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Sample records for multiple ascending doses

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-03-28

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

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

    Science.gov (United States)

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

    2018-04-01

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

  4. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

    Science.gov (United States)

    Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

    2018-02-01

    Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

  5. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

  6. Multiple Ascending Aortic Mural Thrombi and Acute Necrotizing Mediastinitis Secondary to Acute Pancreatitis

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    Byung Kwon Chong

    2016-10-01

    Full Text Available The formation of aortic thrombi is an extremely rare complication of acute pancreatitis. Here we report a case of acute pancreatitis complicated by a paraesophageal pseudocyst, necrotizing mediastinitis, and the formation of multiple thrombi in the ascending aorta. The patient was successfully treated by surgical therapy, which included extensive debridement of the mediastinum and removal of the aortic thrombi under cardiopulmonary bypass. Although esophageal resection was not carried out concomitantly, the lesions were resolved and the patient remained free of complications over 2 years of follow-up care.

  7. Acute Ascending Flaccid Paralysis Secondary to Multiple Trigger Factor Induced Hyperkalemia

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    K. H. D. Thilini Hemachandra

    2018-01-01

    Full Text Available Background. Acute flaccid paralysis is an uncommon, but potentially life threatening, sequel of severe hyperkalemia. Reported primary aetiologies include renal failure, Addison’s disease, potassium sparing diuretics, potassium supplements, and dietary excess. Coconut water, when consumed in excess, has been reported to cause severe hyperkalemia. We report the case of acute ascending flaccid paralysis secondary to hyperkalemia induced by multiple trigger factors—king coconut water, renal failure, diabetes, metabolic acidosis, and potassium sparing diuretics. Case Presentation. A 78-year-old man presented with acute ascending type flaccid paralysis over five-hour duration and subsequently developed preterminal cardiac arrhythmias secondary to severe hyperkalemia (serum potassium: 7.02 mEq/L. He was on Losartan and Spironolactone for ischemic heart disease. Dietary history revealed excessive intake of king coconut water (Cocos nucifera over past one week. Electrocardiogram returned to normal rhythm and serum potassium was 6.1 mEq/L within 2 hours of institution of emergency management for life threatening hyperkalemia. Neurological symptoms completely recovered within twenty-four hours without the need for dialysis. Electromyogram three days after the initial presentation revealed normal findings. Conclusions. The report describes a rare case of secondary hyperkalemic flaccid paralysis induced by multiple trigger factors. It is important that patients with risk factors for hyperkalemia are educated regarding avoiding excess dietary potassium. Regular follow-up of these patients is mandatory with review of medication related side effects and serum electrolytes.

  8. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

    2016-01-01

    reproductive technologies. Methods: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed...... volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F. Conclusions: The single-dose pharmacokinetics of FE 999049 were adequately described by a population...

  9. Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug

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    N. Shafiq

    2014-01-01

    Full Text Available Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85±1.94 h, 13.77±2.05 h, and 878.74±133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

  10. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

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    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  11. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-12-01

    The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

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

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    Kim YH

    2015-06-01

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

  13. Multiple anatomy optimization of accumulated dose

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  14. Multiple anatomy optimization of accumulated dose

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-01

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

  15. Multiple anatomy optimization of accumulated dose.

    Science.gov (United States)

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

    2014-11-01

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

  16. Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study

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    Xu HR

    2016-05-01

    Full Text Available Hongrong Xu,1,* Lei Sheng,1,* Weili Chen,1 Fei Yuan,1 Mengjie Yang,1 Hui Li,1 Xuening Li,1 John Choi,2 Guiyu Zhao,2 Tianxin Hu,2 Yongguo Li,2 Yi Zhang,2 Li Chen2 1Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Clinical Research & Development, Hua Medicine, Shanghai, People’s Republic of China *These authors have contributed equally to this work Background: HMS5552, a novel fourth-generation glucokinase (GK activator, has demonstrated promising effects on glycemic control in preclinical models of type 2 diabetes. This single ascending dose study was conducted to investigate the safety, tolerability, pharmacokinetics (PK, and pharmacodynamics (PD of HMS5552 during its first-in-human exposure.Methods: Sixty healthy subjects were enrolled. In each of six dose-cohorts (5, 10, 15, 25, 35, and 50 mg, ten subjects were randomized with eight subjects receiving the same cohort-dose of HMS5552 and two receiving placebo. Plasma HMS5552 exposure, glucose, and insulin were measured repeatedly during fasting and after a standardized meal. Assessment included safety, PK, and PD endpoints.Results: HMS5552 showed dose-proportional increases in area under the curve 0 to the last quantifiable concentration (AUC0–t and maximum plasma concentration (Cmax. Slopes estimated by linear regression for AUC0–t and Cmax were ~1.0 (0.932 and 0.933, respectively. Geometric mean elimination half-life ranged from 4.48 to 7.51 hours and apparent clearance ranged from 11.5 to 13.1 L/h across all doses. No significant sex effect was observed in PK parameters. HMS5552 also demonstrated dose-related PD responses in terms of maximum glucose change from baseline (% and mean glucose area under effect curve 0–4 hours change from baseline (% (P<0.001. Fifteen adverse events were reported by nine subjects (ten with HMS5552 and five with the placebo. All adverse events were mild in intensity and resolved without any treatment

  17. Pharmacokinetics After Single Ascending Dose, Food Effect, and Safety of Sacubitril/Valsartan (LCZ696), an Angiotensin Receptor and Neprilysin Inhibitor, in Healthy Japanese Subjects.

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    Akahori, Mizuki; Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Zhou, Wei; Sunkara, Gangadhar

    2017-06-01

    LCZ696 (sacubitril/valsartan) is a novel angiotensin receptor neprilysin inhibitor (ARNI) that has been developed for treatment of heart failure patients with reduced ejection fraction and approved in the US, Europe, and many other countries. This randomized, placebo-controlled study was conducted in healthy Japanese male subjects (N = 50) to assess the pharmacokinetics and safety of single ascending oral doses (20-600 mg) of LCZ696. Food effect was also evaluated following administration of 200 mg dose. Plasma and urine samples from 40 subjects receiving LCZ696 were collected to assess pharmacokinetics of LCZ696 analytes (sacubitril, sacubitrilat, and valsartan). Following single oral dose administration of LCZ696, sacubitril and valsartan rapidly appeared in systemic circulation with a dose-linear increase in the exposure to the LCZ696 analytes. Of the administered dose, approximately 0.85 %, 54.0 %, and 8.19 % of sacubitril, sacubitrilat, and valsartan, respectively, were recovered in urine. Food reduced AUC of sacubitril, sacubitrilat, and valsartan by 21, 8, and 40 %, respectively, and C max by 72, 27, and 51 %, respectively. Single oral doses of up to 600 mg of LCZ696 were safe and generally well tolerated in healthy Japanese male subjects.

  18. Clinical study of a new therapy for nerve agent poisoning: Ascending dose tolerance study of HI-6 + atropine

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    Clement, J.G.; Bailey, D.G.; Madill, H.D.; Spence, J.D.

    1993-05-13

    HI-6 was rapidly absorbed from an IM injection site. Maximum HI-6 plasma concentrations of 1.88, 4.96, 8.31 15.0 ug/ml were found 28-36 min after administration and maintained above 4 ug/ml concentration for 0, 39, 112 172.5 min following administration of 62.5, 125, 250 or 500 mg HI-6 + atropine (2 mg), respectively. The calculated half life of HI-6 was 78.2 min following 62.5 mg HI-6 + atropine dose and approximately 64-67 min following 125-500 mg HI-6 + atropine doses. Approximately 50 % of the total dose of HI-6 was eliminated unchanged in the urine. There were significant changes (p < 0.05) in AST, CPK, creatinine and gamma GT following the 500 mg HI-6 + atropine dose but they were not considered to be clinically significant. Urinalysis, hematology and semen analysis over the 24 hr observation period was uneventful. There were no clinically significant changes in heart rate or ECG trace, respiration or blood pressure, visual and mental acuity following HI-6 + atropine.

  19. A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection.

    Directory of Open Access Journals (Sweden)

    Kwablah Awadzi

    2014-06-01

    Full Text Available Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin's safety and efficacy. Effects on the parasite were also assessed.Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44, 4 mg (N = 45 or 8 mg (N = 38 moxidectin or 150 µg/kg ivermectin (N = 45 with 18 months follow up. All ivermectin and 97%-100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%, rash (63% vs. 42%, increased pulse rate (61% vs. 36% and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%. These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01.The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control programmes could help them achieve onchocerciasis elimination

  20. Dose evaluation from multiple detector outputs using convex optimisation

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  1. Multiple cost criteria for occupational dose reduction

    International Nuclear Information System (INIS)

    James, J.Z.

    1983-01-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

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

    International Nuclear Information System (INIS)

    Wang Zhikang; Sun Jianzhong; Zhao Zudan

    2012-01-01

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

  4. ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Rodda, Sree; Tyldesley, Scott; Morris, W. James; Keyes, Mira; Halperin, Ross; Pai, Howard; McKenzie, Michael; Duncan, Graeme; Morton, Gerard; Hamm, Jeremy; Murray, Nevin

    2017-01-01

    Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of

  5. ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rodda, Sree [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Morris, W. James, E-mail: jmorris@bccancer.bc.ca [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Keyes, Mira [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency, Centre for the Southern Interior, Kelowna, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency, Vancouver Island Centre, Victoria, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Morton, Gerard [Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

    2017-06-01

    Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of

  6. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard; Oh, D Alexander; Parikh, Neha; Koch, Christian; Singla, Neil; Yu, Jin; Nalamachu, Srinivas; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants. Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800 mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4 h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24 h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7. Fifty participants (19-53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27-0.60 h post-dose for fentanyl sublingual spray. Peak (C max ) and total (AUC 0- t , AUC 0-∞ ) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800 mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses. Overall, single-dose fentanyl sublingual spray (100-800 mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200 mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses

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

    Directory of Open Access Journals (Sweden)

    Daniel T. C. Cox

    2017-02-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-05-01

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

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  11. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Rodda, Sree [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Centre for the Southern Interior, Vancouver, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Island Centre, Vancouver, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Morton, Gerard [Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

    2017-06-01

    Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. Methods and Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. Results: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). Conclusions: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

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

    DEFF Research Database (Denmark)

    Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-03-06

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Melissa Li

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

  16. Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica.

    Science.gov (United States)

    Okkerse, Pieter; Hay, Justin L; Versage, Eve; Tang, Yongqiang; Galluppi, Gerald; Ravina, Bernard; Verma, Ajay; Williams, Leslie; Aycardi, Ernesto; Groeneveld, Geert Jan

    2016-07-01

    BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study were to evaluate the pharmacokinetic and safety profiles and to determine the effects on pain of ascending doses of intravenous injections of BG00010 in patients with sciatica. This was a randomized, blinded, placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ). Safety and efficacy assessments were used as endpoints. The BG00010 concentration-time data indicated relatively low inter-patient variability and there was a dose-dependent (not dose-proportional) increase in serum exposure from 150 to 1200 μg kg(-1) . The effective half-life was between 40 and 60 h. The most frequently occurring adverse events (AEs) reported by patients receiving BG00010 were headache (67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in greater pain reduction than placebo or lower dose regimens, although a clear dose-response relationship was not seen. The pharmacokinetic profile of BG00010 was characterized by low intra-patient variability. These data from a small sample suggest that BG00010 may have a benefit for patients with sciatica. © 2016 The British Pharmacological Society.

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  19. Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

    Science.gov (United States)

    Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

    2017-04-01

    A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    1996-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    International Nuclear Information System (INIS)

    Denekamp, J.; Harris, S.R.

    1975-01-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

    Zhang, Geoffrey; Huang, T-C; Feygelman, Vladimir; Stevens, Craig; Forster, Kenneth

    2010-01-01

    Currently there are no commercially available tools to generate composite plans across different treatment modalities and/or different planning image sets. Without a composite plan, it may be difficult to perform a meaningful dosimetric evaluation of the overall treatment course. In this paper, we introduce a method to generate composite biological effective dose (BED) plans over multiple radiotherapy treatment modalities and/or multistage plans, using deformable image registration. Two cases were used to demonstrate the method. Case I was prostate cancer treated with intensity-modulated radiation therapy (IMRT) and a permanent seed implant. Case II involved lung cancer treated with two treatment plans generated on two separate computed tomography image sets. Thin-plate spline or optical flow methods were used as appropriate to generate deformation matrices. The deformation matrices were then applied to the dose matrices and the resulting physical doses were converted to BED and added to yield the composite plan. Cell proliferation and sublethal repair were considered in the BED calculations. The difference in BED between normal tissues and tumor volumes was accounted for by using different BED models, α/β values, and cell potential doubling times. The method to generate composite BED plans presented in this paper provides information not available with the traditional simple dose summation or physical dose summation. With the understanding of limitations and uncertainties of the algorithms involved, it may be valuable for the overall treatment plan evaluation.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  10. Combined Repair of Ascending Aortic Pseudoaneurysm and Abdominal Aortic Aneurysm in a Patient with Marfan Syndrome

    OpenAIRE

    Kokotsakis, John N.; Lioulias, Achilleas G.; Foroulis, Christophoros N.; Skouteli, Eleni Anna T.; Milonakis, Michael K.; Bastounis, Elias A.; Boulafendis, Dimitrios G.

    2003-01-01

    Pseudoaneurysms of the ascending aorta after the original inclusion/wrap technique of the Bentall procedure present a difficult surgical management problem and are associated with substantial morbidity and mortality. Patients with Marfan syndrome frequently develop aneurysms and dissections that involve multiple aortic segments. We present the case of a Marfan patient who successfully underwent repair of a giant ascending aortic pseudoaneurysm and concomitant repair of an abdominal aortic ane...

  11. A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

    Science.gov (United States)

    Struys, Michel M R F; Valk, Beatrijs I; Eleveld, Douglas J; Absalom, Anthony R; Meyer, Peter; Meier, Sascha; den Daas, Izaak; Chou, Thomas; van Amsterdam, Kai; Campagna, Jason A; Sweeney, Steven P

    2017-07-01

    Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships. Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer's assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated. Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer's assessment of alertness/sedation and Bispectral Index. This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.

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

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Jordan, T.M.

    2003-01-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Cui Y

    2013-12-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2007-07-01

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

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

    Science.gov (United States)

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

    2012-05-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

  3. Ascending aortic injuries following blunt trauma.

    Science.gov (United States)

    Sun, Xiumei; Hong, Jenny; Lowery, Robert; Goldstein, Steven; Wang, Zuyue; Lindsay, Joseph; Hill, Peter C; Corso, Paul J

    2013-11-01

    The diagnosis and the management of traumatic thoracic aortic injuries have undergone significant changes due to new technology and improved prehospital care. Most of the discussions have focused on descending aortic injuries. In this review, we discuss the recent management of ascending aortic injuries. We found 5 cohort studies on traumatic aortic injuries and 11 case reports describing ascending aortic injuries between 1998 to the present through Medline research. Among case reports, 78.9% of cases were caused by motor vehicle accidents (MVA). 42.1% of patients underwent emergent open repair and the operative mortality was 12.5%. 36.8% underwent delayed repair. Associated injuries occurred in 84.2% of patients. Aortic valve injury was concurrent in 26.3% of patients. The incidence of ascending aortic injury ranged 1.9-20% in cohort studies. Traumatic injuries to the ascending aorta are relatively uncommon among survivors following blunt trauma. Aortography has been replaced by computed tomography and echocardiography as a diagnostic tool. Open repair, either emergent or delayed, remains the treatment of choice. © 2013 Wiley Periodicals, Inc.

  4. Balloon popping with applications to ascending auctions

    NARCIS (Netherlands)

    N.S. Immorlica (Nicole Simone); A. Karlin; M. Mahdian (Mohammad); K. Talwar; A. Sinclair

    2007-01-01

    textabstractWe study the power of ascending auctions in a scenario in which a seller is selling a collection of identical items to anonymous unit-demand bidders. We show that even with full knowledge of the set of bidders' private valuations for the items, if the bidders are ex-ante identical, no

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-15

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Wu Qiuwen; Mohan, Radhe

    2002-01-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  11. Device occlusion of pseudoaneurysm of ascending aorta

    International Nuclear Information System (INIS)

    Agarwal, Mridul; Ray, Mili; Pallavi, M; Sen, Supratim; Ganguly, Debosree; Joshi, Pankaj; Tanti, Sanjay; Chattopadhyay, Amitabh; Bandyopadhyay, Biswajit

    2011-01-01

    Pseudoaneurysm of ascending aorta is an infrequent but well-recognized and potentially fatal complication after cardiac surgeries. The complication can develop early, delayed or late, and the presentation is also varied. We are presenting here two cases of pseudoaneurysm of ascending aorta following cardiac surgery that were successfully managed by the transcatheter method. The first one occurred following coronary artery bypass surgery and the second one occurred following double-valve replacement surgery. The aortic openings of these aneurysms were occluded with 12 mm and 10 mm atrial septal occluders, respectively, with a good outcome. An immediate postprocedure angiogram showed no residual flow into the sac. Six months of follow-up of both cases also showed excellent results

  12. Perforated Solitary Diverticulitis of the Ascending Colon

    Science.gov (United States)

    2005-06-01

    postoperative day 6. DISCUSSION Diverticuli of the right colon exist in approximately 1% to 5% of patients with diverticular disease .1-3 They are...ORIGINAL REPORTS Perforated Solitary Diverticulitis of the Ascending Colon CPT David S. Kauvar, MC, USA, MAJ, Jayson Aydelotte, MC, USA, and MAJ...Michael Harnisch, MC, USA Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas KEY WORDS: solitary colon diverticulum

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

    Science.gov (United States)

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

    2011-05-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  15. Combined Repair of Ascending Aortic Pseudoaneurysm and Abdominal Aortic Aneurysm in a Patient with Marfan Syndrome

    Science.gov (United States)

    Kokotsakis, John N.; Lioulias, Achilleas G.; Foroulis, Christophoros N.; Skouteli, Eleni Anna T.; Milonakis, Michael K.; Bastounis, Elias A.; Boulafendis, Dimitrios G.

    2003-01-01

    Pseudoaneurysms of the ascending aorta after the original inclusion/wrap technique of the Bentall procedure present a difficult surgical management problem and are associated with substantial morbidity and mortality. Patients with Marfan syndrome frequently develop aneurysms and dissections that involve multiple aortic segments. We present the case of a Marfan patient who successfully underwent repair of a giant ascending aortic pseudoaneurysm and concomitant repair of an abdominal aortic aneurysm. An aggressive surgical strategy followed by life-long cardiovascular monitoring is warranted in order to prolong the survival of these patients. (Tex Heart Inst J 2003;30:233–5) PMID:12959210

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

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

    Science.gov (United States)

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

    1993-01-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-01-21

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2016-12-06

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-15

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    1995-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2010-04-01

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

  13. Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

    DEFF Research Database (Denmark)

    Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby

    2012-01-01

    Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m...

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

    Science.gov (United States)

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

    2015-06-01

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

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

    DEFF Research Database (Denmark)

    Hansson, Markus; Gimsing, Peter; Badros, Ashraf

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  19. Surgical exclusion of postsurgical pseudoaneurysm of the ascending aorta

    Science.gov (United States)

    Barik, Ramachandra; Patnaik, Amar Narayana; Kumar, Ravintula Venkata; Mohapatra, Rudra Prasad; Medep, Vikas; Nemani, Lalita

    2014-01-01

    Pseudoaneurysm of ascending aorta after cardiac surgery is rare in children. We report a case of successful surgical exclusion of ascending aortic pseudoaneurysm in a 15-year-old boy. The neck of the aneurysm was in close proximity to the right coronary artery (RCA). PMID:24987261

  20. Surgical exclusion of postsurgical pseudoaneurysm of the ascending aorta

    Energy Technology Data Exchange (ETDEWEB)

    Barik, Ramachandra; Patnaik, Amar Narayana [Department of Cardiology, Nizam' s Institute of Medical Sciences, Hyderabad, Andhra Pradesh (India); Kumar, Ravintula Venkata; Mohapatra, Rudra Prasad [Department of Cardiothoracic Surgery, Nizam' s Institute of Medical Sciences, Hyderabad, Andhra Pradesh (India); Medep, Vikas; Nemani, Lalita [Department of Cardiology, Nizam' s Institute of Medical Sciences, Hyderabad, Andhra Pradesh (India)

    2014-01-01

    Pseudoaneurysm of ascending aorta after cardiac surgery is rare in children. We report a case of successful surgical exclusion of ascending aortic pseudoaneurysm in a 15-year-old boy. The neck of the aneurysm was in close proximity to the right coronary artery (RCA)

  1. Surgical exclusion of postsurgical pseudoaneurysm of the ascending aorta

    Directory of Open Access Journals (Sweden)

    Ramachandra Barik

    2014-01-01

    Full Text Available Pseudoaneurysm of ascending aorta after cardiac surgery is rare in children. We report a case of successful surgical exclusion of ascending aortic pseudoaneurysm in a 15-year-old boy. The neck of the aneurysm was in close proximity to the right coronary artery (RCA.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arlett Espinoza-Jiménez

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  5. Ascending uretero-pyelography in renal failure.

    Science.gov (United States)

    Kingston, R D; Shah, K J; Dawson-Edwards, P

    1977-09-01

    Ascending uretero-pyelography has been carried out over a period of 13 years in 97 consecutive patients with undiagnosed renal failure. Sixty-nine were in a non-obstructive uropathy group while 26 had ureteric obstructions. There were two failures. Over 60% of examinations were performed under local anaesthesia, each examination taking an average of 20 min. There has been no mortality and two anaesthetic complications have been the only significant morbidity. Ureteric injury, urinary infection and renal function have all been investigated and recorded. Five per cent of patients developed urinary infection following AUP but without any major consequences. No significant ureteric injury occurred and no late sequelae were noted. Neither any reaction to contrast medium nor any further deterioration in renal function was observed; AUP was diagnostic in 46% of patients. In the remainder it ruled out obstructive uropathy and gave useful information about the kidneys, ureters and bladder. In experienced hands and with proper facilities AUP is safe and can be helpful in the diagnosis and management of patients in renal failure.

  6. Heat transfer of ascending cryomagma on Europa

    Science.gov (United States)

    Quick, Lynnae C.; Marsh, Bruce D.

    2016-06-01

    Jupiter's moon Europa has a relatively young surface (60-90 Myr on average), which may be due in part to cryovolcanic processes. Current models for both effusive and explosive cryovolcanism on Europa may be expanded and enhanced by linking the potential for cryovolcanism at the surface to subsurface cryomagmatism. The success of cryomagma transport through Europa's crust depends critically on the rate of ascent relative to the rate of solidification. The final transport distance of cryomagma is thus governed by initial melt volume, ascent rate, overall ascent distance, transport mechanism (i.e., diapirism, diking, or ascent in cylindrical conduits), and melt temperature and composition. The last two factors are especially critical in determining the budget of expendable energy before complete solidification. Here we use these factors as constraints to explore conditions under which cryomagma may arrive at Europa's surface to facilitate cryovolcanism. We find that 1-5 km radius warm ice diapirs ascending from the base of a 10 km thick stagnant lid can reach the shallow subsurface in a partially molten state. Cryomagma transport may be further facilitated if diapirs travel along pre-heated ascent paths. Under certain conditions, cryolava transported from 10 km depths in tabular dikes or pipe-like conduits may reach the surface at temperatures exceeding 250 K. Ascent rates for these geometries may be high enough that isothermal transport is approached. Cryomagmas containing significant amounts of low eutectic impurities can also be delivered to Europa's surface by propagating dikes or pipe-like conduits.

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  8. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    International Nuclear Information System (INIS)

    Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V_1_0_0. All of the other measured dosimetric parameters including the V_9_5, V_9_9, and D_1_0_0 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  9. Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

    Science.gov (United States)

    Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of

  10. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

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

    Science.gov (United States)

    Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

    2015-01-01

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

  12. Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection.

    Science.gov (United States)

    Vornhagen, Jay; Armistead, Blair; Santana-Ufret, Verónica; Gendrin, Claire; Merillat, Sean; Coleman, Michelle; Quach, Phoenicia; Boldenow, Erica; Alishetti, Varchita; Leonhard-Melief, Christina; Ngo, Lisa Y; Whidbey, Christopher; Doran, Kelly S; Curtis, Chad; Waldorf, Kristina M Adams; Nance, Elizabeth; Rajagopal, Lakshmi

    2018-04-09

    Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and β-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-05-01

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

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  15. A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-11-15

    Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Nawfel, RD; Young, G

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

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

    Science.gov (United States)

    Demirol, Aygul; Gurgan, Timur

    2009-08-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  2. Adjusting to Chinese Ascendancy in the Global Clothing Industry ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Adjusting to Chinese Ascendancy in the Global Clothing Industry (Africa South of Sahara) ... conference of McGill's Institute for the Study of International Development. ... IDRC partner the World Economic Forum is building a hub for inclusive ...

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

    Science.gov (United States)

    Ben-Ami, Frida; Routtu, Jarkko

    2013-05-03

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Yara Dadalti Fragoso

    2014-09-01

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

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

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

    International Nuclear Information System (INIS)

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

    1977-01-01

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

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

    Science.gov (United States)

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

    2008-07-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

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

    International Nuclear Information System (INIS)

    Hamacher, K.A.; Sgouros, G.

    2001-01-01

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  14. Analysis of autologous platelet-rich plasma during ascending and transverse aortic arch surgery.

    Science.gov (United States)

    Zhou, Shao-Feng; Estrera, Anthony L; Miller, Charles C; Ignacio, Craig; Panthayi, Sreelatha; Loubser, Paul; Sagun, Dean L; Sheinbaum, Roy; Safi, Hazim J

    2013-05-01

    Coagulopathy is a common complication after ascending and transverse arch aortic surgery with profound hypothermic circuit arrest (PHCA). Blood conservation strategies to reduce transfusion have been ongoing and involve multiple treatment modalities in modern cardiac surgery. The purpose of this study is to evaluate the effectiveness of autologous platelet-rich plasma (aPRP) as a blood conservation technique to reduce blood transfusion in ascending and arch aortic surgery. Between 2003 and 2009, we retrospectively reviewed 685 cases of ascending aorta and transverse arch repair using PHCA. A total of 287 patients in which aPRP was used (aPRP group) were compared with 398 patients who did have aPRP (non-aPRP group). Perioperative transfusion requirements and clinical outcomes that included early mortality, postoperative stroke, renal dysfunction, prolonged ventilation, coagulopathy, and length of postoperative intensive care unit stay were analyzed. The data were analyzed by mean and frequency for continuous variables and qualitative variables. To account for potential selection bias, 2 types of propensity analysis were performed. In both unadjusted and adjusted analysis, perioperative transfusions were fewer in the aPRP group compared with the non-aPRP group: (3.9 units fewer packed red blood cells, 4.5 units fewer fresh frozen plasma, 7.9 units fewer platelets, and 6.8 units fewer cryoprecipitate). In all analyses, postoperative morbidity (stroke, duration of mechanical ventilation, and intensive care unit stay) were significantly improved. Hospital mortality rate was not significantly decreased. The utilization of aPRP was associated with a reduction in allogeneic blood transfusions as well as a decrease in early postoperative morbidity during repairs of the ascending and transverse arch aorta using PHCA. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Dean, M.H.

    2002-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cui Y

    2014-03-01

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

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

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  20. Ascending Aortic Dimensions in Former National Football League Athletes.

    Science.gov (United States)

    Gentry, James L; Carruthers, David; Joshi, Parag H; Maroules, Christopher D; Ayers, Colby R; de Lemos, James A; Aagaard, Philip; Hachamovitch, Rory; Desai, Milind Y; Roselli, Eric E; Dunn, Reginald E; Alexander, Kezia; Lincoln, Andrew E; Tucker, Andrew M; Phelan, Dermot M

    2017-11-01

    Ascending aortic dimensions are slightly larger in young competitive athletes compared with sedentary controls, but rarely >40 mm. Whether this finding translates to aortic enlargement in older, former athletes is unknown. This cross-sectional study involved a sample of 206 former National Football League (NFL) athletes compared with 759 male subjects from the DHS-2 (Dallas Heart Study-2; mean age of 57.1 and 53.6 years, respectively, P 40 mm (29.6% versus 8.6%; P history of hypertension, current smoking, diabetes mellitus, and lipid profile, the former NFL athletes still had significantly larger ascending aortas ( P 40 mm after adjusting for the same parameters. Ascending aortic dimensions were significantly larger in a sample of former NFL athletes after adjusting for their size, age, race, and cardiac risk factors. Whether this translates to an increased risk is unknown and requires further evaluation. © 2017 American Heart Association, Inc.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  2. Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice.

    Science.gov (United States)

    Cetkovic-Cvrlje, Marina; Thinamany, Sinduja; Bruner, Kylie A

    2017-12-01

    Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4 + T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action - in the context of T-cell immunity - that seemed to be dose

  3. Surgery for pseudoaneurysm of the ascending aorta under moderate hypothermia

    Directory of Open Access Journals (Sweden)

    Lee Dong-Hyup

    2011-09-01

    Full Text Available Abstract Pseudoaneurysm of the ascending aorta is a rare complication after cardiac surgery. Particularly, pseudoaneurysm due to postoperative infection in the ascending aorta requires surgical treatment with antibiotics. If a large sized pseudoaneurysm is located at the retrosternal space, then there is a very high risk of massive bleeding from rupture during performance of resternotomy. To avoid this risk, we performed femoro-femoral bypass under moderate hypothermia with transient circulatory arrest, and we report here on the successful result of this case.

  4. Monozygotic twins with Marfan's syndrome and ascending aortic aneurysm.

    Science.gov (United States)

    Redruello, Héctor Jorge; Cianciulli, Tomas Francisco; Rostello, Eduardo Fernandez; Recalde, Barbara; Lax, Jorge Alberto; Picone, Victorio Próspero; Belforte, Sandro Mario; Prezioso, Horacio Alberto

    2007-08-01

    Marfan's syndrome is a hereditary connective tissue disease, in which cardiovascular abnormalities (especially aortic root dilatation) are the most important cause of morbidity and mortality. In this report, we describe two 24-year-old twins, with a history of surgery for lens subluxation and severe cardiovascular manifestations secondary to Marfan's syndrome. One of the twins suffered a type A aortic dissection, which required replacement of the ascending aorta, and the other twin had an aneurysmal dilatation of the ascending aorta (46mm) and was prescribed medical treatment with atenolol and periodic controls to detect the presence of a critical diameter (50mm) that would indicate the need for prophylactic surgery.

  5. Single and multiple dose Fluconazole in the treatment of candidia vulvovaginitis: a prospective comparative study

    Directory of Open Access Journals (Sweden)

    Ashrafinia M

    2007-09-01

    Full Text Available  Background: Vulvovaginal candidiasis, the most common type of vaginitis, is usually caused by Candidia albicans. Patients experience a variety of symptoms. There are many types of vulvovaginal candidiasis with various microbial causes, symptoms, host circumstances, recurrence rates, and responses to treatment. The purpose of this study was to find the best method of treatment of complicated vaginitis as determined by its high prevalence, varying symptoms and signs and patient complaints.Methods: In this open clinical trial without placebo control, we studied all patients aged 18 to 65 years, suffering from vaginitis symptoms that presented at the gynecological clinic of Arash Hospital, Tehran, Iran, during the year 2004. After obtaining informed consent, we assessed the response to a treatment of single 150 mg dose of fluconazole in one group, and sequential 150 mg doses of fluconazole in the other. The analysis was performed using SPSS statistical software (version 11.Results: With regard to symptom severity, no significant difference was found between the groups. The rate of excoriation and fissure formation demonstrated significant difference between the two groups (p=0.048. Assessment of clinical and mycological response proved that patients with severe vaginitis treated with sequential doses of fluconazole had a better general status than those in the other group. The difference between the severity of vaginitis and positive response to the treatment in culture was not significant among patients with recurrent vaginitis.Conclusion: Patients with mild to moderate recurrent vaginitis show better response to treatment. The high rate of positive culture on day 35 reconfirms the limitation of fluconazole and other azoles as fungistatic drugs.

  6. Evaluation of multiple scan average dose (MSAD) levels in computerized tomography in Minas Gerais state, Brazil

    International Nuclear Information System (INIS)

    Alonso, Thessa C.; Vieira, Leandro de A.; Barbosa, Nayra V.; Oliveira, Jeyselaine R. de; Cesar, Adriana C.Z.; Silva, Teogenes A. da

    2014-01-01

    Computed Tomography (CT) grows every year and is a diagnostic method that has revolutionized radiology with advances in procedures for obtaining image. However, the indiscriminate use of this method generates relatively high doses in patients. The diagnostic reference levels (DRLs) is a practical tool to promote the evaluation of existing protocols. The optimization and the periodic review of the protocols are important to balance the risk of radiation. The present study aims to conduct a survey of levels of MSAD of Minas Gerais following the procedures recommended by current Brazilian law. (author)

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  8. A Robust Open Ascending-price Multi-unit Auction Protocol against False-name Bids

    Science.gov (United States)

    Iwasaki, Atsushi; Yokoo, Makoto; Terada, Kenji

    This paper develops a new ascending-price multi-unit auction protocol that has following characteristics: (i) it has an open format, (ii) sincere bidding is an equilibrium strategy even if the marginal utilities of each agent can increase and agents can submit false-name bids. False-name bids are bids submitted under fictitious names such as multiple e-mail addresses, which can be done easily in the Internet. This is the first protocol that has these two characteristics. We show that our new protocol outperforms an existing protocol, which satisfies (ii), with respect to the social surplus and the seller's revenue.

  9. Neutron/gamma dose separation by the multiple-ion-chamber technique

    International Nuclear Information System (INIS)

    Goetsch, S.J.

    1983-01-01

    Many mixed n/γ dosimetry systems rely on two dosimeters, one composed of a tissue-equivalent material and the other made from a non-hydrogenous material. The paired chamber technique works well in fields of neutron radiation nearly identical in spectral composition to that in which the dosimeters were calibrated. However, this technique is drastically compromised in phantom due to the degradation of the neutron spectrum. The three-dosimeter technique allows for the fall-off in neutron sensitivity of the two non-hydrogenous dosimeters. Precise and physically meaningful results were obtained with this technique with a D-T source in air and in phantom and with simultaneous D-T neutron and 60 Co gamma ray irradiation in air. The MORSE-CG coupled n/γ three-dimensional Monte Carlo code was employed to calculate neutron and gamma doses in a water phantom. Gamma doses calculated in phantom with this code were generally lower than corresponding ion chamber measurements. This can be explained by the departure of irradiation conditions from ideal narrow-beam geometry. 97 references

  10. Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

    Science.gov (United States)

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

    2016-10-01

    Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose. © 2016 John Wiley & Sons Ltd.

  11. Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

    Directory of Open Access Journals (Sweden)

    Shadi Baniasadi

    Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

  12. Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

    Directory of Open Access Journals (Sweden)

    Shadi Baniasadi

    2013-02-01

    Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

  13. Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.

    Science.gov (United States)

    Lin, Marvin; Yin, Na; Murphy, Barbara; Medof, M Edward; Segerer, Stephan; Heeger, Peter S; Schröppel, Bernd

    2010-09-01

    The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.

  14. Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kirsch Lee E

    2009-12-01

    Full Text Available Abstract Background The population pharmacokinetics of artesunate (AS and its active metabolite dihydroartemisinin (DHA were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka of 3.85 h-1. The population estimates of apparent clearance (CL/F and volume of distribution (V2/F for AS were 1190 L/h with 36.2% inter-individual variability (IIV and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F and central volume of distribution (V3/F were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F and peripheral volume of distribution (V4/F for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in

  15. The development of a methodology to assess population doses from multiple sources and exposure pathways of radioactivity

    International Nuclear Information System (INIS)

    Hancox, J.; Stansby, S.; Thorne, M.

    2002-01-01

    The Environment Agency (EA) has new duties in accordance with the Basic Safety Standards Directive under which it is required to ensure that doses to individuals received from exposure to anthropogenic sources of radioactivity are within defined limits. In order to assess compliance with these requirements, the EA needs to assess the doses to members of the most highly exposed population groups ('critical' groups) from all relevant potential sources of anthropogenic radioactivity and all relevant potential exposure pathways to such radioactivity. The EA has identified a need to develop a methodology for the retrospective assessment of effective doses from multiple sources of radioactive materials and exposure pathways associated with those sources. Under contract to the EA, AEA Technology has undertaken the development of a suitable methodology as part of EA R and D Project P3-070. The methodology developed under this research project has been designed to support the EA in meeting its obligations under the Euratom Basic Safety Standards Directive and is consistent with UK and international approaches to radiation dosimetry and radiological protection. The development and trial application of the methodology is described in this report

  16. Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

    Science.gov (United States)

    Miceli Sopo, S; Greco, M; Monaco, S; Varrasi, G; Di Lorenzo, G; Simeone, G

    2015-01-01

    Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

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

    Science.gov (United States)

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

    2016-11-01

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

  18. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  19. Estimation of effective dose for the diagnosis and follow-up of multiple myeloma using conventional radiology

    International Nuclear Information System (INIS)

    Tsalafoutas, I.; Kostopoulou, H.; Steinhauer, G.; Koukourakis, G.; Yakoumakis, E.

    2012-01-01

    Background and objective: Multiple myeloma (MM) is a haemolytic neoplasm which produces osteolytic lesions and necessitates the periodical radiological examination of the skeleton for monitoring the disease progression. This involves the acquisition of multiple radiographs every 3 to 6 months, depending on the extent and the stage of the disease. Our objective was to estimate the cumulative patient dose during the radiographic investigation of MM. Materials and methods: Sixty eight MM radiographic examinations performed with a digital X-ray unit were recorded on a CD-rom in DICOM format. The DICOM data were extracted using appropriate software (DICOM Info Extractor) and were input into a Microsoft Excel based spreadsheet, containing embedded algorithms for the identification of the radiological examination type and the estimation of entrance surface air kerma (ESAK), dose area product (DAP) and effective dose (E) in each radiograph. The DAP to E conversion coefficients for each examination type were derived using the PCXMC 2.0 Monte Carlo simulation software for the case of a standard adult patient utilizing the irradiation geometry as this was perceived from the images and the DICOM data. Results: The mean values [and ranges] were: for number of radiographs= 14 [7-23], for cumulative ESAK 13 [2-44] mGy, for cumulative DAP= 6 [1.35-16.5] Gycm 2 and for E= 0. [0.14-2.4] mSv. Conclusion: The average E value calculated is smaller than the values of 1.7 and 2.4 mSv reported in the literature and even smaller than the values of 4.8 and 4.1 mSv reported for MM diagnosis using whole-body CT. (authors)

  20. Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

    Science.gov (United States)

    Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica; Merillat, Sean; Whidbey, Christopher; Ngo, Lisa Y.; Adams Waldorf, K. M.

    2016-01-01

    ABSTRACT Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae. However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. PMID:27353757

  1. The problem of calcified ascending aorta during aortocoronary bypass

    Directory of Open Access Journals (Sweden)

    Nežić Duško G.

    2004-01-01

    Full Text Available Heavily calcified ascending aorta significantly increased morbidity and lethality during open-heart surgery. Cannulation and clamping (partial or total of severely atherosclerotic ascending aorta can easily cause damage and rupture of aortic wall, with consequential distal (often fatal embolization with atheromatous debris (brain, myocardium. From June 1998. until June 2000, 11 of 2 136 (0.5% patients who underwent coronary artery bypass grafting were with the severe atheromatous ascending aorta. The site of cannulation was in the aortic arch in three patients (aorta was occluded with Foley catheter in one case, and single clamp technique was used in the other two cases. The femoral artery was the cannulation site in other five cases. Profound hypothermia, ventricular fibrillation, and circulatory arrest, with no cross-clamping or cardioplegia, were used in three patients. Two patients were operated on with extracorporeal circulation, one in normothermia, on the beating heart, the other in moderate hypothermia, on fibrillating heart. In three patients myocardial revascularization was performed on the beating heart, in normothermia, without extracorporeal circulation. Postoperative course was uneventful in all 11 patients. Neither atheroembolism in the peripheral organs, nor atheroembolism of the extramities occurred. The proposed surgical approaches have the potential to reduce the prevalence of stroke and systemic embolization associated with coronary artery bypass grafting in patients with heavily calcified ascending aorta. This result was achieved due to the applied modifications of standard cardiosurgical technique.

  2. Mobile caecum and ascending colon syndrome in a Nigerian adult

    African Journals Online (AJOL)

    posterior peritoneum. Appendectomy and caecopexy, using a lateral peritoneal flap were performed. The diagnosis of mobile caecal syndrome should be considered in patients with chronic right lower quadrant pain, and appendectomy and caecopexy offers a great relief. Keywords: Adult, ascending colon, mobile caecum, ...

  3. Analytical Description of Ascending Motion of Rockets in the Atmosphere

    Science.gov (United States)

    Rodrigues, H.; de Pinho, M. O.; Portes, D., Jr.; Santiago, A.

    2009-01-01

    In continuation of a previous work, we present an analytic study of ascending vertical motion of a rocket subjected to a quadratic drag for the case where the mass-variation law is a linear function of time. We discuss the detailed analytical solution of the model differential equations in closed form. Examples of application are presented and…

  4. 'Ascended far above all the heavens': Rhetorical functioning of ...

    African Journals Online (AJOL)

    This article explores the dynamic yet complex intertextual fusion and reappropriation of (mainly Jewish) traditions in Ephesians as the author's experience and understanding of the ascended Christ. Special attention is given to the probable functioning of Psalm 68:18 (LXX 67:19) in Ephesians 4:1–16. In conclusion, the ...

  5. Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

    Directory of Open Access Journals (Sweden)

    Jay Vornhagen

    2016-06-01

    Full Text Available Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS, or Streptococcus agalactiae. However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth.

  6. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    RESULT. We herein report a case of a 40-year-old male with mucosa - associated lymphoid tissue. [MALT] lymphoma of the transverse colon, ascending colon and caecum. He presented with severe abdominal pains and a centrally located huge abdominal mass for which a surgical resection was done. Histologically.

  7. Coil embolization of an anastomotic leak after ascending aorta replacement

    DEFF Research Database (Denmark)

    Nørgaard, Anders; Andersen, Lars Ib; Haahr, P.E.

    2008-01-01

    treated aneurysm in the ascending thoracic aorta complicated with an anastomotic leak. If a short prosthesis (6 cm) had been available, the anastomotic leak would have been treated with endovascular repair. In lack of this prosthesis, we were forced to treat the patient with a method not generally...

  8. Evaluation of radiation dose in 64-row whole-body CT of multiple injured patients compared to 4-row CT

    International Nuclear Information System (INIS)

    Harrieder, A.; Geyer, L.L.; Koerner, M.; Deak, Z.; Wirth, S.; Reiser, M.; Linsenmaier, U.

    2012-01-01

    Purpose: To evaluate radiation exposure in whole-body CT (WBCT) of multiple injured patients comparing 4-row multidetector computed tomography (MDCT) to 64-row MDCT. Materials and Methods: 200 WBCT studies were retrospectively evaluated: 92 4-row MDCT scans and 108 64-row MDCT scans. Each CT protocol was optimized for the particular CT system. The scan length, CT dose index (CTDI), and dose length product (DLP) were recorded and analyzed for radiation exposure. The mean effective dose was estimated based on conversion factors. Student's t-test was used for statistical analysis. Results: The mean CTDI vol values (mGy) of the thorax and abdomen were significantly reduced with 64-row MDCT (10.2 ± 2.5 vs. 11.4 ± 1.4, p < 0.001; 14.2 ± 3.7 vs. 16.1 ± 1.7, p < 0.001). The DLP values (mGy x cm) of the head and thorax were significantly increased with 64-row MDCT (1305.9 ± 201.1 vs. 849.8 ± 90.9, p < 0,001; 504.4 ± 134.4 vs. 471.5 ± 74.1, p = 0.030). The scan lengths (mm) were significantly increased with 64-row MDCT: head 223.6 ± 35.8 vs. 155.5 ± 12.3 (p < 0.001), thorax 427.4 ± 44.5 vs. 388.3 ± 57.5 (p < 0.001), abdomen 520.3 ± 50.2 vs. 490.8 ± 51.6 (p < 0.001). The estimated mean effective doses (mSv) were 22.4 ± 2.6 (4-row MDCT) and 24.1 ± 4.6 (64-row MDCT; p = 0.001), resulting in a percentage increase of 8 %. Conclusion: The radiation dose per slice of the thorax and abdomen can be significantly decreased by using 64-row MDCT. Due to the technical advances of modern 64-row MDCT systems, the scan field can be adapted to the clinical demands and, if necessary, enlarged without time loss. As a result, the estimated mean effective dose might be increased in WBCT. (orig.)

  9. Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    Deise Riba Coelho

    2014-07-01

    Full Text Available Meglumine antimoniate (MA and sodium stibogluconate are pentavalent antimony (SbV drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous. Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h and a slow (t1/2 >> 24 h elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain. The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

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

    International Nuclear Information System (INIS)

    Azab, Kh.SH.

    2007-01-01

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

  11. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase

    Directory of Open Access Journals (Sweden)

    Milena V. Oliveira

    2016-10-01

    Full Text Available Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking the changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across 2 groups. Emphysema (ELA animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU with a 1-week interval between them. Controls (C received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma was increased compared to C (p = 0.0001. The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p=0.0197. Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways were increased, whereas static lung elastance was reduced compared to C (p=0.0094. After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1beta, keratinocyte-derived chemokine, hepatocyte growth factor, and vascular endothelial growth factor; and collagen fiber content in the pulmonary vessel wall were increased compared to C (p=0.0096. At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during controlled

  12. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  13. Effects of multiple low dose radiation on the apoptosis of splenocytes and immune factor in male diabetic rats

    International Nuclear Information System (INIS)

    Li Yanbo; Guo Caixia; Dong Lihua; Wang Jianfeng; Liu Shuchun; Lu Zhe; Gong Shouliang

    2009-01-01

    Objective: To explore the effect of multiple low dose radiation (LDR) on the apoptosis of splenocytes and immune factors in diabetes mellitus (DM) rats. Methods: The rats were randomly divided into control, DM and DM + LDR groups. The irradiation doses were 25, 50 and 75 mGy, and the irradiated times were 15. At the fourth weekend after the DM rats irradiated, the apoptotic rate and TCRαβ percentage of splenocytes were detected by flow cytometry, and the content of IL-2 in both serum and supernatant of cultured splenocytes were detected by ELISA. Results: Compared with that in the control, the body weight (BW) decreased in the DM and DM + LDR groups,particularly in DM group. The blood glucose (BG) level in the DM + LDR groups was higher than that in the control, but decreased significantly as compared with that in the DM group (P < 0.01). As compared with those in the control, the apoptotic rate in DM + 50 mGy (P < 0.05) and the content of serum IL-2 in DM + 75 mGy group (P < 0.01) all increased significantly, while the content of IL-2 in supernatant of cultured splenocytes decreased significantly in the DM + LDR groups. Compared with those in the DM group, the apoptotic rate and the percentage of TCRαβ in splenocytes in the DM + LDR groups (P < 0.01-P < 0.001) and the content of IL-2 in serum in DM + 50 mGy group (P < 0.01) decreased significantly. Conclusions: The multiple LDR could weaken the loss of BW and increase of BG caused by DM, decrease the splenocyte apoptosis induced by DM, and regulate the immune factors. (authors)

  14. Anti-CD20 Cell Therapies in Multiple Sclerosis—A Fixed Dosing Schedule for Ocrelizumab is Overkill

    Directory of Open Access Journals (Sweden)

    Jagannadha Avasarala

    2017-10-01

    Full Text Available Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS. Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this—Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.

  15. An ascending multi-item auction with financially constrained bidders

    Directory of Open Access Journals (Sweden)

    Gerard van der Laan

    2016-12-01

    Full Text Available Several heterogeneous items are to be sold to a group of potentially budget- constrained bidders. Every bidder has private knowledge of his own valuation of the items and his own budget. Due to budget constraints, bidders may not be able to pay up to their values and typically no Walrasian equilibrium exists. To deal with such markets, we propose the notion of 'equilibrium under allotment' and develop an ascending auction mechanism that always finds such an equilibrium assignment and a corresponding system of prices in finite time. The auction can be viewed as a novel generalization of the ascending auction of Demange et al. (1986 from settings without financial constraints to settings with financial constraints. We examine various strategic and efficiency properties of the auction and its outcome.

  16. Diminutive Porcelain Ascending Aorta With Supravalvular Aortic Stenosis.

    Science.gov (United States)

    Houmsse, Mustafa; McDavid, Asia; Kilic, Ahmet

    2018-05-01

    This report describes the case of a 49-year-old man with a medical history significant for congenital aortic stenosis. The patient presented with progressive shortness of breath and decreased stamina and was found to have a concentric, diminutive porcelain ascending aorta with diffuse supravalvular aortic stenosis. We describe treatment with an aortic root augmentation and Bentall procedure using hypothermic circulatory arrest. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Analytical description of ascending motion of rockets in the atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, H; Pinho, M O de; Portes, D Jr [Centro Federal de Educacao Tecnologica do Rio de Janeiro, 20271-110, Rio de Janeiro, RJ (Brazil); Santiago, A [Instituto de Fisica, Universidade Estadual do Rio de Janeiro, 20559-900, Rio de Janeiro, RJ (Brazil)], E-mail: harg@cbpf.br, E-mail: ajsant@uerj.br

    2009-01-15

    In continuation of a previous work, we present an analytic study of ascending vertical motion of a rocket subjected to a quadratic drag for the case where the mass-variation law is a linear function of time. We discuss the detailed analytical solution of the model differential equations in closed form. Examples of application are presented and discussed. This paper is intended for undergraduate physics teachers and for graduate students.

  18. Intrapericardial bronchogenic cyst adherent to ascending aorta in young patient

    Directory of Open Access Journals (Sweden)

    Reddy Atipo-Galloye

    2014-06-01

    Full Text Available Bronchogenic cysts arise from an abnormal budding of the ventral diverticulum of the foregut or the thracheobronchial tree during embryogenesis. An intrapericardial location is an extremely rare finding. Symptoms are related to cardiac structure compression, but in most case they remain asymptomatic. We present a case of intrapericardial bronchogenic cyst in a young patient, resected entirely with repair of right lateral proximal ascending aorta with PTFE graft.

  19. Deposits formed by ascending vein water (3 type)

    International Nuclear Information System (INIS)

    Komarova, G.V.

    1980-01-01

    Deposits formed by ascending vein waters (3 type), are considered using uranium-bitumen deposit in red-coloured continental sediments of Permo-Triassic as an example. Geological-structural and hydrogeological conditions of mineralization localization and conditions of deposit formation are discussed. Mineralogic-geochemical features and morphology of ore bodies are characterized. Attention is paid to the problem of epigenetic zone in ore-containing rocks and stages of its formation [ru

  20. Organization of ascending spinal projections in Caiman crocodilus.

    Science.gov (United States)

    Ebbesson, S O; Goodman, D C

    1981-01-01

    Ascending spinal projections in the caiman (Caiman crocodilus) were demonstrated with Nauta and Fink-Heimer methods following hemisections of the third spinal segment in a series of twelve animals. These results were compared with earlier data in the literature obtained from a turtle, a snake, and a lizard using the same experimental and histological procedures. The results show remarkable similarities considering that each species represents a different reptilian order with different evolutionary history and habitat. However, the caiman displays several important peculiarities. Although the dorsal funiculus of the caiman contains the largest number of ascending spinal projections of the four species examined, this funiculus has not differentiated into cuneate and gracile fasciculi as is the case in the tegu lizard. The ventro-lateral ascending spinal projections follow a fundamentally similar general morphologic pattern in the four species with only minor variations. The anatomical arrangement in the caiman and tegu lizard appears most similar in the high cervical and the medullary regions; however, this is not the case in midbrain and thalamic regions where considerably more extensive projections are seen in the caiman. In the caiman an extensive spinal connection to the ventro-lateral nucleus of the dorsal thalamus is present; this connection is reminiscent of the mammalian spinal projection to the ventro-basal complex. The caiman has in common with the other three reptilian species a small projection to another dorsal thalamic region that is apparently homologous to the mammalian intralaminar nuclei, which are the destination of the mammalian paleospinothalamic tract.

  1. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Fu J

    2016-04-01

    Full Text Available Jie Fu,1 Lilei Peng,2 Xiaogang Li1 1Department of Neurology, 2Department of Neurosurgery, The Affiliated Hospital of Luzhou Medical College, Luzhou, People’s Republic of China Objective: Vortioxetine is a novel antidepressant approved for the treatment of major depressive disorder by the US Food and Drug Administration in September 2013. This meta-analysis assessed the efficacy and safety of different doses of vortioxetine for generalized anxiety disorder of adults.Methods: PubMed, Cochrane Library, PsycINFO, and Clinical Trials databases were searched from 2000 through 2015. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were searched to identify additional studies. The search was limited to individual randomized controlled trials (RCTs, and there was no language restriction. Four RCTs met the selection criteria. These studies included 1,843 adult patients. Results were expressed as odds ratios (ORs and 95% confidence intervals (CIs. The data were pooled with a random-effects or fixed-effects model.Results: The results showed that multiple doses (2.5, 5, and 10 mg/d of vortioxetine did not significantly improve the generalized anxiety disorder symptoms compared to placebo (OR=1.16, 95% CI=0.84–1.60, Z=0.89, P=0.38; OR=1.41, 95% CI=0.82–2.41, Z=1.25, P=0.21; OR=1.05, 95% CI=0.76–1.46, Z=0.32, P=0.75, respectively. We measured the efficacy of 2.5 mg/d vortioxetine compared to 10 mg/d, and no significant differences were observed. The common adverse effects included nausea and headache. With increased dose, nausea was found to be more frequent in the vortioxetine (5 and 10 mg/d group (OR=2.99, 95% CI=1.31–6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85–4.25, Z=4.85, P<0.00001, respectively, but no significant differences were observed for headache.Conclusion: The results showed no significant improvement in the treatment of generalized anxiety disorder for vortioxetine compared to placebo

  2. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...... and at the end of each day. Both treatments were effective immediately after the first dose and during the subsequent multiple-dose phase. There were no statistically significant differences between ketorolac and Ketogan. The results show that 10-mg doses of ketorolac in intramuscular injections followed by 10......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...

  3. Method of examination of blood microcirculation in skin by multiple using of an identical dose of radioactive Xe/sup 133/ gas

    Energy Technology Data Exchange (ETDEWEB)

    Lewandowski, J.; Bogdanowski, T.; Brzezinska-Wcislo, L. (Slaska Akademia Medyczna, Katowice (Poland))

    1981-01-01

    The introduced method of Xe/sup 133/ gas application on epidermis serves to the investigation of microcirculation of blood within skin. It consists in a single use a dose of radioactive gas which is injected under the plastic membrane adhering to the skin surface. Our method of gaseous Xe/sup 133/ contact with epidermis enabling the multiple utilization of once applied dose to further examination is described.

  4. Evaluation of multiple low doses of copper oxide wire particles compared with levamisole for control of Haemonchus contortus in lambs.

    Science.gov (United States)

    Burke, J M; Miller, J E

    2006-06-30

    High levels of anthelmintic resistance in gastrointestinal nematodes (GIN) of small ruminants have created the need for alternative approaches to parasite control. Copper oxide wire particles (COWP; 2g) have proven effective in decreasing GIN infection in lambs. However, the risk of copper toxicity has limited the usefulness of this approach. Recently, smaller doses (0.5 and 1g) have proven effective in GIN control, reducing the risk of toxicity. The objective of this study was to examine the effectiveness and risk of toxicity using multiple small doses of COWP for GIN control in lambs between weaning and market weight. Dorper crossbred ram lambs were orally administered levamisole (Levasol, 8.0mg/kg; n=8), 0.5g (n=9), or 1g COWP (n=9) at weaning (Day 0; 118+/-2 days of age; late May 2005) and again at 6-week intervals for a total of four treatments. A pooled fecal culture determined that Haemonchus contortus was the predominant gastrointestinal parasite at weaning. Lambs grazed bermudagrass pastures and were supplemented with up to 500g corn/soybean meal and free choice trace mineralized salt. Fecal egg counts (FEC), packed cell volume (PCV), and plasma aspartate aminotransferase (AST) activity were determined every 14 days and lambs weighed every 28 days. GIN infection reached a peak at Day 42 (high FEC, low PCV). COWP effectively reduced FEC on Days 0 and 42 compared with the previous week, but did not reduce FEC on Days 84 and 126 (treatment by time interaction, Pcopper in the liver on Day 155 were greater in COWP-treated lambs (Pcopper toxicity.

  5. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    Science.gov (United States)

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

  6. [Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis].

    Science.gov (United States)

    Rossiev, V A; Makarov, S V; Aleksandrova, I Ia; Dolgikh, G T; Lipshina, S R; Stukalova, T A; Trushina, O A; Fedorova, E Iu; Lipina, L N; Sivak, V F; Korenev, P P; Murashov, B F

    2002-01-01

    To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

  7. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Ocular Pharmacokinetics of Dorzolamide and Brinzolamide After Single and Multiple Topical Dosing: Implications for Effects on Ocular Blood FlowS⃞

    Science.gov (United States)

    Kadam, Rajendra S.; Jadhav, Gajanan; Ogidigben, Miller

    2011-01-01

    Ophthalmic carbonic anhydrase inhibitors have been shown to improve retinal and optic nerve blood flow. However, the relative tissue distributions of commercially available carbonic anhydrase inhibitors to the optic nerve are not known. The objective of this study was to compare the ocular pharmacokinetics and tissue distribution profiles of dorzolamide and brinzolamide after single and multiple topical applications. Pigmented rabbits were treated with single or multiple topical administrations of 30 μl of Trusopt (dorzolamide hydrochloride ophthalmic solution, 2%) to one eye and 30 μl of Azopt (brinzolamide ophthalmic suspension, 1%) to the other eye. Rabbits were euthanized at 10 predetermined time intervals over a period of 24 h, and ocular tissues and plasma samples were collected. For multiple dosing, rabbits were dosed twice per day with an 8-h interval between two doses, groups of rabbits were euthanized at 7, 14, and 21 days at 1 h after the last dose, and ocular tissues and plasma samples were collected. Drug levels in tissue samples were measured using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters (Cmax, Tmax, and AUC0–24) were estimated by noncompartmental analysis. After a single dose, dorzolamide delivery (AUC0–24) to the aqueous humor, anterior sclera, posterior sclera, anterior retina, posterior retina, anterior vitreous, and optic nerve was 2-, 7-, 2.6-, 1.4-, 1.9-, 1.2-, and 9-fold higher than those of brinzolamide. Cmax was 2- to 5-fold higher for dorzolamide than that of brinzolamide in all of the ocular tissue. After multiple dosing, dorzolamide levels in the aqueous humor, sclera, retina, vitreous humor, and optic nerve were higher than those of brinzolamide, but statistical significance was achieved only with aqueous humor, vitreous humor, and optic nerve. Dorzolamide levels in the aqueous humor, anterior vitreous, posterior vitreous, and optic nerve were 1.4- to 3.2-, 2.4- to 2.7-, 2.2- to 4.5-, and 2.4- to

  9. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    Science.gov (United States)

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

  10. Side-effects in ascending cervical myelography using iopamidol and metrizamide - a double blind study

    International Nuclear Information System (INIS)

    Bockenheimer, S.; Eichenlaub, H.

    1986-01-01

    A double blind study was performed to examine the side-effects of Metrizamide (group 1) and of Jopamidol (group 2) in ascending cervical myelography. Both groups were compared to a control group (group 3) comprising patients who had undergone lumbar puncture only. EEG was taken of the patients in groups 1 and 2 before as well as 6 and 24 h after intervention. Side-effects were collected by means of a questionnaire. Response time, concentration, memory and mood were examined psychometrically. Training effects or defensive attitudes in the multiple test examinations were checked against another control group of patients (group 4) which had no myelographic nor lumbar-puncture-induced impairment. Statistical findings corroborated our clinical impression that side-effects occurred after Metrizamide administration at a more than simply random rate. (orig.) [de

  11. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A.; Oturai, D B; Sørensen, P S

    2015-01-01

    BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate...... the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. METHODS: A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference...... population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. RESULTS: Osteopenia was present in 38...

  12. A comparative study of ascending urethrogram and sono-urethrogram in the evaluation of stricture urethra

    Directory of Open Access Journals (Sweden)

    Ravikumar B.R.

    2015-04-01

    Full Text Available To compare the efficacy of sono-urethrogram and ascending urethrogram in the evaluation of stricture urethra. Materials and Methods In this prospective study 40 patients with obstructive lower urinary tract symptoms and suspected to be having stricture urethra were subjected to ascending urethrogram and sonourethrogram. The radiologist was blinded to the findings of ascending urethrogram. All the sonourethrograms were done by the same radiologist. The findings of sonourethrogram & ascending urethrogram were compared with the findings of cystoscopy and intra-operative findings. The specificity, sensitivity,positive predictive value and negative predictive value of each modality in the diagnosis of various urethral anomalies were estimated. Results The sonourethrogram identified stricture disease in all the patients who had abnormal ascending urethrogram. In addition, other abnormalities like spongiofibrosis, diverticula and stones which were not picked up in ascending urethrogram were diagnosed by sonourethrogram. The cystoscopic and intra-operative findings with respect to stricture length, diameter and spongiofibrosis correlated well with sono-urethrogram findings. 5 patients who had stricture in the ascending urethrogram were found to be having the normal urethra in sonourethrogram and confirmed by cystoscopy. Conclusion sonourethrogram is an effective alternative to ascending urethrogram in the evaluation of stricture urethra. It is more sensitive in the diagnosis of anterior urethral strictures than posterior urethral strictures. It is superior to ascending urethrogram in the identification of spongiofibrosis, diameter and length of the stricture. The complications were lower in sonourethrogram group compared to ascending urethrogram.

  13. A comparative study of ascending urethrogram and sono-urethrogram in the evaluation of stricture urethra.

    Science.gov (United States)

    Ravikumar, B R; Tejus, Chiranjeevi; Madappa, K M; Prashant, Dharakh; Dhayanand, G S

    2015-01-01

    To compare the efficacy of sono-urethrogram and ascending urethrogram in the evaluation of stricture urethra. In this prospective study 40 patients with obstructive lower urinary tract symptoms and suspected to be having stricture urethra were subjected to ascending urethrogram and sonourethrogram. The radiologist was blinded to the findings of ascending urethrogram. All the sonourethrograms were done by the same radiologist. The findings of sonourethrogram & ascending urethrogram were compared with the findings of cystoscopy and intra-operative findings. The specificity, sensitivity,positive predictive value and negative predictive value of each modality in the diagnosis of various urethral anomalies were estimated. The sonourethrogram identified stricture disease in all the patients who had abnormal ascending urethrogram. In addition, other abnormalities like spongiofibrosis, diverticula and stones which were not picked up in ascending urethrogram were diagnosed by sonourethrogram. The cystoscopic and intra-operative findings with respect to stricture length, diameter and spongiofibrosis correlated well with sono-urethrogram findings. 5 patients who had stricture in the ascending urethrogram were found to be having the normal urethra in sonourethrogram and confirmed by cystoscopy. sonourethrogram is an effective alternative to ascending urethrogram in the evaluation of stricture urethra. It is more sensitive in the diagnosis of anterior urethral strictures than posterior urethral strictures. It is superior to ascending urethrogram in the identification of spongiofibrosis, diameter and length of the stricture. The complications were lower in sonourethrogram group compared to ascending urethrogram.

  14. Bioluminescence imaging of Chlamydia muridarum ascending infection in mice.

    Directory of Open Access Journals (Sweden)

    Jessica Campbell

    Full Text Available Chlamydial pathogenicity in the upper genital tract relies on chlamydial ascending from the lower genital tract. To monitor chlamydial ascension, we engineered a luciferase-expressing C. muridarum. In cells infected with the luciferase-expressing C. muridarum, luciferase gene expression and enzymatic activity (measured as bioluminescence intensity correlated well along the infection course, suggesting that bioluminescence can be used for monitoring chlamydial replication. Following an intravaginal inoculation with the luciferase-expressing C. muridarum, 8 of 10 mice displayed bioluminescence signal in the lower with 4 also in the upper genital tracts on day 3 after infection. By day 7, all 10 mice developed bioluminescence signal in the upper genital tracts. The bioluminescence signal was maintained in the upper genital tract in 6 and 2 mice by days 14 and 21, respectively. The bioluminescence signal was no longer detectable in any of the mice by day 28. The whole body imaging approach also revealed an unexpected airway infection following the intravaginal inoculation. Although the concomitant airway infection was transient and did not significantly alter the genital tract infection time courses, caution should be taken during data interpretation. The above observations have demonstrated that C. muridarum can not only achieve rapid ascending infection in the genital tract but also cause airway infection following a genital tract inoculation. These findings have laid a foundation for further optimizing the C. muridarum intravaginal infection murine model for understanding chlamydial pathogenic mechanisms.

  15. Ascending connections to the forebrain in the Tegu lizard.

    Science.gov (United States)

    Lohman, A H; van Woerden-Verkley, I

    1978-12-01

    The ascending connections to the striatum and the cortex of the Tegu lizard, Tupinambis nigropunctatus, were studied by means of anterograde fiber degeneration and retrograde axonal transport. The striatum receives projections by way of the dorsal peduncle of the lateral forebrain bundle from four dorsal thalamic nuclei: nucleus rotundus, nucleus reuniens, the posterior part of the dorsal lateral geniculate nucleus and nucleus dorsomedialis. The former three nuclei project to circumscribed areas of the dorsal striatum, whereas nucleus dorsomedialis has a distribution to the whole dorsal striatum. Other sources of origin to the striatum are the mesencephalic reticular formation, substantia nigra and nucleus cerebelli lateralis. With the exception of the latter afferentation all these projections are ipsilateral. The ascending connections to the pallium originate for the major part from nucleus dorsolateralis anterior of the dorsal thalamus. The fibers course in both the medial forebrain bundle and the dorsal peduncle of the lateral forebrain bundle and terminate ipsilaterally in the middle of the molecular layer of the small-celled part of the mediodorsal cortex and bilaterally above the intermediate region of the dorsal cortex. The latter area is reached also by fibers from the septal area. The large-celled part of the mediodorsal cortex receives projections from nucleus raphes superior and the corpus mammillare.

  16. Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

    International Nuclear Information System (INIS)

    Levegrün, Sabine; Pöttgen, Christoph; Wittig, Andrea; Lübcke, Wolfgang; Abu Jawad, Jehad; Stuschke, Martin

    2013-01-01

    Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N mets ) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV mets ) and of the individual metastasis planning target volume (PTV ind met ) were 8.7 ± 8.9 cm 3 (range, 1.3-35.5 cm 3 ) and 2.5 ± 4.5 cm 3 (range, 0.19-24.7 cm 3 ), respectively. Dose distributions in PTV mets and PTV ind met were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N mets was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV mets amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV ind met were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV mets (CN = 0.737 for PTV mets ≤4.32 cm 3 vs CN = 0.848 for PTV mets >4.32 cm 3 , P=.006), in contrast to N mets . The achieved dose conformity to PTV mets , assessed by both CN and PITV, was in all investigated volume strata

  17. Observing System Simulations for ASCENDS: Synthesizing Science Measurement Requirements (Invited)

    Science.gov (United States)

    Kawa, S. R.; Baker, D. F.; Schuh, A. E.; Crowell, S.; Rayner, P. J.; Hammerling, D.; Michalak, A. M.; Wang, J. S.; Eluszkiewicz, J.; Ott, L.; Zaccheo, T.; Abshire, J. B.; Browell, E. V.; Moore, B.; Crisp, D.

    2013-12-01

    The measurement of atmospheric CO2 from space using active (lidar) sensing techniques has several potentially significant advantages in comparison to current and planned passive CO2 instruments. Application of this new technology aims to advance CO2 measurement capability and carbon cycle science into the next decade. The NASA Active Sensing of Carbon Emissions, Nights, Days, and Seasons (ASCENDS) mission has been recommended by the US National Academy of Sciences Decadal Survey for the next generation of space-based CO2 observing systems. ASCENDS is currently planned for launch in 2022. Several possible lidar instrument approaches have been demonstrated in airborne campaigns and the results indicate that such sensors are quite feasible. Studies are now underway to evaluate performance requirements for space mission implementation. Satellite CO2 observations must be highly precise and unbiased in order to accurately infer global carbon source/sink fluxes. Measurement demands are likely to further increase in the wake of GOSAT, OCO-2, and enhanced ground-based in situ and remote sensing CO2 data. The objective of our work is to quantitatively and consistently evaluate the measurement capabilities and requirements for ASCENDS in the context of advancing our knowledge of carbon flux distributions and their dependence on underlying physical processes. Considerations include requirements for precision, relative accuracy, spatial/temporal coverage and resolution, vertical information content, interferences, and possibly the tradeoffs among these parameters, while at the same time framing a mission that can be implemented within a constrained budget. Here, we attempt to synthesize the results of observing system simulation studies, commissioned by the ASCENDS Science Requirements Definition Team, into a coherent set of mission performance guidelines. A variety of forward and inverse model frameworks are employed to reduce the potential dependence of the results on model

  18. GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice.

    Science.gov (United States)

    Wang, Z; Gleichmann, H

    1998-01-01

    In mice, diabetes can be induced by multiple low doses of streptozotocin (MLD-STZ), i.e., 40 mg/kg body wt on each of 5 consecutive days. In this model, diabetes develops only when STZ induces both beta-cell toxicity and T-cell-dependent immune reactions. The target molecule(s) of MLD-STZ-induced beta-cell toxicity are not known, however. In this study, we report that GLUT2 is a target molecule for MLD-STZ toxicity. Ex vivo, a gradual decrement of both GLUT2 protein and mRNA expression was found in pancreatic islets isolated from MLD-STZ-treated C57BL/6 male mice, whereas mRNA expression of beta-actin, glucokinase, and proinsulin remained unaffected. Significant reduction of both GLUT2 protein and mRNA expression was first noted 1 day after the third STZ injection, clearly preceding the onset of hyperglycemia. The extent of reduction increased with the number of STZ injections administered and increased over time, after the last, i.e., fifth, STZ injection. The STZ-induced reduction of GLUT2 protein and mRNA was not due to an essential loss of beta-cells, because ex vivo, not only the total RNA yield and protein content in isolated islets, but also proinsulin mRNA expression, failed to differ significantly in the differently treated groups. Furthermore, islets isolated from MLD-STZ-treated donors responded to the nonglucose secretagogue arginine in a pattern similar to that of solvent-treated donors. Interestingly, the MLD-STZ-induced reduction of both GLUT2 protein and mRNA was prevented by preinjecting mice with 5-thio-D-glucose before each STZ injection. Apparently, GLUT2 is a crucial target molecule of MLD-STZ toxicity, and this toxicity seems to precede the immune reactions against beta-cells.

  19. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

    Science.gov (United States)

    Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

    2018-03-01

    Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

  20. Development of a flattening filter free multiple source model for use as an independent, Monte Carlo, dose calculation, quality assurance tool for clinical trials.

    Science.gov (United States)

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

    2017-09-01

    The Imaging and Radiation Oncology Core-Houston (IROC-H) Quality Assurance Center (formerly the Radiological Physics Center) has reported varying levels of compliance from their anthropomorphic phantom auditing program. IROC-H studies have suggested that one source of disagreement between institution submitted calculated doses and measurement is the accuracy of the institution's treatment planning system dose calculations and heterogeneity corrections used. In order to audit this step of the radiation therapy treatment process, an independent dose calculation tool is needed. Monte Carlo multiple source models for Varian flattening filter free (FFF) 6 MV and FFF 10 MV therapeutic x-ray beams were commissioned based on central axis depth dose data from a 10 × 10 cm 2 field size and dose profiles for a 40 × 40 cm 2 field size. The models were validated against open-field measurements in a water tank for field sizes ranging from 3 × 3 cm 2 to 40 × 40 cm 2 . The models were then benchmarked against IROC-H's anthropomorphic head and neck phantom and lung phantom measurements. Validation results, assessed with a ±2%/2 mm gamma criterion, showed average agreement of 99.9% and 99.0% for central axis depth dose data for FFF 6 MV and FFF 10 MV models, respectively. Dose profile agreement using the same evaluation technique averaged 97.8% and 97.9% for the respective models. Phantom benchmarking comparisons were evaluated with a ±3%/2 mm gamma criterion, and agreement averaged 90.1% and 90.8% for the respective models. Multiple source models for Varian FFF 6 MV and FFF 10 MV beams have been developed, validated, and benchmarked for inclusion in an independent dose calculation quality assurance tool for use in clinical trial audits. © 2017 American Association of Physicists in Medicine.

  1. A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

    Science.gov (United States)

    Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

    2017-06-01

    Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... breast and ascending colon. KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous. Multiple Primary Tumors. MA Adeyanju, AA Ilori. Address for correspondence: Dr. MA Adeyanju,. Department of Surgery, Federal Medical Centre, Ebute Metta,. Lagos, Nigeria. E-mail: mbadeyanju@yahoo.

  3. Estimation of lung tissue doses following exposure to low-LET radiation in the Canadian study of cancer following multiple fluoroscopies

    International Nuclear Information System (INIS)

    Howe, G.R.; Yaffe, M.

    1992-02-01

    Lung tissue doses from exposure to external low-LET radiation have been estimated for each year between 1930 and 1960 for 92,707 tuberculosis patients first treated in Canadian institutions between 1930 and 1952. Many of these patients received multiple chest fluoroscopies together with treatment by artificial pneumothorax, and thus accumulated doses up to 15.7 grays. The estimated doses have been used in a statistical analysis of lung cancer mortality between 1950 and 1987 occurring among 64,698 patients known to be alive at the start of 1950, and followed by linkage to the Canadian national mortality data base. There were substantial variations in the total cumulative lung tissue dose received by the cohort, with 2,490 individuals having doses in excess of 1.7 grays. A total of 1,156 lung cancer deaths was observed in the cohort, and these have been used to estimate relative risks. The most appropriate risk model appears to be a simple linear relative risk function, with an excess relative risk coefficient of 0.089 for an absorbed dose of 1 gray. This contrasts with estimates of relative risk based on the atomic bomb survivors study, for which the excess relative risk coefficient for males 20 years after the first exposure is estimated to be 0.64. The difference is statistically significant. It is postulated that fractionation and dose rate effectiveness factors may account for some of the discrepancy. (Modified author abstract) (14 refs., 20 tabs.)

  4. Numerical Study on 4-1 Coal Seam of Xiaoming Mine in Ascending Mining

    Science.gov (United States)

    Tianwei, Lan; Hongwei, Zhang; Sheng, Li; Weihua, Song; Batugin, A. C.; Guoshui, Tang

    2015-01-01

    Coal seams ascending mining technology is very significant, since it influences the safety production and the liberation of dull coal, speeds up the construction of energy, improves the stability of stope, and reduces or avoids deep hard rock mining induced mine disaster. Combined with the Xiaoming ascending mining mine 4-1, by numerical calculation, the paper analyses ascending mining 4-1 factors, determines the feasibility of ascending mining 4-1 coalbed, and proposes roadway layout program about working face, which has broad economic and social benefits. PMID:25866840

  5. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high).......A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  6. Ascending infection of foot tendons in diabetic patients.

    Science.gov (United States)

    Mismar, Ayman; Yousef, Mohammad; Badran, Darwish; Younes, Nidal

    2013-12-01

    Bone and soft tissue infection in the foot of diabetic patients is a well-described issue in the literature. A sound anatomical knowledge of the foot anatomy and compartments is mandatory to understand the mechanisms of infection spread. We describe four cases of diabetic foot infection complicated by long ascending infection. All did not respond initially to antibiotic treatment and the usual surgical debridement and were cured only after excision of the infected tendons. We highlight a rare but serious complication of the diabetic foot disease not commonly seen by the surgical community. We hope that this report raises the awareness of this condition so that a prompt diagnosis is made and appropriate treatment started, thereby reducing the risk of major lower limb amputations.

  7. Ascending Aortic Wall Cohesion: Comparison of Bicuspid and Tricuspid Valves

    Directory of Open Access Journals (Sweden)

    Jaroslav Benedik

    2012-01-01

    Full Text Available Objectives. Bicuspid aortic valve (AV represents the most common form of congenital AV malformation, which is frequently associated with pathologies of the ascending aorta. We compared the mechanical properties of the aortic wall between patients with bicuspid and tricuspid AV using a new custom-made device mimicking transversal aortic wall shear stress. Methods. Between 03/2010 and 07/2011, 190 consecutive patients undergoing open aortic valve replacement at our institution were prospectively enrolled, presenting either with a bicuspid (group 1, n=44 or a tricuspid (group 2, n=146 AV. Aortic wall specimen were examined with the “dissectometer” resulting in nine specific aortic-wall parameters derived from tensile strength curves (TSC. Results. Patients with a bicuspid AV showed significantly more calcified valves (43.2% versus 15.8%, P<0.001, and a significantly thinner aortic wall (2.04±0.42 mm versus 2.24±0.41 mm, P=0.008. Transesophageal echocardiography diameters (annulus, aortic sinuses, and sinotubular junction were significantly larger in the bicuspid group (P=0.003, P=0.02, P=0.01. We found no difference in the aortic wall cohesion between both groups as revealed by shear stress testing (P=0.72, P=0.40, P=0.41. Conclusion. We observed no differences of TSC in patients presenting with tricuspid or bicuspid AVs. These results may allow us to assume that the morphology of the AV and the pathology of the ascending aorta are independent.

  8. A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

    Science.gov (United States)

    Buck, David; Subramanyam, Rajeev; Varughese, Anna

    2016-01-01

    The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

  9. Anesthetic Implications of Emergent Cesarean Section in a Parturient with Marfan Syndrome Complicated by Ascending Aortic Aneurysm and Heart Failure

    Directory of Open Access Journals (Sweden)

    Young Sung Kim

    2014-07-01

    Full Text Available Cardiovascular comorbidities to the Marfan syndrome may induce hemodynamic instability especially in the parturients during labor or delivery. For anesthesiologists, it is challenging to maintain hemodynamic stability during Cesarean section in those patients with Marfan syndrome. Remifentanil is an ultra-short-acting opioid with rapid onset and offset of action which provides cardiovascular stability during surgery. Together with remifentanil, the use of a laryngeal mask airway can reduce the risk of hypertensive response followed by tracheal intubation. We describe the successful administration of remifentanil and application of laryngeal mask airway for emergent Cesarean section performed under general anesthesia in a patient with Marfan syndrome complicated by ascending aortic aneurysm and heart failure. The use of remifentanil (loading dose of 1 μg/kg for 1 min, 2 min before induction; thereafter continuous infusion dose of 0.1 μg/kg/min was useful to maintain hemodynamic stability of the parturient throughout the surgery without neonatal respiratory depression. Keywords: Ascending Aortic Aneurysm; Cesarean section; Laryngeal mask airway; Marfan syndrome; Remifentanil

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  11. Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Hansen, Per Boye; Penkowa, Milena

    2017-01-01

    show for the first time that bismuth significantly reduces grade 2 stomatitis, febrile neutropenia and infections caused by melphalan in multiple myeloma, where adverse effects also were significantly linked to gender. In lymphoma patients, bismuth significantly reduces diarrhoea relative to placebo......PURPOSE: High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey...

  12. Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

    Science.gov (United States)

    Jamaludin, A; Mohamad, M; Navaratnam, V; Yeoh, P Y; Wernsdorfer, W H

    1990-09-01

    A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

  13. The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.

    Science.gov (United States)

    Görgens, Christian; Guddat, Sven; Bosse, Christina; Geyer, Hans; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

    2017-05-10

    Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis.

    Science.gov (United States)

    Olsson, A; Oturai, D B; Sørensen, P S; Oturai, P S; Oturai, A B

    2015-10-01

    Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. Osteopenia was present in 38% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both lumbar and femoral BMD. Reduced BMD was prevalent in patients with MS. GC treatment appears not to be the primary underlying cause of secondary osteoporosis in MS patients. © The Author(s), 2015.

  15. Thermally assisted OSL application for equivalent dose estimation; comparison of multiple equivalent dose values as well as saturation levels determined by luminescence and ESR techniques for a sedimentary sample collected from a fault gouge

    Energy Technology Data Exchange (ETDEWEB)

    Şahiner, Eren, E-mail: sahiner@ankara.edu.tr; Meriç, Niyazi, E-mail: meric@ankara.edu.tr; Polymeris, George S., E-mail: gspolymeris@ankara.edu.tr

    2017-02-01

    Highlights: • Multiple equivalent dose estimations were carried out. • Additive ESR and regenerative luminescence were applied. • Preliminary SAR results employing TA-OSL signal were discussed. • Saturation levels of ESR and luminescence were investigated. • IRSL{sub 175} and SAR TA-OSL stand as very promising for large doses. - Abstract: Equivalent dose estimation (D{sub e}) constitutes the most important part of either trap-charge dating techniques or dosimetry applications. In the present work, multiple, independent equivalent dose estimation approaches were adopted, using both luminescence and ESR techniques; two different minerals were studied, namely quartz as well as feldspathic polymineral samples. The work is divided into three independent parts, depending on the type of signal employed. Firstly, different D{sub e} estimation approaches were carried out on both polymineral and contaminated quartz, using single aliquot regenerative dose protocols employing conventional OSL and IRSL signals, acquired at different temperatures. Secondly, ESR equivalent dose estimations using the additive dose procedure both at room temperature and at 90 K were discussed. Lastly, for the first time in the literature, a single aliquot regenerative protocol employing a thermally assisted OSL signal originating from Very Deep Traps was applied for natural minerals. Rejection criteria such as recycling and recovery ratios are also presented. The SAR protocol, whenever applied, provided with compatible D{sub e} estimations with great accuracy, independent on either the type of mineral or the stimulation temperature. Low temperature ESR signals resulting from Al and Ti centers indicate very large D{sub e} values due to bleaching in-ability, associated with large uncertainty values. Additionally, dose saturation of different approaches was investigated. For the signal arising from Very Deep Traps in quartz saturation is extended almost by one order of magnitude. It is

  16. Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

    Directory of Open Access Journals (Sweden)

    Kristen Ashley eHorner

    2011-05-01

    Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

  17. Left Ventricular Assist Device Implantation with Concomitant Aortic Valve and Ascending Aortic Replacement.

    Science.gov (United States)

    Huenges, Katharina; Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

    2018-01-01

    Left ventricular assist device (LVAD) is nowadays a routine therapy for patients with advanced heart failure. We present the case of a 74-year-old male patient who was admitted to our center with terminal heart failure in dilated cardiomyopathy and ascending aortic aneurysm with aortic valve regurgitation. The LVAD implantation with simultaneous aortic valve and supracoronary ascending aortic replacement was successfully performed.

  18. Resveratrol increases nitric oxide production in the rat thick ascending limb via Ca2+/calmodulin.

    Science.gov (United States)

    Gonzalez-Vicente, Agustin; Cabral, Pablo D; Garvin, Jeffrey L

    2014-01-01

    The thick ascending limb of the loop of Henle reabsorbs 30% of the NaCl filtered through the glomerulus. Nitric oxide (NO) produced by NO synthase 3 (NOS3) inhibits NaCl absorption by this segment. Resveratrol, a polyphenol, has beneficial cardiovascular and renal effects, many of which are mediated by NO. Resveratrol increases intracellular Ca2+ (Cai) and AMP kinase (AMPK) and NAD-dependent deacetylase sirtuin1 (SIRT1) activities, all of which could activate NO production. We hypothesized that resveratrol stimulates NO production by thick ascending limbs via a Ca2+/calmodulin-dependent mechanism. To test this, the effect of resveratrol on NO bioavailability was measured in thick ascending limb suspensions. Cai was measured in single perfused thick ascending limbs. SIRT1 activity and expression were measured in thick ascending limb lysates. Resveratrol (100 µM) increased NO bioavailability in thick ascending limb suspensions by 1.3±0.2 AFU/mg/min (pthick ascending limbs via a Ca2+/calmodulin dependent mechanism, and SIRT1 and AMPK do not participate. Resveratrol-stimulated NO production in thick ascending limbs may account for part of its beneficial effects.

  19. Sets in Excess Demand in Ascending Auctions with Unit-Demand Bidders

    NARCIS (Netherlands)

    Andersson, T.D.; Andersson, C.; Talman, A.J.J.

    2010-01-01

    This paper analyzes the problem of selling a number of indivisible items to a set of unitdemand bidders. An ascending auction mechanism called the Excess Demand Ascending Auction (EDAA) is defined. The main results demonstrate that EDAA terminates in a finite number of iterations and that the exact

  20. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

    Science.gov (United States)

    Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

    2017-09-01

    Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Angiotensin II stimulates superoxide production by nitric oxide synthase in thick ascending limbs.

    Science.gov (United States)

    Gonzalez-Vicente, Agustin; Saikumar, Jagannath H; Massey, Katherine J; Hong, Nancy J; Dominici, Fernando P; Carretero, Oscar A; Garvin, Jeffrey L

    2016-02-01

    Angiotensin II (Ang II) causes nitric oxide synthase (NOS) to become a source of superoxide (O2 (-)) via a protein kinase C (PKC)-dependent process in endothelial cells. Ang II stimulates both NO and O2 (-) production in thick ascending limbs. We hypothesized that Ang II causes O2 (-) production by NOS in thick ascending limbs via a PKC-dependent mechanism. NO production was measured in isolated rat thick ascending limbs using DAF-FM, whereas O2 (-) was measured in thick ascending limb suspensions using the lucigenin assay. Consistent stimulation of NO was observed with 1 nmol/L Ang II (P thick ascending limbs via a PKC- and NADPH oxidase-dependent process; and (2) the effect of Ang II is not due to limited substrate. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  2. TLD-300 detectors for separate measurement of total and gamma absorbed dose distributions of single, multiple, and moving-field neutron treatments

    International Nuclear Information System (INIS)

    Rassow, J.

    1984-01-01

    Fast neutron therapy requirements, because of the poor depth dose characteristic of present therapeutical sources, are at least as complex in treatment plans as photon therapy. The physical part of the treatment planning is very important; however, it is much more complicated than for photons or electrons owing to the need for: Separation of total and gamma absorbed dose distributions (Dsub(T) and Dsub(G)); and more stringent tissue-equivalence conditions of phantoms than in photon therapy. Therefore, methods of clinical dosimetry for the separate determination of total and gamma absorbed dose distributions in irregularly shaped (inhomogeneous) phantoms are needed. A method using TLD-300 (CaF 2 :Tm) detectors is described, which is able to give an approximate solution of the above-mentioned dosimetric requirements. The two independent doses, Dsub(T) and Dsub(G), can be calculated by an on-line computer analysis of the digitalized glow curve of TLD-300 detectors, irradiated with d(14)+Be neutrons of the cyclotron isocentric neutron therapy facility CIRCE in Essen. Results are presented for depth and lateral absorbed dose distributions (Dsub(T) and Dsub(G)) for fixed neutron beams of different field sizes compared with measurements by standard procedures (TE-TE ionization chamber, GM counter) in an A-150 phantom. The TLD-300 results for multiple and moving-field treatments (with and without wedge filters) in a patient simulating irregularly shaped (inhomogeneous) phantoms, are shown together with computer calculations of these dose distributions. The probable causes for some systematic deviations are discussed, which lead to open problems for further investigations owing to features of the detector material and the evaluation method, but mainly to differences in the composition of phantom materials used for the calculations (standard dose distributions) and TLD-300 measurements. (author)

  3. Dose evaluation using multiple-aliquot quartz OSL: Test of methods and a new protocol for improved accuracy and precision

    DEFF Research Database (Denmark)

    Jain, M.; Bøtter-Jensen, L.; Singhvi, A.K.

    2003-01-01

    -dose-dependent sensitivity changes during the pre-heat, and fundamental variability in the shapes of quartz OSL (blue-green or blue-light stimulated luminescence) decay forms. A new protocol using a combination of 'elevated temperature IR cleaning' (ETIR) and 'component-specific dose normalisation' (CSDN) has been developed....... CSDN accounts for variability in the OSL decay forms and absorbs such sensitivity changes. A combination of ETIR and CSDN protocol increased palaeodose precision from +/-100% to +/-4% in quartz separates from the fluvially transported sands in the Thar desert. A comparison with palaeodose estimates...

  4. Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

    Science.gov (United States)

    Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

    2016-12-01

    While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Atmospheric CO2 Variability Observed From ASCENDS Flight Campaigns

    Science.gov (United States)

    Lin, Bing; Browell, Edward; Campbell, Joel; Choi, Yonghoon; Dobler, Jeremy; Fan, Tai-Fang; Harrison, F. Wallace; Kooi, Susan; Liu, Zhaoyan; Meadows, Byron; hide

    2015-01-01

    Significant atmospheric CO2 variations on various spatiotemporal scales were observed during ASCENDS flight campaigns. For example, around 10-ppm CO2 changes were found within free troposphere in a region of about 200x300 sq km over Iowa during a summer 2014 flight. Even over extended forests, about 2-ppm CO2 column variability was measured within about 500-km distance. For winter times, especially over snow covered ground, relatively less horizontal CO2 variability was observed, likely owing to minimal interactions between the atmosphere and land surface. Inter-annual variations of CO2 drawdown over cornfields in the Mid-West were found to be larger than 5 ppm due to slight differences in the corn growing phase and meteorological conditions even in the same time period of a year. Furthermore, considerable differences in atmospheric CO2 profiles were found during winter and summer campaigns. In the winter CO2 was found to decrease from about 400 ppm in the atmospheric boundary layer (ABL) to about 392 ppm above 10 km, while in the summer CO2 increased from 386 ppm in the ABL to about 396 ppm in free troposphere. These and other CO2 observations are discussed in this presentation.

  7. Optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system

    International Nuclear Information System (INIS)

    Shen, L.; Levine, S.H.; Catchen, G.L.

    1987-01-01

    This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration

  8. Evaluation of the effect of multiple doses of lansoprazole on the pharmacokinetics and safety of ponatinib in healthy subjects.

    Science.gov (United States)

    Narasimhan, Narayana I; Dorer, David J; Davis, Jeffrey; Turner, Christopher D; Sonnichsen, Daryl

    2014-10-01

    In vitro studies have demonstrated that the aqueous solubility of the tyrosine kinase inhibitor ponatinib decreases as pH increases. The primary aim of this study was to assess the effects of the gastric proton pump inhibitor lansoprazole on the pharmacokinetics of ponatinib. The single-dose safety profile of ponatinib with and without coadministration of lansoprazole was also characterized. This was a phase I, open-label, non-randomized, two-period crossover study in 20 healthy subjects aged 18-55 years. Subjects received a single oral dose of ponatinib 45 mg alone on day 1, an oral dose of lansoprazole 60 mg on day 14, and ponatinib 45 mg plus lansoprazole 60 mg on day 15. Lansoprazole coadministration resulted in a 1-h increase in the time to maximum plasma concentration (t max) of ponatinib (6 vs. 5 h post-dose; P lansoprazole versus ponatinib alone (40.67 vs. 53.96 ng/mL). Importantly, lansoprazole did not decrease the overall ponatinib systemic exposure as assessed by the ponatinib area under the plasma concentration-time curve from time zero to infinity (AUC∞ 1,153 ng·h/mL for lansoprazole + ponatinib vs. 1,222 ng·h/mL for ponatinib alone). The safety profile was considered acceptable when ponatinib was administered alone or with lansoprazole. Although coadministration of lansoprazole led to a modest, albeit statistically significant, reduction in ponatinib C max, overall systemic exposure to ponatinib did not change. The findings suggest that no dose adjustment is necessary when ponatinib is administered with drugs that increase gastric pH.

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

    Directory of Open Access Journals (Sweden)

    Jianzhong Shentu

    2017-04-01

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

  10. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a combin......-mg doses of oral ketorolac are as effective as Ketogan for the treatment of pain following orthopaedic surgery. Ketorolac appears to be better tolerated than Ketogan since significantly fewer patients reported adverse events (P = 0.004) when taking ketorolac.......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...... combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...

  11. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  12. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S

    2014-01-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment

  13. Contamination of chlorhexidine cream used to prevent ascending urinary tract infections

    Energy Technology Data Exchange (ETDEWEB)

    Salveson, A.; Bergan, T.

    1981-06-01

    Chlorhexidine-containing cream is often used as an antimicrobial barrier to ascending urinary tract infection in patients with indwelling urethral catheters. The cream is dispensed in small tubes for personal use but repeated use of a tube still entails a potential infection hazard. The extent of cream contamination was analysed by emulsifying it in 1% peptone broth with 1% Tween-80 added as a wetting agent, and culturing quantitatively for bacteria and fungi by membrane filtration. Twenty-three per cent of cream samples and 35% of swabs taken from outside the tube beneath the screw cap demonstrated microbial contamination. Isolates included potential pathogens such as enterococci, staphylococci, Proteus mirabilis, Pseudomonas aeruginosa, opportunists like Moraxella spp. and diphtheroids, and contaminants such as Bacillus spp., micrococci, and a mould of the genus Cladosporium. Contamination of cream with a particular bacterial strain was found to precede urinary tract infection with the same microbe. We recommend that chlorhexidine cream for this use be dispensed in single dose units to ensure sterility.

  14. Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

    Science.gov (United States)

    Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

    2018-03-08

    Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid

  15. Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience.

    Science.gov (United States)

    Cerchione, Claudio; Nappi, Davide; Pareto, Anna E; Romano, Alessandra; Martinelli, Vincenzo; Picardi, Marco; Pane, Fabrizio; Catalano, Lucio

    2018-04-01

    Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.

  16. Technology Advancements for Active Remote Sensing of Carbon Dioxide From Space using the ASCENDS CarbonHawk Experiment Simulator

    Science.gov (United States)

    Obland, M. D.; Liu, Z.; Campbell, J. F.; Lin, B.; Kooi, S. A.; Carrion, W.; Hicks, J.; Fan, T. F.; Nehrir, A. R.; Browell, E. V.; Meadows, B.; Davis, K. J.

    2016-12-01

    This work describes advances in critical lidar technologies and techniques developed as part of the ASCENDS CarbonHawk Experiment Simulator (ACES) system for measuring atmospheric column carbon dioxide (CO2) mixing ratios in support of the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. The ACES design demonstrates advancements in: (1) enhanced power-aperture product through the use and operation of multiple co-aligned laser transmitters and a multi-aperture telescope design; (2) high-efficiency, high-power Erbium-Doped Fiber Amplifiers (EDFAs); (3) high-bandwidth, low-noise HgCdTe detector and transimpedence amplifier (TIA) subsystem capable of long-duration operation; and (4) advanced algorithms for cloud and aerosol discrimination. The ACES instrument, an Intensity-Modulated Continuous-Wave (IM-CW) lidar, was designed for high-altitude aircraft operations and can be directly applied to space instrumentation to meet the ASCENDS mission requirements. Specifically, the lidar simultaneously transmits three IM-CW laser beams from the high power EDFAs operating near 1571 nm. The outgoing laser beams are aligned to the field of view of three fiber-coupled 17.8-cm diameter telescopes, and the backscattered light collected by the same three telescopes is sent to the detector/TIA subsystem, which has a bandwidth of 4.9 MHz and operates service-free with a tactical Dewar and cryocooler. The electronic bandwidth is only slightly higher than 1 MHz, effectively limiting the noise level. Two key laser modulation approaches are being tested to significantly mitigate the effects of thin clouds on the retrieved CO2 column amounts. This work provides an over view of these technologies, the modulation approaches, and results from recent test flights during the Atmospheric Carbon and Transport - America (ACT-America) Earth Venture Suborbital flight campaign.

  17. PREFACE: Eclipse on the Coral Sea: Cycle 24 Ascending

    Science.gov (United States)

    Cally, Paul; Erdélyi, Robert; Norton

    2013-06-01

    A total solar eclipse is the most spectacular and awe-inspiring astronomical phenomenon most people will ever see in their lifetimes. Even hardened solar scientists draw inspiration from it. The eclipse with 2 minutes totality in the early morning of 14 November 2012 (local time) drew over 120 solar researchers (and untold thousands of the general public) to the small and picturesque resort town of Palm Cove just north of Cairns in tropical north Queensland, Australia, and they were rewarded when the clouds parted just before totality to reveal a stunning solar display. Eclipse photograph The eclipse was also the catalyst for an unusually broad and exciting conference held in Palm Cove over the week 12--16 November. Eclipse on the Coral Sea: Cycle 24 Ascending served as GONG 2012, LWS/SDO-5, and SOHO 27, indicating how widely it drew on the various sub-communities within solar physics. Indeed, as we neared the end of the ascending phase of the peculiar Solar Cycle 24, it was the perfect time to bring the whole community together to discuss our Sun's errant recent behaviour, especially as Cycle 24 is the first to be fully observed by the Solar Dynamics Observatory (SDO). The whole-Sun perspective was a driving theme of the conference, with the cycle probed from interior (helioseismology), to atmosphere (the various lines observed by the Atmospheric Imaging Assemble (AIA) aboard SDO, the several instruments on Hinode, and other modern observatories), and beyond (CMEs etc). The quality of the presentations was exceptional, and the many speakers are to be commended for pitching their talks to the broad community present. These proceedings draw from the invited and contributed oral presentations and the posters exhibited in Palm Cove. They give an (incomplete) snapshot of the meeting, illustrating its broad vistas. The published contributions are organized along the lines of the conference sessions, as set out in the Contents, leading off with a provocative view of

  18. Utility of the sore throat pain model in a multiple-dose assessment of the acute analgesic flurbiprofen: a randomized controlled study.

    Science.gov (United States)

    Schachtel, Bernard; Aspley, Sue; Shephard, Adrian; Shea, Timothy; Smith, Gary; Schachtel, Emily

    2014-07-03

    The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Adults (n=198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n=101) or matching placebo lozenges (n=97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (Pflurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all Pflurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010.

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

    International Nuclear Information System (INIS)

    Wu, Q; Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

  1. Innervation of the thick ascending limb of Henle

    International Nuclear Information System (INIS)

    Barajas, L.; Powers, K.V.

    1988-01-01

    The overlap of accumulations of autoradiographic grains (AAGs) on profiles of the thick ascending limb of Henle (TALH) was measured in autoradiograms of sections from rat kidneys with monoaminergic nerves labeled by means of tritiated norepinephrine. The amount of AAG overlap was used as an indirect means of quantifying innervation along the TALHs of superficial, mid-cortical, and juxtamedullary nephrons. The density of innervation along the TALH showed nephron heterogeneity; the juxtamedullary nephrons with a high pre- and postjuxtaglomerular apparatus (JGA) TALH density of innervation and the upper and midcortical nephrons with high TALH innervation densities at the level of the JGA. The pre-JGA TALH of the juxtamedullary nephrons had a significantly higher (P less than 0.001) density of innervation than the midcortical or superficial nephrons. The TALHs of juxtamedullary nephrons were found to have substantially more innervation than the TALHs of the other nephrons. For all three populations of nephrons, the pre-JGA TALH had the greatest amount of innervation. Neural regulation of TALH function would occur mainly along the pre-JGA and level of the JGA TALH. This regulation would increase TALH NaCl reabsorption (decrease luminal NaCl concentration) and therefore influence 1) the urinary concentrating mechanism, and 2) renin secretion via the macula densa mechanism. The innervation of the TALH was predominantly associated with the vasculature of the TALH's own nephron. However, innervation associated with medullary ray capillary beds from deeper nephrons was observed on pre-JGA TALHs from superficial and midcortical nephrons

  2. Bentall procedure in ascending aortic aneurysm: hospital mortality.

    Science.gov (United States)

    Galicia-Tornell, Matilde Myriam; Marín-Solís, Bertha; Fuentes-Orozco, Clotilde; Martínez-Martínez, Manuel; Villalpando-Mendoza, Esteban; Ramírez-Orozco, Fermín

    2010-01-01

    Ascending aortic aneurysm disease (AAAD) shows a low frequency, heterogeneous behavior, high risk of rupture, dissection and mortality, making elective surgery necessary. Several procedures have been developed, and the Bentall technique is considered as the reference standard. The objective was to describe the hospital mortality of AAAD surgically treated using the Bentall procedure. We carried out a descriptive study. Included were 23 patients with AAAD who were operated on between March 1, 2005 and September 30, 2008 at our hospital. Data were obtained from clinical files, and descriptive statistics were selected for analysis. The study population was comprised of 23 patients with an average age of 46 years; 83% were males. Etiology was nonspecific degeneration of the middle layer with valve implication in 43%, bivalve aorta in 22%, Marfan syndrome, Turner's syndrome and poststenotic aneurysms each represented 9%, and Takayasu disease and ankylosing spondylitis 4% each. Associated heart disease was reported in six (26%) patients as follows: aortic coarctation (2), ischemic cardiopathy (1), atrial septal defect (1), severe mitral insufficiency (1) and subaortic membrane (1). Procedures carried out were Bentall surgery in 20 (87%) patients and aortoplasty with valve prosthesis in three (13%) patients. Complications reported were abnormal bleeding with mediastinal exploration (17%), nosocomial pneumonia (13%), arrhythmia (13%), and septic shock (9%). Mortality was reported in three (13%) patients due to septic shock and ventricular fibrillation. Surgical mortality with the Bentall procedure is similar to published results by other specialized centers. Events related to the basic aortic pathology, surgical technique, aortic valve prosthesis and left ventricular dysfunction encourage longterm studies with follow-up.

  3. Innervation of the thick ascending limb of Henle

    Energy Technology Data Exchange (ETDEWEB)

    Barajas, L.; Powers, K.V.

    1988-08-01

    The overlap of accumulations of autoradiographic grains (AAGs) on profiles of the thick ascending limb of Henle (TALH) was measured in autoradiograms of sections from rat kidneys with monoaminergic nerves labeled by means of tritiated norepinephrine. The amount of AAG overlap was used as an indirect means of quantifying innervation along the TALHs of superficial, mid-cortical, and juxtamedullary nephrons. The density of innervation along the TALH showed nephron heterogeneity; the juxtamedullary nephrons with a high pre- and postjuxtaglomerular apparatus (JGA) TALH density of innervation and the upper and midcortical nephrons with high TALH innervation densities at the level of the JGA. The pre-JGA TALH of the juxtamedullary nephrons had a significantly higher (P less than 0.001) density of innervation than the midcortical or superficial nephrons. The TALHs of juxtamedullary nephrons were found to have substantially more innervation than the TALHs of the other nephrons. For all three populations of nephrons, the pre-JGA TALH had the greatest amount of innervation. Neural regulation of TALH function would occur mainly along the pre-JGA and level of the JGA TALH. This regulation would increase TALH NaCl reabsorption (decrease luminal NaCl concentration) and therefore influence 1) the urinary concentrating mechanism, and 2) renin secretion via the macula densa mechanism. The innervation of the TALH was predominantly associated with the vasculature of the TALH's own nephron. However, innervation associated with medullary ray capillary beds from deeper nephrons was observed on pre-JGA TALHs from superficial and midcortical nephrons.

  4. Valve-sparing root and ascending aorta replacement after heart transplantation.

    Science.gov (United States)

    Elhenawy, Abdelsalam M; Feindel, Christopher M; Ross, Heather; Butany, Jagdish; Yau, Terrence M

    2012-12-01

    A 45-year-old female underwent heart transplantation 17 years ago, with a heart from a 15-year-old donor. Recently, she had developed an aneurysm of the donor aortic root and ascending aorta, with severe aortic insufficiency. Two surgical options were considered; retransplantation versus replacement of the aortic root and ascending aorta. A valve-sparing replacement of the aortic root and ascending aortic aneurysm was performed. The donor aorta showed pathologic changes typical of Marfan syndrome. Nineteen months postoperatively, the patient remains in functional class I, with trivial aortic insufficiency. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. ß-cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice

    DEFF Research Database (Denmark)

    Börjesson, A; Rønn, S G; Karlsen, A E

    2011-01-01

    We investigated the impact of ß-cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic......RNA in islet cells and secretion of IL-1Ra into culture medium. MLDSTZ treatment caused gradual hyperglycemia both in the wt mice and in the transgenic mice with the latter tending to be more sensitive. In vitro experiments on wt and transgenic islets did not reveal any differences in sensitivity to damaging...

  6. Prospective study of ascending venogram following total hip replacement or total knee replacement

    Energy Technology Data Exchange (ETDEWEB)

    Youm, Chang Seon; Suh, Jin Seok; Lee, Jong Doo; Park, Chang Yun; Kim, Young Hoo [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    1987-04-15

    The ascending leg venogram was performed in one hundred forty six lower extremities on the 7th day following total hip replacement (THR) or total knee replacement (TKR). The results were as follows; 1.Overall incidence of deep vein thrombosis (DVT) in 146 limbs who underwent THR or TKR was 10%: DVT was detected in 8 limbs among 110 limbs following THR (7%) and 6 limbs among 36 limbs following TKR (17%). 2.The anatomic distribution of DVT was as follows: In THR, 12.5% in FV, 25% in FV and PV, 25% in FV and PV and CV, 12.5% in FV and CV, and 25% in CV. In TKR, 100% in CV. 3.There were many anatomic variations in deep veins of lower extremities: Accessory SFV (41 limbs), double PV(24), accessory SFV and double PV(7), duplication of SFV and PV(3), accessory SFV and multiple PV(2), and accessory SFV and double PV(1). 4.There were multiple SFV in 37%, and 19% of these limbs had DVT. It represented statistically higher than 4% in limbs with a single SFV (P-value < 0.05). 5.The incidence of DVT was 8% in cases of multiple PV, and there was no statistically significant difference between these groups and single PV groups. 6.We could assess number of values from popliteal vein to common femoral vein in 72 limbs. Mean number of value was 5.45 and there was no statistically significant difference between groups having valve over 5 and under 5.

  7. Early infections in patients undergoing high-dose treatment with stem cell support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma

    DEFF Research Database (Denmark)

    Gang, A O; Arpi, M.; Gang, U.J.O.

    2010-01-01

    Background: Infections are life-threatening complications in patients undergoing high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious pathogens is essential to make a safe outpatient setting. Methods: We conducted a retrospective study of 208 patients treated with HDT...... related mortality was similar between the groups. Conclusion: The frequency of isolated pathogens, positive blood cultures, and the diversity of pathogens were higher in MM patients as compared to NHL patients. However, this did not translate into higher transplantation-related mortality, probably because....... The population included non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received prophylactic antibacterial treatment. Results: Pathogens were isolated from 44% of all patients. MM patients more frequently had multiple pathogens in blood cultures (38% versus 25%). Transplantation...

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

    Science.gov (United States)

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

    2011-12-01

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

  9. Dose-Dependent Effects of Multiple Acute Cocaine Injections on Maternal Behavior and Aggression in Sprague-Dawley Rats

    OpenAIRE

    Johns, Josephine M.; Nelson, Christina J.; Meter, Kathleen E.; Lubin, Deborah A.; Couch, C. Destine; Ayers, Andy; Walker, Cheryl H.

    1998-01-01

    Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3), postpartum day 6 (PPD 6) and postpartum day 10 (PPD 10). Dams were observed 30 min following injections for maternal behavior (MB) towar...

  10. Mammalian Toxicity of Munition Compounds. Phase II. Effects of Multiple Doses. Part III. 2,6-Dinitrotoluene

    Science.gov (United States)

    1976-07-01

    and the neuromuscular effects in these dogs were not due to hypocalcemia . The lowest serum calcium concen- tration in these dogs was 4.2 meq/liter...motor end plate might produce a local hypocalcemia . Such a mechanism is purely speculative. Qualitatively and quantitavely, most of the effects of 2,6...I ýNw,- -MIM I/ MIDWEST RESEARCH INS14ITUTE H0q .3L I LU -_ MAMMALIAN TOXICITY OF MUNITIONS COMPOUlNDSPHASE II: EFFECTS OF MiULTIPLE DOSES C* •PART

  11. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.

    Science.gov (United States)

    Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin

    2011-05-01

    Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.

  12. Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

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

    2017-01-01

    The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

  13. Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Overgaard, Jens; Alsner, Jan

    2005-01-01

    cell lines after various ionizing radiation (IR) schemes in order to provide information on potential targets for prevention and to suggest candidate genes for SNP association studies aimed at predicting individual risk of radiation-induced morbidity. PATIENTS AND METHODS: Thirty different human......BACKGROUND AND PURPOSE: Transcriptional profiling of fibroblasts derived from breast cancer patients might improve our understanding of subcutaneous radiation-induced fibrosis. The aim of this study was to get a comprehensive overview of the changes in gene expression in subcutaneous fibroblast...... fibroblast cell lines were included in the study, and two different radiation schemes; single dose experiments with 3.5 Gy or fractionated with 3 x 3.5 Gy. Expression analyses were performed on unexposed and exposed cells after different time points. The IR response was analyzed using the statistical method...

  14. Does three-dimensional transesophageal echocardiography provide incremental value in percutaneous closure of ascending aortic pseudoaneurysm?

    Science.gov (United States)

    Elkaryoni, Ahmed; Hsiung, Ming C; Arisha, Mohammed J; Ahmad, Amier; Nanda, Navin C; Mohamed, Ahmed H; Attia, Doaa; Sachdeva, Ankush; Singh, Lovepreet; Yin, Wei-Hsian

    2017-07-01

    Ascending aortic pseudoaneurysms (AO PSAs), if left untreated, are complicated by a high rate of rupture resulting in significant morbidity and mortality. New transcatheter modalities have emerged as acceptable surgical alternatives for their management. We present a case of an ascending aortic PSA in which intraoperative two- and three-dimensional transesophageal echocardiography (2DTEE and 3DTEE) provided a comprehensive assessment of the PSA in pre- and postclosure settings. © 2017, Wiley Periodicals, Inc.

  15. Neurogenic period of ascending tract neurons in the upper lumbar spinal cord of the rat

    International Nuclear Information System (INIS)

    Nandi, K.N.; Beal, J.A.; Knight, D.S.

    1990-01-01

    Although the neurogenic period for neurons in the lumbar spinal cord has been clearly established (Days 12 through 16 of gestation), it is not known when the neurogenesis of ascending tract neurons is completed within this period. The purpose of the present study was to determine the duration of the neurogenic period for projection neurons of the ascending tracts. To label neurons undergoing mitosis during this period, tritiated thymidine was administered to fetal rats on Embryonic (E) Days E13 through E16 of gestation. Ascending tract neurons of the lumbar cord were later (Postnatal Days 40-50) labeled in each animal with a retrograde tracer, Fluoro-Gold, applied at the site of a hemisection at spinal cord segment C3. Ascending tract neurons which were undergoing mitosis in the upper lumbar cord were double labeled, i.e., labeled with both tritiated thymidine and Fluoro-Gold. On Day E13, 89-92% of the ascending tract neurons were double labeled; on Day E14, 35-37%; and on Day E15, 1-4%. Results showed, then, that some ascending tract neurons were double labeled through Day E15 and were, therefore, proliferating in the final one-third of the neurogenic period. Ascending tract neurons proliferating on Day E15 were confined to laminae III, IV, V, and X and the nucleus dorsalis. Long tract neurons in the superficial dorsal horn (laminae I and II), on the other hand, were found to have completed neurogenesis on Day E14 of gestation. Results of the present study show that spinal neurogenesis of ascending projection neurons continues throughout most of the neurogenic period and does not completely follow the well-established ventral to dorsal gradient

  16. Laparoscopic excision of an ascending colon duplication cyst in an adolescent

    Directory of Open Access Journals (Sweden)

    Heather R. Nolan

    2016-01-01

    Full Text Available Colonic intestinal duplications are infrequent and rarely present past early childhood. We present the case of a large, ascending colon duplication in a 17-year-old boy resected using minimally invasive techniques. This appears to be the first reported case of a laparoscopic en-bloc ascending colon duplication resection in an adolescent. The diagnosis and management of colonic duplications are discussed.

  17. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis

    OpenAIRE

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-01-01

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recogni...

  18. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

    Science.gov (United States)

    Christensen, Steven; Paluch, Ed; Jayawardena, Shyamalie; Daniels, Stephen; Meeves, Suzanne

    2017-05-01

    Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P ibuprofen IR/ER, respectively (P ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses. © 2016, The American College of Clinical Pharmacology.

  19. Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

    Science.gov (United States)

    Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

    2005-07-01

    We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

  20. Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides

    International Nuclear Information System (INIS)

    Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

    2005-01-01

    We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (μg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r = 0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r = 0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA

  1. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

    Science.gov (United States)

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

    2016-12-24

    Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

  2. Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD and Multiple Approaches for Selection of Chemical Point of Departure (PoD.

    Directory of Open Access Journals (Sweden)

    A Francina Webster

    Full Text Available Many regulatory agencies are exploring ways to integrate toxicogenomic data into their chemical risk assessments. The major challenge lies in determining how to distill the complex data produced by high-content, multi-dose gene expression studies into quantitative information. It has been proposed that benchmark dose (BMD values derived from toxicogenomics data be used as point of departure (PoD values in chemical risk assessments. However, there is limited information regarding which genomics platforms are most suitable and how to select appropriate PoD values. In this study, we compared BMD values modeled from RNA sequencing-, microarray-, and qPCR-derived gene expression data from a single study, and explored multiple approaches for selecting a single PoD from these data. The strategies evaluated include several that do not require prior mechanistic knowledge of the compound for selection of the PoD, thus providing approaches for assessing data-poor chemicals. We used RNA extracted from the livers of female mice exposed to non-carcinogenic (0, 2 mg/kg/day, mkd and carcinogenic (4, 8 mkd doses of furan for 21 days. We show that transcriptional BMD values were consistent across technologies and highly predictive of the two-year cancer bioassay-based PoD. We also demonstrate that filtering data based on statistically significant changes in gene expression prior to BMD modeling creates more conservative BMD values. Taken together, this case study on mice exposed to furan demonstrates that high-content toxicogenomics studies produce robust data for BMD modelling that are minimally affected by inter-technology variability and highly predictive of cancer-based PoD doses.

  3. Development of 99mTc imaging method using multiple imaging plates for reduction of patient's dose

    International Nuclear Information System (INIS)

    Ito, Shigeki; Nishizawa, Kunihide; Ariga, Eiji; Saze, Takuya

    2008-01-01

    A system for taking static thyroid 99m Tc images was devised by using multiple imaging plates (IPs) and a low energy high resolution collimator. Sensitivity was represented by using lower detection limits (LDL). The sensitivity and resolution of IP systems using a collimator and 9 IPs were determined by using a 20 ml thyroid phantom, and compared with the sensitivity of gamma cameras. The sensitivity of the IP systems increased in proportion to the number of IPs. The sensitivity and resolution of a probe using 9 IPs and a high resolution collimator were equivalent to or superior to the gamma camera for taking static thyroid 99m Tc images. IP systems can be applied clinically as static nuclear imaging devices as same as a gamma camera. (author)

  4. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  5. Analgesic efficacy of lysine clonixinate plus tramadol versus tramadol in multiple doses following impacted third molar surgery.

    Science.gov (United States)

    Perez-Urizar, J; Martínez-Rider, R; Torres-Roque, I; Garrocho-Rangel, A; Pozos-Guillen, A

    2014-03-01

    This study compared the analgesic and anti-inflammatory efficacy, trismus control, and tolerability of the combination of lysine clonixinate and tramadol (LCT) versus tramadol (T) alone after surgical removal of impacted mandibular third molars. This study was a double-blind, randomized clinical trial, including two study groups of 20 patients each, who exhibited acute pain subsequent to surgical extraction of two mandibular third molars. Pain intensity was quantified over a 96-h period using a visual analogue scale and a 5-point verbal rating scale. Secondary indicators of analgesic and anti-inflammatory efficacy, trismus control, and tolerability were determined. Patients administered LCT exhibited better therapeutic effects that those administered T. Fifty percent of patients in the LCT group rated this therapy as 'excellent analgesia' compared with only 10% in the T group. The onset of the analgesic effect of LCT was significantly faster, without any therapeutic failures. There were no significant differences between the groups with regard to anti-inflammatory effect or trismus. The results of this study suggest that the postsurgical analgesic efficacy of LCT in combination (LC 125 mg + T 25 mg) is superior to that obtained with T alone, administered at the standard dose of 50 mg, for up to 96 h after the extraction of both impacted mandibular third molars. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  6. Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

    International Nuclear Information System (INIS)

    Breeman, Wout A. P.; Jong, Marion de; Bernard, Bert F.; Bakker, Willem H.; Rolleman, Edgar J.; Kwekkeboom, Kik J.; Visser, Theo J.; Krenning, Eric P.

    1997-01-01

    In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin[reg]) is usually discontinued 24-48 h before and after injection with the radioligand 111 In-pentetreotide ([ 111 In-DTPA o ]octreotide) (Octreoscan[reg]) because octreotide competes with radioligand for the same receptors. However, Doerr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 μg) of 111 In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111 In-pentetreotide. Administration of 100 μg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111 In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration

  7. Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

    Directory of Open Access Journals (Sweden)

    Seyed Amir Dadkhahi

    2017-05-01

    Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

  8. Sustainability Instruction in High Doses: Results From Incorporation of Multiple InTeGrate Modules Into an Environmental Science Class

    Science.gov (United States)

    Rademacher, L. K.

    2017-12-01

    The Interdisciplinary Teaching about Earth for a Sustainable Future (InTeGrate) community has developed extensive courses and modules designed for broad adoption into geoscience classrooms in diverse environments. I participated in a three-semester research project designed to test the efficacy of incorporating "high doses" (minimum 3 modules or 18 class periods) of InTeGrate materials into a course, in my case, an introductory environmental science class. InTeGrate materials were developed by groups of instructors from a range of institutions across the US. These materials include an emphasis on systems thinking, interdisciplinary approaches, and sustainability, and those themes are woven throughout the modules. The three semesters included a control in which no InTeGrate materials were used, a pilot in which InTeGrate materials were tested, and a treatment semesters in which tested materials were modified as needed and fully implemented into the course. Data were collected each semester on student attitudes using the InTeGrate Attitudinal Instrument (pre and post), a subset of Geoscience Literacy Exam questions (pre and post), and a series of assessments and essay exam questions (post only). Although results suggest that learning gains were mixed, changes in attitudes pre- and post-instruction were substantial. Changes in attitudes regarding the importance of sustainable employers, the frequency of self-reported individual sustainable actions, and motivation level for creating a sustainable society were observed in the control and treatment semesters, with the treatment semester showing the greatest gains. Importantly, one of the biggest differences between the control and treatment semesters is the reported impact that the course had on influencing students' sustainable behaviors. The treatment semester course impacted students' sustainable behaviors far more than the control semester.

  9. Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.

    Science.gov (United States)

    Van Sanden, Suzy; Ito, Tetsuro; Diels, Joris; Vogel, Martin; Belch, Andrew; Oriol, Albert

    2018-03-01

    Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations. The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies. The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; p  = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p  < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; p  = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p  = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%). The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma. This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these

  10. Efficacy and Safety of Multiple Doses of Exenatide Once-Monthly Suspension in Patients With Type 2 Diabetes: A Phase II Randomized Clinical Trial.

    Science.gov (United States)

    Wysham, Carol H; MacConell, Leigh; Hardy, Elise

    2016-10-01

    This study investigated the efficacy and safety of multiple exenatide once-monthly suspension (QMS) doses of exenatide-containing microspheres in Miglyol referenced against the clinical dose of exenatide once-weekly (QW) microspheres in aqueous solution. In this phase II, randomized, controlled, single-blind study, 121 adults (∼30/arm) with type 2 diabetes and HbA1c 7.1-11.0% (54-97 mmol/mol) were randomized 1:1:1:1 to subcutaneous exenatide QW 2 mg (self-administered) or exenatide QMS 5, 8, or 11 mg (caregiver-administered) for 20 weeks. The primary end point was change in HbA1c. At baseline, mean age was 50 years, HbA1c was 8.5% (69 mmol/mol), fasting plasma glucose (FPG) was 184 mg/dL, and body weight was 98 kg. At week 20, mean ± SD HbA1c reductions were -1.54% ± 1.26% with exenatide QW and -1.29% ± 1.07%, -1.31% ± 1.66%, and -1.45% ± 0.93% with exenatide QMS 5, 8, and 11 mg, respectively (evaluable population: n = 110). There were no significant differences in HbA1c reductions among the exenatide QMS doses. FPG reductions were -34 ± 48 mg/dL with exenatide QW and -25 ± 43, -30 ± 52, and -49 ± 49 mg/dL with exenatide QMS 5, 8, and 11 mg, respectively. Weight decreased with all treatments. For exenatide QMS, nausea (16.7-23.3%) and headache (16.7-26.7%) were the most common adverse events. No major or minor hypoglycemia occurred. All doses of exenatide QMS resulted in efficacy and tolerability profiles consistent with exenatide QW. These results combined with pharmacokinetic and pharmacodynamic modeling could inform dose selection for further development. © 2016 by the American Diabetes Association.

  11. Assessment of pulmonary function using pixel indexes of multiple-slice spiral CT low-dose two-phase scanning in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Zhang Lihua; Wang Yunhua; Jiang Zhongbiao; Zhang Lejun; Sun Wanli; Zhang Chunming

    2012-01-01

    Objective: To explore the values of pixel indexes (PI) with multiple-slice spiral CT low-dose two-phase scanning for assessing the pulmonary function in chronic obstructive pulmonary disease (COPD). Methods: Thirty-six patients with COPD (COPD group)and 30 healthy people (control group)underwent pulmonary function test (PFT). Chest 64-MSCT low-dose (50 mAs) scanning at full inspiration and expiration, routine scanning (100 mAs) at inspiration were performed. The effective dose (ED) was calculated. The lung was divided into three regions (upper, middle, lower). PI of lung were divided into five groups: -960--1024, -910--960, -800--910, -700--800, -400--700. The PI -910 (sum of the PI under -910 HU) of low-dose scanning at each region were measured and calculated using pulmo software. All PI included PIin -910 , PIiex -910 , PIin -910 -PIiex -910 , PIiex -910 /PIin -910 and (PIin -910 -PIiex -910 )/PIin -910 . All patients underwent PFT within 3 days after 64-MSCT canning, FEV1% and FEV1/FVC were selected for comparison. Results: The PIin in three regions (-960 - -1024, -910 - -960, -800 - -910) were statistically significant between normal and COPD groups (U=0.00, 57.00, 20.50, P<0.01). The PIex in all regions were statistically significant (U=0.00, 0.00, 71.52, 191.00, 6.00, P<0.01). PI -910--1024 at expiration and inspiration were correlated with FEV1% and FEV1/FVC (r=-0.548, -0.664, -0.752, -0.781, P<0.01). PIin -910 , PIex -910 ,PIiex -910 /PIin -910 , (PIin -910 -PIex -910 )/PIin -910 had a good correlation with FEV1% and FEV1/FVC (r=-0.548, -0.664, -0.752, -0.781, -0.674, -0.642, 0.674, 0.642, P<0.01). Conclusion: Pixel indexes of 64-MSCT low-dose two-phase scanning can be used to evaluate pulmonary function in COPD patients. (authors)

  12. Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

    DEFF Research Database (Denmark)

    Alkharusi, Amira; Mirecki-Garrido, Mercedes; Ma, Zuheng

    2016-01-01

    Background: Diabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can...... prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity. Methodology: The elevated sensitivity of SOCS2-/- mice to GH and possibly to PRL was the rationale to analyze the effects of multiple low dose streptozotocin (MLDSTZ)-induced diabetes...... in SOCS2-/- mice. Results: We show that 6-month-old SOCS2-/- mice, but not 2-month-old mice, were less sensitive to MLDSTZ-induced diabetes, compared to controls. MLDSTZ treatment induced glucose intolerance in both SOCS2+/+ and SOCS2-/- mice, as shown by glucose tolerance tests, with SOCS2+/+ mice...

  13. Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito, Davide, E-mail: davide.atena@tiscalinet.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Besostri, Valeria, E-mail: valeriabesostri@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Bonaffini, Pietro Andrea, E-mail: pa.bonaffini@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Rossini, Fausto, E-mail: valeriabesostri@hotmail.it [Department of Hematology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Di Lelio, Alessandro, E-mail: valebeso@libero.it [Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Sironi, Sandro, E-mail: sandrosironi@libero.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy)

    2013-12-01

    Purpose: To assess the role of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of patients with suspicion of multiple myeloma (MM). Materials and methods: A total of 138 patients (76 male and 62 female; mean age 63.5 years, range 50–81 years), with early MM, underwent WBLDCT protocol study, performed on 16-slice scanner (Brilliance, Philips Medical System, Eindhoven, The Netherlands): tube voltage 120 kV; tube current time product 40 mAs. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done by using multiplanar reformatted images. The overall dose delivered to each patient was 4.2 mSv. Every patient gave personal informed consent, as required by our institution guidelines. Results: The diagnosis was established either by histopathology or imaging follow-up (size increase of over a period time). In all 138 patients, image resolution was diagnostic, enabling correct classification of multiple myeloma patients. WBLDCT showed a total of 328 pathologic bone findings in 81/138 patients. CT scanning resulted in complete evaluation of the bone lesions in these areas of the skeleton: skull (42), humerus (15), femur (20), ribs (7), scapulae (13), pelvis (35), clavicle (13), sternum (10), cervical (39), dorsal (65), lombar (48) and sacral rachis (21). In 40/81 bone involvement detected by CT was the only CRAB criterion present. Furthermore, WBLDCT demonstrated pleuro-pulmonary lesions in 20 patients (11 infective, 9 as MM localizations) and 1 renal neoplasia. Conclusion: WBLDCT, detecting bone marrow localizations and demonstrating extra-osseous findings, with a fast scanning time and high resolution images, is a reliable imaging-based tool for a proper management of MM patients.

  14. Clinical and prognostic significance of bone marrow abnormalities in the appendicular skeleton detected by low-dose whole-body multidetector computed tomography in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Nishida, Y; Matsue, Y; Suehara, Y; Fukumoto, K; Fujisawa, M; Takeuchi, M; Ouchi, E; Matsue, K

    2015-01-01

    Clinical significance of medullary abnormalities in the appendicular skeleton (AS) detected by low-dose whole-body multidetector computed tomography (MDCT) in patients with multiple myeloma (MM) was investigated. A total of 172 patients with monoclonal gammopathy of undetermined significance (MGUS) (n=17), smoldering MM (n=47) and symptomatic MM (n=108) underwent low-dose MDCT. CT values (CTv) of medullary density of AS⩾0 Hounsfield unit (HU) was considered as abnormal. Percentage of medullary abnormalities and the mean CTv of AS in patients with MGUS, smoldering MM and symptomatic MM were 18, 55 and 62% and −44.5 , −20.3 and 11.2 HU, respectively (P<0.001 and P<0.001). Disease progression of MM was independently associated with high CTv on multivariate analysis. In symptomatic MM, the presence of abnormal medullary lesions was associated with increased incidence of high-risk cytogenetic abnormalities (34.4% vs 7.7% P=0.002) and extramedullary disease (10.4% vs 0% P=0.032). It was also an independent poor prognostic predictor (hazard ratio 3.546, P=0.04). This study showed that CTv of AS by MDCT is correlated with disease progression of MM, and the presence of abnormal medullary lesions is a predictor for poor survival

  15. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma. Final results of phase III US Intergroup Trial S9321

    International Nuclear Information System (INIS)

    Kim, Sung-Won; Tobinai, Kensei

    2007-01-01

    The outline of the title trial is described in comparison with outcomes of other randomized controlled trials. The S9321 trial in US started in 1993 by Southwest Oncology Group, Eastern Cooperative Oncology Group and Cancer and Leukemia Group B, including 11 institutions for performance status 0-2 untreated patients of symptomatic multiple myeloma (MM). Patients were randomized to either group receiving the standard dose therapy (SDT) or high-dose therapy with autologous heamatopoietic stem cell transplantation group (HDT). The former essentially underwent the chemotherapy with vincristine, carmustine, melphalan (MEL) and predonisolone after the remission treatment and the latter, whole body irradiation of total 12 Gy (8 fractions/4 days) as well. An appropriate part of the latter group also received the transplantation of allogenic heamatopoietic stem cells previously treated with MEL and 12-Gy radiation. Patients younger than 70 y of age, 899 cases, were registered in the trial, 86 of whom were eliminated before the remission treatment and 248, at that treatment end. No statistical significance was seen between SDT and HDT in efficacy. It is concluded that, despite the present outcome, HDT should be taken into consideration because novel medicals are being under development and MM is a symptomatic disease originated from different molecular bases. (T.I.)

  16. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

    2016-11-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

  17. Gamma knife radiosurgery for acoustic schwannomas. An analysis of the method of low dose and conformal multiple shots with smaller collimator

    International Nuclear Information System (INIS)

    Fukuoka, Seiji; Takanashi, Masami; Hojo, Atsufumi; Konishi, Masanori; Nakamura, Hirohiko

    2003-01-01

    The purpose of this study was to analyze tumor control and possible complications of gamma knife radiosurgery (GKRS) in patients with acoustic schwannomas treated using low marginal dose and conformal multiple shots with smaller collimators to fit irregular tumor shapes. The authors evaluated 183 patients with follow-up periods ranging from 3 to 11 years. Marginal doses were 9 to 15 Gy (median 12 Gy), with corresponding treatment volumes being between 0.1 and 18.7 ml (median 1.8 ml). The number of isocenter varied from 2 to 24 shots (median 9 shots). The actuarial tumor control rate (resection-free survival) was 96.5%. Useful hearing, trigeminal and facial functions were preserved at 75%, 97.4%, and 100%, respectively. Hydrocephalus was recognized in 5.7% of all patients, and seems to occur in cases with medium sized tumors where mild ventricular enlargement is evident prior to treatment. GKRS proves to be a safe and effective therapy for small to medium sized tumors. However, the indication for larger sized tumors (diameter 3+ cm) should be carefully considered, larger tumors being less easy to control and liable to cause ataxia due to transient expansion. (author)

  18. Ascending colon rotation following patient positional change during CT colonography: a potential pitfall in interpretation

    International Nuclear Information System (INIS)

    Kim, Ji Yeon; Park, Seong Ho; Lee, Seung Soo; Kim, Ah Young; Ha, Hyun Kwon

    2011-01-01

    To investigate the degree and pattern of ascending colonic rotation as patients moved from supine to prone positions during CTC. A search of our CTC and colonoscopy database found 37 patients (43 eligible lesions) who fulfilled the following criteria: colonoscopy-proven sessile polyps ≥6 mm in the straight mid-ascending colon, lesion visualisation in both supine and prone CTC, and optimal colonic distension. A coordinate system was developed to designate the polyp radial location ( ) along the luminal circumference, unaffected by rotation of the torso. The degree/direction of polyp radial location change (i.e. ascending colonic rotation) between supine and prone positions correlated with anthropometric measurements. Movement from supine to prone positions resulted in a change in the radial polyp location of between -23 and 79 (median, 21 ), demonstrating external rotation of the ascending colon in almost all cases (2 to 79 in 36/37 patients and 42/43 lesions). The degree/direction of rotation mildly correlated with the degree of abdominal compression in the anterior-posterior direction in prone position (r = 0.427 [P = 0.004] and r = 0.404 [P = 0.007]). The ascending colon was usually found to rotate externally as patients moved from supine to prone positions, partly dependent on the degree of abdominal compression. (orig.)

  19. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-01-01

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11–33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer–specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8–3.9, p < 0.0001), salvage ADT use (HR 3.9–6.3, p < 0.0001), metastasis (HR 3.7–6.6, p < 0.0001), and PCSM (HR 3.7–16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19–0.38, p < 0.001) and PCSM (HR 0.38–0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3–4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25–0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  20. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    International Nuclear Information System (INIS)

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma

  1. Temperature-based ascendancy derived from a cost or reward function

    International Nuclear Information System (INIS)

    Collins, Dennis

    2001-01-01

    Ulanowicz defines ascendancy in terms of departure from maximum-entropy (proportional) flow; however he does not explain what may cause this departure. Here the ascendancy is derived by minimizing a cost function. At high temperatures (small α>0) the first (min of negative entropy=max entropy) term dominates, but as α increases (temperature decreases), the cost function dominates, causing a departure from maximum entropy, or ascendancy. Riverbed analogy: At high temperature (fast flows) the flow is mostly uniform (max entropy) across the river bed, but at low temperatures (limited flow), the structure of the riverbed (cost function) becomes more important, with some channels being cut off, or evaporated by too much sun, some flows being diverted by rocks, and so on. Also, if the total cost (or reward) term is held constant, the parameter can be considered a Lagrange multiplier, and the problem can be reduced (similar to a Legendre transformation) to a maximum entropy problem, subject to constraints

  2. Dependence of energy characteristics of ascending swirling air flow on velocity of vertical blowing

    Science.gov (United States)

    Volkov, R. E.; Obukhov, A. G.; Kutrunov, V. N.

    2018-05-01

    In the model of a compressible continuous medium, for the complete Navier-Stokes system of equations, an initial boundary problem is proposed that corresponds to the conducted and planned experiments and describes complex three-dimensional flows of a viscous compressible heat-conducting gas in ascending swirling flows that are initiated by a vertical cold blowing. Using parallelization methods, three-dimensional nonstationary flows of a polytropic viscous compressible heat-conducting gas are constructed numerically in different scaled ascending swirling flows under the condition when gravity and Coriolis forces act. With the help of explicit difference schemes and the proposed initial boundary conditions, approximate solutions of the complete system of Navier-Stokes equations are constructed as well as the velocity and energy characteristics of three-dimensional nonstationary gas flows in ascending swirling flows are determined.

  3. Developmental salivary gland depression in the ascending mandibular ramous: A cone-beam computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Christine A.; Ahn, Yoon Hee; Odell, Scott; Mupparapu, Mel; Graham, David Mattew [University of Pennsylvania School of Dental Medicine, Philadelphia (United States)

    2016-09-15

    A static, unilateral, and focal bone depression located lingually within the ascending ramous, identical to the Stafne's bone cavity of the angle of the mandible, is being reported. During development of the mandible, submandibular gland inclusion may lead to the formation of a lingual concavity, which could contain fatty tissue, blood vessels, or soft tissue. However, similar occurrences in the ascending ramous at the level of the parotid gland are extremely rare. Similar cases were previously reported in dry, excavated mandibles, and 3 cases were reported in living patients. A 52-year-old African American male patient was seen for pain in the mandibular teeth. Panoramic radiography showed an unusual concavity within the left ascending ramous. Cone-beam computed tomography confirmed this incidental finding. The patient was cleared for the extraction of non-restorable teeth and scheduled for annual follow-up.

  4. Surgical repair of a pseudoaneurysm of the ascending aorta after aortic valve replacement

    Directory of Open Access Journals (Sweden)

    Almeida Rui Manuel Sequeira de

    2001-01-01

    Full Text Available We report the case of a patient with a pseudoaneurysm of the ascending aortic clinically diagnosed 5 months after surgical replacement of the aortic valve. Diagnosis was confirmed with the aid of two-dimensional echocardiography and helicoidal angiotomography. The corrective surgery, which consisted of a reinforced suture of the communication with the ascending aorta after opening and aspiration of the cavity of the pseudoaneurysm, was successfully performed through a complete sternotomy using extracorporeal circulation, femorofemoral cannulation, and moderate hypothermia, with no aortic clamping.

  5. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis.

    Science.gov (United States)

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-06-30

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recognition of such cases with diverticular colitis preceding ulcerative colitis. There may be a possible pathogenic relationship between the two diseases. 2014 BMJ Publishing Group Ltd.

  6. Axial and Cellular Heterogeneity in Electrolyte Transport Pathways Along the Thick Ascending Limb

    DEFF Research Database (Denmark)

    Dimke, Henrik; Schnermann, Jürgen

    2018-01-01

    The thick ascending limb (TAL) extends from the border of the inner medulla to the renal cortex, thus ascending through regions with wide differences in tissue solute and electrolyte concentrations. Structural and functional differences between TAL cells in the medulla (mTAL) and the cortex (c......TAL, divergent axial and cellular expression of H+transport proteins in TAL have been documented. The reabsorption of the divalent cations Ca2+and Mg2+is highest in cTAL and paralleled by differences in divalent cation permeability and the expression of select claudins. Morphologically, two cell types...

  7. A Comparison of Potential IM-CW Lidar Modulation Techniques for ASCENDS CO2 Column Measurements From Space

    Science.gov (United States)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.; Harrison, F. Wallace; Obland, Michael D.; Ismail, Syed

    2014-01-01

    Global atmospheric carbon dioxide (CO2) measurements through the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) Decadal Survey recommended space mission are critical for improving our understanding of CO2 sources and sinks. IM-CW (Intensity Modulated Continuous Wave) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS science requirements. In previous laboratory and flight experiments we have successfully used linear swept frequency modulation to discriminate surface lidar returns from intermediate aerosol and cloud contamination. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate clouds, which is a requirement for the inversion of the CO2 column-mixing ratio from the instrument optical depth measurements, has been demonstrated with the linear swept frequency modulation technique. We are concurrently investigating advanced techniques to help improve the auto-correlation properties of the transmitted waveform implemented through physical hardware to make cloud rejection more robust in special restricted scenarios. Several different carrier based modulation techniques are compared including orthogonal linear swept, orthogonal non-linear swept, and Binary Phase Shift Keying (BPSK). Techniques are investigated that reduce or eliminate sidelobes. These techniques have excellent auto-correlation properties while possessing a finite bandwidth (by way of a new cyclic digital filter), which will reduce bias error in the presence of multiple scatterers. Our analyses show that the studied modulation techniques can increase the accuracy of CO2 column measurements from space. A comparison of various properties such as signal to noise ratio (SNR) and time-bandwidth product are discussed.

  8. Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters without polycystic ovary syndrome: prediction of effectiveness by multiple parameters related to insulin resistance.

    Science.gov (United States)

    Jinno, Masao; Kondou, Kenichi; Teruya, Koji

    2010-01-01

    Insulin resistance is associated with aging and stress, both common among patients repeatedly failing to conceive with in vitro fertilization (IVF repeaters). In the present study we examined whether low-dose metformin could improve the outcome in IVF repeaters without polycystic ovary syndrome (PCOS). Study I was a preliminary clinical trial aiming at defining indications for therapy; study II was a prospective randomized study. The studies involved a university hospital and a private infertility clinic. We studied 232 women without PCOS who had failed at least twice to conceive by previous IVF. Metformin (500 mg/ day) was administered for 8 to 12 weeks before and during ovarian stimulation (metformin IVF). In study I, IVF outcomes with metformin (n = 33) were compared to outcomes without metformin of previous IVF in the same subjects. A discriminant score (DS) was determined from nine parameters assessed before metformin administration to predict achievement of ongoing pregnancy by metformin IVF. In study II (n = 199), ongoing pregnancy rates were compared prospectively between groups with/without metformin and with DS above/below 0.6647. Study I. Ongoing pregnancy rate improved significantly with metformin compared with previous IVF, and pregnancy correlated significantly with a DS at an optimal threshold of 0.6647 (sensitivity, 0.90; specificity, 0.91). Study II. Ongoing pregnancy and implantation rates were significantly higher in women with a DS above 0.6647 who received metformin (56% and 33%) compared with those having a DS below 0.6647 with metformin (14% and 11%) and those having a DS above/below 0.6647 without metformin (20% and 7.1%/15% and 11%, respectively). Low-dose metformin improved pregnancy rate in IVF repeaters without PCOS, probably by decreasing insulin resistance. Indication can be determined from insulin-resistance-related multiple parameters assessed before metformin administration.

  9. Computed tomography in multiple trauma patients. Technical aspects, work flow, and dose reduction; Polytrauma-Computertomographie. Technische Grundlagen, Workflow und Dosisreduktion

    Energy Technology Data Exchange (ETDEWEB)

    Fellner, F.A. [AKH Linz - Kepler Universitaetsklinikum/JKU, Zentrales Radiologie Institut, Linz (Austria); Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen (Germany); Krieger, J.; Floery, D. [AKH Linz - Kepler Universitaetsklinikum/JKU, Zentrales Radiologie Institut, Linz (Austria); Lechner, N. [AKH Linz - Kepler Universitaetsklinikum/JKU, Abteilung fuer Medizintechnik, Linz (Austria)

    2014-09-15

    Patients with severe, life-threatening trauma require a fast and accurate clinical and imaging diagnostic workup during the first phase of trauma management. Early whole-body computed tomography has clearly been proven to be the current standard of care of these patients. A similar imaging quality can be achieved in the multiple trauma setting compared with routine imaging especially using rapid, latest generation computed tomography (CT) scanners. This article encompasses a detailed view on the use of CT in patients with life-threatening trauma. A special focus is placed on radiological procedures in trauma units and on the methods for CT workup in routine cases and in challenging situations. Another focus discusses the potential of dose reduction of CT scans in multiple trauma as well as the examination of children with severe trauma. Various studies have demonstrated that early whole-body CT positively correlates with low morbidity and mortality and is clearly superior to the use of other imaging modalities. Optimal trauma unit management means a close cooperation between trauma surgeons, anesthesiologists and radiologists, whereby the radiologist is responsible for a rapid and accurate radiological workup and the rapid communication of imaging findings. However, even in the trauma setting, aspects of patient radiation doses should be kept in mind. (orig.) [German] Polytraumatisierte Patienten beduerfen im Rahmen der initialen Schockraumversorgung einer schnellen und exakten klinischen und bildgebenden Diagnostik. Fuer ein optimales Schockraummanagement ist heute die essenzielle Bedeutung einer zeitnah durchgefuehrten Ganzkoerper-CT unbestritten. Insbesondere durch schnelle CT-Scanner der letzten Generationen kann im Rahmen der Schockraum-CT eine aehnlich gute Bildqualitaet wie in der Routinediagnostik erzielt werden. Dieser Artikel beleuchtet den Einsatz der CT im Schockraum bei polytraumatisierten Patienten, wobei das Hauptaugenmerk auf Methoden des

  10. Aortic annulus and ascending aorta: Comparison of preoperative and periooperative measurement in patients with aortic stenosis

    International Nuclear Information System (INIS)

    Smid, Michal; Ferda, Jiri; Baxa, Jan; Cech, Jakub; Hajek, Tomas; Kreuzberg, Boris; Rokyta, Richard

    2010-01-01

    Background: Precise determination of the aortic annulus size constitutes an integral part of the preoperative evaluation prior to aortic valve replacement. It enables the estimation of the size of prosthesis to be implanted. Knowledge of the size of the ascending aorta is required in the preoperative analysis and monitoring of its dilation enables the precise timing of the operation. Our goal was to compare the precision of measurement of the aortic annulus and ascending aorta using magnetic resonance (MR), multidetector-row computed tomography (MDCT), transthoracic echocardiography (TTE), and transoesophageal echocardiography (TEE) in patients with degenerative aortic stenosis. Methods and results: A total of 15 patients scheduled to have aortic valve replacement were enrolled into this prospective study. TTE was performed in all patients and was supplemented with TEE, CT and MR in the majority of patients. The values obtained were compared with perioperative measurements. For the measurement of aortic annulus, MR was found to be the most precise technique, followed by MDCT, TTE, and TEE. For the measurement of ascending aorta, MR again was found to be the most precise technique, followed by MDCT, TEE, and TTE. Conclusion: In our study, magnetic resonance was found to be the most precise technique for the measurement of aortic annulus and ascending aorta in patients with severe degenerative aortic stenosis.

  11. Relationship between aneurism of ascending part of aorta and syndrome of connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Osovska N.Yu.

    2014-11-01

    Full Text Available The paper identifies the main reasons for the development of an aneurysm of the ascending aorta and predictors of its complications in patients of all ages. To determine the cause and age-associated risk factors for aneurysms there were examined 154 patients with the presence of the expansion of the root and / or ascending aorta of more than 40 mm, according to echocardiographic examination. Patients were divided into 4 categories by age: 18-29 years, 30-44 years 45-59 years 60-74 years. Instrumental methods of examination: echocardiography, ECG, ECG monitoring and blood pressure, heart rate variability, ultrasound of internal organs were used. Syndrome of connective tissue dysplasia was established according to the criteria of the working group of the British Society of Rheumatology. Joint hypermobility syndrome was determined according to the Brayton criteria. Statistical processing was carried out by methods of variation statistic program StatSoft "Statistica" v.10.0. It was established that in young and middle aged patients the cause of aneurysm of ascending aorta more often is connective tissue dysplasia syndrome. In older patients the main cause of aneurysm of ascending aorta is associated with left ventricular hypertrophy and decreased contractile function of the heart.

  12. Effects of ascending and descending climbers on space elevator cable dynamics

    Science.gov (United States)

    Ishikawa, Yoji; Otsuka, Kiyotoshi; Yamagiwa, Yoshiki; Doi, Hinata

    2018-04-01

    Based on a mass-point model, the cable dynamics of a space elevator during a climber's travel motion are examined. The cable response during a single operation of one ascending or descending climber is analyzed first, and then, based on the results, the cable dynamics for simultaneous operation of an ascending and a descending climber are evaluated. For the single operation, bending is significant when the climber is traveling near the Earth's surface. The cable also inclines with periodic oscillation as a result of a Coriolis force corresponding to the climber velocity. However, simultaneous operation of ascending and descending climbers can suppress the inclination of the cable by almost a factor of ten. In simultaneous operation, compared to single operation, a descending climber has a smaller amplitude of libration angle and less cable bending, while an ascending climber has a smaller amplitude when the climber is traveling at a higher altitude with climber velocities of 200 km/h and 400 km/h. The phase of the oscillation of the overall cable is found to be close to that of the descending climber. Cable bending is suppressed for any examined climber velocity, but the dependency of this suppression of displacement on climber velocity is not found. In summary, simultaneous operation can surely suppress the inclination of the cable via the cancellation of Coriolis forces by the two climbers.

  13. Asymmetric variations in the tropical ascending branches of Hadley circulations and the associated mechanisms and effects

    Science.gov (United States)

    Sun, Bo

    2018-03-01

    This study investigates the variations in the tropical ascending branches (TABs) of Hadley circulations (HCs) during past decades, using a variety of reanalysis datasets. The northern tropical ascending branch (NTAB) and the southern tropical ascending branch (STAB), which are defined as the ascending branches of the Northern Hemisphere HC and Southern Hemisphere HC, respectively, are identified and analyzed regarding their trends and variability. The reanalysis datasets consistently show a persistent increase in STAB during past decades, whereas they show less consistency in NTAB regarding its decadalto multidecadal variability, which generally features a decreasing trend. These asymmetric trends in STAB and NTAB are attributed to asymmetric trends in the tropical SSTs. The relationship between STAB/NTAB and tropical SSTs is further examined regarding their interannual and decadal- to multidecadal variability. On the interannual time scale, the STAB and NTAB are essentially modulated by the eastern-Pacific type of ENSO, with a strengthened (weakened) STAB (NTAB) under an El Niño condition. On the decadal- to multidecadal time scale, the variability of STAB and NTAB is closely related to the southern tropical SSTs and the meridional asymmetry of global tropical SSTs, respectively. The tropical eastern Pacific SSTs (southern tropical SSTs) dominate the tropical SST-NTAB/STAB relationship on the interannual (decadal- to multidecadal) scale, whereas the NTAB is a passive factor in this relationship. Moreover, a cross-hemispheric relationship between the NTAB/STAB and the HC upper-level meridional winds is revealed.

  14. AVP-stimulated nucleotide secretion in perfused mouse medullary thick ascending limb and cortical collecting duct

    DEFF Research Database (Denmark)

    Odgaard, Elvin V. P.; Prætorius, Helle; Leipziger, Jens Georg

    2009-01-01

    is stimulated remain elusive. Here, we investigate the phenomenon of nucleotide secretion in intact, perfused mouse medullary thick ascending limb (mTAL) and cortical collecting duct (CCD). The nucleotide secretion was monitored by a biosensor adapted to register nucleotides in the tubular outflow...

  15. In Vivo Patellar Tracking and Patellofemoral Cartilage Contacts during Dynamic Stair Ascending

    Science.gov (United States)

    Suzuki, Takashi; Hosseini, Ali; Li, Jing-Sheng; Gill, Thomas J; Li, Guoan

    2012-01-01

    The knowledge of normal patellar tracking is essential for understanding of the knee joint function and for diagnosis of patellar instabilities. This paper investigated the patellar tracking and patellofemoral joint contact locations during a stair ascending activity using a validated dual-fluoroscopic imaging system. The results showed that the patellar flexion angle decreased from 41.9° to 7.5° with the knee extension during stair ascending. During first 80% of the activity, the patella shifted medially about 3.9 mm and then slightly shifted laterally during the last 20% of the ascending activity. Anterior translation of 13 mm of the patella was measured at the early 80% of the activity and then slightly moved posteriorly by about 2 mm at the last 20% of the activity. The path of the cartilage contact points was slightly lateral on the cartilage surfaces of patella and femur. On the patellar cartilage surface, the cartilage contact locations were about 2 mm laterally from heel strike to 60% of the stair ascending activity and moved laterally and reached 5.3 mm at full extension. However, the cartilage contact locations were relatively constant on the femoral cartilage surface (~5 mm lateral). The patellar tracking pattern was consistent with the patellofemoral cartilage contact location pattern. These data could provide baseline knowledge for understanding of normal physiology of the patellofemoral joint and can be used as a reference for clinical evaluation of patellofemoral disorder symptoms. PMID:22840488

  16. In vivo 3-dimensional Magnetic Resonance Wall Shear Stress Estimation in Ascending Aortic Dilatation

    Science.gov (United States)

    Bieging, Erik T.; Frydrychowicz, Alex; Wentland, Andrew; Landgraf, Benjamin R.; Johnson, Kevin M.; Wieben, Oliver; François, Christopher J.

    2011-01-01

    Purpose To estimate surface-based wall shear stress (WSS) and evaluate flow patterns in ascending aortic dilatation (AscAD) using a high-resolution, time-resolved, three-dimensional (3D), three-directional velocity encoded, radially undersampled phase contrast magnetic resonance sequence (4D PC-MRI). Materials and Methods 4D PC-MRI was performed in 11 patients with AscAD (46.3±22.0 years) and 10 healthy volunteers (32.9±13.4 years) after written informed consent and IRB-approval. Following manual vessel wall segmentation of the ascending aorta (MATLAB, The Mathworks, Natick, MA), a 3D surface was created using spline interpolation. Spatial WSS variation based on surface division in 12 segments and temporal variation were evaluated in AscAD and normal aortas. Visual analysis of flow patterns was performed based on streamlines and particle traces using EnSight (v9.0, CEI, Apex, NC). Results AscAD was associated with significantly increased diastolic WSS, decreased systolic to diastolic WSS ratio, and delayed onset of peak WSS (all P wall of the ascending aorta. Vortical flow with highest velocities along the anterior wall and increased helical flow during diastole were observed in AscAD compared to controls. Conclusion Changes in WSS in the ascending aorta of AscAD correspond to observed alterations in flow patterns compared to controls. PMID:21563242

  17. An Exploratory Study of the Ascendancy of Women to the Position of K-12 Superintendent

    Science.gov (United States)

    Hanson, Karen M.

    2011-01-01

    Despite earning over half of the doctoral degrees in education, women are underrepresented in the position of K-12 superintendent. In 2000, although 72% of all classroom teachers were female, only 14% of all superintendents in the United States were women. Research indicates that women experience barriers in their ascendancy to superintendent.…

  18. Inter-observer agreement for the evaluation of bone involvement on Whole Body Low Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM)

    International Nuclear Information System (INIS)

    Zacchino, M.; Minetti, V.; Dore, R.; Calliada, F.; Bonaffini, P.A.; Nasatti, A.; Sironi, S.; Corso, A.; Tinelli, C.

    2015-01-01

    We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. According to Cohen's criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers' experience. (orig.)

  19. Effect of time to infusion of autologous stem cells (24 vs. 48 h) after high-dose melphalan in patients with multiple myeloma.

    Science.gov (United States)

    Talamo, Giampaolo; Rakszawski, Kevin L; Rybka, Witold B; Dolloff, Nathan G; Malysz, Jozef; Berno, Tamara; Zangari, Maurizio

    2012-08-01

    High-dose melphalan (HD-Mel) is considered the current standard of care among the preparative regimens used in autologous peripheral blood stem cell transplantation (SCT) for multiple myeloma (MM), but optimal time and schedule of administration is not defined. We retrospectively analyzed outcomes and toxicities of HD-Mel administered on day -2 vs. day -1 before autologous stem cells infusion. A total of 138 consecutive MM patients treated at Penn State Hershey Cancer Institute between 2007 and 2010 were included in this study. No difference in time to hematopoietic recovery, common SCT-related toxicities, and clinical outcomes was seen between patients who received HD-Mel on day -2 (group A, n = 47), and those who received it on day -1 (group B, n = 91). Prompt and full hematopoietic recovery occurred even when stem cells were infused between 8 and 24 h after completion of chemotherapy. In the absence of prospective and randomized data, we conclude that a single I.V. infusion of HD-Mel on day -1 is a safe and effective practice, and the so-called 'day of rest' before the transplant appears not to be necessary. © 2012 John Wiley & Sons A/S.

  20. Inter-observer agreement for the evaluation of bone involvement on Whole Body Low Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Zacchino, M.; Minetti, V.; Dore, R.; Calliada, F. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Institute of Radiology, Pavia (Italy); Bonaffini, P.A.; Nasatti, A.; Sironi, S. [University of Milano Bicocca, San Gerardo Hospital, Department of Diagnostic Radiology, Monza (Italy); Corso, A. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Division of Hematology, Pavia (Italy); Tinelli, C. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Service of Biometry and Statistics, Pavia (Italy)

    2015-11-15

    We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. According to Cohen's criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers' experience. (orig.)

  1. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

    2016-11-01

    Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

  2. Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebo-controlled, parallel-group, multiple-dose study.

    Science.gov (United States)

    Boulton, Craig; Meiser, Karin; David, Olivier J; Schmouder, Robert

    2012-12-01

    Fingolimod, a first-in-class oral sphingosine 1-phosphate receptor (S1PR) modulator, is approved in many countries for relapsing-remitting multiple sclerosis, at a once-daily 0.5-mg dose. A reduction in peripheral lymphocyte count is an expected consequence of the fingolimod mechanism of S1PR modulation. The authors investigated if this pharmacodynamic effect impacts humoral and cellular immunogenicity. In this double-blind, parallel-group, 4-week study, 72 healthy volunteers were randomized to steady state, fingolimod 0.5 mg, 1.25 mg, or to placebo. The authors compared T-cell dependent and independent responses to the neoantigens, keyhole limpet hemocyanin (KLH), and pneumococcal polysaccharides vaccine (PPV-23), respectively, and additionally recall antigen response (tetanus toxoid [TT]) and delayed-type hypersensitivity (DTH) to KLH, TT, and Candida albicans. Fingolimod caused mild to moderate decreases in anti-KLH and anti-PPV-23 IgG and IgM levels versus placebo. Responder rates were identical between placebo and 0.5-mg groups for anti-KLH IgG (both > 90%) and comparable for anti-PPV-23 IgG (55% and 41%, respectively). Fingolimod did not affect anti-TT immunogenicity, and DTH response did not differ between placebo and fingolimod 0.5-mg groups. Expectedly, lymphocyte count reduced substantially in the fingolimod groups versus placebo but reversed by study end. Fingolimod was well tolerated, and the observed safety profile was consistent with previous reports.

  3. Seawifs Technical Report Series. Volume 2: Analysis of Orbit Selection for Seawifs: Ascending Versus Descending Node

    Science.gov (United States)

    Hooker, Stanford B. (Editor); Firestone, Elaine R. (Editor); Gregg, Watson W.

    1992-01-01

    Due to range safety considerations, the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) ocean color instrument may be required to be launched into a near-noon descending node, as opposed to the ascending node used by the predecessor sensor, the Coastal Zone Color Scanner (CZCS). The relative importance of ascending versus descending near-noon orbits was assessed here to determine if descending node will meet the scientific requirements of SeaWiFS. Analyses focused on ground coverage, local times of coverage, solar and viewing geometries (zenith and azimuth angles), and sun glint. Differences were found in the areas covered by individual orbits, but were not important when taken over a 16 day repeat time. Local time of coverage was also different: for ascending node orbits the Northern Hemisphere was observed in the morning and the Southern Hemisphere in the afternoon, while for descending node orbits the Northern Hemisphere was observed in the afternoon and the Southern in the morning. There were substantial differences in solar azimuth and spacecraft azimuth angles both at equinox and at the Northern Hemisphere summer solstice. Negligible differences in solar and spacecraft zenith angles, relative azimuth angles, and sun glint were obtained at the equinox. However, large differences were found in solar zenith angles, relative azimuths, and sun glint for the solstice. These differences appeared to compensate across the scan, however, an increase in sun glint in descending node over that in ascending node on the western part of the scan was compensated by a decrease on the eastern part of the scan. Thus, no advantage or disadvantage could be conferred upon either ascending node or descending node for noon orbits. Analyses were also performed for ascending and descending node orbits that deviated from a noon equator crossing time. For ascending node, afternoon orbits produced the lowest mean solar zenith angles in the Northern Hemisphere, and morning orbits produced

  4. The road less traveled: transarterial embolization of dural arteriovenous fistulas via the ascending pharyngeal artery.

    Science.gov (United States)

    Gross, Bradley A; Albuquerque, Felipe C; Moon, Karam; McDougall, Cameron G

    2017-01-01

    With the introduction of Onyx, transarterial embolization has become the most common endovascular approach to treating dural arteriovenous fistulas (dAVFs), often via the middle meningeal or occipital arteries. The ascending pharyngeal artery (APA) is a less frequently explored transarterial route because of its small caliber, potential anastomoses to the internal carotid and vertebral arteries, and vital supply to lower cranial nerves. To review our institutional experience and highlight the prevalence of APA supply to dAVFs and cases where it is a safe and effective pedicle for embolization. We reviewed our endovascular database (January 1, 1996 to March 1, 2016) for cranial dAVFs, evaluating dAVF characteristics and embolization results for those treated transarterially via the APA. Of 267 endovascularly treated dAVFs, 68 had APA supply (25%). Of these 68 dAVFs, embolization was carried out via this pedicle in 8 (12%) and 7 were ultimately occluded. No complications, including post-treatment cranial neuropathies or radiographic evidence of non-target embolization, were found. For 5 dAVFs, the APA was selected as the initial pedicle for embolization (two marginal sinus, one distal sigmoid, one cavernous, one tentorial). In four of these five cases, dAVF occlusion was achieved via the initial APA feeding artery pedicle. In one case, near-complete, stagnant occlusion was achieved after APA embolization; complete occlusion was achieved after adjunctive embolization of a single additional middle meningeal artery pedicle. In three other cases of complex transverse/sigmoid dAVFs, the APA was used after multiple attempts via middle meningeal and occipital artery pedicles. Occlusion was not achieved transarterially; two of these three dAVFs were ultimately occluded transvenously. In rare, select cases, the APA is an excellent route for transarterial embolization of cranial dAVFs. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  5. The multiplication constant of a microorganism in a colony is normally reduced by irradiation, but still remains as a characteristic constant: a new approach to determining irradiation pasteurization doses

    International Nuclear Information System (INIS)

    Yarman, T.; Kiyak, N.

    1991-01-01

    This work is based on a previous observation and on a related mathematical modeling regarding the ‘linear growth’ of a colony of microorganisms under given conditions. We had previously shown that the growth rate of the colony is merely proportional to the ‘individual exponential multiplication constant’, β, of the microorganisms. Tiny colonies of penicillium are subjected to different doses of irradiation. The subsequent observation of the colonies' growth rate beautifully furnishes a measure of how the multiplication constant, β, of the microorganism is affected by irradiation. The plot of β with respect to the irradiation dose, shows a linear interdependence between the two quantities. The extrapolation of this plot easily yields the radiation pasteurization dose of the microorganisms in hand

  6. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shefner, Jeremy M; Watson, Mary Lou; Meng, Lisa; Wolff, Andrew A

    2013-12-01

    Abstract Tirasemtiv is a fast skeletal muscle activator that increases the sensitivity of the sarcomere to calcium, increasing the efficiency of muscle contraction when the muscle is stimulated at submaximal contraction frequencies. A previous study showed single doses of tirasemtiv to be well tolerated and associated with potentially important improvements in a variety of functional outcomes. This study determined safety of tirasemtiv when given at doses up to 500 mg daily for three weeks. Tirasemtiv was given as a single daily dose up to 375 mg for two weeks, with and without concomitant riluzole. In a separate cohort, an ascending dose protocol evaluated a total dose of 500 mg daily given in two divided doses. Safety and tolerability were assessed, as well as measures of function, muscle strength and endurance. Results showed that tirasemtiv was well tolerated, with dizziness the most common adverse event. Tirasemtiv approximately doubled the serum concentration of riluzole. Trends were noted for improvement in ALSFRS-R, Maximum Minute Ventilation, and Nasal Inspiratory Pressure. In conclusion, tirasemtiv is well tolerated and can be given safely with a reduced dose of riluzole. Positive trends in multiple exploratory outcome measures support the further study of this agent in ALS.

  7. The imaging assessment and specific endograft design for the endovascular repair of ascending aortic dissection

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-07-01

    Full Text Available Yepeng Zhang,1 Hanfei Tang,1 JianPing Zhou,2 Zhao Liu,1 Changjian Liu,1 Tong Qiao,1 Min Zhou1 1Department of Vascular Surgery, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 2Department of General Surgery, Yixin People’s Hospital, Yixin, People’s Republic of China Background: Endovascular option has been proposed for a very limited and selected number of Stanford type A aortic dissection (TAAD patients. We have performed a computed tomography (CT-based TAAD study to explore appropriate endograft configurations for the ascending aortic pathology. Methods: TAAD patients treated with optimal CT scans were retrospectively reviewed, and their entry tears (ETs were identified using three-dimensional and multiplanar reconstructions in an EndoSize workstation. After generating a centerline of flow, measurements, including numerous morphologic characteristics of anatomy, were evaluated and a selected subset of patients were determined to be suitable for endovascular treatments. Proximal diameter and distal diameter of endograft were selected based on diameters measured at the ET level and at the innominate artery (IA level, with 10% oversizing with respect to the true lumen, but not exceeding the original aortic diameter. The length of the endograft was determined by the distance from the sinotubular junction to IA. Results: This study covered 126 TAAD patients with primary ET in ascending aorta, among which, according to the assumed criteria, 48 (38.1% patients were deemed to be suitable for endovascular treatment. The diameters of ascending aorta from the sinotubular junction to the IA level presented a downward trend, and the proximal diameters differed significantly from distal diameters of the endograft for TAAD (39.9 versus 36.2 mm, P<0.01, implying that the conical endograft might be compatible with the ascending pathology. In the ascending aorta, lengths of the endograft should be 50, 60, 70, 80, and 90 mm in five

  8. Ovarian response to 150 µg corifollitropin alfa in a GnRH-antagonist multiple-dose protocol: a prospective cohort study.

    Science.gov (United States)

    Lerman, Tamara; Depenbusch, Marion; Schultze-Mosgau, Askan; von Otte, Soeren; Scheinhardt, Markus; Koenig, Inke; Kamischke, Axel; Macek, Milan; Schwennicke, Arne; Segerer, Sabine; Griesinger, Georg

    2017-05-01

    The incidence of low (18 oocytes) ovarian response to 150 µg corifollitropin alfa in relation to anti-Müllerian hormone (AMH) and other biomarkers was studied in a multi-centre (n = 5), multi-national, prospective, investigator-initiated, observational cohort study. Infertile women (n = 212), body weight >60 kg, underwent controlled ovarian stimulation in a gonadotrophin-releasing hormone-antagonist multiple-dose protocol. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle day 2 or 3 of a spontaneous menstruation before the administration of 150 µg corifollitropin alfa. Serum AMH showed the best correlation with the number of oocytes obtained among all predictor variables. In receiver-operating characteristic analysis, AMH at a threshold of 0.91 ng/ml showed a sensitivity of 82.4%, specificity of 82.4%, positive predictive value 52.9%and negative predictive value 95.1% for predicting low response (area under the curve [AUC], 95% CI; P-value: 0.853, 0.769-0.936; <0.0001). For predicting high response, the optimal threshold for AMH was 2.58 ng/ml, relating to a sensitivity of 80.0%, specificity 82.1%, positive predictive value 42.5% and negative predictive value 96.1% (AUC, 95% CI; P-value: 0.871, 0.787-0.955; <0.0001). In conclusion, patients with serum AMH concentrations between approximately 0.9 and 2.6 ng/ml were unlikely to show extremes of response. Copyright © 2017. Published by Elsevier Ltd.

  9. Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods

    International Nuclear Information System (INIS)

    Correia, M.J.; Eden, A.R.; Westlund, K.N.; Coulter, J.D.

    1982-01-01

    A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, the authors observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought. (Auth.)

  10. Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods

    Energy Technology Data Exchange (ETDEWEB)

    Correia, M.J.; Eden, A.R.; Westlund, K.N.; Coulter, J.D. (Texas Univ., Galveston (USA). Medical Branch)

    1982-02-25

    A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, the authors observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought.

  11. Viral infection of the pregnant cervix predisposes to ascending bacterial infection

    Science.gov (United States)

    Racicot, Karen; Cardenas, Ingrid; Wünsche, Vera; Aldo, Paulomi; Guller, Seth; Means, Robert; Romero, Roberto; Mor, Gil

    2014-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract (FRT) are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines and anti-microbial peptides (AMPs). If this barrier is compromised, bacteria may enter the uterine cavity leading to preterm birth. Using a mouse model, we demonstrate, for the first time, that viral infection of the cervix, during pregnancy, reduces the capacity of the FRT to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and AMP expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment. PMID:23752614

  12. Delayed Presentation of a Giant Ascending Aortic Aneurysm following Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Tugrul Göncü

    2009-01-01

    Full Text Available Giant ascending aortic aneurysm formation following aortic valve replacement is rare. A 28-year-old man who underwent aortic valve replacement with a prosthetic valve for aortic regurgitation secondary to congenital bicuspid aortic valve about 10 years ago was diagnosed with a giant ascending aortic aneurysm about 16 cm in diameter in follow-up. The aneurysm was resected leaving the functional old mechanical prosthesis in place and implanted a 34-mm Hemashield woven graft, associated with the left and right coronary artery button implantation. Histological findings of the aortic aneurysm wall showed cystic medial necrosis. The postoperative course was uneventful and postoperative examination demonstrated good surgical results.

  13. Phase transformations in an ascending adiabatic mixed-phase cloud volume

    Science.gov (United States)

    Pinsky, M.; Khain, A.; Korolev, A.

    2015-04-01

    Regimes of liquid-ice coexistence that may form in an adiabatic parcel ascending at constant velocity at freezing temperatures are investigated. Four zones with different microphysical structures succeeding one another along the vertical direction have been established. On the basis of a novel balance equation, analytical expressions are derived to determine the conditions specific for each of these zones. In particular, the necessary and sufficient conditions for formation of liquid water phase within an ascending parcel containing only ice particles are determined. The results are compared to findings reported in earlier studies. The role of the Wegener-Bergeron-Findeisen mechanism in the phase transformation is analyzed. The dependence of the phase relaxation time on height in the four zones is investigated on the basis of a novel analytical expression. The results obtained in the study can be instrumental for analysis and interpretation of observed mixed-phase clouds.

  14. Fibrinolytic activity is associated with presence of cystic media degeneration in aneurysms of the ascending aorta

    OpenAIRE

    Borges , Luciano F; Gomez , Delphine; Quintana , Mercedes; Leclercq , Anne; Touat , Ziad; Jondeau , Guillaume; Meilhac , Olivier; Jandrot-Perrus , Martine; Gutierrez , Paulo Sampaio; Freymuller , Edna; Vranckx , Roger; Michel , Jean-Baptiste

    2010-01-01

    Abstract Aims Thoracic Ascending Aortic Aneurysms (TAA) are characterized by elastic fibre breakdown and cystic medial degeneration within the aortic media, associated with progressive SMC rarefaction. The TGF-?/Smad2 signaling pathway is involved in this process. Since pericellular fibrinolytic system activation is able to degrade adhesive proteins, activate MMPs, induce SMC disappearance and increase the bio-availability of TGF-?, we explored the plasminergic system in TAA. ...

  15. Ascending aortic aneurysm and diaphragmatic hernia in a case of Marfan syndrome.

    Science.gov (United States)

    Kothari, Jignesh; Hinduja, Manish; Baria, Kinnaresh; Pandya, Himani

    2017-06-01

    Marfan syndrome commonly affects the skeletal, ocular, and cardiovascular systems. Involvement of the gastrointestinal system is known but uncommon. Intervention depends upon the system involved and the severity of symptoms. Special awareness is required for the diagnosis and management of gastrointestinal involvement in these patients. We report a rare case of simultaneous surgical repair of an ascending aortic aneurysm and a type IV hiatal hernia in a 35-year-old man with Marfan syndrome.

  16. Anatomy of the bovine ascending aorta and brachiocephalic artery found unfavorable for total artificial heart implant.

    Science.gov (United States)

    Karimov, Jamshid H; Sunagawa, Gengo; Such, Kimberly A; Sale, Shiva; Golding, Leonard A R; Moazami, Nader; Fukamachi, Kiyotaka

    2015-12-01

    The biocompatibility assessment of the Cleveland Clinic continuous-flow total artificial heart is an important part of the device developmental program. Surgical and postoperative management are key factors in achieving optimal outcomes. However, the presence of vascular anatomical abnormalities in experimental animal models is often unpredictable and may worsen the expected outcomes. We report a technical impediment encountered during total artificial heart implantation complicated by unfavorable bovine anatomy of the ascending aorta and brachiocephalic arterial trunk.

  17. The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

    Science.gov (United States)

    Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

    2015-02-01

    Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

  18. Arima ascendant

    CERN Multimedia

    1999-01-01

    Editorial which agrees with the decision of Japan's prime minister Keizo Obuchi to retain Akito Arima as minister of education and also appoint him as head of the Science and Technology Agency (5 paragraphs).

  19. Porous Ascend

    DEFF Research Database (Denmark)

    Riiber, Jacob; Tamke, Martin; Ramsgaard Thomsen, Mette

    2012-01-01

    of folded elements, based on the concept of applying recursion to the geometry of the non-periodic Penrose tiling. Within this process the project explores questions regarding the making of bespoke digital design tools, digital production, material behaviour and assemblage strategies. The project points...... towards a novel approach to working with, and reproducing, complexity within collections of architectural components. With no predefined coordinization mapping the ever changing fractal pattern, building proceeds by a locally defined identification and pairing of elements. In this way the project...... demonstrates that we can build without reference to a global position, by solely referencing by means of relations between neighbouring parts. Assembly itself becomes algorithmic. This suggests a more locally adaptive and reactive organization of elements, offering both better interfacing capabilities...

  20. Aorto-right atrial fistula after ascending aortic replacement or aortic value replacement

    International Nuclear Information System (INIS)

    Zhi Aihua; Dai Ruping; Jiang Shiliang; Lu Bin

    2012-01-01

    Objective: To evaluate the CT features of aorto-right atrial fistula after aortic valve replacement (AVR) or ascending aortic replacement. Methods: Eighty-seven patients with aortic-right atrial fistula underwent CT after operation. The CT features were retrospectively analyzed. Fistula was measured according to maximum width of the shunt. Results: Aorto-right atrial fistula was detected in 87 patients after aortic valve replacement or ascending aortic replacement by CT scan. Among them, 25 patients were diagnosed as mild aorto-right atrial fistula, 47 patients as moderate, and 15 patients as severe. Thirty-seven patients underwent follow-up CT.Among them, 10 patients with mild to moderate aorto-right atrial fistula were considered to have complete regression, 8 patients with mild aorto-right atrial fistula considered to have incomplete regression, 14 patients with mild to moderate aorto-right atrial fistula considered to have stable condition, and 5 patients with moderate aorto-right atrial fistula considered to have progression at the 3-month follow-up. Conclusion: CT is a useful tool for defining aorto-right atrial fistula after AVR or ascending aortic replacement and for evaluating it in follow-up. (authors)

  1. What if the Diatoms of the Deep Chlorophyll Maximum Can Ascend?

    Science.gov (United States)

    Villareal, T. A.

    2016-02-01

    Buoyancy regulation is an integral part of diatom ecology via its role in sinking rates and is fundamental to understanding their distribution and abundance. Numerous studies have documented the effects of size and nutrition on sinking rates. Many pelagic diatoms have low intrinsic sinking rates when healthy and nutrient-replete (deep chlorophyll maximum. The potential for ascending behavior adds an additional layer of complexity by allowing both active depth regulation similar to that observed in flagellated taxa and upward transport by some fraction of deep euphotic zone diatom blooms supported by nutrient injection. In this talk, I review the data documenting positive buoyancy in small diatoms, offer direct visual evidence of ascending behavior in common diatoms typical of both oceanic and coastal zones, and note the characteristics of sinking rate distributions within a single species. Buoyancy control leads to bidirectional movement at similar rates across a wide size spectrum of diatoms although the frequency of ascending behavior may be only a small portion of the individual species' abundance. While much remains to be learned, the paradigm of unidirectional downward movement by diatoms is both inaccurate and an oversimplification.

  2. Surgical treatment of ascending aortic complications in Marfan syndrome: early and long-term outcomes.

    Science.gov (United States)

    Favaloro, Roberto R; Casabé, J Horacio; Segura, Mónica; Abud, José; Casas, Jorge; López, Claudio; Dulbecco, Eduardo; Raffaelli, Héctor

    2008-08-01

    Findings in 54 patients (mean age 39 years, range 18-66 years, 25% female) were analyzed. Of these patients, 21 had dissection of the ascending aorta (15 acute and six chronic) and 33 had aneurysm of the ascending aorta. Surgery was classified as emergency surgery in three cases, as urgent in 15, and as scheduled surgery in 36. The Bentall-De Bono procedure was performed in 39 patients, aortic valve reimplantation was carried out in nine, Cabrol's operation was performed in three, and a homograft was used in three. The mean diameter of the ascending aorta was 66.6 mm. Overall, in-hospital mortality was 3.7% (33.3% for emergency surgery vs. 2.8% for scheduled surgery; P< .001). During the mean follow-up period of 4 years (range, 2 months-14 years), seven patients died, including four who died due to type-B aortic dissection. The actuarial survival rate at 2, 5 and 10 years was 94%, 83% and 75%, respectively, with 88%, 67% and 43% of patients, respectively, not requiring reoperation. Elective aortic root replacement was associated with a low risk and a good survival rate.

  3. Acute intramural hematoma of ascending aorta. CT findings and clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Toshio; Sakuyama, Keiko; Hiekata, Tomizou; Yamanaka, Ikuo [St. Marianna Univ., Kanagawa (Japan). Yokohama Seibu Hospital; Kuroki, Kazunori; Ohyama, Yukio; Ishikawa, Tohru; Kawada, Tadanori; Akashi, Katsuya

    1997-12-01

    The purpose of this study was to describe the CT findings and clinical outcomes of nineteen patients with acute intramural hematoma (IMH) of the ascending aorta. Six patients underwent surgery on the emergency basis (3 patients) due to cardiac tamponade (n=2) and dilated aorta (n=1), and on the elective basis (3 patients) due to patent and enlarging false lumen. Among the 13 patients with medical management, four patients died from complications of IMH during the follow-up period (2 days-2.5 years). Transition to aortic dissection or enlargement of an intimal tear was noted in 5 patients (31%) in 1 to 6 weeks after onset. Three patients died of causes not related to IMH. Six patients had been alive 2 to 9 years after onset. Retrospective review revealed 10 patients (53%) as possible surgical candidates, and the other 9 patients as medically treated patients in the long-term follow-up. The surgical group showed cardiac tamponade or shock in 6 patients on admission and had pericardial effusion in all the patients on the initial CT scan. In the patients with acute IMH of the ascending aorta, surgery should be considered for severe clinical symptoms, pericardial effusion and large size of the ascending aorta (more than 4 cm) on CT scan, and for converting to a typical type A aortic dissection. CT scan had a major role in making an early diagnosis, in depicting a dangerous sign, and in monitoring its progression or resolution of IMH. (author)

  4. [A Case Where Rectal Cancer Ileus Caused Perforation in the Ascending Colon].

    Science.gov (United States)

    Machida, Tomohiko; Kobayashi, Masayoshi; Sakai, Kazuki; Hiraoka, Kunihiko; Ichihara, Takao

    2016-11-01

    The patient was a 65-year-old man. He had not defecated for a week in early December 2015, and had noticed abdominal pain and abdominaldistension from 4 days prior. The pain and distension worsened, and the patient was rush transported to our hospital. Via abdominal CT we found free air in the upper abdomen, expansion of the small and large intestines, and notably, significant intestinal tract expansion and a gas reservoir in the ascending colon. We found significant narrowing as well as hypertrophy along the entire circumference of the rectum and suspected gastrointestinal perforation due to rectal cancer ileus. Inflammation findings were abnormally high and we performed emergency surgery. We found a laceration on the ascending colon, which had expanded markedly. We elevated that location and installed a colostomy. Following surgery the patient developed mild SSI and ileus, which were alleviated through conservative treatment. A month after the operation we performed a colonoscopy and found a tumor along the entire circumference of the rectum Rs. It was diagnosed as group V tub1-2 via biopsy. We performed surgery in late January 2016(colostomy closure, laparotomy rectal low anterior resection). We are reporting a rare case where rectal cancer ileus caused perforation in the ascending colon.

  5. Ascending and Descending in Virtual Reality: Simple and Safe System Using Passive Haptics.

    Science.gov (United States)

    Nagao, Ryohei; Matsumoto, Keigo; Narumi, Takuji; Tanikawa, Tomohiro; Hirose, Michitaka

    2018-04-01

    This paper presents a novel interactive system that provides users with virtual reality (VR) experiences, wherein users feel as if they are ascending/descending stairs through passive haptic feedback. The passive haptic stimuli are provided by small bumps under the feet of users; these stimuli are provided to represent the edges of the stairs in the virtual environment. The visual stimuli of the stairs and shoes, provided by head-mounted displays, evoke a visuo-haptic interaction that modifies a user's perception of the floor shape. Our system enables users to experience all types of stairs, such as half-turn and spiral stairs, in a VR setting. We conducted a preliminary user study and two experiments to evaluate the proposed technique. The preliminary user study investigated the effectiveness of the basic idea associated with the proposed technique for the case of a user ascending stairs. The results demonstrated that the passive haptic feedback produced by the small bumps enhanced the user's feeling of presence and sense of ascending. We subsequently performed an experiment to investigate an improved viewpoint manipulation method and the interaction of the manipulation and haptics for both the ascending and descending cases. The experimental results demonstrated that the participants had a feeling of presence and felt a steep stair gradient under the condition of haptic feedback and viewpoint manipulation based on the characteristics of actual stair walking data. However, these results also indicated that the proposed system may not be as effective in providing a sense of descending stairs without an optimization of the haptic stimuli. We then redesigned the shape of the small bumps, and evaluated the design in a second experiment. The results indicated that the best shape to present haptic stimuli is a right triangle cross section in both the ascending and descending cases. Although it is necessary to install small protrusions in the determined direction, by

  6. MO-FG-CAMPUS-TeP1-04: Pseudo-In-Vivo Dose Verification of a New Mono-Isocentric Technique for the Treatment of Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Pappas, E P; Makris, D; Lahanas, V; Papanikolaou, N; Watts, L; Kalaitzakis, G; Boursianis, T; Maris, T; Genitsarios, I; Pappas, E; Stathakis, S

    2016-01-01

    Purpose: To validate dose calculation and delivery accuracy of a recently introduced mono-isocentric technique for the treatment of multiple brain metastases in a realistic clinical case. Methods: Anonymized CT scans of a patient were used to model a hollow phantom that duplicates anatomy of the skull. A 3D printer was used to construct the phantom of a radiologically bone-equivalent material. The hollow phantom was subsequently filled with a polymer gel 3D dosimeter which also acted as a water-equivalent material. Irradiation plan consisted of 5 targets and was identical to the one delivered to the specific patient except for the prescription dose which was optimized to match the gel dose-response characteristics. Dose delivery was performed using a single setup isocenter dynamic conformal arcs technique. Gel dose read-out was carried out by a 1.5 T MRI scanner. All steps of the corresponding patient’s treatment protocol were strictly followed providing an end-to-end quality assurance test. Pseudo-in-vivo measured 3D dose distribution and calculated one were compared in terms of spatial agreement, dose profiles, 3D gamma indices (5%/2mm, 20% dose threshold), DVHs and DVH metrics. Results: MR-identified polymerized areas and calculated high dose regions were found to agree within 1.5 mm for all targets, taking into account all sources of spatial uncertainties involved (i.e., set-up errors, MR-related geometric distortions and registration inaccuracies). Good dosimetric agreement was observed in the vast majority of the examined profiles. 3D gamma index passing rate reached 91%. DVH and corresponding metrics comparison resulted in a satisfying agreement between measured and calculated datasets within targets and selected organs-at-risk. Conclusion: A novel, pseudo-in-vivo QA test was implemented to validate spatial and dosimetric accuracy in treatment of multiple metastases. End-to-end testing demonstrated that our gel dosimetry phantom is suited for such QA

  7. MO-FG-CAMPUS-TeP1-04: Pseudo-In-Vivo Dose Verification of a New Mono-Isocentric Technique for the Treatment of Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Pappas, E P; Makris, D; Lahanas, V [National and Kapodistrian University of Athens, Athens, Attiki (Greece); Papanikolaou, N; Watts, L [University of Texas HSC SA, San Antonio, TX (United States); Kalaitzakis, G; Boursianis, T; Maris, T [University of Crete, Heraklion, Crete (Greece); Genitsarios, I; Pappas, E [Technological Educational Institute Of Athens, Athens, Attiki (Greece); Stathakis, S [Cancer Therapy and Research Center, San Antonio, TX (United States)

    2016-06-15

    Purpose: To validate dose calculation and delivery accuracy of a recently introduced mono-isocentric technique for the treatment of multiple brain metastases in a realistic clinical case. Methods: Anonymized CT scans of a patient were used to model a hollow phantom that duplicates anatomy of the skull. A 3D printer was used to construct the phantom of a radiologically bone-equivalent material. The hollow phantom was subsequently filled with a polymer gel 3D dosimeter which also acted as a water-equivalent material. Irradiation plan consisted of 5 targets and was identical to the one delivered to the specific patient except for the prescription dose which was optimized to match the gel dose-response characteristics. Dose delivery was performed using a single setup isocenter dynamic conformal arcs technique. Gel dose read-out was carried out by a 1.5 T MRI scanner. All steps of the corresponding patient’s treatment protocol were strictly followed providing an end-to-end quality assurance test. Pseudo-in-vivo measured 3D dose distribution and calculated one were compared in terms of spatial agreement, dose profiles, 3D gamma indices (5%/2mm, 20% dose threshold), DVHs and DVH metrics. Results: MR-identified polymerized areas and calculated high dose regions were found to agree within 1.5 mm for all targets, taking into account all sources of spatial uncertainties involved (i.e., set-up errors, MR-related geometric distortions and registration inaccuracies). Good dosimetric agreement was observed in the vast majority of the examined profiles. 3D gamma index passing rate reached 91%. DVH and corresponding metrics comparison resulted in a satisfying agreement between measured and calculated datasets within targets and selected organs-at-risk. Conclusion: A novel, pseudo-in-vivo QA test was implemented to validate spatial and dosimetric accuracy in treatment of multiple metastases. End-to-end testing demonstrated that our gel dosimetry phantom is suited for such QA

  8. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    Science.gov (United States)

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

  9. Two-dimensional echocardiographic and RI angiographic features of aneurysm of the ascending aorta in patients with annuloaortic ectasia

    International Nuclear Information System (INIS)

    Nakamura, Kenji; Suzuki, Shin; Satomi, Gengi

    1981-01-01

    The purpose of this study was to compare the diagnostic value of two-dimensional echocardiography with that of other methods in the detection and localization of aneurysm involving the ascending aorta in patients with annuloaortic ectasia. Two-dimensional echocardiography, RI angiography, CT scan and aortography were performed in 19 patients (12 patients with Marfan's syndrome, 4 with aortitis syndrome and 3 with postoperative perivalvular aneurysm). Eight of 12 patients with Marfan's syndrome had dissection in the ascending aorta which was confirmed at surgery or autopsy. The following observations were obtained. 1) Dissection of the ascending aorta was clearly demonstrated on the two-dimensional echocardiogram in 7 patients by recording the intinal tear and flap, and in these cases the short axis two-dimensional echocardiogram of the ascending aorta was more useful in identifying the site and extent of dissection. 2) In patients with postoperative perivalvular aneurysms, RI angiography proved to be a more useful and sensitive technique in differentiating a leakage into the aneurysm from clots in the aneurysm. 3) CT scanning proved to be an insensitive technique to detect dissection of the ascending aneurysm and to differentiate a leakage from clots in the perivalvular aneurysm. From these observations, we concluded that two-dimensional echocardiography and RI angiography proved to be sensitive techniques in detecting dissection of the ascending aneurysm and evaluating a postoperative aneurysm in patients with annuloaortic ectasia. (author)

  10. Two-dimensional echocardiographic and RI angiographic features of aneurysm of the ascending aorta in patients with annuloaortic ectasia

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, K.; Suzuki, S.; Satomi, G. (Tokyo Women' s Medical Coll. (Japan). Heart Inst. and Hospital)

    1981-03-01

    The purpose of this study was to compare the diagnostic value of two-dimensional echocardiography with that of other methods in the detection and localization of aneurysm involving the ascending aorta in patients with annuloaortic ectasia. Two-dimensional echocardiography, RI angiography, CT scan and aortography were performed in 19 patients (12 patients with Marfan's syndrome, 4 with aortitis syndrome and 3 with postoperative perivalvular aneurysm). Eight of 12 patients with Marfan's syndrome had dissection in the ascending aorta which was confirmed at surgery or autopsy. The following observations were obtained. 1) Dissection of the ascending aorta was clearly demonstrated on the two-dimensional echocardiogram in 7 patients by recording the intinal tear and flap, and in these cases the short axis two-dimensional echocardiogram of the ascending aorta was more useful in identifying the site and extent of dissection. 2) In patients with postoperative perivalvular aneurysms, RI angiography proved to be a more useful and sensitive technique in differentiating a leakage into the aneurysm from clots in the aneurysm. 3) CT scanning proved to be an insensitive technique to detect dissection of the ascending aneurysm and to differentiate a leakage from clots in the perivalvular aneurysm. From these observations, we concluded that two-dimensional echocardiography and RI angiography proved to be sensitive techniques in detecting dissection of the ascending aneurysm and evaluating a postoperative aneurysm in patients with annuloaortic ectasia.

  11. Early infections in patients undergoing high-dose treatment with stem cell support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma

    DEFF Research Database (Denmark)

    Gang, A O; Arpi, M.; Gang, U.J.O.

    2010-01-01

    . The population included non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received prophylactic antibacterial treatment. Results: Pathogens were isolated from 44% of all patients. MM patients more frequently had multiple pathogens in blood cultures (38% versus 25%). Transplantation...

  12. Computer aided display of multiple soft tissue anatomical surfaces for simultaneous structural and area-dose appreciation in 3D-radiationtherapy planning. 115

    International Nuclear Information System (INIS)

    Moore, C.J.; Mott, D.J.; Wilkinson, J.M.

    1987-01-01

    For radiotherapy applications a 3D display that includes soft tissues is required but the presentation of all anatomical structures is often unnecessary and is potentially confusing. A tumour volume and a small number of critical organs, usually embedded within other soft tissue anatomy, are likely to be all that can be clearly displayed when presented in a 3D format. The inclusion of dose data (in the form of isodose lines or surfaces) adds to the complication of any 3D display. A solution to this problem is to incorporate the presentation of dose distribution into the technique used to provide the illusion of 3D. This illusion can be provided by either depth cueing or by the hypothetical illumination of spatially defined object surfaces. The dose distribution from irradiation fields or, in the case of brachytherapy from radioactive sources, can be regarded as a source of illumination for tumour and critical organs. The intensity of illumination at any point on a tissue surface represents the dose at that point. Such an approach also allows the variation of dose over a given surface (and by extension, over the corresponding volume) to be quantified using histogram techniques. This may be of value in analysing and comparing techniques in which vulnerable tissue surfaces are irradiated. The planning of intracavitary treatments for cervical cancer is one application which might benefit from the display approach described above. Here the variation of dose over the mucosal surfaces of the bladder and the rectum is of particular interest, since dose related morbidity has often been reported following these treatments. 7 refs.; 8 figs

  13. 153Sm-lexidronam for augmentation of chemotherapy-based myeloablative regimes in patients with multiple myeloma and other haematological conditions undergoing bone marrow transplantation: a phase I dose-escalation trial

    International Nuclear Information System (INIS)

    Macfarlane, D.J.; Durrant, S.; Gillett, E.A.; Bartlett, M.; Allison, R.; Hicks, R.; Prince, M.

    1999-01-01

    Full text: Total body irradiation (TBI) is a useful conditioning regimen for bone marrow transplantation (BMT), but has unacceptable toxicity in some patients. High doses of bone-seeking radiopharmaceuticals may offer a useful alternative to TBI in BMT patients with marrow-based tumours. Nine patients (5 multiple myeloma [MM], 2 leukaemia, 1 lymphoma, I myelodysplasia) were enrolled in a dose escalation protocol based upon retained skeletal activity. Infused doses have ranged between 18 and 32 GBq of 153 Sm-EDTMP in six patients treated. No adverse effects related to the infusion have been seen. Peripheral blood counts fell from day 7 post-treatment, persisting to the start of cytotoxic conditioning regimen at days 11-14 post-treatment. Five patients have engrafted, with one allogeneic transplant patient dying from acute rejection. Pre-treatment dosimetry was performed by gamma camera and whole-body probe counts. Post-therapy activities were estimated by serial dose meter readings and gamma camera images. The pre-treatment skeletal retention by gamma camera was 1.7-2.4 times the values based on probe data. Retained post-treatment skeletal activity predicted by dosimetry was significantly greater than that actually measured, confirmed in one case by urinary collection. This latter fact is most likely due to the nature of the interaction of 153 Sm-EDTMP with bone at high doses

  14. Characteristics of aortic valve dysfunction and ascending aorta dimensions according to bicuspid aortic valve morphology

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hong Ju [Konkuk University Medical Center, Konkuk University School of Medicine, Department of Cardiovascular Surgery, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Cardiovascular Surgery, Seoul (Korea, Republic of); Shin, Je Kyoun; Chee, Hyun Kun; Kim, Jun Suk [Konkuk University Medical Center, Konkuk University School of Medicine, Department of Cardiovascular Surgery, Seoul (Korea, Republic of); Ko, Sung Min [Konkuk University Medical Center, Konkuk University School of Medicine, Department of Radiology, Seoul (Korea, Republic of)

    2015-07-15

    To characterize aortic valve dysfunction and ascending aorta dimensions according to bicuspid aortic valve (BAV) morphology using computed tomography (CT) and surgical findings. We retrospectively enrolled 209 patients with BAVs who underwent transthoracic echocardiography (TTE) and CT. BAVs were classified as anterior-posterior (BAV-AP) or lateral (BAV-LA) orientation of the cusps and divided according to the presence (raphe+) or absence (raphe-) of a raphe. Ascending aortic dimensions were measured by CT at four levels. BAV-AP was present in 129 patients (61.7 %) and raphe+ in 120 (57.4 %). Sixty-nine patients (33.0 %) had aortic regurgitation (AR), 70 (33.5 %) had aortic stenosis (AS), and 58 (27.8 %) had combined AS and AR. AR was more common in patients with BAV-AP and raphe+; AS was more common with BAV-LA and raphe-.Annulus/body surface area and tubular portion/body surface area diameters in patients with BAV-AP (17.1 ± 2.3 mm/m{sup 2} and 24.2 ± 5.3 mm/m{sup 2}, respectively) and raphe+ (17.3 ± 2.2 mm/m{sup 2} and 24.2 ± 5.5 mm/m{sup 2}, respectively) were significantly different from those with BAV-LA (15.8 ± 1.9 mm/m{sup 2} and 26.4 ± 5.5 mm/m{sup 2}, respectively) and raphe- (15.7 ± 1.9 mm/m{sup 2} and 26.2 ± 5.4 mm/m{sup 2}, respectively). The morphological characteristics of BAV might be associated with the type of valvular dysfunction, and degree and location of an ascending aorta dilatation. (orig.)

  15. Relationship of activity in ascending paths with phase encoding in the lumbar spinal cord

    Directory of Open Access Journals (Sweden)

    O. O. Shugurov

    2012-02-01

    Full Text Available We studied the relationship of discharges phase characteristics in ascending column of spinal cord (SC and specificity of activation of neurones, which generate negative components of evoked potentials of SC. The discharges was recorded from SC at a level of a presence of dorsal column (DC, spinocervical and dorsal spinocerebellar tract in upper lumbar and thoracic segments at a stimulation of a nerve or DC. It is shown, that the phase of the discharges depends on the quantity of synaptic delays in generating chain of such signals. Thus, the phase of a signal can carry the additional information on specificity of activation of the sensory elements in CNS.

  16. Activity of corrosion products in pool type reactors with ascending flow in the core

    International Nuclear Information System (INIS)

    Andrade e Silva, Graciete S. de; Queiroz Bogado Leite, Sergio de

    1995-01-01

    A model for the activity of corrosion products in the water of a pool type reactor with ascending flow is presented. The problem is described by a set of coupled differential equations relating the radioisotope concentrations in the core and pool circuits and taking into account two types of radioactive sources: i) those from radioactive species formed in the fuel cladding, control elements, reflector, etc, and afterwards released to the primary stream by corrosion (named reactor sources) and ii) those formed from non radioactive isotopes entering the primary stream by corrosion of the circuit components and being activated when passing through the core (named circuit sources). (author). 6 refs, 3 figs, 4 tabs

  17. Long-term variations in the geomagnetic activity level Part II: Ascending phases of sunspot cycles

    Directory of Open Access Journals (Sweden)

    V. Mussino

    1994-08-01

    Full Text Available Monthly averages of the Helsinki Ak-values have been reduced to the equivalent aa-indices to extend the aa-data set back to 1844. A periodicity of about five cycles was found for the correlation coefficient (r between geomagnetic indices and sunspot numbers for the ascending phases of sunspot cycles 9 to 22, confirming previous findings based on a minor number of sunspot cycles. The result is useful to researchers in topics related to solar-terrestrial physics, particularly for the interpretation of long-term trends in geomagnetic activity during the past, and to forecast geomagnetic activity levels in the future.

  18. NADPH oxidase 4-derived superoxide mediates flow-stimulated NKCC2 activity in thick ascending limbs.

    Science.gov (United States)

    Saez, Fara; Hong, Nancy J; Garvin, Jeffrey L

    2018-05-01

    Luminal flow augments Na + reabsorption in the thick ascending limb more than can be explained by increased ion delivery. This segment reabsorbs 30% of the filtered load of Na + , playing a key role in its homeostasis. Whether flow elevations enhance Na + -K + -2Cl - cotransporter (NKCC2) activity and the second messenger involved are unknown. We hypothesized that raising luminal flow augments NKCC2 activity by enhancing superoxide ([Formula: see text]) production by NADPH oxidase 4 (NOX4). NKCC2 activity was measured in thick ascending limbs perfused at either 5 or 20 nl/min with and without inhibitors of [Formula: see text] production. Raising luminal flow from 5 to 20 nl/min enhanced NKCC2 activity from 4.8 ± 0.9 to 6.3 ± 1.2 arbitrary fluorescent units (AFU)/s. Maintaining flow at 5 nl/min did not alter NKCC2 activity. The superoxide dismutase mimetic manganese (III) tetrakis (4-benzoic acid) porphyrin chloride blunted NKCC2 activity from 3.5 ± 0.4 to 2.5 ± 0.2 AFU/s when flow was 20 nl/min but not 5 nl/min. When flow was 20 nl/min, NKCC2 activity showed no change with time. The selective NOX1/4 inhibitor GKT-137831 blunted NKCC2 activity when thick ascending limbs were perfused at 20 nl/min from 7.2 ± 1.1 to 4.5 ± 0.8 AFU/s but not at 5 nl/min. The inhibitor also prevented luminal flow from elevating [Formula: see text] production. Allopurinol, a xanthine oxidase inhibitor, had no effect on NKCC2 activity when flow was 20 nl/min. Tetanus toxin prevents flow-induced stimulation of NKCC2 activity. We conclude that elevations in luminal flow enhance NaCl reabsorption in thick ascending limbs by stimulating NKCC2 via NOX4 activation and increased [Formula: see text]. NKCC2 activation is primarily the result of insertion of new transporters in the membrane.

  19. [A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

    Science.gov (United States)

    Takase, Koki; Murata, Kohei; Kagawa, Yoshinori; Nose, Yohei; Kawai, Kenji; Sakamoto, Takuya; Naito, Atsushi; Murakami, Kohei; Katsura, Yoshiteru; Omura, Yoshiaki; Takeno, Atsushi; Nakatsuka, Shinichi; Takeda, Yutaka; Kato, Takeshi; Tamura, Shigeyuki

    2018-01-01

    Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

  20. Speleogenesis along deep regional faults by ascending waters: case studies from Slovakia and Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Bella, P.; Bosák, Pavel

    2012-01-01

    Roč. 41, 2/3 (2012), s. 169-192 ISSN 0583-6050 R&D Projects: GA AV ČR IAA300130701 Institutional research plan: CEZ:AV0Z30130516 Keywords : ascending * speleogenesis * hypogene speleogenesis * Belianska Cave * Jasovská Cave * Plavecká Cave and Shaft * Liskovská Cave * Zápolná Cave * Na Pomezi Cave System Subject RIV: DB - Geology ; Mineralogy Impact factor: 0.542, year: 2012 http://ojs.zrc-sazu.si/carsologica/article/view/556/553

  1. Kinematic characteristics of anterior cruciate ligament deficient knees with concomitant meniscus deficiency during ascending stairs.

    Science.gov (United States)

    Zhang, Yu; Huang, Wenhan; Ma, Limin; Lin, Zefeng; Huang, Huayang; Xia, Hong

    2017-02-01

    It is commonly believed that a torn ACL or a damaged meniscus may be associated with altered knee joint movements. The purpose of this study was to measure the tibiofemoral kinematics of ACL deficiency with concomitant meniscus deficiency. Unilateral knees of 28 ACL deficient participants were studied while ascending stairs. Among these patients, 6 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), 8 had combined ACL and lateral meniscus injuries (group III) and 6 had combined ACL and medial-lateral meniscus injuries (group IV). Both knees were then scanned during a stair climb activity using single fluoroscopic image system. Knee kinematics were measured at 0°, 5°, 10°, 15°, 30° and 60° of flexion during ascending stairs. At 0°, 15° and 30° flexion of the knee, the tibia rotated externally by 13.9 ± 6.1°,13.8 ± 9.5° and 15.9 ± 9.8° in Group I. Group II and III exhibited decreased external rotation from 60° to full extension. Statistical differences were found in 0°, 15°and 30° of flexion for the 2 groups compared with Group I. In general, the tibia showed anterior translation with respect to the femur during ascending stairs. It was further determined that Group III had larger anterior translation compared with Group IV at 0° and 5° of flexion (-6.9 ± 1.7 mm vs. 6.2 ± 11.3 mm, P = 0.041; -9.0 ± 1.8 mm vs. 8.1 ± 13.4 mm, P = 0.044). During ascending stairs the ACL deficient knee with different deficiencies in the meniscus will show significantly different kinematics compared with that of uninjured contralateral knee. Considering the varying effect of meniscus injuries on knee joint kinematics, future studies should concentrate on specific treatment of patients with combined ACL and meniscus injuries to protect the joint from abnormal kinematics and subsequent postoperative degeneration.

  2. Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammer, Daniel; Erichsen, Lars

    2016-01-01

    : Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results...... increased with body weight in accordance with an allometrically scaled power exponent of 0.75 and 1, respectively. Endogenous FSH levels were lower in individuals with higher progesterone levels at baseline and were further suppressed over time with increasing inhibin B levels. Conclusions......: This characterisation of FE 999049 population pharmacokinetics after repeated dosing is in line with previous findings after single-dose administration. The results provide a basis for study design and data evaluation in the future development of recombinant FSH products, and show it can be of importance to account...

  3. Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women.

    Science.gov (United States)

    Hughes, T E; Kim, D D; Marjason, J; Proietto, J; Whitehead, J P; Vath, J E

    2013-09-01

    Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks. Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9). The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was -3.8 kg (95% CI -5.1, -0.9; N = 8) versus -0.6 kg with placebo (-4.5, -0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in β-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged. Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin. Copyright © 2013 The Obesity Society.

  4. Effect of reducing abdominal compression during prone CT colonography on ascending colonic rotation during supine-to-prone positional change

    International Nuclear Information System (INIS)

    Jang, Jong eon; Park, Seong Ho; Lee, Jong Seok; Kim, Hyun Jin; KIm, Ah Young; Ha, Hyun Kwon

    2016-01-01

    To determine the effect of reduced abdominal compression in prone position on ascending colonic movement during supine-to-prone positional change during CT colonography (CTC). Eighteen consecutive patients who had undergone prone CTC scanning with cushion blocks placed under the chest and hip/thigh to reduce abdominal compression and had confirmed sessile polyps ≥ 6 mm in the well-distended, straight, mid-ascending colon, were included. Radial location along the ascending colonic luminal circumference (°) was measured for 24 polyps and 54 colonic teniae on supine and prone CTC images. The supine-to-prone change ranging between -180° and +180° (- and + for internal and external colonic rotations, respectively), was determined. In addition, possible causes of any ascending colonic rotations were explored. Abdominal compression during prone CTC scanning completely disappeared with the use of cushion blocks in 17 of 18 patients. However, some degrees of ascending colonic rotation were still observed, with the radial location changes of -22° to 61° (median, 13.9°) for the polyps and similar degrees for teniae. Fifty-four percent and 56% of polyps and teniae, respectively, showed changes > 10°. The radial location change of the polyps was significantly associated with the degree of anterior shift of the small bowel and mesentery (r = 0.722, p < 0.001) and the degree of posterior displacement of the ascending colon (r = 0.566, p = 0.004) during supine-to-prone positional change. Ascending colonic rotation upon supine-to-prone positional change during CTC, mostly in the form of external rotation, is not eliminated by removing abdominal compression in prone position

  5. Dosing related effects of zoledronic acid on bone markers and creatinine clearance in patients with multiple myeloma and metastatic breast cancer

    DEFF Research Database (Denmark)

    Søe, Kent; Delaissé, Jean-Marie; Jakobsen, Erik H

    2014-01-01

    phase II clinical trial we investigated the effect of Zol treatment on the serum levels of the bone markers collagen type 1 cross-linked C-telopeptide (CTX) and bone specific alkaline phosphatase (bALP) as well as on creatinine clearance (kidney function) in response to dosing and duration of treatment...

  6. The role of oxygen-increased respirator in humans ascending to high altitude

    Directory of Open Access Journals (Sweden)

    Shen Guanghao

    2012-08-01

    Full Text Available Abstract Background Acute mountain sickness (AMS is common for people who live in low altitude areas ascending to the high altitude. Many instruments have been developed to treat mild cases of AMS. However, long-lasting and portable anti-hypoxia equipment for individual is not yet available. Methods Oxygen-increased respirator (OIR has been designed to reduce the risk of acute mountain sickness in acute exposure to low air pressure. It can increase the density of oxygen by increasing total atmospheric pressure in a mask. Male subjects were screened, and eighty-eight were qualified to perform the experiments. The subjects were divided into 5 groups and were involved in some of the tests at 4 different altitudes (Group 1, 2: 3700 m; Group 3,4,5: 4000 m, 4700 m, 5380 m with and without OIR. These tests include heart rate, saturation of peripheral oxygen (SpO2, malondialdehyde (MDA, superoxide dismutase (SOD, blood lactate (BLA and PWC (physical work capacity -170. Results The results showed that higher SpO2, lower heart rate (except during exercise and better recovery of heart rate were observed from all the subjects ’with OIR’ compared with ’without OIR’ (P Conclusions We suggested that OIR may play a useful role in protecting people ascending to high altitude before acclimatization.

  7. Dilation of the ascending aorta in Turner syndrome - a prospective cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Pedersen Erik M

    2011-04-01

    Full Text Available Abstract Background The risk of aortic dissection is 100-fold increased in Turner syndrome (TS. Unfortunately, risk stratification is inadequate due to a lack of insight into the natural course of the syndrome-associated aortopathy. Therefore, this study aimed to prospectively assess aortic dimensions in TS. Methods Eighty adult TS patients were examined twice with a mean follow-up of 2.4 ± 0.4 years, and 67 healthy age and gender-matched controls were examined once. Aortic dimensions were measured at nine predefined positions using 3D, non-contrast and free-breathing cardiovascular magnetic resonance. Transthoracic echocardiography and 24-hour ambulatory blood pressure were also performed. Results At baseline, aortic diameters (body surface area indexed were larger at all positions in TS. Aortic dilation was more prevalent at all positions excluding the distal transverse aortic arch. Aortic diameter increased in the aortic sinus, at the sinotubular junction and in the mid-ascending aorta with growth rates of 0.1 - 0.4 mm/year. Aortic diameters at all other positions were unchanged. The bicuspid aortic valve conferred higher aortic sinus growth rates (p Conclusion A general aortopathy is present in TS with enlargement of the ascending aorta, which is accelerated in the presence of a bicuspid aortic valve.

  8. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  9. ASCENDING WAY INFECTION NEWBORNS AND THE FORMATION OF INTESTINAL MICROBIOCENOSIS OF THE NEWBORN

    Directory of Open Access Journals (Sweden)

    Kunovskaya L. M.

    2013-06-01

    Full Text Available The role and value of the bacterial factor in development pre-natal infection of newborns is studied. It is considered microflora of patrimonial ways of pregnant women, as basic pathogenesis factor of an ascending way infection of newborns. On an example of the spent bacteriological researches correlation communication between microflora of patrimonial ways, placenta and an ascending way infection of newborns is shown. At crops gastric swallowing at newborn children with pre-natal infection of newborns it is ascertained growth aerobic and аanaerobic microflora in the majority (87,7 % supervision in the form of microbes associations gramme-positive coccus Staphylococcus epidermidis and Staphylococcus aureus and Candida. The inclusion in the treatment of Saccharomyces boulardіi contributes to the restoration of intesti­nal microflora in 90 % of newborns. Found significant growth of the colonies of Bifidobacterium spp. (3.7-4,9 lg CFU/ml and Lactobacillus spp. (7.2 lg CFU/ml.

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

    Science.gov (United States)

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

    2009-06-01

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

  11. Evaluation of multiple scan average dose (MSAD) levels in computerized tomography in Minas Gerais state, Brazil; Avaliacao dos niveis de dose media em cortes multiplos (MSAD) em tomografia computadorizada no estado de Minas Gerais

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, Thessa C., E-mail: alonso@cdtn.br [Centro de Desenvolvimento de Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Vieira, Leandro de A.; Barbosa, Nayra V.; Oliveira, Jeyselaine R. de; Cesar, Adriana C.Z. [Secretaria de Vigilancia Sanitaria de Minas Gerais, Belo Horizonte, MG (Brazil); Silva, Teogenes A. da [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear. Programa de Ciencias e Tecnicas Nucleares

    2014-07-01

    Computed Tomography (CT) grows every year and is a diagnostic method that has revolutionized radiology with advances in procedures for obtaining image. However, the indiscriminate use of this method generates relatively high doses in patients. The diagnostic reference levels (DRLs) is a practical tool to promote the evaluation of existing protocols. The optimization and the periodic review of the protocols are important to balance the risk of radiation. The present study aims to conduct a survey of levels of MSAD of Minas Gerais following the procedures recommended by current Brazilian law. (author)

  12. Ascending control of arousal and motivation: role of nucleus incertus and its peptide neuromodulators in behavioural responses to stress.

    Science.gov (United States)

    Ma, S; Gundlach, A L

    2015-06-01

    Arousal is a process that involves the activation of ascending neural pathways originating in the rostral pons that project to the forebrain through the midbrain reticular formation to promote the activation of key cortical, thalamic, hypothalamic and limbic centres. Established modulators of arousal include the cholinergic, serotonergic, noradrenergic and dopaminergic networks originating in the pons and midbrain. Recent data indicate that a population of largely GABAergic projection neurones located in the nucleus incertus (NI) are also involved in arousal and motivational processes. The NI has prominent efferent connections with distinct hypothalamic, amygdalar and thalamic nuclei, in addition to dense projections to key brain regions associated with the generation and pacing of hippocampal activity. The NI receives strong inputs from the prefrontal cortex, lateral habenula and the interpeduncular and median raphe nuclei, suggesting it is highly integrated in circuits regulating higher cognitive behaviours (hippocampal theta rhythm) and emotion. Anatomical and functional studies have revealed that the NI is a rich source of multiple peptide neuromodulators, including relaxin-3, and may mediate extra-hypothalamic effects of the stress hormone corticotrophin-releasing factor, as well as other key modulators such as orexins and oxytocin. This review provides an overview of earlier studies and highlights more recent research that implicates this neural network in the integration of arousal and motivated behaviours and has begun to identify the associated mechanisms. Future research that should help to better clarify the connectivity and function of the NI in major experimental species and humans is also discussed. © 2015 British Society for Neuroendocrinology.

  13. Absorbed Dose Distributions in Small Copper Wire Insulation due to Multiple-Sided Irradiations by 0.4 MeV Electrons

    DEFF Research Database (Denmark)

    Miller, Arne; McLaughlin, W. L.; Pedersen, Walther Batsberg

    1979-01-01

    When scanned electron beams are used to crosslink polymeric insulation of wire and cable, an important goal is to achieve optimum uniformity of absorbed dose distributions. Accurate measurements of dose distributions in a plastic dosimeter simulating a typical insulating material (polyethylene......) surrounding a copper wire core show that equal irradiations from as few as four sides give approximately isotropy and satisfactorily uniform energy depositions around the wire circumference. Electron beams of 0.4 MeV maximum energy were used to irradiate wires having a copper core of 1.0 mm dia....... and insulation thicknesses between 0.4 and 0.8 mm. The plastic dosimeter simulating polyethylene insulations was a thin radiochromic polyvinyl butyral film wrapped several times around the copper wire, such that when unwrapped and analyzed optically on a scanning microspectrophotometer, high-resolution radial...

  14. A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma

    DEFF Research Database (Denmark)

    Søndergaard, Teis Esben; Pedersen, PT; Levin Andersen, Thomas

    2008-01-01

    Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease...... acid phosphatase, TRACP); (ii) bone resorption (collagen fragments CTX and NTX); (iii) bone formation (osteocalcin and aminoterminal propeptide of type I collagen PINP); (iv) cholesterol; (v) regulators of bone metabolism [osteoprotegerin (OPG) and Dickkopf-1 (DKK-1)] and (vi) disease activity...... (monoclonal proteins or free light chains in serum). TRACP activity in serum and levels of collagen fragments (NTX) in urine increased for all patients temporarily during the 7 days of treatment with HD-Sim indicating that osteoclasts may have been stimulated rather than inhibited. The other markers of bone...

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

    Science.gov (United States)

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

    2002-07-01

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

  16. Design and in vitro performance testing of multiple air classifier technology in a new disposable inhaler concept (Twincer (R)) for high powder doses

    NARCIS (Netherlands)

    de Boer, Anne H; Hagedoorn, Paul; Westerman, Elsbeth M; Le Brun, Paul P H; Heijerman, Harry G M; Frijlink, Henderik W

    2006-01-01

    Dry powder inhalation of antibiotics in cystic fibrosis (CF) therapy may be a valuable alternative for wet nebulisation, because it saves time and it improves lung deposition. In this study, it is shown that the use of multiple air classifier technology enables effective dispersion of large amounts

  17. Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

    Science.gov (United States)

    Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

    2016-03-01

    Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

  18. Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

    Science.gov (United States)

    Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

    2015-01-01

    Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

  19. A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor.

    Science.gov (United States)

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Sonnichsen, Daryl

    2012-07-01

    Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects. A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7. No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea. Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing.

  20. Modality-Based Organization of Ascending Somatosensory Axons in the Direct Dorsal Column Pathway

    Science.gov (United States)

    Niu, Jingwen; Ding, Long; Li, Jian J.; Kim, Hyukmin; Liu, Jiakun; Li, Haipeng; Moberly, Andrew; Badea, Tudor C.; Duncan, Ian D.; Son, Young-Jin; Scherer, Steven S.

    2013-01-01

    The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the “somatotopic map” model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial–lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough “somatotopic map” was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway. PMID:24198362

  1. Hybrid aortic repair with antegrade supra-aortic and renovisceral debranching from ascending aorta.

    Science.gov (United States)

    Del Castro-Madrazo, José Antonio; Rivas-Domínguez, Margarita; Fernández-Prendes, Carlota; Zanabili Al-Sibbai, Amer; Llaneza-Coto, José Manuel; Alonso-Pérez, Manuel

    2017-05-01

    Aortic dissection is a life threatening condition. Hybrid repair has been described for the treatment of complex aortic pathology such as thoracoabdominal aortic aneurysms (TAAA) and type A and B dissections, although open and total endovascular repair are also possible. Open surgery is still associated with substantial perioperative morbi-mortality rates, thus less invasive techniques such as endovascular repair and hybrid procedures can achieve good results in centers with experience. We present the case of a patient with a chronic type B dissection and TAAA degeneration that was treated in a single stage hybrid procedure with antegrade supra-aortic and renovisceral debranching from the ascending aorta and TEVAR. At three-year follow up, the patient is free of intervention-related complications.

  2. Mathemimetics II. Demonstratio Mirabilis of FLT by infinitely ascending cubical crystal growth

    Science.gov (United States)

    Trell, Erik

    2012-09-01

    Emulating Nature by observation and ground-up application of its patterns, structures and processes is a classical scientific practice which under the designation of Biomimetics has now been brought to the Nanotechnology scale where even highly complex systems can be realized by continuous or cyclically reiterated assembly of the respective self-similar eigen-elements, modules and algorithms right from their infinitesimal origin. This is actually quite akin to the genuine mathematical art and can find valuable renewed use as here exemplified by the tentatively original Demonstratio Mirabilis of FLT (Fermat's Last Theorem, or, in that case, Triumph) by infinitely ascending sheet-wise cubical crystal growth leading to the binomial `magic triangle' of his close fellow Blaise Pascal.

  3. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan A. [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Clinical Center Nis, Center for Radiology, Nis (Serbia); Vojinovic, Slobodan; Ljubisavljevic, Srdjan [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Clinic for Neurology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-03-15

    To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

  4. Advanced intensity-modulation continuous-wave lidar techniques for ASCENDS CO2 column measurements

    Science.gov (United States)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.; Harrison, F. W.; Obland, Michael D.; Meadows, Byron

    2015-10-01

    Global atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity- Modulated Continuous-Wave (IM-CW) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) modulation technique to uniquely discriminate surface lidar returns from intermediate aerosol and cloud contamination. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of optically thin clouds, thereby eliminating the need to correct for sidelobe bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new hyperfine interpolation techniques that takes advantage of the periodicity of the modulation waveforms. This approach works well for both BPSK and linear swept-frequency modulation techniques. The BPSK technique under investigation has excellent auto-correlation properties while possessing a finite bandwidth. A comparison of BPSK and linear swept-frequency is also discussed in this paper. These results are extended to include Richardson-Lucy deconvolution techniques to extend the resolution of the lidar beyond that implied by limit of the bandwidth of the modulation, where it is shown useful for making tree canopy measurements.

  5. [A new clinical entity: ascending solar iris degeneration. Report of 284 cases].

    Science.gov (United States)

    Laktaoui, A; Kriet, M; Mellaoui, M; El Wafi, A; Bouzidi, A; Douhal, A; Bouia, Y

    2013-01-01

    The observation in a certain number of subjects of an atypical iris depigmentation led us to study this phenomenon. Therefore, the authors engaged in a prospective study of 398 subjects (100 cases in the city of Marrakesh, and 298 in the city of Dakhla). The geography, clinical signs and environmental factors were studied. Depigmentation was observed in 55% of the population of Marrakesh and 77% of the population of Dakhla. It is bilateral, symmetric, very progressive, always begins in the inferior one-third of the iris, and always spares the superior iris covered by the eyelid. By the time the depigmentation reaches the middle one-third, the inferior one-third also begins to demonstrate stromal atrophy: (26 cases). Of the 45 subjects with normal iris pigmentation, 31 cases spend more than 8 hours per day in the shade, and 26 cases constantly use some means of solar protection (sunglasses, caps, "Taraza", "Feroual"). Thus, this acquired iris depigmentation of an ascending nature, accompanied by an advanced stage involving primarily inferior iris atrophy, appears to be closely associated with exposure to the sun. Ascending solar iris degeneration, if we may refer to it as such, is a clinical entity never before reported in the literature. Now that we are faced with this new condition, numerous questions arise, to which future research must respond. Are there other factors in addition to sun exposure, which may lead to the depigmentation? Does this condition lead to further ocular pathology (due to the depigmentation and stromal atrophy)? Must solar protection be prescribed systematically for anyone at risk? Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  6. Developmental plasticity of ascending spinal axons studies using the North American opossum, Didelphis virginiana.

    Science.gov (United States)

    Terman, J R; Wang, X M; Martin, G F

    1999-01-11

    The objectives of the present study were to determine if axons of all ascending tracts grow through the lesion after transection of the thoracic spinal cord during development in the North American opossum, and if so, whether they reach regions of the brain they normally innervate. Opossum pups were subjected to transection of the mid-thoracic cord at PD5, PD8, PD12, PD20, or PD26 and injections of Fast Blue (FB) into the lower thoracic or upper lumbar cord 30-40 days or 6 months later. In the PD5 transected cases, labeled axons were present in all of the supraspinal areas labeled by comparable injections in unlesioned, age-matched controls. In the experimental cases, however, labeled axons appeared to be fewer in number and in some areas more restricted in location than in the controls. When lesions were made at PD8, labeled axons were present in the brain of animals allowed to survive 30-40 days prior to FB injections but they were not observed in those allowed to survive 6 months. When lesions were made at PD12 or later, labeled axons were never found rostral to the lesion. It appears, therefore, that axons of all ascending spinal pathways grow though the lesion after transection of the thoracic cord in developing opossums and that they innervate appropriate areas of the brain. Interestingly, the critical period for such growth is shorter than that for most descending axons, suggesting that factors which influence loss of developmental plasticity are not the same for all axons.

  7. Atmospheric Airborne Pressure Measurements Using the Oxygen A Band for the ASCENDS Mission

    Science.gov (United States)

    Riris, Haris; Rodriguez, Mike; Stephen, Mark; Hasselbrack, William; Allan, Graham; Mao, Jiamping,; Kawa, Stephan R.; Weaver, Clark J.

    2011-01-01

    We report on airborne atmospheric pressure measurements using new fiber-based laser technology and the oxygen A-band at 765 nm. Remote measurements of atmospheric temperature and pressure are required for a number of NASA Earth science missions and specifically for the Active Sensing of CO2 Emissions Over Nights, Days, and Seasons (ASCENDS) mission. Accurate measurements of tropospheric CO2 on a global scale are very important in order to better understand its sources and sinks and to improve predictions on any future climate change. The ultimate goal of a CO2 remote sensing mission, such as ASCENDS, is to derive the CO2 concentration in the atmosphere in terms of mole fraction in unit of parts-per-million (ppmv) with regard to dry air. Therefore, both CO2 and the dry air number of molecules in the atmosphere are needed in deriving this quantity. O2 is a stable molecule and uniformly mixed in the atmosphere. Measuring the O2 absorption in the atmosphere can thus be used to infer the dry air number of molecules and then used to calculate CO2 concentration. With the knowledge of atmospheric water vapor, we can then estimate the total surface pressure needed for CO2 retrievals. Our work, funded by the ESTO IIP program, uses fiber optic technology and non-linear optics to generate 765 nm laser radiation coincident with the Oxygen A-band. Our pulsed, time gated technique uses several on- and off-line wavelengths tuned to the O2 absorption line. The choice of wavelengths allows us to measure the pressure by using two adjacent O2 absorptions in the Oxygen A-band. Our retrieval algorithm fits the O2 lineshapes and derives the pressure. Our measurements compare favorably with a local weather monitor mounted outside our laboratory and a local weather station.

  8. Advanced Intensity-Modulation Continuous-Wave Lidar Techniques for ASCENDS O2 Column Measurements

    Science.gov (United States)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.; Harrison, F. Wallace; Obland, Michael D.; Meadows, Byron

    2015-01-01

    Global atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity- Modulated Continuous-Wave (IM-CW) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) modulation technique to uniquely discriminate surface lidar returns from intermediate aerosol and cloud contamination. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of optically thin clouds, thereby eliminating the need to correct for sidelobe bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new hyperfine interpolation techniques that takes advantage of the periodicity of the modulation waveforms. This approach works well for both BPSK and linear swept-frequency modulation techniques. The BPSK technique under investigation has excellent auto-correlation properties while possessing a finite bandwidth. A comparison of BPSK and linear swept-frequency is also discussed in this paper. These results are extended to include Richardson-Lucy deconvolution techniques to extend the resolution of the lidar beyond that implied by limit of the bandwidth of the modulation, where it is shown useful for making tree canopy measurements.

  9. Axial compartmentation of descending and ascending thin limbs of Henle's loops.

    Science.gov (United States)

    Westrick, Kristen Y; Serack, Bradley; Dantzler, William H; Pannabecker, Thomas L

    2013-02-01

    In the inner medulla, radial organization of nephrons and blood vessels around collecting duct (CD) clusters leads to two lateral interstitial regions and preferential intersegmental fluid and solute flows. As the descending (DTLs) and ascending thin limbs (ATLs) pass through these regions, their transepithelial fluid and solute flows are influenced by variable transepithelial solute gradients and structure-to-structure interactions. The goal of this study was to quantify structure-to-structure interactions, so as to better understand compartmentation and flows of transepithelial water, NaCl, and urea and generation of the axial osmotic gradient. To accomplish this, we determined lateral distances of AQP1-positive and AQP1-negative DTLs and ATLs from their nearest CDs, so as to gauge interactions with intercluster and intracluster lateral regions and interactions with interstitial nodal spaces (INSs). DTLs express reduced AQP1 and low transepithelial water permeability along their deepest segments. Deep AQP1-null segments, prebend segments, and ATLs lie equally near to CDs. Prebend segments and ATLs abut CDs and INSs throughout much of their descent and ascent, respectively; however, the distal 30% of ATLs of the longest loops lie distant from CDs as they approach the outer medullary boundary and have minimal interaction with INSs. These relationships occur regardless of loop length. Finally, we show that ascending vasa recta separate intercluster AQP1-positive DTLs from descending vasa recta, thereby minimizing dilution of gradients that drive solute secretion. We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss.

  10. Anomalous Origin of One Pulmonary Artery From the Ascending Aorta: From Diagnosis to Treatment in Angola.

    Science.gov (United States)

    Manuel, Valdano; Sousa-Uva, Miguel; Morais, Humberto; Magalhães, Manuel P; Pedro, Albino; Miguel, Gade; Nunes, Maria A S; Gamboa, Sebastiana; Júnior, António P F

    2015-10-01

    Anomalous origin of one pulmonary artery is a rare congenital heart disease in which one pulmonary artery branch originates from the ascending aorta. To describe the experience of a cardiothoracic center in an African country to repair anomalous origin of one pulmonary artery in the context of Portugal-Angola collaboration. Between March 2011 and March 2015, four consecutive patients with anomalous origin of pulmonary artery branch underwent surgical correction. The mean age was 1.6 months. The mean weight was 4 kg. All had right pulmonary artery branch originating from the ascending aorta. All patients underwent direct implantation of right pulmonary branch to main pulmonary artery. Two patents had patent ductus arteriosus and one had atrial septal defect. Two patients had pulmonary hypertension. There was no registration of death. The mean cardiopulmonary bypass time was 75.5 ± 4.5 minutes, mean aortic cross-clamping time was 40 ± 5.6 minutes, and mean duration of the postoperative intensive care unit stay was 6.8 ± 5.7 days. At discharge, one patient had residual gradient of 25 mm Hg, the remainder had no significant gradient. The mean follow-up time was 11 months (5-28 months). One week after discharge, one patient presented operative wound dehiscence. At the last follow-up, all patients were alive, and no significant residual gradient or stenosis at site of anastomosis was observed. No reintervention was required. Anomalous origin of one pulmonary artery is a rare but potentially treatable lesion if operated early in life. Direct implantation was a good technique with good short-term results. © The Author(s) 2015.

  11. Aortic allografts in treatment of aortic valve and ascending aorta prosthetic endocarditis

    Directory of Open Access Journals (Sweden)

    S.V. Spiridonov

    2017-03-01

    Full Text Available The aim – to assess short- and long-term results of aortic root replacement using aortic allografts in patients with prosthetic endocarditis. Materials and methods. Since February 2009 until June 2016 aortic valve and ascending aorta replacement using aortic allografts was performed in 26 patients with prosthetic endocarditis. In 50 % of cases at initial operation aortic valve replacement was performed, in another 50 % of cases – aortic valve and ascending aorta replacement. Echocardiography was performed 10 days, 3, 6 and 12 months, 2, 3 and 5 years after surgery. Analysis of long-term results included all cases of deaths, prosthesis-related complications and recurrence of endocarditis. Results. 30-day mortality was 23.1 %. Extracorporeal membranous oxygenation (ECMO was used only in 5 patients (19.2 %. Four patients were weaned from ECMO. We did not observe any allograft-related complications. During follow-up period there were no cases of reoperation due to structural allograft failure. Relapse of infection occurred in 1 patient (3.8 % four years after the operation and led to lethal outcome. Conclusion. Reoperations using allografts are an effective surgical treatment of prosthetic endocarditis. In majority of cases prosthetic endocarditis was caused by gram-positive cocci (Staphylococcus. In 84.6 % of cases it was associated with destruction of paravalvular structures and abscesses formation. Heart failure was a causative factor of different complications in these patients, which required ECMO in 19.2 % of patients. In 80 % of cases patients were weaned from ECMO. Allografts using for the treatment of prosthetic endocarditis is associated with high resistance to infection and with a significant rate of freedom from recurrence of endocarditis within 3 years after surgery.

  12. Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Minglong Shao

    Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

  13. Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

    Science.gov (United States)

    Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

    2018-05-02

    Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Sustainability, Participatory Culture, and the Performance of Democracy: Ascendant Sites of Theory and Practice in Art Education

    Science.gov (United States)

    Blandy, Doug

    2011-01-01

    Art education is a systemic and extensive network within which children, youth, and adults make and learn about material culture. This lecture considers three sites of theory and practice that I see as ascendant in circulating through this network. These sites are sustainability, participatory culture, and performing democracy. I argue that…

  15. Ascending Projections from the Solitary Tract Nucleus to the Hypothalamus : A Phaseolus vulgaris Lectin Tracing Study in the Rat

    NARCIS (Netherlands)

    Horst, G.J. ter; de Boer, P.; Luiten, P.G.M.; Willigen, J.D. van

    1989-01-01

    The course of the ascending pathways originating from the anterior gustatory and posterior visceral sensory part of the solitary tract nucleus and the topographic organization of the projections to the hypothalamus in the rat were studied with anterogradely transported Phuseolus vulgaris lectin. In

  16. Moderate versus deep hypothermic circulatory arrest for ascending aorta and aortic arch surgeries using open distal anastomosis technique

    Directory of Open Access Journals (Sweden)

    Ahmed Abdelgawad

    2017-12-01

    Conclusions: MHCA with ACP achieved very good and comparable results to DHCA with RCP for ascending and aortic reconstruction. Furthermore, MHCA significantly shortened total operative, cardiopulmonary bypass and ischaemic times and, basically, decreased transfusion requirements compared with the former strategy and consequently may lead to better patient's outcome.

  17. Endovascular approach to treat ascending aortic pseudoaneurysm in a patient with previous CABG and very high surgical risk.

    Science.gov (United States)

    Zago, Alexandre C; Saadi, Eduardo K; Zago, Alcides J

    2011-10-01

    Pseudoaneurysm of the ascending aorta is an uncommon pathology and a challenge in high-risk patients who undergo conventional surgery because of high operative morbidity and mortality. Endovascular exclusion of an aortic pseudoaneurysm using an endoprosthesis is a less invasive approach, but few such cases have been reported. Moreover, the use of this approach poses unique therapeutic challenges because there is no specific endoprosthesis for ascending aortic repair, particularly to treat patients with previous coronary artery bypass graft (CABG). We describe the case of a 74-year-old patient who had undergone CABG and later presented with an iatrogenic ascending aortic pseudoaneurysm that occurred during an angiography. This patient was at very high risk for surgical treatment and, therefore, an endovascular approach was adopted: percutaneous coronary intervention for the left main coronary artery, left anterior descending and left circumflex native coronary arteries followed by endovascular endoprosthesis deployment in the ascending aorta to exclude the pseudoaneurysm. Both procedures were successfully performed, and the patient was discharged without complications 4 days later. At 5 months' clinical follow-up, his clinical condition was good and he had no complications. Copyright © 2011 Wiley-Liss, Inc.

  18. Allergenicity evaluation of p-chloro-m-cresol and p-chloro-m-xylenol by non-radioactive murine local lymph-node assay and multiple-dose guinea pig maximization test

    International Nuclear Information System (INIS)

    Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

    2003-01-01

    p-Chloro-m-cresol (PCMC) and p-chloro-m-xylenol (PCMX) are known to cause allergic contact dermatitis. For risk assessment of skin sensitizers, information on dose-response profiles in the induction and elicitation phases and cross-reactivity with analogous chemicals are important. In the non-radioactive local lymph-node assay (LLNA) using 5-bromo-2'-deoxyuridine instead of 3 H-methyl thymidine, significant effect on lymph node cell proliferation was detected at 10% PCMC and 25% PCMX, while in the multiple-dose guinea pig maximization test (GPMT) at least one animal tested in the group was sensitized at a 5 ppm induction dose of either chemical. When mean skin reaction score in an animal group maximally sensitized with each allergen with the GPMT was plotted against log challenge concentration, linear regression lines with high correlations were obtained in both cases. The calculated elicitation threshold was lower for PCMC than PCMX. The area under the linear regression line between the threshold point and 1% of the elicitation concentration, another index of relative elicitation potency, was also greater for PCMC. Bidirectional cross-reactivity between PCMX and PCMC was detected in the GPMT. PCMC was thus identified in both LLNA and GPMT as a stronger sensitizer than PCMX in both the induction and elicitation phases. These results suggest that the non-radioactive LLNA is a simple and useful method for evaluating allergenicity in the induction phase, while the GPMT using a maximally sensitized animal group is more suitable for assessing the dose-response profile and cross-reactivity in the elicitation phase

  19. Evaluation of radiation dose in 64-row whole-body CT of multiple injured patients compared to 4-row CT; Evaluation der Strahlendosis bei Polytrauma-CT-Untersuchungen eines 64-Zeilen-CT im Vergleich zur 4-Zeilen-CT

    Energy Technology Data Exchange (ETDEWEB)

    Harrieder, A.; Geyer, L.L.; Koerner, M.; Deak, Z.; Wirth, S.; Reiser, M.; Linsenmaier, U. [Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2012-05-15

    Purpose: To evaluate radiation exposure in whole-body CT (WBCT) of multiple injured patients comparing 4-row multidetector computed tomography (MDCT) to 64-row MDCT. Materials and Methods: 200 WBCT studies were retrospectively evaluated: 92 4-row MDCT scans and 108 64-row MDCT scans. Each CT protocol was optimized for the particular CT system. The scan length, CT dose index (CTDI), and dose length product (DLP) were recorded and analyzed for radiation exposure. The mean effective dose was estimated based on conversion factors. Student's t-test was used for statistical analysis. Results: The mean CTDI{sub vol} values (mGy) of the thorax and abdomen were significantly reduced with 64-row MDCT (10.2 {+-} 2.5 vs. 11.4 {+-} 1.4, p < 0.001; 14.2 {+-} 3.7 vs. 16.1 {+-} 1.7, p < 0.001). The DLP values (mGy x cm) of the head and thorax were significantly increased with 64-row MDCT (1305.9 {+-} 201.1 vs. 849.8 {+-} 90.9, p < 0,001; 504.4 {+-} 134.4 vs. 471.5 {+-} 74.1, p = 0.030). The scan lengths (mm) were significantly increased with 64-row MDCT: head 223.6 {+-} 35.8 vs. 155.5 {+-} 12.3 (p < 0.001), thorax 427.4 {+-} 44.5 vs. 388.3 {+-} 57.5 (p < 0.001), abdomen 520.3 {+-} 50.2 vs. 490.8 {+-} 51.6 (p < 0.001). The estimated mean effective doses (mSv) were 22.4 {+-} 2.6 (4-row MDCT) and 24.1 {+-} 4.6 (64-row MDCT; p = 0.001), resulting in a percentage increase of 8 %. Conclusion: The radiation dose per slice of the thorax and abdomen can be significantly decreased by using 64-row MDCT. Due to the technical advances of modern 64-row MDCT systems, the scan field can be adapted to the clinical demands and, if necessary, enlarged without time loss. As a result, the estimated mean effective dose might be increased in WBCT. (orig.)

  20. Impact of surgical era on outcomes of patients undergoing elective atherosclerotic ascending aortic aneurysm operations.

    Science.gov (United States)

    Fleck, Tatiana M; Koinig, Herbert; Czerny, Martin; Hutschala, Doris; Wolner, Ernst; Ehrlich, Marek; Grabenwoger, Martin

    2004-08-01

    This retrospective study evaluates, if recent refinements in peri-operative management, have an impact on clinical outcome of patients undergoing elective repair of their ascending thoracic aorta. One hundred sixty five (n = 165) consecutive patients were operated during a 7 year period at our department. The cohort was divided in an early group I (from Jan 1997 to Dec 1999, n = 75) and a late group II (from Jan 2000 to Jan 2003, n = 90). The mean age was 60.9+/-13.1 years in group I versus 58.1+/-13.6 years in group II. In group I 50 patients (66.6%) underwent replacement of the ascending thoracic aorta alone, 17 patients (22.6%) received a composite graft, 8 patients (10.6%) had an additional aortic valve replacement and 14 patients (18.6%) needed concomitant coronary artery bypass grafting. In group II the procedures were as follows: interposition graft alone in 58 patients (64.4%), composite graft in 26 patients (28.8%), aortic valve replacement in 6 (6.6%) and CABG in 11 patients (12.2%). Overall hospital mortality for the entire cohort was 6.6% (11/165) with no significant differences between the early and late group with 6.6% (5/75) and 6.6% (6/90), respectively, P = 0.985. Causes were multi organ failure in 63.3% (n = 7), stroke in 9% (n = 1) myocardial infarction in 18.1% (n = 2) and refractory bleeding in 9% (n = 1). Concomitant CABG, repair of the aortic valve and composite graft, emerged as independent risk factor for mortality in multivariate logistic regression analysis with P = 0.001. Differences, became apparent in ICU as well as hospital stay with a median ICU stay in group I of 7.1+/-12.9 days versus 4.4+/-6.8 days in group II, and median hospital stay of 16.7+/-5.3 days versus 9.5+/-8.4 days for group I and II, P conservation techniques, a substantial reduction of transfusion requirements could be achieved (PRBC from 3.2+/-4 to 1.1+/-1.7 units, FFP 5.2+/-3 to 2.3+/-0.5 units, Platelets from 1.3+/-2 to 0.3+/-0.07 units). Even with the

  1. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.

    Science.gov (United States)

    McKeand, William

    2017-09-01

    Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. All 3 studies enrolled healthy postmenopausal women who were either naturally postmenopausal or had undergone bilateral oophorectomy at least 6 months before the start of the study. Study 1 showed that unconjugated and total (unconjugated and conjugated) bazedoxifene levels increased proportionally with ascending oral doses of bazedoxifene (through the dose range of 5-120 mg). Evaluation with or without food intake was conducted at the 10-mg dose, with no clinically relevant effect on pharmacokinetic parameters. Study 2 showed that bazedoxifene achieved steady state in 1 week and exhibited linear pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the dose range. In accordance with a linear pharmacokinetic profile, mean maximum plasma concentration values increased with increasing dose, with values of 1.6, 6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3, tablet and capsule formulations of bazedoxifene formulations had an estimated oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg based on intravenous administration. The oral formulations had comparable exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was safe and well tolerated in all 3 studies. These pharmacokinetic evaluations in healthy postmenopausal women found that bazedoxifene displayed linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected accumulation

  3. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers.

    Science.gov (United States)

    Markowitz, John S; Donovan, Jennifer L; Devane, C Lindsay; Taylor, Robin M; Ruan, Ying; Wang, Jun-Sheng; Chavin, Kenneth D

    2003-12-01

    Saw palmetto (Serenoa repens) is the most commonly used herbal preparation in the treatment of benign prostatic hyperplasia. The objective of this study was to determine whether a characterized saw palmetto product affects the activity of cytochrome P450 (CYP) 2D6 or 3A4 in healthy volunteers (6 men and 6 women). The probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again after exposure to saw palmetto (320-mg capsule once daily) for 14 days. Dextromethorphan metabolic ratios and alprazolam pharmacokinetics were determined at baseline and after saw palmetto treatment. The mean ratio of dextromethorphan to its metabolite was 0.038 +/- 0.044 at baseline and 0.048 +/- 0.080 after 14 days of saw palmetto administration (P =.704, not significant [NS]), indicating a lack of effect on CYP2D6 activity. The area under the plasma alprazolam concentration versus time curve was 476 +/- 178 h. ng. mL(-1) at baseline and 479 +/- 125 h. ng. mL(-1) after saw palmetto treatment (P =.923, NS), indicating a lack of effect on CYP3A4 activity. The elimination half-life of alprazolam was 11.4 +/- 3.1 hours at baseline and 11.6 +/- 2.7 hours after saw palmetto treatment (P =.770, NS), also indicating a lack of effect on CYP3A4 activity. Our results indicate that extracts of saw palmetto at generally recommended doses are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination. These conclusions must be weighed in the context of the study's limited assessments and regarded as only the initial investigation into the drug interaction potential of saw palmetto.

  4. Blood conservation strategies reduce the need for transfusions in ascending and aortic arch surgery.

    Science.gov (United States)

    Chu, M W A; Losenno, K L; Moore, K; Berta, D; Hewitt, J; Ralley, F

    2013-07-01

    Ascending and aortic arch surgery is associated with higher levels of blood loss and subsequent need for allogeneic blood transfusions. We hypothesized that aggressive, comprehensive blood conservation strategies may limit the need for transfusions and, subsequently, improve postoperative outcomes. Over a five-year period, 189 patients underwent proximal aortic surgery at our institution. Fifty-one patients underwent surgery using a comprehensive blood conservation strategy (BCS), including preoperative hemoglobin optimization, antifibrinolytic therapy, intraoperative acute normovolemic hemodilution, cell salvage and meticulous surgical technique. The remaining 138 patients underwent surgery using conventional techniques (CONV). Patients in the BCS group required fewer transfusions during their hospital stay compared to the conventional group (56.9% vs. 72.5%, p=0.041). When examining elective cases, this trend widens, with 40.0% of BCS patients requiring any transfusions compared to 72.9% patients in the conventional group (p=0.001). Red cell (47.1% vs. 62.3%, p=0.06), plasma (43.1% vs. 61.6%, p=0.02) and platelets (27.5% vs. 47.8%, p=0.01) were also less frequently required in the BCS group than the conventional group, respectively. When a transfusion was required, patients in the BCS group received significantly fewer units of red blood cells (2.8 ± 7.0 units) than the conventional group (5.81 ± 9.5 units; p=0.039). Mortality was similar in both groups (BCS 7.8%, conventional 10.9%, p=0.54); however, there was significantly less morbidity in the BCS group, using a composite of any of 10 major postoperative complications (23.5% vs. 39.1%; p=0.046). Median intensive care unit (ICU) and hospital lengths of stay were 2 and 7 days in the BCS group and 2 and 8 days in the CONV group (p=0.15), respectively. The aggressive use of a comprehensive blood conservation strategy in ascending and aortic arch surgery can significantly reduce the need for blood transfusions

  5. Case report and review of the literature total endovascular repair of acute ascending aortic rupture: a case report and review of the literature.

    Science.gov (United States)

    McCallum, John C; Limmer, Karl K; Perricone, Anthony; Bandyk, Dennis; Kansal, Nikhil

    2013-07-01

    Thoracic aortic endografting has been successfully implemented to treat aneurysmal disease of the distal aortic arch and descending thoracic aorta. Although there are reports of ascending aortic endovascular interventions, the total endovascular repair of a ruptured ascending aorta secondary to a Type A dissection has not been described. We report the case of a 77-year-old patient who presented with a ruptured ascending aortic aneurysm secondary to degeneration of a Stanford type A aortic dissection. His surgical history was significant for orthotropic heart transplant 19 years prior. The dissection, aneurysm, and rupture occurred in the native aorta distal to the ascending aortic suture line. At presentation, he was hemodynamically unstable with a right hemothorax. We placed 3 Medtronic Talent Thoracic Stent Graft devices (Medtronic Inc, Minneapolis, MN) across the suture line in the ascending aorta, excluding the rupture. The patient survived and has been followed to 25 months.

  6. Treatment of multiple sclerosis relapses with high-dose methylprednisolone reduces the evolution of contrast-enhancing lesions into persistent black holes.

    Science.gov (United States)

    Di Gregorio, Maria; Gaetani, Lorenzo; Eusebi, Paolo; Floridi, Piero; Picchioni, Antonella; Rosi, Giovanni; Mancini, Andrea; Floridi, Chiara; Baschieri, Francesca; Gentili, Lucia; Sarchielli, Paola; Calabresi, Paolo; Di Filippo, Massimiliano

    2018-03-01

    The MRI evidence of persistent black holes (pBHs) on T1-weighted images reflects brain tissue loss in multiple sclerosis (MS). The evolution of contrast-enhancing lesions (CELs) into pBHs probably depends on the degree and persistence of focal brain inflammation. The aim of our retrospective study was to evaluate the effect of a single cycle of intravenous methylprednisolone (IVMP), as for MS relapse treatment, on the risk of CELs' evolution into pBHs. We selected 57 patients with CELs on the baseline MRI scan. We evaluated the evolution of CELs into pBHs on a follow-up MRI scan performed after ≥ 6 months in patients exposed and not exposed to IVMP for the treatment of relapse after the baseline MRI. In our cohort, 182 CELs were identified in the baseline MRI and 57 of them (31.3%) evolved into pBHs. In the multivariate analysis, the exposure of CELs to IVMP resulted to be a significant independent protective factor against pBHs' formation (OR 0.28, 95% CI 0.11-0.766, p = 0.005), while ring enhancement pattern and the fact of being symptomatic were significant risk factors for CELs' conversion into pBHs (OR 6.42, 95% CI 2.55-17.27, p < 0.001 and OR 13.19, 95% CI 1.56-288.87, p = 0.037). The exposure of CELs to a cycle of IVMP as for relapse treatment is associated with a lower risk of CELs' evolution into pBHs. Future studies are required to confirm the potential independent protective effect of IVMP on CELs' evolution into pBHs.

  7. Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study.

    Science.gov (United States)

    Jang, Seong Bok; Lee, Yoon Jung; Lim, Lay Ahyoung; Park, Kyung-Mi; Kwon, Bong-Ju; Woo, Jong Soo; Kim, Yong-Il; Park, Min Soo; Kim, Kyung Hwan; Park, Kyungsoo

    2010-01-01

    A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation. The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, open-label, parallelgroup, 2-part study. Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20% of their ideal weight. In part I, each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally (20 mg x 2 tablets) after fasting. In part II, each subject received the same dose of the CR or IR formulation for 8 consecutive days. Blood samples were obtained for 48 hours after the dose in part I and after the first and the last dose in part II. Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety). An adverse event (AE) was defined as any unfavorable sign (including an abnormal laboratory finding) or symptom, regardless of whether it had a causal relationship with the study medication. Serious AEs were defined as any events that are considered life threatening, require hospitalization or prolongation of existing hospitalization, cause persistent or significant disability or incapacity, or result in congenital abnormality, birth defect, or death. AEs were determined based on patient interviews and physical examinations. Twenty-four healthy subjects (17 men, 7 women; mean [SD] age, 29 [7] years; age range, 22-50 years) were enrolled in part I, and 29 subjects (17 men, 12 women; mean age, 33 [9] years; age range, 19-55 years) were enrolled in part II. For simvastatin acid, C

  8. Early results of valve-sparing ascending aortic replacement in type A aortic dissection and aortic insufficiency

    Directory of Open Access Journals (Sweden)

    М. Л. Гордеев

    2016-08-01

    Full Text Available Aim: The study was designed to investigate predictors of effective valve-sparing ascending aortic replacement in patients with Stanford type A aortic dissection combined with aortic insufficiency and to analyze efficacy and safety of this kind of surgery.Methods: From January 2010 to December 2015, 49 patients with Stanford type A aortic dissection combined with aortic insufficiency underwent ascending aortic replacement. All patients were divided into 3 groups: valve-sparing procedures (group 1, n = 11, combined aortic valve and supracoronary ascending aortic replacement (group 2, n = 12, and Bentall procedure (group 3, n = 26. We assessed the initial status of patients, incidence of complications and efficacy of valve-sparing ascending aortic replacement.Results: The hospital mortality rate was 8.2% (4/49 patients. The amount of surgical correction correlated with the initial diameter of the aorta at the level of the sinuses of Valsalva. During the hospital period, none of patients from group 1 developed aortic insufficiency exceeding Grade 2 and the vast majority of patients had trivial aortic regurgitation. The parameters of cardiopulmonary bypass, cross-clamp time and circulatory arrest time did not correlate with the initial size of the ascending aorta and aortic valve blood flow impairment, neither did they influence significantly the incidence and severity of neurological complications. The baseline size of the ascending aorta and degree of aortic regurgitation did not impact the course of the early hospital period.Conclusions: Supracoronary ascending aortic replacement combined with aortic valve repair in ascending aortic dissection and aortic regurgitation is effective and safe. The initial size of the ascending aorta and aortic arch do not influence immediate results. The diameter of the aorta at the level of the sinuses of Valsalva and the condition of aortic valve leaflets could be considered as the limiting factors. Further long

  9. A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

    DEFF Research Database (Denmark)

    Vangsted, Annette J; Klausen, Tobias W; Gimsing, Peter

    2009-01-01

    and Methods: In a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon- as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G...... homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-. Conclusions: Patients who are homozygous carriers...

  10. Virtual Practice of Biochemistry: Ascendant Chromatography on Paper of Amino acids.

    Directory of Open Access Journals (Sweden)

    G. Zanatta

    2010-05-01

    Full Text Available Chromatography is a method used for analyses of mixture components based on different criteria: adsorbility, solubility, molecular mass, ionic charge and affinity. It is an important subject of Biochemistry. This work reports the development and the validation of a software that simulated a laboratory activity named Ascendant Chromatography on Paper of Aminoacids. The organization and the multimedia material collection were done during the 2008/2 semester. The most representative images were inserted into the learning object. The tool used for the software development was Adobe® Flash® CS3. The first application of this object was in Biochemistry I (Pharmacy-UFRGS in 2009/1. Using this experience, a new version was developed which was tested by the students of the same subject in 2009/2. After a 50-minute class (theoretical-practical, the students of both semesters were divided in two groups. Group I answered a questionnaire about chromatography basic concepts and after used the software. Group II was submitted to an inverse protocol. The groups also evaluated the technical aspects of the software animation/simulation and the activity carried out. Associating both applications results (2009/1 and 2009/2, the present learning object can be valid as a support for practical teaching of basic biochemistry.

  11. Cecal perforation with an ascending colon cancer caused by upper gastrointestinal endoscopy

    Directory of Open Access Journals (Sweden)

    Hiroyuki Miyatani

    2009-04-01

    Full Text Available Hiroyuki Miyatani1, Yukio Yoshida1, Hirokazu Kiyozaki21Department of Gastroenterology, Jichi Medical University, Saitama Medical Center, Saitama, Japan; 2Department of Surgery, Jichi Medical University, Saitama Medical Center, Saitama, JapanAbstract: Colonic perforation caused by upper gastrointestinal (GI endoscopy is extremely rare. A 69-year-old woman was referred to our hospital because of abdominal fullness. Colonoscopy could be performed only up to the hepatic flexure due to an elongated colon and residual stools. Because her symptoms improved, upper GI endoscopy was performed 11 days later. The patient developed severe abdominal pain two hours after the examination. Abdominal X-ray and computed tomography showed massive free air. Immediate laparotomy was performed for the intestinal perforation. After removal of stool, a perforation site was detected in the cecum with an invasive ascending colon cancer. Therefore, a right hemicolectomy, ileostomy, and transverse colostomy were performed. Although she developed postoperative septicemia, the patient was discharged 38 days after admission. Seven months postoperatively, the patient died of lung, liver, and brain metastases. Even in cases with a lesion that is not completely obstructed, it is important to note that air insufflations during upper GI endoscopy can perforate the intestinal wall in patients with advanced colon cancer.Keywords: colonic perforation, colon cancer, upper gastrointestinal endoscopy, fecal peritonitis

  12. Ascending paresis as presentation of an unusual association between necrotizing autoimmune myopathy and systemic lupus erythematosus.

    Science.gov (United States)

    García-Reynoso, Marco Julio; Veramendi-Espinoza, Liz Eliana; Ruiz-Garcia, Henry Jeison

    2014-01-01

    A 45 year-old man went to the emergency room due to disease duration of 15 days of insidious onset and progressive course. It began with symmetrical weakness and pain in feet and ankles that extends upward to the knees. Later, this progressed to paraparesis with Creatine phosphokinase levels of 44,270 U/L and respiratory failure that required mechanical ventilation. Electromyography and muscle biopsy of quadriceps were made. The patient responded to corticotherapy in pulses and supporting management. The presentation of ascending paresis suggested the diagnosis of Guillain-Barré syndrome. However, the degree of muscle involvement with rhabdomyolysis explains the neurological damage by itself. The biopsy revealed pathological criteria for necrotizing autoimmune myopathy (NAM), as well as other clinical and laboratory evidence. Patient disease continued and reached criteria for systemic lupus erythematosus (SLE). To our best knowledge, this is the first report of the NAM and SLE association. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  13. The evolution of ecosystem ascendency in a complex systems based model.

    Science.gov (United States)

    Brinck, Katharina; Jensen, Henrik Jeldtoft

    2017-09-07

    General patterns in ecosystem development can shed light on driving forces behind ecosystem formation and recovery and have been of long interest. In recent years, the need for integrative and process oriented approaches to capture ecosystem growth, development and organisation, as well as the scope of information theory as a descriptive tool has been addressed from various sides. However data collection of ecological network flows is difficult and tedious and comprehensive models are lacking. We use a hierarchical version of the Tangled Nature Model of evolutionary ecology to study the relationship between structure, flow and organisation in model ecosystems, their development over evolutionary time scales and their relation to ecosystem stability. Our findings support the validity of ecosystem ascendency as a meaningful measure of ecosystem organisation, which increases over evolutionary time scales and significantly drops during periods of disturbance. The results suggest a general trend towards both higher integrity and increased stability driven by functional and structural ecosystem coadaptation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans.

    Science.gov (United States)

    Qiu, Yunhai; Inui, Koji; Wang, Xiaohong; Nguyen, Binh Thi; Tran, Tuan Diep; Kakigi, Ryusuke

    2004-03-01

    Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region. Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model. (1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P cognitive aspect of second pain perception. The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.

  15. PONDS AND CLIMATE, THE GEOGRAPHICAL ASCENDANCY RELATIONSHIP (“LA BRENNE” CASE STUDY, FRANCE

    Directory of Open Access Journals (Sweden)

    Laurent TOUCHART

    2012-03-01

    Full Text Available Ponds and climate, the geographical ascendancy relationship (“La Brenne” case study, France. The climate influences markedly the volume of water ponds and lakes. However, the role and the influence of "small" water areas, and areas of ponds on the local climate remain poorly understood. Scientific studies for the Great Lakes have been made. Moreover, scientific studies on «small» water areas and areas of ponds do not exist until today. A first approach to study the area of ponds of “La Brenne” (Central Region, France was performed. The monthly climate data from some meteorological stations, with the reference station of “Issoudun”, located away from areas of ponds, were the basis of our analysis. The study focuses on the most representative climatic parameters. These are the temperature, precipitation and relative humidity. This first approach is used to distinguish and clarify the most important cases and relevant parameters in order to achieve a typology of criteria. Our results will be used for further study and quantify the real influence of "small" water areas and areas of ponds on the elements of the local climate.

  16. Density of calcium in the ascending thoracic aorta and risk of incident cardiovascular disease events.

    Science.gov (United States)

    Thomas, Isac C; McClelland, Robyn L; Michos, Erin D; Allison, Matthew A; Forbang, Nketi I; Longstreth, W T; Post, Wendy S; Wong, Nathan D; Budoff, Matthew J; Criqui, Michael H

    2017-10-01

    The volume and density of coronary artery calcium (CAC) both independently predict cardiovascular disease (CVD) beyond standard risk factors, with CAC density inversely associated with incident CVD after accounting for CAC volume. We tested the hypothesis that ascending thoracic aorta calcium (ATAC) volume and density predict incident CVD events independently of CAC. The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of participants without clinical CVD at baseline. ATAC and CAC were measured from baseline cardiac computed tomography (CT). Cox regression models were used to estimate the associations of ATAC volume and density with incident coronary heart disease (CHD) events and CVD events, after adjustment for standard CVD risk factors and CAC volume and density. Among 6811 participants, 234 (3.4%) had prevalent ATAC and 3395 (49.8%) had prevalent CAC. Over 10.3 years, 355 CHD and 562 CVD events occurred. One-standard deviation higher ATAC density was associated with a lower risk of CHD (HR 0.48 [95% CI 0.29-0.79], pdensity was inversely associated with incident CHD and CVD after adjustment for CVD risk factors and CAC volume and density. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Biomechanical analysis of a novel hemipelvic endoprosthesis during ascending and descending stairs.

    Science.gov (United States)

    Liu, Dongxu; Hua, Zikai; Yan, Xinyi; Jin, Zhongmin

    2016-10-01

    In this study, the biomechanical characteristic of a newly developed adjustable hemipelvic prosthesis under dynamic loading conditions was investigated using explicit finite element method. Both intact and reconstructed pelvis models, including pelvis, femur and soft tissues, were established referring to human anatomic data using a solid geometry of a human pelvic bone. Hip contact forces during ascending stairs and descending stairs were imposed on pelvic models. Results showed that maximum von Mises stresses in reconstructed pelvis were 421.85 MPa for prostheses and 109.12 MPa for cortical bone, which were still within a low and elastic range below the yielding strength of Ti-6Al-4V and cortical bone, respectively. Besides, no significant difference of load transferring paths along pelvic rings was observed between the reconstructed pelvis and natural pelvis models. And good agreement was found between the overall distribution of maximum principal stresses in trabecular bones of reconstructed pelvis and natural pelvis, while at limited stances, principal stresses in trabecular bone of reconstructed pelvis were slightly lower than natural pelvis. The results indicated that the load transferring function of pelvis could be restored by this adjustable hemipelvic prosthesis. Moreover, the prosthesis was predicted to have a reliable short- and long-term performance. However, due to the occurrence of slightly lower principal stresses at a few stances, a porous structure applied on the interface between the prosthesis and bone would be studied in future work to obtain better long-term stability. © IMechE 2016.

  18. Volvulus of the ascending colon in a non-rotated midgut: Plain film and MDCT findings.

    Science.gov (United States)

    Camera, Luigi; Calabrese, Milena; Mainenti, Pier Paolo; Masone, Stefania; Vecchio, Walter Del; Persico, Giovanni; Salvatore, Marco

    2012-10-28

    Colonic volvulus is a relatively uncommon cause of large bowel obstruction usually involving mobile, intra-peritoneal, colonic segments. Congenital or acquired anatomic variation may be associated with an increased risk of colonic volvulus which can occasionally involve retro-peritoneal segments. We report a case of 54-year-old female who presented to our Institution to perform a plain abdominal film series for acute onset of cramping abdominal pain. Both the upright and supine films showed signs of acute colonic obstruction which was thought to be due to an internal hernia of the transverse colon into the lesser sac. The patient was therefore submitted to a multi-detector contrast-enhanced computed tomography (CT). CT findings were initially thought to be consistent with the presumed diagnosis of internal hernia but further evaluation and coronal reformatting clearly depicted the presence of a colonic volvulus possibly resulting from a retro-gastric colon. At surgery, a volvulus of the ascending colon was found and a right hemi-colectomy had to be performed. However, a non rotated midgut with a right-sided duodeno-jejunal flexure and a left sided colon was also found at laparotomy and overlooked in the pre-operative CT. Retrospective evaluation of CT images was therefore performed and a number of CT signs of intestinal malrotation could be identified.

  19. PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues

    Science.gov (United States)

    2012-01-01

    Background Radiolabelled bombesin (BN) conjugates are promising radiotracers for imaging and therapy of breast and prostate tumours, in which BN2/gastrin-releasing peptide receptors are overexpressed. We describe the influence of the specific activity of a 177Lu-DOTA-PEG5k-Lys-B analogue on its therapeutic efficacy and compare it with its non-PEGylated counterpart. Methods Derivatisation of a stabilised DOTA-BN(7–14)[Cha13,Nle14] analogue with a linear PEG molecule of 5 kDa (PEG5k) was performed by PEGylation of the ϵ-amino group of a β3hLys-βAla-βAla spacer between the BN sequence and the DOTA chelator. The non-PEGylated and the PEGylated analogues were radiolabelled with 177Lu. In vitro evaluation was performed in human prostate carcinoma PC-3 cells, and in vivo studies were carried out in nude mice bearing PC-3 tumour xenografts. Different specific activities of the PEGylated BN analogue and various dose regimens were evaluated concerning their therapeutic efficacy. Results The specificity and the binding affinity of the BN analogue for BN2/GRP receptors were only slightly reduced by PEGylation. In vitro binding kinetics of the PEGylated analogue was slower since steady-state condition was reached after 4 h. PEGylation improved the stability of BN conjugate in vitro in human plasma by a factor of 5.6. The non-PEGylated BN analogue showed favourable pharmacokinetics already, i.e. fast blood clearance and renal excretion, but PEGylation improved the in vivo behaviour further. One hour after injection, the tumour uptake of the PEG5k-BN derivative was higher compared with that of the non-PEGylated analogue (3.43 ± 0.63% vs. 1.88 ± 0.4% ID/g). Moreover, the increased tumour retention resulted in a twofold higher tumour accumulation at 24 h p.i., and increased tumour-to-non-target ratios (tumour-to-kidney, 0.6 vs. 0.4; tumour-to-liver, 8.8 vs. 5.9, 24 h p.i.). In the therapy study, both 177Lu-labelled BN analogues significantly inhibited tumour

  20. Effect of short-term vs. long-term elevation of dietary protein intake on responsiveness of rat thick ascending limbs to peptide hormones.

    Science.gov (United States)

    Goldstein, David L; Plaga, Kimberly

    2002-10-01

    We compared the renal responses of rats on three diet regimens. Rats received either 8% protein food (low-protein, LP) for 10 weeks following weaning, 8% protein for 9 weeks followed by 1 week on 30% protein (short-term high-protein, SHP), or 30% protein for 10 weeks (high-protein, HP). Kidneys from HP rats were enlarged by approximately 50%, or 20% when corrected for body mass. Most of this hypertrophy resulted from enlargement of the inner stripe of the outer medulla, site of the thick ascending limbs (TAL), and TAL from HP rats were larger in diameter. SHP rats had TAL diameters similar to HP rats, but changes in renal mass or height of renal zones did not reach statistical significance. The activity of adenylyl cyclase (AC) in TAL, measured from the accumulation of cAMP in isolated tubules, increased with dose of both arginine vasopressin (AVP) and glucagon in all rats. However, HP rats had significantly higher hormone-induced AC activity than LP or SHP rats, which were not different from each other. Our results suggest that tubule hypertrophy may precede up-regulation of hormone-sensitive AC activity during the progression of renal response to elevated dietary protein.

  1. Antimicrobial Activity and Morphological Changes of Streptomyces Ascendable and Streptomyces Eighty-three's as Affected by Environmental Conditions and Gamma Radiation

    International Nuclear Information System (INIS)

    Moussa, L.A.A.; Abou El-Nour, S.A.M.; Mansour, F.A.; Serag, M.S.

    2004-01-01

    Fourteen actinomycetes out of thirty isolates were recovered from different Egyptian soils and exhibited antimicrobial activities. Streptomyces ascendable and Streptomyces eighty-three's used in the present work showed the most active antimicrobial potentialities against bacteria, moulds and yeasts. The optimum temperature and acidity for their growth and production of microbial activity were 50 degree and ph 7.0, while the maximum biomass yield and the highest antimicrobial activity were attained 10 days of incubation. Among carbon sources starch at 30 gm/L highly supported the growth and antimicrobial activity by the two species, while sodium nitrate (3 gm/L) and dipotassium hydrogen phosphate (0.75 gm/L) were the most favorable for both isolates. The presence of microelements such as manganese chloride, zinc sulphate, ferrous sulphate and copper sulphate in the growth medium at a concentration of 1 mg/L for each had a good stimulatory effect on the growth and antimicrobial activity for both Streptomyces species. As different irradiation doses were used (up to 5.0 kGy), the high levels clearly affected the morphological characteristics of both tested isolates either in the first or second generation

  2. Successful Percutaneous Coronary Intervention through a Severely Bent Artificial Ascending Aorta Using the DIO Thrombus Aspiration Catheter

    Directory of Open Access Journals (Sweden)

    Akinori Fujikake

    2016-01-01

    Full Text Available A 66-year-old man was admitted to our institute because of chest pain. He had undergone replacement of the ascending aorta due to aortic dissection 9 years previously. We made a diagnosis of acute coronary syndrome, and coronary artery angiography was performed. Although the right coronary artery was successfully cannulated, a severe bend of the artificial aorta made it very difficult to advance the catheter into the left coronary artery. Ultimately, a DIO thrombus aspiration catheter was used to enter the left coronary artery, and a stent was implanted successfully. The DIO catheter is very useful when the selection of a guiding catheter is complicated, such as in the case of severe vessel tortuosity or a bend of the ascending aorta.

  3. Reverse extra-anatomic aortic arch debranching procedure allowing thoracic endovascular aortic repair of a chronic ascending aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Ludovic Canaud, MD, PhD

    2018-06-01

    Full Text Available A 79-year-old woman was admitted with a large chronic dissecting ascending aortic aneurysm starting 5 mm distal to the ostia of the left coronary artery and ending immediately proximal to the innominate artery. A reverse extra-anatomic aortic arch debranching procedure was performed. During the same operative time, through a transapical approach, a thoracic stent graft was deployed with the proximal landing zone just distal to the coronary ostia and the distal landing zone excluding the origin of the left common carotid artery. The postoperative course was uneventful. Computed tomography at 12 months documented patent extra-anatomic aortic arch debranching and no evidence of endoleak. Keywords: Ascending aorta, Thoracic aorta, Aortic dissection, Stent graft

  4. Results of aortic root reimplantation in patients with ascending aortic aneurysm and concomitant aortic insufficiency

    Directory of Open Access Journals (Sweden)

    А. М. Чернявский

    2016-01-01

    Full Text Available Objective. The research was designed to evaluate the results of valve-sparing operations: aortic root reimplantation versus aortic valve reimplantation when repairing an ascending aortic aneurysm with concomitant aortic insufficiency.Methods. Within a blind prospective randomized study conducted over a period from 2011 to 2015, 64 patients underwent aortic valve-sparing surgery. The inclusion criteria were the presence of an aortic aneurysm of the ascending aorta exceeding 4.5 cm and concomitant aortic insufficiency. All patients were divided into two groups: FS-group, aortic root reimplantation (modified Florida Sleeve technique (n = 32 and D-group, aortic valve reimplantation (David procedure (n = 32. The average age of patients was 57±13 (23–73 years in the FS-group and 55±11 (15–72 years in the D-group (p = 0.54. Both groups had 78% of males (p>0.99. A Marfan syndrome was identified in 6% and 9% in the FS-group and D-group respectively (p>0.99. Mean diameter of the sinuses of Valsalva was 51±7 mm and 56±10 mm (p = 0.09, aortic insufficiency 2.6±0.7 and 2.8±0.8 (p = 0.15 in the FS-group and D-group respectively. In the FS-group and D-group LVEDD amounted to 5.5±0.7 mm and 5.9±1.0 mm (p = 0.09 respectively. All patients took echocardiography in the preoperative, postoperative and follow-up periods.Results. In the long-term period, the degree of aortic regurgitation was 1.2±0.1 in the FS-group and 1.3±0.6 in the D-group (p = 0.72. LVEDD was 123±23 mm in the FS-group and 139.6±80 mm in the D-group at follow-up (p = 0.77. There were no statistically significant differences in the analysis of complications. Overall 30-day in-hospital mortality was 7.8%. There were 2 (6.3% deaths in the FS-group and 3 (9.4% in the D-group (p = 0.5.Late mortality was 6.3% in the FS-group and 3.1% in the D-group (p>0.99. Cumulative survival at 4 years was 84.3% and 84.8% in the FS-group and the D-group respectively (p = 0.94. Cumulative freedom from

  5. Repair of an aneurysm of the ascending aorta and arch in an infant with Loeys-Dietz syndrome.

    Science.gov (United States)

    Jaiswal, Pratiksha; Shetty, Varun; Patel, Ebrahim; Shetty, Deviprasad

    2018-05-01

    Aortic aneurysms in childhood are rare disease entities and are usually seen in patients with genetic connective tissue disorders such as Marfans, Ehler-Danlos, and Loeys-Dietz syndrome (LDS). Patients affected with LDS present early in life and have a rapid disease progression. We report a case of repair of an ascending and aortic arch aneurysm in an infant with Loeys-Dietz syndrome. © 2018 Wiley Periodicals, Inc.

  6. Analysis of Systolic Backflow and Secondary Helical Blood Flow in the Ascending Aorta Using Vector Flow Imaging

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse; Kjaergaard, Jesper

    2016-01-01

    echocardiography and pulmonary artery catheter thermodilution, and associated with gender, age, aortic diameter, atherosclerotic plaques, left ventricular ejection fraction and previous myocardial infarctions. Secondary flow was present for all patients. The duration and rotational frequency (p ... that backflow is injurious and that secondary flow is a normal flow phenomenon. The study also shows that transverse oscillation can provide new information on blood flow in the ascending aorta....

  7. Over length quantification of the multiaxial mechanical properties of the ascending, descending and abdominal aorta using Digital Image Correlation.

    Science.gov (United States)

    Peña, Juan A; Corral, Victoria; Martínez, Miguel A; Peña, Estefanía

    2018-01-01

    In this paper, we hypothesize that the biaxial mechanical properties of the aorta may be dependent on arterial location. To demonstrate any possible position-related difference, our study analyzed and compared the biaxial mechanical properties of the ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta stemming from the same porcine subjects, and reported values of constitutive parameters for well-known strain energy functions, showing how these mechanical properties are affected by location along the aorta. When comparing ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta, abdominal tissues were found to be stiffer and highly anisotropic. We found that the aorta changed from a more isotropic to a more anisotropic tissue and became progressively less compliant and stiffer with the distance to the heart. We observed substantial differences in the anisotropy parameter between aortic samples where abdominal samples were more anisotropic and nonlinear than the thoracic samples. The phenomenological model was not able to capture the passive biaxial properties of each specific porcine aorta over a wide range of biaxial deformations, showing the best prediction root mean square error ε=0.2621 for ascending thoracic samples and, especially, the worst for the infrarenal abdominal samples ε=0.3780. The micro-structured model with Bingham orientation density function was able to better predict biaxial deformations (ε=0.1372 for ascending thoracic aorta samples). The root mean square error of the micro-structural model and the micro-structured model with von Mises orientation density function were similar for all positions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Cine MRI of the ascending aorta in the elderly with respect to the flow signal void and aortic valve morphology

    International Nuclear Information System (INIS)

    Nakayama, Masafumi; Kyomasu, Yoshinori; Suzuki, Yasuko; Mashima, Yasuoki; Tanno, Munehiko; Endo, Kazuo; Yamada, Hideo

    1990-01-01

    Cine flow MRI was performed on a 1.5 Tesla system to observe signal intensity of blood flow within the ascending aorta in the elderly who had no aortic stenosis and to determine frequency of the flow signal void. Coronal and sagittal imaging planes of the ascending aorta were obtained in 27 aged patients with no known cardiac diseases (14 men and 13 women, mean age of 76) and 7 young volunteers (7 men, mean age of 24), utilizing ECG-gating, GRASS (gradient-recalled acquisition in steady state), and a flow compensation sequence. The young volunteers presented little or no signal void within the ascending aorta. In 26 (96%) of the 27 aged patients, on the other hand, signal void was demonstrated in the blood flow distal to the aortic valve during systole. The maximum length of the signal void that was measured at 318∼632 msec after the R wave of ECG ranged from 33 to 97 mm. Conventional and Doppler echocardiography was used to evaluate motion and morphology of the aortic valve in 19 of the 27 aged patients. Eighteen of these 19 subjects had aortic signal void on cine MRI. Echocardiography showed sclerotic changes of the aortic valve (i.e., increased echogenicity of the cusps and/or commissure fusion) in 10 (53%) of the 19 subjects. The mean maximum length of the signal void in the 10 patients with aortic valve sclerosis was significantly greater than that in the 9 patients with echocardiographically normal valve (68 vs.45 mm, p<0.01). These results suggest that signal void of blood flow in the ascending aorta, which is recognized as one of the characteristic findings in patients with aortic stenosis, is not a specific feature for this disease but rather a commom one in the elderly particularly those with sclerotic changes of the aortic valve. However, the length of the signal void may distinguish between nonstenotic and stenotic aortic valves. (author)

  9. Aortic root replacement after previous surgical intervention on the aortic valve, aortic root, or ascending aorta.

    Science.gov (United States)

    Kirsch, E W Matthias; Radu, N Costin; Mekontso-Dessap, Armand; Hillion, Marie-Line; Loisance, Daniel

    2006-03-01

    Aortic root replacement after a previous operation on the aortic valve, aortic root, or ascending aorta remains a major challenge. Records of 56 consecutive patients (44 men; mean age, 56.4 +/- 13.6 years) undergoing reoperative aortic root replacement between June 1994 and June 2005 were reviewed retrospectively. Reoperation was performed 9.4 +/- 6.7 years after the last cardiac operation. Indications for reoperation were true aneurysm (n = 14 [25%]), false aneurysm (n = 10 [18%]), dissection or redissection (n = 9 [16%]), structural or nonstructural valve dysfunction (n = 10 [18%]), prosthetic valve-graft infection (n = 12 [21%]), and miscellaneous (n = 1 [2%]). Procedures performed were aortic root replacement (n = 47 [84%]), aortic root replacement plus mitral valve procedure (n = 5 [9%]), and aortic root replacement plus arch replacement (n = 4 [7%]). In 14 (25%) patients coronary artery bypass grafting had to be performed unexpectedly during the same procedure or immediately after the procedure to re-establish coronary perfusion. Hospital mortality reached 17.9% (n = 10). Multivariate logistic regression analysis revealed the need for unplanned perioperative coronary artery bypass grafting as the sole independent risk factor for hospital death (P = .005). Actuarial survival was 83.8% +/- 4.9% at 1 month, 73.0% +/- 6.3% at 1 year, and 65.7% +/- 9.0% at 5 years after the operation. One patient had recurrence of endocarditis 6.7 months after the operation and required repeated homograft aortic root replacement. Reoperative aortic root replacement remains associated with a high postoperative mortality. The need to perform unplanned coronary artery bypass grafting during reoperative aortic root replacement is a major risk factor for hospital death. The optimal technique for coronary reconstruction in this setting remains to be debated.

  10. A patient with ascending aortic dilatation, similar to phenotypes of connective tissue disorders.

    Science.gov (United States)

    Onrat, S T; Emmiler, M; Sivaci, Y; Söylemez, Z; Ozgöz, A; Imirzalioğlu, N

    2009-04-14

    We report on the clinical and molecular findings of a patient who presented alopecia, epicanthus, micrognathia, retrognathia, high arched palate, hypertelorism, Chiari type I malformation, mixed-type hearing loss but with normal heartbeat Q-T interval, malformed earlobes, down-slanted palpebral fissures, downturned corners of the mouth, syndactyly, atopic eczema, and seizures. The patient was a male adult, 23 years old, with short stature (153 cm) and low weight (50.5 kg), due to severe aortic insufficiency and dilatation of the ascending aorta. Conventional cytogenetic screening did not show any chromosomal gains or losses. Molecular genetic screening was conducted for gene mutations involved in various syndromes; the mutations found included [beta-fibrinogen -455 G>A wt/wt (wt/mut), PAI-1 4G/5G (4G/4G), HPA1 a/b (a/a), MTHFR C677T wt/wt (wt/mut), ACE I/D (I/I), and Apo E E3/E4]. Many clinical and molecular genetics findings overlapped with other conditions associated with arterial tortuosity and arterial aneurysms, including the Marfan, Ehler-Danlos, Shprintzen-Goldberg, and Loeys-Dietz syndromes. Although a diagnosis of Shprintzen-Goldberg syndrome was based on clinical findings and radiographic findings indicate other syndromes, aortic root dilatation seems to be a new symptom, similar to phenotypes of connective tissue disorders. The unique grouping of clinical manifestations in this patient and the molecular genetics findings lead us to suggest that this case could be an example of a previously unrecognized syndrome.

  11. Low SWaP Semiconductor Laser Transmitter Modules For ASCENDS Mission Applications

    Science.gov (United States)

    Prasad, Narasimha S.; Rosiewicz, Alex; Coleman, Steven M.

    2012-01-01

    The National Research Council's (NRC) Decadal Survey (DS) of Earth Science and Applications from Space has identified the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) as an important atmospheric science mission. NASA Langley Research Center, working with its partners, is developing fiber laser architecture based intensity modulated CW laser absorption spectrometer for measuring XCO2 in the 1571 nm spectral band. In support of this measurement, remote sensing of O2 in the 1260 nm spectral band for surface pressure measurements is also being developed. In this paper, we will present recent progress made in the development of advanced transmitter modules for CO2 and O2 sensing. Advanced DFB seed laser modules incorporating low-noise variable laser bias current supply and low-noise variable temperature control circuit have been developed. The 1571 nm modules operate at >80 mW and could be tuned continuously over the wavelength range of 1569-1574nm at a rate of 2 pm/mV. Fine tuning was demonstrated by adjusting the laser drive at a rate of 0.7 pm/mV. Heterodyne linewidth measurements have been performed showing linewidth 200 kHz and frequency jitter 75 MHz. In the case of 1260 nm DFB laser modules, we have shown continuous tuning over a range of 1261.4 - 1262.6 nm by changing chip operating temperature and 1261.0 - 1262.0 nm by changing the laser diode drive level. In addition, we have created a new laser package configuration which has been shown to improve the TEC coefficient of performance by a factor of 5 and improved the overall efficiency of the laser module by a factor of 2.

  12. Angiotensin II stimulates basolateral 50-pS K channels in the thick ascending limb.

    Science.gov (United States)

    Wang, Mingxiao; Luan, Haiyan; Wu, Peng; Fan, Lili; Wang, Lijun; Duan, Xinpeng; Zhang, Dandan; Wang, Wen-Hui; Gu, Ruimin

    2014-03-01

    We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.

  13. Computational predictions of damage propagation preceding dissection of ascending thoracic aortic aneurysms.

    Science.gov (United States)

    Mousavi, S Jamaleddin; Farzaneh, Solmaz; Avril, Stéphane

    2018-04-01

    Dissections of ascending thoracic aortic aneurysms (ATAAs) cause significant morbidity and mortality worldwide. They occur when a tear in the intima-media of the aorta permits the penetration of the blood and the subsequent delamination and separation of the wall in 2 layers, forming a false channel. To predict computationally the risk of tear formation, stress analyses should be performed layer-specifically and they should consider internal or residual stresses that exist in the tissue. In the present paper, we propose a novel layer-specific damage model based on the constrained mixture theory, which intrinsically takes into account these internal stresses and can predict appropriately the tear formation. The model is implemented in finite-element commercial software Abaqus coupled with user material subroutine. Its capability is tested by applying it to the simulation of different exemplary situations, going from in vitro bulge inflation experiments on aortic samples to in vivo overpressurizing of patient-specific ATAAs. The simulations reveal that damage correctly starts from the intimal layer (luminal side) and propagates across the media as a tear but never hits the adventitia. This scenario is typically the first stage of development of an acute dissection, which is predicted for pressures of about 2.5 times the diastolic pressure by the model after calibrating the parameters against experimental data performed on collected ATAA samples. Further validations on a larger cohort of patients should hopefully confirm the potential of the model in predicting patient-specific damage evolution and possible risk of dissection during aneurysm growth for clinical applications. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

    Science.gov (United States)

    García-Herrera, Claudio M; Celentano, Diego J; Herrera, Emilio A

    2017-03-01

    Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

  15. Comparative study of measured heart cycle phase durations: standard lead ECG versus original ascending aorta lead ECG

    Directory of Open Access Journals (Sweden)

    Sergey V. Kolmakov

    2012-11-01

    Full Text Available Aims The present paper aims at evaluating the existing difference in duration measurements of the same heart cycle phases in the standard V3, V4, V5, V6 leads ECG versus original HDA lead ECG of the ascending aorta. Materials and methods The method of changing the filter pass band is used. Its essence is in artificial changing of the conditions of the signal recording carrying the informative indications of the initial information used in hemodynamic equations. The method also enables calculating the percentage deviation from the initial values. The principle of balance of the blood volume entering the heart and the blood volume leaving the heart is used to trace the minimal deviations and their respective recording conditions. Results In each of the V3, V4, V5, V6 ECG leads durations of the same phases have different values. The values measured on the ECG of the ascending aorta and those measured using the standard V4 ECG lead differ slightly. Conclusion For heart cycle phase analysis it is possible to use only the ECG of the ascending aorta and V4 standard lead ECG. Using conventional standard ECG leads causes an error up to 25%.

  16. Coil embolization of a false aneurysm with aorto-cutaneous fistula after prosthetic graft replacement of the ascending aorta

    International Nuclear Information System (INIS)

    Miguel, Bruno; Camilleri, Lionel; Gabrillargues, Jean; Macheda, Bruno; Kubota, Hiroshi; Ravel, Anne; Riberolles, Charles de; Boyer, Louis

    2000-01-01

    Aim: To report palliative embolization of a false aneurysm over the distal suture line of an ascending aorta graft replacement. Material and Method: A 78-year-old male patient was admitted for increasing bleeding of a chronic Manubrium ulceration, 20 months after coronary artery bypass complicated by perioperative ascending aorta dissection requiring prosthetic graft replacement. One month later, he underwent epiploplasty for a mediastinitis followed by long-term antibiotic therapy. Five months later, he presented with a Manubrium ulceration of the sternotomy. Spiral computerized tomography (CT) and aortography revealed a 20 mm anterior peri-prosthetic false aneurysm with a wide neck. Advanced age, active mediastinitis and patient's objection led us to perform percutaneous occlusion according to the Moret remodeling technique while protecting the coils release with balloon catheter inflation. Results: No post-operative complication was observed and at 1-year follow-up the patient was doing well with no recurrent bleeding. Magnetic resonance imaging (MRI) and spiral CT controls confirmed coils stability without any internal flow. Conclusion: Percutaneous coils embolization of a large false aneurysm in the ascending aorta can be a palliative treatment in a surgically unsuited patient

  17. Clinical application of AcMAR (accelerated multiple-arc radiotherapy) for head and neck tumors. Results of a randomized, two-dose study in Kitami Red-Cross General Hospital

    International Nuclear Information System (INIS)

    Arimoto, Takuro; Yamazaki, Akira; Yonesaka, Akio; Matsuzawa, Tooru; Kanai, Naoki

    2003-01-01

    Enhanced acute mucositis is the limiting factor for accelerated, hyperfractionated radiotherapy in head and neck (H and N) squamous cell carcinomas (SCCs). We have developed a simple, new form of conformal radiotherapy, accelerated multiple arc radiotherapy (AcMAR), which covers the target volume by combined, segmental, and rotational arc fields. Two to three rotational fields were placed with CT guidance, each covering the primary tumor and lymph nodes separately. The optimal inter-isocenter distance was determined by 3D dose calculation. The surface area of oro-pharyngeal mucosa irradiated by more than a 50% dose by this method was reduced by 37-73% compared to that with a conventional parallel opposing technic. Dose searching, randomized two-dose study was initiated in Kitami Red-cross General Hospital (KRCGH) in January 1995, and 101 patients were registered and completed AcMAR in Oct 2000. All the patients were followed for up to 96 months (24-96 mo, median 48 mo) at the time of analysis. Fifty-one out of 101 patients were Stage III (17) and IV (34). Primary site of tumors were; 38 larynx, 25 oropharynx, 15 hypopharynx, 13 oral cavity, and 10 other miscellaneous sites. Patients were randomly allocated either to 60 Gy/24 fr/bid/3 wks to gross tumor volume (GTV) (Group A), or 66 Gy/33 fr/bid/4 wks to GTV (Group B). Forty Gy/16 fr/bid/2 wks was given to the volume of prophylactic'' irradiation in both groups of patients. Results were as follows: All the patients, except for one, completed AcMAR without treatment interruption. Acute mucositis at the site of high-dose irradiation was intense; 72% of Group A and 62.5% of Group B experienced World Health Organization (WHO) Grade 3 (confluent) mucositis focally. Fifty-one out of 53 in Group A and 48/48 in Group B, however, could maintain oral food intake (WHO Grade 1 or 2) even at the peak of their mucositis, because of the limited area of severe mucositis. With regard to late morbidity, however, 6/46 (followed >24 mo

  18. A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

    Science.gov (United States)

    Nath, Sayantan; Ghosh, Sankar Kumar; Choudhury, Yashmin

    A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg -1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg -1 bw daily) and metformin (50mgkg -1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy.

    Science.gov (United States)

    Talamo, Giampaolo; Angtuaco, Edgardo; Walker, Ronald C; Dong, Li; Miceli, Marisa H; Zangari, Maurizio; Tricot, Guido; Barlogie, Bart; Anaissie, Elias

    2005-08-01

    To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

  20. TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

    Science.gov (United States)

    Garvin, Jeffrey L.

    2014-01-01

    Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min (n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min (P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min (P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min (P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min (P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL. PMID:24966090

  1. Dose limits

    International Nuclear Information System (INIS)

    Fitoussi, L.

    1987-12-01

    The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

  2. Pulsed Lidar Measurements of Atmospheric CO2 Column Absorption and Range During the ASCENDS 2009-2011 Airborne Campaigns

    Science.gov (United States)

    Abshire, J. B.; Weaver, C. J.; Riris, H.; Mao, J.; Sun, X.; Allan, G. R.; Hasselbrack, W. E.; Browell, E. V.

    2012-01-01

    We have developed a pulsed lidar technique for measuring the tropospheric CO2 concentrations as a candidate for NASA's ASCENDS mission and have demonstrated the CO2 and O2 measurements from aircraft. Our technique uses two pulsed lasers allowing simultaneous measurement of a single CO2 absorption line near 1572 nm, O2 extinction in the Oxygen A-band, surface height and backscatter profile. The lasers are stepped in wavelength across the CO2 line and an O2 line doublet during the measurement. The column densities for the CO2 and O2 are estimated from the differential optical depths (DOD) of the scanned absorption lines via the IPDA technique. For the 2009 ASCENDS campaign we flew the CO2 lidar only on a Lear-25 aircraft, and measured the absorption line shapes of the CO2 line using 20 wavelength samples per scan. Measurements were made at stepped altitudes from 3 to 12.6 km over the Lamont OK, central Illinois, North Carolina, and over the Virginia Eastern Shore. Although the received signal energies were weaker than expected for ASCENDS, clear C02 line shapes were observed at all altitudes. Most flights had 5-6 altitude steps with 200-300 seconds of recorded measurements per step. We averaged every 10 seconds of measurements and used a cross-correlation approach to estimate the range to the scattering surface and the echo pulse energy at each wavelength. We then solved for the best-fit CO2 absorption line shape, and calculated the DOD of the fitted CO2 line, and computed its statistics at the various altitude steps. We compared them to CO2 optical depths calculated from spectroscopy based on HITRAN 2008 and the column number densities calculated from the airborne in-situ readings. The 2009 measurements have been analyzed in detail and they were similar on all flights. The results show clear CO2 line shape and absorption signals, which follow the expected changes with aircraft altitude from 3 to 13 km. They showed the expected nearly the linear dependence of DOD vs

  3. Dilatation of the ascending aorta is associated with presence of aortic regurgitation in patients after repair of tetralogy of Fallot

    Science.gov (United States)

    Ordovas, Karen Gomes; Keedy, Alexander; Naeger, David M.; Kallianos, Kimberly; Foster, Elyse; Liu, Jing; Saloner, David; Hope, Michael D.

    2016-01-01

    To evaluate the association between aortic morphology and elasticity with aortic regurgitation in surgically corrected of tetralogy of Fallot (TOF) patients. We retrospectively identified 72 consecutive patients with surgically corrected TOF and 27 healthy controls who underwent cardiac MRI evaluation. Velocity-encoded cine MRI was used to quantify degree of aortic regurgitation (AR) in TOF patients. Ascending aorta diameters were measured at standard levels on MRA images. Aortic pulse-wave velocity (PWV) was quantified with MRI. Morphological and functional MRI variables were compared between groups of TOF patients with and without clinically relevant AR and controls. The association between aortic morphology and elasticity with the presence of AR was evaluated using univariate and multivariate logistic regression. The majority of TOF patients had only trace AR. Nine TOF patients (12 %) had an AR fraction higher than 15 %. Indexed aorta diameter at the sinotubular junction (p = 0.007), at the RPA level (p = 0.006), and low left ventricular ejection fraction (LVEF) (p = 0.015) showed the strongest associations with the presence of at least mild AR, which persisted after controlling for age and gender. Increased ascending aorta dimension is associated with AR in patients after repair of TOF. LVEF was also low in the group of patients with relevant AR compared to those without, suggesting even mild to moderate AR may contribute to LV dysfunction in these patients. Enlarged ascending aorta may be an indication for precise quantification of regurgitant fraction with MRI, since symptomatic patients may need aortic valve repair when moderate regurgitation is present. PMID:27240599

  4. Interactions Between Epinephrine, Ascending Vagal Fibers and Central Noradrenergic Systems in Modulating Memory for Emotionally Arousing Events.

    Directory of Open Access Journals (Sweden)

    Cedric L. Williams

    2012-06-01

    Full Text Available It is well established that exposure to emotionally laden events initiates secretion of the arousal related hormone epinephrine in the periphery. These neuroendocrine changes and the subsequent increase in peripheral physiological output play an integral role in modulating brain systems involved in memory formation. The impermeability of the blood brain barrier to epinephrine represents an important obstacle in understanding how peripheral hormones initiate neurochemical changes in the brain that lead to effective memory formation. This obstacle necessitated the identity of a putative pathway capable of conveying physiological changes produced by epinephrine to limbic structures that incorporate arousal and affect related information into memory. A major theme of the proposed studies is that ascending fibers of the vagus nerve may represent such a mechanism. This hypothesis was tested by evaluating the contribution of ascending vagal fibers in modulating memory for responses learned under behavioral conditions that produce emotional arousal by manipulating appetitive stimuli. A combination of electrophysiological recording of vagal afferent fibers and in vivo microdialysis was employed in a second study to simultaneously assess how elevations in peripheral levels of epinephrine affect vagal nerve discharge and the subsequent potentiation of norepinephrine release in the basolateral amygdala. The final study used double immunohistochemistry labeling of c-fos and dopamine beta hydroxylase, the enzyme for norepinephrine synthesis to determine if epinephrine administration alone or stimulation of the vagus nerve at an intensity identical to that which improved memory in Experiment 1 produces similar patterns of neuronal activity in brain areas involved in processing memory for emotional events. Findings emerging from this collection of studies establish the importance of ascending fibers of the vagus nerve as an essential pathway for conveying the

  5. A resected case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage

    Directory of Open Access Journals (Sweden)

    Masaki Wakasugi

    Full Text Available Introduction: Medullary carcinoma is a rare type of colorectal adenocarcinoma, and omental infarction is a rare cause of acute abdomen. Presentation of case: A 72-year-old woman underwent single-incision laparoscopic right hemicolectomy for ascending colon cancer. Pathological examination showed a medullary carcinoma (MC of T4aN0M0 Stage IIB. Her postoperative course was uneventful, and she was discharged on postoperative day (POD 6. From POD 7, she suffered from fever, and she returned to the hospital on POD 9. Plain computed tomography showed free air beside the anastomotic site around the elevated density of fat tissue and gallbladder wall thickening with a gallstone. Suspecting anastomotic leakage with acute cholecystitis, probe laparotomy was performed. Intraoperative observation confirmed omental infarction with acute cholecystitis, and no leakage was found at the anastomotic site. Therefore, the necrotic part of the greater omentum was resected, and cholecystectomy was performed. She has remained well, with no evidence of recurrent cancer during the 12 months of follow-up without chemotherapy after the surgery for MC of the ascending colon. Discussion: MC should be distinguished from other more aggressive, non-glandular tumors of the colon because MC appears to have a better survival outcome than undifferentiated colon adenocarcinoma. Omental infarction should be considered in the differential diagnosis of acute abdomen after surgery. Conclusion: A rare case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage is presented. Keywords: Medullary carcinoma, Colon cancer, Omental infarction, Omental torsion

  6. Computed tomography (CT) of acute diverticulitis of the cecum and ascending colon; Computertomographie bei akuter rechtsseitiger Kolondivertikulitis

    Energy Technology Data Exchange (ETDEWEB)

    Ferstl, F.J.; Obert, R. [St. Theresienkrankenhaus Nuernberg (DE). Radiologisch-Nuklearmedizinisches Zentrum (RNZ)

    2004-09-01

    Acute diverticulitis of the cecum and ascending colon, also called right-sided diverticulitis, represents a relatively rare disorder in the western hemisphere. Pseudodiverticula and, less frequently, solitary congenital diverticula are regarded as the underlying causes of acute diverticulitis. We report the helical CT findings in four patients with acute right-sided colonic diverticulitis. The CT was performed with a collimation of 8 mm, a pitch of 1.5 and an increment of 8 mm, and with variable administration of intravenous, oral and rectal contrast material. In two of the four patients, the acute diverticulitis was detected in the cecum and ascending colon, respectively. In two patients, the diagnosis could be confirmed during surgery and subsequent histologic examination of the resected specimen. On the initial CT studies, acute diverticulitis was correctly diagnosed in two patients and suspected in one patient without identifying and inflamed diverticulum. In one patient, the offending diverticulum in the ascending colon caused an inflammatory pseudotumor at the level of the ileocecal region. This process was initially mistaken as Crohn's disease. The CT diagnosis of a right-sided colonic diverticulitis is based on an inflamed diverticulum in the center of pericolic inflammatory changes and a preserved wall enhancement (target sign). Other CT findings, such as fatty pericolic infiltration and colon wall thickening, are rather non-specific and can also be found in a number of different ileocolic disorders, especially in colon cancer. In selected cases, the diagnosis can only be established by follow up CT after the pericolic infiltration has markedly subsided and an offending diverticulum has emerged. (orig.)

  7. MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms

    Science.gov (United States)

    Tscheuschler, Anke; Meffert, Philipp; Beyersdorf, Friedhelm; Heilmann, Claudia; Kocher, Nadja; Uffelmann, Xenia; Discher, Philipp; Siepe, Matthias; Kari, Fabian A.

    2016-01-01

    Objective The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress. Methods Serum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair. Results Pro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue—and serum MMP-2

  8. Double versus single high-dose melphalan 200 mg/m2 and autologous stem cell transplantation for multiple myeloma: a region-based study in 484 patients from the Nordic area

    Science.gov (United States)

    Björkstrand, Bo; Klausen, Tobias W.; Remes, Kari; Gruber, Astrid; Knudsen, Lene M.; Bergmann, Olav J.; Lenhoff, Stig; Johnsen, Hans E.

    2009-01-01

    Autologous stem cell transplantation is still considered the standard of care in young patients with multiple myeloma (MM). This disease is the most common indication for high-dose therapy (HDT) supported by hematopoietic stem cell transplantation and much data support the benefit of this procedure. Results of randomized studies are in favor of tandem autologous transplantation although the effect on overall survival is unclear. Based on sequential registration trials in the Nordic area, we aimed to evaluate the outcome of conventional single or double HDT. During 1994–2000 we registered a total of 484 previously untreated patients under the age of 60 years at diagnosis who on a regional basis initially were treated with single [Trial NMSG #5/94 and #7/98 (N=383)] or double [Trial Huddinge Karolinska Turku Herlev (N=101)] high-dose melphalan (200 mg/m2) therapy supported by autologous stem cell transplantation. A complete or very good partial response was achieved by 40% of patients in the single transplant group and 60% of patients in the double transplant group (p=0.0006). The probability of surviving progression free for five years after the diagnosis was 25% (95% CL 18–32%) in the singletransplant group and 46% (95% CL 33–55%) in the double transplant group (p=0.0014). The estimated overall five-year survival rate was 60% in the single transplant group and 64% in the doubletransplant (p=0.9). In a multivariate analysis of variables, including single versus double transplantation, β2 microglobulin level, age, sex and disease stage, only β2 microglobulin level was predictive for overall survival (p>0.0001) and progression free survival (p=0.001). In accordance with these results, a 1:1 case-control matched comparison between double and single transplantation did not identify significant differences in overall and progression free survival. In this retrospective analysis up front double transplantation with melphalan (200 mg/m2) as compared to single

  9. Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography.

    Science.gov (United States)

    Caro-Domínguez, Pablo; Compton, Gregory; Humpl, Tilman; Manson, David E

    2016-09-01

    The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT-measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children.

  10. Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography

    International Nuclear Information System (INIS)

    Caro-Dominguez, Pablo; Manson, David E.; Compton, Gregory; Humpl, Tilman

    2016-01-01

    The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT-measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children. (orig.)

  11. Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Caro-Dominguez, Pablo; Manson, David E. [University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, Toronto, ON (Canada); Compton, Gregory [University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, Toronto, ON (Canada); Epworth Hospital, Epworth Medical Imaging, Richmond, VIC (Australia); Humpl, Tilman [University of Toronto, Division of Cardiology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON (Canada)

    2016-09-15

    The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT-measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children. (orig.)

  12. Controllable dose

    International Nuclear Information System (INIS)

    Alvarez R, J.T.; Anaya M, R.A.

    2004-01-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  13. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial.

    Science.gov (United States)

    Chan, Dennis; Binks, Sophie; Nicholas, Jennifer M; Frost, Chris; Cardoso, M Jorge; Ourselin, Sebastien; Wilkie, David; Nicholas, Richard; Chataway, Jeremy

    2017-08-01

    In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348. Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6-7·8; pmultiple sclerosis treatment trials. The Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a

  14. Elevated serum alpha-fetoprotein in poorly differentiated adenocarcinoma with neuroendocrine differentiation of the ascending colon: a case report.

    Science.gov (United States)

    Lin, Hung-Hsin; Chang, Chia-Chu; Yang, Shung-Haur; Chang, Shih-Ching; Chen, Wei-Shone; Liang, Wen-Yih; Lin, Jen-Kou; Jiang, Jeng-Kai

    2016-03-15

    Colorectal cancer (CRC) is the most common form of cancer and the third leading cause of death in Taiwan. Serum alpha-fetoprotein (AFP) has been extensively used as a biomarker for hepatocellular carcinoma (HCC) and yolk sac tumors. This case report presents a 90-year-old woman with right abdominal pain and poor appetite for 1 week. The computed tomography (CT) showed wall thickening in the proximal ascending colon with ruptured appendicitis. Preoperative serum AFP was high. There was no definite liver metastasis or other abnormal findings in the hepatobiliary systems. After initial empirical antibiotic treatment, we performed laparoscopic right hemicolectomy. The pathological assessment was poorly differentiated adenocarcinoma with neuroendocrine differentiation in the ascending colon. The tumor cells did not produce AFP. Amazingly, the follow-up serum AFP level 1 month after the surgery declined to normal range. The patient had an uneventful course after the surgery and was free of recurrence or metastasis within 5 months of follow-up. AFP may be a useful tumor marker in poorly differentiated colorectal cancer with neuroendocrine component patients and a prediction of early treatment response.

  15. Towards the evaluation of the pathological state of ascending thoracic aneurysms: integration of in-vivo measurements and hemodynamic simulations

    Science.gov (United States)

    Boccadifuoco, Alessandro; Mariotti, Alessandro; Celi, Simona; Martini, Nicola; Salvetti, Maria Vittoria

    2016-11-01

    Ascending thoracic aortic aneurysms are cardiovascular diseases consisting in a dilation of the ascending thoracic aorta. Since indicating a weakness of the arterial wall, they can lead to major complications with significant mortality rate. Clinical decisions about surgery are currently based on the maximum aortic diameter, but this single index does not seem a reliable indicator of the pathological state of the aorta. Numerical simulations of the blood flow inside the aneurysm may give supplementary information by quantifying important indices that are difficult to be measured, like the wall shear stress. Our aim is to develop an efficient platform in which in-vivo measurements are used to perform the hemodynamic simulations on a patient-specific basis. In particular, we used real geometries of thoracic aorta and focused on the use of clinical information to impose accurate boundary conditions at the inlet/outlets of the computational model. Stochastic analysis was also performed, to evaluate how uncertainties in the boundary parameters affect the main hemodynamic indicators, by considering both rigid and deformable walls. Stochastic calibration of numerical parameters against clinical data is in progress and results will be possibly shown.

  16. Elevation of Matrix Metalloproteinases in Different Areas of Ascending Aortic Aneurysms in Patients with Bicuspid and Tricuspid Aortic Valves

    Directory of Open Access Journals (Sweden)

    Salah A. Mohamed

    2012-01-01

    Full Text Available Our aim is to investigate the elevation of matrix proteins in tissues obtained from distal, above the sinotubular junction (proximal, concave, and convex sites of aneurysms in the ascending aorta using a simultaneous multiplex protein detection system. Tissues were collected from 41 patients with ascending aortic aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV, whereas 10 had a tricuspid aortic valve (TAV. Concave and convex aortic site samples were collected from all patients, whereas proximal and distal convexity samples were obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous detection of matrix metalloproteinases (MMPs and their inhibitors (TIMPs was performed at each of the four aortic sites. MMP-2 levels were higher in the concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels were higher in the convex sites than in the concave sites, as were MMP-9 levels. In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly elevated in the sinotubular proximal aorta of BAV patients. Simultaneous detection of MMPs and TIMPs revealed different levels at different aortic sites in the same patient.

  17. Return to learn: Transitioning to school and through ascending levels of academic support for students following a concussion.

    Science.gov (United States)

    McAvoy, Karen; Eagan-Johnson, Brenda; Halstead, Mark

    2018-01-01

    The purpose of this article is to familiarize healthcare providers and parents with educational language, laws, and processes as they relate to a comprehensive ascending level of academic supports as it pertains to promoting a smooth and supported transition to school following a concussion. Returning to learn (RTL) following a concussion is of parallel importance to returning to sport (RTS). A successful RTL is a critical part of concussion management. Many RTL articles advise healthcare providers and parents to request formalized educational supports, also known as Tier 2 or Tier 3 services, for children with concussion as they return to school. Premature requests for formal (Tier 2 or 3) educational services, rather than allowing for immediate informal educational supports (known as Tier 1), can actually delay academic supports and have the potential to cause adversarial relationships between parents and schools. Additionally, this practice contradicts current research demonstrating the need for fast, flexible, temporary academic supports within the first month post-injury. Allowing school districts to direct the application of existing ascending levels of educational support for students with concussion as they return to school can promote robust and positive outcomes.

  18. Computational modeling of blood flow in the aorta--insights into eccentric dilatation of the ascending aorta after surgery for coarctation.

    Science.gov (United States)

    Szopos, Marcela; Poussineau, Nicole; Maday, Yvon; Canniffe, Carla; Celermajer, David S; Bonnet, Damien; Ou, Phalla

    2014-10-01

    To assess whether combining a computational modeling technique with data from patient magnetic resonance imaging studies can detect different fluid dynamics and vascular biomechanical properties of the ascending and horizontal aorta in patients with angulated "gothic" arch geometry compared with those with normal "Romanesque" arch geometry after aortic coarctation repair. Advanced computational fluid dynamics techniques (coupled Navier-Stokes and elastodynamics equations) were used to predict the fluid-wall interactions in large arteries. We modeled the fluid dynamics and shear stress in the ascending and horizontal aorta in cases of "gothic" arch and normal "Romanesque" aortic arch geometry. A total of 30 patients after aortic coarctation repair prospectively underwent 3-dimensional magnetic resonance imaging angiography of the thoracic aorta. Measurements of the ascending and horizontal aorta were assessed using multiplanar reformatting images. Our computational model demonstrated that wall shear stress is greater in those with an angulated "gothic" aortic arch than in those with a "Romanesque" arch. In particular, wall shear stress affected the anterior and posterior segments of the ascending aorta and the inferior and superior segments of the horizontal aorta (vs the left and right segments). In vivo, a "gothic" arch was associated with dilatation of the ascending and horizontal aorta, which was eccentric rather than concentric (Pgothic" aortic arch after repair of coarctation. This suggests that patients with an angulated "gothic" aortic arch might warrant increased surveillance for aortic complications. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Angiotensin II-induced hypertension blunts thick ascending limb NO production by reducing NO synthase 3 expression and enhancing threonine 495 phosphorylation.

    Science.gov (United States)

    Ramseyer, Vanesa D; Gonzalez-Vicente, Agustin; Carretero, Oscar A; Garvin, Jeffrey L

    2015-01-15

    Thick ascending limbs reabsorb 30% of the filtered NaCl load. Nitric oxide (NO) produced by NO synthase 3 (NOS3) inhibits NaCl transport by this segment. In contrast, chronic angiotensin II (ANG II) infusion increases net thick ascending limb transport. NOS3 activity is regulated by changes in expression and phosphorylation at threonine 495 (T495) and serine 1177 (S1177), inhibitory and stimulatory sites, respectively. We hypothesized that NO production by thick ascending limbs is impaired by chronic ANG II infusion, due to reduced NOS3 expression, increased phosphorylation of T495, and decreased phosphorylation of S1177. Rats were infused with 200 ng·kg(-1)·min(-1) ANG II or vehicle for 1 and 5 days. ANG II infusion for 5 days decreased NOS3 expression by 40 ± 12% (P thick ascending limbs from ANG II-infused animals [ANG II -0.01 ± 0.06 arbitrary fluorescence units (AFU)/min vs. 0.17 ± 0.02 AFU/min in controls; P thick ascending limbs is impaired due to decreased NOS3 expression and altered phosphorylation. Copyright © 2015 the American Physiological Society.

  20. Autologous platelet-rich plasma reduces transfusions during ascending aortic arch repair: a prospective, randomized, controlled trial.

    Science.gov (United States)

    Zhou, Shao Feng; Estrera, Anthony L; Loubser, Paul; Ignacio, Craig; Panthayi, Sreelatha; Miller, Charles; Sheinbaum, Roy; Safi, Hazim J

    2015-04-01

    Blood conservation using autologous platelet-rich plasma (aPRP), a technique of whole blood harvest that separates red blood cells from plasma and platelets before cardiopulmonary bypass with retransfusion of the preserved platelets after completion of cardiopulmonary bypass, has not been studied extensively. We sought to prospectively determine whether aPRP reduces blood transfusions during ascending and transverse aortic arch repair. We randomly assigned 80 patients undergoing elective ascending and transverse aortic arch repair using deep hypothermic circulatory arrest to receive either aPRP (n = 38) or no aPRP (n = 42). Volume of aPRP retransfused was 726 ± 124 mL. The primary end point was transfusion amount. Secondary end points were death, stroke, renal failure, pulmonary failure, and transfusion costs. Perioperative transfusion rate was defined as blood transfusions given during surgery and up to 72 hours afterward. The surgeon and intensivist were blinded to the treatment arm. Because an anesthesiologist initiated the protocol, the surgeon was not aware of aPRP collection, as this occurred only after the sterile drape was in place. In addition, because cell salvage was performed on all cases, differentiation in perfusionist activities (during spinning of aPRP) was not evident. Platelet, fresh frozen plasma, and cryoprecipitate intraoperative transfusions were performed only after heparin was reversed and the patient was judged as coagulopathic on the basis of associated criteria: cryoprecipitate transfusion for fibrinogen level less than 150 μg/dL, platelet transfusion for platelet count less than 80,000, and fresh frozen plasma when thromboelastogram test was suggestive or a partial thromboplastin time was greater than 55 seconds, and prothrombin time was greater than 1.6 seconds. Early mortality, stroke, and respiratory complications were similar between groups. Only acute renal failure was reduced in the aPRP group, 7% versus 0% (p platelets by 56

  1. Modified conduit preparation creates a pseudosinus in an aortic valve-sparing procedure for aneurysm of the ascending aorta.

    Science.gov (United States)

    Cochran, R P; Kunzelman, K S; Eddy, A C; Hofer, B O; Verrier, E D

    1995-06-01

    Mechanical valved conduit replacement of the aortic root is a durable and appropriate procedure for many diseases of the ascending aorta, but may sacrifice an anatomically salvageable aortic valve. For young active patients and for patients with "systemic" arterial disease (atherosclerosis, Marfan's syndrome) who may require future operations, life-long anticoagulation with its attendant thromboembolic versus hemorrhagic risks is not ideal. Several techniques have been suggested as aortic valve-sparing options. Recently, a procedure was described that combines the freehand homograft techniques with the standard Bentall techniques (David procedure). This innovative technique replaces the ascending aorta with a Dacron cylinder, spares the aortic valve, and restores competence and thus offers an excellent alternative. The durability of this procedure that places the aortic valve inside a cylindrical conduit without sinuses of Valsalva is unknown. In selected patients, we have used this technique to spare the aortic valve. On the basis of experimental data and preliminary computer modeling, with the hope of improving the durability, we have modified the conduit to create a "pseudosinus" in our most recent nine patients. We have done the David procedure in 10 patients. The pseudosinus modification was done in the most recent nine patients. Patients' ages ranged from 37 to 71 years (mean 49.9 years). There were five female and five male patients. Five patients had Marfan's syndrome and five patients had annuloaortic ectasia. There has been no mortality and all patients have had both early and late follow-up echocardiography. Five patients have zero to trace aortic insufficiency, four patients have trace to mild aortic insufficiency, and one patient has mild or "1+" aortic insufficiency. Aortic insufficiency has not progressed in any patient during the 18 months of follow-up. The patient with 1+ aortic insufficiency has no activity limits, good ventricular function, and

  2. Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994-2004

    DEFF Research Database (Denmark)

    Vangsted, Annette Juul; Klausen, Tobias W; Andersen, Niels F

    2010-01-01

    To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting.......To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting....

  3. Maduración sexual en niños con diabetes mellitus tipo 1 tratados con dosis múltiples de insulina Sexual maturation in children presenting with Type 1 diabetes mellitus treated with multiple dose of insulin.

    Directory of Open Access Journals (Sweden)

    Tania Espinosa Reyes

    2007-04-01

    Infantile Endocrinlogy. A non-concurrent prospective study of medical records of patients treated withmultiple dose of insulin, from 32 boys and 28 girls resident in urban areas lenghwise followed by clinical examinatio and periodic biochemical determinarions fron onset of 1 MD to achieve its final height. Metabolic control was assessed by means of glycolised hemoglobin (HbA1 performed quarterly, and classified by Institution criteria as good (G; 10 %. Mean age with a testicular volume of 4 mL was of 12,5 ? 8 years; in girls onset of breast development contrasted with average age of 11,4 years, and menarche occured at 12,9 ? 1,2 years. Also, it was confirmed that 31 patients have a B metabolic control (51,6 %, 11 R (36,7 %, and 7 M (11,7 %. It was conclude that treatment with multiple dose of insulin has a favourable end decisive influence on degree of metabolic control, whith allows a appropriate pubertal development in patients presenting 1 MD.

  4. Ascending-ramp biphasic waveform has a lower defibrillation threshold and releases less troponin I than a truncated exponential biphasic waveform.

    Science.gov (United States)

    Huang, Jian; Walcott, Gregory P; Ruse, Richard B; Bohanan, Scott J; Killingsworth, Cheryl R; Ideker, Raymond E

    2012-09-11

    We tested the hypothesis that the shape of the shock waveform affects not only the defibrillation threshold but also the amount of cardiac damage. Defibrillation thresholds were determined for 11 waveforms-3 ascending-ramp waveforms, 3 descending-ramp waveforms, 3 rectilinear first-phase biphasic waveforms, a Gurvich waveform, and a truncated exponential biphasic waveform-in 6 pigs with electrodes in the right ventricular apex and superior vena cava. The ascending, descending, and rectilinear waveforms had 4-, 8-, and 16-millisecond first phases and a 3.5-millisecond rectilinear second phase that was half the voltage of the first phase. The exponential biphasic waveform had a 60% first-phase and a 50% second-phase tilt. In a second study, we attempted to defibrillate after 10 seconds of ventricular fibrillation with a single ≈30-J shock (6 pigs successfully defibrillated with 8-millisecond ascending, 8-millisecond rectilinear, and truncated exponential biphasic waveforms). Troponin I blood levels were determined before and 2 to 10 hours after the shock. The lowest-energy defibrillation threshold was for the 8-milliseconds ascending ramp (14.6±7.3 J [mean±SD]), which was significantly less than for the truncated exponential (19.6±6.3 J). Six hours after shock, troponin I was significantly less for the ascending-ramp waveform (0.80±0.54 ng/mL) than for the truncated exponential (1.92±0.47 ng/mL) or the rectilinear waveform (1.17±0.45 ng/mL). The ascending ramp has a significantly lower defibrillation threshold and at ≈30 J causes 58% less troponin I release than the truncated exponential biphasic shock. Therefore, the shock waveform affects both the defibrillation threshold and the amount of cardiac damage.

  5. Traditional Cardiovascular Risk Factors and Their Relation to Future Surgery for Valvular Heart Disease or Ascending Aortic Disease: A Case-Referent Study.

    Science.gov (United States)

    Ljungberg, Johan; Johansson, Bengt; Engström, Karl Gunnar; Albertsson, Elin; Holmer, Paul; Norberg, Margareta; Bergdahl, Ingvar A; Söderberg, Stefan

    2017-05-05

    Risk factors for developing heart valve and ascending aortic disease are based mainly on retrospective data. To elucidate these factors in a prospective manner, we have performed a nested case-referent study using data from large, population-based surveys. A total of 777 patients operated for heart valve disease or disease of the ascending aorta had previously participated in population-based health surveys in Northern Sweden. Median time (interquartile range) from survey to surgery was 10.5 (9.0) years. Primary indications for surgery were aortic stenosis (41%), aortic regurgitation (12%), mitral regurgitation (23%), and dilatation/dissection of the ascending aorta (17%). For each case, referents were allocated, matched for age, sex, and geographical area. In multivariable models, surgery for aortic stenosis was predicted by hypertension, high cholesterol levels, diabetes mellitus, and active smoking. Surgery for aortic regurgitation was associated with a low cholesterol level, whereas a high cholesterol level predicted surgery for mitral regurgitation. Hypertension, blood pressure, and previous smoking predicted surgery for disease of the ascending aorta whereas diabetes mellitus was associated with reduced risk. After exclusion of cases with coronary atherosclerosis, only the inverse associations between cholesterol and aortic regurgitation and between diabetes mellitus and disease of the ascending aorta remained. This is the first truly prospective study of traditional cardiovascular risk factors and their association with valvular heart disease and disease of the ascending aorta. We confirm the strong association between traditional risk factors and aortic stenosis, but only in patients with concomitant coronary artery disease. In isolated valvular heart disease, the impact of traditional risk factors is varying. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial.

    Science.gov (United States)

    Schmitt, Thomas; Goldschmidt, Hartmut; Neben, Kai; Freiberger, Anja; Hüsing, Johannes; Gronkowski, Martina; Thalheimer, Markus; Pelzl, Le Hang; Mikus, Gerd; Burhenne, Jürgen; Ho, Anthony D; Egerer, Gerlinde

    2014-10-20

    The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial. Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m(2) was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index-Emesis (FLIE) questionnaire on days -1 and 6. Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001). The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life. © 2014 by American Society of Clinical Oncology.

  7. Dose and dose rate monitor

    International Nuclear Information System (INIS)

    Novakova, O.; Ryba, J.; Slezak, V.; Svobodova, B.; Viererbl, L.

    1984-10-01

    The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137 Cs, 241 Am and 109 Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10 -2 to 10 3 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

  8. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Keirstead Hans S

    2007-09-01

    Full Text Available Abstract Background Chronic spinal cord injury (SCI can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4, 28 (n = 4, 120 (n = 4, 450 (n = 5, or 540 (n = 5 days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures. Results Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil. Conclusion Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of

  9. Chlamydial variants differ in ability to ascend the genital tract in the guinea pig model of chlamydial genital infection.

    Science.gov (United States)

    Yeruva, Laxmi; Bowlin, Anne K; Spencer, Nicole; Maurelli, Anthony T; Rank, Roger G

    2015-08-01

    An important question in the study of chlamydial genital tract disease is why some women develop severe upper tract disease while others have mild or even "silent" infections with or without pathology. Animal studies suggest that the pathological outcome of an infection is dependent upon both the composition of the infecting chlamydial population and the genotype of the host, along with host physiological effects, such as the cyclical production of reproductive hormones and even the size of the infecting inoculum or the number of repeated infections. In this study, we compared two variants of Chlamydia caviae, contrasting in virulence, with respect to their abilities to ascend the guinea pig genital tract. We then determined the effect of combining the two variants on the course of infection and on the bacterial loads of the two variants in the genital tract. Although the variants individually had similar infection kinetics in the cervix, SP6, the virulent variant, could be isolated from the oviducts more often and in greater numbers than the attenuated variant, AZ2. SP6 also elicited higher levels of interleukin 8 (IL-8) in the lower genital tract and increased leukocyte infiltration in the cervix and uterus compared to AZ2. When the two variants were combined in a mixed infection, SP6 outcompeted AZ2 in the lower genital tract; however, AZ2 was able to ascend the genital tract as readily as SP6. These data suggest that the ability of SP6 to elicit an inflammatory response in the lower genital tract facilitates the spread of both variants to the oviducts. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the COFRASA/GENERAC study.

    Science.gov (United States)

    Kerneis, Caroline; Pasi, Nicoletta; Arangalage, Dimitri; Nguyen, Virginia; Mathieu, Tiffany; Verdonk, Constance; Codogno, Isabelle; Ou, Phalla; Duval, Xavier; Tubiana, Sarah; Cimadevilla, Claire; Vahanian, Alec; Messika-Zeitoun, And David

    2017-07-25

    Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P  0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  11. 125I-[Tyr0,D-Trp8]somatostatin-14 binding sites in the locus coeruleus of the rat are located on both ascending and descending projecting noradrenergic cells

    International Nuclear Information System (INIS)

    Epelbaum, J.; Bluet-Pajot, M.T.; Llorens-Cortes, C.; Kordon, C.; Mounier, F.; Senut, M.C.; Videau, C.

    1990-01-01

    Radioautographic determinations of 125I-[Tyr0,D-Trp8]somatostatin-14 (125I-SRIF) binding sites were performed on frozen serial sections of the locus coeruleus (LC) of control rats and of rats subjected to either bilateral microinjections of 6 hydroxydopamine (6-OHDA) into the LC or unilateral microinjection into the ascending noradrenergic bundles. These experiments were performed in order to determine whether 125I-SRIF binding was localized to noradrenergic-containing cells and in which regions the cells which contain the binding sites are projecting. The extent of the lesions was assessed by measuring norepinephrine (NE) levels in the hippocampus (88% decrease as compared to sham-operated animals) for bilateral LC lesions and in the frontal cortex (87% reduction vs. contralateral side) for unilateral bundle lesions. In control rats, 125I-SRIF binding sites were restricted to the boundaries of the LC and followed closely the distribution of tyrosine hydroxylase-labeled cells. Three weeks after bilateral injections of 6-OHDA, 125I-SRIF binding decreased by 79% in all regions of the LC. In contrast, unilateral destruction of the ascending noradrenergic bundles resulted in a moderate decrease only in the middle part of the LC with a more important effect in the dorsal (55%) than in the ventral (24%) portion of the nucleus. These data demonstrate that: (1) most SRIF receptors in the LC are located in the vicinity of NE-containing cell bodies and (2) NE-containing cells bearing SRIF receptors project to the forebrain as well as to other terminal areas located more caudally in the brain. These data suggest a general role for SRIF in the control of the multiple functions of the LC

  12. Measurement of patient radiation doses in certain urography procedures

    International Nuclear Information System (INIS)

    Sulieman, A.; Barakat, H.; Zailae, A.; Abuderman, A.; Theodorou, K.

    2015-01-01

    Patients are exposed to significant radiation doses during diagnostic and interventional urological procedures. This study aimed to measure patient entrance surface air kerma (ESAK) and to estimate the effective dose during intravenous urography (IVU), extracorporeal shock-wave lithotripsy (ESWL), and ascending urethrogram (ASU) procedures. ESAK was measured in patients using calibrated thermo luminance dosimeters, GR200A). Effective doses (E) were calculated using the National Radiological Protection Board (NRPB) software. A total of 179 procedures were investigated. 27.9 % of the patients underwent IVU procedures, 27.9 % underwent ESWL procedures and 44.2 % underwent ASU procedures. The mean ESAK was 2.1, 4.18 and 4.9 mGy for IVU, ESWL, and ASU procedures, respectively. Differences in patient ESAK for the same procedure were observed. The mean ESAK values were comparable with those in previous studies. (authors)

  13. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function