type 1 AV block and syncope Symptoms: Syncope Medication: — Clinical Procedure: Trazodone and omeprazole withheld Specialty: Cardiology Objective: Unexpected drug reaction Background: This case report highlights serious cardiovascular adverse effects with a conventional dose of trazodone as a result of its potential interaction with omeprazole. Case Report: A 54-year-old man who was a former smoker, with dyslipidemia, coronary artery disease, and anxiety disorder developed lightheadedness and syncope the morning of admission. He was taking trazodone 50 mg daily, omeprazole 20 mg daily, and simvastatin 20 mg at bedtime. He doubled the dose of trazodone 50 mg on the night prior to presentation to calm his anxiety. An electrocardiogram revealed sinus rhythm at 60 beats per minute and second-degree Mobitz type 1 atrioventricular (AV) block with 5:4 AV conduction. Results of basic metabolic panel, thyroid-stimulating hormone, and chest radiograph were normal. A transthoracic echocardiogram revealed aortic valve sclerosis. We tested for Lyme disease given his history of hunting in the woods 8 months prior to presentation, but the titer was negative. Trazodone and omeprazole were discontinued. By the 3rd day of medication discontinuation, all symptoms had resolved and the frequency of second-degree AV Mobitz type 1 AV block had decreased to once per hour. Conclusions: Due diligence and meticulous attention to detail needs to be exercised to uncover drug interactions as potential causes of lethal and nonlethal patient symptomatology, as in this case of syncope caused by concomitant use of trazodone and a widely prescribed medication, omeprazole. PMID:26017199

  13. Evaluation of omeprazole genotoxicity in a battery of in vitro and in vivo assays.

    PubMed

    Martelli, A; Mattioli, F; Mereto, E; Brambilla Campart, G; Sini, D; Bergamaschi, G; Brambilla, G

    1998-09-01

    Omeprazole, a proton pump inhibitor of wide use in the treatment of gastric acid-related disorders, was evaluated for its genotoxic effects in both rat and human cultured cells and in the intact rat. DNA repair synthesis, as revealed by autoradiography, was detected in primary cultures of metabolically competent rat hepatocytes exposed to concentrations ranging from 10 to 100 mg/l, but the responses cannot be considered as clearly positive. Under the same experimental conditions any significant evidence of DNA repair was absent in primary hepatocytes from two human donors. At the same concentrations a modest but dose-related increase of micronucleated cells, that reached the level of statistical significance at 33 mg/l, was present in primary rat hepatocytes and in one of two human donors. In human lymphocytes exposed to subtoxic concentrations ranging from 0.78 to 12.5 mg/l a reproducible concentration dependent clastogenic effect was absent. In partially hepatectomized female rats treated with a single p.o. dose of 1000 mg/kg, the frequency of micronucleated cells was 5.2-fold higher than in controls in the liver, but only 2.0-fold higher in polychromatic erythrocytes of the bone marrow. In rats of the same sex given azoxymethane as initiator of colon carcinogenesis the oral administration for 8 successive weeks of 10 mg/kg omeprazole on alternate days increased the response to azoxymethane, as indicated by the occurrence in colon mucosa of a modest but statistically significant increase in both the average number and size of aberrant crypt foci. Taken as a whole, our results suggest that omeprazole behaves as a weak genotoxic agent for the rat liver. Reliable information about the potential genotoxic risk to humans requires further studies on primary cells from a wide number of donors.

  14. LTC1877 High Efficiency Regulator Total Ionizing Dose Test Report

    NASA Technical Reports Server (NTRS)

    Oldham, Timothy; Pellish, Jonathan; Boutte, Alvin

    2012-01-01

    This report presents total ionizing dose evaluation data for the Linear Technology Corporation LTC1877 high efficiency monolithic synchronous step-down regulator. Data sheet parameters were tracked as a function of ionizing dose up to a total of 20 krad(SiO2). Control devices were also used.

  15. Key Technologies for Ultra High Dose CMOS Applications

    SciTech Connect

    Jeon, Y.; Koo, I.; Singh, V.; Oh, J.; Jin, S.; Lee, J.; Rouh, K.; Ju, M.; Jeon, S.; Ku, J.; Lee, S. B.; Lee, S. W.; Ok, M. T.; Butterbaugh, J.; Lee, A.; Kim, K.; Lee, S. W.; Ju, K. J.; Park, J. W.

    2008-11-03

    The trend towards shrinking advanced microelectronic Logic and DRAM devices will require ultra high dose implantation. One ultra high dose application in DRAM, being rapidly adopted in production is Dual Poly Gate (DPG). Three main challenges existed for the adoption of this high dose dual poly gate (DPG) doping applications: monitoring of high dose implantation, photoresist stripping and maintaining high throughput. In this paper we present how these challenges have been addressed. VSEA's plasma doping (PLAD) tool offers several unique advantages for DPG applications. When compared to conventional or molecular beam line implanters or other immersion techniques, PLAD delivers 3 to 7 times higher throughput (compared to traditional ion implanter) without dopant penetration through the thin doped polysilicon layer into the gate oxide. It also improves P{sup +} poly silicon DPG device properties at superior throughput. In this work we demonstrate how hot spray photoresist strip processing eliminates the need for multiple-tools required for wet+ash+wet process. In addition to PLAD's patented in-situ dose control metrology we also demonstrate an ex-situ high dose implantation metrology using spectroscopic ellipsometer (SE) and spectroscopic reflectometer (SR). The technique shows good correlation (R{sup 2}{approx}0.99) between implant dose and damaged layer thickness.

  16. Pharmacokinetics of high-dose metoclopramide in cancer patients.

    PubMed

    McGovern, E M; Grevel, J; Bryson, S M

    1986-01-01

    The introduction of new cytotoxic drug regimens has been associated with an increase in the incidence and severity of adverse effects. This in turn has highlighted the need for more effective adjuvant therapy. The use of metoclopramide for the prophylaxis of nausea and vomiting, in high intravenous doses (50 to 1000 mg), has become established since 1981. As a lipid-soluble drug, metoclopramide has a large volume of distribution. The reported mean values after high doses range between 2.8 and 4.6 L/kg. The mean values for total body clearance and terminal half-life range from 0.31 to 0.69 L/kg/h and from 4.5 to 8.8 hours, respectively. The values of these pharmacokinetic parameters are essentially similar to those obtained after conventional doses (less than 50mg). Pharmacokinetic parameters appear unaffected by age, although no high-dose study has been conducted in children. Bodyweight is apparently correlated with clearance. An influence of renal function indices on terminal half-life and clearance has been shown, which is rather surprising since renal clearance accounts for only 20% of the total clearance. No thorough investigations exist which examine the influence of hepatic disease, cancer type and cytotoxic drug regimen on the disposition of metoclopramide. A relationship between dose (or concentration) and therapeutic or adverse effects of metoclopramide is outlined. The therapeutic benefit of high doses (up to 14 mg/kg) may be dependent on age, and on the combination of cytotoxic drugs. The advantages of high doses of metoclopramide are most apparent when the drug is used as protection against the adverse effects of high doses of cisplatin (greater than 60 mg/m2). Despite considerable pharmacokinetic variability, intravenous administration of high doses of metoclopramide is relatively safe due to its large therapeutic index.

  17. Patient-specific dose calculation methods for high-dose-rate iridium-192 brachytherapy

    NASA Astrophysics Data System (ADS)

    Poon, Emily S.

    In high-dose-rate 192Ir brachytherapy, the radiation dose received by the patient is calculated according to the AAPM Task Group 43 (TG-43) formalism. This table-based dose superposition method uses dosimetry parameters derived with the radioactive 192Ir source centered in a water phantom. It neglects the dose perturbations caused by inhomogeneities, such as the patient anatomy, applicators, shielding, and radiographic contrast solution. In this work, we evaluated the dosimetric characteristics of a shielded rectal applicator with an endocavitary balloon injected with contrast solution. The dose distributions around this applicator were calculated by the GEANT4 Monte Carlo (MC) code and measured by ionization chamber and GAFCHROMIC EBT film. A patient-specific dose calculation study was then carried out for 40 rectal treatment plans. The PTRAN_CT MC code was used to calculate the dose based on computed tomography (CT) images. This study involved the development of BrachyGUI, an integrated treatment planning tool that can process DICOM-RT data and create PTRAN_CT input initialization files. BrachyGUI also comes with dose calculation and evaluation capabilities. We proposed a novel scatter correction method to account for the reduction in backscatter radiation near tissue-air interfaces. The first step requires calculating the doses contributed by primary and scattered photons separately, assuming a full scatter environment. The scatter dose in the patient is subsequently adjusted using a factor derived by MC calculations, which depends on the distances between the point of interest, the 192Ir source, and the body contour. The method was validated for multicatheter breast brachytherapy, in which the target and skin doses for 18 patient plans agreed with PTRAN_CT calculations better than 1%. Finally, we developed a CT-based analytical dose calculation method. It corrects for the photon attenuation and scatter based upon the radiological paths determined by ray tracing

  18. Relevance of high-dose chemotherapy in solid tumours.

    PubMed

    Nieboer, P; de Vries, E G E; Mulder, N H; van der Graaf, W T A

    2005-05-01

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.

  19. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice

    PubMed Central

    Lim, S.; Jatakanon, A.; Gordon, D.; Macdonald, C.; Chung, K. F.; Barnes, P.

    2000-01-01

    BACKGROUND—Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.
METHODS—In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 µg beclomethasone dipropionate (BDP) daily and inhaled β2 agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 µg BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 µg BDP) over a six month period was examined.
RESULTS—One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.
CONCLUSION—There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

 PMID:10992535

  20. High-dose neutron detector development

    SciTech Connect

    Henzlova, Daniela; Menlove, Howard Olsen

    2016-01-14

    The development of advanced sustainable nuclear fuel cycles relying on used nuclear fuel is one of the key programs pursued by the DOE Office of Nuclear Energy to minimize waste generation, limit proliferation risk and maximize energy production using nuclear energy. Safeguarding of advanced nuclear fuel cycles is essential to ensure the safety and security of the nuclear material. Current non-destructive assay (NDA) systems typically employ fission chambers or 3He-based tubes for the measurement of used fuel. Fission chambers are capable of withstanding the high gamma-ray backgrounds; however, they provide very low detection efficiency on the order of 0.01%. To benefit from the additional information provided by correlated neutron counting [1] higher detection efficiencies are required. 3He-based designs allow for higher detection efficiencies; however, at the expense of slow signal rise time characteristics and higher sensitivity to the gamma-ray backgrounds. It is therefore desirable to evaluate and develop technologies with potential to exceed performance parameters of standard fission chamber-based or 3He-based detection systems currently used in the NDA instrumentation.

  1. 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

  2. Necrosis and Apoptosis in Hepatocellular Carcinoma Following Low-Dose Versus High-Dose Preoperative Chemoembolization

    SciTech Connect

    Lu Wei Li Yanhao He Xiaofeng; Zhao Jianbo; Chen Yong; Mei Quelin

    2008-11-15

    Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI, and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p > 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 {+-} 11.1%, 87.1 {+-} 12.5%, and 7.3 {+-} 3.5%, respectively. There was no significant difference between group A and group B (p > 0.05), while statistical difference was found between group A and group C (p < 0.001) and between group B and group C (p < 0.001). Apoptosis indexes in the three groups were 11.0 {+-} 4.0%, 10.7 {+-} 3.9%, and 5.6 {+-} 2.6%, respectively. Statistical difference exhibited between group A and group C (p < 0.001) and group B versus group C (p < 0.001). No significant difference was observed between group A and group B (p > 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.

  3. Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix

    SciTech Connect

    Akine, Y.; Tokita, N.; Ogino, T.; Kajiura, Y.; Tsukiyama, I.; Egawa, S. )

    1990-12-01

    By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

  4. Transport through liquid membranes containing omeprazole and lansoprazole.

    PubMed

    Nagappa, A N; Pandi, P V; Mishra, P K; Girish, Rahul K; Shanmukh, I

    2002-12-01

    Omeprazole and lansoprazole, the therapeutically important drugs belonging to proton pump inhibitor category are extensively used in the treatment of gastric ulcers. Transport through liquid membranes generated by these drugs in lecithin-cholesterol mixture in series with a supporting membrane has been studied. The data obtained show the formation of liquid membrane in series with the supporting membrane. Transport of cations, chloride and bicarbonate ions in the presence liquid membranes generated by omeprazole and lanzoprazole indicate the modification in the permeability of various permeants.

  5. 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.

  6. 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

  7. Omeprazole and SCH 28080 inhibit acid secretion by the turtle urinary bladder.

    PubMed

    Graber, M L; Devine, P

    1993-01-01

    There is now convincing evidence that in addition to the vacuolar-type H(+)-ATPase, a gastric-type H+/K(+)-ATPase participates in acidification by the distal nephron. To determine whether a similar pump exists in the turtle bladder, we examined the dependence of acid secretion on mucosal K+, and the effects of supposedly specific inhibitors of the gastric H+/K(+)-ATPase, omeprazole and SCH 28080. In CO2-stimulated bladders both drugs produced dose-dependent inhibition of electrogenic H+ secretion measured as the reverse short-circuit current (RSCC). At the highest concentrations tested, H+ secretion decreased 45 +/- 16% with mucosal and 20 +/- 7% with serosal omeprazole (P < 0.01). SCH 28080 at 400 microM produced essentially complete inhibition of H+ secretion with either mucosal or serosal application. When H+ secretion was purposefully inhibited by DIDS or an adverse mucosal pH gradient, SCH 28080 had no effect on RSCC. Removing mucosal K+ (measured K+ < 50 microM), with or without mucosal barium, had no effect on RSCC. The inhibition of RSCC by omeprazole was reversed by mercaptoethanol. Finally, HCO3 secretion, as measured by either RSCC or pH-stat titration, increased significantly in response to 400 microM SCH 28080. The results demonstrate that these compounds inhibit acid secretion by the turtle bladder but stimulate the secretion of base. In view of the total independence of acid secretion on potassium, it is unlikely that any of the bladder's acid secretion is mediated by an H+/K(+)-ATPase. The most reasonable interpretation of the data is that omeprazole and SCH 28080, previously thought to be specific inhibitors of the H+/K(+)-ATPase, also inhibit the vacuolar H(+)-ATPase of the turtle bladder. The results also indicate that HCO3 secretion by the bladder employ a different mechanism of H+ transport than is used for acid secretion; there is no simple reversal of polarity in the acid- versus base-secreting cells.

  8. Low-dose heparin versus full-dose heparin with high-dose aprotinin during cardiopulmonary bypass. A preliminary report.

    PubMed Central

    von Segesser, L K; Garcia, E; Turina, M I

    1993-01-01

    Perfusion during cardiopulmonary bypass with low-dose heparin (activated clotting time, > 180 sec) versus full-dose heparin (activated clotting time, > 480 sec) combined with high-dose aprotinin was evaluated prospectively. Fifteen patients undergoing elective myocardial revascularization were randomly assigned to 1 of 2 groups. No significant differences between the groups were found for age, sex, body surface area, preoperative hematocrit level, duration of cardiopulmonary bypass, aortic cross-clamp time, mean number of bypasses per patient, or mean number of arterial grafts per patient. In all patients, heparin-coated cardiopulmonary bypass equipment was used, including heparinized hollow-fiber membrane oxygenators and tubing sets. In each group, protamine sulfate was given equivalent to the heparin loading dose; additional doses were administered according to the ACT. The mean total dosage of heparin was 9.5 +/- 1.4 x 10(3) IU for the group given low systemic heparinization (Group 1) compared with 34.6 +/- 3.4 x 10(3) IU for the group given full systemic heparinization in combination with high-dose aprotinin (Group 2) (p < 0.0001). The mean amount of aprotinin administered in Group 2 was 5.6 +/- 0.3 x 10(6) KIU; aprotinin was not used in Group 1. The mean protamine dosage necessary in Group 1, 7.0 +/- 0.9 x 10(3) IU, was significantly less than the 22.9 +/- 3.2 x 10(3) IU needed in Group 2 (p < 0.0001). In Group 1, shed blood recovery was achieved by a red-cell spinning device; in Group 2, cardiotomy suction was used. The total chest tube drainage (i.e., postoperative blood loss) per patient in Group 1 totaled 432 +/- 162 mL/m2; in Group 2, it was 311 +/- 111 mL/m2 (difference not significant). Transfusion requirements comprised a mean volume of 143 +/- 165 mL/m2 concentrated homologous red blood cells per patient in Group 1 and 416 +/- 128 mL/m2 in Group 2 (p < 0.01). Heparin-coated perfusion equipment allowed a significantly lower dosage of systemic heparin

  9. 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.

  10. 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

  11. 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

  12. Reporting small bowel dose in cervix cancer high-dose-rate brachytherapy.

    PubMed

    Liao, Yixiang; Dandekar, Virag; Chu, James C H; Turian, Julius; Bernard, Damian; Kiel, Krystyna

    2016-01-01

    Small bowel (SB) is an organ at risk (OAR) that may potentially develop toxicity after radiotherapy for cervix cancer. However, its dose from brachytherapy (BT) is not systematically reported as in other OARs, even with image-guided brachytherapy (IGBT). This study aims to introduce consideration of quantified objectives for SB in BT plan optimization and to evaluate the feasibility of sparing SB while maintaining adequate target coverage. In all, 13 patients were included in this retrospective study. All patients were treated with external beam radiotherapy (EBRT) 45Gy in 25 fractions followed by high dose rate (HDR)-BT boost of 28Gy in 4 fractions using tandem/ring applicator. Magnetic resonance imaging (MRI) and computed tomographic (CT) images were obtained to define the gross tumor volume (GTV), high-risk clinical target volume (HR-CTV) and OARs (rectum, bladder, sigmoid colon, and SB). Treatment plans were generated for each patient using GEC-ESTRO recommendations based on the first CT/MRI. Treatment plans were revised to reduce SB dose when the [Formula: see text] dose to SB was > 5Gy, while maintaining other OAR constraints. For the 7 patients with 2 sets of CT and MRI studies, the interfraction variation of the most exposed SB was analyzed. Plan revisions were done in 6 of 13 cases owing to high [Formula: see text] of SB. An average reduction of 19% in [Formula: see text] was achieved. Meeting SB and other OAR constraints resulted in less than optimal target coverage in 2 patients (D90 of HR-CTV < 77Gyαβ10). The highest interfraction variation was observed for SB at 16 ± 59%, as opposed to 28 ± 27% for rectum and 21 ± 16% for bladder. Prospective reporting of SB dose could provide data required to establish a potential correlation with radiation-induced late complication for SB.

  13. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Chang, Jee Suk; Wang, Michael L.C.; Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun; Song, Si Young; Seong, Jinsil

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  14. Efficacy, Dose Reduction, and Resistance to High-dose Fluticasone in Patients with Eosinophilic Esophagitis

    PubMed Central

    Butz, Bridget K.; Wen, Ting; Gleich, Gerald J.; Furuta, Glenn T.; Spergel, Jonathan; King, Eileen; Kramer, Robert E.; Collins, Margaret H.; Stucke, Emily; Mangeot, Colleen; Jackson, W. Daniel; O’Gorman, Molly; Abonia, J. Pablo; Pentiuk, Scott; Putnam, Philip E.; Rothenberg, Marc E.

    2014-01-01

    Background & Aims We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. Methods We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants 3–30 years old with active EoE. Twenty-eight participants received FP and 14 received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary endpoint was histologic evidence for CR. Secondary endpoints were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. Results After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P=.0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P=.041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects that did not respond to FP. Conclusions Daily administration of a high dose of FP induces histologic remission in 65%–77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%–93% of patients that initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance

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

    PubMed

    Teixeira, Maria Inês; Caldas, Linda V E

    2012-07-01

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

  16. 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.

  17. 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.

  18. Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite.

    PubMed

    Boulenc, Xavier; Djebli, Nassim; Shi, Juan; Perrin, Laurent; Brian, William; Van Horn, Robert; Hurbin, Fabrice

    2012-01-01

    Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses. CYP2C19 involvements were estimated to be from 58 to 67% in intermediate metabolizers (IMs), from 58 to 72% in extensive metabolizers (EMs), and from 56 to 74% in ultrarapid metabolizers (UMs), depending on the study and the dose. For this purpose, a static model was proposed to estimate the net contribution of a given enzyme to the secondary metabolite formation. This static model was compared with a dynamic approach (Simcyp model) and showed good consistency. In parallel, in vitro investigations showed that omeprazole is a mechanism-based inhibitor of CYP2C19 with K(I) of 8.56 μM and K(inact) of 0.156 min(-1). These values were combined with the net CYP2C19 contribution to the active metabolite formation, through a static approach, to predict the inhibitory effect at 80-mg omeprazole doses in EM, IM, and UM CYP2C19 populations, with good consistency, compared with observed clinical values.

  19. High-dose allergen exposure leads to tolerance.

    PubMed

    Woodfolk, Judith A

    2005-02-01

    Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, high-titer IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment.

  20. A bio-analytical hydrophilic interaction LC-MS/MS method for the simultaneous quantification of omeprazole and lansoprazole in human plasma in support of a pharmacokinetic omeprazole study in children.

    PubMed

    De Smet, Julie; Boussery, Koen; De Cock, Pieter; De Paepe, Peter; Remon, Jean-Paul; Van Winckel, Myriam; Van Bocxlaer, Jan

    2010-03-01

    A hydrophilic interaction LC method with MS/MS was developed and validated for the simultaneous quantification of omeprazole and lansoprazole in human plasma. Chromatographic separation was achieved on a Betasil silica column using a high organic mobile phase (eluent A: ACN/formic acid 997.5:2.5 v/v; eluent B: water/formic acid 997.5:2.5 v/v) and gradient elution. The mass spectrometer was operated in the Multiple Reaction Monitoring mode. Prior to chromatography, liquid-liquid extraction with ethyl acetate was used and the organic layer was diluted with ACN, allowing direct injection on column. The method showed acceptable linearity, high precision (RSD%<10.5%), accuracy (88.9-109.3%) and selectivity in the two concentration ranges studied: 1.5-100 and 5-2000 ng/mL. The LOQ was established at 1.5 and 5 ng/mL for the two concentration ranges. Lack of variability in matrix effects was demonstrated and mean extraction recovery for omeprazole and lansoprazole was determined in the low (56.3-67.7%) and high (45.3-44.3%) concentration range, respectively. Additionally, plasma samples were found to be stable after three freeze-thaw cycles and for at least 15 h after extraction. This assay was successfully applied to a pharmacokinetic omeprazole study in children with cerebral palsy and mental retardation.

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

    PubMed

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

    2016-12-01

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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Tolerability of high doses of lercanidipine versus high doses of other dihydropyridines in daily clinical practice: the TOLERANCE Study.

    PubMed

    Barrios, Vivencio; Escobar, Carlos; de la Figuera, Mariano; Llisterri, Jose Luis; Honorato, Jesus; Segura, Julián; Calderón, Alberto

    2008-01-01

    The TOLERANCE study was aimed to compare the tolerability of high doses of lercanidipine (20 mg) with that of other frequently used dihydropyridines (amlodipine 10 mg/nifedipine GITS 60 mg) in the treatment of essential hypertension in daily clinical practice. It was an observational, transversal, multicentre study performed in a Primary Care Setting. A total of 650 evaluable patients with essential hypertension and age > or = 18 years were included. They had been treated with high doses of lercanidipine (n= 446) or amlodipine/nifedipine GITS (n= 204) during at least 1 month and previously with low doses (10 mg, 5 mg, and 30 mg, respectively) of the same drugs. The main objective was to compare the rates of vasodilation-related adverse events between both groups. Rates of signs and symptoms related to vasodilation were significantly higher (P < 0.001) in the amlodipine/nifedipine GITS group (76.8%, CI 95%[70.7; 82.9]) than in lercanidipine group (60.8%, [56.1;65.5]). Blood pressure control (< 140/90 mmHg or <130/80 for diabetics) and type of concomitant antihypertensive medications were similar in both groups. Treatment compliance was good (around 93%) and fairly comparable in both groups. Most adverse events with lercanidipine were mild (74.5% vs. 64% in amlodipine/nifedipine GITS group, P= 0.035) whereas severe adverse event rates did not differ significantly between groups (2.8% vs. 3.6%). In conclusion, treatment with lercanidipine at high doses is associated with a lower rate of adverse events related to vasodilation compared to high doses of amlodipine or nifedipine GITS in clinical practice.

  7. 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.

  8. 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.

  9. 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.

  10. High-dose neutron irradiation performance of dielectric mirrors

    DOE PAGES

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

    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

  11. 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.

  12. 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.

  13. Postoperative high-dose intravenous iron sucrose with low dose erythropoietin therapy after total hip replacement.

    PubMed

    Yoon, Jiyeol; Kim, Sungmin; Lee, Soo Chan; Lim, Hongsub

    2010-12-01

    Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B(12), vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.

  14. SU-E-T-165: Characterization of Dose Distributions in High-Dose-Rate Surface Brachytherapy

    SciTech Connect

    Buzurovic, I; Hansen, J; Bhagwat, M; O’Farrell, D; Damato, A; Friesen, S; Devlin, P; Cormack, R

    2015-06-15

    Purpose: To characterize dose distributions in high-dose-rate(HDR) surface brachytherapy using an Ir-125 source for different geometries, field sizes and topology of the clinical targets(CT). To investigate the depth doses at the central axis(CAX), edges of the treatment fields(E), and lateral dose distributions(L) present when using flap applicators in skin cancer treatments. Methods: When malignancies diagnosed on the skin are treated, various geometries of the CT require proper adaptation of the flap or custom-made applicators to the treatment site. Consequently, the dose at the depth on CAX and field edges changes with variation of the curvatures and size of the applicators. To assess the dose distributions, we created a total of 10 treatment plans(TP) for 10×10 and 20×20 field sizes(FS) with a step size of 1cm. The geometry of the applicators was: planar(PA), curved to 30(CA30) and 60(CA60) degrees with respect to the CAX, half-cylinder(HC), and cylindrical shape(CS). One additional TP was created in which the applicators were positioned to form a dome shape(DS) with a diameter of 16cm. This TP was used to emulate treatment of the average sized scalp. All TPs were optimized to deliver a prescription dose at 8mm equidistantly from the planes containing the dwell positions. This optimization is equivalent to the clinical arrangement since the SSD for the flap applicators is 5mm and the prescription depth is 3mm in the majority of clinical cases. Results: The depths (in mm) of the isodose lines were: FS(10×10):PA[90%(9.1CAX,8.0E,7.6L),50%(28.3CAX,20E,17.3L), 25%(51.1CAX,40E,27L)],CA30[90%(10.3CAX,8.2E,7.9L),50%(32.1CAX, 16.2E,15.8L),25%(61.3CAX,36.7E,31.8L)],CA60[90%(12.2CAX,6.1E,6.3L ),50%(47CAX,14E,16.6L),25%(70.8CAX,31.9E,35.4L)],HC[90%(11.1CA X,6.3E,7.3L),50%(38.3CAX,14.6E,16.1L),25%(66.2CAX,33.8E,34.2L)];FS (20×20):PA[90%(11.1CAX,9.0E,7.0L),50%(34.4CAX,21.9E,15.3L),25%(7 0.4CAX,50.9E,34.8L)],CA30[90%(10.9CAX,7.5E,7.1L),50%(38.8CAX,16. 7E,15.4L),25

  15. 21 CFR 520.1615 - Omeprazole.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  16. 21 CFR 520.1615 - Omeprazole.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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...

  17. 21 CFR 520.1615 - Omeprazole.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  18. 21 CFR 520.1615 - Omeprazole.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  19. 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...

  20. Comparison of planned and measured rectal dose in-vivo during high dose rate Cobalt-60 brachytherapy of cervical cancer.

    PubMed

    Zaman, Z K; Ung, N M; Malik, R A; Ho, G F; Phua, V C E; Jamalludin, Z; Baharuldin, M T H; Ng, K H

    2014-12-01

    Cobalt-60 (Co-60) is a relatively new source for the application of high-dose rate (HDR) brachytherapy. Radiation dose to the rectum is often a limiting factor in achieving the full prescribed dose to the target during brachytherapy of cervical cancer. The aim of this study was to measure radiation doses to the rectum in-vivo during HDR Co-60 brachytherapy. A total of eleven HDR brachytherapy treatments of cervical cancer were recruited in this study. A series of diodes incorporated in a rectal probe was inserted into the patient's rectum during each brachytherapy procedure. Real-time measured rectal doses were compared to calculated doses by the treatment planning system (TPS). The differences between calculated and measured dose ranged from 8.5% to 41.2%. This corresponds to absolute dose differences ranging from 0.3 Gy to 1.5 Gy. A linear relationship was observed between calculated and measured doses with linear regression R(2) value of 0.88, indicating close association between the measured and calculated doses. In general, absorbed doses for the rectum as calculated by TPS were observed to be higher than the doses measured using the diode probe. In-vivo dosimetry is an important quality assurance method for HDR brachytherapy of cervical cancer. It provides information that can contribute to the reduction of errors and discrepancies in dose delivery. Our study has shown that in-vivo dosimetry is feasible and can be performed to estimate the dose to the rectum during HDR brachytherapy using Co-60.

  1. 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.

  2. Formation of titanium silicides by high dose ion implantation

    NASA Astrophysics Data System (ADS)

    Salvi, V. P.; Vidwans, S. V.; Rangwala, A. A.; Arora, B. M.; Kuldeep; Jain, Animesh K.

    1987-09-01

    We have investigated titanium silicide formation using high dose (˜ 2 × 10 21 ions/m 2) ion implantation of 30 keV, 48Ti + ions a room temperature into two different types of Si substrates: (a) n-type <111> single crystals and (b) amorphous Si films (˜ 200 nm thick) vacuum deposited onto a thermally grown SiO 2 layer. XRD and RBS techniques were employed to characterize various silicide phases and their depth distribution in as-implanted as well as in annealed samples. We find that a mixture of TiSi, TiSi 2 and Ti 5Si 4 silicides is formed by high dose implantation. Out of these, TiSi; was found to be the dominant phase. The composition of these silicide layers is practically uniform with depth and remains unaltered on heat treatment up to 750° C. The electrical properties of silicide layers have also been investigated using sheet resistance measurements. The resistivity of as-implanted layers is rather high ( ˜ 10 μΩ m), but drops sharply by nearly a factor of 20 after a post-implantation anneal above 800° C. The resistivity of silicide layers thus obtained compare well with silicides prepared by other techniques.

  3. 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; ...

    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

  4. Can point doses predict volumetric dose to rectum and bladder: a CT-based planning study in high dose rate intracavitary brachytherapy of cervical carcinoma?

    PubMed Central

    Patil, V M; Patel, F D; Chakraborty, S; Oinam, A S; Sharma, S C

    2011-01-01

    Objective Point doses, as defined by the International Commission on Radiation Units and Measurements (ICRU), are classically used to evaluate doses to the rectum and bladder in high dose rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer. Several studies have shown good correlation between the ICRU point doses and the volumetric doses to these organs. In the present study we attempted to evaluate whether this correlation could be used to predict the volumetric doses to these organs. Methods A total of 150 HDR-ICBT insertions performed between December 2006 and June 2008 were randomly divided into two groups. Group A (n=50) was used to derive the correlation between the point and volumetric doses using regression analysis. This was tested in Group B (n=100) insertions using studentised residuals and Bland–Altman plots. Results Significant correlations were obtained for all volumetric doses and ICRU point doses for rectum and bladder in Group A insertions. The strongest correlation was found for the dose to 2 cc volumes (D2cc). The correlation coefficients for bladder and rectal D2cc versus the respective ICRU point doses were 0.82 and 0.77, respectively (p<0.001). Statistical validation of equations generated in Group B showed mean studentised residual values of 0.001 and 0.000 for the bladder and rectum. However, Bland–Altman analysis showed that the error range for these equations for bladder and rectum were ±64% and ±41% of the point A dose, respectively, which makes these equations unreliable for clinical use. Conclusion Volumetric imaging is essential to obtain proper information about volumetric doses. PMID:21511749

  5. 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.

  6. Determination of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry.

    PubMed

    Kanazawa, Hideko; Okada, Akiko; Matsushima, Yoshikazu; Yokota, Hiromitsu; Okubo, Shigeo; Mashige, Fumiko; Nakahara, Kazuhiko

    2002-03-08

    Omeprazole is a benzimidazole compound that acts as a proton-pump inhibitor. Because the metabolism of omeprazole is mainly catalyzed by cytochrome P-450 (CYP) 3A4 and CYP2C19. the genetic polymorphism of CYP2C19 could be of clinical concern in the treatment of acid-related diseases with omeprazole. Therefore, a reliable method for omeprazole phenotyping is desirable in clinical situations. This study has demonstrated the determination of omeprazole and its metabolites in human plasma by liquid chromatography-three-dimensional quadrupole mass spectrometry with a sonic spray ionization interface. The analytical column was YMC-Pack Pro C18(50x2.0 mm I.D.) using acetonitrile-50 mM ammonium acetate (pH 7.25) (1:4) at a flow-rate of 0.2 ml/min. The drift voltage was 30 V. The sampling aperture was heated at 110 degrees C and Shield temperature was 230 degrees C. In the mass spectrum, the molecular ions of omeprazole, hydroxyomeprazole and omeprazole sulfone were clearly observed as base peaks. This method is sufficiently sensitive and accurate for pharmacokinetic studies of omeprazol.

  7. The effects of clopidogrel and omeprazole on platelet function in normal dogs.

    PubMed

    Thames, B E; Lovvorn, J; Papich, M G; Wills, R; Archer, T; Mackin, A; Thomason, J

    2017-04-01

    Omeprazole is used concurrently with clopidogrel to reduce gastrointestinal adverse effects. In humans, the concurrent use of these two drugs can reduce the antiplatelet efficacy of clopidogrel. Our objective was to determine the effects of omeprazole and clopidogrel on platelet function in healthy dogs. A crossover study utilized turbidimetric aggregometry (ADP and collagen) and the PFA-100(®) with the collagen/ADP cartridge to evaluate platelet function in eight healthy dogs during the administration of clopidogrel (1 mg/kg/24 h p.o.), omeprazole (1 mg/kg/24 h p.o.), and a combination of clopidogrel and omeprazole. Drug metabolite concentrations were also measured. Compared to pretreatment, on Days 3 and 5, with ADP as the agonist, there was a significant decrease in maximum amplitude on aggregometry for both clopidogrel and clopidogrel/omeprazole groups. The following revealed no significant differences between clopidogrel and clopidogrel/omeprazole groups when compared on Days 3 and 5: maximum amplitude on aggregometry with ADP or collagen agonists, and PFA-100(®) closure times. When compared to the clopidogrel group, clopidogrel metabolite concentrations in the clopidogrel/omeprazole group were significantly higher on Days 3 and 5. The concurrent administration of omeprazole and clopidogrel in healthy dogs was associated with an increase in the plasma concentration of an inactive metabolite of clopidogrel, but does not significantly alter the antiplatelet effects of clopidogrel.

  8. 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

  9. Efficacy of Low-Dose Corticosteroid Therapy Versus High-Dose Corticosteroid Therapy in Bell's Palsy in Children.

    PubMed

    Arican, Pinar; Dundar, Nihal Olgac; Gencpinar, Pinar; Cavusoglu, Dilek

    2017-01-01

    Bell's palsy is the most common cause of acute peripheral facial nerve paralysis, but the optimal dose of corticosteroids in pediatric patients is still unclear. This retrospective study aimed to evaluate the efficacy of low-dose corticosteroid therapy compared with high-dose corticosteroid therapy in children with Bell's palsy. Patients were divided into 2 groups based on the dose of oral prednisolone regimen initiated. The severity of idiopathic facial nerve paralysis was graded according to the House-Brackmann Grading Scale. The patients were re-assessed in terms of recovery rate at the first, third, and sixth months of treatment. There was no significant difference in complete recovery between the 2 groups after 1, 3, and 6 months of treatment. In our study, we concluded that even at a dose of 1 mg/kg/d, oral prednisolone was highly effective in the treatment of Bell's palsy in children.

  10. 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…

  11. High to Low Dose Extrapolation of Experimental Animal Carcinogenesis Studies,

    DTIC Science & Technology

    with its inherent limitations. A number of commonly used mathematical models of dose - response necessary for this extrapolation, will be discussed...thresholds; incorporation of background, or spontaneous responses; modification of the dose - response by pharmacokinetic processes. (Author)

  12. 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.

  13. Randomised crossover trial of tripotassium dicitrato bismuthate versus high dose cimetidine for duodenal ulcers resistant to standard dose of cimetidine.

    PubMed

    Lam, S K; Lee, N W; Koo, J; Hui, W M; Fok, K H; Ng, M

    1984-07-01

    Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.

  14. 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.

  15. 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.

  16. High-Dose Vitamin D Failed to Curb Heart Disease in Study

    MedlinePlus

    ... medlineplus.gov/news/fullstory_164472.html High-Dose Vitamin D Failed to Curb Heart Disease in Study ... 5, 2017 (HealthDay News) -- Taking high doses of vitamin D once a month won't lower your ...

  17. High Doses of Vitamin D Fail to Cut Cancer Risk, Study Finds

    MedlinePlus

    ... gov/news/fullstory_164325.html High Doses of Vitamin D Fail to Cut Cancer Risk, Study Finds ... March 28, 2017 (HealthDay News) -- High doses of vitamin D supplements may not lower older women's risk ...

  18. 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.

  19. High-dose thiamine improves the symptoms of fibromyalgia.

    PubMed

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-05-20

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms.

  20. Pharmacokinetics of high-dose intravenous melatonin in humans.

    PubMed

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette M; Fenger, Andreas Q; Petersen, Marian C; Rosenberg, Jacob; Gögenur, Ismail

    2016-03-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

  1. 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.

  2. Volumetric (3D) bladder dose parameters are more reproducible than point (2D) dose parameters in vaginal vault high-dose-rate brachytherapy

    PubMed Central

    Sapienza, Lucas Gomes; Flosi, Adriana; Aiza, Antonio; de Assis Pellizzon, Antonio Cassio; Chojniak, Rubens; Baiocchi, Glauco

    2016-01-01

    There is no consensus on the use of computed tomography in vaginal cuff brachytherapy (VCB) planning. The purpose of this study was to prospectively determine the reproducibility of point bladder dose parameters (DICRU and maximum dose), compared with volumetric-based parameters. Twenty-two patients who were treated with high-dose-rate (HDR) VCB underwent simulation by computed tomography (CT-scan) with a Foley catheter at standard tension (position A) and extra tension (position B). CT-scan determined the bladder ICRU dose point in both positions and compared the displacement and recorded dose. Volumetric parameters (D0.1cc, D1.0cc, D2.0cc, D4.0cc and D50%) and point dose parameters were compared. The average spatial shift in ICRU dose point in the vertical, longitudinal and lateral directions was 2.91 mm (range: 0.10–9.00), 12.04 mm (range: 4.50–24.50) and 2.65 mm (range: 0.60–8.80), respectively. The DICRU ratio for positions A and B was 1.64 (p < 0.001). Moreover, a decrease in Dmax was observed (p = 0.016). Tension level of the urinary catheter did not affect the volumetric parameters. Our data suggest that point parameters (DICRU and Dmax) are not reproducible and are not the ideal choice for dose reporting. PMID:27296459

  3. 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

  4. Improving low-dose blood-brain barrier permeability quantification using sparse high-dose induced prior for Patlak model.

    PubMed

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

    2014-08-01

    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.

  5. 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.

  6. Antagonism by idazoxan at low dose but not high dose, of the natriuretic action of moxonidine.

    PubMed Central

    Allan, D. R.; Penner, S. B.; Smyth, D. D.

    1996-01-01

    1. Recent studies concerning the imidazoline receptor have utilized idazoxan as a specific imidazoline receptor antagonist. The aim of the present study was to describe the in vivo effects of various doses of idazoxan on renal function, in the presence and absence of moxonidine, an I1 imidazoline receptor agonist. 2. In anaesthetized, unilaterally nephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusion of moxonidine (3 nmol kg-1 min-1) increased urine flow rate, sodium excretion and osmolar clearance without altering free water clearance. Pretreatment with intravenous idazoxan at 0.1 and 0.3 mg kg-1 produced a dose-related decrease in the renal actions of moxonidine. However, a higher dose of idazoxan (1 mg kg-1) was not as effective as the 0.3 mg kg-1 dose in blocking the effects of moxonidine. 3. In a separate series of experiments, the direct renal actions of idazoxan alone were investigated. Idazoxan at 0.3 mg kg-1 failed to alter urine flow rate and sodium excretion. However, idazoxan at 1 mg kg-1 produced a significant increase in urine flow rate and sodium excretion in association with an increase in osmolar clearance. 4. These results do not prove but are consistent with low doses of idazoxan antagonizing the sites stimulated by moxonidine (renal imidazoline receptors). However, at higher doses, idazoxan may function as a partial agonist and/or interact with other receptors to increase urine flow rate, independent of imidazoline receptor blockade. These studies underscore the importance of the dose of idazoxan administered when this antagonist is used as a tool to investigate imidazoline receptors. PMID:8825339

  7. Impact of high dose vitamin C on platelet function

    PubMed Central

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

    2017-01-01

    AIM To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of VitC used here correspond to plasma VitC levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography (TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate (ATP) secretion in response to collagen or adenosine diphosphate (ADP); and flow cytometry, for changes in expression of CD-31, CD41a, CD62p and CD63. In addition, PLT intracellular VitC content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time (PT), partial thrombplastin time (PTT), functional fibrinogen] and Lipidomics analysis (UPLC ESI-MS/MS). RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P < 0.05). VitC supplementation did not significantly change PT and PTT values, or functional fibrinogen levels over the 8 d exposure period (P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle (P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to

  8. '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.

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

    NASA Astrophysics Data System (ADS)

    Mejía, C. A. Reynoso; Burgos, A. E. Buenfil; Trejo, C. Ruiz; García, A. Mota; Durán, E. Trejo; Ponce, M. Rodríguez; de Buen, I. Gamboa

    2010-12-01

    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.

  10. 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.

  11. Formulation and Evaluation of Omeprazole Tablets for Duodenal Ulcer

    PubMed Central

    Choudhury, A.; Das, S.; Bahadur, S.; Saha, S.; Roy, A.

    2010-01-01

    Omeprazole pellets containing mucoadhesive tablets were developed by direct punch method. Three mucoadhesive polymers namely hydroxypropylemethylcellulose K4M, sodium carboxy methylcellulose, carbopol-934P and ethyl cellulose were used for preparation of tablets which intended for prolong action may be due to the attachment with intestinal mucosa for relief from active duodenal ulcer. Mucoadhesive tablets were coated with respective polymer and coated with Eudragit L100 to fabricate enteric coated tablets. The prepared tablets were evaluated for different physical parameters and dissolution study were performed in three dissolution mediums like 0.1N hydrochloric acid for 2h, pH 6.5 and pH 7.8 phosphate buffer solution for 12hr. Sodium carboxymethylcellulose showed above 95% release within 10 h where as carbopol-934P showed slow release about 88% to 92% over a period of 12 h. having excellent mucoadhesive strength but ethyl cellulose containing tablets showed less than 65% release. The release mechanism of all formulation was diffusion controlled confirmed from Higuchi’s plot. Thus, the present study concluded that, carbopol-934P containing mucoadhesive tablets of omeprazole pellets can be used for local action in the ulcer disease as well as for oral controlled release drug delivery. PMID:21218061

  12. Effects of cisapride on ulcer formation and gastric secretion in rats: comparison with ranitidine and omeprazol.

    PubMed

    Alarcón de la Lastra, C; Martin, M J; La Casa, M; López, A; Motilva, V

    1996-12-01

    1. The antiulcerogenic effects of cisapride, a potent benzamide-stimulating gastrointestinal motility agent, were studied on cold-resistant and pylorus-ligated gastric ulcers. Acidity, composition of gastric secretion, and quantitative and qualitative changes on mucus glycoprotein content were also determined. These effects were compared with those of ranitidine (50 mg/kg) and omeprazol (10 mg/kg). 2. Oral cisapride (10-100 mg/kg) dose-relatedly and significantly (P < 0.01, P < 0.05) decreased the severity of the lesions induced by cold-resistant stress. In stressed rats, cisapride increased the amount of mucus secretion and markedly enhanced the glycoprotein content. Morphometric evaluation of mucus secretion revealed a significant increase in both the PAS area (neutral glycoproteins) and Alcian blue area (sulfated glycoproteins). 3. In 4 h pyloric-ligated animals, cisapride (10-100 mg/kg) showed a significant reduction in the number and severity of ulcers (P < 0.01) and histamine concentration (P < 0.01, P < 0.001). In addition, at the highest doses (50-100 mg/kg), cisapride produced a significant decreases in acidity; however, it did not alter the gastric volume secretion or pepsin concentrations. 4. These results suggest that cisapride shows antiulcerogenic effects which could possibly be explained through antisecretory and cytoprotective mechanisms involving an enhancement of cuality and production of gastric mucus.

  13. 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

  14. Omeprazole versus famotidine in the healing and relapse of duodenal ulcer.

    PubMed

    Misra, S C; Dasarathy, S; Sharma, M P

    1993-08-01

    Sixty patients with symptomatic duodenal ulcer were randomized to receive either omeprazole (20 mg each morning) or famotidine (40 mg at night time) for 2-4 weeks in a double-blind parallel group clinical trial. Healing rates were higher with omeprazole in comparison with famotidine after 2 weeks (77% vs. 40%, P < 0.001) and 4 weeks (93% vs. 80%, P = 0.2) of treatment. Assessment of daily diary cards completed by all patients revealed that omeprazole rapidly relieved ulcer-related day pain and nocturnal pain in comparison to famotidine. Treatment with omeprazole for 2 weeks was also associated with lower cumulative antacid intake (P < 0.05) and reduced absenteeism from work. Helicobacter pylori infection was present in all patients and remained unaffected by treatment with either of the drugs. None of the drugs produced any significant adverse effects. During 6 months follow-up of all the patients after ulcer healing (without maintenance therapy), ulcer relapse was seen in 40% of omeprazole- and 37% of famotidine-treated patients (P > 0.1). The duration of ulcer-free period following initial healing of ulcer was also similar in both the groups (median time: 22 weeks for omeprazole, 21 weeks for famotidine). We conclude that omeprazole is superior to famotidine in rapidly healing duodenal ulcers and achieving more rapid pain relief, but does not influence subsequent ulcer relapse.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

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

  17. The role of omeprazole (40 mg) in the treatment of gastric Helicobacter pylori infection.

    PubMed

    Wagner, S; Varrentrapp, M; Haruma, K; Lange, P; Müller, M J; Schorn, T; Soudah, B; Bär, W; Gebel, M

    1991-11-01

    The efficacy of omeprazole in the elimination of Helicobacter pylori was investigated in a prospective randomized-controlled trial. 50 patients with upper gastrointestinal symptoms and chronic active H. pylori-associated gastritis were allocated to one of the following four therapeutic schedules: 1) omeprazole 40 mg/d for 4 weeks (n = 13); 2) bismuth subsalicylate (BSS) 3 x 600 mg for 4 weeks (n = 12); 3) omeprazole plus BSS for 4 weeks (n = 13); 4) triple therapy (BSS for 4 weeks, amoxicillin 3 x 750 mg and metronidazole 3 x 400 mg for 10 days) (n = 12). Clinical symptoms, endoscopic and histologic findings, and H. pylori status were reassessed immediately after therapy, and 1 and 6 months later. After cessation of therapy bacterial clearance rates were: 1) omeprazole 2/13 (15%); 2) BSS 6/12 (50%); 3) omeprazole plus BSS 5/13 (38%); 4) triple therapy 10/12 (83%). The degree of density of gastric mucosal infestation with H. pylori and the degree of activity of gastritis was reduced in all treatment groups but was most prominent after triple therapy. Clinical symptoms improved in all treatment groups. One and six months after completion of therapy H. pylori eradication rates were: 1) omeprazole 0/13 (0%); 2) BSS 1/12 (8%); 3) omeprazole plus BSS 1/13 (8%); 4) triple therapy 10/12 (83%). Our study shows that 40 mg/d omeprazole is ineffective in eradicating H. pylori. Dual therapy with omeprazole and bismuth subsalicylate does not improve bacterial elimination. Only triple therapy effectively eradicates H. pylori.

  18. 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.

  19. Dose-dependent high-resolution electron ptychography

    SciTech Connect

    D'Alfonso, A. J.; Allen, L. J.; Sawada, H.; Kirkland, A. I.

    2016-02-07

    Recent reports of electron ptychography at atomic resolution have ushered in a new era of coherent diffractive imaging in the context of electron microscopy. We report and discuss electron ptychography under variable electron dose conditions, exploring the prospects of an approach which has considerable potential for imaging where low dose is needed.

  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.

  1. CT based three dimensional dose-volume evaluations for high-dose rate intracavitary brachytherapy for cervical cancer

    PubMed Central

    2014-01-01

    Background In this study, high risk clinical target volumes (HR-CTVs) according to GEC-ESTRO guideline were contoured retrospectively based on CT images taken at the time of high-dose rate intracavitary brachytherapy (HDR-ICBT) and correlation between clinical outcome and dose of HR-CTV were analyzed. Methods Our study population consists of 51 patients with cervical cancer (Stages IB-IVA) treated with 50 Gy external beam radiotherapy (EBRT) using central shield combined with 2–5 times of 6 Gy HDR-ICBT with or without weekly cisplatin. Dose calculation was based on Manchester system and prescribed dose of 6 Gy were delivered for point A. CT images taken at the time of each HDR-ICBT were reviewed and HR-CTVs were contoured. Doses were converted to the equivalent dose in 2 Gy (EQD2) by applying the linear quadratic model (α/β = 10 Gy). Results Three-year overall survival, Progression-free survival, and local control rate was 82.4%, 85.3% and 91.7%, respectively. Median cumulative dose of HR-CTV D90 was 65.0 Gy (52.7-101.7 Gy). Median length from tandem to the most lateral edge of HR-CTV at the first ICBT was 29.2 mm (range, 18.0-51.9 mm). On univariate analysis, both LCR and PFS was significantly favorable in those patients D90 for HR-CTV was 60 Gy or greater (p = 0.001 and 0.03, respectively). PFS was significantly favorable in those patients maximum length from tandem to edge of HR-CTV at first ICBT was shorter than 3.5 cm (p = 0.042). Conclusion Volume-dose showed a relationship to the clinical outcome in CT based brachytherapy for cervical carcinoma. PMID:24938757

  2. Theoretically required urinary flow during high-dose methotrexate infusion.

    PubMed

    Sasaki, K; Tanaka, J; Fujimoto, T

    1984-01-01

    The renal excretion of methotrexate (MTX) and its major metabolite 7-hydroxymethotrexate (7-OH-MTX) was analysed in 12 children with malignancies during 52 courses of high-dose methotrexate (H-D-MTX) infusion at dosages ranging from 0.7 to 8.4 g/m2. The peak concentrations of both MTX and 7-OH-MTX exceeded the aqueous solubilities of these compounds at low pH (less than or equal to 6.0). The cumulative MTX excretion in urine was 75%-98% of the administered amount of MTX, and the cumulative 7-OH-MTX excretion in the urine was 3%-15%. The theoretically required urinary flow (TRUF) was estimated as the minimum urine volume needed for complete resolution of MTX and its metabolites in urine. TRUF during MTX infusion from 0 to 6 h and from 6 to 12 h was correlated with the dosage of MTX, and these values were 0.1-1.8 ml/min/m2 at pH 7.0, 0.5-11.1 ml/min/m2 at pH 6.0, and 1.9-42.2 ml/min/m2 at pH 5.0 with dosages of 0.7 to 8.4 g/m2. The value of the theoretically required urinary flow is important to ensure adequate hydration and the optimum alkalinization schedule for massive MTX infusion.

  3. High-dose naltrexone therapy for cocaine-alcohol dependence.

    PubMed

    Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard

    2009-01-01

    This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.

  4. Wernicke's encephalopathy in a child with high dose thiamine therapy

    PubMed Central

    Park, So Won; Yi, Yoon Young; Han, Jung Woo; Kim, Heung Dong; Lee, Joon Soo

    2014-01-01

    Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously. PMID:25550705

  5. The application of high dose food irradiation in South Africa

    NASA Astrophysics Data System (ADS)

    de Bruyn, Ingrid Nine

    2000-03-01

    During the 1950s to the end of the 1970s the United States Army developed the basic methodology to produce shelf-stable irradiated meat, seafood and poultry products. These products are normally packed without gravy, sauce or brine, as liquid is not required to sterilize the product as in the canning process. This leads to the distinctive "dried cooked" taste normally associated with roasts opposed to the casserole taste usually associated with tinned meats. The Biogam group at the Atomic Energy Corporation of South Africa is currently producing shelf-stable irradiated meats on a commercial basis. The meats are cooked, chilled, portioned, vacuum packed and irradiated to the required minimum dose of 45 kGy at a temperature of between -20 and -40°C to ensure absolute sterility even under tropical conditions. The product is packaged in a high quality four layer laminate pouch and will therefore not rust or burst even under adverse weather conditions and can be guaranteed for more than two years as long as the integrity of the packaging is maintained. Safari operators in remote parts of Africa, mountaineers, yachtsmen, canoeists and geological survey teams currently use shelf-stable irradiated meat products produced in South Africa.

  6. Displacement damage effects in silicon MEMS at high proton doses

    NASA Astrophysics Data System (ADS)

    Gomes, João; Shea, Herbert R.

    2011-02-01

    We report on a study of the sensitivity of silicon MEMS to proton radiation and mitigation strategies. MEMS can degrade due to ionizing radiation (electron-hole pair creation) and non-ionizing radiation (displacement damage), such as electrons, trapped and solar protons, or cosmic rays, typically found in a space environment. Over the past few years there has been several reports on the effects of ionizing radiation in silicon MEMS, with failure generally linked to trapped charge in dielectrics. However there is near complete lack of studies on displacement damage effects in silicon- MEMS: how does silicon change mechanically due to proton irradiation? We report on an investigation on the susceptibility of 50 μm thick SOI-based MEMS resonators to displacement damages due to proton beams, with energies from 1 to 60 MeV, and annealing of this damage. We measure ppm changes on the Young's modulus and Poisson ratio by means of accurately monitoring the resonant frequency of devices in vacuum using a Laser Doppler Vibrometer. We observed for the first time an increase (up to 0.05%) of the Young's modulus of single-crystal silicon electromagnetically-actuated micromirrors after exposure to low energy protons (1-4 MeV) at high absorbed doses ~ 100 Mrad (Si). This investigation will contribute to a better understanding of the susceptibility of silicon-based MEMS to displacement damages frequently encountered in a space radiation environment, and allow appropriated design margin and shielding to be implemented.

  7. 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

  8. High-dose-rate brachytherapy in uterine cervical carcinoma

    SciTech Connect

    Patel, Firuza D. . E-mail: patelfd@glide.net.in; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-05-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  9. 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.

  10. Effects of omeprazole on iron absorption: preliminary study.

    PubMed

    Tempel, Mila; Chawla, Anupama; Messina, Catherine; Celiker, Mahmut Yaşar

    2013-09-01

    Amaç: Giderek artan sayıda pediatrik ve yetişkin hastalar proton pompa inhibitörleri (PPI) ile tedavi edilmektedir. PPI’ların mide asidini inhibe ettikleri bilinmektedir. Heme’e bağlı olmayan demir ferroz şekline geçerek absorb edilebilmesi için mide asidi gerektirir. Diyetteki demirin yüzde doksanı ve tedavide kullanılan demirin yüzde yüzü heme’e bağlı olmayan durumdadır. Bilgimize göre PPI’ların demir absobsiyonunda nasıl etki ettiği insanlarda araştırılmamıstır. Araştırmamız omeprazol tedavisi ile demir absorbsiyonu arasındaki ilişkiyi sağlıklı kişilerde incelemiştir.Gereç ve Yöntemler: Haziran 2010 ile Mart 2011 arasında 9 sağlıklı gönüllüyü çalışmamiz için davet ettik. Kronik hastalığı veya anemisi olan kişilerle PPI tedavisinde olan kişileri dışladık. Serum demir konsantrasyonunu demir alımından 1, 2, ve 3 saat sonra ölçtük (kontrol grubu). Bu ölçümleri bir sonraki ziyarette 4 günlük oral 40 mg dozunda omeprazol tedavisinden sonra tekrarladık (tedavi grubu).Bulgular: Ortalama yaşları 33 yıl olan 8 erkek ve 1 kadın gönüllü çalışmamıza katıldı. Kontrol grubu ile tedavi grubu arasında bazal, 1 saat, 2 saat, ve 3 saat sonraki demir konsantrasyonları arasında istatistiksel anlamlı bir fark görülmedi. Sonuç: Sağlıklı kişilerde kısa bir zaman sürecince verilen omeprazol oral olarak alınan demirin absorbsiyonunu etkilemez.

  11. [Side effects of postoperative irradiation of uterine cancer with high dose rate iridium and low dose rate radium].

    PubMed

    Kucera, H; Unel, N; Weghaupt, K

    1986-02-01

    A report is given about reversible and irreversible complications following postoperative irradiation in cases of endometrial carcinoma. Intravaginal brachytherapy was performed. In advanced cases or in cases with poor prognosis (tumor grading) percutaneous irradiation was added (Co60). In 156 cases low-dose-rate irradiation (Ra226) and in 143 cases high-dose-rate irradiation (Ir192) was applied intravaginally. Reversible complications (cystitis, proctitis) could be observed following Radium in 7%, following Iridium in 14%. Irreversible complications (fistulas, stenoses): 1.9% following Radium and 3.5% following Iridium. When high-dose-rate irradiation was combined with percutaneous Co60 therapy, reversible complications occurred in 22.8%. After changing the Iridium-therapy scheme (reduction of dose from 10 to 7 Gy and irradiation only of the upper two thirds of the vagina) complications only could be observed in the same level as in Radium-therapy. High-dose-rate irradiation does not need hospitalization of the patients.

  12. 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.

  13. 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.

  14. Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

    PubMed

    Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

    2015-12-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD.

  15. Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer – between options

    PubMed Central

    2013-01-01

    Purpose Permanent low-dose-rate (LDR-BT) and temporary high-dose-rate (HDR-BT) brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never to be conducted comparing these two forms of brachytherapy, a comparative analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. The aim of this paper is to look for possible similarities and differences between both brachytherapy modalities. Indications and contraindications for monotherapy and for brachytherapy as a boost to external beam radiation therapy (EBRT) are presented. It is suggested that each of these techniques has attributes that advocates for one or the other. First, they represent the extreme ends of the spectrum with respect to dose rate and fractionation, and therefore have inherently different radiobiological properties. Low-dose-rate brachytherapy has the great advantage of being practically a one-time procedure, and enjoys a long-term follow-up database supporting its excellent outcomes and low morbidity. Low-dose-rate brachytherapy has been a gold standard for prostate brachytherapy in low risk patients since many years. On the other hand, HDR is a fairly invasive procedure requiring several sessions associated with a brief hospital stay. Although lacking in significant long-term data, it possesses the technical advantage of control over its postimplant dosimetry (by modulating the source dwell time and position), which is absent in LDR brachytherapy. This important difference in dosimetric control allows HDR doses to be escalated safely, a flexibility that does not exist for LDR brachytherapy. Conclusions Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy, using current dose regimens. At present, all available clinical data regarding these two techniques

  16. 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

  17. High Dose Hyperfractionated Radiotherapy for Adults with Glioblastomas

    SciTech Connect

    Koukourakis, Michael; Scarlatos, John; Yiannakakis, Dimitrios; Kordiolis, Nicolas; Zambatis, Haralambos; Sotiropoulou, Anastasia

    2015-01-15

    From 1989 to 1991, 27 patients with glioblastoma multiforme or anaplastic astrocytoma of the brain were treated with radiotherapy. Fifteen of twenty-seven patients were treated through limited volume fields, with a thrice-a-day (1.1 Gy/f) or twice-a-day (1.4 Gy/f) hyperfractionated regimen to a total physical dose of 62–92 Gy (median dose 76 Gy). The remaining 12 were treated with whole brain irradiation (40 Gy of total conventionally fractionated dose) and a localised boost to a total dose of 60 Gy. The hyperfractionated regimen was well tolerated and there was no sign of increased brain oedema to indicate the insertion of a split. Of six patients who received a NTD10 (normalised total dose for α/β =10) higher than 71 Gy, five showed CR (83% CR rate) versus three of 21 patients who received a lower NTD10 (14% CR rate). For 13 patients who received a NTD10 higher than 66 Gy, the 18-months survival was 61% (8/13) versus 28% (4/14) for 14 patients who received a NTD10 less than 66 Gy. As far as the late morbidity is concerned, of six patients treated with 76-92 Gy of physical dose, none died because of radiation-induced brain necrosis within 18-42 months of follow-up, and three of them are without evidence of disease 18-31 months after the end of radiation treatment. None of our 15 patients who received less than whole brain irradiation relapsed outside the radiation portals. The present study strongly suggests the use of limited volume hyperfractionated radiotherapy schemes, so as to increase the local tumor dose (NTD10) to values higher than 79 Gy, at the same time keeping the NTD2 (NTD for α/β = 2) below 68 Gy.

  18. [Omeprazole: a new treatment for paranasal sinus polyps in Widal syndrome. Preliminary study].

    PubMed

    Serra, J; Piñas, J; Arnaiz, J A; Quesada, P; Naches, S; Lorente, J; Carne, X

    1998-05-01

    A preliminary report is made of the potential therapeutic effect of omeprazol in reducing nasosinusal polyps. This study is based on the empirical observation of nasal airflow improvement in patients suffering from nasosinusal polyposis after administering omeprazol. Different phases of the study suggested that patients with Widal's syndrome benefited the most. Based on the results of this study, we have undertaken a randomized, parallel, double-blind, placebo-controlled clinical trial.

  19. Efficacy of omeprazole for the prevention of exercise-induced gastritis in racing Alaskan sled dogs.

    PubMed

    Davis, M S; Willard, M D; Nelson, S L; McCullough, S M; Mandsager, R E; Roberts, J; Payton, M E

    2003-01-01

    Exercise-induced gastritis and gastric ulcers are common in humans and horses, and recently have been described in racing sled dogs. The cause of exercise-induced gastric disease is not completely understood in any species, but pharmacologic suppression of acid secretion is an effective treatment in humans and horses. Thus, we tested the hypothesis that omeprazole, a proton-pump inhibitor shown to reduce gastric acid secretion in dogs, would reduce the severity of exercise-induced gastric disease. Three teams of 16 dogs each competing in the 2002 Iditarod Sled Dog Race were recruited for participation. Within each team, dogs were randomly assigned to either treatment (20 mg omeprazole PO q24h) or placebo. Treatments were administered until either completion of the race or withdrawal of an individual dog from competition. Gastric endoscopy was performed in all dogs 24 hours after completion or withdrawal, and the gastric mucosa was scored by using a subjective severity score (0 = normal, 3 = numerous bleeding ulcers). Treatment with omeprazole significantly reduced mean gastricseverity score compared to placebo (omeprazole: 0.65 +/- 0.17, placebo: 1.09 +/- 0.18; P = .028), but also was associated with increased frequency of diarrhea during the race (omeprazole 54%, placebo 21%; P = .017). Examination of our data suggests that omeprazole may be an effective treatment for exercise-induced gastric disease in racing sled dogs. However, further investigation regarding the cause and clinical relevance of diarrhea associated with omeprazole treatment must be conducted before omeprazole can be recommended for routine prophylactic treatment in these athletes.

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

    SciTech Connect

    Gonzalez-Azcorra, S. A.; Ruiz-Trejo, C.; Buenfil, A. E.; Mota-Garcia, A.; Poitevin-Chacon, M. A.; Santamaria-Torruco, B. J.; Rodriguez-Ponce, M.; Herrera-Martinez, F. P.; Gamboa de Buen, I.

    2008-08-11

    In this prospective study, rectal dose was measured 'in vivo' using TLD-100 crystals (3x3x1 mm{sup 3}), 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 Cancerologia (INCan)

  1. [Partial regression of Barret esophagus with high grade dysplasia and adenocarcinoma after photocoagulation and endocurietherapy under antisecretory treatment].

    PubMed

    Fremond, L; Bouché, O; Diébold, M D; Demange, L; Zeitoun, P; Thiefin, G

    1995-01-01

    Barrett's oesophagus is a premalignant condition. The possibility of eradicating at least partially the metaplastic epithelium has been reported recently. In this case report, a patient with Barrett's oesophagus complicated by high grade dysplasia and focal adenocarcinoma was treated by Nd:Yag laser then high dose rate intraluminal irradiation while on omeprazole 40 mg/day. A partial eradication of Barrett's oesophagus and a transient tumoural regression were obtained. Histologically, residual specialized-type glandular tissue was observed beneath regenerative squamous epithelium. Four months after intraluminal irradiation, a local tumoural recurrence was detected while the area of restored squamous epithelium was unchanged on omeprazole 40 mg/day. This indicates that physical destruction of Barrett's oesophagus associated with potent antisecretory treatment can induce a regression of the metaplastic epithelium, even in presence of high grade dysplasia. The persistence of specialized-type glands beneath the squamous epithelium raises important issues about its potential malignant degeneration.

  2. 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.

  3. High-Dose-Rate Prostate Brachytherapy Consistently Results in High Quality Dosimetry

    SciTech Connect

    White, Evan C.; Kamrava, Mitchell R.; Demarco, John; Park, Sang-June; Wang, Pin-Chieh; Kayode, Oluwatosin; Steinberg, Michael L.; Demanes, D. Jeffrey

    2013-02-01

    Purpose: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results: The mean prostate ultrasound volume was 38.7 {+-} 13.4 cm{sup 3} (range: 11.7-108.6 cm{sup 3}). The mean CTV was 75.1 {+-} 20.6 cm{sup 3} (range: 33.4-156.5 cm{sup 3}). The mean D90 was 109.2% {+-} 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% {+-} 0.05%, 99.5% {+-} 0.8%, 25.4% {+-} 4.2%, and 7.8% {+-} 1.4%. The mean dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} for organs at risk were: Urethra: 107.3% {+-} 3.0%, 101.1% {+-} 14.6%, and 47.9% {+-} 34.8%; bladder wall: 79.5% {+-} 5.1%, 69.8% {+-} 4.9%, and 64.3% {+-} 5.0%; bladder balloon: 70.3% {+-} 6.8%, 59.1% {+-} 6.6%, and 52.3% {+-} 6.2%; rectum: 76.3% {+-} 2.5%, 70.2% {+-} 3.3%, and 66.3% {+-} 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

  4. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2011-06-01

    requirements depending on rectal and bladder doses. The class solution in inverse planned HDR prostate brachythe - rapy for dose escalation of a DIL...High-dose-rate brachyther- apy without external beam irradiation for locally advanced prostate cancer. Radiother Oncol 2006; 80: 62-68. 7. Galalae RM... prostate brachytherapy for dose escalation of DIL defined by combined MRI/MRSI. Radiother Oncol 2008; 88: 148-155. 16. Pouliot J, Kim Y, Lessard E et al

  5. Application of nickel zinc ferrite/graphene nanocomposite as a modifier for fabrication of a sensitive electrochemical sensor for determination of omeprazole in real samples.

    PubMed

    Afkhami, Abbas; Bahiraei, Atousa; Madrakian, Tayyebeh

    2017-06-01

    In the present study, a simple and highly sensitive sensor for the determination of omeprazole based on nickel-zinc ferrite/graphene modified glassy carbon electrode is reported. The morphology and electro analytical performance of the fabricated sensor were characterized with X-ray diffraction spectrometry, Fourier transform infrared spectrometry, scanning electron microscopy, electrochemical impedance spectroscopy, cyclic voltammetry, differential pulse voltammetry and operation of the sensor. Results were compared with those achieved at the graphene modified glassy carbon electrode and bare glassy carbon electrode. Under the optimized experimental conditions, linear response was over the range of 0.03-100.0µmolL(-1). The lower detection limit was found to be 0.015µmolL(-1). The effect of different interferences on the anodic current response of OMZ was investigated. By measuring the concentrations of omeprazole in plasma and pharmaceutical samples, the practical application of the modified electrode was evaluated. This revealed that the nickel-zinc ferrite/graphene modified glassy carbon electrode shows excellent analytical performance for the determination of omeprazole with a very low detection limit, high sensitivity, and very good accuracy.

  6. Phase I dose escalation study of high dose carfilzomib monotherapy for Japanese patients with relapsed or refractory multiple myeloma.

    PubMed

    Iida, Shinsuke; Tobinai, Kensei; Taniwaki, Masafumi; Shumiya, Yoshihisa; Nakamura, Toru; Chou, Takaaki

    2016-11-01

    We conducted a multicenter, open-label Phase I study of single-agent carfilzomib in Japanese patients with relapsed or refractory multiple myeloma. The primary endpoints were tolerability and safety. Carfilzomib was administrated for 30 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, doses for days 1 and 2 were 20 mg/m(2), followed by 45 or 56 mg/m(2). Three and four subjects were enrolled in the 20/45 mg/m(2) cohort and 20/56 mg/m(2) cohort. No dose-limiting toxicity was observed, and the tolerability of carfilzomib was confirmed. Pyrexia, hypertension, nausea and vomiting were considered as noteworthy adverse events (AE) when carfilzomib was administered at high doses. Moreover, pyrexia, blood creatinine increased, and body weight gain were observed as acute dose effects. These findings suggest that addition of dexamethasone is important to alleviate acute dose effect. The overall response rates of the 20/45 mg/m(2) and 20/56 mg/m(2) cohort were 66.7 % (two out of three) and 50 % (two out of four), respectively. Carfilzomib administrated at up to 20/56 mg/m(2) was well tolerated and seemed active in Japanese patients with relapsed or refractory multiple myeloma.

  7. 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.

  8. 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, M; Maloy, S

    2013-01-01

    Static fracture toughness tests have been performed for high dose HT9 steel using miniature disk compact tension (DCT) specimens to expand the knowledge base for fast reactor core materials. The HT9 steel DCT specimens were from the ACO-3 duct of the Fast Flux Test Facility (FFTF), which achieved high doses in the range of 3 148 dpa at 378 504oC. 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 m occurred in room temperature tests when irradiation temperature was below 400 C, while ductile fracture with stable crack growth was observed in all tests at higher irradiation temperatures. No fracture toughness less than 100 MPa m 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 dose range 3 148 dpa. A post upper-shelf behavior was observed for the non-irradiated 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.

  9. 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

  10. Sense and nonsense of high-dose cytarabine for acute myeloid leukemia.

    PubMed

    Löwenberg, Bob

    2013-01-03

    High-dose cytarabine applied during remission induction or as consolidation after attainment of a complete remission has become an established element in the treatment of adults with acute myeloid leukemia. Recent evidence has challenged the need for these exceptionally high-dose levels of cytarabine. In this review, we present a reappraisal of the usefulness of high-dose cytarabine for acute myeloid leukemia treatment.

  11. Total Ionizing Dose Effects on High Resolution (12-/14-bit) Analog-to-Digital Converters

    NASA Technical Reports Server (NTRS)

    Lee, C. I.; Rax, B. G.; Johnson, A. H.

    1994-01-01

    This paper reports total dose radiation test results for high resolution 12-/14-bit A/D converters. Small changes in internal components can cause these devices to fail their specifications at relatively low total dose levels. Degradation of signal-to-noise ratio becomes increasingly importamt for high accuracy converters. Rebound effects in the thick-oxide MOS devices causes these responses to be different at low and high dose rates, which is a major concern for space applications.

  12. Analysis of high-dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer.

    PubMed

    Sudahar, H; Kurup, P G G; Murali, V; Mahadev, P; Velmurugan, J

    2013-01-01

    The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high-dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30Gy in 3 fractions of HDR brachytherapy regimen. The D5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86Gy. The mean HDR fractionation equivalent dose, D98%, was 27.93 ± 0.84Gy. The V100% of the prostate target was 95.57% ± 3.47%. The V100% of the bladder and the rectum were 717.16 and 79.6mm(3), respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D98% to D80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D10% and D5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.

  13. 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

  14. High dose of ascorbic acid induces cell death in mesothelioma cells.

    PubMed

    Takemura, Yukitoshi; Satoh, Motohiko; Satoh, Kiyotoshi; Hamada, Hironobu; Sekido, Yoshitaka; Kubota, Shunichiro

    2010-04-02

    Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

  15. The impact of cobalt-60 source age on biologically effective dose in high-dose functional Gamma Knife radiosurgery.

    PubMed

    Kann, Benjamin H; Yu, James B; Stahl, John M; Bond, James E; Loiselle, Christopher; Chiang, Veronica L; Bindra, Ranjit S; Gerrard, Jason L; Carlson, David J

    2016-12-01

    replacement resulted in an immediate relative BED increase of 11.7% for GKRS-based TN management with 85 Gy, 15.6% for thalamotomy with 130 Gy, and 18.6% for capsulotomy with 180 Gy. Over the course of the 63-month lifespan of the cobalt-60 source, BED decreased annually by 2.2% for TN management, 3.0% for thalamotomy, and 3.5% for capsulotomy. CONCLUSIONS Use of a new cobalt-60 source after replacement of an old source substantially increases the predicted BED for functional GKRS treatments for the same physical dose prescription. Source age, dose rate, and treatment time should be considered in the study of outcomes after high-dose functional GKRS treatments. Animal and clinical studies are needed to determine how this potential change in BED contributes to GKRS toxicity and whether technical adjustments should be made to reduce dose rates or prescription doses with newer cobalt-60 sources.

  16. 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.

  17. Fast, three-dimensional, MR Imaging for polymer gel dosimetric applications involving high dose and steep dose gradients

    NASA Astrophysics Data System (ADS)

    Sandilos, Panagiotis; Baras, Panagiotis; Georgiou, Evangelos; Dardoufas, Konstantinos; Karaiskos, Pantelis; Papagiannis, Panagiotis; Paschalis, Theodoros; Tatsis, Elias; Torrens, Michael; Vlahos, Lampros

    2006-12-01

    Polymer gels constitute water equivalent integrating detectors, which, combined with magnetic resonance imaging (MRI), can provide accurate three dimensional (3D) dose distributions in contemporary radiotherapy applications where the small field dimensions and steep dose gradients induce limitations to conventional dosimeters. One of the main obstacles for adapting the method for routine use in the clinical setting is the cost effectiveness of the MRI readout method. Currently, optimized Carr-Purcell-Meiboom-Gill (CPMG) multiple spin echo imaging pulse sequences are commonly used which however result in long imaging times. This work evaluates the efficiency of 3D, dual-echo, k-space segmented turbo spin echo (TSE) scanning sequences for accurate dosimetry with sub-millimetre spatial resolution in strenuous radiation therapy applications. PABIG polymer gel dosimeters were irradiated with an 192Ir High Dose Rate brachytherapy source, the 4 mm and 8 mm collimator helmets of a gamma knife unit and a custom made x-knife collimator of 1 cm diameter. Profile and dose distribution measurements using TSE are benchmarked against corresponding findings obtained by the commonly used, but time consuming, CPMG sequence as well as treatment planning calculations, Monte Carlo (MC) simulations and film measurements. The implementation of a high Turbo factor was found to provide comparable accuracy, allowing a 64-fold MRI scan acceleration compared to conventional multi-echo sequences. The availability of TSE sequences in typical MRI installations greatly facilitates the introduction of polymer gel dosimetry in the clinical environment as a practicable tool for the determination of full 3D dose distributions in contemporary radiotherapy applications.

  18. 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

  19. Pharmacokinetics of omeprazole after intravenous and oral administration to rats with liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Lee, Dae Y; Lee, Inchul; Lee, Myung G

    2007-02-07

    The aim of this study is to report the pharmacokinetics of omeprazole after intravenous (20 mg/kg) and oral (40 mg/kg) administration to rats with liver cirrhosis induced by dimethylnitrosamine (cirrhotic rats) with respect to CYP isozyme changes. The expressions of CYP1A2 and 3A1 decreased in cirrhotic rats and omeprazole is reported to be mainly metabolized via CYP1A1/2, 2D1, and 3A1/2 in male Sprague-Dawley rats. Hence, the pharmacokinetics of omeprazole could be changed in cirrhotic rats. After intravenous administration to cirrhotic rats, the AUC (1180 microg min/ml versus 474 microg min/ml) and CL(NR) (17.4 ml/min/kg versus 42.3 ml/min/kg) of omeprazole were significantly greater and slower, respectively, than the controls. This could be due to decrease in the expressions of CYP1A2 and 3A1 in cirrhotic rats. The significantly slower CL(NR) could be supported by significantly slower in vitro CL(int) for the disappearance of omeprazole from hepatic microsomal study (0.102 ml/min/mg protein versus 0.144 ml/min/mg protein) and slower hepatic blood flow rate in cirrhotic rats. After oral administration to cirrhotic rats, the AUC difference was considerably greater (451% versus 149%) than that after intravenous administration, possibly due to decrease in intestinal first-pass effect of omeprazole in addition to decrease in hepatic metabolism of omeprazole in cirrhotic rats.

  20. Global convergence analysis of fast multiobjective gradient-based dose optimization algorithms for high-dose-rate brachytherapy.

    PubMed

    Lahanas, M; Baltas, D; Giannouli, S

    2003-03-07

    We consider the problem of the global convergence of gradient-based optimization algorithms for interstitial high-dose-rate (HDR) brachytherapy dose optimization using variance-based objectives. Possible local minima could lead to only sub-optimal solutions. We perform a configuration space analysis using a representative set of the entire non-dominated solution space. A set of three prostate implants is used in this study. We compare the results obtained by conjugate gradient algorithms, two variable metric algorithms and fast-simulated annealing. For the variable metric algorithm BFGS from numerical recipes, large fluctuations are observed. The limited memory L-BFGS algorithm and the conjugate gradient algorithm FRPR are globally convergent. Local minima or degenerate states are not observed. We study the possibility of obtaining a representative set of non-dominated solutions using optimal solution rearrangement and a warm start mechanism. For the surface and volume dose variance and their derivatives, a method is proposed which significantly reduces the number of required operations. The optimization time, ignoring a preprocessing step, is independent of the number of sampling points in the planning target volume. Multiobjective dose optimization in HDR brachytherapy using L-BFGS and a new modified computation method for the objectives and derivatives has been accelerated, depending on the number of sampling points, by a factor in the range 10-100.

  1. 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).

  2. Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

    NASA Technical Reports Server (NTRS)

    McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

    2012-01-01

    Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

  3. The effect of high dose rate transient gamma radiation on high-energy optical fibers

    NASA Astrophysics Data System (ADS)

    Akinci, A.; Bowden, M. D.; Cheeseman, M. C.; Knowles, S. L.; Meister, D. C.; Pecak, S. N.; Simmons Potter, K.

    2009-08-01

    High power laser systems have a number of uses in a variety of scientific and defense applications, for example laser induced breakdown spectroscopy (LIBS) or laser-triggered switches. In general, high power optical fibers are used to deliver the laser energy from the source to the target in preference to free space beams. In certain cases, such as nuclear reactors, these optical systems are expected to operate in ionizing radiation environments. In this paper, a variety of modern, currently available commercial off-the-shelf (COTS) optical fiber designs have been assessed for successful operation in the transient gamma radiation environment produced by the HERMES III accelerator at Sandia National Laboratories, USA. The performance of these fibers was evaluated for high (~1 MW) and low (<1 W) optical power transmission during high dose rate, high total dose gamma irradiation. A significant reduction in low optical power transmission to 32% of maximum was observed for low OH- content fibers, and 35% of maximum for high OH- fibers. The high OH- fibers were observed to recover to 80% transmission within 1 μs and 100% transmission within 1 ms. High optical power transmission losses followed generally similar trends to the low optical power transmission losses, though evidence for an optical power dependent recovery was observed. For 10-20 mJ, 15 ns laser pulses, around 46% was transmitted coincident with the radiation pulse, recovering to 70% transmission within 40 ns of the radiation pulse. All fibers were observed to completely recover within a few minutes for high optical powers. High optical power densities in excess of 1 GW/cm2 were successfully transmitted during the period of highest loss without any observed damage to the optical fibers.

  4. Effects of administration of high dose hydrocortisone on Bell's palsy.

    PubMed

    Watanabe, S; Kenmochi, M; Kinoshita, H; Kato, I

    1996-01-01

    As an improved maintenance therapy for Bell's palsy, Stennert recently introduced large-dose steroid administration in the early stage of the disease with i.v. infusion of low-molecular dextran. The steroid administration aims at improving the microcirculation. This therapy achieved a 96% complete healing rate. However, because of side-effects such as hepatic and renal disorders or gastric ulcer, this therapy has not been widely used. In the present study, we investigated an improved treatment method based on Stennert's method. It has a much lower incidence of side effects, and can be used in routine clinical practice. The medicines employed in our therapy were hydrocortisone sodium succinate (Solu-cortef), hydroxymethylated starch (Hespander) and D-mannitol (Manitol). Subjects were 53 Bell's palsy patients for whom treatment could be started within 2 weeks from the onset of the disease. Curative rate in the patients who received large-dose administration of Solu-cortef was 96.2% in the 24th week, and the therapy was considered to be applicable in routine clinical practice for Bell's palsy.

  5. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy

    PubMed Central

    Wang, Chunyu; Fu, Xiaolong; Cai, Xuwei; Wu, Xianghua; Hu, Xichun; Fan, Min; Xiang, Jiaqing; Zhang, Yawei; Chen, Haiquan; Jiang, Guoliang; Zhao, Kuaile

    2016-01-01

    Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09–0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC. PMID:26766917

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

    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 √m 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 √m 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.

  8. Effect of high-dose intravenous eletriptan on coronary artery diameter.

    PubMed

    Goldstein, J A; Massey, K D; Kirby, S; Gibson, M; Hettiarachchi, J; Rankin, A J; Jackson, N C

    2004-07-01

    The goal of this study was to evaluate the coronary vasoconstrictive effects of high doses of eletriptan compared with a standard dose of sumatriptan. Patients with no clinically significant coronary artery disease were randomized to receive high-dose intravenous eletriptan (n = 24) vs a standard dose of sumatriptan (n = 18; 6 mg subcutaneously) vs placebo (n = 18). Serial angiograms were obtained. The primary non-inferiority analysis found equivalence between the mean maximum change in left anterior descending coronary artery diameter for eletriptan, -22%[95% confidence interval (CI) -26, -19], and sumatriptan, -19% (95% CI -22, -16). The change due to placebo was -16% (95% CI -20, -12). No individual cases of clinically significant vasoconstriction were observed. The results confirm that eletriptan has a broad cardiovascular safety margin, with plasma concentrations comparable to three to five times the Cmax of an oral 80-mg dose associated with modest vasoconstriction equivalent to standard therapeutic doses of sumatriptan.

  9. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery.

    PubMed

    Kirkpatrick, John P; Meyer, Jeffrey J; Marks, Lawrence B

    2008-10-01

    The linear-quadratic (LQ) model is widely used to model the effect of total dose and dose per fraction in conventionally fractionated radiotherapy. Much of the data used to generate the model are obtained in vitro at doses well below those used in radiosurgery. Clinically, the LQ model often underestimates tumor control observed at radiosurgical doses. The underlying mechanisms implied by the LQ model do not reflect the vascular and stromal damage produced at the high doses per fraction encountered in radiosurgery and ignore the impact of radioresistant subpopulations of cells. The appropriate modeling of both tumor control and normal tissue toxicity in radiosurgery requires the application of emerging understanding of molecular-, cellular-, and tissue-level effects of high-dose/fraction-ionizing radiation and the role of cancer stem cells.

  10. 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.

  11. Randomised, double blind comparison of omeprazole and cimetidine in the treatment of symptomatic gastric ulcer.

    PubMed Central

    Bate, C M; Wilkinson, S P; Bradby, G V; Bateson, M C; Hislop, W S; Crowe, J P; Willoughby, C P; Peers, E M; Richardson, P D

    1989-01-01

    In a randomised, double blind, parallel group study in patients with symptomatic gastric ulcer (94% greater than or equal to 5 mm diameter), 102 received omeprazole 20 mg om and 87 cimetidine 400 mg bd. After four weeks 73% and 58% (p less than 0.05) respectively had healed (eight weeks: 84% and 75%, ns). After four weeks, a greater proportion (81%) of omeprazole treated patients was symptom free than of those receiving cimetidine (60%; p less than 0.01). Over the first two weeks, patients receiving omeprazole had less day pain, less night pain and took fewer antacids than those receiving cimetidine (all p less than 0.05). The difference between omeprazole and cimetidine was not appreciably affected by age, smoking, size of the ulcer and trial centre. Tolerability was similar in the two treatment groups. In the treatment of symptomatic gastric ulcer, omeprazole relieves the symptoms more quickly than cimetidine and heals a greater proportion of ulcers within four weeks. PMID:2684802

  12. Effects of omeprazole on healing of naturally-occurring gastric ulcers in thoroughbred racehorses.

    PubMed

    Murray, M J; Haven, M L; Eichorn, E S; Zhang, D; Eagleson, J; Hickey, G J

    1997-11-01

    Seventeen Thoroughbred horses with moderate to severe gastric ulceration were purchased from a race track within 10 days of racing and were treated once daily with either omeprazole (9 horses) or vehicle (8 horses) and evaluated gastroscopically for ulcer healing. Horses were administered omeprazole (1.5 mg/kg bwt/day) or vehicle by nasogastric tube once daily. Gastroscopic examination was performed on Days 0, 4, 7, 11, 14, 17, 21, 24 and 28, until lesions healed completely. Selected images of gastric lesions were captured by computer at each endoscopic examination, with a measuring caliper included in captured images. The area and perimeter of lesions were measured by computer and healing rates of specific lesions were determined by calculating the rate of linear advance of the margins toward the centre of the lesion. Additionally, the number of days to complete healing of the entire gastric squamous mucosa was compared between treatment groups. Gastric lesions healed at a significantly faster rate in horses receiving omeprazole than in vehicle-treated horses (P < 0.001). Complete healing of the entire stomach occurred in 10-21 days in omeprazole-treated horses, and 14-28 days in 3 of 8 vehicle-treated horses, with the remaining vehicle-treated horses having unhealed lesions on Day 28. In addition, 5 vehicle-treated horses developed new lesions in the squamous epithelial mucosa during the trial; no new lesions were observed in the omeprazole-treated group.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Comparison of high-dose and low-dose insulin by continuous intravenous infusion in the treatment of diabetic ketoacidosis in children.

    PubMed

    Burghen, G A; Etteldorf, J N; Fisher, J N; Kitabchi, A Q

    1980-01-01

    We studied the efficacy of low-dose (0.1 U/kg/h) and high-dose (1..0 U/kg/h) insulin, given randomly to children with diabetic ketoacidosis (DKA) by continuous intravenous infusion without a loading dose. Plasma glucose reached 250 mg/dl in 3.4 +/- 0.4 h with the high-dose insulin group compared with 5.4 +/- 0.5 h with the low-dose insulin group (P < 0.01). During the first 12 h of therapy, plasma glucose fell below 100 mg/dl in 2 of 16 in the low-dose compared with 12 of 16 in the high-dose patients. The decrement of ketone bodies, cortisol, and glucagon was similar in both groups. The number of hours required for HCO3(-) greater than or equal to meq/l and arterial blood pH greater than or equal to 7.30 were not significantly different in the two groups. Hypokalemia (K < 3.4 meq/L) occurred in 3 of 16 low-dose and 10 of 16 high-dose patients. The data show that low-dose insulin, with a slower rate of glucose decrease, is as effective as a high dose for the treatment of DKA in children with less incidence of hypokalemia and decreased potential for hypoglycemia.

  18. Omeprazole does not enhance the metabolism of phenacetin, a marker of CYP1A2 activity, in healthy volunteers.

    PubMed

    Xiaodong, S; Gatti, G; Bartoli, A; Cipolla, G; Crema, F; Perucca, E

    1994-06-01

    Omeprazole has been reported to increase cytochrome P450IA2 (CYP1A2) activity in vitro, but whether this effect also occurs in vivo is controversial. To clarify this issue, the effect of omeprazole (20 mg/day for 8 days) on the kinetics and metabolism of phenacetin, an in vivo marker of CYP1A2 activity, was examined in 10 healthy volunteers. The pharmacokinetic parameters of phenacetin and metabolically derived paracetamol on the 8th day of omeprazole administration were very similar to those observed in a control session in the absence of omeprazole administration, the only significant difference being a higher peak plasma phenacetin concentration during omeprazole treatment. It is concluded that at the dosage used omeprazole does not increase the rate of oxidative and conjugative reactions involved in the metabolism of phenacetin and paracetamol respectively. These data are consistent with the hypothesis that omeprazole is generally devoid of inducing effects on CYP1A2 activity in vivo, at least in a Caucasian population with a low prevalence of the omeprazole-mephenytoin poor metabolizer phenotype.

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

    PubMed Central

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

    2017-01-01

    Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries, but they have a high potential for tolerance, dependence and misuse. High-dose BZD misuse represents an emerging addiction phenomenon, but data on quality of life (QoL) in high-dose BZD misusers are scant. This study aimed to explore QoL in high-dose BZD misuse. We recruited 267 high-dose BZD misusers, compared the QoL scores in those who took BZD only to poly-drug misusers, and explored the role of demographic and clinical covariates through multivariable analysis. Our data confirmed worse QoL in high-dose BZD misusers and showed that (a) QoL scores were not negatively influenced by the misuse of alcohol or other drugs, or by coexisting psychiatric disorders; (b) demographic variables turned out to be the most significant predictors of QoL scores; (c) BZD intake significantly and negatively influenced QoL. Physical and psychological dimensions of QoL are significantly lower in high-dose BZD misusers with no significant effect of comorbidities. Our data suggest that the main reason for poor QoL in these patients is high-dose BZD intake per se. QoL should be considered among outcome measures in these patients. PMID:28054975

  20. 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).

  1. High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion.

    PubMed

    Fields, K K; Elfenbein, G J; Perkins, J B; Janssen, W E; Ballester, O F; Hiemenz, J W; Zorsky, P E; Kronish, L E; Foody, M C

    1994-10-01

    We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.

  2. 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

  3. 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

  4. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy. Addendum

    DTIC Science & Technology

    2009-06-01

    compromising the dose coverage of the prostate and the protection to the urethra , rectum, and bladder for prostate cancer patients treated with High...fusion, dose escalation, prostate cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...18 4 INTRODUCTION Research Project Description Men with prostate cancer , in particular those with advanced

  5. 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...

  6. The effects of intermittent high asbestos exposure (peak dose levels) on the lungs of rats.

    PubMed Central

    Davis, J. M.; Beckett, S. T.; Bolton, R. E.; Donaldson, K.

    1980-01-01

    Four groups of rats were treated by inhalation with the UICC preparations of amosite or chrysotile in order to explore the effects of intermittent high dust concentrations (peak dosing). For each of the 2 asbestos types one group of rats was treated for 5 days each week, 7 h a day, for 1 year. Two other groups were treated with amosite or chrysotile at 5 times the previous dose for 1 day each week for 1 year. Results showed that the lung dust levels of both chrysotile or amosite in the lungs of rats after the 12-month inhalation period were similar regardless of whether "peak" or "even" dosing had been used. During the following 6 months, asbestos was cleared from the "peak" chrysotile group more slowly than the "even" chrysotile group but clearance from the "peak" amosite group was faster than that found after "even" dosing with amosite. Levels of early peribronchial fibrosis were generally lower for the "peak" dosing groups than for "even" dosing although levels of interstitial fibrosis were slightly higher following "peak" dosing. The incidence of pulmonary neoplasms did not differ between the "peak"-dosing and "even"-dosing experiments. These findings therefore give no indication that short periods of high dust exposure in an asbestos factory would result in a significantly greater hazard than would be indicated by the raised overall dust counts for the day in question. Images Fig. 3 PMID:7426382

  7. An ultra-high dose of electron radiation response of Germanium Flat Fiber and TLD-100

    NASA Astrophysics Data System (ADS)

    Alawiah, A.; Amin, Y. M.; Abdul-Rashid, H. A.; Abdullah, W. S. Wan; Maah, M. J.; Bradley, D. A.

    2017-01-01

    The thermoluminescence (TL) response of Germanium Flat Fiber (GFF) and TLD-100 irradiated with 2.5 MeV electrons for the doses up to 1 MGy were studied and compared. The aim was to evaluate the TL supralinearity response at an ultra-high dose (UHD) range and to investigate the change in kinetic parameters of the glow peaks, as the doses increases up to 1 MGy. It is found that the critical dose limit (CDL) of GFF is 5 times higher as compared to TLD-100. CDL is determined by the dose at the maximum supralinearity, f(D)max. It is also found that annealing the TLD-100 and GFF with temperature more than 400 °C is required to reset it back to its original condition, following radiation doses up to 1 MGy. It is also noticed the strange behavior of Peak 4 (TLD-100), which tends to be invisible at the lower dose (<10 kGy) and starts to be appeared at the critical dose limit of 10 kGy. This result might be an important clue to understand the behavior of TLD-100 at extremely high dose range. For both samples, it is observed that the TL intensity is not saturated within the UHD range studied.

  8. [Development of a perforated peptic ulcer in a child during high dose prednisolone treatment].

    PubMed

    Moll Harboe, Kirstine; Midtgaard, Helle; Wewer, Vibeke; Cortes, Dina

    2012-09-24

    Since perforated peptic ulcer is uncommon in children proton pump inhibitor prophylaxis is not routinely recommended when children are treated with high dose steroids. We describe a case of perforated ulcer in a six-year-old patient with nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not suspected due to uncharacteristic symptoms. The child developed peritoneal signs and surgery revealed a perforated peptic ulcer in the stomach. We recommend treatment with proton pump inhibitors if children, who are treated with high dose steroids develop abdominal symptoms, which can be caused by an ulcus.

  9. "Half-half" blisters in bullous pemphigoid successfully treated with adjuvant high-dose intravenous immunoglobulin.

    PubMed

    Pacheco, David; Lopes, Leonor; Soares-Almeida, Luis; Marques, Manuel Sacramento; Filipe, Paulo

    2012-09-01

    Bullous pemphigoid is a rare, autoimmune blistering disease. Its clinical presentation is tense blisters that may arise on normal-appearing or erythematous skin. Bullous pemphigoid refractory to systemic corticosteroids in combination with immunosuppressants such as azathioprine and mycophenolate mofetil may benefit from adjuvant high-dose intravenous immunoglobulin (IVIg). We describe a particular case with an unusual clinical presentation unresponsive to systemic corticosteroids plus azathioprine, in which the addition of high-dose IVIg was successful. The combined therapy of systemic corticosteroids and azathioprine plus high-dose IVIg can be an option in refractory cases due to its efficiency and tolerability.

  10. Absolute and relative dose measurements with Gafchromic trade mark sign EBT film for high energy electron beams with different doses per pulse

    SciTech Connect

    Fiandra, Christian; Ragona, Riccardo; Ricardi, Umberto; Anglesio, Silvia; Giglioli, Francesca Romana

    2008-12-15

    The authors have evaluated the accuracy, in absolute and relative dose measurements, of the Gafchromic trade mark sign EBT film in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value of less than 0.1 mGy/pulse. However, very high dose-per-pulse electron beams are employed in certain linear accelerators dedicated to intraoperatory radiation therapy (IORT). In this study, the absorbed dose measurements with Gafchromic trade mark sign EBT in both low (less than 0.3 mGy per pulse) and high (30 and 70 mGy per pulse) dose-per-pulse electron beams were compared with ferrous sulfate chemical Fricke dosimetry (operated by the Italian Primary Standard Dosimetry Laboratory), a method independent of the dose per pulse. A summary of Gafchromic trade mark sign EBT in relative and absolute beam output determination is reported. This study demonstrates the independence of Gafchromic trade mark sign EBT absorption as a function of dose per pulse at different dose levels. A good agreement (within 3%) was found with Fricke dosimeters for plane-base IORT applicators. Comparison with a diode detector is presented for relative dose measurements, showing acceptable agreement both in the steep dose falloff zone and in the homogeneous dose region. This work also provides experimental values for recombination correction factor (K{sub sat}) of a Roos (plane parallel) ionization chamber calculated on the basis of theoretical models for charge recombination.

  11. Comparison of high dose and low dose folic acid supplementation on prevalence, onset and severity of preeclampsia

    PubMed Central

    Shahraki, Azar Danesh; Dehkordi, Nastaran Zamani; Lotfizadeh, Masoud

    2016-01-01

    Background: Folic acid supplementation had previously mentioned as a protective factor against the onset of preeclampsia (PE). In this study, we aimed to compare the effect of high dose (5 mg daily) and low dose (1 mg daily) of folic acid supplementation on prevalence, onset and severity of PE. Materials and Methods: Pregnant women who were in the first trimester and referred to prenatal care university hospitals of Isfahan, Iran during October 2013–May 2015 were included in this study, then they were randomly divided into two groups of 5 mg and 1 mg (treated with daily 5 mg and 1 mg of folic acid, respectively), both groups received folic acid from the first trimester of pregnancy to 42 days after termination. Blood pressure, body mass index (BMI), and some urine and blood biochemistry parameters were measured. SPSS-22 used for statistical analysis. Results: A total of 943 pregnant women participated in the study (450 women in 1 mg group and 450 women in 5 mg group). Incidence rate of PE was 3.8% in 1 mg group and 2.4% in 5 mg group. In a comparison of preeclamptic patients in 1 mg and 5 mg group, no significant differences were seen regarding age, BMI, laboratory data, the severity of the disease, and onset (early or late) (P > 0.05). Conclusion: Although our findings support that administration of high dose folic acid may decrease the prevalence of PE, there is not enough data to support that higher amount of folic acid administration can reduce the severity of presentation's signs or ameliorate the laboratory data and the onset of PE. PMID:28217630

  12. A Phase 2 Trial on the Effect of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

    DTIC Science & Technology

    2014-10-01

    of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1) PRINCIPAL INVESTIGATOR: David...High-dose Vitamin D Supplementation on Bone Mass in Adults with 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0487 5c...processes have taken more time than anticipated in the Statement of Work. This study has received an IND from the FDA to use high-dose vitamin D in the

  13. High-order noise analysis for low dose iterative image reconstruction methods: ASIR, IRIS, and MBAI

    NASA Astrophysics Data System (ADS)

    Do, Synho; Singh, Sarabjeet; Kalra, Mannudeep K.; Karl, W. Clem; Brady, Thomas J.; Pien, Homer

    2011-03-01

    Iterative reconstruction techniques (IRTs) has been shown to suppress noise significantly in low dose CT imaging. However, medical doctors hesitate to accept this new technology because visual impression of IRT images are different from full-dose filtered back-projection (FBP) images. Most common noise measurements such as the mean and standard deviation of homogeneous region in the image that do not provide sufficient characterization of noise statistics when probability density function becomes non-Gaussian. In this study, we measure L-moments of intensity values of images acquired at 10% of normal dose and reconstructed by IRT methods of two state-of-art clinical scanners (i.e., GE HDCT and Siemens DSCT flash) by keeping dosage level identical to each other. The high- and low-dose scans (i.e., 10% of high dose) were acquired from each scanner and L-moments of noise patches were calculated for the comparison.

  14. High dose eicosapentaenoic acid ethyl ester: effects on lipids and neutrophil leukotriene production in normal volunteers.

    PubMed Central

    Hawthorne, A B; Filipowicz, B L; Edwards, T J; Hawkey, C J

    1990-01-01

    1. A 93% pure ethyl ester of eicosapentaenoic acid was investigated for tolerability and biochemical effects on neutrophil leukotriene synthesis and plasma lipoproteins when given in high dose. Six healthy volunteers received 6 g eicosapentaenoic acid ethyl ester daily for 6 weeks, followed by a 4 week wash-out and then 18 g daily for 6 weeks. 2. There was inhibition of neutrophil leukotriene B4 and 5-hydroxyeicosatetraenoic acid synthesis, with no significant differences between low and high dose. 3. There was a dose dependent increase in leukotriene B5 and 5-hydroxyeicosatetraenoic acid acid synthesis. 4. Plasma triglycerides were reduced maximally on 6 g daily, with no greater suppression at 18 g daily. 5. Plasma cholesterol was only suppressed significantly at 18 g daily. 6. The 6 g daily dose was well tolerated but the 18 g daily dose produced diarrhoea and steatorrhoea. PMID:2169832

  15. 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

  16. 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.

  17. Spatially resolved measurement of high doses in microbeam radiation therapy using samarium doped fluorophosphate glasses

    SciTech Connect

    Okada, Go; Morrell, Brian; Koughia, Cyril; Kasap, Safa; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean

    2011-09-19

    The measurement of spatially resolved high doses in microbeam radiation therapy has always been a challenging task, where a combination of high dose response and high spatial resolution (microns) is required for synchrotron radiation peaked around 50 keV. The x-ray induced Sm{sup 3+}{yields} Sm{sup 2+} valence conversion in Sm{sup 3+} doped fluorophosphates glasses has been tested for use in x-ray dosimetry for microbeam radiation therapy. The conversion efficiency depends almost linearly on the dose of irradiation up to {approx}5 Gy and saturates at doses exceeding {approx}80 Gy. The conversion shows strong correlation with x-ray induced absorbance of the glass which is related to the formation of phosphorus-oxygen hole centers. When irradiated through a microslit collimator, a good spatial resolution and high ''peak-to-valley'' contrast have been observed by means of confocal photoluminescence microscopy.

  18. High-dose monoclonal antibodies via the subcutaneous route: challenges and technical solutions, an industry perspective.

    PubMed

    Narasimhan, Chakravarthy; Mach, Henryk; Shameem, Mohammed

    2012-07-01

    This review summarizes the various challenges in product development involved in subcutaneous administration of high-dose monoclonal antibodies and attempts to provide an industry perspective of some of the available technologies and potential avenues to overcome these challenges.

  19. Measurement of photoneutron dose produced by wedge filters of a high energy linac using polycarbonate films.

    PubMed

    Hashemi, Seyed Mehdi; Hashemi-Malayeri, Bijan; Raisali, Gholamreza; Shokrani, Parvaneh; Sharafi, Ali Akbar; Torkzadeh, Falamarz

    2008-05-01

    Radiotherapy represents the most widely spread technique to control and treat cancer. To increase the treatment efficiency, high energy linacs are used. However, applying high energy photon beams leads to a non-negligible dose of neutrons contaminating therapeutic beams. In addition, using conventional linacs necessitates applying wedge filters in some clinical conditions. However, there is not enough information on the effect of these filters on the photoneutrons produced. The aim of this study was to investigate the change of photoneutron dose equivalent due to the use of linac wedge filters. A high energy (18 MV) linear accelerator (Elekta SL 75/25) was studied. Polycarbonate films were used to measure the dose equivalent of photoneutrons. After electrochemical etching of the films, the neutron dose equivalent was calculated using Hp(10) factor, and its variation on the patient plane at 0, 5, 10, 50 and 100 cm from the center of the X-ray beam was determined. By increasing the distance from the center of the X-ray beam towards the periphery, the photoneutron dose equivalent decreased rapidly for the open and wedged fields. Increasing of the field size increased the photoneutron dose equivalent. The use of wedge filter increased the proportion of the neutron dose equivalent. The increase can be accounted for by the selective absorption of the high energy photons by the wedge filter.

  20. [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].

    PubMed

    Selle, Frédéric; Gligorov, Joseph; Soares, Daniele G; Lotz, Jean-Pierre

    2016-10-01

    The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.

  1. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

    PubMed Central

    Di Caprio, Roberta; Di Costanzo, Luisa; Monfrecola, Giuseppe

    2015-01-01

    Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled. PMID:25977597

  2. 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.

  3. Pharmacopeial methodologies for determining aerodynamic mass distributions of ultra-high dose inhaler medicines.

    PubMed

    Wong, William; Crapper, John; Chan, Hak-Kim; Traini, Daniela; Young, Paul M

    2010-03-11

    Three different impactor methodologies, the Andersen cascade impactor (ACI), next-generation impactor (NGI) and multistage-liquid impinger (MSLI) were studied to determine their performance when testing ultra-high dose dry powder formulations. Cumulative doses of spray-dried mannitol (Aridol) were delivered to each impactor at a flow rate of 60Lmin(-1) (up to a max dose of 800mg delivering 20 sequential 40mg capsules). In general, total drug collected in both the ACI and NGI falls below the range 85-115% of label claim criteria recommended by the United States of America Food and Drug Administration (FDA) at nominal mannitol doses exceeding 20mg and 200mg, respectively. In comparison analysis of the MSLI data, over a 5-800mg cumulative dosing range, indicated that the percentage of nominal dose recovered from the MSLI was within the +/-15% limits set in this study. Furthermore all samples, apart from the 5mg and 10mg analysis were within 5% of the nominal cumulative dose. While the MSLI is not routinely used for regulatory submission, the use of this impinger when studying ultra-high dose formulations should be considered as a complementary and comparative source of aerosol deposition data.

  4. 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

  5. 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

  6. High-dose fractionated radiation therapy for select patients with brain metastases

    SciTech Connect

    Pezner, R.D.; Lipsett, J.A.; Archambeau, J.O.; Fine, R.M.; Moss, W.T.

    1981-08-01

    Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites. The risk of radiotherapy side effects in the brain is discussed.

  7. High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

    NASA Astrophysics Data System (ADS)

    Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

    2017-01-01

    Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased

  8. 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.

  9. Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin.

    PubMed

    de la Peña, Amparo; Ma, Xiaosu; Reddy, Shobha; Ovalle, Fernando; Bergenstal, Richard M; Jackson, Jeffrey A

    2014-07-01

    Pharmacokinetic/pharmacodynamic (PK/PD) studies of human regular U-500 insulin (U-500R) at high doses commonly used in clinical practice (>100 units) have not been performed. The current analysis applied PK/PD modeling/simulation to fit the data and simulate single-dose and steady-state PK/PD of U-500R high-dose regimens. Data from 3 single-dose euglycemic clamp studies in healthy obese and normal-weight patients, and normal-weight patients with type 1 diabetes were used to build the model. The model was sequential (PK inputs fed into PD component). PK was described using a 1-compartment model with first-order absorption and elimination. The model estimated separate absorption rate constants for U-500R and human regular U-100 insulin. The PD component used an effect compartment model, parameterized in terms of maximum pharmacologic effect (E(max)) and concentration to achieve 50% of E(max). The model described the data well. Steady-state PK for once-daily (QD), twice-daily (BID), or thrice-daily (TID) administration appeared to be reached 24 hours after the first dose. At steady-state, QD dosing showed the greatest fluctuations in PK/PD. BID dosing showed a gradual increase in insulin action with each dose and a fairly stable basal insulin effect. For TID dosing, activity was maintained throughout the dosing interval. PK/PD modeling/simulation of high U-500R doses supports BID or TID administration with an extended duration of activity relative to QD. TID dosing may provide slightly better full-day insulin effect. Additional PK/PD studies and randomized controlled trials of U-500R are needed to validate model predictions in patients with insulin-resistant diabetes requiring high-dose insulin.

  10. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

    PubMed

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-11-20

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

  11. 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

  12. 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.

  13. 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.

  14. Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury

    PubMed Central

    Ota, Kazuhiro; Takeuchi, Toshihisa; Nouda, Sadaharu; Ozaki, Haruhiko; Kawaguchi, Shinpei; Takahashi, Yoshiaki; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Kuramoto, Takanori; Higuchi, Kazuhide

    2016-01-01

    Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20–65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary. PMID:27895392

  15. Polybutadiene and Styrene-Butadiene rubbers for high-dose dosimetry

    SciTech Connect

    Oliveira, Lucas N.; Vieira, Silvio L.; Schimidt, Fernando; Antonio, Patricia L.; Caldas, Linda V.E.

    2015-07-01

    Polybutadiene and Styrene-Butadiene are synthetical rubbers used widely for pneumatic tires manufacturing. In this research, the dosimeter characteristics of those rubbers were studied for application in high-dose dosimetry. The rubber samples were irradiated with doses of 10 Gy up to 10 kGy, using a {sup 60}Co Gamma Cell-220 system (dose rate of 1.089 kGy/h) and their readings were taken on a Fourier Transform Infrared Spectroscopy-FTIR system (model Frontier/Perkin Elmer). The ratios of two absorbance peaks were taken for each kind of rubber spectrum, Polybutadiene (1306/1130 cm{sup -1}) and Styrene-Butadiene (1449/1306 cm{sup -1}). The ratio calculated was used as the response to the irradiation, and is not uniform across the sample. From the results, it can be concluded for both rubbers: a) the dose-response curves may be useful for high-dose dosimetry (greater than 250 Gy); b) their response for reproducibility presented standard deviations lower than 2.5%; c) the relative sensitivity was higher for Styrene-Butadiene (1.86 kGy{sup -1}) than for Polybutadiene (1.81 kGy{sup -1}), d) for doses of 10 kGy to 200 kGy, there was no variation in the dosimetric response. Both types of rubber samples showed usefulness as high-dose dosimeters. (authors)

  16. Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer.

    PubMed

    Schöttle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Florin, Alexandra; Rokitta, Dennis; Hinze, Yvonne; Dietlein, Felix; Plenker, Dennis; König, Katharina; Albus, Kerstin; Heuckmann, Johannes M; Rauh, Daniel; Franz, Thomas; Neumaier, Bernd; Fuhr, Uwe; Heukamp, Lukas C; Ullrich, Roland T

    2015-11-17

    Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy.

  17. High and low dose radiation effects on mammary adenocarcinoma cells - an epigenetic connection.

    PubMed

    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.

  18. 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

  19. 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.

  20. 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.

  1. Can high dose rates used in cancer radiotherapy change therapeutic effectiveness?

    PubMed Central

    Konopacka, Maria; Sochanik, Aleksander; Ślosarek, Krzysztof

    2017-01-01

    Current cancer radiotherapy relies on increasingly high dose rates of ionising radiation (100–2400 cGy/min). It is possible that changing dose rates is not paralleled by treatment effectiveness. Irradiating cancer cells is assumed to induce molecular alterations that ultimately lead to apoptotic death. Studies comparing the efficacy of radiation-induced DNA damage and apoptotic death in relation to varying dose rates do not provide unequivocal data. Whereas some have demonstrated higher dose rates (single dose) to effectively kill cancer cells, others claim the opposite. Recent gene expression studies in cells subject to variable dose rates stress alterations in molecular signalling, especially in the expression of genes linked to cell survival, immune response, and tumour progression. Novel irradiation techniques of modern cancer treatment do not rely anymore on maintaining absolute constancy of dose rates during radiation emission: instead, timing and exposure areas are regulated temporally and spatially by modulating the dose rate and beam shape. Such conditions may be reflected in tumour cells’ response to irradiation, and this is supported by the references provided. PMID:28239281

  2. Clinical effect of preoperative high-dose atorvastatin against no-reflow after PCI

    PubMed Central

    Liu, Wenbo; Zou, Zhipeng; Jiang, Haipeng; Li, Qiang; Guo, Fangming; Wang, Zhen; Zhu, Hongguang

    2017-01-01

    The aim of the present study was to evaluate the use of preoperative high-dose atorvastatin to prevent the no-reflow phenomenon after percutaneous coronary intervention (PCI). A total of 138 patients with ST-segment elevation myocardial infarction, admitted from March 2014 to January 2015, were enrolled and randomly divided into 3 groups of 46 individuals each. The groups included a control group in which patients were not treated with atorvastatin before PCI; a conventional-dose atorvastatin treatment group in which patients received a single dose of 20 mg at bedtime one day prior to PCI; and a high-dose atorvastatin treatment group in which patients were treated with 40 mg divided in two doses the day before PCI. The treatment effects were assessed by re-examining the echocardiography, high-sensitivity C-reactive protein and brain natriuretic peptide (BNP) levels after the PCI. The follow-up examinations included determinations of ultrasound imaging indicators and the contact with patients was maintained for a whole year. The CTFC (frame), pro-BNP, CK-MB peak and WMSI levels of the patients in the high-dose treatment group were significantly lower than those in the conventional dose or the control group. Trombolysis in myocardial infarction ≤2 and myocardial blush grade ≤1 levels were significantly lower than those in the conventional dose group (P=0.01) or those in the control group (P=0.01), although the echocardiographic indicators of the three groups were not significantly different (P<0.05). Nevertheless, it was found that there were significantly fewer adverse cardiovascular events in the high-dose group (P<0.05 in both cases). During the follow-up period, thromboembolism and restenosis were most infrequent in the high-dose atorvastatin group. Based on our findings the oral administration of high-dose atorvastatin before bedtime, one day before the procedure, can effectively prevent no-reflow cases, reduce adverse events and improve the long

  3. 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.

  4. Quantification of omeprazole degradation by enteric coating polymers: an UV-VIS spectroscopy study.

    PubMed

    Riedel, A; Leopold, C S

    2005-02-01

    The aim of this study was to investigate the degradation of the acid-labile proton-pump-inhibitor omeprazole in organic polymer solutions and aqueous dispersions of enteric coating polymers by UV spectroscopy. Furthermore, data were compared with those obtained in a previous HPLC study. For comparative purposes the cationic Eudragit RS 100 and the monomeric acid acetic acid were included in this study. The discolorations of degraded omeprazole solutions were analysed by VIS spectroscopy. UV-VIS spectra were recorded after preparation of the solutions and after 180 min of storage. The change of absorption was calculated as the difference of the absorption values at 305 nm. Degradation of omeprazole depends on the amount of acidic groups in the polymer structure. This decomposition manifests itself in a shifting of the absorption maximum to lower wavelengths and a decrease of absorption intensity. UV-VIS spectroscopy was used to determine the extent of degradation induced by enteric polymers. A good correlation of these results with previous HPLC data was found when excluding UV absorbing polymers. Nevertheless, values obtained by UV-VIS spectroscopy were always lower than those obtained by HPLC. For evaluation of the discoloration of degraded omeprazole solutions, VIS spectroscopy is a simple and fast method.

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

    PubMed Central

    Shah, Jan Muhammad; Qureshi, Toufique Ahmed; Shah, Tahmina; Shah, Qurban Ali; Arain, Muhammad Asif; Bhutto, Zohaib Ahmed; Saeed, Muhammad; Siyal, Farman Ali

    2016-01-01

    Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex) with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w.) and high doses (40 and 60 mg) of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin on all timings, and increased (p<0.05) the serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate-pyruvate transaminase (SGPT) levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg) significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01) increased at all timing points. Creatinine values were altered (p<0.01, <0.05) in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05) for 72 h and 60 mg persisted same effect (p<0.01) up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05) at all timings. The bilirubin indexes also (p<0.05) elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin. PMID:27847425

  6. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: the Gastrointestinal Tumor Study Group. [X ray

    SciTech Connect

    Moertel, C.G.; Frytak, S.; Hahn, R.G.

    1981-10-15

    One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 5 1/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level. The toxic reactions related to the treatment are discussed.

  7. Comparison of consolidation strategies in acute myeloid leukemia: high-dose cytarabine alone versus intermediate-dose cytarabine combined with anthracyclines.

    PubMed

    Kim, Dae Sik; Kang, Ka-Won; Lee, Se Ryeon; Park, Yong; Sung, Hwa Jung; Kim, Seok Jin; Choi, Chul Won; Kim, Byung Soo

    2015-09-01

    We compared the efficacy of high-dose cytarabine alone to that of intermediate-dose cytarabine combined with anthracyclines as consolidation therapy. Patients enrolled in the Korea University acute myeloid leukemia (AML) registry received remission induction chemotherapy with the same standard induction regimen (idarubicin and cytarabine 3 + 7). Postremission therapy was performed for three or four cycles according to one of the following regimens: high-dose cytarabine (3 g/m(2)) or combination of intermediate-dose cytarabine (1 g/m(2)) with anthracyclines (idarubicin or mitoxantrone). Among the 443 AML patients enrolled in the registry, 145 patients received consolidation chemotherapy. The median overall survival (OS) and relapse-free survival (RFS) in the high-dose cytarabine group were significantly longer than those in the anthracycline combination group (OS, not reached vs. 16.6 months, p = 0.045; RFS, 38.6 months vs. 11.0 months, p = 0.011). The median duration of neutropenia was longer in the anthracycline combination group than in the high-dose cytarabine group (8 vs. 10 days, p = 0.001). This study suggests that high-dose cytarabine consolidation may produce superior outcomes than combination treatment with intermediate-dose cytarabine and anthracyclines and that the addition of anthracyclines during AML consolidation has limited value as compared to cytarabine intensification.

  8. 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.

  9. Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer

    PubMed Central

    Petsuksiri, J; Chansilpa, Y; Hoskin, P J

    2014-01-01

    Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90–100% and 70–90%, respectively). PMID:24807067

  10. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

  11. 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.

  12. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2010-06-01

    prostate and the protection to the urethra , rectum, and bladder for prostate cancer patients treated with High Dose Rate (HDR) brachytherapy. The multi...and the protection to the urethra , rectum and bladder for prostate cancer patients treated with HDR brachytherapy. BODY The feasibility...of the DIL without compromising the dose coverage of the prostate and the protection to the urethra , rectum, and bladder for prostate cancer patients

  13. Effects of long term low- and high-dose sodium arsenite exposure in human transitional cells

    PubMed Central

    He, Jianming; Wang, Feng; Luo, Fen; Chen, Xuedan; Liang, Xi; Jiang, Wenbin; Huang, Zhizhong; Lei, Jiafan; Shan, Fabo; Xu, Xueqing

    2017-01-01

    Epidemiological studies have revealed the association between increased risk of bladder cancer and chronic arsenic exposure. Here, we explored biological effects of arsenic in T24. Microarray analysis was applied to analyze mRNA in T24 following 0, 2 or 5 μM sodium arsenite (As) exposure for 72 hours. Long term (up to 140 days) low-dose (200 nM) and high-dose (1,000 nM) As decreased E-cadherin protein level through different mechanisms because the mRNA levels of E-cadherin increased following low-dose As exposure but decreased following high-dose As exposure. Long term As increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Low-dose As exposure resulted in a change in the morphology of T24 cells from an epithelial to a mesenchymal-like appearance. Knockdown of E-cadherin increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Cell proliferation and growth of T24 with or without As exposure for 100 days were assayed using EdU and WST, respectively. Low-dose As exposure increased cell proliferation and growth while high-dose As exposure decreased both. Long term As activated p53 on account of increasing protein levels of p53, p-p53 (Ser15), and mRNA levels of p21. These demonstrate that arsenic exposure exerts multiple effects. Long term low- or high-dose arsenic induces epithelial-mesenchymal transition, likely via downregulation of E-cadherin, activates p53, and differently affects cell proliferation/growth. PMID:28337271

  14. Early effects of oral administration of omeprazole and roxatidine on intragastric pH

    PubMed Central

    Iida, Hiroshi; Kato, Shingo; Sekino, Yusuke; Sakai, Eiji; Uchiyama, Takashi; Endo, Hiroki; Hosono, Kunihiro; Sakamoto, Yasunari; Fujita, Koji; Yoneda, Masato; Koide, Tomoko; Takahashi, Hirokazu; Tokoro, Chikako; Goto, Ayumu; Abe, Yasunobu; Kobayashi, Noritoshi; Kubota, Kensuke; Gotoh, Eiji; Maeda, Shin; Nakajima, Atsushi; Inamori, Masahiko

    2012-01-01

    Objective: The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress-related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods: Ten Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral administration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period. Results: During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole (median: 4.45 vs. 2.65; P=0.0367). Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg (median: 90.6% vs. 55.2%, P=0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively). Conclusions: In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg. PMID:22205617

  15. 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

  16. 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

  17. Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose Tigecycline.

    PubMed

    Vila, Andrea; Pagella, Hugo; Amadio, Claudio; Leiva, Alejandro

    2016-12-01

    Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline. Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30-60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is

  18. Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose Tigecycline

    PubMed Central

    Pagella, Hugo; Leiva, Alejandro

    2016-01-01

    Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline. Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30–60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is

  19. 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.

  20. Comparative dosimetry of GammaMed Plus high-dose rate 192Ir brachytherapy source

    PubMed Central

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

    2010-01-01

    The comparative dosimetry of GammaMed (GM) Plus high-dose rate brachytherapy source was performed by an experiment using 0.1-cc thimble ionization chamber and simulation-based study using EGSnrc code. In-water dose measurements were performed with 0.1-cc chamber to derive the radial dose function (r = 0.8 to 20.0 cm) and anisotropy function (r = 5.0 cm with polar angle from 10° to 170°). The nonuniformity correction factor for 0.1-cc chamber was applied for in-water measurements at shorter distances from the source. The EGSnrc code was used to derive the dose rate constant (Λ), radial dose function gL(r) and anisotropy function F(r, θ) of GM Plus source. The dosimetric data derived using EGSnrc code in our study were in very good agreement relative to published data for GM Plus source. The radial dose function up to 12 cm derived from measured dose using 0.1-cc chamber was in agreement within ±3% of data derived by the simulation study. PMID:20927220

  1. 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.

  2. Mapping of dose distribution from IMRT onto MRI-guided high dose rate brachytherapy using deformable image registration for cervical cancer treatments: preliminary study with commercially available software

    PubMed Central

    Huq, M. Saiful; Houser, Chris; Beriwal, Sushil; Michalski, Dariusz

    2014-01-01

    Purpose For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV). Material and methods Nine cervical cancer patients were treated to a total dose of 45 Gy in 25 fractions using intensity-modulated radiation therapy (IMRT), followed by MRI-based 3D high dose rate (HDR) brachytherapy. Retrospectively, the IMRT planning CT images were fused with the MR image for each fraction of brachytherapy using deformable image registration. The deformed IMRT dose onto MR images were converted to EQD2 and compared to the uniform dose assumption. Results For all patients, the EQD2 from the EBRT phase was significantly higher with deformable registration than with the conventional uniform dose distribution assumption. The mean EQD2 ± SD for HR-CTV D90 was 45.7 ± 0.7 Gy vs. 44.3 Gy for deformable vs. uniform dose distribution, respectively (p < 0.001). The dose to 2 cc of the bladder, rectum, and sigmoid was 46.4 ± 1.2 Gy, 46.2 ± 1.0 Gy, and 48.0 ± 2.5 Gy, respectively with deformable dose distribution, and was significantly higher than with uniform dose distribution (43.2 Gy for all OAR, p < 0.001). Conclusions This study reveals that deformed EBRT dose distribution to HR-CTV and OARs in MR images for brachytherapy is technically feasible, and achieves differences compared to a uniform dose distribution. Therefore, the assumption that EBRT contributes the same dose value may need to be carefully investigated further based on deformable image registration. PMID:25097559

  3. Objective method to report planner-independent skin/rib maximal dose in balloon-based high dose rate (HDR) brachytherapy for breast cancer

    SciTech Connect

    Kim, Yongbok; Trombetta, Mark G.

    2011-04-15

    Purpose: An objective method was proposed and compared with a manual selection method to determine planner-independent skin and rib maximal dose in balloon-based high dose rate (HDR) brachytherapy planning. Methods: The maximal dose to skin and rib was objectively extracted from a dose volume histogram (DVH) of skin and rib volumes. A virtual skin volume was produced by expanding the skin surface in three dimensions (3D) external to the breast with a certain thickness in the planning computed tomography (CT) images. Therefore, the maximal dose to this volume occurs on the skin surface the same with a conventional manual selection method. The rib was also delineated in the planning CT images and its maximal dose was extracted from its DVH. The absolute (Abdiff=|D{sub max}{sup Man}-D{sub max}{sup DVH}|) and relative (Rediff[%]=100x(|D{sub max}{sup Man}-D{sub max}{sup DVH}|)/D{sub max}{sup DVH}) maximal skin and rib dose differences between the manual selection method (D{sub max}{sup Man}) and the objective method (D{sub max}{sup DVH}) were measured for 50 balloon-based HDR (25 MammoSite and 25 Contura) patients. Results: The average{+-}standard deviation of maximal dose difference was 1.67%{+-}1.69% of the prescribed dose (PD). No statistical difference was observed between MammoSite and Contura patients for both Abdiff and Rediff[%] values. However, a statistically significant difference (p value <0.0001) was observed in maximal rib dose difference compared with maximal skin dose difference for both Abdiff (2.30%{+-}1.71% vs 1.05%{+-}1.43%) and Rediff[%] (2.32%{+-}1.79% vs 1.21%{+-}1.41%). In general, rib has a more irregular contour and it is more proximally located to the balloon for 50 HDR patients. Due to the inverse square law factor, more dose difference was observed in higher dose range (D{sub max}>90%) compared with lower dose range (D{sub max}<90%): 2.16%{+-}1.93% vs 1.19%{+-}1.25% with p value of 0.0049. However, the Rediff[%] analysis eliminated the

  4. The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model.

    PubMed

    Garofalo, Michael; Bennett, Alexander; Farese, Ann M; Harper, Jamie; Ward, Amanda; Taylor-Howell, Cheryl; Cui, Wanchang; Gibbs, Allison; Lasio, Giovanni; Jackson, William; MacVittie, Thomas J

    2014-01-01

    Several radiation dose- and time-dependent tissue sequelae develop following acute high-dose radiation exposure. One of the recognized delayed effects of such exposures is lung injury, characterized by respiratory failure as a result of pneumonitis that may subsequently develop into lung fibrosis. Since this pulmonary subsyndrome may be associated with high morbidity and mortality, comprehensive treatment following high-dose irradiation will ideally include treatments that mitigate both the acute hematologic and gastrointestinal subsyndromes as well as the delayed pulmonary syndrome. Currently, there are no drugs approved by the Food and Drug Administration to counteract the effects of acute radiation exposure. Moreover, there are no relevant large animal models of radiation-induced lung injury that permit efficacy testing of new generation medical countermeasures in combination with medical management protocols under the FDA animal rule criteria. Herein is described a nonhuman primate model of delayed lung injury resulting from whole thorax lung irradiation. Rhesus macaques were exposed to 6 MV photon radiation over a dose range of 9.0-12.0 Gy and medical management administered according to a standardized treatment protocol. The primary endpoint was all-cause mortality at 180 d. A comparative multiparameter analysis is provided, focusing on the lethal dose response relationship characterized by a lethal dose50/180 of 10.27 Gy [9.88, 10.66] and slope of 1.112 probits per linear dose. Latency, incidence, and severity of lung injury were evaluated through clinical and radiographic parameters including respiratory rate, saturation of peripheral oxygen, corticosteroid requirements, and serial computed tomography. Gross anatomical and histological analyses were performed to assess radiation-induced injury. The model defines the dose response relationship and time course of the delayed pulmonary sequelae and consequent morbidity and mortality. Therefore, it may provide

  5. 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

  6. D-Shuttle project: measurement and comparison of individual doses of high school students.

    PubMed

    Hara, T; Anzai, S; Saito, M; Fijiwara, Y

    2016-09-27

    In 2014, a team of high school students and teachers measured individual exposure doses using D-Shuttle dosimeters. In total, 216 students and teachers participated in the project, with the cooperation of 12 high schools in Japan (six from Fukushima Prefecture), four from France, eight from Poland, and two from Belarus. The participants wore the dosimeters for 2 weeks and recorded their locations in diary charts. The distribution of annual exposure doses for each school and region, estimated from the measured results, overlapped. It was concluded that the external exposure of high school students in Fukushima Prefecture was not markedly higher compared with that of students from other regions.

  7. 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.

  8. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    PubMed

    Yang, Yang; Jing, Xiao-Peng; Zhang, Shou-Peng; Gu, Run-Xia; Tang, Fang-Xu; Wang, Xiu-Lian; Xiong, Yan; Qiu, Mei; Sun, Xu-Ying; Ke, Dan; Wang, Jian-Zhi; Liu, Rong

    2013-01-01

    Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.

  9. High-dose-rate brachytherapy boost for prostate cancer: rationale and technique.

    PubMed

    Morton, Gerard C

    2014-10-01

    High-dose-rate brachytherapy (HDR) is a method of conformal dose escalation to the prostate. It can be used as a local boost in combination with external beam radiotherapy, with a high degree of efficacy and low rate of long term toxicity. Data consistently reports relapse free survival rates of greater than 90% for intermediate risk patients and greater than 80% for high risk. Results are superior to those achieved with external beam radiotherapy alone. A wide range of dose and fractionation is reported, however, we have found that a single 15 Gy HDR combined with hypofractionated radiotherapy to a dose of 37.5 Gy in 15 fractions is well tolerated and is associated with a long term relapse-free survival of over 90%. Either CT-based or trans-rectal ultrasound-based planning may be used. The latter enables treatment delivery without having to move the patient with risk of catheter displacement. We have found it to be an efficient and quick method of treatment, allowing catheter insertion, planning, and treatment delivery to be completed in less than 90 minutes. High-dose-rate boost should be considered the treatment of choice for many men with high and intermediate risk prostate cancer.

  10. High dose and low dose Lactobacilli acidophilus exerted differential immune modulating effects on T cell immune responses induced by an oral human rotavirus vaccine in gnotobiotic pigs

    PubMed Central

    Wen, Ke; Li, Guohua; Bui, Tammy; Liu, Fangning; Li, Yanru; Kocher, Jacob; Lin, Lin; Yang, Xingdong; Yuan, Lijuan

    2011-01-01

    Background Strain-specific effects of probiotics in pro- or anti-inflammatory immune responses have been well recognized. Several proinflammatory Lactobacillus strains have been shown to act as adjuvants to enhance the immunogenicity of vaccines. However, dose effects of probiotics in modulating immune responses are not clearly understood. This study examined the dose effects of Lactobacillus acidophilus (LA) NCFM strain on T cell immune responses to rotavirus vaccination in a gnotobiotic (Gn) pig model. Methods Frequencies of IFN-γ producing CD4+ and CD8+ T cell and IL-10 and TGF-β producing CD4+CD25+ and CD4+CD25- regulatory T (Treg) cell responses were determined in the intestinal and systemic lymphoid tissues of Gn pigs vaccinated with an oral human rotavirus vaccine in conjunction with low dose (5 feedings; up to 106 colony forming units [CFU]/dose) or high dose (14 feedings; up to 109 CFU/dose) or without LA feeding. Results Low dose LA significantly promoted IFN-γ producing T cell responses and down-regulated Treg cell responses and their TGF-β and IL-10 productions in all the tissues compared to the high dose LA and control groups. To the contrary, high dose LA increased the frequencies of Treg cells in most of the tissues compared to the control groups. The dose effects of LA on IFN-γ producing T cell and CD4+CD25- Treg cell immune responses were similar in the intestinal and systemic lymphoid tissues and were independent from the vaccination. Conclusion Thus the same probiotic strain in different doses can either promote or suppress IFN-γ producing T cell or Treg cell immune responses. These findings have significant implications in the use of probiotic lactobacilli as immunostimulatory versus immunoregulatory agents. Probiotics can be ineffective or even detrimental if not used at the optimal dosage for the appropriate purposes. PMID:22178726

  11. The Effect of High-Dose Ionizing Radiation on the Astrobiological Model Lichen Circinaria gyrosa.

    PubMed

    de la Torre, Rosa; Miller, Ana Zélia; Cubero, Beatriz; Martín-Cerezo, M Luisa; Raguse, Marina; Meeßen, Joachim

    2017-02-01

    The lichen Circinaria gyrosa is an astrobiological model defined by its high capacity of resistance to space conditions and to a simulated martian environment. Therefore, it became part of the currently operated BIOMEX experiment on board the International Space Station and the recent STARLIFE campaign to study the effects of four types of space-relevant ionizing radiation. The samples were irradiated with helium and iron ions at doses up to 2 kGy, with X-rays at doses up to 5 kGy and with γ rays at doses from 6 to 113 kGy. Results on C. gyrosa's resistance to simulated space ionizing radiation and its post-irradiation viability were obtained by (i) chlorophyll a fluorescence of photosystem II (PSII), (ii) epifluorescence microscopy, (iii) confocal laser scanning microscopy (CLSM), and (iv) field emission scanning electron microscopy (FESEM). Results of photosynthetic activity and epifluorescence show no significant changes up to a dose of 1 kGy (helium ions), 2 kGy (iron ions), 5 kGy (X-rays)-the maximum doses applied for those radiation qualities-as well as a dose of 6 kGy of γ irradiation, which was the lowest dose applied for this low linear energy transfer (LET) radiation. Significant damage in a dose-related manner was observed only at much higher doses of γ irradiation (up to 113 kGy). These data corroborate the findings of the parallel STARLIFE studies on the effects of ionizing radiation on the lichen Circinaria gyrosa, its isolated photobiont, and the lichen Xanthoria elegans. Key Words: Simulated space ionizing radiation-Gamma rays-Extremotolerance-Lichens-Circinaria gyrosa-Photosynthetic activity. Astrobiology 17, 145-153.

  12. Single versus multichannel applicator in high-dose-rate vaginal brachytherapy optimized by inverse treatment planning

    PubMed Central

    Constantinescu, Camelia; Hassouna, Ashraf H.; Eltaher, Maha M.; Ghassal, Noor M.; Awad, Nesreen A.

    2014-01-01

    Purpose To retrospectively compare the potential dosimetric advantages of a multichannel vaginal applicator vs. a single channel one in intracavitary vaginal high-dose-rate (HDR) brachytherapy after hysterectomy, and evaluate the dosimetric advantage of fractional re-planning. Material and methods We randomly selected 12 patients with endometrial carcinoma, who received adjuvant vaginal cuff HDR brachytherapy using a multichannel applicator. For each brachytherapy fraction, two inverse treatment plans (for central channel and multichannel loadings) were performed and compared. The advantage of fractional re-planning was also investigated. Results Dose-volume-histogram (DVH) analysis showed limited, but statistically significant difference (p = 0.007) regarding clinical-target-volume dose coverage between single and multichannel approaches. For the organs-at-risk rectum and bladder, the use of multichannel applicator demonstrated a noticeable dose reduction, when compared to single channel, but statistically significant for rectum only (p = 0.0001). For D2cc of rectum, an average fractional dose of 6.1 ± 0.7 Gy resulted for single channel vs. 5.1 ± 0.6 Gy for multichannel. For D2cc of bladder, an average fractional dose of 5 ± 0.9 Gy occurred for single channel vs. 4.9 ± 0.8 Gy for multichannel. The dosimetric benefit of fractional re-planning was demonstrated: DVH analysis showed large, but not statistically significant differences between first fraction plan and fractional re-planning, due to large inter-fraction variations for rectum and bladder positioning and filling. Conclusions Vaginal HDR brachytherapy using a multichannel vaginal applicator and inverse planning provides dosimetric advantages over single channel cylinder, by reducing the dose to organs at risk without compromising the target volume coverage, but at the expense of an increased vaginal mucosa dose. Due to large inter-fraction dose variations, we recommend individual fraction treatment plan

  13. The Effect of High-Dose Ionizing Radiation on the Astrobiological Model Lichen Circinaria gyrosa

    NASA Astrophysics Data System (ADS)

    de la Torre, Rosa; Zélia Miller, Ana; Cubero, Beatriz; Martín-Cerezo, M. Luisa; Raguse, Marina; Meeßen, Joachim

    2017-02-01

    The lichen Circinaria gyrosa is an astrobiological model defined by its high capacity of resistance to space conditions and to a simulated martian environment. Therefore, it became part of the currently operated BIOMEX experiment on board the International Space Station and the recent STARLIFE campaign to study the effects of four types of space-relevant ionizing radiation. The samples were irradiated with helium and iron ions at doses up to 2 kGy, with X-rays at doses up to 5 kGy and with γ rays at doses from 6 to 113 kGy. Results on C. gyrosa's resistance to simulated space ionizing radiation and its post-irradiation viability were obtained by (i) chlorophyll a fluorescence of photosystem II (PSII), (ii) epifluorescence microscopy, (iii) confocal laser scanning microscopy (CLSM), and (iv) field emission scanning electron microscopy (FESEM). Results of photosynthetic activity and epifluorescence show no significant changes up to a dose of 1 kGy (helium ions), 2 kGy (iron ions), 5 kGy (X-rays) - the maximum doses applied for those radiation qualities - as well as a dose of 6 kGy of γ irradiation, which was the lowest dose applied for this low linear energy transfer (LET) radiation. Significant damage in a dose-related manner was observed only at much higher doses of γ irradiation (up to 113 kGy). These data corroborate the findings of the parallel STARLIFE studies on the effects of ionizing radiation on the lichen Circinaria gyrosa, its isolated photobiont, and the lichen Xanthoria elegans.

  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 grid algorithm for high throughput fitting of dose-response curve data.

    PubMed

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-10-21

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program's performance in reproducing the actual values that were used to generate the simulated data and compared it with the DRC package for the language and environment R and the XLfit add-in for Microsoft Excel. The Grid program was robust and consistently recovered the actual values for both complete and partial curves with or without noise. Both DRC and XLfit performed well on data without noise, but they were sensitive to and their performance degraded rapidly with increasing noise. The Grid program is automated and scalable to millions of dose-response curves, and it is able to process 100,000 dose-response curves from high throughput screening experiment per CPU hour. The Grid program has the potential of greatly increasing the productivity of large-scale dose-response data analysis and early drug discovery processes, and it is also applicable to many other curve fitting problems in chemical, biological, and medical sciences.

  17. High dose anakinra for treatment of severe neonatal Kawasaki disease: a case report

    PubMed Central

    2014-01-01

    We report an 11-week-old female who presented with Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS). The infant presented to the hospital with persistent fever, cough, diarrhea, and emesis, among other symptoms. Her condition quickly began to decompensate, and she developed classic features (conjunctivitis, rash, cracked lips, distal extremity edema) prompting a diagnosis of acute KD. The patient was treated with standard therapy for KD including three doses of intravenous immunoglobulin (IVIG), aspirin, and high dose glucocorticoids with no change in her condition. Due to a high suspicion for MAS, high dose anakinra therapy was initiated resulting in dramatic clinical improvements. She also received one dose of infliximab for concern for coronary artery changes, and over the course of several months, anakinra and high dose glucocorticoids were tapered. Nearly complete reversal of echocardiogram changes were observed after 8 months, and the infant is now off all immunosuppressive therapy. In this case report, we briefly review the importance of early recognition of MAS in pediatric patient populations with rheumatic diseases, and we suggest early initiation of anakinra therapy as a rapid and effective treatment option. PMID:25045337

  18. 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.

  19. Influence of early high-dose steroid treatment on Bell's palsy evolution.

    PubMed

    Lagalla, G; Logullo, F; Di Bella, P; Provinciali, L; Ceravolo, M G

    2002-09-01

    The objective of this double-blind, randomized, placebo-controlled study was to test the efficacy of high-dose prednisone, administered as early as possible, in modifying the natural progression of Bell's palsy. Sixty-two consecutive patients, enrolled within 72 hours of facial palsy onset, were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy (group A) or polyvitaminic therapy alone (group B). Clinical grading of facial muscle strength and length of absence from work were evaluated. An early worsening of facial muscle strength was observed in controls, leading to the divergence in the trends of the grading scores in the two groups; this result was not confirmed in the long-term follow-up. Treated patients returned to work earlier than controls. In conclusion, early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell's palsy.

  20. [Omeprazol and ezomeprazol pharmacokinetics, duration of antisecretory effect, and reasons for their probable changes in duodenal ulcer].

    PubMed

    Serebrova, S Iu; Starodubtsev, A K; Pisarev, V V; Kondratenko, S N; Vasilenko, G F; Dobrovol'skiĭ, O V

    2009-01-01

    There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability.

  1. 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.

  2. 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

  3. 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

  4. Possible use of EPDM in radioactive waste disposal: Long term low dose rate and short term high dose rate irradiation in aquatic and atmospheric environment

    NASA Astrophysics Data System (ADS)

    Hacıoğlu, Fırat; Özdemir, Tonguç; Çavdar, Seda; Usanmaz, Ali

    2013-02-01

    In this study, changes in the properties of ethylene propylene diene terpolymer (EPDM) irradiated with different dose rates in ambient atmosphere and aqueous environment were investigated. Irradiations were carried out both with low dose and high dose rate irradiation sources. EPDM samples which were differentiated from each other by peroxide type and 5-ethylidene 2-norbornene (ENB) contents were used. Long term low dose rate irradiations were carried out for the duration of up to 2.5 years (total dose of 1178 kGy) in two different irradiation environments. Dose rates (both high and low), irradiation environments (in aquatic and open to atmosphere), and peroxide types (aliphatic or aromatic) were the parameters studied. Characterization of irradiated EPDM samples were performed by hardness, compression, tensile, dynamic mechanical analysis (DMA), TGA-FTIR, ATR-FTIR, XRD and SEM tests. It was observed that the irradiation in water environment led to a lower degree of degradation when compared to that of irradiation open to atmosphere for the same irradiation dose. In addition, irradiation environment, peroxide type and dose rate had effects on the extent of change in the properties of EPDM. It was observed that EPDM is relatively radiation resistant and a candidate polymer for usage in radioactive waste management.

  5. Progressive muscle weakness after high-dose steroids in two children with CIDP.

    PubMed

    Rostasy, Kevin M; Diepold, Katharina; Buckard, Johannes; Brockmann, Knut; Wilken, Bernd; Hanefeld, Folker

    2003-09-01

    Corticosteroids and intravenous immunoglobulins belong to the first line of treatment in chronic inflammatory demyelinating polyneuropathy. In patients with a progressive course, plasma exchange and immunomodulatory drugs are added to the regimen. To reduce the side effects of long-term oral prednisolone, high-dose pulsatile intravenous methylprednisolone treatment has been advocated. We report two children with chronic inflammatory demyelinating polyneuropathy who, after high-dose intravenous pulsatile methylprednisolone, experienced a significant clinical deterioration with profound loss of muscle strength. Both patients improved after changing treatment to immunoglobulins in one and cyclosporine combined with immunoglobulins and oral prednisolone in the other.

  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. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.

    PubMed

    Herrlinger, Ulrich; Küker, Wilhelm; Uhl, Martin; Blaicher, Hans-Peter; Karnath, Hans-Otto; Kanz, Lothar; Bamberg, Michael; Weller, Michael

    2005-06-01

    The NOA-03 trial explored high-dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole-brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high-dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long-term surviving patients.

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

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation

    SciTech Connect

    Speiser, B.L. ); Spratling, L.

    1993-03-15

    The purpose of the study was to describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree. Patients were treated by protocol with medium dose rate, 47 patients receiving 1000 cGy at a 5 mm depth times three fractions, high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving cGy at a 10 mm depth for three fractions followed by bronchoscopy. Incidence of this entity was 9% for the first group, 12% for the second, and 13% for the third group. Reactions were grade 1 consisting of mild inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient; grade 2, thicker complete white circumferential membrane with cough and/or obstructive problems requiring intervention; grade 3, severe inflammatory response with marked membranous exudate and mild fibrotic reaction; and grade 4 a predominant fibrotic reaction with progressive stenosis. Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included: large cell carcinoma histology, curative intent, prior laser photoresection, and/or concurrent external radiation. Survival was the strongest predictor of the reaction. Radiation bronchitis and stenosis is a new clinical entity that must be identified in bronchial brachytherapy patients and treated appropriately. 23 refs., 3 figs., 7 tabs.

  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. Dosimetric perturbations of a lead shield for surface and interstitial high-dose-rate brachytherapy.

    PubMed

    Candela-Juan, Cristian; Granero, Domingo; Vijande, Javier; Ballester, Facundo; Perez-Calatayud, Jose; Rivard, Mark J

    2014-06-01

    In surface and interstitial high-dose-rate brachytherapy with either (60)Co, (192)Ir, or (169)Yb sources, some radiosensitive organs near the surface may be exposed to high absorbed doses. This may be reduced by covering the implants with a lead shield on the body surface, which results in dosimetric perturbations. Monte Carlo simulations in Geant4 were performed for the three radionuclides placed at a single dwell position. Four different shield thicknesses (0, 3, 6, and 10 mm) and three different source depths (0, 5, and 10 mm) in water were considered, with the lead shield placed at the phantom surface. Backscatter dose enhancement and transmission data were obtained for the lead shields. Results were corrected to account for a realistic clinical case with multiple dwell positions. The range of the high backscatter dose enhancement in water is 3 mm for (60)Co and 1 mm for both (192)Ir and (169)Yb. Transmission data for (60)Co and (192)Ir are smaller than those reported by Papagiannis et al (2008 Med. Phys. 35 4898-4906) for brachytherapy facility shielding; for (169)Yb, the difference is negligible. In conclusion, the backscatter overdose produced by the lead shield can be avoided by just adding a few millimetres of bolus. Transmission data provided in this work as a function of lead thickness can be used to estimate healthy organ equivalent dose saving. Use of a lead shield is justified.

  13. Neutron dose measurements with the GSI ball at high-energy accelerators.

    PubMed

    Fehrenbacher, G; Gutermuth, F; Kozlova, E; Radon, T; Schuetz, R

    2007-01-01

    A moderator-type neutron monitor containing pairs of TLD 600/700 elements (Harshaw) modified with the addition of a lead layer (GSI ball) for the measurement of the ambient dose equivalent from neutrons at medium- and high-energy accelerators, is introduced in this work. Measurements were performed with the Gesellschaft für Schwerionenforschung (GSI) ball as well as with conventional polyethylene (PE) spheres at the high-energy accelerator SPS at European Organization for Nuclear Research [CERN (CERF)] and in Cave A of the heavy-ion synchrotron SIS at GSI. The measured dose values are compared with dose values derived from calculated neutron spectra folded with dose conversion coefficients. The estimated reading of the spheres calculated by means of the response functions and the neutron spectra is also included in the comparison. The analysis of the measurements shows that the PE/Pb sphere gives an improved estimate on the ambient dose equivalent of the neutron radiation transmitted through shielding of medium- and high-energy accelerators.

  14. Rectal Dose and Source Strength of the High-Dose-Rate Iridium-192 Both Affect Late Rectal Bleeding After Intracavitary Radiation Therapy for Uterine Cervical Carcinoma

    SciTech Connect

    Isohashi, Fumiaki; Yoshioka, Yasuo; Koizumi, Masahiko

    2010-07-01

    Purpose: The purpose of this study was to reconfirm our previous findings that the rectal dose and source strength both affect late rectal bleeding after high-dose-rate intracavitary brachytherapy (HDR-ICBT), by using a rectal dose calculated in accordance with the definitions of the International Commission on Radiation Units and Measurements Report 38 (ICRU{sub RP}) or of dose-volume histogram (DVH) parameters by the Groupe Europeen de Curietherapie of the European Society for Therapeutic Radiology and Oncology. Methods and Materials: Sixty-two patients who underwent HDR-ICBT and were followed up for 1 year or more were studied. The rectal dose for ICBT was calculated by using the ICRP{sub RP} based on orthogonal radiographs or the DVH parameters based on computed tomography (CT). The total dose was calculated as the biologically equivalent dose expressed in 2-Gy fractions (EQD{sub 2}). The relationship between averaged source strength or the EQD{sub 2} and late rectal bleeding was then analyzed. Results: When patients were divided into four groups according to rectal EQD{sub 2} ({>=} or dose) and source strength ({>=} or <2.4 cGy.m{sup 2}.h{sup -1}), the group with both a high EQD{sub 2} and a high source strength showed a significantly greater probability of rectal bleeding for ICRU{sub RP}, D{sub 2cc}, and D{sub 1cc}. The patients with a median rectal dose above the threshold level did not show a greater frequency of rectal bleeding unless the source strength exceeded 2.4 cGy.m{sup 2}.h{sup -1}. Conclusions: Our results obtained with data based on ICRU{sub RP} and CT-based DVH parameters indicate that rectal dose and source strength both affect rectal bleeding after HDR-ICBT.

  15. 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.

  16. Compatibility of the Linear-Quadratic Formalism and Biologically Effective Dose Concept to High-Dose-Per-Fraction Irradiation in a Murine Tumor

    SciTech Connect

    Otsuka, Shinya; Shibamoto, Yuta; Iwata, Hiromitsu; Murata, Rumi; Sugie, Chikao; Ito, Masato; Ogino, Hiroyuki

    2011-12-01

    Purpose: To evaluate the compliance of linear-quadratic (LQ) model calculations in the high-dose range as used in stereotactic irradiation in a murine tumor model. Methods and Materials: Female 10-week-old Balb/c mice bearing 1-cm-diameter EMT6 tumors in the hind legs were used. Single doses of 10-25 Gy were compared with 2-5 fractions of 4-13 Gy given at 4-hour intervals. Cell survival after irradiation was determined by an in vivo-in vitro assay. Using an {alpha}/{beta} ratio determined for in vitro EMT6 cells and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually measured equivalent single doses for the hypofractionated doses. These fractionation schedules were also compared simultaneously to investigate the concordance/divergence of dose-survival curves plotted against actual radiation doses and biologically effective doses (BED). Results: Equivalent single doses for hypofractionated doses calculated from LQ formalism were lower than actually measured doses by 21%-31% in the 2- or 3-fraction experiments and by 27%-42% in the 4- or 5-fraction experiments. The differences were all significant. When a higher {alpha}/{beta} ratio was assumed, the discrepancy became smaller. In direct comparison of the 2- to 5-fraction schedules, respective dose-response curves almost overlapped when cell survival was plotted against actual radiation doses. However, the curves tended to shift downward by increasing the fraction number when cell survival was plotted against BED calculated using an {alpha}/{beta} ratio of 3.5 Gy for in vitro EMT6 cells. Conclusion: Conversion of hypofractionated radiation doses to single doses using the LQ formalism underestimated the in vivo effect of hypofractionated radiation by approximately 20%-40%. The discrepancy appeared to be larger than that seen in the previous in vitro study and tended to increase with the fraction number. BED appeared to be an unreliable measure

  17. Low and high dose UVB regulation of transcription factor NF-E2-related factor 2.

    PubMed

    Kannan, Sankaranarayanan; Jaiswal, Anil K

    2006-09-01

    Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response element (ARE)-mediated expression and coordinated induction of chemoprotective proteins in response to chemical stress. In this report, we investigated Nrf2 response to low and high dose UVB irradiation. Low dose (7.5 J/m(2)) UVB exposure of mouse hepatoma, mouse keratinocyte, and human skin fibroblast cells led to the nuclear accumulation of Nrf2 and up-regulation of ARE-mediated gene expression. On the contrary, and intriguingly, high dose (20 J/m(2)) UVB exposure of cells led to the nuclear exclusion of Nrf2 and down-regulation of chemoprotective gene expression with possible implications in UVB carcinogenesis. We investigated the mechanism by which high dose UVB induced the nuclear exclusion of Nrf2. Prior treatment with nuclear export inhibitor, leptomycin B, abrogated the UVB-induced nuclear exclusion of Nrf2, indicating that the decrease of Nrf2 in the nucleus was due to the nuclear export of Nrf2. High dose UVB increased the phosphorylation of Nrf2Y568 which stimulated the nuclear export of Nrf2. Mutation of Nrf2Y568 to phenylalanine and src kinase inhibitor PP2 abrogated/reduced the UVB-induced phosphorylation of Nrf2Y568 and nuclear exclusion of Nrf2. Transfection with src family member Fyn small interfering RNA resulted in the nuclear accumulation of Nrf2 and an increase in the expression and UVB induction of ARE-mediated gene expression. UVB exposure also induced the nuclear localization of Fyn. These results suggest that high dose UVB induced the activation/nuclear localization of Fyn which led to increased phosphorylation of Nrf2Y568 and enhanced nuclear export of Nrf2. This resulted in nuclear exclusion of Nrf2 and down-regulation of ARE-mediated chemoprotective gene expression.

  18. 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.

  19. 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

  20. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously

    SciTech Connect

    Urtasun, R.C.; Rabin, H.R.; Partington, J.

    1983-01-01

    This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%.

  1. Comparison of 24-hour intragastric pH using four liquid formulations of lansoprazole and omeprazole.

    PubMed

    Sharma, V K

    1999-12-01

    The results of previous studies evaluating the effect of four liquid formulations of proton-pump inhibitors on 24-hour intragastric pH are described. Patients with a gastrostomy who were resident in a Veterans Affairs medical center or its affiliated nursing home were eligible for enrollment in one of four open-label studies in which each patient served as his own control. Patients underwent 24-hour intragastric pH studies before and after receiving seven consecutive days of one of the following liquid formulations of a proton-pump inhibitor administered once daily: omeprazole granules 20 mg in orange juice, lansoprazole granules 30 mg in orange juice, simplified omeprazole suspension 20 mg, and simplified lansoprazole suspension 30 mg. The suspensions were prepared with 10 mL of 8.4% sodium bicarbonate solution. Mean intragastric pH was measured, as was the time pH stayed above 3.0 and 4.0 during the 24-hour period. Six to 14 patients participated in each study. The mean posttreatment pH was 4.9+/-0.8, 4.7+/-0.6, 4.1+/-1.5, and 5.1+/-1.1 for omeprazole granules in orange juice, lansoprazole granules in orange juice, simplified omeprazole suspension, and simplified lansoprazole suspension, respectively. Both drugs in orange juice maintained pH above 4.0 longer than 14 hours and above 3.0 for close to 20 hours, which are the levels deemed optimal for healing erosive esophagitis and duodenal ulcers, respectively. Simplified lansoprazole suspension maintained pH above those thresholds for the optimal times, but simplified omeprazole suspension did not (20 and 15 hr above 3.0, 17 and 12 hr above 4.0 for lansoprazole and omeprazole, respectively). Further development of liquid formulations of proton-pump inhibitors may have important implications for the treatment of acid-related diseases in patients, including children, who are unable to swallow capsules.

  2. 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.

  3. 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.

  4. High-dose radiation-induced meningiomas following acute lymphoblastic leukemia in children.

    PubMed

    Salvati, M; Cervoni, L; Artico, M

    1996-05-01

    The authors review three personal cases of patients who developed cerebral meningiomas following high-dose radiotherapy for acute lymphoblastic leukemia. Two patients were female and one male. Their ages when the leukemia appeared were between 11 and 15 years. All patients were treated with a course of prophylactic irradiation to the neuraxis for a total dose of 24 Gy. After an average interval of 10.4 years, all three patients presented a meningioma; histologically, one was meningothelial and two were fibrous. All three meningiomas presented atypical features. At follow-up 1, 4, and 4 years respectively after surgery, none of these patients presents neurological deficits or neuroradiological signs of recurrence. Forty-nine cases of high-dose radiation-induced meningioma are also reviewed.

  5. A study of high-dose lenalidomide induction and low-dose lenalidomide maintenance therapy for patients with hypomethylating agent refractory myelodysplastic syndrome.

    PubMed

    Cherian, Mathew A; Tibes, Raoul; Gao, Feng; Fletcher, Theresa; Fiala, Mark; Uy, Geoffrey L; Westervelt, Peter; Jacoby, Meagan A; Cashen, Amanda F; Stockerl-Goldstein, Keith; DiPersio, John F; Vij, Ravi

    2016-11-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by bone marrow failure which frequently progress to acute myeloid leukemia. Patients who fail to respond to, or progress on first-line DNA hypomethylating agents (HMA) have a poor prognosis. Conventionally dosed lenalidomide has activity in 5q-MDS. In other subtypes, it may reduce RBC transfusion requirements but does not result in cytogenetic responses. We previously reported that high-dose lenalidomide induction (50 mg/day) results in complete remissions in a high fraction of patients. We, therefore, conducted a Phase 2 trial of the same regimen in MDS refractory to HMA. Marrow complete remissions were seen in 33% of patients and hematological improvement in 8% of patients. Significant infections complicated more than 50% of cases. Future trials to explore alternative dosing schedules of high-dose lenalidomide to increase efficacy while decreasing toxicity are warranted.

  6. 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

  7. High Dose Astaxanthin Lowers Blood Pressure and Increases Insulin Sensitivity in Rats: Are These Effects Interdependent?

    PubMed Central

    Preuss, Harry G.; Echard, Bobby; Yamashita, Eiji; Perricone, Nicholas V.

    2011-01-01

    The present investigation in Sprague-Dawley rats (SD) was designed to examine effects of astaxanthin (Asta) at different doses on elevated blood pressure (BP) and glucose-insulin perturbations produced by heavy sucrose ingestion. We also examined effects of Asta on BP during restraint stress. SD were divided into six groups each containing eight rats. All SD ate a basic diet of ground regular rat chow with sucrose added at 30% w/w. The Control group received only the basic diet containing added sucrose, while the other five groups each received the same diet with added test material: captopril, (30 mg/Kg), pioglitazone (15.0 mg/Kg), low Asta (25 mg/Kg), medium Asta (50 mg/kg) or high Asta (100 mg/Kg). Many tests were carried out to examine the mechanisms behind the effects of Asta on BP (serum ACE activity, losartan challenge, and LNAME challenge) and the glucose-insulin system (glucose tolerance, HOMA measurement, and insulin challenge). In SD, a relatively low dose of Asta decreased SBP, but produced no major changes in the glucose-insulin system simulating results from a previous study using Zucker Fatty Rats. Increasing the dose of Asta resulted in both a lowering of elevated systolic BP and enhanced insulin sensitivity determined by many different estimations. BP lowering was consistent with changes in the renin-angiotensin (RAS) and nitric oxide (NO) systems. At the examined doses of each, captopril lowered BP in SD without influencing glucose-insulin metabolism, whereas pioglitazone favorably affected glucose-insulin metabolism while showing essentially no effects on BP. Accordingly, Asta beneficially affects both sucrose-induced elevations of BP and insulin resistance at relatively high doses in SD. Also, Asta at higher doses lessens restraint stress, whereas, captopril and pioglitazone did not at the doses examined, even though they influenced the BP and glucose-insulin systems respectively. PMID:21326955

  8. 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

  9. Nephrotoxicity of high-dose ifosfamide/carboplatin/etoposide in adults undergoing autologous stem cell transplantation.

    PubMed

    Agaliotis, D P; Ballester, O F; Mattox, T; Hiemenz, J W; Fields, K K; Zorsky, P E; Goldstein, S C; Perkins, J B; Rosen, R M; Elfenbein, G J

    1997-11-01

    The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.

  10. Neutron spectra and dose equivalents calculated in tissue for high-energy radiation therapy

    PubMed Central

    Kry, Stephen F.; Howell, Rebecca M.; Salehpour, Mohammad; Followill, David S.

    2009-01-01

    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

  11. High-dose chemoradiotherapy (HDC) in the Ewing family of tumors (EFT).

    PubMed

    Burdach, S; Jürgens, H

    2002-02-01

    EFT is defined by the expression of ews/ets fusion genes. The type of the fusion transcript impacts on the clinical biology. EFT requires risk adapted treatment. A risk-adapted treatment is determined by tumor localisation, tumor stage and volume. For metastatic and relapsed disease the pattern of spread and the time of relapse are the determinants of risk stratification. Staging of Ewing tumors has been considerably improved by magnetic resonance imaging and modern isotope scanning techniques. However, the determination of the extent of the metastatic spread in particular number of involved bones remains an unresolved issue. The prognosis for high-risk Ewing tumors has been improved by multimodal and high-dose radio/chemotherapy (HDC). The concepts for high-dose therapy in Ewing tumors are based on dose response and dose intensity relationships. In single agent HDC most experience exists with Melphalan. Several chemotherapeutic agents have been used in combination HDC with or without TBI such as Adriamycin, BCNU, Busulphan, Carboplatin, Cyclophosphamide, Etoposide, Melphalan, Thiotepa Procarbazin and Vincristine. To date, superiority of any high-dose chemotherapy regimen has not been established. However, the clinical biology, the pattern of spread and the time of relapse determine the prognosis of patient who are eligible for HDC. In particular, patients with multifocal bone or bone marrow metastases have a poorer prognosis than patients with lung metastases. In addition, patients with a relapse within 24 months have a poorer prognosis than patients with a relapse later than 24 months after diagnosis. This review will analyze the results of single- and multi-agent chemotherapy with respect to agent combination, dose and risk stratum of patient population. Future therapeutic modalities for the treatment of EFT might encompass immunotherapeutic and genetic strategies including allogeneic stem cell transplantation.

  12. 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

  13. High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

    PubMed Central

    Wada, Akinori; Kohno, Naoaki

    2017-01-01

    Purpose To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT). Material and methods From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT). The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%), 61 patients with 2 high-risk factors (43%), and 22 patients with 3 high-risk factors (15%) including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS) rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF) rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS) rate of 97.2%, and an overall survival (OS) rate of 95.5%. Conclusions High-dose (BED ≥ 220 Gy) radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further. PMID:28344597

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

    PubMed Central

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-01-01

    Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03–1.15]) and basopenia (OR: 6.77; CI 95%: [2.01–22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

  15. High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis.

    PubMed

    Gopal, Ajay K; Gooley, Theodore A; Maloney, David G; Petersdorf, Stephen H; Eary, Janet F; Rajendran, Joseph G; Bush, Sharon A; Durack, Lawrence D; Golden, Jane; Martin, Paul J; Matthews, Dana C; Appelbaum, Frederick R; Bernstein, Irwin D; Press, Oliver W

    2003-10-01

    We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.

  16. 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

  17. Reversible myoclonus, asterixis, and tremor associated with high dose trimethoprim-sulfamethoxazole: a case report

    PubMed Central

    Foo, Dominic

    2016-01-01

    Case Diagnosis Reversible myoclonus, tremor, and asterixis induced by high dose trimethoprim-sulfamethoxazole. Case Description The patient was a 66-year-old male with T9 AIS1 C quadriplegia secondary to spinal cord compression by a tumor due to large B cell lymphoma. Subsequent to tumor resection and chemotherapy, the patient was discovered to have Pneumocystis jiroveci pneumonia (PJP). Once started on high dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy (15.6 mg/kg/day of trimethoprim) for the treatment of PJP, he displayed bilateral upper extremity myoclonic jerks at rest, asterixis, and postural tremor. Symptoms resolved once TMP-SMX therapy was discontinued. Discussion Myoclonus, asterixis, and tremor have been linked to high dose TMP-SMX therapy as a toxic side effect. Our patient's symptoms did improve with levetiracetam therapy, but did not fully resolve until TMP-SMX was discontinued. Conclusions This is thought to be the first reported case of reversible myoclonus, tremor, and asterixis induced by high dose TMP-SMX in the spinal cord injury population. Early recognition of TMP-SMX induced complications were of key importance as they negatively impacted the rehabilitation process. We also recommend consideration of symptomatic treatment with levetiracetam for the duration of required TMP-SMX therapy as it appeared to mitigate the severity of our patient's movement disorders. PMID:26111222

  18. Study of high-dose x-ray radiation damage of silicon sensors

    NASA Astrophysics Data System (ADS)

    Schwandt, Joern; Fretwurst, Eckhart; Klanner, Robert; Pintilie, Ioana; Zhang, Jiaguo

    2013-05-01

    The high intensity and high repetition rate of the XFEL, the European X-ray Free-Electron Laser presently under construction in Hamburg, results in X-ray doses of up to 1 GGy in silicon sensors for 3 years of operation. Within the AGIPD Collaboration the Hamburg group has systematically studied X-ray-radiation damage using test structures and segmented sensors fabricated on high-ohmic n-type silicon. MOS Capacitors and Gate- Controlled Diodes from 4 vendors with different crystal orientations and different technological parameters, as well as strip sensors have been irradiated in the dose range between 10 kGy and 1 GGy. Current-Voltage, Capacitance/Conductance-Voltage and Thermal Dielectric Relaxation Current measurements were used to extract oxide-charge densities, interface-trap densities and surface-current densities as function of dose and annealing conditions. The results have been implemented into TCAD simulations, and the radiation performance of strip sensors and guard-ring structures simulated and compared to experimental results. Finally, with the help of detailed TCAD simulations, the layout and technological parameters of the AGIPD pixel sensor have been optimized. It is found that the optimization for sensors exposed to high X-ray doses is significantly different than for non-irradiated sensors, and that the specifications of the AGIPD sensor can be met. In 2012 sensors have been ordered, the first batch has been delivered recently, and first results on a comparison between simulations and measurements will be presented.

  19. 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,...

  20. 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.

  1. Enhancement of isodense subdural hematoma on delayed-high-dose contrast computed tomography

    SciTech Connect

    Miller, D.L.; Hinck, V.C.

    1983-02-01

    A case is presented in which bilateral, isodense subdural hematomas, not readily apparent on immediate rapid-high-dose computed tomography, became enhanced and clearly visible on delayed scans. If difficulty is encountered in interpreting the immediate scan of a patient suspected of having isodense subdural hematoma, further scans after a one-hour delay may resolve the dilemma.

  2. 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...

  3. Radiotherapy dose enhancement using BNCT in conventional LINACs high-energy treatment: Simulation and experiment

    PubMed Central

    Alikaniotis, Katia; Borla, Oscar; Monti, Valeria; Vivaldo, Gianna; Zanini, Alba; Giannini, Gianrossano

    2016-01-01

    Aim To employ the thermal neutron background that affects the patient during a traditional high-energy radiotherapy treatment for BNCT (Boron Neutron Capture Therapy) in order to enhance radiotherapy effectiveness. Background Conventional high-energy (15–25 MV) linear accelerators (LINACs) for radiotherapy produce fast secondary neutrons in the gantry with a mean energy of about 1 MeV due to (γ, n) reaction. This neutron flux, isotropically distributed, is considered as an unavoidable undesired dose during the treatment. Considering the moderating effect of human body, a thermal neutron fluence is localized in the tumour area: this neutron background could be employed for BNCT by previously administering 10B-Phenyl-Alanine (10BPA) to the patient. Materials and methods Monte Carlo simulations (MCNP4B-GN code) were performed to estimate the total amount of neutrons outside and inside human body during a traditional X-ray radiotherapy treatment. Moreover, a simplified tissue equivalent anthropomorphic phantom was used together with bubble detectors for thermal and fast neutron to evaluate the moderation effect of human body. Results Simulation and experimental results confirm the thermal neutron background during radiotherapy of 1.55E07 cm−2 Gy−1. The BNCT equivalent dose delivered at 4 cm depth in phantom is 1.5 mGy-eq/Gy, that is about 3 Gy-eq (4% of X-rays dose) for a 70 Gy IMRT treatment. Conclusions The thermal neutron component during a traditional high-energy radiotherapy treatment could produce a localized BNCT effect, with a localized therapeutic dose enhancement, corresponding to 4% or more of photon dose, following tumour characteristics. This BNCT additional dose could thus improve radiotherapy, acting as a localized radio-sensitizer. PMID:26933394

  4. 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.

  5. Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration.

    PubMed

    Escobar, Leslie; Andresen, Max; Downey, Patricio; Gai, Maria Nella; Regueira, Tomás; Bórquez, Tamara; Lipman, Jeffrey; Roberts, Jason A

    2014-08-01

    This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V(1)), 11.8L; volume of distribution of peripheral compartment (V(2)), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.

  6. Activation of hip prostheses in high energy radiotherapy and resultant dose to nearby tissue.

    PubMed

    Keehan, Stephanie; Smith, Ryan L; Millar, Jeremy; Esser, Max; Taylor, Michael L; Lonski, Peta; Kron, Tomas; Franich, Rick D

    2017-03-01

    High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high-density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross-sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in- and out-of field at various distances from the beam isocenter to assess activation caused in-field by photo-activation, and neutron activation which occurs both in and out-of-field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma-ray emissions and their half-lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD-100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in-field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. (53) Fe, (56) Mn, and (52) V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

  7. 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

  8. 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

  9. Single enantiomer versus racemate: chiral distinction in the proton pump inhibitors omeprazole and esomeprazole.

    PubMed

    Marom, Hili; Pogodin, Sergey; Agranat, Israel

    2014-04-01

    Chiral distinction in the proton pump inhibitor drugs omeprazole and in its chiral-switch esomeprazole magnesium was studied employing the Density Functional Theory (DFT) method. At B3LYP/6-311G(d,p), the 6-methoxy∙∙∙6-methoxy and 5-methoxy∙∙∙5-methoxy homochiral and heterochiral dimers were calculated. The chiral distinction free energies (ΔΔG(298,(RS-SS))) between the cyclic C2-(S,S)- and Ci-(R,S)-dimers with two intermolecular hydrogen bonds are 3.8, 1.9 (with BSSE counterpoise correction), and -6.9 (with D3 dispersion and BSSE counterpoise corrections) kJ/mol. Adding water as an implicit solvent (polarized continuum model [PCM] model) resulted in a chiral distinction energy of -3.3 kJ/mol, indicating a reversal of the order of the relative stabilities of C2-(S,S)- and Ci-(R,S)-dimers. The chiral distinction free energies between the corresponding (less stable) C1-dimers with one intermolecular hydrogen bond are -9.3, -5.8 (with BSSE CC), 17.6 (D3 + BSSE CC), and -3.2 (H2O) kJ/mol. The results highlight the contention that omeprazole is not just a superposition of its enantiomer constituents. They are consistent with the pharmacological evidence of enantiomer-enantiomer interactions in omeprazole versus esomeprazole and the differences between the drugs omeprazole and esomeprazole magnesium and support the lodged application for regulatory supplementary protection certificate (SPC) exclusivity for the esomeprazole-related combination drug Vimovo.

  10. Development and evaluation of omeprazole pellets fabricated by sieving-spheronization and extrusion - spheronization process.

    PubMed

    Karim, Sabiha; Baie, Saringat H; Hay, Yuen Kah; Bukhari, Nadeem Irfan

    2014-05-01

    Pelletized dosage forms can be prepared by different methods which, in general, are time consuming and labor intensive. The current study was carried out to investigate the feasibility of preparing the spherical pellets of omeprazole by sieving-spheronization. An optimized formulation was also prepared by extrusion-spheronization process to compare the physical parameters between these two methods. The omeprazole pellets were consisted of microcrystalline cellulose, polyvinylpyrrolidone K 30, sodium lauryl sulphate and polyethylene glycol 6000. The omeprazole delay release system was developed by coating the prepared pellets with aqueous dispersion of Kollicoat 30 DP. The moisture content, spheronization speed and residence time found to influence the final properties of omeprazole pellets prepared by extrusion-spheronization and sieving-spheronization. The Mann-Whitney test revealed that both methods produced closely similar characteristics of the pellets in terms of, friability (p=0.553), flowability (p=0.677), hardness (p=0.103) and density (bulk, p=0.514, tapped, p=0.149) except particle size distribution (p=0.004). The percent drug release from the coated formulation prepared by sieving-spheronization and extrusion spheronization was observed to be 84.12 ± 1.10% and 82.67 ± 0.96%, respectively. Dissolution profiles of both formulations were similar as indicated by values of f1 and f2, 1.52 and 89.38, respectively. The coated formulation prepared by sieving-spheronization and commercial reference product, Zimore ® also showed similar dissolution profiles (f1=1.22, f2=91.52). The pellets could be prepared using sieving-spheronization. The process is simple, easy, less time- and labor-consuming and economical as compared to extrusion-spheronization process.

  11. Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma.

    PubMed

    Gor, Parul; Alnouti, Yazen; Reed, Gregory A

    2011-07-15

    Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a "cocktail". This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5'-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0-1000ng/ml for omeprazole, omeprazole sulfone, 5'-hydroxyomeprazole, and fexofenadine; 0.1-100ng/ml for buspirone, and 1.0-100ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 and 16.1%, and the accuracy ranged from 86 to 115% for all analytes. Inter-day precision and accuracy ranged from 0.3 to 14% and from 90 to 110%, respectively. The lower limits of quantification were 0.1ng/ml for buspirone and 1ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.

  12. Buspirone, fexofenadine, and omeprazole: Quantification of probe drugs and their metabolites in human plasma

    PubMed Central

    Gor, Parul; Alnouti, Yazen; Reed, Gregory A.

    2011-01-01

    Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a —cocktail . This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5 mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0–1000 ng/ml for omeprazole, omeprazole sulfone, 5-hydroxyomeprazole, and fexofenadine; 0.1-100 ng/ml for buspirone, and 1.0-100 ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 –16.1%, and the accuracy ranged from 86 -115% for all analytes. Inter-day precision and accuracy ranged from 0.3 – 14% and from 90 – 110%, respectively. The lower limits of quantification were 0.1 ng/ml for buspirone and 1 ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies. PMID:21546194

  13. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'

    NASA Astrophysics Data System (ADS)

    Salter, Bill J.; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-01

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min-1) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach.

  14. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'.

    PubMed

    Salter, Bill J; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-07

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min(-1)) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach.

  15. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids.

    PubMed

    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.

  16. 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

  17. Radiochromic film measurement of anisotropy function for high-dose-rate Ir-192 brachytherapy source.

    PubMed

    Sharma, S D; Bianchi, C; Conte, L; Novario, R; Bhatt, B C

    2004-09-07

    The dose distribution produced by the high-dose-rate (HDR) 192Ir source is inherently anisotropic due to self-absorption by the high-density source core, oblique filtration by the source capsule and the asymmetric geometry of the source capsule. To account for the dose distribution anisotropy of brachytherapy sources, AAPM Task Group No 43 has included a two-dimensional anisotropy function, F(r, theta), in the recommended dose calculation formalism. Gafchromic HS radiochromic film (RCF) was used to measure anisotropy function for microSelectron HDR 192Ir source (classic/old design). Measurements were carried out in a water phantom using specially fabricated PMMA cylinders at radial distances 1, 2, 3, 4 and 5 cm. The data so generated are comparable to both experimental and Monte Carlo calculated values for this source reported earlier by other authors. The RCF method described in this paper is comparatively high resolution, simple to use and is a general method, which can be applied for other brachytherapy sources as well.

  18. 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.

  19. 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.

  20. Slow, spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets: isolation and structural characterization of the toxic antioxidants 3H-benzimidazole-2-thiones.

    PubMed

    Rajab, A; Touma, M; Rudler, H; Afonso, C; Seuleiman, M

    2013-09-01

    The spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets upon long-term and forced storage conditions was determined by high performance liquid chromatography (HPLC). The more abundant products could be isolated by liquid chromatography and their molecular weights determined by Mass Spectrometry (MS). Their structures, established according to their spectroscopic data, were compared to those of either the literature or of authentic samples. Thus lansoprazole led mainly to a mixture of 3H-benzimidazole-2-thione (2a) and 3H-benzimidazole-2-one (2c), omeprazole mainly to a mixture of 5-methoxy-3H-benzimidazole-2-thione (1a) and 2-hydroxymethyl-3, 5-dimethyl-4-methoxypyridine (1b), and pantoprazole, to 5-difluoromethoxy-3H-benzimidazole-2-thione (3a) and 2-hydroxymethyl-3, 4-dimethoxypyridine (3b). Although some of the degradation products had already been observed under different conditions, the detection of benzimidazole-2-thiones is unprecedented and their involvement as possible physiological, yet toxic antioxidants must be emphasized. Plausible, unified mechanisms for the formation of the different degradation products observed herein and in previous papers from the literature are suggested.

  1. 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.

  2. 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

  3. 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.

  4. [High-dose magnesium sulfate in the treatment of aconite poisoning].

    PubMed

    Clara, A; Rauch, S; Überbacher, C A; Felgenhauer, N; Drüge, G

    2015-05-01

    This article reports the case of a 62-year-old male patient who ingested the roots of Monkshood (Aconitum napellus) and white hellebore (Veratrum album) dissolved in alcohol with a suicidal intention and suffered cardiotoxic and neurotoxic symptoms. After contacting the Poison Information Centre ventricular arrhythmia was treated with high-dose magnesium sulphate as the only antiarrhythmic agent and subsequently a stable sinus rhythm could be established after approximately 3 h. Aconitum napellus is considered the most poisonous plant in Europe and it is found in gardens, the Alps and the Highlands. Poisoning is mainly caused by the alkaloid aconite that leads to persistent opening and activation of voltage-dependent sodium channels resulting in severe cardiac and neurological toxicity. As no specific antidote is known so far, poisoning is associated with a high mortality. The therapy with high-dose magnesium sulphate is based on in vitro and animal experiments as well as limited clinical case reports.

  5. The ASTEROID trial: coronary plaque regression with high-dose statin therapy.

    PubMed

    Chhatriwalla, Adnan K; Nicholls, Stephen J; Nissen, Steven E

    2006-11-01

    A Study To Evaluate the effect of Rosuvastatin On Intravascular ultrasound-Derived coronary atheroma burden (ASTEROID) investigated the impact of high-dose rosuvastatin therapy on the rate of atheroma progression in patients with coronary artery disease. Serial intravascular ultrasound (IVUS) was performed in 349 patients at baseline and following 24 months of therapy with rosuvastatin 40 mg/day. Rosuvastatin therapy lowered low-density lipoprotein cholesterol to 60.8 mg/dl and raised high-density lipoprotein cholesterol by 14.7%. This was associated with a significant reduction in all IVUS measures of atheroma burden. These results suggest that intensive modification of lipid levels with high-dose statin therapy can promote atheroma regression. Further studies will be required to determine whether this benefit is associated with a reduction in clinical events.

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

    PubMed Central

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

    2011-01-01

    Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

  7. High-dose Daptomycin Therapy for Staphylococcal Endocarditis and When to Apply It

    PubMed Central

    Smith, Jordan R.; Claeys, Kimberly; Barber, Katie E.; Rybak, Michael J.

    2014-01-01

    Infective endocarditis (IE) continues to present a large burden to the healthcare system. Staphylococcus aureus, the leading pathogen associated with the disease, has always proven difficult to treat. Increasing numbers of S. aureus isolates are demonstrating reduced susceptibility to vancomycin, and therapeutic options are limited. Daptomycin is frequently employed when vancomycin therapy proves unsuccessful or when vancomycin MIC values rise above 1 mg/L. Currently, daptomycin is FDA-approved at a dose of 6 mg/kg/day for the treatment of S. aureus bacteremia and associated right-sided endocarditis. However, numerous in vitro and clinical studies suggest that daptomycin doses up to 12 mg/kg/day may provide improved efficacy and resistance prevention. Additionally, high-dose daptomycin has demonstrated excellent safety. Together, these data suggest a role for high-dose daptomycin in staphylococcal IE patients who are severely ill, previously failed therapy with vancomycin, or possess a S. aureus isolate with an elevated vancomycin MIC. PMID:25165017

  8. 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.

  9. 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.

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

    PubMed

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

    2010-04-01

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

  11. 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

  12. High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings

    PubMed Central

    Calver, Leonie; Isbister, Geoffrey K

    2014-01-01

    Aims To investigate the QT interval after high dose droperidol using continuous 12-lead Holter recordings. Methods This was a prospective study of patients given droperidol with a continuous Holter recording. Patients were recruited from the DORM II study which included patients with aggression presenting to the emergency department. Patients initially received 10 mg droperidol as part of a standardized sedation protocol. An additional 10 mg dose was given after 15 min if required and further doses at the clinical toxicologist's discretion. Continuous 12-lead Holter recordings were obtained for 2–24 h utilizing high resolution digital recordings with automated QT interval measurement. Electrocardiograms were extracted hourly from Holter recordings. The QT interval was plotted against heart rate (HR) on the QT nomogram to determine if it was abnormal. QTcF (Fridericia's HR correction) was calculated and >500 ms was defined as abnormal. Results Forty-six patients had Holter recordings after 10–40 mg droperidol and 316 QT–HR pairs were included. There were 32 abnormal QT measurements in four patients, three given 10 mg and one 20 mg. In three of the four patients QTcF >500 ms but only in one taking methadone was the timing of QTcF >500 ms consistent with droperidol dosing. Of the three other patients, one took amphetamines, one still had QT prolongation 24 h after droperidol and one took a lamotrigine overdose. No patient given >30 mg had a prolonged QT. There were no arrhythmias. Conclusion QT prolongation was observed with high dose droperidol. However, there was little evidence supporting droperidol being the cause and QT prolongation was more likely due to pre-existing conditions or other drugs. PMID:24168079

  13. 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

  14. 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

  15. 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

  16. 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.

  17. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    SciTech Connect

    Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  18. 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

  19. Effects of high-dose selegiline on morphine reinforcement and precipitated withdrawal in dependent rats.

    PubMed

    Grasing, K; He, S

    2005-02-01

    Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with high-dose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding

  20. 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.

  1. Inhibition of gastric perception of mild distention by omeprazole in volunteers

    PubMed Central

    Iida, Akihito; Kaneko, Hiroshi; Konagaya, Toshihiro; Funaki, Yasushi; Tokudome, Kentaro; Izawa, Shinya; Tamura, Yasuhiro; Mizuno, Mari; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

    2012-01-01

    AIM: To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. METHODS: A double lumen polyvinyl tube with a plastic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure (MDP) was determined after a 30-min adaptation period. Isobaric distensions were performed in stepwise increments of 2 mmHg (2 min each) starting from the MDP. Subjects were instructed to score feelings at the end of every step using a graphic rating scale: 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but significant; 5, severe discomfort; and 6, unbearable pain. After this first test, subjects received omeprazole (20 mg, after dinner) once daily for 1 wk. A second test was performed on the last day of treatment. RESULTS: No adverse effects were observed. Mean MDP before and after treatment was 6.3 ± 0.3 mmHg and 6.2 ± 0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pressure required to reach scores of 1 (P = 0.019) and 2 (P = 0.017) as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling < 1 at MDP, and mean (± SE) abdominal discomfort scores at MDP were 0.13 ± 0.09 and 0.04 ± 0.04, respectively. Mean scores induced by each MDP + 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 (mmHg) were 1.1 ± 0.3, 2.0 ± 0.4, 2.9 ± 0.5, 3.3 ± 0.4, 4.6 ± 0.3, 5.2 ± 0.3, 5.5 ± 0.2, 5.5 ± 0.3, 5.7 ± 0.3, and 5.4, respectively. After omeprazole, abdominal feeling scores for the same incremental pressures over MDP were 0.3 ± 0.1, 0.8 ± 0.1, 2.0 ± 0.4, 2.8 ± 0.4, 3.8 ± 0.4, 4.6 ± 0.4, 4.9 ± 0.3, 5.4 ± 0.4, 5.2

  2. An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals.

    PubMed

    Scala, R A; Bevan, C; Beyer, B K

    1992-08-01

    A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

  3. The trail of the development of high-dose-rate brachytherapy for cervical cancer in Japan.

    PubMed

    Inoue, Toshihiko

    2003-07-01

    The differences in radiotherapeutic treatment systems for cervical cancer between the United States and Japan can be attributed either to the tolerance of high-risk organs, or dosimetry itself. High-dose-rate (HDR) brachytherapy is the standard treatment for uterine cervix carcinoma in Japan. In addition, HDR Co-60 afterloading machines have been gradually replaced with Ir-192 micro-source afterloading machines during the past ten years. This implies that it has now become impossible to conduct a prospective comparative study of HDR versus low-dose-rate (LDR) brachytherapy for cervical cancer in Japan. An examination of the history of HDR intracavitary radiotherapy for uterine cervix carcinoma in Japan led us to the conclusion that HDR intracavitary brachytherapy for the treatment of cervical cancer is as effective as LDR intracavitary brachytherapy in terms of both survival and complications. In Japan, studies on the former can be drawn from a long experience of more than 35 years.

  4. High-dose intravenous therapy with immune globulin before delivery for idiopathic thrombocytopenic purpura.

    PubMed Central

    Adderley, R. J.; Rogers, P. C.; Shaw, D.; Wadsworth, L. D.

    1984-01-01

    A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter. PMID:6423252

  5. Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma

    PubMed Central

    Thavendiranathan, P; Verhaert, D; Kendra, K L; Raman, S V

    2011-01-01

    High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T2 weighted imaging and T1 weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T1 and T2 weighted CMRI techniques to diagnose IL-2 induced myocarditis. PMID:21511746

  6. Vitamin D insufficiency underlies unexpected hypocalcemia following high dose glucocorticoid therapy.

    PubMed

    Kinoshita, Yuka; Masuoka, Kazuhiro; Miyakoshi, Shigesaburo; Taniguchi, Shuichi; Takeuchi, Yasuhiro

    2008-01-01

    Vitamin D insufficiency is a reemerging and common health problem for skeletal system. Pharmacological application of glucocorticoid inhibits intestinal calcium absorption and stimulates tubular calcium excretion, thus induces severely negative calcium balance. We report a patient presenting symptomatic hypocalcemia following high dose glucocorticoid administration. After a pulse-therapy with methylprednisolone, hypocalcemia with muscle cramp developed in association with hypercalciuria and secondary hyperparathyroidism in the absence of hypomagnesemia. Circulating level of 1,25-dihydroxyvitamin D was in a reference range, while that of 25-hydroxyvitamin D was insufficient. Treatment with alfacalcidol of 1 mug/day promptly improved serum calcium level within a couple of weeks. Vitamin D insufficiency could be a serious problem in patients with high dose glucocorticoid therapy.

  7. 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.

  8. High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

    PubMed

    Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

    2001-07-01

    Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

  9. High-dose-rate and pulsed-dose-rate brachytherapy for oral cavity cancer and oropharynx cancer

    PubMed Central

    2010-01-01

    Interstitial brachytherapy represents the treatment of choice for small tumours, regionally localized in the oral cavity and the oropharynx. In the technical setting, continuous low-dose-rate (LDR) brachytherapy represented for many years the gold standard for administering radiation in head and neck brachytherapy. Large series of head and neck cancer patients treated with LDR brachytherapy have been reported, constituting an invaluable source of clinical data and the gold standard to compare results of new techniques. Nowadays, LDR brachytherapy competes with fractionated HDR and hyperfractionated PDR. In the paper an overview of the different time-dose-fraction alternatives to LDR brachytherapy in head and neck cancer is presented, as well as the radiobiological basis of different dose-rate schedules, the linear-quadratic model, interconversion of fractionation schedules and the repair half-times for early- and late-responding tissues. In subsequent sections essentials of switching from LDR to HDR and from LDR to PDR are discussed. Selected clinical results using HDR and PDR brachytherapy in oral cavity and oropharynx cancer are presented. PMID:28050175

  10. 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

  11. Developing A Directional High-Dose Rate (d-HDR) Brachytherapy Source

    NASA Astrophysics Data System (ADS)

    Heredia, Athena Yvonne

    Conventional sources used in brachytherapy provide nearly isotropic or radially symmetric dose distributions. Optimizations of dose distributions have been limited to varied dwell times at specified locations within a given treatment volume, or manipulations in source position for seed implantation techniques. In years past, intensity modulated brachytherapy (IMBT) has been used to reduce the amount of radiation to surrounding sensitive structures in select intracavitary cases by adding space or partial shields. Previous work done by Lin et al., at the University of Wisconsin-Madison, has shown potential improvements in conformality for brachytherapy treatments using a directionally shielded low dose rate (LDR) source for treatments in breast and prostate. Directional brachytherapy sources irradiate approximately half of the radial angles around the source, and adequately shield a quarter of the radial angles on the opposite side, with sharp gradient zones between the treated half and shielded quarter. With internally shielded sources, the radiation can be preferentially emitted in such a way as to reduce toxicities in surrounding critical organs. The objective of this work is to present findings obtained in the development of a new directional high dose rate (d-HDR) source. To this goal, 103Pd (Z = 46) is reintroduced as a potential radionuclide for use in HDR brachytherapy. 103Pd has a low average photon energy (21 keV) and relatively short half -life (17 days), which is why it has historically been used in low dose rate applications and implantation techniques. Pd-103 has a carrier-free specific activity of 75000 Ci/g. Using cyclotron produced 103Pd, near carrier-free specific activities can be achieved, providing suitability for high dose rate applications. The evolution of the d-HDR source using Monte Carlo simulations is presented, along with dosimetric parameters used to fully characterize the source. In addition, a discussion on how to obtain elemental

  12. 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

  13. 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.

  14. High Dose of Lamivudine and Resistance in Patients with Chronic Hepatitis B

    PubMed Central

    Wani, Hamid Ullah; Al Kaabi, Saad; Singh, Rajvir; John, Anil; Derbala, Moutaz; Al-Mohannadi, Muneera J.

    2014-01-01

    Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B. PMID:25349729

  15. High dose of Lamivudine and resistance in patients with chronic hepatitis B.

    PubMed

    Wani, Hamid Ullah; Al Kaabi, Saad; Sharma, Manik; Singh, Rajvir; John, Anil; Derbala, Moutaz; Al-Mohannadi, Muneera J

    2014-01-01

    Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B.

  16. Implementation and Evaluation 
of a High-Dose Cytarabine Neurologic Assessment Tool.

    PubMed

    Szoch, Stephanie; Snow Kaiser, Karen

    2015-06-01

    Patients receiving high-dose cytarabine as part of their chemotherapy regimen have a chance of experiencing neurotoxicities. Prompt identification of signs and symptoms can greatly reduce the chance of patients sustaining permanent neurologic damage. This article describes the development and successful implementation of an evidence-based, standardized neurologic assessment and documentation tool that was evaluated using a clinical utility questionnaire and an adherence audit.

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

    PubMed Central

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

    2016-01-01

    Purpose The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT). Material and methods In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of “skin cancer”, “high dose rate brachytherapy”, “squamous cell carcinoma”, “basal cell carcinoma”, and “non melanoma skin cancer“ was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Results Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Conclusions Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy. PMID:28115960

  18. High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL production.

    PubMed

    Roglans, Núria; Verd, Joan C; Peris, Cristina; Alegret, Marta; Vázquez, Manuel; Adzet, Tomás; Díaz, Cristina; Hernández, Gonzalo; Laguna, Juan C; Sánchez, Rosa M

    2002-05-01

    Treatments with high doses of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors may induce the expression of sterol regulatory element binding protein (SREBP)-target genes, causing different effects from those attributed to the reduction of hepatic cholesterol content. The aim of this study was to investigate the effects of high doses of statins on the key enzymes involved in VLDL production in normolipidemic rats. To examine whether the effects caused by statin treatment are a consequence of HMG-CoA reductase inhibition, we tested the effect of atorvastatin on these enzymes in mevalonate-fed rats. Atorvastatin and simvastatin enhanced not only HMG-CoA reductase but also the expression of the SREBP-2 gene itself. As a result of the overexpression of SREBP-2 caused by the statin treatment, genes regulated basically by SREBP-1, as FA synthase and acetyl-coenzyme A carboxylase, were also induced and their mRNA levels increased. DAG acyltransferase and microsomal TG transfer protein mRNA levels as well as phosphatidate phosphohydrolase activity were increased by both statins. Simvastatin raised liver cholesterol content, ACAT mRNA levels, and CTP:phosphocholine cytidylyltransferase activity, whereas it reduced liver DAG and phospholipid content. Mevalonate feeding reversed all changes induced by the atorvastatin treatment. These results show that treatment with high doses of statins induces key enzymes controlling rat liver lipid synthesis and VLDL assembly, probably as a result of SREBP-2 overexpression. Despite the induction of the key enzymes involved in VLDL production, both statins markedly reduced plasma TG levels, suggesting that different mechanisms may be involved in the hypotriglyceridemic effect of statins at high or low doses.

  19. 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

  20. Safety of high-dose doripenem in adult patients with cystic fibrosis

    PubMed Central

    Strawbridge, Seth; Nailor, Michael D.

    2016-01-01

    Background: High doses of β-lactam antibiotics have been advocated for acute pulmonary exacerbations caused by Pseudomonas aeruginosa in patients with cystic fibrosis (CF) secondary to high minimum inhibitory concentrations (MIC) of the infecting organisms. Some β-lactam antibiotics have increased elimination in CF patients. This case series examines the safety of high-dose doripenem (HDD), 2 g intravenously every 8 hours, which is 4 times the labeled dose, in CF patients. Methods: This was a retrospective, single site, chart review of all CF patients given HDD during a 3-year period. Adverse events were prospectively defined using labeled definitions within the package insert and the medical literature. A standard case report form was used to collect demographic details, antibiotic lengths of therapy and adverse events. Results: A total of 17 patients (9 males), with a median age of 24 years, contributed 43 unique visits and 382 HDD exposure days. Mean duration of inpatient doripenem use was 8.9 days. Concurrent antibiotics were common, with a median number of additional antibiotics per admission of three. The median number of adverse effects documented was two. The most common adverse event was anemia, which was identified in 41 of 43 visits, but was present on admission in 31 instances. One patient developed leukopenia for 1 day, but returned to normal without dose adjustment. There were three instances of Clostridium difficile infection. One patient was documented to have an allergic reaction that led to discontinuation, but was ultimately rechallenged without adverse effect. Other common adverse events were gastrointestinal in origin. No other possible adverse effects led to discontinuation of the drug. Conclusions: In adult patients with CF, HDD in combination with other antibiotics did not lead to adverse effects necessitating discontinuation. HDD should be considered in this selected patient population, particularly when high MIC organisms are identified

  1. Total ionizing dose effects in high voltage devices for flash memory

    NASA Astrophysics Data System (ADS)

    Liu, Zhangli; Hu, Zhiyuan; Zhang, Zhengxuan; Shao, Hua; Chen, Ming; Bi, Dawei; Ning, Bingxu; Wang, Ru; Zou, Shichang

    2010-12-01

    The effect of size and substrate bias conditions after irradiation on the total ionizing dose response of high voltage devices for flash memory has been investigated. Different sensitivity of transistors with different gate width was observed, which is well known as the radiation induced narrow channel effect. A charge sharing model was used to explain this effect. The negative substrate bias voltage after irradiation showed considerable impact on the parasitic transistor's response by suppressing leakage current.

  2. Intensive combined modality therapy including low-dose TBI in high-risk Ewing's sarcoma patients

    SciTech Connect

    Kinsella, T.J.; Glaubiger, D.; Diesseroth, A.; Makuch, R.; Waller, B.; Pizzo, P.; Glatstein, E.

    1983-12-01

    Twenty-four high-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiaiton (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patterns of granulocyte recovery following consolidative therapy (including TBI and ABMI) were recognized. The time to platelet recovery was different for the groups with early and late granulocyte recovery. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. It is concluded that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

  3. Tests of the linear, no-threshold dose-response relationship for high-LET radiation

    SciTech Connect

    Cohen, B.L.

    1987-05-01

    It is pointed out that induction of lung cancer by exposure to Rn daughters, applied at high doses to miners and at low doses to exposures in homes, provides a very stringent and sensitive test of the linear, no-threshold dose-response relationship for high-LET radiation, because this relationship predicts that a substantial fraction of lung cancer among non-smokers is due to average Rn levels. Therefore, it predicts an easily observable elevation of lung cancer rates in areas where Rn levels are many times greater than the average, especially at times before cigarette smoking began to have important effects on lung cancer statistics. While more data are needed (and will be forthcoming), some of the early indications of these studies are reviewed here. Several cases are now known where average Rn levels are very high, and in all of these cases lung cancer rates are well below average. Methods for analyzing these data are discussed, and it is concluded that, based on current evidence, they indicate at least a factor of 4 disagreement with linear, no-threshold predictions.

  4. 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.

  5. Use of high-dose chemotherapy in front-line therapy of childhood malignant glioma.

    PubMed

    Massimino, Maura; Biassoni, Veronica

    2006-05-01

    Brain tumors are the second most common cancer in pediatric patients and the main cause from death of malignant tumors in this age group. High-grade or malignant glioma, among which anaplastic astrocytomas and glioblastoma are the most prevalent histotypes, represent 10% of pediatric brain tumors and, taken as a whole, are the second most frequent malignant histotype after medulloblastoma. Apart from complete excision followed by full-dose local radiotherapy, chemotherapy appears to provide some benefit to the final outcome. Different trials have explored the role of high-dose chemotherapy that, theoretically, could give an advantage to these patients by overcoming the blood-brain barrier, cell chemoresistance and inducing a wider number of responses. However, it is still doubtful if more responses translate into better outcome and it is not fully understood which patients can experience a true benefit from this treatment strategy. New protocols under evaluation include new agents with specific biological targets, multiple cycles of high-dose chemotherapy, and vaccination, as an immunotherapeutic approach.

  6. 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.

  7. Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro

    NASA Technical Reports Server (NTRS)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1986-01-01

    The effects of the low- and high-LET radiation (by X-rays, Co-60, and heavy ions) on the transformation of neoplastic cells were studied using cultured C3H10T1/2 mouse embryo cells. The transformed colonies in the confluent cell monolayers were recognized as focuses composed of highly polar fibroblastic multilayered criss-cross arrays of densely stained cells. For the low-LET radiation, there was a decrease in cell killing and cell transformation frequency when cells were irradiated with fractionated doses and at a low dose rate, indicating that cultured mammalian cells can repair both subtransformation and potential transformation lesions. No sparing effect, however, was found for the high-LET radiation. An enhancement of cell transformation was observed for low-dose/rate argon (400 MeV/u; 120 keV/micron) and iron particles (600 MeV/u; 200 keV/micron). The molecular mechanism for this enhancement effect is not known.

  8. A fatal outcome in a patient with glioblastoma multiforme after receiving high-dose methotrexate.

    PubMed

    Price, Samantha; Harless, William; Rikhye, Somi; Altaha, Ramin

    2008-03-01

    The most common adult primary brain tumor is glioblastoma multiforme (GBM). Current treatment is surgical resection, adjuvant radiation and chemotherapy, which can extend the median survival 20-36 weeks (Mansky et al. Central nervous system tumors. In Abraham J, Allegra CJ, Gulley J, eds. Bethesda Handbook of clinical oncology, 2nd edn. Philadelphia, Pennsylvania: Lippincott Williams and Wilkins, 2000: 440-2; Knox S. Intracranial tumors. In Pillot G, Chantler M, Magiera H, Peles S, et al., eds. The Washington Manual Hematology and Oncology Subspecialty Consult. Philadelphia, Pennsylvania: Lippincott Williams and Wilkins, 2004: 204-6.). But treatment efficacy is limited, mandating the exploration of more effective treatments. We report on a patient with GBM treated as per a clinical protocol with high-dose methotrexate (12 g/m(2)), who expired within hours after the initiation of treatment secondary to transtentorial herniation. Although it is not completely clear what caused the patient's herniation, we think that high-dose methotrexate therapy may have played a crucial role. We suggest that high-dose methotrexate should be used cautiously in patients with GBM.

  9. High-dose oral acyclovir in acute herpes zoster ophthalmicus: the end of the corticosteroid era.

    PubMed

    Herbort, C P; Buechi, E R; Piguet, B; Zografos, L; Fitting, P

    1991-01-01

    Systemic acyclovir (ACV), a new potent anti-herpes drug, was shown to reduce effectively the morbidity in the acute phase of herpes zoster ophthalmicus (AHZO). Using high dose oral ACV (5 X 800 mg/day) our aim in this study was: (1) to compare disease profiles in the ACV-treated group and in a group of zoster patients having had no ACV, analysed retrospectively; (2) to establish if high-dose ACV was able to prevent severe long term complications of AHZO; and (3) to determine the present role of corticosteroids in AHZO. From 1984 to 1988, 48 patients with AHZO of less than 3 days' duration were included. All patients received at least 7 days of oral ACV (5 X 800 mg/d) associated with topical ACV. Steroids were not given unless severe uveitis occurred. Follow-up was 2 years in 43 patients and 1 year in all 48 patients. Main conclusions from our study are: 1. Ocular involvement occurred in 67% of ACV-treated cases, a rate comparable to our retrospective group (59%) and to the literature (71%). However the rate of severe long term complications was minimal (4%) when compared to our non-treated retrospective group (21%). 2. Steroid treatment was not necessary in any of the ACV-treated patients. 3. ACV was well tolerated and did not have to be discontinued in any of the patients. High dose ACV and avoidance of steroids seems to eliminate the severe complications of AHZO.

  10. 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

  11. Tandem-ring dwell time ratio in Nigeria: dose comparisons of two loading patterns in standard high-dose-rate brachytherapy planning for cervical cancer

    PubMed Central

    Ibhade, Obed Rachel; Idayat, Akinlade Bidemi; Atara I., Ntekim

    2015-01-01

    Purpose In high-dose-rate (HDR) brachytherapy (BT), the source dwell times and dwell positions are essential treatment planning parameters. An optimal choice of these factors is fundamental to obtain the desired target coverage with the lowest achievable dose to the organs at risk (OARs). This study evaluates relevant dose parameters in cervix brachytherapy in order to assess existing tandem-ring dwell time ratio used at the first HDR BT center in Nigeria, and compare it with an alternative source loading pattern. Material and methods At the Radiotherapy Department, University College Hospital (UCH), Ibadan, Nigeria, a total of 370 standard treatment plans in two alternative sets were generated with HDR basic 2.6 software for one hundred and eighty five cervical cancer patients. The initial 185 individual plans were created for clinical treatment using the tandem-ring dwell time ratio of 1 : 1. Modifying the initial applicator loading ratio, the second set of plans with related dose data were also obtained for study purposes only. Total reference air kerma (TRAK), total time index (TTI), ICRU volume, treatment time, point B dose, ICRU bladder dose, and rectal points dose were evaluated for both sets of plans. Results The means of all evaluated dose parameters decreased when the existing tandem-ring dwell time ratio (1 : 1) was modified to other dwell weightings (1 : 1 – 3 : 1). These reductions were 13.43% (ICRU volume), 9.83% (rectal dose), 6.68% (point B dose), 6.08% (treatment time), 5.90% (TRAK), 5.88% (TTI), and 1.08% (bladder dose). Correspondingly, coefficients of variation changed by –7.98%, –5.02%, –5.23%, –4.20%, –3.93%, 8.65%, and 3.96% from the existing pattern to the alternative one. Conclusion Tandem-ring dwell time ratio has significant influence on dosimetric parameters. This study has indicated the need to modify the existing planning approach at UCH. PMID:26034498

  12. 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

  13. 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

  14. High-dose immunosuppressant alters the immunological status of New Zealand white rabbits following skin transplantation

    PubMed Central

    CHENG, PEILUN; ZHONG, LIMING; JIANG, ZESHENG; WANG, YAN; PAN, MINGXIN; GAO, YI

    2015-01-01

    The aim of this study was to investigate the effect of an immunosuppressant on the immunological status of New Zealand white rabbits after skin grafting, and to evaluate a method for monitoring the immunological status of subjects with skin transplants. The rabbits were randomly divided into allograft rejection, autograft tolerance, nontransplant, allograft low-dose immunosuppressant and allograft high-dose immunosuppressant groups. The rabbits in the low- and high-dose immunosuppressant groups were treated with cyclosporine A intravenously 8 h prior to skin transplantation and once daily following transplantation at doses of 2 and 25 mg/kg, respectively. At 12 days after skin transplantation, the spleens of donor (female) rabbits and recipient (male) rabbits were harvested for the preparation of single-cell suspensions. The splenocytes from recipient and donor rabbits were labeled with 0.3 or 6 µM carboxy fluorescein diacetate succinimidyl ester, respectively, and a mixed cell suspension was prepared. The final preparation was intravenously injected into recipient New Zealand white rabbits. The ratio of the two fluorescently labeled cell populations in the peripheral blood was measured using flow cytometry at 1, 2, 4 and 8 h after the injection, and the cell death rate was calculated. Histological analysis was also performed on samples collected at the time of splenectomy. The cell death rates of the allograft rejection and low-dose immunosuppressant groups reached their highest levels 8 h after the injection of spleen cell suspension. Allogeneic spleen cells from donor male rabbits were almost completely removed within 8 h of injection. The cell death rate increased slowly in the nontransplant, autograft and high-dose immunosuppressant groups without specificity. This study provides a specific method for the in vivo monitoring of the immunological status of patients after skin grafting. This method can quickly and accurately detect the immunological status of

  15. High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: early experience with 84 patients

    SciTech Connect

    Akine, Y.; Arimoto, H.; Ogino, T.; Kajiura, Y.; Tsukiyama, I.; Egawa, S.; Yamada, T.; Tanemura, K.; Tsunematsu, R.; Ohmi, K.

    1988-05-01

    Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.

  16. Evaluation of neuropathic pain occurring after high-dose-rate interstitial brachytherapy of oral tongue

    PubMed Central

    Sharma, Suresh C.; Kapoor, Rakesh; Ahuja, Chirag K.; Oinam, Arun S.; Ghoshal, Sushmita

    2015-01-01

    Purpose To recognize neuropathic pain as a complication of high-dose-rate (HDR) interstitial brachytherapy of oral tongue and to evaluate the possible causes of neuropathy. Material and methods Twenty one patients who underwent interstitial brachytherapy for early cancer of oral tongue were evaluated. The patients either underwent primary brachytherapy (42-48 Gy at 3-4 Gy/fraction) or a boost (18-24 Gy at 3 Gy/fraction) after external radiation to 40 Gy. Lingual nerve was the nerve concerned and the sublingual space (SLS) was contoured as its surrogate. Dosimetric parameters were correlated with onset of pain. Results Ten patients out of 21 (47.61%) developed painful neuropathy. Five patients of six (5/6) who underwent primary brachytherapy developed neuropathy. Five out of 15 (5/15) patients who underwent brachytherapy as a boost developed neuropathy. The patients who underwent primary brachytherapy were ten times more likely to develop neuropathy. Among the patients receiving boost treatment, the equivalent dose at 2 Gy/fraction (EQD2) to 2 cc of SLS was higher (39.25 Gy) in the patients who developed pain compared to those without pain (10.29 Gy). Conclusions This is the first report to recognize neuropathic pain as a complication of HDR brachytherapy of oral tongue. Patients undergoing primary brachytherapy were more likely to develop pain. Among other factors like dose to SLS, number of catheters, size of the primary tumor, and the dose rate, only dose to 2 cc of the SLS correlated with onset of pain. The SLS (containing the lingual nerve) may be considered an organ at risk to prevent the occurrence of this complication. PMID:26034495

  17. 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...

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

    PubMed Central

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

    2004-01-01

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

  19. Comparison of the effects of low-dose vs. high-dose aminophylline on lung function in experimental meconium aspiration syndrome.

    PubMed

    Mokra, D; Drgova, A; Mokry, J; Pullmann, R; Redfors, B; Petraskova, M; Calkovska, A

    2008-12-01

    Due to missing information on appropriate dosing of aminophylline in meconium aspiration syndrome (MAS), this study compared effects of high-dose and low-dose aminophylline on lung function of animals with MAS. Meconium-instilled rabbits were treated by low-dose (LD, 1.0 mg/kg), or high-dose (HD, 2.0 mg/kg) aminophylline at 0.5 and 2.5 h after meconium instillation, or were left untreated. Within 5 h of oxygen ventilation, HD-aminophylline improved gas exchange, reduced pulmonary shunts and ventilatory pressures, and decreased edema formation and lung neutrophils. LD-aminophylline enhanced lung function to a lower extent than HD-aminophylline, and failed to reduce lung edema and the number of lung neutrophils. Both treatments decreased lung peroxidation, with a stronger effect of HD-aminophylline on lipid oxidation and of LD-aminophylline on protein oxidation. Tracheal reactivity to histamine decreased after HD-aminophylline, while lung tissue reactivity was more reduced after LD-aminophylline. Although LD-aminophylline showed some anti-inflammatory potential, HD-aminophylline improved most of the parameters more effectively.

  20. Omeprazole, a specific inhibitor of gastric (H/sup +/-K/sup +/)-ATPase, is a H/sup +/-activated oxidizing agent of sulfhydryl groups

    SciTech Connect

    Im, W.B.; Sih, J.C.; Blakeman, D.P.; McGrath, J.P.

    1985-04-25

    Omeprazole (5-methoxy-2-(((4-methoxy-3,5- dimethylpyridinyl)methyl)sulfinyl)-1H-benzimidazole) appeared to inhibit gastric (H/sup +/-K/sup +/)-ATPase by oxidizing its essential sulfhydryl groups, since the gastric ATPase inactivated by the drug in vivo or in vitro recovered its K+-dependent ATP hydrolyzing activity upon incubation with mercaptoethanol. Biological reducing agents like cysteine or glutathione, however, were unable to reverse the inhibitory effect of omeprazole. Moreover, acidic environments enhanced the potency of omeprazole. The chemical reactivity of omeprazole with mercaptans is also consistent with the biological action of omeprazole. The N-sulfenylated compound reacted at neutral pH with another stoichiometric amount of ethyl mercaptan to produce omeprazole sulfide quantitatively. The gastric polypeptides of 100 kilodaltons representing (H/sup +/-K/sup +/)-ATPase in the rat gastric mucosa or isolated hog gastric membranes were covalently labeled with (/sup 14/C)omeprazole. The radioactive label bound to the ATPase, however, could not be displaced by mercaptoethanol under the identical conditions where the ATPase activity was fully restored. These observations suggest that the essential sulfhydryl groups which reacted with omeprazole did not form a stable covalent bond with the drug, but rather that they further reacted with adjacent sulfhydryl groups to form disulfides which could be reduced by mercaptoethanol.

  1. Low and high dose measurement by Agfa personal monitoring film and FD-III-B badge dosimeter system.

    PubMed

    Mihai, F; Bercea, S; Stochioiu, A; Celarel, A; Udup, E; Tudor, I

    2010-01-01

    This paper presents the measurement of the dose equivalent Hp(10) to low (0.005-1) mSv and high (20-1000) mSv doses by exposure at (241)Am and (173)Cs radiation sources of the halide film with FB-III-D dosimeter system. Accuracy of measurements, standard error of the dose mean value (SEM) and some comments about ability to reread of dosimetric films were determined. A good accuracy was obtained over the important dose ranges. In the low dose range, under 0.1 mSv, the SEM values of the (241)Am doses, recorded on the film under plastic filter, are between -21.36% and +47.51%. For 0.1-500 mSv (137)Cs dose range the SEM values are from -9.55% to +7.24%.

  2. The efficacy of high-dose penicillin for community-acquired pneumonia diagnosed by pneumococcal urine antigen test.

    PubMed

    Oka, Hideaki; Ueda, Atsuhisa; Watanuki, Yuji; Tsukiji, Jun; Kuroda, Hideyo; Akashi, Syunsuke; Hirai, Yoshihiro; Fuyuki, Toshiharu; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2009-04-01

    We analyzed the efficacy of both the Streptococcus pneumoniae urine antigen test as a quick diagnostic tool and the administration of high-dose penicillin in response to a positive S. pneumoniae urine antigen test. We conducted a retrospective analysis of 48 cases of pneumococcal pneumonia, in which the patients were treated with high-dose penicillin. All the cases were diagnosed by a positive urine antigen test. Treatment with high-dose penicillin was effective in 43 of the 48 patients. This treatment was also effective in 12 of 16 culture-confirmed cases with low susceptibility to penicillin. Eleven patients who were positive for the S. pneumoniae urine antigen test but culture-negative showed clinical improvement with high-dose penicillin. Pneumonia caused by S. pneumoniae appeared to be treated safely and effectively with high-dose penicillin based on positive results of the urine antigen test, as penicillin resistance was unlikely to be a problem.

  3. High-dose melphalan and total body irradiation with bone marrow transplantation for refractory malignancies.

    PubMed

    Spitzer, G; Jagannath, S; Dicke, K A; Armitage, J; Zander, A R; Vellekoop, L; Horwitz, L; Cabanillas, F; Zagars, G K; Velasquez, W S

    1986-06-01

    We investigated if high dose melphalan and total body irradiation could be administered to adult patients with acceptable toxicity. Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m2-140 mg/m2) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). An occasional patient may be cured by this approach. The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. The combination warrants further investigation in a less heavily pretreated population to determine more accurately the complete response rate.

  4. The impact of high and low dose ionising radiation on the central nervous system.

    PubMed

    Betlazar, Calina; Middleton, Ryan J; Banati, Richard B; Liu, Guo-Jun

    2016-10-01

    Responses of the central nervous system (CNS) to stressors and injuries, such as ionising radiation, are modulated by the concomitant responses of the brains innate immune effector cells, microglia. Exposure to high doses of ionising radiation in brain tissue leads to the expression and release of biochemical mediators of 'neuroinflammation', such as pro-inflammatory cytokines and reactive oxygen species (ROS), leading to tissue destruction. Contrastingly, low dose ionising radiation may reduce vulnerability to subsequent exposure of ionising radiation, largely through the stimulation of adaptive responses, such as antioxidant defences. These disparate responses may be reflective of non-linear differential microglial activation at low and high doses, manifesting as an anti-inflammatory or pro-inflammatory functional state. Biomarkers of pathology in the brain, such as the mitochondrial Translocator Protein 18kDa (TSPO), have facilitated in vivo characterisation of microglial activation and 'neuroinflammation' in many pathological states of the CNS, though the exact function of TSPO in these responses remains elusive. Based on the known responsiveness of TSPO expression to a wide range of noxious stimuli, we discuss TSPO as a potential biomarker of radiation-induced effects.

  5. 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.

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

    PubMed

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

    2015-02-01

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

  7. High and Low Dose OPG-Fc Cause Osteopetrosis-Like Changes in Infant Mice

    PubMed Central

    Bargman, Renee; Posham, Ram; Boskey, Adele; Carter, Erin; DiCarlo, Edward; Verdelis, Kostas; Raggio, Cathleen; Pleshko, Nancy

    2014-01-01

    Background Receptor Activator of Nuclear Factor-κB ligand (RANKL) inhibitors are being considered for use in children with osteogenesis imperfecta (OI). We sought to assess efficacy of two doses of a RANKL inhibitor, OPG-Fc, in a growing animal model of OI, the col1α2-deficient mouse (oim/oim) and its wildtype controls (+/+). Methods Treated mice showed runting and radiographic evidence of osteopetrosis with either high (20 mg/kg twice weekly) or low dose (1 mg/kg/week) OPG-Fc. Because of this adverse event, OPG-Fc treatment was halted and the mice were euthanized or monitored for recovery with monthly radiographs and assessment of serum osteoclast activity (TRACP-5b) until 25 weeks of age. Results Twelve weeks of OPG-Fc treatment resulted in radiographic and histologic osteopetrosis with no evidence of bone modeling and negative Tartrate-resistant acid phosphatase (TRAP) staining, root dentin abnormalities, and TRACP-5b activity suppression. Signs of recovery appeared four to eight weeks post-treatment cessation. Conclusion Both high and low dose OPG-Fc treatment resulted in osteopetrotic changes in infant mice, an outcome not seen in studies with the RANKL inhibitor RANK – Immunoglobulin Fc segment complex (RANK-Fc), or in studies with older animals. Further investigations of RANKL inhibitors prior to their consideration for use in children are necessary. PMID:22926546

  8. [High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia].

    PubMed

    Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

    2005-03-01

    A 12 year-old girl was treated with prophylatic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylatic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed.

  9. 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.

  10. High-dose ifosfamide and mesna in advanced breast cancer. A phase II study.

    PubMed

    Sanchiz, F; Milla, A

    1990-01-01

    Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (including anthracyclines). They were included in a trial to receive 6 g/m3 ifosfamide, mixed with 6 g/m2 mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2-8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation.

  11. 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.

  12. Development of Optimized AAV Serotype Vectors for High-Efficiency Transduction at Further Reduced Doses.

    PubMed

    Ling, Chen; Li, Baozheng; Ma, Wenqin; Srivastava, Arun

    2016-08-01

    We have described the development of capsid-modified next-generation AAV vectors for both AAV2 and AAV3 serotypes, in which specific surface-exposed tyrosine (Y), serine (S), threonine (T), and lysine (K) residues on viral capsids were modified to achieve high-efficiency transduction at lower doses. We have also described the development of genome-modified AAV vectors, in which the transcriptionally inactive, single-stranded AAV genome was modified to achieve improved transgene expression. Here, we describe that combination of capsid modifications and genome modifications leads to the generation of optimized AAV serotype vectors, which transduce cells and tissues more efficiently, both in vitro and in vivo, at ∼20-30-fold reduced doses. These studies have significant implications in the potential use of the optimized AAV serotype vectors in human gene therapy.

  13. Radiation doses in alternative commercial high-level waste management systems

    SciTech Connect

    Schneider, K.J.; Pelto, P.J.; Lavender, J.C.; Daling, P.M.; Fecht, B.A.

    1986-01-01

    In the commercial high-level waste management system, potential changes are being considered that will augment the benefits of an integral monitored retrievable storage (MRS) facility. The US Department of Energy (DOE) has recognized that alternative options could be implemented in the authorized waste management system (i.e., without an integral MRS facility) to potentially achieve some of the same beneficial effects of the integral MRS system. This paper summarizes those DOE-sponsored analyses related to radiation doses resulting from changes in the waste management system. This report presents generic analyses of aggregated radiation dose impacts to the public and occupational workers, of nine postulated changes in the operation of a spent-fuel management system without an MRS facility.

  14. 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.

  15. Effect of early administration of lower dose versus high dose of fresh mitochondria on reducing monocrotaline-induced pulmonary artery hypertension in rat

    PubMed Central

    Huang, Tien-Hung; Chung, Sheng-Ying; Chua, Sarah; Chai, Han-Tan; Sheu, Jiunn-Jye; Chen, Yi-Ling; Chen, Chih-Hung; Chang, Hsueh-Wen; Tong, Meng-Shen; Sung, Pei-Hsun; Sun, Cheuk-Kwan; Lu, Hung-I; Yip, Hon-Kan

    2016-01-01

    Objective: This study aim to investigate whether early mitochondrial administration would be effective and whether high-dose mitochondria (15000 μg/rat) would be more effective than low-dose mitochondria (1500 μg/rat) for attenuating the monocrotaline (MCT/65 mg/kg/rat)-induced pulmonary artery hypertension (PAH) in rat. Method and results: Male-adult SD rats (n = 32) were randomized categorized into groups 1 (sham-control), 2 (PAH), 3 (PAH + low-dose mitochondria), and 4 (PAH + high-dose mitochondria). Mitochondria were admitted at day 5 and rats were sacrificed at day 35 post-MCT treatment. By day 35, oxygen saturation (saO2) was highest in group 1 and lowest in group 2, and significantly higher in group 3 than in group 4 (P<0.001). Conversely, right ventricular systolic blood pressure showed an opposite pattern compared with saO2 among all groups (P<0.001). Histological integrity of alveolar sacs exhibited a pattern identical to saO2, whereas lung crowding score and number of muscularized artery displayed an opposite pattern (all P<0.001). The protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (Bax, cleaved caspase-3 and PARP), fibrosis (p-Smad3, TGF-β), mitochondrial-damage (cytosolic cytochrome-C), and hypoxia-smooth muscle proliferative factors (HIF-α, connexin43, TRPCs) showed an opposite pattern compared, whereas anti-fibrosis (p-Smad1/5, BMP-2) and mitochondrial integrity (mitochondrial cytochrome-C) exhibited an identical pattern to saO2 in all groups (all P<0.001). Conclusion: Low dose is superior to high dose of mitochondria for protecting against MCT-induced PAH. The paradoxical beneficial effect may imply therapy with 15000 μg/rat mitochondria is overdose in this situation. PMID:28077992

  16. Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy

    PubMed Central

    Campos, Luciana Tourinho; de Almeida, Carlos Eduardo Veloso

    2015-01-01

    Introduction The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®); it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21), which is also from BEBIG. Objective and Methods The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the

  17. 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.

  18. In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy

    SciTech Connect

    Streitparth, Florian; Pech, Maciej; Boehmig, Michael; Ruehl, Ricarda; Peters, Nils; Wieners, Gero; Steinberg, Johannes; Lopez-Haenninen, Enrique; Felix, Roland; Wust, Peter; Ricke, Jens . E-mail: jens.ricke@medizin.uni-magdeburg.de

    2006-08-01

    Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies. Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical data derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically. Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D{sub 1ml}) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D{sub 1ml} of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01). Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D{sub 1ml} of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data.

  19. Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

    PubMed

    Guttu, K; Røsok, B; Gislason, H; Fändriks, L; Svanes, K; Grønbech, J E

    1991-04-01

    In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

  20. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

    PubMed Central

    Sotirchos, Elias S.; Bhargava, Pavan; Eckstein, Christopher; Van Haren, Keith; Baynes, Moira; Ntranos, Achilles; Gocke, Anne; Steinman, Lawrence; Mowry, Ellen M.

    2016-01-01

    Objective: To study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS). Methods: In this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months. Results: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0–44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0–13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17+CD4+ T cells (p = 0.016), CD161+CD4+ T cells (p = 0.03), and effector memory CD4+ T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4+ T cells (p = 0.018) and naive CD4+ T cells (p = 0.04). These effects were not observed in the low-dose group. Conclusions: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4+ T cells and decreased proportion of effector memory CD4+ T cells with concomitant increase in central memory CD4+ T cells and naive CD4+ T cells. Classification of evidence: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects. PMID:26718578

  1. 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

  2. High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study

    PubMed Central

    Spooner, Luke; Fernandes, Kimberly; Martins, Diana; Juurlink, David; Mamdani, Muhammad; Paterson, J. Michael; Singh, Samantha; Gomes, Tara

    2016-01-01

    Aims To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity. Design Interventional time-series analysis. Setting Ontario, Canada, from 2003 to 2014. Participants Ontario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014. Interventions Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario’s Narcotics Safety and Awareness Act (NSAA; November 2011). Measurements Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions. Findings Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59). Conclusions Although the

  3. 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

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

    PubMed

    Palmer, Antony; Bradley, David; Nisbet, Andrew

    2012-06-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2015-01-01

    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 (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/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

  7. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice

    PubMed Central

    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. PMID:26272953

  8. Effect of feeding nitrite, ascorbate, hemin, and omeprazole on excretion of fecal total apparent N-nitroso compounds in mice.

    PubMed

    Mirvish, Sidney S; Davis, Michael E; Lisowyj, Michal P; Gaikwad, Nilesh W

    2008-12-01

    It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current project, adult Swiss mice were fed a semipurified diet and water containing additives for 7 days. Feces from individual mice was collected on day 7, dried, and extracted with water. Extracts were analyzed for ANC as before. Feeding 2.0 g sodium nitrite (NaNO2)/L drinking water raised fecal ANC levels from 5 to 63 nmol/g feces. In a dose-response study, fecal ANC levels were proportional to the nitrite concentration squared. Even 32 mg NaNO2/L raised fecal ANC levels 2.3-fold (P < 0.05). In other results, 64, 125, and 250 mg hemin/kg diet, fed with 2 g NaNO2/L water, showed 2.3, 2.2, and 4.6 times the ANC level for nitrite alone. Sodium nitrate (12 g/L water) did not affect fecal ANC output. Omeprazole (400 mg/kg diet) and sodium ascorbate (23 g/kg diet), when fed with 1 g NaNO2/L water, lowered fecal ANC levels by 65 and 41%, indicating that, when nitrite was fed, acid-catalyzed reactions in the stomach produced ANC, which passed down the gut to the feces. Tests indicated that nitrosothiols constituted about 20% of fecal and hot dog ANC. The observed effect of NaNO2 is thus far not consistent with the proposed hypothesis. The enhancement by hemin may help explain why red meat is a cause of colon cancer.

  9. 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.

  10. 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.

  11. 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