Revisiting the thermal effect on shock wave propagation in weakly ionized plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Qianhong, E-mail: zhou-qianhong@iapcm.ac.cn; Dong, Zhiwei; Yang, Wei

2016-07-15

Many researchers have investigated shock propagation in weakly ionized plasmas and observed the following anomalous effects: shock acceleration, shock recovery, shock weakening, shock spreading, and splitting. It was generally accepted that the thermal effect can explain most of the experimental results. However, little attention was paid to the shock recovery. In this paper, the shock wave propagation in weakly ionized plasmas is studied by fluid simulation. It is found that the shock acceleration, weakening, and splitting appear after it enters the plasma (thermal) region. The shock splits into two parts right after it leaves the thermal region. The distance betweenmore » the splitted shocks keeps decreasing until they recover to one. This paper can explain a whole set of features of the shock wave propagation in weakly ionized plasmas. It is also found that both the shock curvature and the splitting present the same photoacoustic deflection (PAD) signals, so they cannot be distinguished by the PAD experiments.« less

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2010-08-02

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Accuracy of tablet splitting and liquid measurements: an examination of who, what and how.

PubMed

Abu-Geras, Dana; Hadziomerovic, Dunja; Leau, Andrew; Khan, Ramzan Nazim; Gudka, Sajni; Locher, Cornelia; Razaghikashani, Maryam; Lim, Lee Yong

2017-05-01

To examine factors that might affect the ability of patients to accurately halve tablets or measure a 5-ml liquid dose. Eighty-eight participants split four different placebo tablets by hand and using a tablet splitter, while 85 participants measured 5 ml of water, 0.5% methylcellulose (MC) and 1% MC using a syringe and dosing cup. Accuracy of manipulation was determined by mass measurements. The general population was less able than pharmacy students to break tablets into equal parts, although age, gender and prior experience were insignificant factors. Greater accuracy of tablet halving was observed with tablet splitter, with scored tablets split more equally than unscored tablets. Tablet size did not affect the accuracy of splitting. However, >25% of small scored tablets failed to be split by hand, and 41% of large unscored tablets were split into >2 portions in the tablet splitter. In liquid measurement, the syringe provided more accurate volume measurements than the dosing cup, with higher accuracy observed for the more viscous MC solutions than water. Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations. © 2016 Royal Pharmaceutical Society.

A comparison of students' and jury panelists' decision-making in split recovery cases.

PubMed

Fox, Paul; Wingrove, Twila; Pfeifer, Courtney

2011-01-01

This study was designed to assess jury decision-making for 289 participants reading a medical malpractice vignette as a function of participant type (undergraduate students or jury panelists), punitive damage award apportionment (none, half, or all to the plaintiff), and compensation previously assigned to the plaintiff (low, medium, or high). We found several sample differences. Overall, jury panelists awarded more money for punitive damages. Jury panelists were also more affected by compensatory-relevant information when making punitive decisions, including assigning punitive damages and rating the fairness of the traditional apportionment scheme, where the plaintiff receives all of the money. Compared with students, more jury panelists were in favor of the plaintiff receiving the entire punitive award. Most students endorsed split recovery. The authors suggest that psycholegal research conducted solely with student samples, rather than community members, may misestimate the likely behavior of actual juries. The implications of the study for split recovery policy are also discussed. Copyright © 2011 John Wiley & Sons, Ltd.

Decorporation Approach after Rat Lung Contamination with Plutonium: Evaluation of the Key Parameters Influencing the Efficacy of a Protracted Chelation Treatment.

PubMed

Grémy, Olivier; Coudert, Sylvie; Renault, Daniel; Miccoli, Laurent

2017-11-01

While the efficacy of a protracted zinc (Zn)- or calcium (Ca)-diethylenetriaminepentaacetic acid (DTPA) treatment in reducing transuranic body burden has already been demonstrated, questions about therapeutic variables remain. In response to this, we designed animal experiments primarily to assess both the effect of fractionation of a given dose and the effect of the frequency of dose fraction, with the same total dose. In our study, rats were contaminated intravenously with plutonium (Pu) then treated several days later with Ca-DTPA given at once or in various split-dose regimens cumulating to the same total dose and spread over several days. Similar efficacies were induced by the injection of the total dose or by splitting the dose in several smaller doses, independent of the number of doses and the dose level per injection. In a second study, rats were pulmonary contaminated, and three weeks later they received a Ca-DTPA dose 11-fold higher than the maximal daily recommended dose, administered either as a single bolus or as numerous multiple injections cumulating to the same dose, based on different injection frequency schedules. Independent of frequency schedule, the various split-dose regimens spread over weeks/months were as efficient as single delivery of the total dose in mobilizing lung plutonium, and had a therapeutic advantage for removal of retained hepatic and bone plutonium burdens. We concluded that cumulative dose level was a therapeutic variable of greater importance than the distribution of split doses for the success of a repeated treatment regimen on retained tissue plutonium. In addition, pulmonary administration of clodronate, which aims at killing alveolar macrophages and subsequently releasing their plutonium content, and which is associated with a continuous Ca-DTPA infusion regimen, suggested that the efficacy of injected Ca-DTPA in decorporating lung deposit is limited, due to its restricted penetration into alveolar macrophages and not because plutonium, as a physicochemical form, is unavailable for chelation.

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J; Craft, D; Hong, T

2014-06-15

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cellmore » repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes.« less

Mutation induction in haploid yeast after split-dose radiation-exposure. I. Fractionated UV-irradiation.

PubMed

Schenk, K; Zölzer, F; Kiefer, J

1989-01-01

Mutation induction was investigated in wild-type haploid yeast Saccharomyces cerevisiae after split-dose UV-irradiation. Cells were exposed to fractionated 254 nm-UV-doses separated by intervals from 0 to 6 h with incubation either on non-nutrient or nutrient agar between. The test parameter was resistance to canavanine. If modifications of sensitivity due to incubation are appropriately taken into account there is no change of mutation frequency.

An improved adaptive interpolation clock recovery loop based on phase splitting algorithm for coherent optical communication system

NASA Astrophysics Data System (ADS)

Liu, Xuan; Liu, Bo; Zhang, Li-jia; Xin, Xiang-jun; Zhang, Qi; Wang, Yong-jun; Tian, Qing-hua; Tian, Feng; Mao, Ya-ya

2018-01-01

Traditional clock recovery scheme achieves timing adjustment by digital interpolation, thus recovering the sampling sequence. Based on this, an improved clock recovery architecture joint channel equalization for coherent optical communication system is presented in this paper. The loop is different from the traditional clock recovery. In order to reduce the interpolation error caused by the distortion in the frequency domain of the interpolator and to suppress the spectral mirroring generated by the sampling rate change, the proposed algorithm joint equalization, improves the original interpolator in the loop, along with adaptive filtering, and makes error compensation for the original signals according to the balanced pre-filtering signals. Then the signals are adaptive interpolated through the feedback loop. Furthermore, the phase splitting timing recovery algorithm is adopted in this paper. The time error is calculated according to the improved algorithm when there is no transition between the adjacent symbols, making calculated timing error more accurate. Meanwhile, Carrier coarse synchronization module is placed before the beginning of timing recovery to eliminate the larger frequency offset interference, which effectively adjust the sampling clock phase. In this paper, the simulation results show that the timing error is greatly reduced after the loop is changed. Based on the phase splitting algorithm, the BER and MSE are better than those in the unvaried architecture. In the fiber channel, using MQAM modulation format, after 100 km-transmission of single-mode fiber, especially when ROF(roll-off factor) values tends to 0, the algorithm shows a better clock performance under different ROFs. When SNR values are less than 8, the BER could achieve 10-2 to 10-1 magnitude. Furthermore, the proposed timing recovery is more suitable for the situation with low SNR values.

Can Recovery Foot Placement Affect Older Adults' Slip-Fall Severity?

PubMed

Wang, Shuaijie; Liu, Xuan; Lee, Anna; Pai, Yi-Chung

2017-08-01

Following a slip occurred in the overground walking, a fall can be classified into two exclusive categories: feet-forward fall or split fall. The purposes of this study were to investigate whether the placement of the recovery foot would determine the slip types, the likelihood of fall, and the severity associated with each fall. The fall severity was estimated based on the impact velocity of body segments or trunk orientation upon fall arrest. One hundred ninety-five participants experienced a novel, unannounced slip while walking on a 7-m walkway. Kinematics of a full-body marker set was collected by a motion capture system which was synchronized with the force plates and loadcell. The results showed that the recovery foot landing position relative to the projected center of mass position at the recovery foot touchdown determined the slip type by 90.8%. Feet-forward slips led to significantly lower rate of falls than did split slips (47.6 vs. 67.8%, p < 0.01). Yet, feet-forward falls were much more dangerous because they were associated with significantly greater estimated maximum hip impact velocity (p < 0.001) and trunk backward leaning angle (p < 0.001) in comparison to split falls.

Tablet Splitting of Antiepileptic Drugs in Pediatric Epilepsy: Potential Effect on Plasma Drug Concentrations.

PubMed

Nidanapu, Ravi Prasad; Rajan, Sundaram; Mahadevan, Subramanian; Gitanjali, Batmanabane

2016-12-01

Tablet splitting is the process of dividing a tablet into portions to obtain a prescribed dose of medication. Very few studies have investigated whether split parts of a tablet deliver the expected amount of drug to patients. Our objectives were to evaluate the split parts of adult-dose tablet formulations for percentage of weight deviation, weight uniformity, weight loss, drug content, and the content uniformity of four antiepileptic drugs (AEDs) prescribed to pediatric patients. We also measured AED plasma concentrations in the children. We chose to study first-line AEDs (phenytoin sodium [PHE], sodium valproate [SVA], carbamazepine, and phenobarbitone) as they are routinely prescribed in India. We asked caregivers to perform the same splitting process they follow in their homes on three whole tablets during their routine visit to the outpatient department. After caregivers split the tablets, we studied the weight and content of the split parts. We also used high-performance liquid chromatography to study plasma drug concentrations in children who had received split AEDs for at least 4 months. A total of 168 caregivers participated in the study, and we analyzed 1098 split tablet parts. In total, 539 (49.0 %) split parts were above the specified limit of the 2010 Indian Pharmacopeia (IP) acceptable percentage weight deviation (PHE 169 [48.8 %], SVA 187 [51.9 %], carbamazepine 56 [41.1 %], phenobarbitone 127 [49.6 %]); 456 (41.5 %) split parts were outside the proxy IP specification for drug content (PHE 135 [39.0 %], SVA 140 [38.8 %], carbamazepine 51 [37.5 %], phenobarbitone 130 [50.7 %]), and 253 split parts were outside the acceptable content uniformity range of <85 % and >115 % (PHE 85 [24.5 %], SVA 98 [27.2 %], carbamazepine 14 [10.2 %], phenobarbitone 56 [21.8 %]). In total, 130 (72.2 %) patients had plasma drug concentrations outside the therapeutic range (PHE 36 [72.0 %], SVA 39 [78.0 %], carbamazepine 34 [68.0 %], phenobarbitone 21 [70.0 %]). Splitting adult-dosage formulations of AEDs results in patients not receiving the optimal dose. Plasma drug concentrations are also not optimal. Pediatric dosage formulations should be preferred to splitting adult-dosage formulations in pediatric epilepsy.

Comparison of image quality and radiation dose between split-filter dual-energy images and single-energy images in single-source abdominal CT.

PubMed

Euler, André; Obmann, Markus M; Szucs-Farkas, Zsolt; Mileto, Achille; Zaehringer, Caroline; Falkowski, Anna L; Winkel, David J; Marin, Daniele; Stieltjes, Bram; Krauss, Bernhard; Schindera, Sebastian T

2018-02-19

To compare image quality and radiation dose of abdominal split-filter dual-energy CT (SF-DECT) combined with monoenergetic imaging to single-energy CT (SECT) with automatic tube voltage selection (ATVS). Two-hundred single-source abdominal CT scans were performed as SECT with ATVS (n = 100) and SF-DECT (n = 100). SF-DECT scans were reconstructed and subdivided into composed images (SF-CI) and monoenergetic images at 55 keV (SF-MI). Objective and subjective image quality were compared among single-energy images (SEI), SF-CI and SF-MI. CNR and FOM were separately calculated for the liver (e.g. CNR liv ) and the portal vein (CNR pv ). Radiation dose was compared using size-specific dose estimate (SSDE). Results of the three groups were compared using non-parametric tests. Image noise of SF-CI was 18% lower compared to SEI and 48% lower compared to SF-MI (p < 0.001). Composed images yielded higher CNR liv over single-energy images (23.4 vs. 20.9; p < 0.001), whereas CNR pv was significantly lower (3.5 vs. 5.2; p < 0.001). Monoenergetic images overcame this inferiority in CNR pv and achieved similar results compared to single-energy images (5.1 vs. 5.2; p > 0.628). Subjective sharpness was equal between single-energy and monoenergetic images and diagnostic confidence was equal between single-energy and composed images. FOM liv was highest for SF-CI. FOM pv was equal for SEI and SF-MI (p = 0.78). SSDE was significant lower for SF-DECT compared to SECT (p < 0.022). The combined use of split-filter dual-energy CT images provides comparable objective and subjective image quality at lower radiation dose compared to single-energy CT with ATVS. • Split-filter dual-energy results in 18% lower noise compared to single-energy with ATVS. • Split-filter dual-energy results in 11% lower SSDE compared to single-energy with ATVS. • Spectral shaping of split-filter dual-energy leads to an increased dose-efficiency.

What plant and soil testing from 16 sites in eight midwestern states tells us about split nitrogen applications

USDA-ARS?s Scientific Manuscript database

It is hypothesized that split-nitrogen (N) relative to single near-planting applications improve corn (Zea mays L.) production, N recovery efficiency, and lessen environmental impacts of fertilization. However, these hypotheses have not been fully tested. A 16-site study across eight US Midwestern s...

75 FR 12775 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... manufactured goods (ductless split HVAC systems) are not produced in the U.S. in sufficient and reasonably... Valley Housing Authority for the installation of a ductless split system during the LaCreole Manor Heating, Ventilation and Air Conditioning (HVAC) and Water Distribution Replacement Project. FOR FURTHER...

Dose calculation algorithm of fast fine-heterogeneity correction for heavy charged particle radiotherapy.

PubMed

Kanematsu, Nobuyuki

2011-04-01

This work addresses computing techniques for dose calculations in treatment planning with proton and ion beams, based on an efficient kernel-convolution method referred to as grid-dose spreading (GDS) and accurate heterogeneity-correction method referred to as Gaussian beam splitting. The original GDS algorithm suffered from distortion of dose distribution for beams tilted with respect to the dose-grid axes. Use of intermediate grids normal to the beam field has solved the beam-tilting distortion. Interplay of arrangement between beams and grids was found as another intrinsic source of artifact. Inclusion of rectangular-kernel convolution in beam transport, to share the beam contribution among the nearest grids in a regulatory manner, has solved the interplay problem. This algorithmic framework was applied to a tilted proton pencil beam and a broad carbon-ion beam. In these cases, while the elementary pencil beams individually split into several tens, the calculation time increased only by several times with the GDS algorithm. The GDS and beam-splitting methods will complementarily enable accurate and efficient dose calculations for radiotherapy with protons and ions. Copyright © 2010 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Long-Term Immunogenicity of an Inactivated Split-Virion 2009 Pandemic Influenza A H1N1 Virus Vaccine with or without Aluminum Adjuvant in Mice

PubMed Central

Xu, Wenting; Zheng, Mei; Zhou, Feng

2015-01-01

In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of thousands of people. Vaccination is the most effective means of controlling an epidemic of influenza and reducing the mortality rate. In this study, the long-term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was observed as long as 15 months (450 days) after immunization in a mouse model. Female BALB/c mice were immunized intraperitoneally with different doses of aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10× 50% lethal dose [LD50]) of homologous virus 450 days after immunization. The results showed that the supplemented aluminum adjuvant not only effectively enhanced the protective effect of the vaccine but also reduced the immunizing dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody level of mice immunized with the H1N1 split vaccine. The IgG level was correlated to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion 2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long-term protection against lethal influenza virus challenge in mice. PMID:25589552

Optimal preparation-to-colonoscopy interval in split-dose PEG bowel preparation determines satisfactory bowel preparation quality: an observational prospective study.

PubMed

Seo, Eun Hee; Kim, Tae Oh; Park, Min Jae; Joo, Hee Rin; Heo, Nae Yun; Park, Jongha; Park, Seung Ha; Yang, Sung Yeon; Moon, Young Soo

2012-03-01

Several factors influence bowel preparation quality. Recent studies have indicated that the time interval between bowel preparation and the start of colonoscopy is also important in determining bowel preparation quality. To evaluate the influence of the preparation-to-colonoscopy (PC) interval (the interval of time between the last polyethylene glycol dose ingestion and the start of the colonoscopy) on bowel preparation quality in the split-dose method for colonoscopy. Prospective observational study. University medical center. A total of 366 consecutive outpatients undergoing colonoscopy. Split-dose bowel preparation and colonoscopy. The quality of bowel preparation was assessed by using the Ottawa Bowel Preparation Scale according to the PC interval, and other factors that might influence bowel preparation quality were analyzed. Colonoscopies with a PC interval of 3 to 5 hours had the best bowel preparation quality score in the whole, right, mid, and rectosigmoid colon according to the Ottawa Bowel Preparation Scale. In multivariate analysis, the PC interval (odds ratio [OR] 1.85; 95% CI, 1.18-2.86), the amount of PEG ingested (OR 4.34; 95% CI, 1.08-16.66), and compliance with diet instructions (OR 2.22l 95% CI, 1.33-3.70) were significant contributors to satisfactory bowel preparation. Nonrandomized controlled, single-center trial. The optimal time interval between the last dose of the agent and the start of colonoscopy is one of the important factors to determine satisfactory bowel preparation quality in split-dose polyethylene glycol bowel preparation. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

30 CFR 75.207 - Pillar recovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... be left in place. (b) Before mining is started in a pillar split or lift— (1) At least two rows of... leading into the split or lift. (c) Before mining is started on a final stump— (1) At least 2 rows of... shall be installed between the lift to be started and the area where pillars have been extracted. These...

30 CFR 75.207 - Pillar recovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

... be left in place. (b) Before mining is started in a pillar split or lift— (1) At least two rows of... leading into the split or lift. (c) Before mining is started on a final stump— (1) At least 2 rows of... shall be installed between the lift to be started and the area where pillars have been extracted. These...

Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan.

PubMed

Chou, Chia-Lin; Hsu, Chia-Chen; Chou, Chia-Yu; Chen, Tzeng-Ji; Chou, Li-Fang; Chou, Yueh-Ching

2015-12-01

Tablet splitting or pill splitting frequently occurs in daily medical practice. For drugs with special pharmacokinetic characters, such as drugs with narrow therapeutic index (NTI), unequal split tablets might lead to erroneous dose titration and it even cause toxicity. The aim of this study was to investigate the frequency of prescribing split NTI drugs at ambulatory setting in Taiwan. A population-based retrospective study was conducted using the National Health Insurance Research Database in Taiwan. All ambulatory visits were analyzed from the longitudinal cohort datasets of the National Health Insurance Research Database. The details of ambulatory prescriptions containing NTI drugs were extracted by using the claims datasets of one million beneficiaries from National Healthcare Insurance Research Database in 2010 in Taiwan. The analyses were stratified by dosage form, patient age and the number of prescribed tablets in a single dose for each NTI drugs. Main outcome measures Number and distinct dosage forms of available NTI drug items in Taiwan, number of prescriptions involved split NTI drugs, and number of patients received split NTI drugs. A total of 148,548 patients had received 512,398 prescriptions of NTI drugs and 41.8 % (n = 62,121) of patients had received 36.3 % (n = 185,936) of NTI drug prescriptions in form of split tablets. The percentage of splitting was highest in digoxin prescriptions (81.0 %), followed by warfarin (72.0 %). In the elderly patients, split tablets were very prevalent with digoxin (82.4 %) and warfarin (84.5 %). NTI drugs were frequently prescribed to be taken in split forms in Taiwan. Interventions may be needed to provide effective and convenient NTI drug use. Further studies are needed to evaluate the clinical outcome of inappropriate split NTI drugs.

Time series evaluation of an intervention to increase statin tablet splitting by general practitioners.

PubMed

Polinski, Jennifer M; Schneeweiss, Sebastian; Maclure, Malcolm; Marshall, Blair; Ramsden, Samuel; Dormuth, Colin

2011-02-01

Tablet splitting, in which a higher-dose tablet is split to get 2 doses, reduces patients' drug costs. Statins can be split safely. General practitioners (GPs) may not direct their patients to split statins because of safety concerns or unawareness of costs. Medical chart inserts provide cost-effective education to physicians. The aim of this study was to assess whether providing GPs with statin-splitting chart inserts would increase splitting rates, and to identify predictors of splitting. In 2005 and 2006, we faxed a statin chart insert to British Columbia GPs with a request for a telephone interview. Consenting GPs were mailed 3 statin chart inserts and interviewed by phone (the intervention). In an interrupted time series, we compared monthly rates of statin-splitting prescriptions among intervention and nonintervention GPs before, during, and after the intervention. In multivariate logistic regressions accounting for patient clustering, predictors of splitting included physician and patient demographics and the specific statin prescribed. Of 5051 GPs reached, 282 (6%) agreed to the intervention. Before the intervention, GPs' splitting rate was 2.6%; after intervention, GPs' splitting rate was 7.5%. The rate for the nonintervention GPs was 4.4%. Intervention GPs were 1.68 (95% CI, 1.12-2.53) times more likely to prescribe splitting after the intervention than were nonintervention GPs. Other predictors were a patient's female sex (odds ratio [OR] = 1.26; 95% CI, 1.18-1.34), lower patient income (OR = 1.33; 95% CI, 1.18-1.34), and a lack of drug insurance (OR = 1.89; 95% CI, 1.69-2.04). An inexpensive intervention was effective in producing a sustained increase in GPs' splitting rate during 22 months of observed follow-up. Expanding statin-splitting education to all GPs might reduce prescription costs for many patients and payors. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Time series evaluation of an intervention to increase statin tablet splitting by general practitioners

PubMed Central

Polinski, Jennifer M.; Schneeweiss, Sebastian; Maclure, Malcolm; Marshall, Blair; Ramsden, Samuel; Dormuth, Colin

2011-01-01

Background Tablet splitting, in which a higher-dose tablet is split to get two doses, reduces patients’ drug costs. Statins can be split safely. General practitioners (GPs) may not direct their patients to split statins because of safety concerns or unawareness of costs. Medical chart inserts provide cost-effective education to physicians. We evaluated whether providing GPs with statin splitting chart inserts would increase splitting rates and identified predictors of splitting. Methods In 2005–2006, we faxed a statin chart insert to British Columbia GPs with a request for a telephone interview. Consenting GPs were mailed 3 statin chart inserts and interviewed by phone (the intervention). In an interrupted time series, we compared monthly rates of statin splitting prescriptions among intervention and non-intervention GPs before, during, and after the intervention. In multivariate logistic regressions accounting for patient clustering, predictors of splitting included physician and patient demographics and the specific statin prescribed. Results Of 5,051 GPs reached, 282 (6%) agreed to the intervention. Before the intervention, GPs’ splitting rate was 2.6%; after, intervention GPs’ splitting rate was 7.5%, non-intervention GPs’ was 4.4%. Intervention GPs were 1.68 (95% CI 1.12–2.53) times more likely to prescribe splitting after the intervention than were non-intervention GPs. Other predictors were a patient’s female sex (OR=1.26, 95% CI 1.18–1.34), lower patient income (OR=1.33, 95% CI 1.18–1.34), and no drug insurance (OR=1.89, 95% CI 1.69–2.04). Interpretation An inexpensive intervention was effective in producing a sustained increase in GPs’ splitting rate during 22 months of observed follow-up. Expanding statin splitting education to all GPs could reduce prescription costs for many patients and payors. PMID:21497707

Optimal field-splitting algorithm in intensity-modulated radiotherapy: Evaluations using head-and-neck and female pelvic IMRT cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dou, Xin; Kim, Yusung, E-mail: yusung-kim@uiowa.edu; Bayouth, John E.

2013-04-01

To develop an optimal field-splitting algorithm of minimal complexity and verify the algorithm using head-and-neck (H and N) and female pelvic intensity-modulated radiotherapy (IMRT) cases. An optimal field-splitting algorithm was developed in which a large intensity map (IM) was split into multiple sub-IMs (≥2). The algorithm reduced the total complexity by minimizing the monitor units (MU) delivered and segment number of each sub-IM. The algorithm was verified through comparison studies with the algorithm as used in a commercial treatment planning system. Seven IMRT, H and N, and female pelvic cancer cases (54 IMs) were analyzed by MU, segment numbers, andmore » dose distributions. The optimal field-splitting algorithm was found to reduce both total MU and the total number of segments. We found on average a 7.9 ± 11.8% and 9.6 ± 18.2% reduction in MU and segment numbers for H and N IMRT cases with an 11.9 ± 17.4% and 11.1 ± 13.7% reduction for female pelvic cases. The overall percent (absolute) reduction in the numbers of MU and segments were found to be on average −9.7 ± 14.6% (−15 ± 25 MU) and −10.3 ± 16.3% (−3 ± 5), respectively. In addition, all dose distributions from the optimal field-splitting method showed improved dose distributions. The optimal field-splitting algorithm shows considerable improvements in both total MU and total segment number. The algorithm is expected to be beneficial for the radiotherapy treatment of large-field IMRT.« less

Mutation induction in haploid yeast after split-dose radiation exposure. II. Combination of UV-irradiation and X-rays.

PubMed

Keller, B; Zölzer, F; Kiefer, J

2004-01-01

Split-dose protocols can be used to investigate the kinetics of recovery from radiation damage and to elucidate the mechanisms of cell inactivation and mutation induction. In this study, a haploid strain of the yeast, Saccharomyces cerevisiae, wild-type with regard to radiation sensitivity, was irradiated with 254-nm ultraviolet (UV) light and then exposed to X-rays after incubation for 0-6 hr. The cells were incubated either on nutrient medium or salt agar between the treatments. Loss of reproductive ability and mutation to canavanine resistance were measured. When the X-ray exposure immediately followed UV-irradiation, the X-ray survival curves had the same slope irrespective of the pretreatment, while the X-ray mutation induction curves were changed from linear to linear quadratic with increasing UV fluence. Incubations up to about 3 hr on nutrient medium between the treatments led to synergism with respect to cell inactivation and antagonism with respect to mutation, but after 4-6 hr the two treatments acted independently. Incubation on salt agar did not cause any change in the survival curves, but there was a strong suppression of X-ray-induced mutation with increasing UV fluence. On the basis of these results, we suggest that mutation after combined UV and X-ray exposure is affected not only by the induction and suppression of DNA repair processes, but also by radiation-induced modifications of cell-cycle progression and changes in the expression of the mutant phenotype. Copyright 2004 Wiley-Liss, Inc.

Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium.

PubMed

Shah, Rakhi B; Collier, Jarrod S; Sayeed, Vilayat A; Bryant, Arthur; Habib, Muhammad J; Khan, Mansoor A

2010-09-01

Levothyroxine is a narrow therapeutic index, and to avoid adverse effect associated with under or excessive dosage, the dose response is carefully titrated. The tablets are marketed with a score providing an option to split. However, there are no systematic studies evaluating the effect of splitting on dose accuracy, and current study was undertaken to evaluate effects of splitting and potential causes for uniformity failures by measuring assay and content uniformity in whole and split tablets. Stability was evaluated by assaying drug for a period of 8 weeks. Effect of formulation factors on splittability was evaluated by a systematic investigation of formulation factors by preparing levothyroxine tablets in house by varying the type of excipients (binder, diluent, disintegrant, glidant) or by varying the processing factors (granulating liquid, mixing type, compression pressure). The tablets were analyzed using novel analytical tool such as near infrared chemical imaging to visualize the distribution of levothyroxine. Assay was not significantly different for whole versus split tablets irrespective of method of splitting (hand or splitter), and splitting also had no measurable impact on the stability. Split tablets either by hand or splitter showed higher rate of content uniformity failures as compared to whole tablets. Tablet splitter produced more fragmentation and, hence, more content uniformity and friability failures. Chemical imaging data revealed that the distribution of levothyroxine was heterogeneous and was dependent on type of binder and the process used in the manufacture of tablets. Splitting such tablets could prove detrimental if sub- or super-potency becomes an issue.

Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta-analysis of randomized trials.

PubMed

Restellini, Sophie; Kherad, Omar; Menard, Charles; Martel, Myriam; Barkun, Alan N

2018-02-01

BACKGROUND AND STUDY AIMS : Recommendations on adjuvant use with bowel preparations remain disparate. We performed a meta-analysis determining the clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens.  Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials from January 1980 to April 2016 that assessed preparations with or without adjuvants, given in split and non-split dosing, and PEG high- (> 3 L) or low-dose (≤ 2 L) regimens. Bowel cleansing efficacy was the primary outcome. Secondary outcomes included patient willingness to repeat the procedure, and polyp and adenoma detection rates.  Of 3093 citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an adjuvant compared with no adjuvant, irrespective of the type of preparation and mode of administration, yielded improvements in bowel cleanliness (odds ratio [OR] 1.23 [1.01 - 1.51]) without greater willingness to repeat (OR 1.40 [0.91 - 2.15]). Adjuvants combined with high-dose PEG significantly improved colon cleansing (OR 1.96 [1.32 - 2.94]). The odds for achieving adequate preparation with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR 0.95 [0.73 - 1.22]), but yielded improved tolerance (OR 3.22 [1.85 - 5.55]). However, split high-dose PEG yielded superior cleanliness to low-dose PEG with adjuvants (OR 2.53 [1.25 - 5.13]). No differences were noted for OSS and PICO comparisons, or for any products regarding polyp or adenoma detection rates.  Critical heterogeneity precludes firm conclusion on the impact of adjuvants with existing bowel preparations. Additional research is required to better characterize the methods of administration and resulting roles of adjuvants in an era of split-dosing. © Georg Thieme Verlag KG Stuttgart · New York.

Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis.

PubMed

Edstein, M D; Nasveld, P E; Kocisko, D A; Kitchener, S J; Gatton, M L; Rieckmann, K H

2007-03-01

In an open-label sequential cohort study, we compared gastrointestinal (GI) disturbances and plasma tafenoquine concentrations after administration of single-dose (400mg daily x 3 days; n=76 males, 11 females) and split-dose (200 mg twice daily x 3 days; n=73 males, 13 females) tafenoquine regimens in healthy Australian Defence Force volunteers for post-exposure malaria prophylaxis. The female and male volunteers had comparable demographic characteristics (age, weight, height) in the single- and split-dose treatment groups. GI disturbances were generally mild and self-limiting for both groups. The frequency of nausea and abdominal distress was over two-fold higher in females than in males for both treatment groups. Reporting of GI disturbances in the single-dose group differed significantly between males and females, but this gender difference was not seen for the split-dose group. In those volunteers who experienced GI disturbances, the mean plasma tafenoquine concentrations 12 h after the last dose of tafenoquine were approximately 1.3-fold higher in females than in males (means+/-SD: 737+/-118 ng/ml vs. 581+/-113 ng/ml). These preliminary findings suggest that further studies are required in a larger number of females to determine whether there is a need to reduce the dose of tafenoquine to minimise GI disturbances in females.

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.

PubMed

Wu, Jiang; Liu, Shu-Zhen; Dong, Shan-Shan; Dong, Xiao-Ping; Zhang, Wu-Li; Lu, Min; Li, Chang-Gui; Zhou, Ji-Chen; Fang, Han-Hua; Liu, Yan; Liu, Li-Ying; Qiu, Yuan-Zheng; Gao, Qiang; Zhang, Xiao-Mei; Chen, Jiang-Ting; Zhong, Xiang; Yin, Wei-Dong; Feng, Zi-Jian

2010-08-31

Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays. 5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did. The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 microg dose induced immune response complying with European Union licensure criteria. (c) 2010 Elsevier Ltd. All rights reserved.

Split-course, high-dose palliative pelvic radiotherapy for locally progressive hormone-refractory prostate cancer.

PubMed

Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

2012-06-01

Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of heat recovery water heater system on the performance of residential split air conditioner using hydrocarbon refrigerant (HCR22)

NASA Astrophysics Data System (ADS)

Aziz, A.; Thalal; Amri, I.; Herisiswanto; Mainil, A. K.

2017-09-01

This This paper presents the performance of residential split air conditioner (RSAC) using hydrocarbon refrigerant (HCR22) as the effect on the use of heat recovery water heater system (HRWHS). In this study, RSAC was modified with addition of dummy condenser (trombone coil type) as heat recovery water heater system (HRWHS). This HRWHS is installed between a compressor and a condenser by absorbing a part of condenser waste heat. The results show that RSAC with HRWHS is adequate to generate hot water with the temperature range about 46.58˚C - 48.81˚C when compared to without HRWHS and the use of dummy condenser does not give significant effect to the split air conditioner performance. When the use of HRWHS, the refrigerant charge has increase about 19.05%, the compressor power consumption has slightly increase about 1.42% where cooling capacity almost the same with slightly different about 0.39%. The condenser heat rejection is lower about 2.68% and the COP has slightly increased about 1.05% when compared to without HRWHS. The use of HRWHS provide free hot water, it means there is energy saving for heating water without negative impact to the system performance of RSAC.

Adverse drug reactions and outcome of short course anti-tuberculosis drugs between single daily dose and split drug dose (BID) in pulmonary tuberculosis.

PubMed

Chuchottaworn, Charoen; Saipan, Benjawan; Kittisup, Chomnapa; Cheewakul, Krisana

2012-08-01

Standard six months short course regimen for treatment of pulmonary tuberculosis is very effective and is recommended as standard treatment. But this regimen composes of many drugs and causes high adverse drug reactions especially gastrointestinal irritation. Spitted administration of drugs to two times a day may reduce adverse drug reactions. To study adverse drug reactions and outcome of single daily versus split drug (two times a day) administration of standard six month short course regimen in newly diagnosed pulmonary tuberculosis. Newly diagnosed pulmonary tuberculosis patients of the Central Chest Institute of Thailand were randomized to receive standard six months regimen once daily or two times a day (split drug). Patients were followed-up every two weeks and a questionnaire was used to detect adverse drug reactions. Outcome of treatment was evaluated according to national tuberculosis treatment guideline. 122 pulmonary tuberculosis were eligible for the present study and 61 patients were enrolled to each group of once daily or split drug regimen. Pulmonary tuberculosis patients who received split drug regimen had a higher cure rate but not statistical significance because of lower transfer out rate. Adverse drug reactions were similar in both groups of patients who received once daily and split drug regimen. Although split drug group had lower gastrointestinal adverse drug reactions. Split drug regimen has the same cure rate of treatment as single daily regimen and same adverse drug reactions.

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

PubMed

Hamer, Ann M; Hartung, Daniel M; Haxby, Dean G; Ketchum, Kathy L; Pollack, David A

2006-01-01

One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.

Nitrogen split dose fertilization, plant age and frost effects on phytochemical content and sensory properties of curly kale (Brassica oleracea L. var. sabellica).

PubMed

Groenbaek, Marie; Jensen, Sidsel; Neugart, Susanne; Schreiner, Monika; Kidmose, Ulla; Kristensen, Hanne L

2016-04-15

We investigated how concentrations of sensory relevant compounds: glucosinolates (GLSs), flavonoid glycosides, hydroxycinnamic acid derivatives and sugars in kale responded to split dose and reduced nitrogen (N) fertilization, plant age and controlled frost exposure. In addition, frost effects on sensory properties combined with N supply were assessed. Seventeen week old kale plants showed decreased aliphatic GLSs at split dose N fertilization; whereas reduced N increased aliphatic and total GLSs. Ontogenetic effects were demonstrated for all compounds: sugars, aliphatic and total GLSs increased throughout plant development, whereas kaempferol and total flavonoid glycosides showed higher concentrations in 13 week old plants. Controlled frost exposure altered sugar composition slightly, but not GLSs or flavonoid glycosides. Reduced N supply resulted in less bitterness, astringency and pungent aroma, whereas frost exposure mainly influenced aroma and texture. N treatment explained most of the sensory variation. Producers should not rely on frost only to obtain altered sensory properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Zero-order metoprolol pharmacokinetics after therapeutic doses: severe toxicity and cardiogenic shock.

PubMed

Isbister, Geoffrey K; Ang, Karyn; Gorman, Kieron; Cooper, Joyce; Mostafa, Ahmed; Roberts, Michael S

2016-11-01

Acute beta-blocker overdose can cause severe cardiac dysfunction. Chronic toxicity is rare but potentially severe. We report therapeutic dosing of metoprolol resulting in unusual pharmacokinetics and toxicity, given high-dose insulin therapy for treatment. A 90-year-old female presented with hypotension, tachycardia and severe cardiac dysfunction after commencing a rapidly increasing metoprolol dose of 250 mg split daily. She was admitted to intensive care and given high-dose insulin therapy (10 U/kg/h), noradrenaline, adrenaline and dobutamine for severe cardiac dysfunction (cardiac index, 0.76 L/min/m 2 ). She developed acute renal failure, ischaemic hepatitis and disseminated intravascular coagulopathy. Inotropes and high-dose insulin were weaned over four days with complete recovery. Metoprolol was quantified with liquid chromatography-tandem mass spectrometry and concentration-time data were analysed using MONOLIX ® vs 4.3 ( www.lixoft.com ). Admission metoprolol concentration was 2.39 μg/mL (therapeutic reference range: 0.035-0.5 μg/mL). Data best fitted a one compartmental model with Michaelis-Menten kinetics and zero order elimination at high concentrations. Final parameter estimates were V, 63.4 L, maximum rate [V m ], 9.57 mg h -1 , Michaelis constant [K m ], 1.97 mg L -1 . Predicted elimination half-life decreased from 20 h over time until there was first order elimination with a half-life 9 h. The time course of cardiac dysfunction was longer than acute overdose but consistent with prolonged zero order elimination of metoprolol, suggesting the patient was a poor CYP2D6 metaboliser. High-dose insulin euglycaemia appeared to be effective in combination with vasoconstrictors/inotropes.

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

PubMed

Kimura, S; Gomibuchi, F; Shimoda, H; Ikezawa, Y; Segawa, H; Kaneko, F; Uchiyama, S; Homma, T

2000-04-01

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

INFLUENCE OF TABLET SPLITTING ON CONTENT UNIFORMITY OF LISINOPRIL/ HYDROCHLORTHIAZIDE TABLETS

PubMed Central

Vranić, Edina; Uzunović, Alija

2007-01-01

Dose-related adverse effects of medications are a major problem in modern medical practice. The “correct” dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril-hydrochlorothiazide scored tablets labeled to contain 20/12,5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12,5 mg in the whole tablet) were: 49,60 ±3,29% and 49,29±0,60 % (lisinopril); 50,33±3,50% and 50,69±1,95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy PMID:18039191

Improved speed and stability of ST-segment recovery with reduced-dose tenecteplase and eptifibatide compared with full-dose tenecteplase for acute ST-segment elevation myocardial infarction.

PubMed

Roe, Matthew T; Green, Cynthia L; Giugliano, Robert P; Gibson, C Michael; Baran, Kenneth; Greenberg, Mark; Palmeri, Sebastian T; Crater, Suzanne; Trollinger, Kathleen; Hannan, Karen; Harrington, Robert A; Krucoff, Mitchell W

2004-02-18

This sub-study of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial evaluated of the impact of combination reperfusion therapy with reduced-dose tenecteplase plus eptifibatide on continuous ST-segment recovery and angiographic results. Combination therapy with reduced-dose fibrinolytics and glycoprotein IIb/IIIa inhibitors for ST-segment elevation myocardial infarction improves biomarkers of reperfusion success but has not reduced mortality when compared with full-dose fibrinolytics. We evaluated 140 patients enrolled in the INTEGRITI trial with 24-h continuous 12-lead ST-segment monitoring and angiography at 60 min. The dose-combination regimen of 50% of standard-dose tenecteplase (0.27 microg/kg) plus high-dose eptifibatide (2 boluses of 180 microg/kg separated by 10 min, 2.0 microg/kg/min infusion) was compared with full-dose tenecteplase (0.53 microg/kg). The dose-confirmation regimen of reduced-dose tenecteplase plus high-dose eptifibatide was associated with a faster median time to stable ST-segment recovery (55 vs. 98 min, p = 0.06), improved stable ST-segment recovery by 2 h (89.6% vs. 67.7%, p = 0.02), and less recurrent ischemia (34.0% vs. 57.1%, p = 0.05) when compared with full-dose tenecteplase. Continuously updated ST-segment recovery analyses demonstrated a modest trend toward greater ST-segment recovery at 30 min (57.7% vs. 40.6%, p = 0.13) and 60 min (82.7% vs. 65.6%, p = 0.08) with this regimen. These findings correlated with improved angiographic results at 60 min. Combination therapy with reduced-dose tenecteplase and eptifibatide leads to faster, more stable ST-segment recovery and improved angiographic flow patterns, compared with full-dose tenecteplase. These findings question the relationship between biomarkers of reperfusion success and clinical outcomes.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

PubMed

Simão, Vinícius Augusto; Berloffa Belardin, Larissa; Araújo Leite, Gabriel Adan; de Almeida Chuffa, Luiz Gustavo; Camargo, Isabel Cristina Cherici

2015-10-01

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Split Flow Online Solid-Phase Extraction Coupled with Inductively Coupled Plasma Mass Spectrometry System for One-Shot Data Acquisition of Quantification and Recovery Efficiency.

PubMed

Furukawa, Makoto; Takagai, Yoshitaka

2016-10-04

Online solid-phase extraction (SPE) coupled with inductively coupled plasma mass spectrometry (ICPMS) is a useful tool in automatic sequential analysis. However, it cannot simultaneously quantify the analytical targets and their recovery percentages (R%) in one-shot samples. We propose a system that simultaneously acquires both data in a single sample injection. The main flowline of the online solid-phase extraction is divided into main and split flows. The split flow line (i.e., bypass line), which circumvents the SPE column, was placed on the main flow line. Under program-controlled switching of the automatic valve, the ICPMS sequentially measures the targets in a sample before and after column preconcentration and determines the target concentrations and the R% on the SPE column. This paper describes the system development and two demonstrations to exhibit the analytical significance, i.e., the ultratrace amounts of radioactive strontium ( 90 Sr) using commercial Sr-trap resin and multielement adsorbability on the SPE column. This system is applicable to other flow analyses and detectors in online solid phase extraction.

Reactor Experiments at the University of Minnesota.

DTIC Science & Technology

1987-07-15

metallurgy; zinc, zinc oxide; solar thermal,’ solar Pi% thermoelectrochemical’ water splitting, separation devices; reactors e, ? 20. AeSiRACT (Continue oe...reported. Water splitting, recovery of hydrogen 4. and sulfur from hydrogen sulfide, electrolysis of zinc oxide in vapor and liquid phases, oil...CH4-CO2 reforming process. 2. Hydrogen production from water and the production of hydrogen and sulfur (or ammonia and sulfuric acid) from H2S. 3

Organic and inorganic fertilizer effect on soil CO2 flux, microbial biomass, and growth of Nigella sativa L.

NASA Astrophysics Data System (ADS)

Salehi, Aliyeh; Fallah, Seyfollah; Sourki, Ali Abasi

2017-01-01

Cattle manure has a high carbon/nitrogen ratio and may not decompose; therefore, full-dose application of urea fertilizer might improve biological properties by increasing manure decomposition. This study aimed to investigate the effect of combining cattle manure and urea fertilizer on soil CO2 flux, microbial biomass carbon, and dry matter accumulation during Nigella sativa L. (black cumin) growth under field conditions. The treatments were control, cattle manure, urea, different levels of split and full-dose integrated fertilizer. The results showed that integrated application of cattle manure and chemical fertilizer significantly increased microbial biomass carbon by 10%, soil organic carbon by 2.45%, total N by 3.27%, mineral N at the flowering stage by 7.57%, and CO2 flux by 9% over solitary urea application. Integrated application increased microbial biomass carbon by 10% over the solitary application and the full-dose application by 5% over the split application. The soil properties and growth parameters of N. sativa L. benefited more from the full-dose application than the split application of urea. Cattle manure combined with chemical fertilizer and the full-dose application of urea increased fertilizer efficiency and improved biological soil parameters and plant growth. This method decreased the cost of top dressing urea fertilizer and proved beneficial for the environment and medicinal plant health.

Results of quality-control sampling of water, bed sediment, and tissue in the Western Lake Michigan Drainages study unit of the National Water-Quality Assessment Program

USGS Publications Warehouse

Fitzgerald, S.A.

1997-01-01

This report contains the quality control results of the Western Lake Michigan Drainages study unit of the National Water Quality Assessment Program. Quality control samples were collected in the same manner and contemporaneously with environmental samples during the first highintensity study phase in the unit (1992 through 1995) and amounted to approximately 15 percent of all samples collected. The accuracy and precision of hundreds of chemical analyses of surface and ground-water, bed sediment, and tissue was determined through the collection and analysis of field blanks, field replicates and splits, matrix spikes, and surrogates. Despite the several detections of analytes in the field blanks, the concentrations of most constituents in the environmental samples will likely be an order of magnitude or higher than those in the blanks. However, frequent detections, and high concentrations, of dissolved organic carbon (DOC) in several surface and ground-water blanks are probably significant with respect to commonly measured environmental concentrations, and the environmental data will have to be qualified accordingly. The precision of sampling of water on a percent basis, as determined from replicates and splits, was generally proportional to the concentration of the constituents, with constituents present in relatively high concentrations generally having less sampling variability than those with relatively low concentrations. In general, analytes with relatively high variability between replicates were present at concentrations near the reporting limit or were associated with relatively small absolute concentration differences, or both. Precision of replicates compared to that for splits in bed sediment samples was similar, thus eliminating sampling as a major source of variability in analyte concentrations. In the case the phthalates in bed sediment, contamination in either the field or laboratory could have caused the relatively large variability between replicate samples and between split samples.Variability of analyte concentrations in tissue samples was relatively low, being 29 percent or less for all constituents. Recoveries of most laboratory schedule 2001/2010 pesticide spike compounds in surfacewater samples were reasonably good. Low intrinsic method recovery resulted in relatively low recovery forp,p'-DDE, metribuzin, and propargite. In the case of propargite, decomposition with the environmental sample matrices was also indicated. Recoveries of two compounds, cyanazine and thiobencarb, might have been biased high due to interferences. The one laboratory schedule 2050/2051 field matrix pesticide spike indicated numerous operational problems with this method that biased recoveries either low or high. Recoveries of pesticides from both pesticide schedules in field spikes of ground-water samples generally were similar to those of field matrix spikes of surface- water samples. High maximum recoveries were noted for tebuthiuron, disulfoton, DCPA, and permethrin, which indicates the possible presence of interferents in the matrices for these compounds. Problems in the recoveries of pesticides on schedule 2050/2051 from ground-water samples generally were the same as those for surfacewater samples. Recoveries of VOCs in field matrix spikes were reasonable when consideration was given for the use of the micropipettor that delivered only about 80 percent on average of the nominal mass of spiked analytes. Finally, the recoveries of most surrogate compounds in surface and ground-water samples were reasonable. Problems in sample handling (for example, spillage) were likely not the cause of any of the low recoveries of spiked compounds.

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

PubMed Central

Greinert, R.; Volkmer, B.; Henning, S.; Breitbart, E. W.; Greulich, K. O.; Cardoso, M. C.; Rapp, Alexander

2012-01-01

UVA (320–400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G1-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer. PMID:22941639

Use of FSH in two different regimens for ovarian superstimulation prior to ovum pick up and in vitro embryo production in Holstein cows.

PubMed

da Silva, Júlio César Barboza; Ferreira, Roberta Machado; Maturana Filho, Milton; Naves, Julianne de Rezende; Santin, Thiago; Pugliesi, Guilherme; Madureira, Ed Hoffmann

2017-03-01

We aimed with the present study to evaluate the effects of FSH treatment (200 mg) split in four or six administrations on ovarian follicle stimulation and in vitro oocyte competence for embryo production in dairy cows with synchronized follicular wave emergence. On random days of the estrous cycle (Day 0), non-lactating Holstein cows received a progesterone (P4)-releasing intravaginal device and 2 mg estradiol benzoate IM. On Day 3, they received 0.530 mg sodium cloprostenol (PGF2α) IM. Control cows (n = 35) received no further treatments, whereas FSH-treated cows received 200 mg FSH split in four (FSH4 group; n = 33) or six (FSH6 group; n = 33) administration regimens. Starting on Day 4, cows in FSH4 group received 200 mg FSH split in four equivalent doses of 50 mg 12 h apart. Cows in FSH6 group received the same total FSH dose split in six equivalent doses of 33.3 mg 12 h apart, but treatments started on Day 3. On Day 7 AM (36 h of "coasting" period for FSH-treated groups), the P4 devices were removed and cows were subjected to ovum pick up (OPU). Viable oocytes were in vitro fertilized using sexed-sorted semen. Although FSH treatment did not (P > 0.1) increase the total number of follicles (Control, 53.2 ± 4.5 vs. FSH-treated, 51.4 ± 3.1), the two hormonal stimulation regimens, FSH4 and FSH6, increased the number of medium follicles (6-10 mm; 5.2 ± 0.5 vs. 18.1 ± 1.4; P < 0.0001) and reduced the number of small follicles (2-5.9 mm; 46.3 ± 5.1 vs. 31.0 ± 2.4 P < 0.0001). Also, FSH treatment or regimen did not increase (P > 0.1) the number of viable oocytes (Control, 12.6 ± 1.26 vs. FSH-treated, 12.70 ± 1.03), recovery rate (Control, 36.5% vs. FSH-treated, 36%) and the number of in vitro produced blastocyst (Control, 4.1 ± 0.52 vs. FSH-treated 4.3 ± 0.5). We concluded that FSH stimulation protocol proposed herein is effective to stimulate the growth of small antral follicle population prior to OPU, but it was ineffective to improve in vitro oocyte competence for embryo production in non-lactating Holstein cows with synchronized follicular wave emergence. Copyright © 2017 Elsevier Inc. All rights reserved.

Split radiator design for heat rejection optimization for a waste heat recovery system

DOEpatents

Ernst, Timothy C.; Nelson, Christopher R.

2016-10-18

A cooling system provides improved heat recovery by providing a split core radiator for both engine cooling and condenser cooling for a Rankine cycle (RC). The cooling system includes a radiator having a first cooling core portion and a second cooling core portion. An engine cooling loop is fluidly connected the second cooling core portion. A condenser of an RC has a cooling loop fluidly connected to the first cooling core portion. A valve is provided between the engine cooling loop and the condenser cooling loop adjustably control the flow of coolant in the condenser cooling loop into the engine cooling loop. The cooling system includes a controller communicatively coupled to the valve and adapted to determine a load requirement for the internal combustion engine and adjust the valve in accordance with the engine load requirement.

Successful Recovery and Transplantation of 11 Organs Including Face, Bilateral Upper Extremities, and Thoracic and Abdominal Organs From a Single Deceased Organ Donor.

PubMed

Tullius, Stefan G; Pomahac, Bohdan; Kim, Heung Bae; Carty, Matthew J; Talbot, Simon G; Nelson, Helen M; Delmonico, Francis L

2016-10-01

We report on the to date largest recovery of 11 organs from a single deceased donor with the transplantation of face, bilateral upper extremities, heart, 1 lung, liver (split for 2 recipients), kidneys, pancreas, and intestine. Although logistically challenging, this case demonstrates the feasibility and safety of the recovery of multiple thoracic and abdominal organs with multiple vascular composite allotransplants and tissues. Our experience of 8 additional successful multiple vascular composite allotransplants, thoracic, and abdominal organ recoveries suggests that such procedures are readily accomplishable from the same deceased donor.

Femtosecond laser-induced subwavelength ripples formed by asymmetrical grating splitting

NASA Astrophysics Data System (ADS)

Feng, Pin; Jiang, Lan; Li, Xin; Zhang, Kaihu; Shi, Xuesong; Li, Bo; Lu, Yongfeng

2016-05-01

The formation process and mechanism of subwavelength ripples were studied upon irradiation of ZnO by a femtosecond laser (800 nm, 50 fs, 1 kHz). An abnormally asymmetrical grating-splitting phenomenon was discovered. At relatively high laser fluences (F = 0.51-0.63 J/cm2), near-wavelength ripples were split asymmetrically to create subwavelength laser-induced periodic surface structures (LIPSS) with dual gaps (˜230 nm and ˜430 nm) on the primary grooves. At relatively low laser fluences (F = 0.4-0.45 J/cm2), near-wavelength ripples were split symmetrically, leading to the formation of uniform subwavelength structures with a period of ˜340 nm. The splitting phenomena are related to the varying laser beam dose induced by the overlapping during line scanning. The two grating-splitting types further imply that the dominated mechanism for LIPSS formation may be changed under different processing conditions.

A new low-volume isosmotic polyethylene glycol solution plus bisacodyl versus split-dose 4 L polyethylene glycol for bowel cleansing prior to colonoscopy: a randomised controlled trial.

PubMed

Cesaro, Paola; Hassan, Cesare; Spada, Cristiano; Petruzziello, Lucio; Vitale, Giovanna; Costamagna, Guido

2013-01-01

4-L polyethylene glycol preparations are effective for colon cleansing before colonoscopy. However, large volume and unpleasant taste reduce tolerability and acceptability limiting patient compliance. A new isosmotic low-volume polyethylene glycol preparation with citrates and simethicone plus bisacodyl has been developed to improve patient compliance and tolerability. To compare the efficacy of 2 different regimens of preparation vs a split-dose of polyethylene glycol solution. In this randomised, blinded, comparative study, 153 patients were allocated to 3 arms. Arm 1 (n=52) received bisacodyl and 2-L polyethylene glycol with citrates and simethicone the day before the procedure. Arm 2 (n=50) received bisacodyl the day before and 2-L polyethylene glycol with citrates and simethicone on the day of colonoscopy. Control group (n=51) received a split-dose of 4-L polyethylene glycol. Cleansing was evaluated according to Ottawa scale. The mean Ottawa score was not different in the 3 groups. Excellent cleansing was observed more frequently in arm 2 (70%) than in controls (49%) (p<0.05). No serious adverse events were observed in the 3 regimens. The willingness to repeat the same bowel preparation was superior in arms 1 and 2 than in controls (p<0.001). New low-volume preparations seem to be as effective as the split 4-L polyethylene glycol regimen, showing a better tolerability and acceptability. Copyright © 2012. Published by Elsevier Ltd.

SU-E-T-433: Field-In-Field Irradiation for Breast Cancer with VERO-4DRT System: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayashi, N; Mizuno, T; Takada, Y

2015-06-15

Purpose: The Vero-4DRT system is a dedicated system for high precision radiation therapy. However, the field size is limited at 15 cm x 15 cm and shapes by using multi-leaf collimator (MLC) without X-Jaw and Y-Jaw. Therefore VERO-4DRT system is not available to simple wedged irradiation for breast cancer. In this study, we suppose FIF with ring and/or tilt/pan angles whole breast irradiation (FIFWBI). The purpose of this study is to verify the feasibility of FIFWBI with VERO-4DRT system. Methods: As fundamental evaluation, we performed commissioning test with phantom. The absorbed dose evaluation at several reference points and dose distributionmore » including split area were performed. We planned 10 demonstrative shapes in phantom for measuring these contents with i-plan workstation (BrainLAB). As clinical evaluation, the dose distribution and dose indexes were evaluated with actual patient data. Five patients with breast cancer were designed FIFWBI radiotherapy plan with split fields. Then, the dose distribution and dose indexes (including Dmax, Dmin, D95, D5 and Homogeneity index) were evaluated in these plans. Results: As the results of fundamental evaluation, all absorbed dose errors between calculated and measured doses were within 2%. The gamma passing rates with 2 mm/3% criteria in all cases were 96±2%. As the results of clinical evaluation, the values of Dmax, D95, D50, D5, and Homogeneity Index were 41.7±0.90 Gy, 49.4±0.34 Gy, 52.26±0.24 Gy, and 1.39±0.03, respectively. For Japanese breast cancer patients, this technique was feasible. However, the large split region was happened in FIFWBI in case of patient with large breast. Conclusion: We evaluated the FIFWBI technique with VERO-4DRT system. This technique is feasible for Japanese patients, but the patient with large breast should be disagreed with this technique.« less

X-Ray-Induced Chromosome Aberrations in Mouse Dictyate Oocytes. II. Fractionation and Dose Rate Effects

PubMed Central

Brewen, J. G.; Payne, H. S.; Adler, I. D.

1977-01-01

Split-dose experiments were done on maturing dictyate oocytes to determine if the magnitude of the first dose influenced the "rejoining time" of radiation-induced chromosomal lesions. A total dose of 400r was split into various combinations with varying fractionation intervals. The data derived from analyzing interchanges indicate that there is no difference in the rejoining time whether the first dose was 100, 200, or 300r. It thus appears that the radiation dose in the ranges studied does not significantly alter the rate of repair of the chromosomal lesions. This conclusion is contrary to that which has been propounded to explain the nonlinear dose curves obtained for specific locus mutations. Chronic 60Co γ-ray exposures were given to female mice over an 8-day period. The exposures were delivered during the period of peak sensitivity, i.e., 8–16 days prior to ovulation. The doses given were 117, 240, 348, and 483r. The aberration yields observed were dramatically lower than for comparable doses of acute X rays even when the RBE of γ rays compared with X rays is taken into account. The large drop in yields at the low dose rates is interpreted as resulting from a large two-track component in the acute curve, and as being independent of effects on repair systems. PMID:604163

Dopant profile modeling by rare event enhanced domain-following molecular dynamics

DOEpatents

Beardmore, Keith M.; Jensen, Niels G.

2002-01-01

A computer-implemented molecular dynamics-based process simulates a distribution of ions implanted in a semiconductor substrate. The properties of the semiconductor substrate and ion dose to be simulated are first initialized, including an initial set of splitting depths that contain an equal number of virtual ions implanted in each substrate volume determined by the splitting depths. A first ion with selected velocity is input onto an impact position of the substrate that defines a first domain for the first ion during a first timestep, where the first domain includes only those atoms of the substrate that exert a force on the ion. A first position and velocity of the first ion is determined after the first timestep and a second domain of the first ion is formed at the first position. The first ion is split into first and second virtual ions if the first ion has passed through a splitting interval. The process then follows each virtual ion until all of the virtual ions have come to rest. A new ion is input to the surface and the process repeats until all of the ion dose has been input. The resulting ion rest positions form the simulated implant distribution.

Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

USGS Publications Warehouse

Fleming, W.J.; Bradbury, S.P.

1981-01-01

Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

Regional radiation dose susceptibility within the parotid gland: Effects on salivary loss and recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, Haley, E-mail: hdclark@phas.ubc.ca; Reinsberg, Stefan; Hovan, Allan

2015-04-15

Purpose: Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head-and-neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose-dependence of salivary output loss and recovery in a prospective study. Methods: Salivary output was collected from patients undergoing radiotherapy treatment for head-and-neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose-dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearman’s rank correlation coefficients, local linear regression) and parametric (least-summore » of squares, least-median of squares) techniques. Results: Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left- and right parotid combined dose φ = min (D{sub L},  45 Gy) + min (D{sub R},  45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A{sub 3m} = 0.0604 Gy{sup −1} and A{sub 1y} = 0.0379 Gy{sup −1}. Recovery was not significantly associated with dose. Hints of lateral organ sub-segment dose–response dimorphism were observed. Conclusions: Sub-segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post-treatment. It seems unlikely that a population’s mean recovery will exceed 20%–30% of baseline output at 1 yr after radiotherapy treatment using current (whole-organ based) clinical guidelines.« less

Effects of gamma irradiation on the performance of Jatropha (Jatropha curcas L.) accessions

NASA Astrophysics Data System (ADS)

Surahman, M.; Santosa, E.; Agusta, H.; Aisyah, S. I.; Nisya, F. N.

2018-03-01

This study aimed to assess the effects of mutation by using gamma ray on the performance of jatropha plants. The study was conducted at PAIR BATAN. Jatropha seeds obtained from the collection farm of SBRC LPPM IPB and PT Indocement Tunggal Prakarsa Tbk in Gunung Putri, Bogor, were irradiated. The irradiated seeds were grown in Jonggol Trial Farm of IPB. Gamma irradiation was conducted by using a GCM 4000A device. Treatments consisted of irradiation doses, irradiation methods, and accessions. Irradiation doses given were 175, 200, 225 Gy, and no irradiation (control). Irradiation methods consisted of acute, intermittent, and split-dose. Accessions used in this study were Dompu, Medan, Bima, Lombok, ITP II, IP2P, and Thailand. Results of the study were analysed until 5 months after planting showed that gamma ray mutation gave stimulating and inhibiting effects on similar traits. Irradiation dose of 225 Gy was good to be given in acute, intermittent, and split-dose methods. Irradiation effects were found to be significant in jatropha accessions. Effects of irradiation on production will be published soon.

Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets.

PubMed

Music, Nedzad; Reber, Adrian J; Kim, Min-Chul; York, Ian A; Kang, Sang-Moo

2016-01-20

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine ("Split") alone, influenza split vaccine supplemented with M2e5x VLP ("Split+M2e5x"), M2e5x VLP alone ("M2e5x"), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. Published by Elsevier Ltd.

Modeling of beam customization devices in the pencil-beam splitting algorithm for heavy charged particle radiotherapy.

PubMed

Kanematsu, Nobuyuki

2011-03-07

A broad-beam-delivery system for radiotherapy with protons or ions often employs multiple collimators and a range-compensating filter, which offer complex and potentially useful beam customization. It is however difficult for conventional pencil-beam algorithms to deal with fine structures of these devices due to beam-size growth during transport. This study aims to avoid the difficulty with a novel computational model. The pencil beams are initially defined at the range-compensating filter with angular-acceptance correction for upstream collimation followed by stopping and scattering. They are individually transported with possible splitting near the aperture edge of a downstream collimator to form a sharp field edge. The dose distribution for a carbon-ion beam was calculated and compared with existing experimental data. The penumbra sizes of various collimator edges agreed between them to a submillimeter level. This beam-customization model will be used in the greater framework of the pencil-beam splitting algorithm for accurate and efficient patient dose calculation.

TH-CD-202-04: Evaluation of Virtual Non-Contrast Images From a Novel Split-Filter Dual-Energy CT Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, J; Szczykutowicz, T; Bayouth, J

Purpose: To compare the ability of two dual-energy CT techniques, a novel split-filter single-source technique of superior temporal resolution against an established sequential-scan technique, to remove iodine contrast from images with minimal impact on CT number accuracy. Methods: A phantom containing 8 tissue substitute materials and vials of varying iodine concentrations (1.7–20.1 mg I /mL) was imaged using a Siemens Edge CT scanner. Dual-energy virtual non-contrast (VNC) images were generated using the novel split-filter technique, in which a 120kVp spectrum is filtered by tin and gold to create high- and low-energy spectra with < 1 second temporal separation between themore » acquisition of low- and high-energy data. Additionally, VNC images were generated with the sequential-scan technique (80 and 140kVp) for comparison. CT number accuracy was evaluated for all materials at 15, 25, and 35mGy CTDIvol. Results: The spectral separation was greater for the sequential-scan technique than the split-filter technique with dual-energy ratios of 2.18 and 1.26, respectively. Both techniques successfully removed iodine contrast, resulting in mean CT numbers within 60HU of 0HU (split-filter) and 40HU of 0HU (sequential-scan) for all iodine concentrations. Additionally, for iodine vials of varying diameter (2–20 mm) with the same concentration (9.9 mg I /mL), the system accurately detected iodine for all sizes investigated. Both dual-energy techniques resulted in reduced CT numbers for bone materials (by >400HU for the densest bone). Increasing the imaging dose did not improve the CT number accuracy for bone in VNC images. Conclusion: VNC images from the split-filter technique successfully removed iodine contrast. These results demonstrate a potential for improving dose calculation accuracy and reducing patient imaging dose, while achieving superior temporal resolution in comparison sequential scans. For both techniques, inaccuracies in CT numbers for bone materials necessitate consideration for radiation therapy treatment planning.« less

Dynamics of functional failures and recovery in complex road networks

NASA Astrophysics Data System (ADS)

Zhan, Xianyuan; Ukkusuri, Satish V.; Rao, P. Suresh C.

2017-11-01

We propose a new framework for modeling the evolution of functional failures and recoveries in complex networks, with traffic congestion on road networks as the case study. Differently from conventional approaches, we transform the evolution of functional states into an equivalent dynamic structural process: dual-vertex splitting and coalescing embedded within the original network structure. The proposed model successfully explains traffic congestion and recovery patterns at the city scale based on high-resolution data from two megacities. Numerical analysis shows that certain network structural attributes can amplify or suppress cascading functional failures. Our approach represents a new general framework to model functional failures and recoveries in flow-based networks and allows understanding of the interplay between structure and function for flow-induced failure propagation and recovery.

76 FR 71593 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

..., Ventilation and Air Conditioning (HVAC) system for the Plymouth Hall Apartments project, and to the... on the basis that the relevant manufactured goods (split HVAC systems) are not produced in the U.S...

Influence of Harvest Aid Herbicides on Seed Germination, Seedling Vigor and Milling Quality Traits of Red Lentil (Lens culinaris L.).

PubMed

Subedi, Maya; Willenborg, Christian J; Vandenberg, Albert

2017-01-01

Most red lentil produced worldwide is consumed in dehulled form, and post-harvest milling and splitting qualities are major concerns in the secondary processing industry. Lentil producers in northern temperate regions usually apply pre-harvest desiccants as harvest aids to accelerate the lentil crop drying process and facilitate harvesting operations. This paper reports on field studies conducted at Scott and Saskatoon, Saskatchewan, Canada in the 2012 and 2013 cropping seasons to evaluate whether herbicides applied as harvest aids alone or tank mixed with glyphosate affect seed germination, seedling vigor, milling, and splitting qualities. The site-year by desiccant treatment interaction for seed germination, vigor, and milling recovery yields was significant. Glyphosate applied alone or as tank mix with other herbicides (except diquat) reduced seed germination and seedling vigor at Saskatoon and Scott in 2012 only. Pyraflufen-ethyl (20 g ai ha -1 ) applied with glyphosate as well as saflufenacil (36 g ai ha -1 ) decreased dehulling efficiency, while saflufenacil and/or glufosinate with glyphosate reduced milling recovery and football recovery, although these effects were inconsistent. Application of diquat alone or in combination with glyphosate exhibited more consistent dehulling efficiency gains and increases in milling recovery yield. Significant but negative associations were observed between glyphosate residue in seeds and seed germination ( r = -0.84, p < 0.001), seed vigor ( r = -0.62, p < 0.001), dehulling efficiency ( r = -0.55, p < 0.001), and milling recovery ( r = -0.62, p < 0.001). These results indicate application of diquat alone or in combination with glyphosate may be a preferred option for lentil growers to improve milling recovery yield.

Influence of Harvest Aid Herbicides on Seed Germination, Seedling Vigor and Milling Quality Traits of Red Lentil (Lens culinaris L.)

PubMed Central

Subedi, Maya; Willenborg, Christian J.; Vandenberg, Albert

2017-01-01

Most red lentil produced worldwide is consumed in dehulled form, and post-harvest milling and splitting qualities are major concerns in the secondary processing industry. Lentil producers in northern temperate regions usually apply pre-harvest desiccants as harvest aids to accelerate the lentil crop drying process and facilitate harvesting operations. This paper reports on field studies conducted at Scott and Saskatoon, Saskatchewan, Canada in the 2012 and 2013 cropping seasons to evaluate whether herbicides applied as harvest aids alone or tank mixed with glyphosate affect seed germination, seedling vigor, milling, and splitting qualities. The site-year by desiccant treatment interaction for seed germination, vigor, and milling recovery yields was significant. Glyphosate applied alone or as tank mix with other herbicides (except diquat) reduced seed germination and seedling vigor at Saskatoon and Scott in 2012 only. Pyraflufen-ethyl (20 g ai ha−1) applied with glyphosate as well as saflufenacil (36 g ai ha−1) decreased dehulling efficiency, while saflufenacil and/or glufosinate with glyphosate reduced milling recovery and football recovery, although these effects were inconsistent. Application of diquat alone or in combination with glyphosate exhibited more consistent dehulling efficiency gains and increases in milling recovery yield. Significant but negative associations were observed between glyphosate residue in seeds and seed germination (r = −0.84, p < 0.001), seed vigor (r = −0.62, p < 0.001), dehulling efficiency (r = −0.55, p < 0.001), and milling recovery (r = −0.62, p < 0.001). These results indicate application of diquat alone or in combination with glyphosate may be a preferred option for lentil growers to improve milling recovery yield. PMID:28352275

Methods for assisting recovery of damaged brain and spinal cord using arrays of X-Ray microplanar beams

DOEpatents

Dilmanian, F. Avraham; McDonald, III, John W.

2007-12-04

A method of assisting recovery of an injury site of brain or spinal cord injury includes providing a therapeutic dose of X-ray radiation to the injury site through an array of parallel microplanar beams. The dose at least temporarily removes regeneration inhibitors from the irradiated regions. Substantially unirradiated cells surviving between the microplanar beams migrate to the in-beam irradiated portion and assist in recovery. The dose may be administered in dose fractions over several sessions, separated in time, using angle-variable intersecting microbeam arrays (AVIMA). Additional doses may be administered by varying the orientation of the microplanar beams. The method may be enhanced by injecting stem cells into the injury site.

Methods for assisting recovery of damaged brain and spinal cord using arrays of X-ray microplanar beams

DOEpatents

Dilmanian, F. Avraham; McDonald, III, John W.

2007-01-02

A method of assisting recovery of an injury site of brain or spinal cord injury includes providing a therapeutic dose of X-ray radiation to the injury site through an array of parallel microplanar beams. The dose at least temporarily removes regeneration inhibitors from the irradiated regions. Substantially unirradiated cells surviving between the microplanar beams migrate to the in-beam irradiated portion and assist in recovery. The dose may be administered in dose fractions over several sessions, separated in time, using angle-variable intersecting microbeam arrays (AVIMA). Additional doses may be administered by varying the orientation of the microplanar beams. The method may be enhanced by injecting stem cells into the injury site.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2015-10-01

demonstrated locomotor recovery in mice receiving 40mg/kg DFA up to 3 hours following spinal cord injury -We demonstrated improved locomotor recovery...health, as evaluated by body weight -We identified no added locomotor recovery due to multiple, successive doses of DFA. Moreover, additional doses...bladder function Significance: We have identified robust locomotor recovery in both mild and severe spinal cord injured mice that received DFA up

Antagonism of atracurium with neostigmine. Effect of dose on speed of recovery.

PubMed

Goldhill, D R; Carter, J A; Suresh, D; Whitehead, J P; Flynn, P J

1991-06-01

In 36 patients in whom anaesthesia was maintained with nitrous oxide and 0.5% isoflurane an atracurium-induced neuromuscular block was either allowed to recover spontaneously or antagonised with one of four doses of neostigmine (15 micrograms/kg, 35 micrograms/kg, 55 micrograms/kg or 75 micrograms/kg). The recovery times to a train-of-four ratio of 0.5, 0.75 and 0.9 were recorded. In patients given neostigmine, antagonism was at an average T1 of between 8.8% and 14.9%. There was no difference in the recovery times between the patients given neostigmine 35 micrograms/kg, 55 micrograms/kg or 75 micrograms/kg. Recovery after neostigmine 15 micrograms/kg was significantly slower than after the higher doses. One patient given neostigmine 75 micrograms/kg showed an unusual bimodal pattern of recovery. There appears to be no benefit in giving a larger dose than 35 micrograms/kg of neostogmine as a single bolus.

The influence of intrinsic sympathomimetic activity and beta-1 receptor selectivity on the recovery of finger skin temperature after finger cooling in normotensive subjects.

PubMed

Lenders, J W; Salemans, J; de Boo, T; Lemmens, W A; Thien, T; van't Laar, A

1986-03-01

A double-blind randomized study was designed to investigate differences in the recovery of finger skin temperature after finger cooling during dosing with placebo or one of four beta-blockers: propranolol, atenolol, pindolol, and acebutolol. In 11 normotensive nonsmoking subjects, finger skin temperature was measured with a thermocouple before and 20 minutes after immersion of one hand in a water bath at 16 degrees C. This finger cooling test caused no significant changes in systemic hemodynamics such as arterial blood pressure, heart rate, and forearm blood flow. The recovery of finger skin temperature during propranolol dosing was better than that during pindolol and atenolol dosing. There were no differences between the recoveries of skin temperature during pindolol, atenolol, and acebutolol dosing. Thus we could demonstrate no favorable effect of intrinsic sympathomimetic activity or beta 1-selectivity on the recovery of finger skin temperature after finger cooling.

Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets

PubMed Central

Music, Nedzad; Reber, Adrian J.; Kim, Min-Chul; York, Ian A.; Kang, Sang-Moo

2015-01-01

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine (“Split”) alone, influenza split vaccine supplemented with M2e5x VLP (“Split+M2e5x”), M2e5x VLP alone (“M2e5x”), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. PMID:26709639

A comparison between succinylcholine and rocuronium on the recovery profile of the laryngeal muscles during intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective porcine model.

PubMed

Lu, I-Cheng; Chang, Pi-Ying; Hsu, Hung-Te; Tseng, Kuang-Yi; Wu, Che-Wei; Lee, Ka-Wo; Ho, Kuen-Yao; Chiang, Feng-Yu

2013-09-01

The use of succinylcholine and rocuronium are reportedly feasible during intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) in thyroid surgery. This study aimed to investigate and compare the recovery profiles of succinylcholine and rocuronium on the laryngeal muscle during IONM of the RLN in a porcine model. Nine male Duroc-Landrace piglets were anesthetized with thiamylal and underwent tracheal intubation without neuromuscular blocking agents (NMBAs). Needle electrodes were inserted into the vocalis muscles through the cricothyroid ligament. The RLN was exposed and stimulated. Electromyographic (EMG) signals were obtained before and after the intravenous administration of a NMBA. The EMG amplitudes were measured before and after (at 1-minute intervals) the administration of the study drug until complete recovery. The study NMBA regimen included succinylcholine (1 mg/kg), low-dose rocuronium (0.3 mg/kg), and standard dose rocuronium (0.6 mg/kg). The maximal neuromuscular blockade and 80% recovery (i.e., duration) of the control responses were recorded and analyzed. The 80% recovery of the control response for succinylcholine (1 mg/kg) was 19.7 ± 1.5 minutes; low-dose rocuronium (0.3 mg/kg), 16.3 ± 2.5 minutes; and standard dose rocuronium (0.6 mg/kg), 29.3 ± 5.7 minutes. Succinylcholine (1 mg/kg) and low-dose rocuronium (0.3 mg/kg) had significantly shorter durations than standard dose rocuronium (0.6 mg/kg). The EMG signal recovery returned to baseline within 30 minutes in the succinylcholine and low-dose rocuronium groups, but it did not return to baseline until 1 hour after surgery in the rocuronium (0.6 mg/kg) group. In this study, succinylcholine (1 mg/kg) and low-dose rocuronium (0.3 mg/kg) had favorable recovery profiles on the laryngeal muscle. It is recommended that low-dose rocuronium may replace succinylcholine for the induction of general anesthesia during IONM of the RLN in thyroid surgery. Copyright © 2013. Published by Elsevier B.V.

MiraLAX is not as effective as GoLytely in bowel cleansing before screening colonoscopies.

PubMed

Hjelkrem, Michael; Stengel, Joel; Liu, Mark; Jones, David P; Harrison, Stephen A

2011-04-01

Successful colonoscopies require good bowel preparations-poor bowel preparations can increase medical costs, rates of missed lesions, and procedure duration. The combination of polyethylene glycol (PEG) 3350 without electrolytes (MiraLAX; Schering-Plough Healthcare Products, Inc, Kenilworth, NJ) and 64 oz of Gatorade (PepsiCo, Inc, Purchase, NY) has gained popularity as a bowel preparation regimen. However, the efficacy and tolerability of this approach has not been compared with standard bowel preparations in clinical trials. We compared split-dose (PEG) 3350 with electrolytes (GoLytely; Braintree Laboratories, Inc, Braintree, MA) with split-dose MiraLAX alone and in combination with pretreatment medications (bisacodyl or lubiprostone) to determine the efficacy and patient tolerability of MiraLAX as an agent for bowel preparation. We performed a prospective, randomized, blinded, controlled trial at a tertiary care center. Patients (n=403) were randomly assigned to groups given GoLytely, MiraLAX, MiraLAX with bisacodyl (10 mg), or MiraLAX with lubiprostone (24 μg). MiraLAX was combined with 64 oz of Gatorade. All patients were surveyed regarding preparation satisfaction and tolerability. The Ottawa bowel preparation scale was used to grade colon cleanliness. GoLytely was more effective at bowel cleansing (average Ottawa score, 5.1) than MiraLAX alone (average Ottawa score, 6.9) or in combination with lubiprostone (average Ottawa score, 6.8), or bisacodyl (average Ottawa score, 6.3) (P<.001). MiraLAX was associated with a trend toward longer procedure duration (P=.096). Groups given MiraLAX rated the overall experience as more satisfactory than those given GoLytely (P<.001). There were no differences between polyp detection rates (P=.346) or adverse events (P=.823). Split-dose MiraLAX in 64 oz of Gatorade is not as effective as 4 L split-dose GoLytely in bowel cleansing for screening colonoscopies. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats.

PubMed

Belardin, Larissa Berloffa; Simão, Vinícius Augusto; Leite, Gabriel Adan Araújo; Chuffa, Luiz Gustavo de Almeida; Camargo, Isabel Cristina Cherici

2014-04-01

This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30-day recovery (2), and 60-day recovery (3). At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day). Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity. Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers. Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent. We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response. © 2014 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ren; Trindade, Alexandre; Instituto Gulbenkian de Ciencia, Oeiras

Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the densitymore » of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.« less

Fast sparse recovery and coherence factor weighting in optoacoustic tomography

NASA Astrophysics Data System (ADS)

He, Hailong; Prakash, Jaya; Buehler, Andreas; Ntziachristos, Vasilis

2017-03-01

Sparse recovery algorithms have shown great potential to reconstruct images with limited view datasets in optoacoustic tomography, with a disadvantage of being computational expensive. In this paper, we improve the fast convergent Split Augmented Lagrangian Shrinkage Algorithm (SALSA) method based on least square QR (LSQR) formulation for performing accelerated reconstructions. Further, coherence factor is calculated to weight the final reconstruction result, which can further reduce artifacts arising in limited-view scenarios and acoustically heterogeneous mediums. Several phantom and biological experiments indicate that the accelerated SALSA method with coherence factor (ASALSA-CF) can provide improved reconstructions and much faster convergence compared to existing sparse recovery methods.

Sci—Fri PM: Topics — 06: The influence of regional dose sensitivity on salivary loss and recovery in the parotid gland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, H; BC Cancer Agency, Surrey, B.C.; BC Cancer Agency, Vancouver, B.C.

Purpose: The Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC 2010) survey of radiation dose-volume effects on salivary gland function has called for improved understanding of intragland dose sensitivity and the effectiveness of partial sparing in salivary glands. Regional dose susceptibility of sagittally- and coronally-sub-segmented parotid gland has been studied. Specifically, we examine whether individual consideration of sub-segments leads to improved prediction of xerostomia compared with whole parotid mean dose. Methods: Data from 102 patients treated for head-and-neck cancers at the BC Cancer Agency were used in this study. Whole mouth stimulated saliva was collected before (baseline), threemore » months, and one year after cessation of radiotherapy. Organ volumes were contoured using treatment planning CT images and sub-segmented into regional portions. Both non-parametric (local regression) and parametric (mean dose exponential fitting) methods were employed. A bootstrap technique was used for reliability estimation and cross-comparison. Results: Salivary loss is described well using non-parametric and mean dose models. Parametric fits suggest a significant distinction in dose response between medial-lateral and anterior-posterior aspects of the parotid (p<0.01). Least-squares and least-median squares estimates differ significantly (p<0.00001), indicating fits may be skewed by noise or outliers. Salivary recovery exhibits a weakly arched dose response: the highest recovery is seen at intermediate doses. Conclusions: Salivary function loss is strongly dose dependent. In contrast no useful dose dependence was observed for function recovery. Regional dose dependence was observed, but may have resulted from a bias in dose distributions.« less

Sugammadex and Ideal Body Weight in Bariatric Surgery

PubMed Central

Alessandri, Francesco; Wefki Abdelgawwad Shousha, Ahmed Abdelgawwad; Sabba, Antonio; Cutolo, Alessandra

2013-01-01

Background. The obese patients have differences in body composition, drug distribution, and metabolism. Sugammadex at T 2 recovery in a dose of 2 mg kg−1 of real body weight (RBW) can completely reverse the NMB block; in our study we investigated the safety and efficacy of Sugammadex dose based on their ideal body weight (IBW). Methods. 40 patients of both sexes undergoing laparoscopic bariatric surgery were enrolled divided into 2 groups according to the dose of Sugammadex: the first received a dose of 2 mg kg−1 of IBW and the second received a dose of 2 mg kg−1 of RBW. Both were anesthetized with doses calculated according to the IBW: fentanyl 2 μg kg−1, propofol 3 mg kg−1, rocuronium 0,6 mg kg−1, oxygen, air, and desflurane (6–8%). Maintenance doses of rocuronium were 1/4 of the intubation dose. Sugammadex was administrated at T 2 recovery. Results. The durations of intubation and maintenance doses of rocuronium were similar in both groups. In IBW group, the T 4/T 1 value of 0.9 was reached in 151 ± 44 seconds and in 121 ± 55 seconds in RBW group (P = 0.07). Discussion. Recovery times to T 4/T 1 of 0.9 are surprisingly similar in both groups without observing any postoperative residual curarization. Conclusion. Sugammadex doses calculated according to the IBW are certainly safe for a rapid recovery and absence of PORC. PMID:23840203

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aburano, T.; Takayama, T.; Nakajima, K.

The three different methods to evaluate the alterations of split renal function following continued captopril treatment were studied in patients with hypertension. Five patients had unilateral and 2 had bilateral renal artery stenosis, and 13 had normal renal arteries. The studies were performed the day prior to receiving captopril (baseline), and 6th or 7th day following continued captorpril treatment (37.5mg or 75mg/day): Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 iodohippuran and Tc-99m DTPA were measured respectively by the methods using kidney counting corrected for depth and dose, described by Schlegel and Gates.more » And Tc-99m DMSA uptake was also evaluated qualitatively. In most of patients with renal artery stenosis, split GFR and Tc-99m DMSA uptake in the affected kidney were markedly decreased 6th or 7th day following continued captorpril treatment. These findings suggest that the captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For this purpose, split GFR determination and Tc-99m DMSA study are more useful than split ERPF determination.« less

Systematic review and meta-analysis of colon cleansing preparations in patients with inflammatory bowel disease

PubMed Central

Restellini, Sophie; Kherad, Omar; Bessissow, Talat; Ménard, Charles; Martel, Myriam; Taheri Tanjani, Maryam; Lakatos, Peter L; Barkun, Alan N

2017-01-01

AIM To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease. METHODS Systematic searches were performed (January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high (> 3 L) or low-volume (2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-to-repeat the procedure and side effects/complications. RESULTS Out of 439 citations, 4 trials fulfilled our inclusion criteria (n = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol (PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume vs PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84 (0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations vs high-volume; OR = 5.11 (1.31-20.0). CONCLUSION In inflammatory bowel disease population, PEG low-volume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-to-repeat. Further additional research is urgently required to compare contemporary products in this population. PMID:28932092

Systematic review and meta-analysis of colon cleansing preparations in patients with inflammatory bowel disease.

PubMed

Restellini, Sophie; Kherad, Omar; Bessissow, Talat; Ménard, Charles; Martel, Myriam; Taheri Tanjani, Maryam; Lakatos, Peter L; Barkun, Alan N

2017-08-28

To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease. Systematic searches were performed (January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high (> 3 L) or low-volume (2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-to-repeat the procedure and side effects/complications. Out of 439 citations, 4 trials fulfilled our inclusion criteria ( n = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol (PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume vs PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84 (0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations vs high-volume; OR = 5.11 (1.31-20.0). In inflammatory bowel disease population, PEG low-volume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-to-repeat. Further additional research is urgently required to compare contemporary products in this population.

Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: A prospective, randomized, double-blinded, placebo controlled, clinical trial.

PubMed

De Oliveira, Gildasio S; Rodes, Meghan E; Bialek, Jane; Kendall, Mark C; McCarthy, Robert J

2017-11-15

Few systemic drug interventions are efficacious to improve patient reported quality of recovery after ambulatory surgery. We aimed to evaluate whether a single dose systemic acetaminophen improve quality of recovery in female patients undergoing ambulatory breast surgery. We hypothesized that patients receiving a single dose systemic acetaminophen at the end of the surgical procedure would have a better global quality of postsurgical recovery compared to the ones receiving saline. The study was a prospective randomized double blinded, placebo controlled, clinical trial. Healthy female subjects were randomized to receive 1 g single dose systemic acetaminophen at the end of the surgery or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. The association between opioid consumption and quality of recovery was evaluated using Spearman rho. P < .05 was used to reject the null hypothesis for the primary outcome. Seventy subjects were randomized and sixty-five completed the study. Patients' baseline characteristics and surgical factors were similar between the study groups. There was a clinically significant difference in the global QoR-40 scores between the acetaminophen and the saline groups, median (IQR) of 189 (183 to 194) and 183 (175 to 190), respectively, P = .01. In addition, there was an inverse relationship (Spearman's rho= -0.33) between oral opioid consumption at home (oral morphine equivalents) and 24 hour postoperative quality of recovery, P = .007. A single dose of systemic acetaminophen improves patient reported quality of recovery after ambulatory breast surgery. The use of systemic acetaminophen is an efficacious strategy to improve patient perceived quality of postsurgical recovery and analgesic outcomes after hospital discharge for ambulatory breast surgery. © 2017 Wiley Periodicals, Inc.

Sparsity constrained split feasibility for dose-volume constraints in inverse planning of intensity-modulated photon or proton therapy

NASA Astrophysics Data System (ADS)

Penfold, Scott; Zalas, Rafał; Casiraghi, Margherita; Brooke, Mark; Censor, Yair; Schulte, Reinhard

2017-05-01

A split feasibility formulation for the inverse problem of intensity-modulated radiation therapy treatment planning with dose-volume constraints included in the planning algorithm is presented. It involves a new type of sparsity constraint that enables the inclusion of a percentage-violation constraint in the model problem and its handling by continuous (as opposed to integer) methods. We propose an iterative algorithmic framework for solving such a problem by applying the feasibility-seeking CQ-algorithm of Byrne combined with the automatic relaxation method that uses cyclic projections. Detailed implementation instructions are furnished. Functionality of the algorithm was demonstrated through the creation of an intensity-modulated proton therapy plan for a simple 2D C-shaped geometry and also for a realistic base-of-skull chordoma treatment site. Monte Carlo simulations of proton pencil beams of varying energy were conducted to obtain dose distributions for the 2D test case. A research release of the Pinnacle 3 proton treatment planning system was used to extract pencil beam doses for a clinical base-of-skull chordoma case. In both cases the beamlet doses were calculated to satisfy dose-volume constraints according to our new algorithm. Examination of the dose-volume histograms following inverse planning with our algorithm demonstrated that it performed as intended. The application of our proposed algorithm to dose-volume constraint inverse planning was successfully demonstrated. Comparison with optimized dose distributions from the research release of the Pinnacle 3 treatment planning system showed the algorithm could achieve equivalent or superior results.

Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems.

PubMed

Mandal, Tapas K; Das, Nildari S

2010-02-01

Intraperitoneal injection of cannabis extract at low doses (total doses ranging from 40 mg to 60 mg per mouse) induced adverse effect on testes and oxidative stress. At low doses, there was a significant increase in lipid peroxidation and decrease in testicular lipid content, but the effects were significantly less at higher doses and at the withdrawal of cannabis treatment (recovery dose). There was a marked decrease in antioxidant enzyme profiles (superoxide dismutase, catalase and glutathione peroxidase) and glutathione content at low doses, but these effects were higher at higher dose and at withdrawal of the treatment (recovery effect). Histology revealed significant shrinkage of tubular diameter and detrimental changes in seminiferous epithelium of testis with resulting lowered serum testosterone and pituitary gonadotropins (follicular stimulating [FSH] and luteinizing hormones [LH]) levels at low doses. But at higher doses and particularly at withdrawal of the treatment, regression of various germ cell layers of testes through the revival of testosterone hormone and pituitary gonadotropins (FSH and LH) were observed, indicating that recovery effects on testes became operative possibly through the corrective measure of endogenous testicular antioxidant enzymes profiles and pituitary gonadotropins hormones feedback mechanisms.

Comparison of Gavage, Water Bottle, and a High-Moisture Diet Bolus as Dosing Methods for Quantitative D-xylose Administration to B6D2F1 (Mus musculus) Mice

NASA Technical Reports Server (NTRS)

Zimmer, J. Paul; Lewis, Sherry M.; Moyer, Jerry L.

1993-01-01

Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.

Detection of the valvular split within the second heart sound using the reassigned smoothed pseudo Wigner–Ville distribution

PubMed Central

2013-01-01

Background In this paper, we developed a novel algorithm to detect the valvular split between the aortic and pulmonary components in the second heart sound which is a valuable medical information. Methods The algorithm is based on the Reassigned smoothed pseudo Wigner–Ville distribution which is a modified time–frequency distribution of the Wigner–Ville distribution. A preprocessing amplitude recovery procedure is carried out on the analysed heart sound to improve the readability of the time–frequency representation. The simulated S2 heart sounds were generated by an overlapping frequency modulated chirp–based model at different valvular split durations. Results Simulated and real heart sounds are processed to highlight the performance of the proposed approach. The algorithm is also validated on real heart sounds of the LGB–IRCM (Laboratoire de Génie biomédical–Institut de recherches cliniques de Montréal) cardiac valve database. The A2–P2 valvular split is accurately detected by processing the obtained RSPWVD representations for both simulated and real data. PMID:23631738

Relapse risk after autologous stem cell transplantation in patients with lymphoma based on CD34+ cell dose.

PubMed

Sorigue, Marc; Sancho, Juan-Manuel; Morgades, Mireia; Moreno, Miriam; Grífols, Juan-Ramon; Alonso, Eva; Juncà, Jordi; Ferrà, Christelle; Batlle, Montserrat; Vives, Susana; Motlló, Cristina; García-Caro, Montserrat; Navarro, Jose-Tomás; Millà, Fuensanta; Feliu, Evarist; Ribera, Josep-María

2017-04-01

It is unclear whether higher CD34 + cell doses infused for ASCT have any influence on survival or relapse in patients with lymphoma. We analyzed the correlation of infused CD34 + cell dose with relapse, survival, and hematopoietic recovery in 146 consecutive patients undergoing ASCT for lymphoma. Higher doses (>5 × 10 6 /kg) were significantly correlated with earlier hematopoietic recovery, fewer infectious episodes, lower transfusion needs. No differences were observed in lymphoma outcomes (4-year relapse incidence of 38% [95%CI: 29%-48%] in the lower dose group versus 51% [95%CI: 30%-69%] in the higher dose group, 10-year OS probabilities of 58% [95%CI: 48%-68%] versus 75% [95%CI: 59%-91%], 10-year DFS probabilities of 47% [95%CI: 37%-57%] versus 42% [95%CI: 23%-61%], p = NS for all outcomes). In this series, a higher infused CD34 + cell dose did not correlate with survival or relapse but correlated with earlier hematopoietic recovery and lower resource consumption.

The practice and clinical implications of tablet splitting in international health

PubMed Central

Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N

2014-01-01

Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766

GaAs MMIC: recovery from upset by x-ray pulse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armendariz, M.G.; Castle, J.G. Jr.

1986-01-01

Tolerance for fast neutrons and total ionizing dose is a feature of GaAs microwave monolithic integrated circuits (MMIC). However, upset during an ionizing pulse is expected to occur and delayed recovery due to backgating may be a problem. The purpose of this study of an experimental MMIC design is to observe the recovery of oscillator power output following upset by a short ionizing pulse as a function of applied bias, dose per pulse and case temperature.

Recurrent exposure to welding fumes induces insufficient recovery from inflammation.

PubMed

Yang, Mi Jin; Yang, Young Su; Sung, Jae Hyuck; Kim, Jin Sung; Cho, Kyu Hyuk; Lim, Chae Woong; Chung, Yong Hyun; Kim, Hyeon Yeong; Yang, Jung Sun; Yu, Il Je; Song, Chang Woo

2009-02-01

Previous studies on welding-fume-induced lung fibrosis have indicated that recovery is possible when the degree of exposure is short-term and moderate. However, this study investigated the recovery after recurrent exposure to welding fumes, as welders are invariably re-exposed to welding fumes after recovering from radiographic pneumoconiosis. Thus, to investigate the disease and recovery processes of welding-fume-induced pneumoconiosis in the case of recurrent welding-fume exposure, rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes with a total suspended particulate (TSP) concentration of 51.4 +/- 2.8 mg/m(3) (low dose) or 84.6 +/- 2.9 mg/m(3) (high dose) for 2 h/day in an inhalation chamber for 1 mo and then allowed to recover from the inflammation for 1 mo. Thereafter, the rats were exposed again to MMA-SS with a TSP concentration of 44.1 +/- 8.8 mg/m(3) (low dose) or 80.1 +/- 9.8 mg/m(3) (high dose) for another 30 d and then allowed to recover from the inflammation for 1 mo. The recovery from the first exposure was then compared with that from the second exposure. The first and second exposures to MMA-SS welding fumes were found to produce significant increases in the lung weights and inflammatory parameters, including total cell numbers, alveolar macrophages (AMs), polymorphonuclear cells (PMNs), lymphocytes, and lactate dehydrogenase (LDH) in the bronchoalveolar lavage fluid (BALF) when compared with the unexposed controls. Following the first and second recovery, a significant reduction in inflammatory parameters of BALF was observed between the exposure and recovery groups. Histopathological observations showed foamy or pigmented macrophage accumulation, cellular debris, or pigment from burst macrophages after the first or second exposure. Following the first or second recovery, cellular debris or pigment from burst macrophages was cleared away from the lungs and accumulation of foamy or pigmented macrophages was decreased when compared to previous exposure. Reactive hyperplasia was noticed after second exposure or either recovery. However, significant differences were observed between the first and second exposure or the first and second recovery. In particular, the number of PMNs was significantly higher after the second exposure than after the first exposure. Also, all cell types in the BALF were significantly elevated in the high-dose second recovery group than in the first recovery group, indicating an incomplete recovery from second exposure. In conclusion, these results indicated that the lung damage caused by the second welding-fume exposure was more difficult to recover from than the first exposure.

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Effect of the use of combination uridine triphosphate, cytidine monophosphate, and hydroxycobalamin on the recovery of neurosensory disturbance after bilateral sagittal split osteotomy: a randomized, double-blind trial.

PubMed

Vieira, C L; Vasconcelos, B C do E; Leão, J C; Laureano Filho, J R

2016-02-01

The change in neurosensory lesions that develop after bilateral sagittal split osteotomy (BSSO) was explored, and the influence of the application of combination uridine triphosphate (UTP), cytidine monophosphate (CMP), and hydroxycobalamin (vitamin B12) on patient outcomes was assessed. This was a randomized, controlled, double-blind trial. The study sample comprised 12 patients, each evaluated on both sides (thus 24 sides). All patients fulfilled defined selection criteria. Changes in the lesions were measured both subjectively and objectively. The sample was divided into two patient groups: an experimental group receiving medication and a control group receiving placebo. The statistical analysis was performed using SPSS software. Lesions in both groups improved and no statistically significant difference between the groups was observed at any time. 'Severe' injuries in the experimental group were more likely to exhibit a significant improvement after 6 months. Based on the results of the present study, it is concluded that the combination UTP, CMP, and hydroxycobalamin did not influence recovery from neurosensory disorders. Copyright © 2015. Published by Elsevier Ltd.

PEGylated G-CSF (BBT-015), GM-CSF (BBT-007), and IL-11 (BBT-059) analogs enhance survival and hematopoietic cell recovery in a mouse model of the hematopoietic syndrome of the acute radiation syndrome.

PubMed

Plett, Paul Artur; Chua, Hui Lin; Sampson, Carol H; Katz, Barry P; Fam, Christine M; Anderson, Lana J; Cox, George N; Orschell, Christie M

2014-01-01

Hematopoietic growth factors (HGF) are recommended therapy for high dose radiation exposure, but unfavorable administration schedules requiring early and repeat dosing limit the logistical ease with which they can be used. In this report, using a previously described murine model of H-ARS, survival efficacy and effect on hematopoietic recovery of unique PEGylated HGF were investigated. The PEGylated-HGFs possess longer half-lives and more potent hematopoietic properties than corresponding non-PEGylated-HGFs. C57BL/6 mice underwent single dose lethal irradiation (7.76-8.72 Gy, Cs, 0.62-1.02 Gy min) and were treated with various dosing regimens of 0.1, 0.3, and 1.0 mg kg of analogs of human PEG-G-CSF, murine PEG-GM-CSF, or human PEG-IL-11. Mice were administered one of the HGF analogs at 24-28 h post irradiation, and in some studies, additional doses given every other day (beginning with the 24-28 h dose) for a total of three or nine doses. Thirty-day (30 d) survival was significantly increased with only one dose of 0.3 mg kg of PEG-G-CSF and PEG-IL-11 or three doses of 0.3 mg kg of PEG-GM-CSF (p ≤ 0.006). Enhanced survival correlated with consistently and significantly enhanced WBC, NE, RBC, and PLT recovery for PEG-G- and PEG-GM-CSF, and enhanced RBC and PLT recovery for PEG-IL-11 (p ≤ 0.05). Longer administration schedules or higher doses did not provide a significant additional survival benefit over the shorter, lower dose, schedules. These data demonstrate the efficacy of BBT's PEG-HGF to provide significantly increased survival with fewer injections and lower drug doses, which may have significant economic and logistical value in the aftermath of a radiation event.

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming.

PubMed

Isbister, G K; Jayamanne, S; Mohamed, F; Dawson, A H; Maduwage, K; Gawarammana, I; Lalloo, D G; de Silva, H J; Scorgie, F E; Lincz, L F; Buckley, N A

2017-04-01

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

The Advantages of Collimator Optimization for Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Doozan, Brian

The goal of this study was to improve dosimetry for pelvic, lung, head and neck, and other cancers sites with aspherical planning target volumes (PTV) using a new algorithm for collimator optimization for intensity modulated radiation therapy (IMRT) that minimizes the x-jaw gap (CAX) and the area of the jaws (CAA) for each treatment field. A retroactive study on the effects of collimator optimization of 20 patients was performed by comparing metric results for new collimator optimization techniques in Eclipse version 11.0. Keeping all other parameters equal, multiple plans are created using four collimator techniques: CA 0, all fields have collimators set to 0°, CAE, using the Eclipse collimator optimization, CAA, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles are found by evaluating each field beam's eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of fields that are calculated to split. Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX method with a p-value of 0.01 from an ANOVA test. The average maximum dose remained within 1.1% difference between all four methods with the lowest given by CAX. The maximum dose to the most at risk organ was best spared by the CAA method, which decreased by 0.62% compared to the CA0. Minimizing the x-jaws significantly reduced the number of split fields from 61 to 37. In every metric tested the CAX optimization produced comparable or superior results compared to the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, lowered the maximum dose, minimized the dose to the surrounding OAR, and decreased the monitor units. This is achieved while maintaining the same control of the PTV.

Recovery of damage in rad-hard MOS devices during and after irradiation by electrons, protons, alphas, and gamma rays

NASA Technical Reports Server (NTRS)

Brucker, G. J.; Van Gunten, O.; Stassinopoulos, E. G.; Shapiro, P.; August, L. S.; Jordan, T. M.

1983-01-01

This paper reports on the recovery properties of rad-hard MOS devices during and after irradiation by electrons, protons, alphas, and gamma rays. The results indicated that complex recovery properties controlled the damage sensitivities of the tested parts. The results also indicated that damage sensitivities depended on dose rate, total dose, supply bias, gate bias, transistor type, radiation source, and particle energy. The complex nature of these dependencies make interpretation of LSI device performance in space (exposure to entire electron and proton spectra) difficult, if not impossible, without respective ground tests and analyses. Complete recovery of n-channel shifts was observed, in some cases within hours after irradiation, with equilibrium values of threshold voltages greater than their pre-irradiation values. This effect depended on total dose, radiation source, and gate bias during exposure. In contrast, the p-channel shifts recovered only 20 percent within 30 days after irradiation.

Investigation of high temperature annealing effectiveness for recovery of radiation-induced structural changes and properties of 18Cr-10Ni-Ti austenitic stainless steels

NASA Astrophysics Data System (ADS)

Gurovich, B. A.; Kuleshova, E. A.; Frolov, A. S.; Maltsev, D. A.; Prikhodko, K. E.; Fedotova, S. V.; Margolin, B. Z.; Sorokin, A. A.

2015-10-01

A complex study of structural state and properties of 18Cr-10Ni-Ti austenitic stainless steel after irradiation in BOR-60 fast research reactor (in the temperature range 330-400 °С up to damaging doses of 145 dpa) and in VVER-1000 light water reactor (at temperature ∼320 °С and damaging doses ∼12-14 dpa) was performed. The possibility of recovery of structural-phase state and mechanical properties to the level almost corresponding to the initial state by the recovery annealing was studied. The principal possibility of the recovery annealing of pressurized water reactor internals that ensures almost complete recovery of its mechanical properties and microstructure was shown. The optimal mode of recovery annealing was established: 1000 °C during 120 h.

Vertical Motion Simulator Experiment on Stall Recovery Guidance

NASA Technical Reports Server (NTRS)

Schuet, Stefan; Lombaerts, Thomas; Stepanyan, Vahram; Kaneshige, John; Shish, Kimberlee; Robinson, Peter; Hardy, Gordon H.

2017-01-01

A stall recovery guidance system was designed to help pilots improve their stall recovery performance when the current aircraft state may be unrecognized under various complicating operational factors. Candidate guidance algorithms were connected to the split-cue pitch and roll flight directors that are standard on large transport commercial aircraft. A new thrust guidance algorithm and cue was also developed to help pilots prevent the combination of excessive thrust and nose-up stabilizer trim. The overall system was designed to reinforce the current FAA recommended stall recovery procedure. A general transport aircraft model, similar to a Boeing 757, with an extended aerodynamic database for improved stall dynamics simulation fidelity was integrated into the Vertical Motion Simulator at NASA Ames Research Center. A detailed study of the guidance system was then conducted across four stall scenarios with 30 commercial and 10 research test pilots, and the results are reported.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Merchant, Thomas E.; Gajjar, Amar

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametricmore » maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.« less

Promoting Abstinence from Cocaine and Heroin with a Methadone Dose Increase and a Novel Contingency

PubMed Central

Schmittner, John; Umbricht, Annie; Schroeder, Jennifer R.; Moolchan, Eric T.; Preston, Kenzie L.

2010-01-01

To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 X 3 (Dose X Contingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100 mg/day, double blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or “split”). The “split” contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was “split” between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The Split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose Noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required. PMID:19101098

Blueberry effects on dark vision and recovery after photobleaching: placebo-controlled crossover studies.

PubMed

Kalt, Wilhelmina; McDonald, Jane E; Fillmore, Sherry A E; Tremblay, Francois

2014-11-19

Clinical evidence for anthocyanin benefits in night vision is controversial. This paper presents two human trials investigating blueberry anthocyanin effects on dark adaptation, functional night vision, and vision recovery after retinal photobleaching. One trial, S2 (n = 72), employed a 3 week intervention and a 3 week washout, two anthocyanin doses (271 and 7.11 mg cyanidin 3-glucoside equivalents (C3g eq)), and placebo. The other trial, L1 (n = 59), employed a 12 week intervention and an 8 week washout and tested one dose (346 mg C3g eq) and placebo. In both S2 and L1 neither dark adaptation nor night vision was improved by anthocyanin intake. However, in both trials anthocyanin consumption hastened the recovery of visual acuity after photobleaching. In S2 both anthocyanin doses were effective (P = 0.014), and in L1 recovery was improved at 8 weeks (P = 0.027) and 12 weeks (P = 0.030). Although photobleaching recovery was hastened by anthocyanins, it is not known whether this improvement would have an impact on everyday vision.

Flow of foams in two-dimensional disordered porous media

NASA Astrophysics Data System (ADS)

Dollet, Benjamin; Geraud, Baudouin; Jones, Sian A.; Meheust, Yves; Cantat, Isabelle; Institut de Physique de Rennes Team; Geosciences Rennes Team

2015-11-01

Liquid foams are a yield stress fluid with elastic properties. When a foam flow is confined by solid walls, viscous dissipation arises from the contact zones between soap films and walls, giving very peculiar friction laws. In particular, foams potentially invade narrow pores much more efficiently than Newtonian fluids, which is of great importance for enhanced oil recovery. To quantify this effect, we study experimentally flows of foam in a model two-dimensional porous medium, consisting of an assembly of circular obstacles placed randomly in a Hele-Shaw cell, and use image analysis to quantify foam flow at the local scale. We show that bubbles split as they flow through the porous medium, by a mechanism of film pinching during contact with an obstacle, yielding two daughter bubbles per split bubble. We quantify the evolution of the bubble size distribution as a function of the distance along the porous medium, the splitting probability as a function of bubble size, and the probability distribution function of the daughter bubbles. We propose an evolution equation to model this splitting phenomenon and compare it successfully to the experiments, showing how at long distance, the porous medium itself dictates the size distribution of the foam.

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials.

PubMed

Stoffel, Nicole U; Cercamondi, Colin I; Brittenham, Gary; Zeder, Christophe; Geurts-Moespot, Anneke J; Swinkels, Dorine W; Moretti, Diego; Zimmermann, Michael B

2017-11-01

Current guidelines to treat iron deficiency recommend daily provision of ferrous iron divided through the day to increase absorption. However, daily dosing and split dosing might increase serum hepcidin and decrease iron absorption from subsequent doses. Our study aim was to compare iron absorption from oral iron supplements given on consecutive versus alternate days and given as single morning doses versus twice-daily split dosing. We did two prospective, open-label, randomised controlled trials assessing iron absorption using ( 54 Fe)-labelled, ( 57 Fe)-labelled, or ( 58 Fe)-labelled ferrous sulfate in iron-depleted (serum ferritin ≤25 μg/L) women aged 18-40 years recruited from ETH Zurich and the University of Zurich, Switzerland. In study 1, women were randomly assigned (1:1) to two groups. One group was given 60 mg iron at 0800 h (±1 h) on consecutive days for 14 days, and the other group was given the same doses on alternate days for 28 days. In study 2, women were assigned to two groups, stratified by serum ferritin so that two groups with similar iron statuses could be formed. One group was given 120 mg iron at 0800 h (±1 h) and the other was given the dose split into two divided doses of 60 mg at 0800 h (±1 h) and 1700 h (±1 h) for three consecutive days. 14 days after the final dose, the groups were each crossed over to the other regimen. Within-individual comparisons were done. The co-primary outcomes in both studies were iron bioavailability (total and fractional iron absorption), assessed by measuring the isotopic label abundance in erythrocytes 14 days after administration, and serum hepcidin. Group allocations in both studies were not masked and primary and safety analyses were done on an intention-to-treat basis. The studies were registered at ClinicalTrials.gov, numbers NCT02175888 (study 1) and NCT02177851 (study 2) and are complete. For study 1, 40 women were enrolled on Oct 15-29, 2015. 21 women were assigned to the consecutive-day group and 19 to the alternate-day group. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), geometric mean (-SD, +SD) cumulative fractional iron absorptions were 16·3% (9·3, 28·8) in the consecutive-day group versus 21·8% (13·7, 34·6) in the alternate-day group (p=0·0013), and cumulative total iron absorption was 131·0 mg (71·4, 240·5) versus 175·3 mg (110·3, 278·5; p=0·0010). During the first 14 days of supplementation in both groups, serum hepcidin was higher in the consecutive-day group than the alternate-day group (p=0·0031). In study 2, 20 women were enrolled between Aug 13 and 18, 2015. Ten women were assigned to receive once-daily dosing and ten were assigned to receive twice-daily divided dosing. No significant differences were seen in fractional (day 1-3 geometric mean: 11·8% [7·1, 19·4] once daily vs 13·1% [8·2, 20·7] twice daily; p=0·33) or total iron absorption (day 1-3: 44·3 mg [29·4, 66·7] once daily vs 49·4 [35·2, 69·4] twice daily; p=0·33) between the two dosing regimens. Twice-daily divided doses resulted in a higher serum hepcidin concentration than once-daily dosing (p=0·013). No grade 3 or 4 adverse events were reported in either study. In iron-depleted women, providing iron supplements daily as divided doses increases serum hepcidin and reduces iron absorption. Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen. These findings should be confirmed in iron-deficient anaemic patients. Swiss National Science Foundation, Bern, Switzerland. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors predicting haematopoietic recovery in patients undergoing autologous transplantation: 11-year experience from a single centre.

PubMed

Bai, Lijun; Xia, Wei; Wong, Kelly; Reid, Cassandra; Ward, Christopher; Greenwood, Matthew

2014-10-01

Engraftment outcomes following autologous transplantation correlate poorly to infused stem cell number. We evaluated 446 consecutive patients who underwent autologous transplantation at our centre between 2001 and 2012. The impact of pre-transplant and collection factors together with CD34(+) dosing ranges on engraftment, hospital length of stay (LOS) and survival endpoints were assessed in order to identify factors which might be optimized to improve outcomes for patients undergoing autologous transplantation using haemopoietic progenitor cells-apheresis (HPC-A). Infused CD34(+) cell dose correlated to platelet but not neutrophil recovery. Time to platelet engraftment was significantly delayed in those receiving low versus medium or high CD34(+) doses. Non-remission status was associated with slower neutrophil and platelet recovery. Increasing neutrophil contamination of HPC-A was strongly associated with slower neutrophil recovery with infused neutrophil dose/kg recipient body weight ≥3 × 10(8)/kg having a significant impact on time to neutrophil engraftment (p = 0.001). Higher neutrophil doses/kg in HPC-A were associated with days of granulocyte colony stimulation factor (G-CSF) use, HPC-A volumes >500 ml and higher NCC in HPC-A. High infused neutrophil dose/kg and age >65 years were associated with longer hospital LOS (p = 0.002 and 0.011 respectively). Only age, disease and disease status predicted disease-free survival (DFS) and overall survival (OS) in our cohort (p < 0.005). Non-relapse mortality was not affected by low dose of CD34(+) (<2 × 10(6)/kg). In conclusion, our study shows that CD34(+) remains a useful and convenient marker for assessing haemotopoietic stem cell content and overall engraftment capacity post-transplant. Neutrophil contamination of HPC-A appears to be a key factor delaying neutrophil recovery. Steps to minimize the degree of neutrophil contamination in HPC-A product may be associated with more rapid neutrophil engraftment and reduced hospital LOS.

Elements That Define Recovery: The Experiential Perspective

PubMed Central

Kaskutas, Lee Ann; Borkman, Thomasina J; Laudet, Alexandre; Ritter, Lois A; Witbrodt, Jane; Subbaraman, Meenakshi Sabina; Stunz, Aina; Bond, Jason

2014-01-01

Objective: Although recovery increasingly guides substance use disorder services and policy, definitions of recovery continue to lack specificity, thereby hindering measure development and research. The goal of this study was to move the substance use disorders field beyond broad definitions by empirically identifying the domains and specific elements of recovery as experienced by persons in recovery from diverse pathways. Method: An Internet-based survey was completed by 9,341 individuals (54% female) who self-identified as being in recovery, recovered, in medication-assisted recovery, or as having had a problem with alcohol or drugs (but no longer do). Respondents were recruited via extensive outreach with treatment and recovery organizations, electronic media, and self-help groups. The survey included 47 recovery elements developed through qualitative work followed by an iterative reduction process. Exploratory and confirmatory factor analyses were conducted using split-half samples, followed by sensitivity analyses for key sample groupings. Results: Four recovery domains with 35 recovery elements emerged: abstinence in recovery, essentials of recovery, enriched recovery, and spirituality of recovery. The four-factor structure was robust regardless of length of recovery, 12-step or treatment exposure, and current substance use status. Four uncommon elements did not load on any factor but are presented to indicate the diversity of definitions. Conclusions: Our empirical findings offer specific items that can be used in evaluating recovery-oriented systems of care. Researchers studying recovery should include measures that extend beyond substance use and encompass elements such as those examined here—e.g., self-care, concern for others, personal growth, and developing ways of being that sustain change in substance use. PMID:25343658

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Storb, R.; Raff, R.F.; Graham, T.

1993-03-20

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionatedmore » total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.« less

Hybrid quantitative MRI using chemical shift displacement and recovery-based simultaneous water and lipid imaging: A preliminary study.

PubMed

Ohno, Naoki; Miyati, Tosiaki; Suzuki, Shuto; Kan, Hirohito; Aoki, Toshitaka; Nakamura, Yoshitaka; Hiramatsu, Yuki; Kobayashi, Satoshi; Gabata, Toshifumi

2018-07-01

To suppress olefinic signals and enable simultaneous and quantitative estimation of multiple functional parameters associated with water and lipid, we investigated a modified method using chemical shift displacement and recovery-based separation of lipid tissue (SPLIT) involving acquisitions with different inversion times (TIs), echo times (TEs), and b-values. Single-shot diffusion echo-planar imaging (SSD-EPI) with multiple b-values (0-3000 s/mm 2 ) was performed without fat suppression to separate water and lipid images using the chemical shift displacement of lipid signals in the phase-encoding direction. An inversion pulse (TI = 292 ms) was applied to SSD-EPI to remove olefinic signals. Consecutively, SSD-EPI (b = 0 s/mm 2 ) was performed with TI = 0 ms and TE = 31.8 ms for T 1 and T 2 measurements, respectively. Under these conditions, transverse water and lipid images at the maximum diameter of the right calf were obtained in six healthy subjects. T 1 , T 2 , and the apparent diffusion coefficients (ADC) were then calculated for the tibialis anterior (TA), gastrocnemius (GM), and soleus (SL) muscles, tibialis bone marrow (TB), and subcutaneous fat (SF). Perfusion-related (D*) and restricted diffusion coefficients (D) were calculated for the muscles. Lastly, the lipid fractions (LF) of the muscles were determined after T 1 and T 2 corrections. The modified SPLIT method facilitated sufficient separation of water and lipid images of the calf, and the inversion pulse with TI of 292 ms effectively suppressed olefinic signals. All quantitative parameters obtained with the modified SPLIT method were found to be in general agreement with those previously reported in the literature. The modified SPLIT technique enabled sufficient suppression of olefinic signals and simultaneous acquisition of quantitative parameters including diffusion, perfusion, T 1 and T 2 relaxation times, and LF. Copyright © 2018. Published by Elsevier Inc.

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy

PubMed Central

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-01-01

AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy. PMID:24044042

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

PubMed

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-09-16

To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy.

Fungal decontamination and enhancement of shelf life of edible split beans of wild legume Canavalia maritima by the electron beam irradiation

NASA Astrophysics Data System (ADS)

Supriya, P.; Sridhar, K. R.; Ganesh, S.

2014-03-01

Ripened split beans of the coastal sand dune wild legume Canavalia maritima serve as one of the traditional nutritional sources of the coastal dwellers in Southwest coast of India. Nine fungi were isolated from the unirradiated dry beans by plating on the potato dextrose agar medium. Toxigenic fungus Aspergillus niger showed the highest incidence (33-50%) followed by Aspergillus flavus (14-20%) and Penicillium chrysogenum (7-13%). Unirradiated dry beans and irradiated dry beans with electron beam doses 2.5, 5, 10 and 15 kGy were monitored for occurrence of fungal species and their incidence during 0, 3 and 6 months storage period under laboratory conditions. Irradiation resulted in dose-dependent decrease in fungal species (5-7, 4-6, 3-6 and 0 on irradiation at 0, 2.5, 5 and 10 or 15 kGy, respectively) as well as incidence (80-99, 19-46, 13-21 and 0%, respectively). Although aflatoxins (B1 and B2) were found below detectable level (<2 ng/g) in 0, 3 and 6 months stored unirradiated and irradiated beans (2.5 and 5 kGy), they were not present in beans irradiated with 10 and 15 kGy. In spite of occurrence of toxigenic fungus Aspergillus ochraceus in unirradiated and irradiated beans (2.5 and 5 kGy) stored for 3 and 6 months, the beans were devoid of ochratoxin-A. Electron beam irradiation dose 10 kGy could be recommended for fungal decontamination and improvement of shelf life of C. maritima ripened dry split beans.

Patients with History of Colonoscopy Are Less Likely to Achieve High Quality Preparation After Implementing Split-Dose Bowel Preparation.

PubMed

Madhoun, M F; Bitar, H; Parava, P; Bashir, M H; Zia, H

2017-01-01

Anecdotally, we observed that patients who had previous colonoscopies were less likely to follow newly implemented split-dose bowel preparation (SDBP) instructions. We investigated whether the indication for colonoscopy is an independent factor for achieving high quality bowel preparation among patients asked to follow SDBP. We performed a retrospective study of data from 1478 patients who received outpatient colonoscopies in 2014 (the year of SDBP implementation) at our Veterans Affairs Medical Center. We collected information related to demographics and factors known to affect bowel preparations. Reasons for colonoscopy were dichotomized into surveillance (previous colonoscopy) vs. non-surveillance (positive occult blood test or screening). Bowel preparation quality was scored using the Boston Bowel Preparation Scale (BBPS), and was categorized as either excellent vs. not excellent (BBPS≥7 vs. BBPS<7), or adequate vs. inadequate (BBPS≥6 vs. BBPS<6). Bowel preparation quality was excellent in 60% of colonoscopies and adequate in 84% of colonoscopies. Thirty-six percent (535) were surveillance colonoscopies. In multivariate logistic regression analysis, more patients in the non-surveillance group achieved excellent (OR 0.8 ; 95% CI [0.7-0.8], P <0.0001) and adequate (OR 0.8 ; 95% CI [0.7-0.9], P <0.006) bowel preparation than did patients in the surveillance group. Patients with a prior colonoscopy might not follow the split-dose bowel preparation instructions. Educational interventions emphasizing the benefits of SDBP in this group of patients may help ensure compliance and prevent the habitual use of day-before preparations. © Acta Gastro-Enterologica Belgica.

Recovery of brain and plasma cholinesterase activities in ducklings exposed to organophosphorus pesticides

USGS Publications Warehouse

Fleming, W.J.

1981-01-01

Brain and plasma cholinesterase (ChE) activities were determined for mallard ducklings (Anas platyrhynchos) exposed to dicrotophos and fenthion. Recovery rates of brain ChE did not differ between ducklings administered a single oral dose vs. a 2-week dietary dose of these organophosphates. Exposure to the organophosphates, followed by recovery of brain ChE, did not significantly affect the degree of brain ChE inhibition or the recovery of ChE activity at a subsequent exposure. Recovery of brain ChE activity followed the general model Y = a + b(logX) with rapid recovery to about 50% of normal, followed by a slower rate of recovery until normal ChE activity levels were attained. Fenthion and dicrotophos-inhibited brain ChE were only slightly reactivated in vitro by pyridine-2-aldoxime methiodide, which suggested that spontaneous reactivation was not a primary method of recovery of ChE activity. Recovery of brain ChE activity can be modeled for interpretation of sublethal inhibition of brain ChE activities in wild birds following environmental applications of organophosphates. Plasma ChE activity is inferior to brain ChE activity for environmental monitoring, because of its rapid recovery and large degree of variation among individuals.

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

PubMed

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

2017-01-01

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

Development and validation of a questionnaire to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes.

PubMed

Koontz, Michaela B; Cuttler, Leona; Palmert, Mark R; O'Riordan, Maryann; Borawski, Elaine A; McConnell, Judy; Kern, Elizabeth O

2010-03-01

OBJECTIVE The American Diabetes Association advocates insulin regimens for youth with type 1 diabetes that involve adjusting insulin dose based on carbohydrate intake and blood glucose level. Implementing these regimens requires knowledge about carbohydrate content of foods and subsequent calculations of insulin dose, skills that may be difficult to gauge in practice. Therefore, we sought to develop and validate a questionnaire, the PedCarbQuiz (PCQ), to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS After development by an expert panel, the PCQ was administered to 75 youth with type 1 diabetes or their parents. Reliability was assessed by Cronbach alpha and split-half testing. To assess validity, scores were correlated with A1C, expert assessments, parent educational level, and complexity of insulin regimen. RESULTS PCQ mean score was 87 +/- 9.7% (range 42-98%). Cronbach alpha was 0.88, and correlation of split halves was 0.59 (P < 0.0001). Higher PCQ scores correlated significantly with lower A1C (r = -0.29, P = 0.01) and expert assessments (r = 0.56, P < 0.001). Scores were significantly higher in parents with college degrees than in those without (P = 0.01) and in participants with more complex insulin regimens (P = 0.003). CONCLUSIONS The PCQ is a novel, easily administered instrument to assess knowledge about carbohydrates and insulin dosing calculations. Initial analyses support the reliability and validity of the PCQ.

Did Earth-approaching asteroids 3551, 3908, or 4055 produce meteorites?

NASA Technical Reports Server (NTRS)

Gustafson, Bo A. S.; Williams, I. P.

1992-01-01

Orbital integrations show that Amor asteroid 3908 could have ejected one out of four plausible groups of meteorite producing fireballs during a collision in the asteroid belt. It was suggested by others that such a collision may also have split asteroids 3551 and 3908. A member of this group of fireballs is listed as one of the better possibilities for recovery.

A history of the treatment of appendicitis in children: lessons learned.

PubMed

Hamill, James K; Hill, Andrew G

2016-10-01

During the latter half of the 19th century, surgeons increasingly reported performing appendicectomies. Fitz from Harvard, Groves from Canada and Tait from Britain all recorded successful removal of the appendix. McBurney described the point of maximal tenderness in classic appendicitis and also the muscle-splitting incision centred on this point. Priority is given to McArthur in describing the lateral muscle-splitting incision. The direction of the cutaneous incision was later modified by Elliott and Lanz. Incisions that healed well were essential to recovery. Appendicectomy became a 'fashionable' operation after the London surgeon, Treves, removed the appendix of King Edward VII. Through the 20th century, the mortality from appendicitis fell notably with the advent of sulphonamide and penicillin, improvements in fluid therapy and safer anaesthesia. By 1990, diagnostic delay was the main cause of death. Semm performed the first laparoscopic appendicectomy in 1990, roundly criticized at the time for what is now a routine procedure. We view contemporary debates on the indications for appendicectomy, the best approach and how to optimize recovery in the light of the history of this intriguing disease. © 2016 Royal Australasian College of Surgeons.

Reducing nitrogen losses through ammonia volatilization and surface runoff to improve apparent nitrogen recovery of double cropping of late rice using controlled release urea.

PubMed

Li, Pengfei; Lu, Jianwei; Hou, Wenfeng; Pan, Yonghui; Wang, Yang; Khan, Muhammad Rizwan; Ren, Tao; Cong, Rihuan; Li, Xiaokun

2017-04-01

Controlled release fertilizer can reduce nitrogen losses to the environment while increasing grain yield and improving apparent nitrogen recovery (ANR) of rice. However, few studies have evaluated the comparative efficacy of different polymer-coated urea products on nitrogen (N) losses, ANR, and N uptake of rice. A 2-year field experiment was conducted to compare the effects of three different types of polymer-coated urea fertilizer on nitrogen losses through NH 3 volatilization and surface runoff to the environment, ANR, grain yield, and N uptake as compared to conventional urea of rice. Six treatments including (1) control with 0 kg N ha -1 (CK), (2) basal application of urea (U b ), (3) split application (U s ) of urea (50% at transplanting, 25% at tillering, and 25% at panicle stages), (4) CRU-1 (polyurethane-coated urea), (5) CRU-2 (degradable polymer-coated urea), and (6) CRU-3 (water-based polymer-coated urea) all applied at 165 kg N ha -1 . It was found that CRU-2 resulted in the highest grain yield and panicle numbers among the N fertilization treatments in 2013 and 2014. Applying CRU could help increase N uptake in rice, reduce N losses through NH 3 volatilization and surface runoff, and hence improve ANR. Its single dose can meet the nutrient demand of the rice plant. Controlled release urea could be adopted as an effective mitigation alternative to retard N losses through NH 3 volatilization and surface runoff while improving ANR of double cropping of late rice.

Methods for assisting recovery of damaged brain and spinal cord and treating various diseases using arrays of x-ray microplanar beams

DOEpatents

Dilmanian, F Avraham [Yaphank, NY; Anchel, David J [Rocky Point, NY; Gaudette, Glenn [Holden, MA; Romanelli, Pantaleo [Monteroduni, IT; Hainfeld, James [Shoreham, NY

2010-06-29

A method of assisting recovery of an injury site of the central nervous system (CNS) or treating a disease includes providing a therapeutic dose of X-ray radiation to a target volume through an array of parallel microplanar beams. The dose to treat CNS injury temporarily removes regeneration inhibitors from the irradiated site. Substantially unirradiated cells surviving between beams migrate to the in-beam portion and assist recovery. The dose may be staggered in fractions over sessions using angle-variable intersecting microbeam arrays (AVIMA). Additional doses are administered by varying the orientation of the beams. The method is enhanced by injecting stem cells into the injury site. One array or the AVIMA method is applied to ablate selected cells in a target volume associated with disease for palliative or curative effect. Atrial fibrillation is treated by irradiating the atrial wall to destroy myocardial cells while continuously rotating the subject.

Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients.

PubMed

Lee, Sue J; Ter Kuile, Feiko O; Price, Ric N; Luxemburger, Christine; Nosten, François

2017-01-01

Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

Recovery concept in a Norwegian setting to be examined by the assertive community treatment model and mixed methods.

PubMed

Lofthus, Ann-Mari; Westerlund, Heidi; Bjørgen, Dagfinn; Lindstrøm, Jonas Christoffer; Lauveng, Arnhild; Rose, Diana; Ruud, Torleif; Heiervang, Kristin

2018-02-01

Recovery is a crucial concept in the mental health field. The research of recovery is split into the categories of personal, social and clinical recovery. The purpose of this study was to explore the fragmented concept of recovery in light of assertive community treatment (ACT) in Norway. The study has a mixed methods design with a pragmatic approach. The Questionnaire about the Process of Recovery and open-ended questions posed to 70 participants from 12 ACT teams in Norway, gathered by the "Users interview users" method, are combined with interviews or focus groups with eight of these participants. Surprisingly those under a community treatment order (CTO) report the highest degree of personal recovery. The qualitative material shows that the service users interpreted the concept of recovery differently than researchers and professionals. The ACT service users highlighted three important elements: flexible treatment, medication and access to a car. They emphasized the necessity for basic needs to be met in order to experience a meaningful recovery process, and these basic needs may be of even greater importance to those under CTOs. Their experiences should imply a greater emphasis on securing basic needs such as secure housing, sounder finances and access to the normal benefits offered by society. © 2016 Australian College of Mental Health Nurses Inc.

Use of Sugammadex in Patients With Obesity: A Pooled Analysis.

PubMed

Monk, Terri G; Rietbergen, Henk; Woo, Tiffany; Fennema, Hein

A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.

Successful Treatment of Plantar Hyperkeratosis in the Form of Recurrent Corns With Split-Thickness Sole Skin Graft.

PubMed

Wang, Chi-Yu; Chang, Chun-Kai; Chou, Chang-Yi; Wu, Chien-Ju; Chu, Tzi-Shiang; Chiao, Hao-Yu; Chen, Chun-Yu; Chen, Tim-Mo; Tzeng, Yuan-Sheng

2018-02-01

Plantar hyperkeratosis, such as corns and calluses, is common in older people and associated with pain, mobility impairment, and functional limitations. It usually develops on the palms, knees, or soles of feet, especially under the heels or balls. There are several treatment methods for plantar hyperkeratosis, such as salicylic acid plaster and scalpel debridement, and conservative modalities, such as using a shoe insert and properly fitting shoes. We present an effective method of reconstructing the wound after corn excision using a split-thickness sole skin graft (STSSG). We harvested the skin graft from the arch of the sole using the dermatome with a skin thickness of 14/1000th inches. Because the split-thickness skin graft, harvested from the sole arch near the distal sole, is much thicker than the split-thickness skin graft from the thigh, it is more resistant to weight and friction. The healed wound with STSSG coverage over the distal sole was intact, and the donor site over the sole arch had healed without complication during the outpatient follow-up, 3 months after surgery. The recovery time of STSSG for corn excision is shorter than that with traditional treatment. Therefore, STSSG can be a reliable alternative treatment for recurrent palmoplantar hyperkeratosis.

The White Diet is preferred, better tolerated, and non-inferior to a clear-fluid diet for bowel preparation: A randomized controlled trial.

PubMed

Butt, Joshua; Bunn, Cate; Paul, Eldho; Gibson, Peter; Brown, Gregor

2016-02-01

Dietary restrictions contribute to the unpleasantness of bowel preparation for colonoscopy. We compare the effectiveness and tolerability of a low residue diet of white-colored foods ("White Diet") with a clear-fluid diet the day prior to colonoscopy in an endoscopist-blinded randomized non-inferiority trial. Adults undergoing outpatient colonoscopy were randomized with stratification by procedure timing to a White Diet or clear-fluid diet. All received a 2-L polyethylene glycol lavage solution with ascorbate, sodium sulfate, and electrolytes, the day-before for morning and as a split-dose for afternoon procedures. The primary end-point was successful bowel preparation (A or B on the Harefield Cleansing Scale). Regimen tolerance/acceptance was assessed by questionnaire. An intention-to-treat analysis with a predefined non-inferiority margin of 15% was used to compare efficacy. A total of 226 patients (average age 52 years, 51% male) were randomized (111 clear diet, 115 White Diet). Bowel preparation was successful in 91% on the clear-fluid diet vs 84.4% on the White Diet, difference being -6.6% (lower one sided 95% CI -13.8%), with no difference according to diet. The split-dose regimen (in 55%) had a higher success rate than day-before regimen (96% vs 80%, p < 0.001). The White Diet was preferred with less hunger and interference with daily activities (p < 0.001). Procedural/withdrawal time and polyp/adenoma detection were similar between groups. The White Diet was preferred and better tolerated by patients without detriment to the success of bowel preparation or colonoscopy performance, especially with the split-dose regimen. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

An Automated Inpatient Split-dose Bowel Preparation System Improves Colonoscopy Quality and Reduces Repeat Procedures.

PubMed

Yadlapati, Rena; Johnston, Elyse R; Gluskin, Adam B; Gregory, Dyanna L; Cyrus, Rachel; Werth, Lindsay; Ciolino, Jody D; Grande, David P; Keswani, Rajesh N

2017-07-19

Inpatient colonoscopy preparations are often inadequate, compromising patient safety and procedure quality, while resulting in greater hospital costs. The aims of this study were to: (1) design and implement an electronic inpatient split-dose bowel preparation order set; (2) assess the intervention's impact upon preparation adequacy, repeated colonoscopies, hospital days, and costs. We conducted a single center prospective pragmatic quasiexperimental study of hospitalized adults undergoing colonoscopy. The experimental intervention was designed using DMAIC (define, measure, analyze, improve, and control) methodology. Prospective data collected over 12 months were compared with data from a historical preintervention cohort. The primary outcome was bowel preparation quality and secondary outcomes included number of repeated procedures, hospital days, and costs. On the basis of a Delphi method and DMAIC process, we created an electronic inpatient bowel preparation order set inclusive of a split-dose bowel preparation algorithm, automated orders for rescue medications, and nursing bowel preparation checks. The analysis data set included 969 patients, 445 (46%) in the postintervention group. The adequacy of bowel preparation significantly increased following intervention (86% vs. 43%; P<0.01) and proportion of repeated procedures decreased (2.0% vs. 4.6%; P=0.03). Mean hospital days from bowel preparation initiation to discharge decreased from 8.0 to 6.9 days (P=0.02). The intervention resulted in an estimated 1-year cost-savings of $46,076 based on a reduction in excess hospital days associated with repeated and delayed procedures. Our interdisciplinary initiative targeting inpatient colonoscopy preparations significantly improved quality and reduced repeat procedures, and hospital days. Other institutions should consider utilizing this framework to improve inpatient colonoscopy value.

The impact of diet liberalization on bowel preparation for colonoscopy.

PubMed

Walter, James; Francis, Gloria; Matro, Rebecca; Kedika, Ramalinga; Grosso, Rachael; Keith, Scott W; Kastenberg, David

2017-04-01

Background and study aims  Dietary restrictions are integral to colonoscopy preparation and impact patient satisfaction. Utilizing split-dose, lower-volume polyethylene glycol 3350-electrolyte solution (PEG-ELS), this study compared colon preparation adequacy of a low-residue diet to clear liquids using a validated grading scale. Patients and methods  This was a prospective, randomized, single-blinded, single-center non-inferiority study evaluating diet the day prior to outpatient colonoscopy. Subjects were randomized to a Low-Residue diet for breakfast and lunch, or Clears only. All subjects received split dose PEG-ELS. The primary endpoint was preparation adequacy using the Boston Bowel Preparation Scale (BBPS), with adequate defined as a score > 5. Secondary endpoints included mean BBPS scores for the entire colon and individual segments, satisfaction, adverse events, polyp and adenoma detection rates, and impact on sleep and daily activities. Results  Final analysis included 140 subjects, 72 assigned to Clears and 68 to Low-Residue. The Low-Residue diet was non-inferior to Clears (risk difference = - 5.08 %, P  = 0.04) after adjusting for age. Mean colon cleansing scores were not significantly different overall and for individual colonic segments. Satisfaction with the Low-Residue diet was significantly greater ( P  = 0.01). The adenoma detection rate was not statistically significantly different between study groups, but the number of adenomas detected was significantly greater with Clears ( P  = 0.01). Adverse events and impact on sleep and activities did not differ significantly between diet arms. Conclusions  A low-residue diet for breakfast and lunch the day prior to colonoscopy was non-inferior to clear liquids alone for achieving adequate colon cleansing when using split dose PEG-ELS.

Recovery from manual metal arc-stainless steel welding-fume exposure induced lung fibrosis in Sprague-Dawley rats.

PubMed

Yu, Il Je; Song, Kyung Seuk; Chang, Hee Kyung; Han, Jeong Hee; Chung, Yong Hyun; Han, Kuy Tae; Chung, Kyu Hyuck; Chung, Ho Keun

2003-08-28

Welders with radiographic pneumoconiosis abnormalities have exhibited a gradual clearing of the X-ray identified effects following removal from exposure. In some cases, the pulmonary fibrosis associated with welding fumes appears in a more severe form in welders. Accordingly, to investigate the disease and recovery process of pneumoconiosis induced by welding-fume exposure, rats were exposed to welding fumes with concentrations of 63.6+/-4.1 mg/m(3) (low dose) and 107.1+/-6.3 mg/m(3) (high dose) of total suspended particulate for 2 h per day in an inhalation chamber for a total of 2 h or 15, 30, 60 or 90 days. Thereafter, the rats were no longer exposed and allowed to recover from the welding fume-induced lung fibrosis for 90 days. When compared to the unexposed control group, the lung weights significantly increased in both the low- and high-dose rats from day 15 to 90. A histopathological examination combined with fibrosis-specific staining revealed that the lungs from the low-dose rats did not exhibit any significant progressive fibrotic changes. Whereas, the lungs from the high-dose rats exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Recovery, evaluated based on the body and lung weights and a histopathological examination, was observed in both the high and low-dose rats that were exposed up to 30 days. The rats exposed for 60-90 days at the low dose also recovered from the fibrosis, yet the rats exposed for 60-90 days at the high dose did not fully recover. Consequently, recovery from pneumoconiosis induced by welding-fume exposure was observed when the degree of exposure was short-term and moderate.

Immobilization of grizzly bears (Ursus arctos) with dexmedetomidine, tiletamine, and zolazepam.

PubMed

Teisberg, Justin E; Farley, Sean D; Nelson, O Lynne; Hilderbrand, Grant V; Madel, Michael J; Owen, Patricia A; Erlenbach, Joy A; Robbins, Charles T

2014-01-01

Safe and effective immobilization of grizzly bears (Ursus arctos) is essential for research and management. Fast induction of anesthesia, maintenance of healthy vital rates, and predictable recoveries are priorities. From September 2010 to May 2012, we investigated these attributes in captive and wild grizzly bears anesthetized with a combination of a reversible α2 agonist (dexmedetomidine [dexM], the dextrorotatory enantiomer of medetomidine) and a nonreversible N-methyl-d-aspartate (NMDA) agonist and tranquilizer (tiletamine and zolazepam [TZ], respectively). A smaller-than-expected dose of the combination (1.23 mg tiletamine, 1.23 mg zolazepam, and 6.04 µg dexmedetomidine per kg bear) produced reliable, fast ataxia (3.7 ± 0.5 min, x̄±SE) and workable anesthesia (8.1 ± 0.6 min) in captive adult grizzly bears. For wild bears darted from a helicopter, a dose of 2.06 mg tiletamine, 2.06 mg zolazepam, and 10.1 µg dexmedetomidine/kg produced ataxia in 2.5 ± 0.3 min and anesthesia in 5.5 ± 1.0 min. Contrary to published accounts of bear anesthesia with medetomidine, tiletamine, and zolazepam, this combination did not cause hypoxemia or hypoventilation, although mild bradycardia (<50 beats per min) occurred in most bears during the active season. With captive bears, effective dose rates during hibernation were approximately half those during the active season. The time to first signs of recovery after the initial injection of dexMTZ was influenced by heart rate (P<0.001) and drug dose (P<0.001). Intravenous (IV) injection of the reversal agent, atipamezole, significantly decreased recovery time (i.e., standing on all four feet and reacting to the surrounding environment) relative to intramuscular injection. Recovery times (25 ± 8 min) following IV injections of the recommended dose of atipamezole (10 µg/µg of dexmedetomidine) and half that dose (5 µg/µg) did not differ. However, we recommend use of the full dose based on the appearance of a more complete recovery. Field trials confirmed that the dexMTZ + atipamezole protocol is safe, reliable, and predictable when administered to wild grizzly bears, especially during helicopter capture operations.

Dynamic splitting of Gaussian pencil beams in heterogeneity-correction algorithms for radiotherapy with heavy charged particles.

PubMed

Kanematsu, Nobuyuki; Komori, Masataka; Yonai, Shunsuke; Ishizaki, Azusa

2009-04-07

The pencil-beam algorithm is valid only when elementary Gaussian beams are small enough compared to the lateral heterogeneity of a medium, which is not always true in actual radiotherapy with protons and ions. This work addresses a solution for the problem. We found approximate self-similarity of Gaussian distributions, with which Gaussian beams can split into narrower and deflecting daughter beams when their sizes have overreached lateral heterogeneity in the beam-transport calculation. The effectiveness was assessed in a carbon-ion beam experiment in the presence of steep range compensation, where the splitting calculation reproduced a detour effect amounting to about 10% in dose or as large as the lateral particle disequilibrium effect. The efficiency was analyzed in calculations for carbon-ion and proton radiations with a heterogeneous phantom model, where the beam splitting increased computing times by factors of 4.7 and 3.2. The present method generally improves the accuracy of the pencil-beam algorithm without severe inefficiency. It will therefore be useful for treatment planning and potentially other demanding applications.

Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury

PubMed Central

Moreno, Georgina; Woller, Sarah; Puga, Denise; Hoy, Kevin; Balden, Robyn; Grau, James W.

2009-01-01

Abstract Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90 μg) of intrathecal morphine 24 h after a moderate contusion injury. The 90-μg dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90 μg of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord. PMID:19388818

Raman spectroscopy for the analytical quality control of low-dose break-scored tablets.

PubMed

Gómez, Diego A; Coello, Jordi; Maspoch, Santiago

2016-05-30

Quality control of solid dosage forms involves the analysis of end products according to well-defined criteria, including the assessment of the uniformity of dosage units (UDU). However, in the case of break-scored tablets, given that tablet splitting is widespread as a means to adjust doses, the uniform distribution of the active pharmaceutical ingredient (API) in all the possible fractions of the tablet must be assessed. A general procedure to accomplish with both issues, using Raman spectroscopy, is presented. It is based on the acquisition of a collection of spectra in different regions of the tablet, that later can be selected to determine the amount of API in the potential fractions that can result after splitting. The procedure has been applied to two commercial products, Sintrom 1 and Sintrom 4, with API (acenocoumarol) mass proportion of 2% and 0.7% respectively. Partial Least Squares (PLS) calibration models were constructed for the quantification of acenocoumarol in whole tablets using HPLC as a reference analytical method. Once validated, the calibration models were used to determine the API content in the different potential fragments of the scored Sintrom 4 tablets. Fragment mass measurements were also performed to estimate the range of masses of the halves and quarters that could result after tablet splitting. The results show that Raman spectroscopy can be an alternative analytical procedure to assess the uniformity of content, both in whole tablets as in its potential fragments, and that Sintrom 4 tablets can be perfectly split in halves, but some cautions have to be taken when considering the fragmentation in quarters. A practical alternative to the use of UDU test for the assessment of tablet fragments is proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

Absence of a dose-fractionation effect on neoplastic transformation induced by fission-spectrum neutrons in C3H 10T1/2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saran, A.; Pazzaglia, S.; Coppola, M.

1991-06-01

We have investigated the effect of fission-spectrum neutron dose fractionation on neoplastic transformation of exponentially growing C3H 10T1/2 cells. Total doses of 10.8, 27, 54, and 108 cGy were given in single doses or in five equal fractions delivered at 24-h intervals in the biological channel of the RSV-TAPIRO reactor at CRE-Casaccia. Both cell inactivation and neoplastic transformation were more effectively induced by fission neutrons than by 250-kVp X rays. No significant effect on cell survival or neoplastic transformation was observed with split doses compared to single doses of fission-spectrum neutrons. Neutron RBE values relative to X rays determined frommore » data for survival and neoplastic transformation were comparable.« less

A jaw calibration method to provide a homogeneous dose distribution in the matching region when using a monoisocentric beam split technique.

PubMed

Cenizo, E; García-Pareja, S; Galán, P; Bodineau, C; Caudepón, F; Casado, F J

2011-05-01

Asymmetric collimators are currently available in most of linear accelerators. They involve a lot of clinical improvements, such as the monoisocentric beam split technique that is more and more used in many external radiotherapy treatments. The tolerance established for each independent jaw positioning is 1 mm. Within this tolerance, a gap or overlap of the collimators up to 2 mm can occur in the half beams matching region, causing dose heterogeneities up to 40%. In order to solve this dosimetric problem, we propose an accurate jaw calibration method based on the Monte Carlo modeling of linac photon beams. Simulating different jaw misalignments, the dose distribution occurring in the matching region for each particular configuration is precisely known, so we can relate the misalignment of the jaws with the maximum heterogeneity produced. From experimental measurements using film dosimetry, and taking into account Monte Carlo results, we obtain the actual misalignment of each jaw. By direct inspection of the readings of the potentiometers that control the position of the jaws, high precision correction can be performed, adjusting the obtained misalignments. In the linac studied, the dose heterogeneity in the junction performed with X jaws (those farther from the source), and 6 MV photon beam was initially over 12%, although each jaw was within the tolerance in position. After jaw calibration, the heterogeneity was reduced to below 3%. With this method, we are able to reduce the positioning accuracy to 0.2 mm. Consequently, the dose distribution in the junction of abutted fields is highly smoothed, achieving the maximum dose heterogeneity to be less than 3%.

Optimization of 64-MDCT urography: effect of dual-phase imaging with furosemide on collecting system opacification and radiation dose.

PubMed

Portnoy, Orith; Guranda, Larisa; Apter, Sara; Eiss, David; Amitai, Marianne Michal; Konen, Eli

2011-11-01

The purpose of this study was to compare opacification of the urinary collecting system and radiation dose associated with three-phase 64-MDCT urographic protocols and those associated with a split-bolus dual-phase protocol including furosemide. Images from 150 CT urographic examinations performed with three scanning protocols were retrospectively evaluated. Group A consisted of 50 sequentially registered patients who underwent a three-phase protocol with saline infusion. Group B consisted of 50 sequentially registered patients who underwent a reduced-radiation three-phase protocol with saline. Group C consisted of 50 sequentially registered patients who underwent a dual-phase split-bolus protocol that included a low-dose furosemide injection. Opacification of the urinary collecting system was evaluated with segmental binary scoring. Contrast artifacts were evaluated, and radiation doses were recorded. Results were compared by analysis of variance. A significant reduction in mean effective radiation dose was found between groups A and B (p < 0.001) and between groups B and C (p < 0.001), resulting in 65% reduction between groups A and C (p < 0.001). This reduction did not significantly affect opacification score in any of the 12 urinary segments (p = 0.079). In addition, dense contrast artifacts overlying the renal parenchyma observed with the three-phase protocols (groups A and B) were avoided with the dual-phase protocol (group C) (p < 0.001). A dual-phase protocol with furosemide injection is the preferable technique for CT urography. In comparison with commonly used three-phase protocols, the dual-phase protocol significantly reduces radiation exposure dose without reduction in image quality.

Bi-tangential hybrid IMRT for sparing the shoulder in whole breast irradiation.

PubMed

Farace, P; Deidda, M A; Iamundo de Cumis, I; Iamundo de Curtis, I; Deiana, E; Farigu, R; Lay, G; Porru, S

2013-11-01

A bi-tangential technique is proposed to reduce undesired doses to the shoulder produced by standard tangential irradiation. A total of 6 patients affected by shoulder pain and reduced functional capacity after whole-breast irradiation were retrospectively analysed. The standard tangential plan used for treatment was compared with (1) a single bi-tangential plan where, to spare the shoulder, the lateral open tangent was split into two half-beams at isocentre, with the superior portion rotated by 10-20° medially with respect to the standard lateral beam; (2) a double bi-tangential plan, where both the tangential open beams were split. The planning target volume (PTV) coverage and the dose to the portion of muscles and axilla included in the standard tangential beams were compared. PTV95 % of standard plan (91.9 ± 3.8) was not significantly different from single bi-tangential plan (91.8 ± 3.4); a small but significant (p < 0.01) decrease was observed with the double bi-tangential plan (90.1 ± 3.7). A marked dose reduction to the muscle was produced by the single bi-tangential plan around 30-40 Gy. The application of the double bi-tangential technique further reduced the volume receiving around 20 Gy, but did not markedly affect the higher doses. The dose to the axilla was reduced both in the single and the double bi-tangential plans. The single bi-tangential technique would have been able to reduce the dose to shoulder and axilla, without compromising target coverage. This simple technique is valuable for irradiation after axillary lymph node dissection or in patients without dissection due to negative or low-volume sentinel lymph node disease.

[Retrospective analysis of patients with thrombocytopenia after patent ductus arteriosus interventional occlusion].

PubMed

Liao, Qi-wei; Zhang, Wei-hua; Guang, Xue-feng; Lu, Yi-bing

2013-03-01

To explore the risk factors of patent ductus arteriosus (PDA) patients with thrombocytopenia after PDA interventional occlusion. Thrombocytopenia occurred in 14 out of 350 patients underwent PDA occlusion. Age, gender, body weight, PDA size, occluder size, mean pulmonary arterial pressure, the dose of heparin, the manufacturer of occluder, residual shunt after operation were analyzed. The recovery time of different grades of thrombocytopenia was observed. Multivariate logistic regression showed that the PDA size (OR = 2.238, P < 0.05), the dose of heparin (OR = 3.247, P < 0.05), residual shunt after operation (OR = 1.912, P < 0.01) were the independent risk factors of thrombocytopenia after PDA occlusion. The recovery time of mild thrombocytopenia was (7 ± 2) days without treatment. The recovery time of moderate thrombocytopenia was (12 ± 4) days with glucocorticoids treatment. The recovery time of severe thrombocytopenia was (21 ± 7) days with platelet transfusion. The occluder size, dose of heparin, residual shunt are the independent risk factors of thrombocytopenia after PDA interventional occlusion. Recover time of thrombocytopenia after PDA interventional occlusion is closely related to the severity of thrombocytopenia.

The similia principle: results obtained in a cellular model system.

PubMed

Wiegant, Fred; Van Wijk, Roeland

2010-01-01

This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized. Copyright 2009 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Low-dose D-methionine and N-acetyl-L-cysteine for protection from permanent noise-induced hearing loss in chinchillas.

PubMed

Clifford, Royce E; Coleman, John K M; Balough, Ben J; Liu, Jianzhong; Kopke, Richard D; Jackson, Ronald L

2011-12-01

Despite efforts at public health awareness and stringent industrial standards for hearing protection, noise-induced hearing loss (NIHL) remains a formidable public health concern. Although many antioxidants have proven to be beneficial in the laboratory for prevention of permanent NIHL, low-dose combinations of compounds with different biochemical mechanisms of action may allow long-term administration with fewer side effects and equal efficacy. The mixture of D-methionine and N-acetyl-L-cysteine administered at levels less than 10% of standard dosing has not been previously reported. Twenty-six female adult Chinchilla laniger were placed in 4 study groups, consisting of (1) a group receiving combination 12.5 mg/kg each D-methionine and N-acetyl-L-cysteine (DMET/NAC group), (2) a group receiving 12.5 mg/kg D-methionine (DMET-only group), (3) a group receiving 12.5 mg/kg N-acetyl-L-cysteine (NAC-only group), and (4) saline controls. Laboratory. All groups received twice-daily intraperitoneal injections 2 days prior to noise exposure, 1 hour before and after exposure on day 3, and for 2 days subsequently, totaling 10 doses of 125 mg/kg for each antioxidant over 5 days. Although NAC-only animals paralleled saline control recovery during 3 weeks, the DMET-only group revealed gradual improvement with statistically significant recovery in the middle frequencies. The DMET/NAC group showed significant improvement at most frequencies compared with controls (P < .001 and P < .05). Significant recovery of hearing was observed following continuous noise exposure with either DMET only or a combination of low-dose DMET/NAC, demonstrating a considerably lower dose of antioxidants required than previously reported for hearing recovery following acoustic trauma.

Development and Validation of a Questionnaire to Assess Carbohydrate and Insulin-Dosing Knowledge in Youth With Type 1 Diabetes

PubMed Central

Koontz, Michaela B.; Cuttler, Leona; Palmert, Mark R.; O'Riordan, MaryAnn; Borawski, Elaine A.; McConnell, Judy; Kern, Elizabeth O.

2010-01-01

OBJECTIVE The American Diabetes Association advocates insulin regimens for youth with type 1 diabetes that involve adjusting insulin dose based on carbohydrate intake and blood glucose level. Implementing these regimens requires knowledge about carbohydrate content of foods and subsequent calculations of insulin dose, skills that may be difficult to gauge in practice. Therefore, we sought to develop and validate a questionnaire, the PedCarbQuiz (PCQ), to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS After development by an expert panel, the PCQ was administered to 75 youth with type 1 diabetes or their parents. Reliability was assessed by Cronbach α and split-half testing. To assess validity, scores were correlated with A1C, expert assessments, parent educational level, and complexity of insulin regimen. RESULTS PCQ mean score was 87 ± 9.7% (range 42–98%). Cronbach α was 0.88, and correlation of split halves was 0.59 (P < 0.0001). Higher PCQ scores correlated significantly with lower A1C (r = −0.29, P = 0.01) and expert assessments (r = 0.56, P < 0.001). Scores were significantly higher in parents with college degrees than in those without (P = 0.01) and in participants with more complex insulin regimens (P = 0.003). CONCLUSIONS The PCQ is a novel, easily administered instrument to assess knowledge about carbohydrates and insulin dosing calculations. Initial analyses support the reliability and validity of the PCQ. PMID:20007940

Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial.

PubMed

Wunderink, Lex; Nieboer, Roeline M; Wiersma, Durk; Sytema, Sjoerd; Nienhuis, Fokko J

2013-09-01

Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR. One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. isrctn.org Identifier: ISRCTN16228411.

3D splint prototype system for applications in muscular rehab by transcutaneous electrical nerve stimulation (TENS)

NASA Astrophysics Data System (ADS)

Saldaña-Martínez, M. I.; Guzmán-González, J. V.; Barajas-González, O. G.; Guzman-Ramos, V.; García-Garza, A. K.; González-García, R. B.; García-Ramírez, M. A.

2017-03-01

It is quite common that patients with ligamentous ruptures, tendonitis, tenosynovitis or sprains are foreseen the use of ad hoc splints for a swift recovery. In this paper, we propose a rehabilitation split that is focused on upper-limb injuries. By considering that upper-limb patient shows a set of different characteristics, our proposal personalizes and prints the splint custom made though a digital model that is generated by a 3D commercial scanner. To fabricate the 3D scanned model the Stereolithography material (SLA) is considered due to the properties that this material offers. In order to complement the recovery process, an electronic system is implemented within the splint design. This system generates a set of pulses for a fix period of time that focuses mainly on a certain group of muscles to allow a fast recovery process known as Transcutaneous Electrical Nerve Stimulation Principle (TENS).

Retrofitting the Williams Energy Services Ignacio Plant for higher throughput and recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lynch, J.T.; Pitman, R.N.

1999-07-01

The Ignacio Plant located near Durango, Colorado was originally designed to process 346 MMscfd of feed gas and to recover approximately 82% of the contained ethane. Based on increasing volumes of available feed gas, Williams Energy Services (WES) undertook a study to investigate alternatives for increasing plant capacity and ethane recovery. This study led to the selection of Ortloff's Recycle Split-Vapor (RSV) process for retrofitting the existing facility because it offered several very important advantages: maximum utilization of existing equipment, a 30% increase in plant feed handling capacity and an increase in average ethane recovery to 94% without adding residuemore » compressors. This paper presents the comparative case analysis that led to the selection of the RSV design. It also describes the modifications required for the retrofit, all of which can be accomplished with minimum plant down time. The modified Ignacio Plant is scheduled for startup in March 1999.« less

Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging

NASA Astrophysics Data System (ADS)

Lee, Jason J. S.; Tsai, Chia-Jung; Lo, Man-Kuok; Huang, Yung-Hui; Chen, Chien-Chuan; Wu, Jay; Tyan, Yeu-Sheng; Wu, Tung-Hsin

2008-05-01

A new type of normoxic polymer gel dosimeter, named MAGAT responses well to absorbed dose even when manufacturing in the presence of normal levels of oxygen. The aim of this study was to evaluate dose response, diffusion effect and cumulated dose response under multiple fractional irradiations of the MAGAT gel dosimeter using Multiple Spin-Echo (MSE) Magnetic Resonance (MR) sequence. Dose response was performed by irradiating MAGAT-gel-filled testing vials with a 6 MV linear accelerator and a linear relationship was present with doses from 0 to 6 Gy, but gradually, a bi-exponential function result was obtained with given doses up to 20 Gy. No significant difference in dose response was present between single and cumulated doses (p > 0.05). For study of diffusion effect, edge sharpness of the R2 map imaging between two split doses was smaller than 1 cm of dose profile penumbra between 20% and 80%. In conclusion, the MAGAT polymer gel dosimeter with MSE MR imaging is a promising method for dose verification in clinical radiation therapy practice.

Limited recovery of soil microbial activity after transient exposure to gasoline vapors.

PubMed

Modrzyński, Jakub J; Christensen, Jan H; Mayer, Philipp; Brandt, Kristian K

2016-09-01

During gasoline spills complex mixtures of toxic volatile organic compounds (VOCs) are released to terrestrial environments. Gasoline VOCs exert baseline toxicity (narcosis) and may thus broadly affect soil biota. We assessed the functional resilience (i.e. resistance and recovery of microbial functions) in soil microbial communities transiently exposed to gasoline vapors by passive dosing via headspace for 40 days followed by a recovery phase of 84 days. Chemical exposure was characterized with GC-MS, whereas microbial activity was monitored as soil respiration (CO2 release) and soil bacterial growth ([(3)H]leucine incorporation). Microbial activity was strongly stimulated and inhibited at low and high exposure levels, respectively. Microbial growth efficiency decreased with increasing exposure, but rebounded during the recovery phase for low-dose treatments. Although benzene, toluene, ethylbenzene and xylene (BTEX) concentrations decreased by 83-97% during the recovery phase, microbial activity in high-dose treatments did not recover and numbers of viable bacteria were 3-4 orders of magnitude lower than in control soil. Re-inoculation with active soil microorganisms failed to restore microbial activity indicating residual soil toxicity, which could not be attributed to BTEX, but rather to mixture toxicity of more persistent gasoline constituents or degradation products. Our results indicate a limited potential for functional recovery of soil microbial communities after transient exposure to high, but environmentally relevant, levels of gasoline VOCs which therefore may compromise ecosystem services provided by microorganisms even after extensive soil VOC dissipation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electrodialysis-based separation process for salt recovery and recycling from waste water

DOEpatents

Tsai, S.P.

1997-07-08

A method for recovering salt from a process stream containing organic contaminants is provided, comprising directing the waste stream to a desalting electrodialysis unit so as to create a concentrated and purified salt permeate and an organic contaminants-containing stream, and contacting said concentrated salt permeate to a water-splitting electrodialysis unit so as to convert the salt to its corresponding base and acid. 6 figs.

Electrodialysis-based separation process for salt recovery and recycling from waste water

DOEpatents

Tsai, Shih-Perng

1997-01-01

A method for recovering salt from a process stream containing organic contaminants is provided, comprising directing the waste stream to a desalting electrodialysis unit so as to create a concentrated and purified salt permeate and an organic contaminants containing stream, and contacting said concentrated salt permeate to a water-splitting electrodialysis unit so as to convert the salt to its corresponding base and acid.

Titrated propofol induction vs. continuous infusion in children undergoing magnetic resonance imaging.

PubMed

Cho, J E; Kim, W O; Chang, D J; Choi, E M; Oh, S Y; Kil, H K

2010-04-01

Propofol is the popular intravenous (i.v.) anaesthetic for paediatric sedation because of its rapid onset and recovery. We compared the efficacy and safety of a single dose and conventional infusion of propofol for sedation in children who underwent magnetic resonance imaging (MRI). This was a double-blind, randomized-controlled study. One hundred and sixty children were assigned to group I (single dose) or II (infusion). Sedation was induced with i.v. propofol 2 mg/kg, and supplemental doses of propofol 0.5 mg/kg were administered until adequate sedation was achieved. After the induction of sedation, we treated patients with a continuous infusion of normal saline at a rate of 0.3 ml/kg/h in group I and the same volume of propofol in group II. In case of inadequate sedation, additional propofol 0.5 mg/kg was administered and the infusion rate was increased by 0.05 ml/kg/h. Induction time, sedation time, recovery time, additional sedation and adverse events were recorded. Recovery time was significantly shorter in group I compared with group II [0 (0-3) vs. 1 (0-3), respectively, P<0.001]. Group I (single dose) had significantly more patients with recovery time 0 compared with group II (infusion) (65/80 vs. 36/80, respectively, P<0.001). Induction and sedation times were not significantly different between groups. There was no significant difference in the frequency of additional sedation and adverse events between groups. A single dose of propofol without a continuous infusion can provide appropriate sedation in children undergoing MRI for <30 min.

Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler.

PubMed

de Boer, Anne H; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

2012-09-01

To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer™ dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer™. CFD computations showed that the flow split of the Twincer™ is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico-chemical properties of the drug formulation with respect to dispersion and retention behaviour. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

The fate of mitochondrial loci in rho minus mutants induced by ultraviolet irradiation of Saccharomyces cerevisiae: effects of different post-irradiation treatments.

PubMed

Heude, M; Moustacchi, E

1979-09-01

Three main features regarding the loss of mitochondrial genetic markers among rho- mutants induced by ultraviolet irradiation are reported: (a) the frequency of loss of six loci examined increases with UV dose; (b) preferential loss of one region of the mitochondrial genome observed in spontaneous rho- mutants is enhanced by UV; and (c) the loss of each marker results from large deletions. Marker loss in rho- mutants was also investigated under conditions that modulate rho- induction. Liquid holding of irradiated exponential or stationary phase cells, as well as a split-dose regime applied to stationary phase cells, results in rho- mutants in which the loss of markers is correlated with rho- induction: the more sensitive the cells are to rho- induction, the more frequent are the marker losses among rho- clones derived from these cells. This correlation is not found in exponential-phase cells submitted to a split-dose treatment, suggesting that a different mechanism is involved in the latter case. It is known that UV-induced pyrimidine dimers are not excised in a controlled manner in mitochondrial DNA. However, our studies indicate that an accurate repair mechanism (of the recombinational type ?) can lead to the restoration of mitochondrial genetic information in growing cells.

Sleep inertia during a simulated 6-h on/6-h off fixed split duty schedule.

PubMed

Hilditch, Cassie J; Short, Michelle; Van Dongen, Hans P A; Centofanti, Stephanie A; Dorrian, Jillian; Kohler, Mark; Banks, Siobhan

Sleep inertia is a safety concern for shift workers returning to work soon after waking up. Split duty schedules offer an alternative to longer shift periods, but introduce additional wake-ups and may therefore increase risk of sleep inertia. This study investigated sleep inertia across a split duty schedule. Sixteen participants (age range 21-36 years; 10 females) participated in a 9-day laboratory study with two baseline nights (10 h time in bed, [TIB]), four 24-h periods of a 6-h on/6-h off split duty schedule (5-h TIB in off period; 10-h TIB per 24 h) and two recovery nights. Two complementary rosters were evaluated, with the timing of sleep and wake alternating between the two rosters (2 am/2 pm wake-up roster versus 8 am/8 pm wake-up roster). At 2, 17, 32 and 47 min after scheduled awakening, participants completed an 8-min inertia test bout, which included a 3-min psychomotor vigilance test (PVT-B), a 3-min Digit-Symbol Substitution Task (DSST), the Karolinska Sleepiness Scale (KSS), and the Samn-Perelli Fatigue Scale (SP-Fatigue). Further testing occurred every 2 h during scheduled wakefulness. Performance was consistently degraded and subjective sleepiness/fatigue was consistently increased during the inertia testing period as compared to other testing times. Morning wake-ups (2 am and 8 am) were associated with higher levels of sleep inertia than later wake-ups (2 pm and 8 pm). These results suggest that split duty workers should recognise the potential for sleep inertia after waking, especially during the morning hours.

[Divisibility of warfarin and fluindione tablets tested in elderly patients and their family circle].

PubMed

Pautas, Eric; Despres, Jérémie; Peyron, Isabelle; Golmard, Jean-Louis; Grange, Jennifer; Koenig, Nelly; Gouronnec, Adeline; Mitha, Nathalie; Siguret, Virginie; Gouin-Thibault, Isabelle

2011-06-01

Vitamin K antagonist tablets are often split to fractionate the dose by elderly patients. We performed a study in order to assess the divisibility of one dosage strength of score-lined warfarin and of score-lined fluindione. Due to a recent change in the pharmaceutical form of fluindione in order to improve the divisibility, the study was performed over 2 different periods (with the « old » and with the « new » pharmaceutical form). In each period, 10 patients mean aged 82 years, 10 relatives, 10 nurses, 10 medical doctors) were asked to split in half warfarin tablets (W2 1(st) period et W2 2(d) period) and fluindione tablets (F2 et F'2), and to split fluindione tablets into 4 fragments (F4 et F'4). The first end-point was the accuracy of splitting estimated by the difference between the real and the expected weight of fragmented tablets. The statistical analysis was performed using an ANOVA test with 2 variables, subject and drug. The difference between the 2 periods were analyzed using an ANOVA test with 2 variables, subject and period. Over the 2 periods, the differences between real and expected weight were of 4.65% for W2 1(st) phase, 9.48% for F2, 15.35% for F4, 5.56% for W2 2(d )period, 4.30% for F'2, and 6.98% for F'4. The quality of splitting was statistically poorer in the elderly patient group compared to other subjects. This study was not design to assess the clinical relevance (bleeding or thromboembolism) or the anticoagulation control of the variations in drug mass due to inappropriate splitting of tablets. However, split form of drugs should be prescribe with caution to elderly patients.

Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen.

PubMed

Nagaya, Tadanobu; Sato, Kazuhide; Harada, Toshiko; Nakamura, Yuko; Choyke, Peter L; Kobayashi, Hisataka

2015-01-01

Triple-negative breast cancer (TNBC) is considered one of the most aggressive subtypes of breast cancer. Near infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that employs an antibody-photosensitizer conjugate (APC) followed by exposure of NIR light for activating selective cytotoxicity on targeted cancer cells and may have application to TNBC. In order to minimize the dose of APC while maximizing the therapeutic effects, dosing of the APC and NIR light need to be optimized. In this study, we investigate in vitro and in vivo efficacy of cetuximab (cet)-IR700 NIR-PIT on two breast cancer models MDAMB231 (TNBC, EGFR moderate) and MDAMB468 (TNBC, EGFR high) cell lines, and demonstrate a method to optimize the dosing APC and NIR light. After validating in vitro cell-specific cytotoxicity, NIR-PIT therapeutic effects were investigated in mouse models using cell lines derived from TNBC tumors. Tumor-bearing mice were separated into 4 groups for the following treatments: (1) no treatment (control); (2) 300 μg of cet-IR700 i.v., (APC i.v. only); (3) NIR light exposure only, NIR light was administered at 50 J/cm2 on day 1 and 100 J/cm2 on day 2 (NIR light only); (4) 300 μg of cet-IR700 i.v., NIR light was administered at 50 J/cm2 on day 1 after injection and 100 J/cm2 of light on day 2 after injection (one shot NIR-PIT). To compare different treatment regimens with a fixed dose of APC, we added the following treatments (5) 100 μg of cet-IR700 i.v., NIR light administered at 50 J/cm2 on day 1 and 50 μg of cet-IR700 i.v. immediately after NIR-PIT, then NIR light was administered at 100 J/cm2 on day 2, which were performed two times every week ("two split" NIR-PIT) and (6) 100 μg of cet-IR700 i.v., NIR light was administered at 50 J/cm2 on day 1 and 100 J/cm2 on day 2, which were performed three times per week ("three split" NIR-PIT). Both specific binding and NIR-PIT effects were greater with MDAMB468 than MDAMB231 cells in vitro. Tumor accumulation of cet-IR700 in MDAMB468 tumors was significantly higher (p < 0.05) than in MDAMB231 tumors in vivo. Tumor growth and survival of MDAMB231 tumor bearing mice was significantly lower in the NIR-PIT treatment group (p < 0.05). In MDAMB468 bearing mice, tumor growth and survival was significantly improved in the NIR-PIT treatment groups in all treatment regimens (one shot NIR-PIT; p < 0.05, "two split" NIR-PIT; p < 0.01, "three split" NIR-PIT; p < 0.001) compared with control groups. NIR-PIT for TNBC was effective regardless of expression of EGFR, however, greater cell killing was shown with higher EGFR expression tumor in vitro. In all treatment regimens, NIR-PIT suppressed tumor growth, resulting in significantly prolonged survival that further improved by splitting the APC dose and using repeated light exposures.

What is the ideal dose and power output of low-level laser therapy (810 nm) on muscle performance and post-exercise recovery? Study protocol for a double-blind, randomized, placebo-controlled trial.

PubMed

de Oliveira, Adriano Rodrigues; Vanin, Adriane Aver; De Marchi, Thiago; Antonialli, Fernanda Colella; Grandinetti, Vanessa dos Santos; de Paiva, Paulo Roberto Vicente; Albuquerque Pontes, Gianna Móes; Santos, Larissa Aline; Aleixo Junior, Ivo de Oliveira; de Carvalho, Paulo de Tarso Camillo; Bjordal, Jan Magnus; Leal-Junior, Ernesto Cesar Pinto

2014-02-27

Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose-response pattern. The protocol for this study is registered with the Protocol Registry System, ClinicalTrials.gov identifier NCT01844271.

Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.

PubMed

Rex, Douglas K; Katz, Philip O; Bertiger, Gerald; Vanner, Stephen; Hookey, Lawrence C; Alderfer, Vivian; Joseph, Raymond E

2013-07-01

New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). Multicenter, assessor-blinded, randomized, noninferiority study. University hospitals, academic medical centers, and private clinics across the United States. Adults preparing for colonoscopy. P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets (P < .0001). Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Randomized Clinical Trial of the Innovative Bilayered Wound Dressing Made of Silk and Gelatin: Safety and Efficacy Tests Using a Split-Thickness Skin Graft Model

PubMed Central

Hasatsri, Sukhontha; Angspatt, Apichai

2015-01-01

We developed the novel silk fibroin-based bilayered wound dressing for the treatment of partial thickness wounds. And it showed relevant characteristics and accelerated the healing of full-thickness wounds in a rat model. This study is the clinical evaluation of the bilayered wound dressing to confirm its safety and efficacy for the treatment of split-thickness skin donor sites. The safety test was performed using a patch model and no evidence of marked and severe cutaneous reactions was found. The efficacy test of the bilayered wound dressing was conducted on 23 patients with 30 split-thickness skin graft donor sites to evaluate healing time, pain score, skin barrier function, and systemic reaction in comparison to Bactigras. We found that the healing time of donor site wounds treated with the bilayered wound dressing (11 ± 6 days) was significantly faster than those treated with Bactigras (14 ± 6 days) (p = 10−6). The wound sites treated with the bilayered wound dressing showed significantly less pain and more rapid skin functional barrier recovery than those treated with Bactigras (p = 10−5). Therefore, these results confirmed the clinical safety and efficacy of the bilayered wound dressing for the treatment of split-thickness skin graft donor sites. PMID:26221170

Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

PubMed

Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

2016-01-01

Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Charge-coupled-device X-ray detector performance model

NASA Technical Reports Server (NTRS)

Bautz, M. W.; Berman, G. E.; Doty, J. P.; Ricker, G. R.

1987-01-01

A model that predicts the performance characteristics of CCD detectors being developed for use in X-ray imaging is presented. The model accounts for the interactions of both X-rays and charged particles with the CCD and simulates the transport and loss of charge in the detector. Predicted performance parameters include detective and net quantum efficiencies, split-event probability, and a parameter characterizing the effective thickness presented by the detector to cosmic-ray protons. The predicted performance of two CCDs of different epitaxial layer thicknesses is compared. The model predicts that in each device incomplete recovery of the charge liberated by a photon of energy between 0.1 and 10 keV is very likely to be accompanied by charge splitting between adjacent pixels. The implications of the model predictions for CCD data processing algorithms are briefly discussed.

A randomized, controlled trial of oral sulfate solution plus polyethylene glycol as a bowel preparation for colonoscopy.

PubMed

Rex, Douglas K; McGowan, John; Cleveland, Mark vB; Di Palma, Jack A

2014-09-01

No bowel preparation for colonoscopy is optimal with regard to efficacy, safety, and tolerability. New options for bowel preparation are needed. To compare a new hybrid preparation consisting of a reduced dose of oral sulfate solution (OSS) plus 2 L of sulfate-free electrolyte lavage solution (SF-ELS) with 2 low-volume preparations based on polyethylene glycol electrolyte lavage solution (PEG-ELS). Two randomized, controlled trials. Twenty-four U.S. centers. A total of 737 outpatients undergoing colonoscopy. In study 1, OSS plus SF-ELS was given as a split dose, and in study 2, OSS plus SF-ELS was given in its entirety the evening before colonoscopy. In study 1, the active control was 2 L of PEG-ELS plus ascorbic acid (PEG-EA) given as a split dose. In study 2, the control was 10 mg of bisacodyl plus 2 L of SF-ELS taken the evening before colonoscopy. Rates of successful (good or excellent) bowel preparation. In study 1, the rates of successful (excellent or good) preparation with OSS plus SF-ELS and PEG-EA were identical at 93.5% for split-dose preparation. OSS plus SF-ELS was noninferior to PEG-EA (P < .001). In study 2, OSS plus SF-ELS resulted in successful preparation in 89.8% of patients compared with 83.5% with bisacodyl plus SF-ELS in a same-day preparation regimen. OSS plus SF-ELS was noninferior to bisacodyl plus SF-ELS (P <.001). In study 1, vomiting was more frequent with OSS plus SF-ELS (13.5% vs 6.7%; P = .042), and bloating was rated worse with PEG-EA (P = .025). In study 2, overall discomfort was rated worse with OSS plus SF-ELS (mean score 2.1 vs 1.8; P = .032). There were no deaths in either study and no serious adverse events considered related to the preparation. Bowel cleansing was not scored by colon segment. Adenoma detection was not compared between the regimens. OSS plus SF-ELS is a new, safe, and effective bowel preparation for colonoscopy. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10.

PubMed

Ghadjar, Pirus; Hayoz, Stefanie; Bernhard, Jürg; Zwahlen, Daniel R; Stein, Jürgen; Hölscher, Tobias; Gut, Philipp; Polat, Bülent; Hildebrandt, Guido; Müller, Arndt-Christian; Putora, Paul Martin; Papachristofilou, Alexandros; Schär, Corinne; Dal Pra, Alan; Biaggi Rudolf, Christine; Wust, Peter; Aebersold, Daniel M; Thalmann, George N

2018-02-01

Adjuvant radiation therapy (aRT) after radical prostatectomy (RP) is associated with impaired urinary continence recovery as compared to surveillance. Less is known regarding the effect of salvage radiation therapy (sRT) dose intensification on continence outcomes. Urinary continence recovery was investigated within a multicentre randomized trial in biochemically recurrent prostate cancer patients who received either 64 Gy (32 fractions) or 70 Gy (35 fractions) sRT. Incontinence was assessed using Common Toxicity Criteria for Adverse Events v4.0 at baseline, at the end of sRT and 3 months afterward. Quality of life (QoL) was assessed with the EORTC QoL questionnaires C30 and PR25 at baseline and 3 months after completion of sRT. A total of 344 patients were evaluable. At baseline 233 (68%) of patients were fully continent and 14% in both arms became incontinent three months after treatment. Of the remaining 111 (32%) patients being incontinent at baseline, continence recovery was achieved 3 months after sRT by 44% vs. 41% with 64 vs. 70 Gy, respectively (p = 0.8). This analysis is limited by its short follow-up. Dose intensification of sRT had no impact on early urinary continence recovery or prevalence of de novo incontinence. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vitro Skin Penetration of Petrolatum and Soybean Oil and Effects of Glyceryl Monooleate.

PubMed

Intarakumhaeng, Rattikorn; Shi, Zhanquan; Wanasathop, Apipa; Stella, Q Ching; Wei, Karl S; Styczynski, P B; Li, Chuiying; Smith, Edward D; Li, S Kevin

2018-06-06

Petrolatum and soybean oil are common ingredients incorporated in topical skin formulations for skin protection and moisturization. However, the stratum corneum (SC) penetration kinetics of these two cosmetic ingredients has not been systematically studied. Glyceryl monooleate (GlyMOle) has been shown to enhance skin penetration of various compounds. It was hypothesized that GlyMOle could enhance skin penetration of petrolatum and soybean oil. The present study aimed to examine the in vitro skin penetration of petrolatum and soybean oil in the presence or absence of GlyMOle. Skin permeation experiments were conducted using the in vitro Franz diffusion cell model with split-thickness human skin and human epidermal membrane (HEM). The effect of permeant dose and the kinetics of permeant penetration were examined with and without GlyMOle in vitro. Petrolatum and soybean oil were found to permeate across HEM, and no effect of GlyMOle on skin permeation into the receptor chamber was observed. GlyMOle enhanced the penetration of petrolatum into the split-thickness skin at 50 μg dose (petrolatum:GlyMOle, 49:1, w/w). However, no effect of GlyMOle on petrolatum penetration was observed at 200 μg dose (petrolatum:GlyMOle, 49:1, w/w), indicating a dose-dependent effect. GlyMOle at the level used in the study did not enhance the penetration of soybean oil with 50 and 200 μg doses at any time points. GlyMOle was a skin penetration enhancer for petrolatum under the in vitro conditions identified in the present study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

PubMed

Lemoine, Adrien; Mazoit, Jean X; Bonnet, Francis

2016-11-01

Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. Systematic review of clinical trials. Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

The accuracy, precision and sustainability of different techniques for tablet subdivision: breaking by hand and the use of tablet splitters or a kitchen knife.

PubMed

van Riet-Nales, Diana A; Doeve, Myrthe E; Nicia, Agnes E; Teerenstra, Steven; Notenboom, Kim; Hekster, Yechiel A; van den Bemt, Bart J F

2014-05-15

Tablets are frequently subdivided to lower the dose, to facilitate swallowing by e.g. children or older people or to save costs. Splitting devices are commonly used when hand breaking is difficult or painful. Three techniques for tablet subdivision were investigated: hand breaking, tablet splitter, kitchen knife. A best case drug (paracetamol), tablet (round, flat, uncoated, 500 mg) and operator (24-year student) were applied. Hundred tablets were subdivided by hand and by three devices of each of the following types: Fit & Healthy, Health Care Logistics, Lifetime, PillAid, PillTool, Pilomat tablet splitter; Blokker kitchen knife. The intra and inter device accuracy, precision and sustainability were investigated. The compliance to (adapted) regulatory requirements was investigated also. The accuracy and precision of hand broken tablets was 104/97% resp. 2.8/3.2% (one part per tablet considered; parts right/left side operator). The right/left accuracies of the splitting devices varied between 60 and 133%; the precisions 4.0 and 29.6%. The devices did not deteriorate over 100-fold use. Only hand broken tablets complied with all regulatory requirements. Health care professionals should realize that tablet splitting may result in inaccurate dosing. Authorities should undertake appropriate measures to assure good function of tablet splitters and, where feasible, to reduce the need for their use. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Recovery from Cyclophosphamide Overdose in a Dog.

PubMed

Finlay, Jessica Renee; Wyatt, Kenneth; North, Courtney

An adult female spayed dog was evaluated after inadvertently receiving a total dose of 1,750 mg oral cyclophosphamide, equivalent to 2,303 mg/m 2 , over 21 days (days -21 to 0). Nine days after the last dose of cyclophosphamide (day +9), the dog was evaluated at Perth Veterinary Specialists. Physical examination revealed mucosal pallor, a grade 2/6 systolic heart murmur, and severe hemorrhagic cystitis. Severe nonregenerative pancytopenia was detected on hematology. Broad spectrum antibiotics, two fresh whole blood transfusions, granulocyte colony stimulating factor, and tranexamic acid were administered. Five days after presentation (day +14), the peripheral neutrophil count had recovered, and by 12 days (day +21) the complete blood count was near normal. A second episode of thrombocytopenia (day +51) was managed with vincristine, prednisolone, and melatonin. The dog made a complete recovery with no long-term complications at the time of writing. To the author's knowledge, this is the highest inadvertently administered dose of cyclophosphamide to result in complete recovery.

Intestinal radiation syndrome: sepsis and endotoxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presencemore » of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This case study describes a DOE Zero Energy Ready home in Vassalboro, Maine, that scored HERS 35 without PV and HERS 11 with PV. This 1,200 ft2 home has 10.5-inch-thick double-walls with 3 layers of mineral wool batt insulation, an R-20 insulated slab, R-70 cellulose in the attic, extensive air sealing, a mini-split heat pump, an heat recovery ventilator, solar water heating, LED lighting, 3.9 kWh PV, and triple-pane windows.

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (4). 6-month repeated dose intravenous toxicity study in rats with 1-month recovery test].

PubMed

Yamaguchi, K; Aze, Y; Shimizu, K; Shichino, Y; Oku, H; Mori, H; Shinomiya, K; Ueda, H; Suzuki, Y; Oida, H; Nishibata, K; Tanaka, M; Yanagizawa, Y; Nanba, T; Nishiyama, K; Yonezawa, H; Fujita, T

1998-07-01

A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 18.75, 37.5 or 75 mg/kg. ONO-5046.Na did not affect clinical signs, body weight, food consumption, opthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology at any dose. These results indicate that the NOAEL of ONO-5046.Na in rats is 75 mg/kg/day for both sexes in this study.

Procedure for maximizing oocyte harvest for in vitro embryo production in small ruminants.

PubMed

Gibbons, A; Pereyra Bonnet, F; Cueto, M I; Catala, M; Salamone, D F; Gonzalez-Bulnes, A

2007-08-01

Possible effects of repeated hormonal treatments and laparoscopic ovum pick-up (LOPU) on the efficiency of oocyte recovery rate and quality were determined in sheep and goats. In six adult Merino sheep and five Criolla goats, ovarian status was synchronized by a prostaglandin F(2 alpha) analogue and the insertion of an intravaginal sponge 48 h later. Follicle development was stimulated by a single dose of FSH (60 mg NIH-FSH-P1) plus a single dose of equine chorionic gonadotrophin (eCG; 300 UI). The first FSH/eCG doses were administered 48 h after the sponge insertion, being repeated every 4 days to complete a total of four treatments in sheep and three in goats. Follicles in both ovaries were categorized according to their diameter and follicular fluid was aspirated under laparoscopic observation without a vacuum pump. In sheep, during a 12-day-period, a total of 347 follicles were aspirated with a recovery rate of 46.9%. In goats, during an 8-day-period, 219 follicles were aspirated with a recovery rate of 45.6%. In both species, there were no significant differences in the number of aspirated follicles, oocyte recovery rate and good quality oocyte recovery rate. However, in sheep the oocyte recovery rate was higher for large follicles, whereas in goats no such effect was detected. In summary, current results indicate that retrieval of oocytes can be maximized, without affecting oocyte quality, by repeating 'oneshot' FSH/eCG regimes and LOPUs at intervals as short as 4 days.

Monte Carlo method for calculating the radiation skyshine produced by electron accelerators

NASA Astrophysics Data System (ADS)

Kong, Chaocheng; Li, Quanfeng; Chen, Huaibi; Du, Taibin; Cheng, Cheng; Tang, Chuanxiang; Zhu, Li; Zhang, Hui; Pei, Zhigang; Ming, Shenjin

2005-06-01

Using the MCNP4C Monte Carlo code, the X-ray skyshine produced by 9 MeV, 15 MeV and 21 MeV electron linear accelerators were calculated respectively with a new two-step method combined with the split and roulette variance reduction technique. Results of the Monte Carlo simulation, the empirical formulas used for skyshine calculation and the dose measurements were analyzed and compared. In conclusion, the skyshine dose measurements agreed reasonably with the results computed by the Monte Carlo method, but deviated from computational results given by empirical formulas. The effect on skyshine dose caused by different structures of accelerator head is also discussed in this paper.

Pharmacokinetics and anesthetic and cardiopulmonary effects of propofol in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

PubMed

Hawkins, Michelle G; Wright, Bonnie D; Pascoe, Peter J; Kass, Philip H; Maxwell, Lara K; Tell, Lisa A

2003-06-01

To determine induction doses, anesthetic constant rate infusions (CRI), and cardiopulmonary effects of propofol in red-tailed hawks and great horned owls and propofol pharmacokinetics in the owls during CRI. 6 red-tailed hawks and 6 great horned owls. The CRI dose necessary for a loss of withdrawal reflex was determined via specific stimuli. Anesthesia was induced by IV administration of propofol (1 mg/kg/min) and maintained by CRI at the predetermined dose for 30 minutes. Heart and respiratory rates, arterial blood pressures, and blood gas tensions were obtained in awake birds and at various times after induction. End-tidal CO2 (ETCO2) concentration and esophageal temperature were obtained after induction. Propofol plasma concentrations were obtained after induction and after completion of the CRI in the owls. Recovery times were recorded. Mean +/- SD doses for induction and CRI were 4.48 +/- 1.09 mg/kg and 0.48 +/- 0.06 mg/kg/min, respectively, for hawks and 3.36 +/- 0.71 mg/kg and 0.56 +/- 0.15 mg/kg/min, respectively, for owls. Significant increases in PaCO2, HCO3, and ETCO2 in hawks and owls and significant decreases in arterial pH in hawks were detected. A 2-compartment model best described the owl pharmacodynamic data. Recovery times after infusion were prolonged and varied widely. Central nervous system excitatory signs were observed during recovery. Effects on blood pressure were minimal, but effective ventilation was reduced, suggesting the need for careful monitoring during anesthesia. Prolonged recovery periods with moderate-to-severe excitatory CNS signs may occur in these species at these doses.

Cysteine reversal of the novel neuromuscular blocking drug CW002 in dogs: pharmacodynamics, acute cardiovascular effects, and preliminary toxicology.

PubMed

Sunaga, Hiroshi; Malhotra, Jaideep K; Yoon, Edward; Savarese, John J; Heerdt, Paul M

2010-04-01

CW002 is a neuromuscular blocking drug that is inactivated by endogenous L-cysteine. This study determined the exogenous L-cysteine dose-response relationship for CW002 reversal along with acute cardiovascular effects and organ toxicity in dogs. Six dogs were each studied four times during isoflurane-nitrous oxide anesthesia and recording of muscle twitch, arterial pressure, and heart rate. CW002 (0.08 mg/kg or 9 x ED95) was injected, and the time to spontaneous muscle recovery was determined. CW002 was then administered again followed 1 min later by 10, 20, 50, or 100 mg/kg L-cysteine (1 dose/experiment). After twitch recovery, CW002 was given a third time to determine whether residual L-cysteine influenced duration. Preliminary toxicology was performed in an additional group of dogs that received CW002 followed by vehicle (n = 8) or 200 mg/kg L-cysteine (n = 8). Animals were awakened and observed for 2 or 14 days before sacrificing and anatomic, biochemical, and histopathologic analyses. L-cysteine at all doses accelerated recovery from CW002, with both 50 and 100 mg/kg decreasing median duration from more than 70 min to less than 5 min. After reversal, duration of a subsequent CW002 dose was also decreased in a dose-dependent manner. Over the studied dose range, L-cysteine had less than 10% effect on blood pressure and heart rate. Animals receiving a single 200-mg/kg dose of L-cysteine showed no clinical, anatomic, biochemical, or histologic evidence of organ toxicity. The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe.

PubMed

Fahlman, A; Loveridge, A; Wenham, C; Foggin, C; Arnemo, J M; Nyman, G

2005-12-01

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.

Decreased coronary vasodilatory capacity in hypertrophic cardiomyopathy determined by split-dose thallium-dipyridamole myocardial scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koga, Y.; Yamaguchi, R.; Ogata, M.

1990-05-01

Split-dose thallium-dipyridamole myocardial scintigraphy was performed in patients with nonobstructive hypertrophic cardiomyopathy (HC) who had angiographically normal coronary arteries. The dipyridamole-induced increases in thallium-201 uptake, calculated to evaluate coronary vasodilatory capacity, were significantly lower in 30 patients with HC than in 13 control subjects (177 +/- 58 vs 281 +/- 46%) and the reductions were observed in both the septal and lateral segments. The reductions of the septal segment in HC patients were significantly greater than those in 10 hypertensive patients with comparable degrees of septal hypertrophy. Of patients with HC, 16 had increases in thallium uptake well below themore » normal range. Compared with those having normal increases, these patients had significantly lower exercise duration (11 vs 15 minutes), with 33% having ST depression develop at a workload less than or equal to 80 watts. These data indicate that approximately one-half of patients with HC have impaired coronary vasodilatory capacity that could be an important pathophysiologic abnormality of HC resulting in the development of myocardial ischemia and the impairment of cardiac performance during exercise.« less

Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration outpatient laparoscopy. I. A randomized comparison with conventional dose hyperbaric lidocaine.

PubMed

Vaghadia, H; McLeod, D H; Mitchell, G W; Merrick, P M; Chilvers, C R

1997-01-01

A randomized, single-blind trial of two spinal anesthetic solutions for outpatient laparoscopy was conducted to compare intraoperative conditions and postoperative recovery. Thirty women (ASA physical status I and II) were assigned to one of two groups. Group I patients received a small-dose hypobaric solution of 1% lidocaine 25 mg made up to 3 mL by the addition of fentanyl 25 micrograms. Group II patients received a conventional-dose hyperbaric solution of 5% lidocaine 75 mg (in 7.5% dextrose) made up to 3 mL by the addition of 1.5 mL 10% dextrose. All patients received 500 mL of crystalloid preloading. Spinal anesthesia was performed at L2-3 or L3-4 with a 27-gauge Quincke point needle. Surgery commenced when the level of sensory anesthesia reached T-6. Intraoperative hypotension requiring treatment with ephedrine occurred in 54% of Group II patients but not in any Group I patients. Median (range) time for full motor recovery was 50 (0-95) min in Group I patients compared to 90 (50-120) min in Group II patients (P = 0.0005). Sensory recovery also occurred faster in Group I patients (100 +/- 22 min) compared with Group II patients (140 +/- 27 min, P = 0.0001). Postoperative headache occurred in 38% of all patients and 70% of these were postural in nature. Oral analgesia was the only treatment required. Spinal anesthesia did not result in a significant incidence of postoperative backache. On follow-up, 96% said they found spinal needle insertion acceptable, 93% found surgery comfortable, and 90% said they would request spinal anesthesia for laparoscopy in future. Overall, this study found spinal anesthesia for outpatient laparoscopy to have high patient acceptance and a comparable complication rate to other studies. The small-dose hypobaric lidocaine-fentanyl technique has advantages over conventional-dose hyperbaric lidocaine of no hypotension and faster recovery.

Quantitative Comparison of PET and Bremsstrahlung SPECT for Imaging the In Vivo Yttrium-90 Microsphere Distribution after Liver Radioembolization

PubMed Central

Elschot, Mattijs; Vermolen, Bart J.; Lam, Marnix G. E. H.; de Keizer, Bart; van den Bosch, Maurice A. A. J.; de Jong, Hugo W. A. M.

2013-01-01

Background After yttrium-90 (90Y) microsphere radioembolization (RE), evaluation of extrahepatic activity and liver dosimetry is typically performed on 90Y Bremsstrahlung SPECT images. Since these images demonstrate a low quantitative accuracy, 90Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of 90Y and on the accuracy of liver dosimetry. Methodology/Principal Findings SPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF) PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere) to 11% (37-mm sphere) for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data. Conclusions/Significance In this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the assessment of the 90Y microsphere distribution after radioembolization. PMID:23405207

Elemental mercury neurotoxicity and clinical recovery of function: A review of findings, and implications for occupational health.

PubMed

Calabrese, Edward J; Iavicoli, Ivo; Calabrese, Vittorio; Cory-Slechta, Deborah A; Giordano, James

2018-05-01

This paper assessed approximately 30 studies, mostly involving occupationally exposed subjects, concerning the extent to which those who developed elemental mercury (Hg)-induced central and/or peripheral neurotoxicities from chronic or acute exposures recover functionality and/or performance. While some recovery occurred in the vast majority of cases, the extent of such recoveries varied considerably by individual and endpoint. Factors accounting for the extensive inter-individual variation in toxicity and recovery were not specifically assessed such as age, gender, diet, environmental enrichment, chelation strategies and dose-rate. While the data indicate that psychomotor endpoints often show substantial and relatively rapid (i.e., 2-6 months) recovery and that neuropsychological endpoints display slower and less complete recovery, generalizations are difficult due to highly variable study designs, use of different endpoints measured between studies, different Hg exposures based on blood/urine concentrations and Hg dose-rates, the poor capacity for replicating findings due to the unpredictable/episodic nature of harmful exposures to elemental Hg, and the inconsistency of the initiation of studies after induced toxicities and the differing periods of follow up during recovery periods. Finally, there is strikingly limited animal model literature on the topic of recovery/reversibility of elemental Hg toxicity, a factor which significantly contributes to the overall marked uncertainties for predicting the rate and magnitude of recovery and the factors that affect it. Copyright © 2018 Elsevier Inc. All rights reserved.

Cutaneous estradiol permeation, penetration and metabolism in pig and man.

PubMed

Mahmoud, A; Haberland, A; Dürrfeld, M; Heydeck, D; Wagner, S; Schafer-Korting, M

2005-01-01

Drug development in dermatotherapy and also development of transdermal therapeutic systems (TTS) demand high-predictive in vitro models to estimate drug levels in skin and systemic uptake. Here we compare three ready-to-use models, reconstructed human epidermis, split porcine skin and the perfused porcine forelimb. 17beta-Estradiol (E(2)), which is highly metabolized by skin cells, serves as model drug since E(2) application is of high relevance in hormone replacement therapy while topical E(2) may promote wound healing. E(2) TTS, gel and an ethanolic solution were investigated for cutaneous penetration, permeation and metabolism. E(2) TTS enabled an E(2) uptake of 42.9% of the applied dose accompanied by a high percentage of E(2) metabolism (30% of the penetrated dose) in the perfused porcine forelimb. In Franz cell experiments with reconstructed human epidermis and split porcine skin, the gel allowed an E(2) uptake of 41.7 and 22.9% of the applied dose accompanied by a high E(2) metabolism (42.6 and 28.6% of the penetrated dose). Due to toxic effects of the vehicle, this was not true with an ethanolic solution, then E(2) permeation and metabolism were clearly diminished. Most importantly, the in vitro models proved to be predictive with respect to the E(2)/estrone ratio in female plasma under transdermal hormone replacement therapy. In vitro tests should reduce the need for both animal and human studies for cutaneous uptake and metabolism in the future. Copyright 2005 S. Karger AG, Basel.

Ant colony algorithm implementation in electron and photon Monte Carlo transport: application to the commissioning of radiosurgery photon beams.

PubMed

García-Pareja, S; Galán, P; Manzano, F; Brualla, L; Lallena, A M

2010-07-01

In this work, the authors describe an approach which has been developed to drive the application of different variance-reduction techniques to the Monte Carlo simulation of photon and electron transport in clinical accelerators. The new approach considers the following techniques: Russian roulette, splitting, a modified version of the directional bremsstrahlung splitting, and the azimuthal particle redistribution. Their application is controlled by an ant colony algorithm based on an importance map. The procedure has been applied to radiosurgery beams. Specifically, the authors have calculated depth-dose profiles, off-axis ratios, and output factors, quantities usually considered in the commissioning of these beams. The agreement between Monte Carlo results and the corresponding measurements is within approximately 3%/0.3 mm for the central axis percentage depth dose and the dose profiles. The importance map generated in the calculation can be used to discuss simulation details in the different parts of the geometry in a simple way. The simulation CPU times are comparable to those needed within other approaches common in this field. The new approach is competitive with those previously used in this kind of problems (PSF generation or source models) and has some practical advantages that make it to be a good tool to simulate the radiation transport in problems where the quantities of interest are difficult to obtain because of low statistics.

Caffeine enhances the speed of the recovery of the hypothalamo-pituitary-adrenocortical axis after chronic prednisolone administration in the rat.

PubMed

Marzouk, H F; Zuyderwijk, J; Uitterlinden, P; van Koetsveld, P; Blijd, J J; Abou-Hashim, E M; el-Kannishy, M H; de Jong, F H; Lamberts, S W

1991-11-01

Chronic administration of corticosteroids results in a suppression of the hypothalamo-pituitary-adrenocortical (HPA) axis. The time course of the recovery of the HPA axis depends on the dose and duration of corticosteroid administration. We investigated the recovery of the HPA axis after 14 days of prednisolone administration to rats at a dose of 2.0 mg/rat/day via the drinking water (188 mumol/l). The in vitro corticosterone production by dispersed adrenal cells in response to increasing concentrations of ACTH had recovered 3 days after stopping prednisolone administration. In parallel the initially suppressed plasma corticosterone concentrations had recovered after 3 days, while the pituitary ACTH content had recovered after 5 days. We investigated the possibility to enhance the speed of the recovery of the HPA axis by the simultaneous administration of two drugs with known CRF-stimulating activity via the drinking water. Caffeine in a dose of 100 mg/kg body weight enhanced the recovery of the prednisolone-suppressed HPA axis significantly. One day after the end of prednisolone administration a significant increase in the adrenal weight, in the corticosterone production by dispersed adrenal cells, as well as in the plasma corticosterone concentrations, and in the pituitary ACTH content was observed in the caffeine-treated rats. Chlorimipramine (20 mg/kg body weight), on the other hand, did not influence the prednisolone-mediated suppression of the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex steroid receptors profiling is influenced by nandrolone decanoate in the ampulla of the fallopian tube: Post-treatment and post-recovery analyses.

PubMed

Andrade, G H B; Simão, V A; Souza, B R; Chuffa, L G A; Camargo, I C C

2018-02-01

Anabolic androgenic steroids (AAS) are recommended for therapeutic clinic, but their use has increased in recent decades for aesthetic reasons. No study has evaluated the impact of AAS in the fallopian tube, after treatment and recovery periods. Herein, the aim of study was to investigate the effects of Nandrolone Decanoate (ND), administered in different doses (1.87; 3.75; 7.5 and 15 mg/kg) on the ampulla of the fallopian tube in rats, following post-treatment (PT; 15 consecutive days) and post-recovery (PR; 30 consecutive days) periods. The control group received mineral oil. Estrous cycle was monitored daily during both periods and in sequence the rats (n = 8/group/period) were killed. All ND-treated animals showed estral acyclicity during the PT and PR periods, but the histomorphometric changes in the fallopian tube varied according to the ND dose level. The expression of AR, ERα and ERβ varied in the nucleus and cytoplasm of epithelial cells. No AR expression was observed in the stroma. The muscle cells exhibited variation in immunostaining. In conclusion, ND promoted histomorphometric and immunohistochemical changes in the ampullary portion of the fallopian tube after treatment and recovery periods in a dose-independent manner. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exact Recovery of Chaotic Systems from Highly Corrupted Data

DTIC Science & Technology

2016-08-01

dimension to reconstruct a state space which preserves the topological properties of the original system. In [CM87, RS92], the authors use the singular...in high dimensional nonlinear functional spaces [Spr94, SL00, LCC04]. In this work, we bring together connections between compressed sensing, splitting... compact , connected attractor Λ and the flow admits a unique so-called “physical" measure µ with supp(µ) = Λ. An invariant probability measure µ for a flow

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera)

PubMed Central

Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538

Coping with seismic vulnerability: small manufacturing firms in western Athens.

PubMed

Sapountzaki, Kalliopi

2005-06-01

This paper attempts to contribute to international discourse on the responsibility of macro structures (economic and political) and private agencies for the production and distribution of vulnerability. It does so by focusing on an individual economic entity, small manufacturing firms (SMFs), in a specific location, western Athens, Greece. By evaluating the losses that SMFs sustained in the earthquake of 7 September 1999, the paper points to variations in vulnerability levels among such firms and highlights the 'sources' of vulnerability they confront. Furthermore, the SMF recovery cycle is systematically monitored in parallel with relevant public policies and state reactions to private recovery methods. The analysis illustrates processes that externalise recovery costs, alter the relationship between physical and socio-economic vulnerability and shift the vulnerability load from macro structures to individual agencies or vice versa. It is based on two methodological approaches: the division of vulnerability into three constituent components (exposure, resistance and resilience); and the conceptual split between producers and carriers of vulnerability.

FACTORS AFFECTING THE CHAIN LENGTH OF GROUP A STREPTOCOCCI

PubMed Central

Ekstedt, Richard D.; Stollerman, Gene H.

1960-01-01

Group A streptococci which grew in long chains in the presence of homologous anti-M antibody were split into their original length by the addition of an excess of homologous M protein to the culture. The chain-splitting reaction showed temperature and pH optima (37°C., 7.5) and was completely inhibited at 0°C. or by heat-killing the long chains at 56°C. prior to the addition of M protein. Addition of sublethal doses of HgCl2, or of penicillin, inhibited the chain-splitting reaction. Pneumococci behaved in entirely comparable fashion to streptococci in similar experiments. Virulent strains of streptococci formed the shortest chains when broth media was enriched with serum. The chain-shortening effect of serum enrichment of the media was most apparent with encapsulated strains and under cultural conditions that favored capsule formation. Loss of capsules by mutation or by unfavorable growth conditions resulted in increase in chain length. The activity of the chain-splitting mechanism seemed to be independent of M protein, however, since encapsulated M-negative variants also formed very short chain in serum-enriched media. The physical presence of the capsule was not essential for chain shortening since enzymatic removal of the capsule with hyaluronidase during growth did not affect chain length. These results strongly suggest that chain-splitting of streptococci and pneumococci occurs by an active metabolic mechanism, presumably enzymatic, which is inhibited by the union of surface antigens with specific antibody. PMID:13726267

Recovery from prolonged deep rocuronium-induced neuromuscular blockade: A randomized comparison of sugammadex reversal with spontaneous recovery.

PubMed

Rahe-Meyer, N; Berger, C; Wittmann, M; Solomon, C; Abels, E A M; Rietbergen, H; Reuter, D A

2015-07-01

Deep neuromuscular blockade (NMB) may not always be maintained to the end of surgery and the depth of block may be allowed to gradually diminish over time, particularly if reversal of NMB is not routinely performed. The current study aimed to assess recovery from deep rocuronium-induced NMB with sugammadex compared with placebo, provide data regarding the extent of residual blockade after deep rocuronium-induced NMB (placebo group), and to determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). This was a randomized, placebo-controlled, safety-assessor-blinded study in adult patients of American Society of Anesthesiologists Class I to III. Patients with clinically relevant kidney or liver insufficiency were excluded. Anesthesia was administered as routinely practiced at each study site. Rocuronium 0.6 mg/kg was administered for intubation, with maintenance doses of 0.1-0.2 mg/kg as needed. After the last rocuronium dose, at deep NMB (target depth 1-2 post-tetanic counts), patients received a single dose of sugammadex 4.0 mg/kg or placebo as randomized. The primary endpoint was time from sugammadex or placebo administration to recovery of the train-of-four (TOF) ratio to 0.9. Safety was assessed through monitoring of adverse events, vital signs and physical examination. Patients were also assessed for evidence of residual or recurrence of NMB. With this design, the study will provide data regarding the extent of residual blockade under these conditions (placebo group), and determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). Recovery to a TOF ratio of ≥ 0.9 with sugammadex was significantly faster (~ 40 times) than spontaneous recovery: geometric mean (95 % confidence interval) times were 2.2 (1.9-2.5) and 89.8 (80.1-100.7) min, respectively (p < 0.0001, N = 134); maximum spontaneous recovery was 289.8 min. Safety was comparable between groups, with no recurrence of blockade. This study confirms a prolonged residual blockade in patients who did not receive sugammadex, with median time to recovery > 1.5 h in the placebo group and one patient taking 4.8 h to achieve a safe level of neuromuscular function recovery following deep NMB. In contrast, sugammadex provided complete and reliable recovery of neuromuscular function (median time to recovery of 2.0 min). Thus, deep NMB with rocuronium until the end of the operation may be possible in combination with sugammadex reversal.

[G-CSF administration following autologous peripheral blood stem cell transplantation--the effect of G-CSF level on neutrophil recovery].

PubMed

Saigo, K; Sugimoto, T; Matsuo, M; Narita, H; Ryo, R; Kumagai, S

2000-03-01

We studied the usefulness of rhG-CSF (filgrastim) administration in patients who received autologous peripheral blood stem cell transplantation (PBSCT) combined with super-high dose chemotherapy. Twenty patients received 0-8.3 micrograms/kg/day filgrastim after PBSCT. There was a significant relationship between G-CSF dose and the neutrophil recovery rate, and the highest levels of serum G-CSF tended to correlate with neutrophil recovery rate. The highest G-CSF level after 75 micrograms injection in normal volunteers is reported to be 1,500 pg/ml. On the other hand, as one patient in our series exhibited extremely high endogenous G-CSF of 11,500 pg/ml, measurements of G-CSF might reduce the over-administration of rhG-CSF.

Wurtzite/zinc-blende electronic-band alignment in basal-plane stacking faults in semi-polar GaN

NASA Astrophysics Data System (ADS)

Monavarian, Morteza; Hafiz, Shopan; Izyumskaya, Natalia; Das, Saikat; Özgür, Ümit; Morkoç, Hadis; Avrutin, Vitaliy

2016-02-01

Heteroepitaxial semipolar and nonpolar GaN layers often suffer from high densities of extended defects including basal plane stacking faults (BSFs). BSFs which are considered as inclusions of cubic zinc-blende phase in wurtzite matrix act as quantum wells strongly affecting device performance. Band alignment in BSFs has been discussed as type of band alignment at the wurtzite/zinc blende interface governs the response in differential transmission; fast decay after the pulse followed by slow recovery due to spatial splitting of electrons and heavy holes for type- II band alignment in contrast to decay with no recovery in case of type I band alignment. Based on the results, band alignment is demonstrated to be of type II in zinc-blende segments in wurtzite matrix as in BSFs.

Final Radiological Assessment of External Exposure for CLEAR-Line Americium Recovery Operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, Adam C.; Belooussova, Olga N.; Hetrick, Lucas Duane

2014-11-12

Los Alamos National Laboratory is currently planning to implement an americium recovery program. The americium, ordinarily isotopically pure 241Am, would be extracted from existing Pu materials, converted to an oxide and shipped to support fabrication of americium oxide-beryllium neutron sources. These operations would occur in the currently proposed Chloride Extraction and Actinide Recovery (CLEAR) line of glove boxes. This glove box line would be collocated with the currently-operational Experimental Chloride Extraction Line (EXCEL). The focus of this document is to provide an in-depth assessment of the currently planned radiation protection measures and to determine whether or not further design workmore » is required to satisfy design-goal and ALARA requirements. Further, this document presents a history of americium recovery operations in the Department of Energy and high-level descriptions of the CLEAR line operations to provide a basis of comparison. Under the working assumptions adopted by this study, it was found that the evaluated design appears to mitigate doses to a level that satisfies the ALARA-in-design requirements of 10 CFR 835 as implemented by the Los Alamos National Laboratory procedure P121. The analyses indicate that extremity doses would also meet design requirements. Dose-rate calculations were performed using the radiation transport code MCNP5 and doses were estimated using a time-motion study developed in consort with the subject matter expert. A copy of this report and all supporting documentation are located on the Radiological Engineering server at Y:\\Rad Engineering\\2013 PROJECTS\\TA-55 Clear Line.« less

Effect of heat stress on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in some vertebrate species.

PubMed

Mohamed, M I; Rahman, T A

1982-01-01

1. The variations in 5-HT and 5-HIAA levels following heat exposure and split heat doses were determined in the different brain regions of Gerbillus pyramidum, Streptopelia senegalensis aegyptiaca and Agama stellio. 2. Heat exposure was found to be associated with an increase in the levels of the two indole compounds. 3. The 5-HT concentrations increased markedly in the three species following the first heat dose and decreased following the second dose in the various brain regions except in the cerebellum of Agama. 4. The increased 5-HT levels when animals are exposed to high temperature probably represent a response to activate heat-loss mechanisms and to depress heat production.

Unit-dose assay of tropine alkaloids and their synthetic analogs.

PubMed

Gomaa, C; Taha, A

1975-08-01

A charge-transfer spectrophotometric method was developed for unit-dose assay of the tropine alkaloids and some of their synthetic analogs. The high molar absorptivities of the charge-transfer bands of the alkaloids with iodine in ethylene dichloride resulted in improved recoveries and good precision, particularly at the low dose levels of pediatric and hypodermic tablets.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

PubMed

Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

2017-10-05

One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications.

PubMed

Hill, Shaynan W; Varker, Andrew S; Karlage, Kelly; Myrdal, Paul B

2009-04-01

Cost savings can be achieved with the practice of tablet splitting. Previous research has shown weight nonuniformity within tablet halves. However, limited research to date has found that the potential dose inaccuracy resulting from splitting tablets does not significantly affect clinical outcomes. To determine the drug content and weight in split half-tablets of 6 commonly split medications using drug assay analysis. This study was performed by 2 fourth-year pharmacy students using 30 randomly selected tablets of each of the following 6 medications: warfarin sodium 5 milligrams (mg), simvastatin 80 mg, metoprolol succinate 200 mg, metoprolol tartrate 25 mg, citalopram 40 mg, and lisinopril 40 mg. A randomly selected half of the tablets were split by a single pharmacy student using a tablet cutter, and the remaining tablets were kept whole. Drug content was analyzed for 15 whole tablets and 30 half-tablets for each of the 6 drugs using high performance liquid chromatography, an analytical tool used to identify and quantify substances in solution. Drug content uniformity was assessed by comparing drug content within half-tablets with one-half of the drug content mean found for all whole tablets in the sample. Weight uniformity was assessed by comparing half-tablet weights, as determined by a Mettler analytical balance, with one-half of the mean weight for whole tablets in the sample. The percentages by which each whole tablet's or half-tablet's drug content and weight differed from sample mean values were compared with proxy United States Pharmacopeia (USP) specification ranges for drug content (95%-105% for warfarin sodium and 90%-110% for the other 5 drugs). Additionally, these outcomes were compared for nonscored versus scored tablets. The percent relative standard deviation (%RSD, ratio of the standard deviation to the mean), a commonly used measure of the repeatability and precision of assays used to analyze drug content, was also calculated in order to determine whether the drugs met proxy USP specification for %RSD (less than 6% for all drugs studied). A total of 43 of 180 half-tablets (23.9%) differed from sample mean values by a percentage that fell outside of proxy USP specification for drug content; warfarin sodium (11 of 30 half-tablets, 36.7%), simvastatin (3 of 30 half-tablets, 10.0%) metoprolol succinate (10 of 30 half-tablets, 33.3%), metoprolol tartrate (4 of 30 half-tablets, 13.3%), citalopram (5 of 30 half-tablets, 16.7%), and lisinopril (10 of 30 half-tablets, 33.3%). Half-tablets outside of proxy USP specification for weight included warfarin sodium (10 of 30 half-tablets, 33.3%), metoprolol succinate (6 of 30 half-tablets, 20%), and lisinopril (7 of 30 half-tablets, 23.3%). The %RSDs for drug content and weight fell outside of the proxy USP specification for %RSD for metoprolol succinate (drug content = 8.98%, weight = 7.70%) and lisinopril (drug content = 10.41%, weight = 8.13%). Mean percent weight loss after splitting was less than 1% for all drugs except lisinopril, which had an average weight loss of 1.25%. The total numbers of scored (nonscored) tablet halves that fell outside of proxy USP specification were 20 (23) for drug content and 10 (13) for weight. When measuring drug content, the numbers of out-of-range half-tablets for scored (nonscored) drugs were 36 (44) at 95%-105%, 9 (23) at 90%-110%, 0 (10) at 85%-115%, and 0 (1) at 75%-125%. When measuring weight, the numbers of out-of-range half-tablets for scored (nonscored) drugs were 28 (38) at 95%-105%, 0 (14) at 90%-110%, 0 (3) at 85%-115%, and 0 (0) at 75%-125%. Dose variation exceeded a proxy USP specification for more than one-third of sampled half-tablets of warfarin sodium, metoprolol succinate, and lisinopril and appeared to be greater for nonscored tablets as compared with scored tablets. Drug content variation in half-tablets appeared to be attributable primarily to weight variation occurring when tablets powder or fragment during the splitting process. Therefore, equal daily doses will be determined by the ability of patients to split tablets perfectly in half.

Wind tunnel performance results of swirl recovery vanes as tested with an advanced high speed propeller

NASA Technical Reports Server (NTRS)

Gazzaniga, John A.; Rose, Gayle E.

1992-01-01

Tests of swirl recovery vanes designed for use in conjunction with advanced high speed propellers were carried out at the NASA Lewis Research Center. The eight bladed 62.23 cm vanes were tested with a 62.23 cm SR = 7A high speed propeller in the NASA Lewis 2.44 x 1.83 m Supersonic Wind Tunnel for a Mach number range of 0.60 to 0.80. At the design operating condition for cruise of Mach 0.80 at an advance ratio of 3.26, the vane contribution to the total efficiency approached 2 percent. At lower off-design Mach numbers, the vane efficiency is even higher, approaching 4.5 percent for the Mach 0.60 condition. Use of the swirl recovery vanes essentially shifts the peak of the high speed propeller efficiency to a higher operating speed. This allows a greater degree of freedom in the selection of rpm over a wider operating range. Another unique result of the swirl recovery vane configuration is their essentially constant torque split between the propeller and the swirl vanes over a wide range of operating conditions for the design vane angle.

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, R.P.

1991-01-01

An in vitro system using neuroglia from neonatal rat brain was developed to examining the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute [gamma]-radiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. It was concluded that oligodendrocytes in irradiated cultures had significantly lower functional capacity than did unirradiated controls. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. At DIC 14, the group irradiated in a single fraction had significantly lower oligodendrocyte counts than any group given split doses; all irradiated cultures had marked depression of MBP synthesis, but to significant differences referable to time interval between doses. At DIC 21, cultures irradiated at intervals of 0 h to 2 h had similar oligodendrocyte counts to one another, but these counts were significantly lower than in cultures irradiated at intervals of 4 h to 6 h; MBP levels remained depressed at DIC 21 for all irradiated cultures. The oligodendrocyte response to dose rate (0.03 to 1.97 Gy/min) was evaluated at DIC 14 and DIC 21. Exposure at 0.03 Gy/min suppressed oligodendrocyte counts at DIC 21 less than did higher dose rates in 5-Gy irradiated cultures.« less

Pharmacodynamic Comparison of Rocuronium Bromide between Patients from the Plateau Area and from the Plain Area.

PubMed

Xie, Min; Huang, Jianxin; Li, Peng; Ou, Zhiyan; Hou, Jing

2016-06-23

We aimed to conduct a pharmacodynamic comparison of rocuronium bromide between patients from the plateau area and from the plain area. A total of 104 patients who received laparoscopic cholecystectomy in Sichuan Provincial People's Hospital and Aba Autonomous Prefecture People's Hospital from October 2015 to December 2015 were included in this study. Among them, 46 patients were from the plateau area and 58 were from the plain area. Both groups received total intravenous anesthesia (TIVA) with a dose of 0.6mg/kg rocuronium bromide during induction. In the meantime, neuromuscular block was monitored using a train-of-four (TOF) stimulation mode. The onset time (time to achieve the lowest TOF value after the injection of rocuronium bromide), duration of maximal neuromuscular block (duration of lowest T1 value), time to 25% recovery, time to 75% recovery, recovery index (time from 25% recovery to 75% recovery), time to extubation, length of stay in Post Anesthesia Care Unit (PACU) and muscle strength upon PACU discharge were all recorded. The onset time, time to 25% recovery, time to 75% recovery and time to extubation were all significantly prolonged in patients from the plateau area after receiving one single dose of rocuronium bromide (P<0.05). However, both groups didn't show any significant difference in maximal neuromuscular block, recovery index (time from 25% recovery to 75% recovery), length of stay in PACU or muscle strength upon PACU discharge (P>0.05). Compared to patients from the plain area, patients from the plateau area showed prolonged onset time of rocuronium bromide, reduced metabolic capabilities and longer duration of muscular relaxation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Recovery of adrenal function in a patient with confirmed Addison's disease.

PubMed

Baxter, M; Gorick, S; Swords, F M

2013-01-01

Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Partial recovery from Addison's disease is possible although uncommon.Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.As further reports of adrenal axis recovery emerge, this may influence the counselling given to patients with Addison's disease in the future.

Recovery of adrenal function in a patient with confirmed Addison's disease

PubMed Central

Baxter, M; Gorick, S; Swords, F M

2013-01-01

Summary Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Learning points Partial recovery from Addison's disease is possible although uncommon.Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.As further reports of adrenal axis recovery emerge, this may influence the counselling given to patients with Addison's disease in the future. PMID:24683477

Interactive Dose Shaping - efficient strategies for CPU-based real-time treatment planning

NASA Astrophysics Data System (ADS)

Ziegenhein, P.; Kamerling, C. P.; Oelfke, U.

2014-03-01

Conventional intensity modulated radiation therapy (IMRT) treatment planning is based on the traditional concept of iterative optimization using an objective function specified by dose volume histogram constraints for pre-segmented VOIs. This indirect approach suffers from unavoidable shortcomings: i) The control of local dose features is limited to segmented VOIs. ii) Any objective function is a mathematical measure of the plan quality, i.e., is not able to define the clinically optimal treatment plan. iii) Adapting an existing plan to changed patient anatomy as detected by IGRT procedures is difficult. To overcome these shortcomings, we introduce the method of Interactive Dose Shaping (IDS) as a new paradigm for IMRT treatment planning. IDS allows for a direct and interactive manipulation of local dose features in real-time. The key element driving the IDS process is a two-step Dose Modification and Recovery (DMR) strategy: A local dose modification is initiated by the user which translates into modified fluence patterns. This also affects existing desired dose features elsewhere which is compensated by a heuristic recovery process. The IDS paradigm was implemented together with a CPU-based ultra-fast dose calculation and a 3D GUI for dose manipulation and visualization. A local dose feature can be implemented via the DMR strategy within 1-2 seconds. By imposing a series of local dose features, equal plan qualities could be achieved compared to conventional planning for prostate and head and neck cases within 1-2 minutes. The idea of Interactive Dose Shaping for treatment planning has been introduced and first applications of this concept have been realized.

Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,.

PubMed

Kaufhold, N; Schaller, S J; Stäuble, C G; Baumüller, E; Ulm, K; Blobner, M; Fink, H

2016-02-01

The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2. Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively. Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively. A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2. NCT01006720. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation

PubMed Central

Amrolia, Persis J.; Muccioli-Casadei, Giada; Huls, Helen; Adams, Stuart; Durett, April; Gee, Adrian; Yvon, Eric; Weiss, Heidi; Cobbold, Mark; Gaspar, H. Bobby; Rooney, Cliona; Kuehnle, Ingrid; Ghetie, Victor; Schindler, John; Krance, Robert; Heslop, Helen E.; Veys, Paul; Vitetta, Ellen; Brenner, Malcolm K.

2006-01-01

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell–depleted haploidentical SCT. Eight patients were treated at 104 cells/kg/dose, and 8 patients received 105 cells/kg/dose. Patients receiving 105 cells/kg/dose showed significantly improved T-cell recovery at 3, 4, and 5 months after SCT compared with those receiving 104 cells/kg/dose (P < .05). Accelerated T-cell recovery occurred as a result of expansion of the effector memory (CD45RA–CCR-7-) population (P < .05), suggesting that protective T-cell responses are likely to be long lived. T-cell–receptor signal joint excision circles (TRECs) were not detected in reconstituting T cells in dose-level 2 patients, indicating they are likely to be derived from the infused allodepleted cells. Spectratyping of the T cells at 4 months demonstrated a polyclonal Vβ repertoire. Using tetramer and enzyme-linked immunospot (ELISPOT) assays, we have observed cytomegalovirus (CMV)– and Epstein-Barr virus (EBV)–specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach. PMID:16741253

Preventing and Managing Toxicities of High-Dose Methotrexate.

PubMed

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

2016-12-01

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

Preventing and Managing Toxicities of High-Dose Methotrexate

PubMed Central

McCormick, John; Pui, Ching-Hon; Buddington, Randall K.; Harvey, R. Donald

2016-01-01

High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%–12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated. Implications for Practice: High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity. PMID:27496039

Systematic review of spinal anaesthesia using bupivacaine for ambulatory knee arthroscopy.

PubMed

Nair, G S; Abrishami, A; Lermitte, J; Chung, F

2009-03-01

The use of lidocaine in spinal anaesthesia is associated with transient neurological syndrome (TNS). Bupivacaine has a lower incidence of TNS as an alternative but it may have a prolonged action. This study systematically reviews the literature about the recovery profile of patients undergoing spinal anaesthesia, using bupivacaine for arthroscopic knee surgery. We identified 17 eligible randomized clinical trials (RCTs) (1268 patients). All the articles in this review, except one, used hyperbaric bupivacaine. Five trials compared different doses of bupivacaine (range 3-15 mg). Large doses of bupivacaine (10 and 15 mg) were associated with delayed recovery, and supine positioning was associated with a high incidence of failure. With unilateral positioning, a dose as low as 4-5 mg seems to be sufficient. Five trials comparing bupivacaine or levobupivacaine with ropivacaine showed no significant difference in the time to home discharge. When bupivacaine was combined with fentanyl in two trials, marginal delay in recovery was found [time to discharge (min); weighted mean difference (WMD) 14.1, 95% CI 11.9-40.1] and increased nausea and pruritus but had reduced postoperative pain. Unilateral and bilateral spinal anaesthesia were assessed in two trials, and the latter group was associated with early recovery and discharge [time to discharge (min); WMD -41.6, 95% CI -63.6 to -19.6). The results of our systematic review suggest that 4-5 mg of hyperbaric bupivacaine can effectively produce spinal anaesthesia for knee arthroscopy with unilateral positioning. Ropivacaine or the addition of adjuvants did not improve the recovery time. There is a need for tighter RCTs with more consistent endpoints.

Temporal aspects of tumorigenic response to individual and mixed carcinogens. [Response of mouse skin to benzo(a)pyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert, R.E.; Burns, F.J.

1976-02-01

Results are reported from experiments that involved either single or multiple doses of benzo(a)pyrene in mouse skin followed by prolonged observation. Preliminary results indicate linearity in dose and time and no evidence of recovery or enhancement for multiple doses of initiator given for extended periods of time. (auth)

Pupillographic evaluation of the time course of atropine effects in the mouse eye.

PubMed

Schaeffel, Frank; Burkhardt, Eva

2005-03-01

The nonselective muscarinic antagonist atropine is currently the most potent drug against myopia development in both humans and animal models. However, the mechanism by which myopia is suppressed is still unknown, and the time course of its action is not well documented. Therefore, we have studied the duration of mydriasis in the mouse, a new model of myopia, after topical application of a single eye drop with different doses of atropine. The light-induced pupil response of the C57BL/6 (B6) wildtype strain was studied in alert mice that were restrained by grasping their necks. A video image-processing program detected the pupil and measured its diameter at 25 Hz sampling rate. To stimulate, an arrangement of green LEDs, which was attached to the recording video camera, could be flashed for 40 ms by pressing a key on the keyboard. A single drop of atropine solution (1, 0.5, or 0.1%) was instilled in one eye and the recovery of the pupil responses was followed for at least 150 h. Both eyes were measured. 1) Under the defined stimulation conditions, untreated wildtype mice displayed a pupil constriction of 23.7 +/- 2.4%. 2) All doses of atropine caused complete suppression of the pupil responses in the treated eyes within 1 min. 3) The pupil responses of the fellow eyes remained unaffected and were not different from those in untreated animals. 4) The recovery from mydriasis was very slow and did not show clear differences with dose. The extrapolated duration of complete recovery was about 10 d (0.1%: 217 h; 0.5%: 230 h; 1%: 294 h). Atropine caused a longlasting suppression of the pupil responses in the mouse eye. That the duration of recovery was not obviously dose-dependent suggests that all doses used in this study were saturating the receptors in the iris musculature.

A Comparison of Fospropofol to Midazolam for Moderate Sedation During Outpatient Dental Procedures

PubMed Central

Yen, Philip; Prior, Simon; Riley, Cara; Johnston, William; Smiley, Megann; Thikkurissy, Sarat

2013-01-01

Moderate intravenous (IV) sedation combined with local anesthesia is common for outpatient oral surgery procedures. An ideal sedative agent must be safe and well tolerated by patients and practitioners. This study evaluated fospropofol, a relatively new sedative/hypnotic, in comparison to midazolam, a commonly used benzodiazepine, for IV moderate sedation during oral and maxillofacial surgery. Sixty patients were randomly assigned to either the fospropofol or the midazolam group. Each participant received 1 μg/kg of fentanyl prior to administration of the selected sedative. Those in the fospropofol group received an initial dose of 6.5 mg/kg, with 1.6 mg/kg supplemental doses as needed. Those in the midazolam group received initial doses of 0.05 mg/kg, followed by 0.02 mg/kg supplemental doses. The quality of sedation in each patient was evaluated with regard to (a) onset of sedation, maintenance, and recovery profile; (b) patient and surgeon satisfaction; and (c) hemodynamic stability and adverse effects. The fospropofol group demonstrated shorter physical recovery times than midazolam patients, taking a mean of 11.6 minutes versus 18.4 minutes for physical recovery (P = .007). Cognitive recovery comparison did not find any difference with a mean of 7.5 minutes versus 8.8 minutes between the 2 drug groups (P = .123). The fospropofol group had a higher rate of local anesthetic injection recall (90.5 vs 44.4%, P = .004). Other parameters of recall were comparable. Two adverse effects demonstrated significance, with more patients in the midazolam group experiencing tachycardia (48.2 vs 9.4%, P = .001), and more patients in the fospropofol group experiencing perineal discomfort (40.6 vs 0, P < .001). No significant difference was found in any other measures of sedation safety, maintenance, or satisfaction. Fospropofol, when administered intravenously by a dentist anesthesiologist at the indicated dose in this study, appears to be a safe, well-tolerated alternative to midazolam for intravenous moderate sedation during minor oral surgery procedures. PMID:24423419

Single-phase Whole-body 64-MDCT Split-bolus Protocol for Pediatric Oncology: Diagnostic Efficacy and Dose Radiation.

PubMed

Scialpi, Michele; Schiavone, Raffaele; D'Andrea, Alfredo; Palumbo, Isabella; Magli, Michelle; Gravante, Sabrina; Falcone, Giuseppe; De Filippi, Claudio; Manganaro, Lucia; Palumbo, Barbara

2015-05-01

To evaluate the image quality and the diagnostic efficacy by single-phase whole-body 64-slice multidetector CT (MDCT) for pediatric oncology. Chest-abdomen-pelvis CT examinations with single-phase split-bolus technique were evaluated for T: detection and delineation of primary tumor (assessment of the extent of the lesion to neighboring tissues), N: regional lymph nodes and M: distant metastasis. Quality scores (5-point scale) were assessed by two radiologists on parenchymal and vascular enhancement. Accurate TNM staging in term of detection and delineation of primary tumor, regional lymph nodes and distant metastasis was obtained in all cases. On the image quality and severity artifact, the Kappa value for the interobserver agreement measure obtained from the analysis was 0.754, (p<0.001), characterizing a very good agreement between observers. Single-pass total body CT split-bolus technique reached the highest overall image quality and an accurate TNM staging in pediatric patients with cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prophylaxis of thromboembolism in bariatric surgery with parnaparin.

PubMed

Forestieri, Pietro; Quarto, Gennaro; De Caterina, Maurizio; Cuocolo, Alberto; Pilone, Vincenzo; Formato, Antonio; Ruocco, Aldo; Ferrari, Patrizio

2007-12-01

There are limited data on appropriate dosing of low-molecular-weight heparins (LMWHs) for venous thromboembolism (VTE) prophylaxis in bariatric surgery. The primary objective of this preliminary study was to evaluate the preoperative effects of increasing doses of the LMWH parnaparin on coagulation in severely obese patients undergoing bariatric surgery. Severely obese patients (BMI > 50 kg/m(2)) were administered three increasing single doses of parnaparin (3200, 4250, and 6400 IU) on the three consecutive days leading up to biliointestinal bypass surgery. Activated partial thromboplastin time (APTT), anti-factor IIa and anti-factor Xa levels were measured 1 h before and 4 h after dosing. The highest dose (6400 IU/day) was continued from the day of surgery until day 30 (recovery period). Intermittent pneumatic compression and stockings were applied during surgery and the recovery period, respectively. Lower limb echoDoppler and phleboscintigraphy, and pulmonary scintigraphy were used for VTE detection. Ten patients (mean BMI 52.4 kg/m(2)) were recruited into this study. During the preoperative dosing phase, parnaparin dose-dependently prolonged APTT, with the 6400 IU dose significantly prolonging APTT versus the lower doses. Meanwhile, anti-factor Xa and anti-factor IIa activity was increased by the 4250 and 6400 IU doses. After surgery, one patient with heparin resistance experienced pulmonary embolization. No bleeding complications were observed. The dose-response data reported in this preliminary study suggest that parnaparin doses of 4250 and 6400 IU may provide effective prophylaxis for VTE in patients undergoing bariatric surgery. However, given the small number of patients, larger, well-controlled trials are required to confirm these findings.

A PENELOPE-based system for the automated Monte Carlo simulation of clinacs and voxelized geometries - application to far-from-axis fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sempau, Josep; Badal, Andreu; Brualla, Lorenzo

Purpose: Two new codes, PENEASY and PENEASYLINAC, which automate the Monte Carlo simulation of Varian Clinacs of the 600, 1800, 2100, and 2300 series, together with their electron applicators and multileaf collimators, are introduced. The challenging case of a relatively small and far-from-axis field has been studied with these tools. Methods: PENEASY is a modular, general-purpose main program for the PENELOPE Monte Carlo system that includes various source models, tallies and variance-reduction techniques (VRT). The code includes a new geometry model that allows the superposition of voxels and objects limited by quadric surfaces. A variant of the VRT known asmore » particle splitting, called fan splitting, is also introduced. PENEASYLINAC, in turn, automatically generates detailed geometry and configuration files to simulate linacs with PENEASY. These tools are applied to the generation of phase-space files, and of the corresponding absorbed dose distributions in water, for two 6 MV photon beams from a Varian Clinac 2100 C/D: a 40 x 40 cm{sup 2} centered field; and a 3 x 5 cm{sup 2} field centered at (4.5, -11.5) cm from the beam central axis. This latter configuration implies the largest possible over-traveling values of two of the jaws. Simulation results for the depth dose and lateral profiles at various depths are compared, by using the gamma index, with experimental values obtained with a PTW 31002 ionization chamber. The contribution of several VRTs to the computing speed of the more demanding off-axis case is analyzed. Results: For the 40 x 40 cm{sup 2} field, the percentages {gamma}{sub 1} and {gamma}{sub 1.2} of voxels with gamma indices (using 0.2 cm and 2% criteria) larger than unity and larger than 1.2 are 0.2% and 0%, respectively. For the 3 x 5 cm{sup 2} field, {gamma}{sub 1} = 0%. These figures indicate an excellent agreement between simulation and experiment. The dose distribution for the off-axis case with voxels of 2.5 x 2.5 x 2.5 mm{sup 3} and an average standard statistical uncertainty of 2% (1{sigma}) is computed in 3.1 h on a single core of a 2.8 GHz Intel Core 2 Duo processor. This result is obtained with the optimal combination of the tested VRTs. In particular, fan splitting for the off-axis case accelerates execution by a factor of 240 with respect to standard particle splitting. Conclusions: PENEASY and PENEASYLINAC can simulate the considered Varian Clinacs both in an accurate and efficient manner. Fan splitting is crucial to achieve simulation results for the off-axis field in an affordable amount of CPU time. Work to include Elekta linacs and to develop a graphical interface that will facilitate user input is underway.« less

Expression of a clostridial [FeFe]-hydrogenase in Chlamydomonas reinhardtii prolongs photo-production of hydrogen from water splitting

DOE PAGES

Noone, Seth; Ratcliff, Kathleen; Davis, ReAnna; ...

2016-12-24

The high oxygen (O 2) sensitivity of green algal [FeFe]-hydrogenases is a significant limitation for the sustained production of hydrogen gas (H 2) from photosynthetic water splitting. To address this limitation we replaced the native [FeFe]-hydrogenases with a more O 2-tolerant clostridial [FeFe]-hydrogenase CaI in Chlamydomonas reinhardtii strain D66ΔHYD ( hydA1– hydA2–) that contains insertionally inactivated [FeFe]-hydrogenases genes. Expression and translocation of CaI in D66ΔHYD led to the recovery of H 2 photoproduction at ~ 20% of the rates of the wild-type parent strain D66. We show for the first time that a bacterial [FeFe]-hydrogenase can be expressed, localized andmore » matured to a catalytically active form that couples to photosynthetic electron transport in the green alga C. reinhardtii. The lower rates of O 2 inactivation of CaI led to more sustained H 2 photoproduction when cultures were challenged with O 2 or kept under prolonged illumination at solar intensities. Lastly, these results provide new insights into the requisites for attaining photobiological H 2 production from water splitting using a more O 2-tolerant hydrogenase.« less

Enhancing Effect of Continuous Cobalt-60 Gamma-Radiation on Susceptibility to Anaphylactic Shock in Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hale, William M.; Stoner, Richard D.

1958-05-01

Continuous exposure to gamma -radiation at a dose rate of 4 rep/hr enhanced the severity of anaphylactnic shock ln mice sensitized with tetanus toxoid and challenged 1 hour or 7 days postradiation with fluid tetanus toxoid. A sharp increase in susceptibility to fatal anaphylaxis was observed as the accumulated dose was increased from 192 to 288 rep. Recovery from the enhancing effect of continuous gamma -radiation began during the second week postradiation; complete recovery occurred during the third week after an accumulated dose of 672 rep. Anaphylactic shock was demonstrable in mice sensitized 6 months before challenge with the specificmore » antigen. An enhanced susceptibility to fatal anaphylaxis was obtained when these animals were given an accumulated dose of 288 rep and challenged 1 hour postradiation. Passive anaphylaxis was more severe in irradiated mice sensitized with homopogous antitoxin 1 hour postradiation and challenged the following day with tetanus toxoid. The antihistaminic agent Thephorin afforded complete protection from fatal anaphypaxis in irradiated mice. (auth)« less

Using on-site liver 3-D reconstruction and volumetric calculations in split liver transplantation.

PubMed

Reichman, Trevor W; Fiorello, Brittany; Carmody, Ian; Bohorquez, Humberto; Cohen, Ari; Seal, John; Bruce, David; Loss, George E

2016-12-01

Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout© liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g (930-1458 g) for the extended right lobe donors and 312 g (222-396 g) for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts, respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight. On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.

Piezosurgery for the Lingual Split Technique in Lingual Positioned Impacted Mandibular Third Molar Removal: A Retrospective Study.

PubMed

Ge, Jing; Yang, Chi; Zheng, Jiawei; Qian, Wentao

2016-03-01

The aim of this study was to evaluate the effect and safety of lingual split technique using piezosurgery for the extraction of lingual positioned impacted mandibular 3rd molars with the goal of proposing a more minimally invasive choice for this common surgery.Eighty-nine consecutive patients with 110 lingual positioned impacted mandibular 3rd molars requiring extraction were performed the lingual split technique using piezosurgery. One sagittal osteotomy line and 2 transverse osteotomy line were designed for lingual and occlusal bone removal. The success rate, operative time, postoperative outcome, and major complications (including nerve injury, mandible fracture, severe hematoma or edema, and severe pyogenic infection) were documented and analyzed.All impacted mandibular 3rd molars were successfully removed (110/110). The average time of operation was 14.6 minutes (ranged from 7 to 28 minutes). One hundred and seven extraction sites (97.3%) were primary healing. Pain, mouth opening, swelling, and PoSSe scores on postoperative 7-day were 0.34 ± 0.63, 3.88 ± 0.66(cm), 2.4 ± 0.2(cm), and 23.7 ± 5.9, respectively. There were 6 cases (5.5%) had lingual nerve disturbance and 3 cases (2.7%) developed inferior alveolar nerve impairment, and achieved full recovery within 2 months by neurotrophic drug treatment.Our study suggested piezosurgery for lingual split technique provided an effective way for the extraction of lingual positioned and deeply impacted mandibular 3rd molar.

Piezosurgery for the Lingual Split Technique in Lingual Positioned Impacted Mandibular Third Molar Removal

PubMed Central

Ge, Jing; Yang, Chi; Zheng, Jiawei; Qian, Wentao

2016-01-01

Abstract The aim of this study was to evaluate the effect and safety of lingual split technique using piezosurgery for the extraction of lingual positioned impacted mandibular 3rd molars with the goal of proposing a more minimally invasive choice for this common surgery. Eighty-nine consecutive patients with 110 lingual positioned impacted mandibular 3rd molars requiring extraction were performed the lingual split technique using piezosurgery. One sagittal osteotomy line and 2 transverse osteotomy line were designed for lingual and occlusal bone removal. The success rate, operative time, postoperative outcome, and major complications (including nerve injury, mandible fracture, severe hematoma or edema, and severe pyogenic infection) were documented and analyzed. All impacted mandibular 3rd molars were successfully removed (110/110). The average time of operation was 14.6 minutes (ranged from 7 to 28 minutes). One hundred and seven extraction sites (97.3%) were primary healing. Pain, mouth opening, swelling, and PoSSe scores on postoperative 7-day were 0.34 ± 0.63, 3.88 ± 0.66(cm), 2.4 ± 0.2(cm), and 23.7 ± 5.9, respectively. There were 6 cases (5.5%) had lingual nerve disturbance and 3 cases (2.7%) developed inferior alveolar nerve impairment, and achieved full recovery within 2 months by neurotrophic drug treatment. Our study suggested piezosurgery for lingual split technique provided an effective way for the extraction of lingual positioned and deeply impacted mandibular 3rd molar. PMID:27015214

Remission and recovery associated with lurasidone in the treatment of major depressive disorder with subthreshold hypomanic symptoms (mixed features): post-hoc analysis of a randomized, placebo-controlled study with longer-term extension.

PubMed

Goldberg, Joseph F; Ng-Mak, Daisy; Siu, Cynthia; Chuang, Chien-Chia; Rajagopalan, Krithika; Loebel, Antony

2017-04-01

This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features). Patients with MDD plus two or three manic symptoms (defined as per the DSM-5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20-60 mg/day (n=109) or placebo (n=100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n=48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery-Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤3) at week 6, and at both months 1 and 3 of the extension study ("sustained recovery"). A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed cross-sectionally) compared to placebo (12.2%, p=0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p=0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%). In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.

The short Synacthen (corticotropin) test can be used to predict recovery of hypothalamo-pituitary-adrenal axis function.

PubMed

Pofi, Riccardo; Feliciano, Chona; Sbardella, Emilia; Argese, Nicola; Woods, Conor P; Grossman, Ashley B; Jafar-Mohammadi, Bahram; Gleeson, Helena; Lenzi, Andrea; Isidori, Andrea M; Tomlinson, Jeremy W

2018-05-25

The 250μg Short Synacthen (corticotropin) Test (SST) is the most commonly used tool to assess hypothalamo-pituitary-adrenal (HPA) axis function. There are many potentially reversible causes of adrenal insufficiency (AI), but currently no data to guide clinicians as to the frequency of repeat testing or likelihood of HPA axis recovery. To use the SST results to predict recovery of adrenal function. A retrospective analysis of data from 1912 SSTs. 776 patients with reversible causes of AI were identified who had at least two SSTs performed. A subgroup analysis was performed on individuals previously treated with suppressive doses of glucocorticoids (n=110). Recovery of HPA axis function. SST 30-minute cortisol levels above or below 350nmol/L (12.7μg/dL) best predicted HPA axis recovery (AUC ROC=0.85; median recovery time 334 vs. 1368 days, p=8.5x10-13): 99% of patients with a 30-minute cortisol >350nmol/L recovered adrenal function within 4-years, compared with 49% in those with cortisol levels <350nmol/L. In patients exposed to suppressive doses of glucocorticoids, delta cortisol (30-minute - basal) was the best predictor of recovery (AUC ROC = 0.77; median recovery time 262 vs. 974 days, p=7.0x10-6). No patient with a delta cortisol <100nmol (3.6μg/dL) and a subsequent random cortisol <200nmol/L (7.3μg/dL) measured approximately 1-year later recovered HPA axis function. Cortisol levels across an SST can be used to predict recovery of AI and may guide the frequency of repeat testing and inform both clinicians and patients as to the likelihood of restoration of HPA axis function.

Alcohol: impact on sports performance and recovery in male athletes.

PubMed

Barnes, Matthew J

2014-07-01

Alcohol is the most commonly used recreational drug globally and its consumption, often in large volume, is deeply embedded in many aspects of Western society. Indeed, athletes are not exempt from the influence alcohol has on society; they often consume greater volumes of alcohol through bingeing behaviour compared with the general population, yet it is often expected and recommended that athletes abstain from alcohol to avoid the negative impact this drug may have on recovery and sporting performance. While this recommendation may seem sensible, the impact alcohol has on recovery and sports performance is complicated and depends on many factors, including the timing of alcohol consumption post-exercise, recovery time required before recommencing training/competition, injury status and dose of alcohol being consumed. In general, acute alcohol consumption, at the levels often consumed by athletes, may negatively alter normal immunoendocrine function, blood flow and protein synthesis so that recovery from skeletal muscle injury may be impaired. Other factors related to recovery, such as rehydration and glycogen resynthesis, may be affected to a lesser extent. Those responsible for the wellbeing of athletes, including the athlete themselves, should carefully monitor habitual alcohol consumption so that the generic negative health and social outcomes associated with heavy alcohol use are avoided. Additionally, if athletes are to consume alcohol after sport/exercise, a dose of approximately 0.5 g/kg body weight is unlikely to impact most aspects of recovery and may therefore be recommended if alcohol is to be consumed during this period.

Multilineage hematopoietic recovery by a single injection of pegylated recombinant human megakaryocyte growth and development factor in myelosuppressed mice.

PubMed

Shibuya, K; Akahori, H; Takahashi, K; Tahara, E; Kato, T; Miyazaki, H

1998-01-01

Previous studies have shown that daily multiple administration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) markedly stimulates thrombopoiesis and effectively ameliorates thrombocytopenia, and in most cases anemia and neutropenia, in myelosuppressed animals. In this study, we evaluated the effects of a single intravenous injection of PEG-rHuMGDF on hematopoietic recovery after sublethal total-body irradiation in mice. A single injection of PEG-rHuMGDF (1 to 640 microg/kg) 1 hour after irradiation accelerated platelet, red blood cell (RBC), and white blood cell (WBC) recovery in a dose-dependent fashion. In the bone marrow of vehicle-treated mice, megakaryocytic, erythroid, and myeloid progenitors, as well as day 12 colony-forming unit-spleen (CFU-S), were dramatically decreased much earlier than the nadirs of peripheral blood cells, whereas megakaryocytes were modestly decreased. Treatment with PEG-rHuMGDF (80 microg/kg, an optimal dose) 1 hour after irradiation resulted in more rapid recovery of these four hematopoietic progenitors and also significantly facilitated megakaryocyte recovery. In addition, the same PEG-rHuMGDF administration schedule expanded bone marrow cells capable of rescuing lethally irradiated recipient mice. As the interval between irradiation and PEG-rHuMGDF treatment was longer, its effects on hematopoietic recovery were attenuated. In contrast to the effects of PEG-rHuMGDF, a single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 1 hour after irradiation exclusively accelerated WBC recovery, but only to a similar extent as PEG-rHuMGDF (80 microg/kg) treatment even when rhG-CSF doses were escalated to 1,000 microg/kg. This appeared related to different pharmacokinetics of these two factors after a single injection in irradiated mice. The concentrations of PEG-rHuMGDF after injection persisted in the plasma for a longer time compared with rhG-CSF. These results indicate that a single injection of PEG-rHuMGDF at an early time after irradiation is able to effectively improve thrombocytopenia, anemia, and leukopenia with concomitant accelerated recovery of both primitive and committed hematopoietic progenitors in irradiated mice. Our data also show that compared with the rhG-CSF shown to exert multilineage effects on hematopoiesis, PEG-rHuMGDF has more wide-ranging effects on peripheral blood cell recovery.

Benefits of High-dose Steroid + Hespander + Mannitol Administration in the Treatment of Bell's Palsy.

PubMed

Furukawa, Takatoshi; Abe, Yasuhiro; Ito, Tsukasa; Kubota, Toshinori; Kakehata, Seiji

2017-02-01

Large-scale investigations have not been recently conducted on the efficacy of high-dose steroid administration of prednisolone (PSL) for Bell's palsy. We compared treatment results between normal-dose steroid (PSL 60 mg/d) and high-dose steroid (PSL 200 mg/d) + Hespander + Mannitol administration. We also investigated the recovery rate for antiviral agents. Retrospective case review. Tertiary referral center. A total of 675 patients with Bell's palsy who had grade V and grade VI on the House-Brackmann (HB) scale were treated in our department between 1995 and 2014. These patients could be divided into a normal-dose group and high-dose group. We separately assessed treatment outcomes for HB grade V patients and HB grade VI patients. Logistic regression analysis was also performed to investigate factors that can impact treatment outcomes, i.e., sex, age, days to start of treatment, PSL dosage, and antiviral drug administration. Recovery rates were significantly better in the high-dose steroid + Hespander + Mannitol group in comparison with the normal-dose steroid group for HB grade V (100% versus 77.7%) and HB grade VI (92.5% versus 68.2%). Additional effects of antiviral agents were only shown in the normal-dose group. Significant factors for treatment outcomes were PSL 200 mg/d administration and early initiation of treatment. Insignificant factors were sex, age, and the antiviral agent. We showed the high-dose steroid + Hespander + Mannitol administration produced significantly better outcomes than normal-dose steroid administration in the treatment of patients with Bell's palsy.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Phototherapy in skeletal muscle performance and recovery after exercise: effect of combination of super-pulsed laser and light-emitting diodes.

PubMed

Antonialli, Fernanda Colella; De Marchi, Thiago; Tomazoni, Shaiane Silva; Vanin, Adriane Aver; dos Santos Grandinetti, Vanessa; de Paiva, Paulo Roberto Vicente; Pinto, Henrique Dantas; Miranda, Eduardo Foschini; de Tarso Camillo de Carvalho, Paulo; Leal-Junior, Ernesto Cesar Pinto

2014-11-01

Recent studies with phototherapy have shown positive results in enhancement of performance and improvement of recovery when applied before exercise. However, several factors still remain unknown such as therapeutic windows, optimal treatment parameters, and effects of combination of different light sources (laser and LEDs). The aim of this study was to evaluate the effects of phototherapy with the combination of different light sources on skeletal muscle performance and post-exercise recovery, and to establish the optimal energy dose. A randomized, double-blinded, placebo-controlled trial with participation of 40 male healthy untrained volunteers was performed. A single phototherapy intervention was performed immediately after pre-exercise (baseline) maximum voluntary contraction (MVC) with a cluster of 12 diodes (4 of 905 nm lasers-0.3125 mW each, 4 of 875 nm LEDs-17.5 mW each, and 4 of 670 nm LEDs-15 mW each- manufactured by Multi Radiance Medical™) and dose of 10, 30, and 50 J or placebo in six sites of quadriceps. MVC, delayed onset muscle soreness (DOMS), and creatine kinase (CK) activity were analyzed. Assessments were performed before, 1 min, 1, 24, 48, 72, and 96 h after eccentric exercise protocol employed to induce fatigue. Phototherapy increased (p < 0.05) MVC was compared to placebo from immediately after to 96 h after exercise with 10 or 30 J doses (better results with 30 J dose). DOMS was significantly decreased compared to placebo (p < 0.05) with 30 J dose from 24 to 96 h after exercise, and with 50 J dose from immediately after to 96 h after exercise. CK activity was significantly decreased (p < 0.05) compared to placebo with all phototherapy doses from 1 to 96 h after exercise (except for 50 J dose at 96 h). Pre-exercise phototherapy with combination of low-level laser and LEDs, mainly with 30 J dose, significantly increases performance, decreases DOMS, and improves biochemical marker related to skeletal muscle damage.

Improving recovery of ECG signal with deterministic guarantees using split signal for multiple supports of matching pursuit (SS-MSMP) algorithm.

PubMed

Tawfic, Israa Shaker; Kayhan, Sema Koc

2017-02-01

Compressed sensing (CS) is a new field used for signal acquisition and design of sensor that made a large drooping in the cost of acquiring sparse signals. In this paper, new algorithms are developed to improve the performance of the greedy algorithms. In this paper, a new greedy pursuit algorithm, SS-MSMP (Split Signal for Multiple Support of Matching Pursuit), is introduced and theoretical analyses are given. The SS-MSMP is suggested for sparse data acquisition, in order to reconstruct analog and efficient signals via a small set of general measurements. This paper proposes a new fast method which depends on a study of the behavior of the support indices through picking the best estimation of the corrosion between residual and measurement matrix. The term multiple supports originates from an algorithm; in each iteration, the best support indices are picked based on maximum quality created by discovering correlation for a particular length of support. We depend on this new algorithm upon our previous derivative of halting condition that we produce for Least Support Orthogonal Matching Pursuit (LS-OMP) for clear and noisy signal. For better reconstructed results, SS-MSMP algorithm provides the recovery of support set for long signals such as signals used in WBAN. Numerical experiments demonstrate that the new suggested algorithm performs well compared to existing algorithms in terms of many factors used for reconstruction performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

EFFECTIVENESS OF THE ANESTHETIC AQUI-S® 20E IN MARINE FINFISH AND ELASMOBRANCHS.

PubMed

Silbernagel, Constance; Yochem, Pamela

2016-04-01

Immersion anesthetics are used in hatchery settings by veterinarians, field biologists, and laboratory researchers to aid in handling finfish for medical procedures, research purposes, and moderating perceived stress responses. The only Food and Drug Administration- (FDA) approved anesthetic for food fish, tricaine methanesulfonate, requires a 21-d withdrawal period prior to harvest. Ten percent eugenol (AQUI-S® 20E) has been gaining momentum for FDA approval because of its 0-d withdrawal time if fish are not of harvestable size within 72 h of exposure. We performed two trials to determine appropriate anesthetic doses for two cultured marine finfish: Atractoscion nobilis (white seabass, WSB) and Seriola lalandi (California yellowtail, YT). Fish were held in a treated water bath for 10 min or until opercular beat rate slowed to a rate of <2 beats/min. Based on these results, we conducted a field trial with wild Paralabrax maculatofasciatus (spotted bay bass), Paralabrax nebulifer (barred sand bass), Paralichthys californicus (California halibut), Triakis semifasciata (leopard shark), and Mustelus californicus (grey smooth-hound) at a single dosing regime, with animals held 5-10 min in anesthetic baths. Anesthetic dosing of 35-55 mg L(-1) provided relatively fast induction and good anesthetic maintenance in cultured and wild finfish. Anesthetic induction times were comparable among S. lalandi and A. nobilis at 35-mg L(-1) to 75-mg L(-1) doses, but recovery times were variable. Mortality rates of 20-90% were observed at higher doses (75 mg L(-1) and 100 mg L(-1), A. nobilis; 55 mg L(-1) and 75 mg L(-1), S. lalandi). The apparent increase in sensitivity of S. lalandi may have been associated with nutritional stress in the fish tested. There were no differences in time to anesthesia or recovery among wild finfish species tested at a single dose. Anesthetic induction, maintenance, and recovery were less predictable in the elasmobranch species tested and additional trials are needed to determine optimal dosing.

Compositional dependence of defect mobility and damage buildup in Al xGa 1- xAs

NASA Astrophysics Data System (ADS)

Stonert, A.; Turos, A.; Nowicki, L.; Breeger, B.; Wendler, E.; Wesch, W.

2001-04-01

Defect transformations at low temperatures in ion implanted Al xGa 1- xAs (0⩽ x⩽1) ternary compounds were studied. Experiments consisted of ion implantation with 150 keV N or 200 keV Ar ions with different doses at temperatures between 18 and 77 K, and in situ RBS/channeling measurements at selected temperatures. An important recovery stage attributed to the defect mobility in the Ga(Al) sublattice was revealed near 280 K. For x>0.5 this stage was largely suppressed. Instead, a continuous damage recovery at low temperatures was observed. It was noticed that defect recombination can also be produced upon prolonged storage at the implantation temperature. For AlAs ( x=1) the 280 K stage disappeared completely and only a small defect recovery at low temperatures was noticed. Upon N- or Ar-ion bombardment, after an incubation period, a sharp crystalline-to-amorphous transition appeared. The amorphization dose increases with increasing x and is a factor of 10 higher for x=0.96 than that for x=0. A further increase of the dose by a factor of 15 was required to amorphize AlAs ( x=1).

Characterization and recovery of Deep Sub Micron (DSM) technologies behavior under radiation

NASA Technical Reports Server (NTRS)

Stoica, Adrian; Wang, Xiao

2005-01-01

This paper serves a twofold purpose: characterize the behavior of a reconfigurable chip exposed to radiation; and demonstrate a method for functionality recovery due to Total Ionizing Dose (TID) effects. The experiments are performed using a PL developed reconfigurable device, a Field Programmable Transistor Array (FPTA). The paper initially describes experiments on the characterization of the NMOS transistor behavior for TID values up to 300krad. The behavior of analog and digital circuits downloaded onto the FPTA chip is also assessed for TID effects. This paper also presents a novel approach for circuit functionality recovery due to radiation effects based on Evolvable Hardware. The key idea is to reconfigure a programmable device, in-situ, to compensate, or bypass its degraded or damaged components. Experiments with total radiation dose up to 300kRad show that while the functionality of a variety of circuits, including digital gates, a rectifier and a Digital to Analog Converter implemented on a FPTA-2 chip is degraded/lost at levels before 200kRad, the correct functionality can be recovered through the proposed evolutionary approach and the chips are able to survive higher radiation, for several functions in excess of total radiation dose of 250kRad.

A comparison of ketamine + midazolam to propofol for procedural sedation for lumbar puncture in pediatric oncology by nonanesthesiologists-a randomized comparative trial.

PubMed

Chayapathi, Varsha; Kalra, Manas; Bakshi, Anita S; Mahajan, Amita

2018-05-04

Both ketamine-midazolam and propofol are frequently used in pediatric oncology units for procedural sedation. However, there are no prospective, randomized comparative trials (RCT) comparing the two groups when the procedure is performed by nonanesthesiologists. To compare ketamine + midazolam (group A) and propofol (group B) as sedative agents for intrathecal chemotherapy with regard to efficacy, side effects, time to induction, time to recovery, and smoothness of recovery. A partially-blinded RCT was conducted between August 2015 and March 2017 after gaining institutional ethics committee approval. Children aged 1-12 years requiring intravenous sedation for intrathecal chemotherapy were included. Patients were allocated to two treatment arms using computer-generated randomization tables, after obtaining written consent. The initial doses used were: ketamine 2 mg/kg, midazolam 0.2 mg/kg, and propofol 2.5 mg/kg, as per standard recommendations. The patient, parents, and person analyzing the data were blinded. Time to sedation, dose required, depth of sedation, vital parameters, time and smoothness of recovery, and emergence phenomena were documented. We enrolled 152 patients (76 each in group A and B). Nine patients had a failure of sedation (all in group B). Mean time to sedation and recovery was shorter in group B (P < 0.001). Transient drop in saturation was more frequent in group B, without statistical significance (P = 0.174). Mean depth of sedation was greater in group A (P < 0.001). Emergence symptoms were more frequently experienced in group A (P < 0.001). Ketamine-midazolam combination is safer and more effective. Propofol is faster in onset and recovery, and has smoother emergence with poor efficacy at recommended initial doses. © 2018 Wiley Periodicals, Inc.

Effect of contrast water therapy duration on recovery of cycling performance: a dose-response study.

PubMed

Versey, Nathan; Halson, Shona; Dawson, Brian

2011-01-01

This study investigated whether contrast water therapy (CWT) has a dose-response effect on recovery from high-intensity cycling. Eleven trained male cyclists completed four trials, each commencing with a 75-min cycling protocol containing six sets of five 15-s sprints and three 5-min time-trials in thermoneutral conditions. Ten minutes post-exercise, participants performed one of four recovery protocols: CWT for 6 min (CWT6), 12 min (CWT12), or 18 min (CWT18) duration, or a seated rest control trial. The CWT commenced in hot water (38.4 ± 0.6°C) and alternated between hot and cold water (14.6 ± 0.3°C) every minute with a 5-s changeover. The cycling protocol was repeated 2 h after completion of exercise bout one. Prior to exercise bout two, core temperature was lower in CWT12 (-0.19 ± 0.14°C, mean ± 90% CL) and CWT18 (-0.21 ± 0.10°C) than control. Compared with control, CWT6 substantially improved time-trial (1.5 ± 2.1%) and sprint performance (3.0 ± 3.1%), and CWT12 substantially improved sprint total work (4.3 ± 3.4%) and peak power (2.7 ± 3.8%) in exercise bout two. All CWT conditions generally improved thermal sensation, whole body fatigue and muscle soreness compared with control, but no differences existed between conditions in heart rate or rating of perceived exertion. In conclusion, CWT duration did not have a dose-response effect on recovery from high-intensity cycling; however, CWT for up to 12 min assisted recovery of cycling performance.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, J; Hill, G; Spiegel, J

Purpose: To investigate the clinical and dosimetric benefits of automatic gating of left breast mixed with breath-hold technique. Methods: Two Active Breathing Control systems, ABC2.0 and ABC3.0, were used during simulation and treatment delivery. The two systems are different such that ABC2.0 is a breath-hold system without beam control capability, while ABC3.0 has capability in both breath-hold and beam gating. At simulation, each patient was scanned twice: one with free breathing (FB) and one with breath hold through ABC. Treatment plan was generated on the CT with ABC. The same plan was also recalculated on the CT with FB. Thesemore » two plans were compared to assess plan quality. For treatments with ABC2.0, beams with MU > 55 were manually split into multiple subfields. All subfields were identical and shared the total MU. For treatment with ABC3.0, beam splitting was unnecessary. Instead, treatment was delivered in gating mode mixed with breath-hold technique. Treatment delivery efficiency using the two systems was compared. Results: The prescribed dose was 50.4Gy at 1.8Gy/fraction. The maximum heart dose averaged over 10 patients was 46.0±2.5Gy and 24.5±12.2Gy for treatments with FB and with ABC respectively. The corresponding heart V10 was 13.2±3.6% and 1.0±1.6% respectively. The averaged MUs were 99.8±7.5 for LMT, 99.2±9.4 for LLT. For treatment with ABC2.0, normally the original beam was split into 2 subfields. The averaged total time to delivery all beams was 4.3±0.4min for treatments with ABC2.0 and 3.3±0.6min for treatments with ABC3.0 in gating mode. Conclusion: Treatment with ABC tremendously reduced heart dose. Compared to treatments with ABC2.0, gating with ABC3.0 reduced the total treatment time by 23%. Use of ABC3.0 improved the delivery efficiency, and eliminated the possibility of mistreatments. The latter may happen with ABC2.0 where beam is not terminated when breath signal falls outside of the treatment window.« less

Muscle-splitting approach to superior and inferior gluteal vessels: versatile source of recipient vessels for free-tissue transfer to sacral, gluteal, and ischial regions.

PubMed

Park, S

2000-07-01

The superior gluteal vessel has been reported as a recipient in free-tissue transfer for the coverage of complex soft-tissue defects in the lumbosacral region, where a suitable recipient vessel is difficult to find. The characteristics of proximity, vessel caliber, and constancy make the superior gluteal vessel preferable to previously reported recipient vessels. However, there are technical difficulties in microsurgery (e.g., short pedicle length and deep location) and muscle injury (transection of the muscle) associated with use of the superior gluteal vessel. The purpose of this article is to present a modification of an approach to the gluteal vessel to alleviate technical difficulties and minimize muscle injury. From August of 1997 to January of 1999, six patients received microvascular transfer of the latissimus dorsi muscle or myocutaneous flap to the sacral (4) and ischial (2) regions. The causes of defects were tumor (1), trauma (1), and pressure sores (4). A muscle-splitting approach was used on the superior gluteal vessel and was later applied to the inferior gluteal vessel. The gluteus maximus muscle was split as needed in the direction of its fibers, and the perforators were dissected down to the superior or inferior gluteal artery and vein deep into the muscle. The follow-up period ranged from 6 to 22 months, and all of the flaps survived with complete recovery of the lesion. The major drawbacks of using the superior and inferior gluteal vessels can be overcome with the muscle-splitting approach, which provides increased accessibility and additional length to the vascular pedicle while causing minimal injury to the muscle itself. It also proves to be an easy, safe, and reliable method of dissection. When free-tissue transfer to sacral, gluteal, and ischial regions is indicated, the muscle-splitting approach to the superior and inferior gluteal vessels is a recommended option in the selection of a recipient vessel.

SU-G-TeP2-11: Initial Evaluation of a Novel Split-Filter Dual-Energy CT for Use in Radiation Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, J; Huang, J; Szczykutowicz, T

2016-06-15

Purpose: To perform an initial evaluation of a novel split-filter dual-energy CT (DECT) system with the goal of understanding the clinical utility and limitations of the system for radiation therapy. Methods: Several phantoms were imaged using the split-filter DECT technique on the Siemens Edge CT scanner using a range of clinically-relevant doses. The optimum-contrast reconstruction, the mixed reconstruction, and the monoenergetic reconstructions (ranging from 40 keV to 190 keV) were evaluated. Each image was analyzed for CT number accuracy, uniformity, noise, low-contrast visibility (LCV), spatial resolution and geometric distortion. For comparison purposes, all parameters were evaluated on 120 kVp single-energymore » CT (SECT) scans used for treatment planning, as well as, a sequential-scan DECT technique for corresponding doses. Results: For all DECT reconstructions no observable geometric distortion was found. Both the optimal-contrast and mixed images demonstrated slight improvements in LCV and noise when compared to the SECT, and slight reductions in CT number accuracy and spatial resolution. The CT numbers trended as expected for the monoenergetic reconstructions, with CT number accuracy within 50 HU for materials of density <2 g/cm3. Spatial resolution increased with energy, and for monoenergetic reconstructions >70 keV the spatial resolution exceeded that of the SECT. The noise in the monoenergetic reconstructions increased with decreasing energy. Thus, the image uniformity, signal-to-noise ratio and LCV were diminished at lower energies (70 keV). Applying iterative reconstruction techniques to the low-energy images reduced noise and improved LCV. The signal-to-noise ratio was stable for energies >100 keV. Conclusion: The initial commissioning of the novel split-filter DECT technology demonstrated favorable results for clinical implementation. The mixed reconstruction showed potential as a replacement for the treatment planning SECT. The image parameters for the monoenergetic reconstructions varied appropriately with energy. This work provides an initial understanding of the limitations and potential applications for monoenergetic imaging.« less

Using the Multiplicative Schwarz Alternating Algorithm (MSAA) for Solving the Large Linear System of Equations Related to Global Gravity Field Recovery up to Degree and Order 120

NASA Astrophysics Data System (ADS)

Safari, A.; Sharifi, M. A.; Amjadiparvar, B.

2010-05-01

The GRACE mission has substantiated the low-low satellite-to-satellite tracking (LL-SST) concept. The LL-SST configuration can be combined with the previously realized high-low SST concept in the CHAMP mission to provide a much higher accuracy. The line of sight (LOS) acceleration difference between the GRACE satellite pair is the mostly used observable for mapping the global gravity field of the Earth in terms of spherical harmonic coefficients. In this paper, mathematical formulae for LOS acceleration difference observations have been derived and the corresponding linear system of equations has been set up for spherical harmonic up to degree and order 120. The total number of unknowns is 14641. Such a linear equation system can be solved with iterative solvers or direct solvers. However, the runtime of direct methods or that of iterative solvers without a suitable preconditioner increases tremendously. This is the reason why we need a more sophisticated method to solve the linear system of problems with a large number of unknowns. Multiplicative variant of the Schwarz alternating algorithm is a domain decomposition method, which allows it to split the normal matrix of the system into several smaller overlaped submatrices. In each iteration step the multiplicative variant of the Schwarz alternating algorithm solves linear systems with the matrices obtained from the splitting successively. It reduces both runtime and memory requirements drastically. In this paper we propose the Multiplicative Schwarz Alternating Algorithm (MSAA) for solving the large linear system of gravity field recovery. The proposed algorithm has been tested on the International Association of Geodesy (IAG)-simulated data of the GRACE mission. The achieved results indicate the validity and efficiency of the proposed algorithm in solving the linear system of equations from accuracy and runtime points of view. Keywords: Gravity field recovery, Multiplicative Schwarz Alternating Algorithm, Low-Low Satellite-to-Satellite Tracking

Effects of alfaxalone administered intravenously to healthy yearling loggerhead sea turtles (Caretta caretta) at three different doses.

PubMed

Phillips, Brianne E; Posner, Lysa P; Lewbart, Gregory A; Christiansen, Emily F; Harms, Craig A

2017-04-15

OBJECTIVE To compare physiologic and anesthetic effects of alfaxalone administered IV to yearling loggerhead sea turtles (Caretta caretta) at 3 different doses. DESIGN Randomized crossover study. ANIMALS 9 healthy yearling loggerhead sea turtles. PROCEDURES Animals received each of 3 doses of alfaxalone (3 mg/kg [1.4 mg/lb], 5 mg/kg [2.3 mg/lb], or 10 mg/kg [4.5 mg/lb]) administered IV in randomly assigned order, with a minimum 7-day washout period between doses. Endotracheal intubation was attempted following anesthetic induction, and heart rate, sedation depth, cloacal temperature, and respirations were monitored. Times to first effect, induction, first voluntary muscle movement, first respiration, and recovery were recorded. Venous blood gas analysis was performed at 0 and 30 minutes. Assisted ventilation was performed if apnea persisted 30 minutes following induction. RESULTS Median anesthetic induction time for all 3 doses was 2 minutes. Endotracheal intubation was accomplished in all turtles following induction. Heart rate significantly increased after the 3- and 5-mg/kg doses were administered. Median intervals from alfaxalone administration to first spontaneous respiration were 16, 22, and 54 minutes for the 3-, 5-, and 10-mg/kg doses, respectively, and median intervals to recovery were 28, 46, and 90 minutes, respectively. Assisted ventilation was required for 1 turtle after receiving the 5-mg/kg dose and for 5 turtles after receiving the 10-mg/kg dose. The 10-mg/kg dose resulted in respiratory acidosis and marked hypoxemia at 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE IV alfaxalone administration to loggerhead sea turtles resulted in a rapid anesthetic induction and dose-dependent duration of sedation. Assisted ventilation is recommended if the 10 mg/kg dose is administered.

The Progressive Fragmentation of 332P/Ikeya-Murakami

NASA Astrophysics Data System (ADS)

Kleyna, J. T.; Ye, Q.-Z.; Hui, M.-T.; Meech, K. J.; Wainscoat, R.; Micheli, M.; Keane, J. V.; Weaver, H. A.; Weryk, R.

2016-08-01

We describe 2016 January-April observations of the fragments of 332P/Ikeya-Murakami, a comet earlier observed in a 2010 October outburst. We present photometry of the fragments and perform simulations to infer the time of breakup. We argue that the eastern-most rapidly brightening fragment (F4) best corresponds to the original nucleus, rather than the initial bright fragment F1. We compute radial and tangential nongravitational parameters, A 1 = (1.5 ± 0.4) × 10-8 au day-2 and (7.2 ± 1.9) × 10-9 au day-2 both are consistent with zero at the 4σ level. Monte Carlo simulations indicate that the fragments were emitted on the outbound journey well after the 2010 outburst, with bright fragment F1 splitting in early 2014 and the fainter fragments within months of the 2016 January recovery. Western fragment F7 is the oldest, dating from 2011. We suggest that the delayed onset of the splitting is consistent with a self-propagating crystallization of water ice.

Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

PubMed

Kotronoulas, Aristotelis; Pizarro, Nieves; Serra, Aida; Robledo, Patricia; Joglar, Jesús; Rubió, Laura; Hernaéz, Alvaro; Tormos, Carmen; Motilva, Ma José; Fitó, Montserrat; Covas, Maria-Isabel; Solà, Rosa; Farré, Magí; Saez, Guillermo; de la Torre, Rafael

2013-11-01

Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested. Copyright © 2013. Published by Elsevier Ltd.

Promoting recovery-oriented practice in mental health services: a quasi-experimental mixed-methods study.

PubMed

Gilburt, Helen; Slade, Mike; Bird, Victoria; Oduola, Sheri; Craig, Tom K J

2013-06-13

Recovery has become an increasingly prominent concept in mental health policy internationally. However, there is a lack of guidance regarding organisational transformation towards a recovery orientation. This study evaluated the implementation of recovery-orientated practice through training across a system of mental health services. The intervention comprised four full-day workshops and an in-team half-day session on supporting recovery. It was offered to 383 staff in 22 multidisciplinary community and rehabilitation teams providing mental health services across two contiguous regions. A quasi-experimental design was used for evaluation, comparing behavioural intent with staff from a third contiguous region. Behavioural intent was rated by coding points of action on the care plans of a random sample of 700 patients (400 intervention, 300 control), before and three months after the intervention. Action points were coded for (a) focus of action, using predetermined categories of care; and (b) responsibility for action. Qualitative inquiry was used to explore staff understanding of recovery, implementation in services and the wider system, and the perceived impact of the intervention. Semi-structured interviews were conducted with 16 intervention group team leaders post-training and an inductive thematic analysis undertaken. A total of 342 (89%) staff received the intervention. Care plans of patients in the intervention group had significantly more changes with evidence of change in the content of patient's care plans (OR 10.94. 95% CI 7.01-17.07) and the attributed responsibility for the actions detailed (OR 2.95, 95% CI 1.68-5.18). Nine themes emerged from the qualitative analysis split into two superordinate categories. 'Recovery, individual and practice', describes the perception and provision of recovery orientated care by individuals and at a team level. It includes themes on care provision, the role of hope, language of recovery, ownership and multidisciplinarity. 'Systemic implementation', describes organizational implementation and includes themes on hierarchy and role definition, training approaches, measures of recovery and resources. Training can provide an important mechanism for instigating change in promoting recovery-orientated practice. However, the challenge of systemically implementing recovery approaches requires further consideration of the conceptual elements of recovery, its measurement, and maximising and demonstrating organizational commitment.

Pre-exercise β-hydroxy-β-methylbutyrate free-acid supplementation improves work capacity recovery: a randomized, double-blinded, placebo-controlled study.

PubMed

Correia, Ana Luiza Matias; de Lima, Filipe Dinato; Bottaro, Martim; Vieira, Amilton; da Fonseca, Andrew Correa; Lima, Ricardo M

2018-02-08

The purpose of this study was to investigate the effects of a single-dose of β-hydroxy-β-methylbutyrate free acid (HMB-FA) supplementation on muscle recovery after a high-intensity exercise bout. Twenty-three trained young males were randomly assigned to receive either a single-dose supplementation of 3g of HMB-FA (n = 12; age 22.8 ± 3.0 years) or placebo (PLA; n = 11; age 22.9 ± 3.1 years). A muscle damage protocol was applied 60 minutes after supplementation, and consisted of seven sets of 20 drop jumps from a 60-cm box with 2-min rest intervals between sets. Muscle swelling, countermovement jump (CMJ), maximal voluntary isometric torque (MVIT) and work capacity (WC) were measured before, immediately after, 24, 48 and 72 hours after the exercise protocol. Muscle swelling, CMJ and MVIT changed similarly in both groups after the exercise protocol (p < 0.001), but returned to pre-exercise levels after 24 hours in both groups. WC decreased similarly in both groups after the exercise protocol (p < 0.01). For HMB-FA, WC returned to pre-exercise level 24 hours after exercise protocol. However, on PLA, WC did not return to pre-exercise level even 72 hours after the exercise protocol. In summary, a single-dose of HMB-FA supplementation improved WC recovery after a high-intensity exercise bout. However, HMB-FA did not affect the time-course of muscle swelling, MVIT and CMJ recovery.

Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice

PubMed Central

Markowitz, Geoffrey J.; Kadam, Shilpa D.; Smith, Dani R.; Johnston, Michael V.; Comi, Anne M.

2011-01-01

Neonatal stroke presents with seizures that are usually treated with phenobarbital. We hypothesized that anticonvulsants would attenuate ischemic injury, but that the dose-dependent effects of standard anticonvulsants would impact important age-dependent and injury-dependent consequences. In this study, ischemia induced by unilateral carotid ligation in postnatal day 12 (P12) CD1 mice was immediately followed by an i.p. dose of vehicle, low-dose or high-dose phenobarbital. Severity of acute behavioral seizures was scored. 5-bromo-2’-deoxyuridine (BrdU) was administered from P18-P20, behavioral testing performed, and mice perfused at P40. Atrophy quantification and counts of BrdU/NeuN-labeled cells in the dentate gyrus were performed. Blood phenobarbital concentrations were measured. 30 mg/kg phenobarbital reduced acute seizures and chronic brain injury, and restored normal weight gain and exploratory behavior. By comparison, 60 mg/kg was a less efficacious anticonvulsant, was not neuroprotective, did not restore normal weight gain, and impaired behavioral and cognitive recovery. Hippocampal neurogenesis was not different between treatment groups. These results suggest a protective effect of lower-dose phenobarbital, but a lack of this effect at higher concentrations after stroke in P12 mice. PMID:21481568

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.

PubMed

Soto, Roy; Jahr, Jonathan S; Pavlin, Janet; Sabo, Daniel; Philip, Beverly K; Egan, Talmage D; Rowe, Everton; de Bie, Joris; Woo, Tiffany

Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

After low and high dose-rate interstitial brachytherapy followed by IMRT radiotherapy for intermediate and high risk prostate cancer.

PubMed

Nakamura, Satoshi; Murakami, Naoya; Inaba, Koji; Wakita, Akihisa; Kobayashi, Kazuma; Takahashi, Kana; Okamoto, Hiroyuki; Umezawa, Rei; Morota, Madoka; Sumi, Minako; Igaki, Hiroshi; Ito, Yoshinori; Itami, Jun

2016-05-03

The study aimed to compare urinary symptoms in patients with clinically localized prostate cancer after a combination of either low-dose-rate or high-dose-rate interstitial brachytherapy along with intensity-modulated radiation therapy (LDR-ISBT + IMRT or HDR-ISBT + IMRT). From June 2009 to April 2014, 16 and 22 patients were treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT, respectively. No patient from these groups was excluded from this study. The prescribed dose of LDR-ISBT, HDR-ISBT, and IMRT was 115 Gy, 20 Gy in 2 fractions, and 46 Gy in 23 fractions, respectively. Obstructive and irritative urinary symptoms were assessed by the International Prostate Symptom Score (IPSS) examined before and after treatments. After ISBT, IPSS was evaluated in the 1st and 4th weeks, then every 2-3 months for the 1st year, and every 6 months thereafter. The median follow-up of the patients treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT was 1070.5 days and 1048.5 days, respectively (p = 0.321). The IPSS-increment in the LDR-ISBT + IMRT group was greater than that in the HDR-ISBT + IMRT between 91 and 180 days after ISBT (p = 0.015). In the LDR-ISBT + IMRT group, the IPSS took longer time to return to the initial level than in the HDR-ISBT + IMRT group (in LDR-ISBT + IMRT group, the recovery time was 90 days later). The dose to urethra showed a statistically significant association with the IPSS-increment in the irritative urinary symptoms (p = 0.011). Clinical outcomes were comparable between both the groups. Both therapeutic modalities are safe and well suited for patients with clinically localized prostate cancer; however, it took patients longer to recover from LDR-ISBT + IMRT than from HDR-ISBT + IMRT. It is possible that fast dose delivery induced early symptoms and early recovery, while gradual dose delivery induced late symptoms and late recovery. Urethral dose reductions were associated with small increments in IPSS.

Effects of adenosine receptor agonist on the rocuroniuminduced neuromuscular block and sugammadex-induced recovery.

PubMed

Kim, Yong Beom; Lee, Sangseok; Choi, Hey Ran; In, Junyong; Chang, Young Jin; Kim, Ha Jung; Ro, Young Jin; Yang, Hong-Seuk

2018-04-25

Several types of receptors are found at neuromuscular presynaptic membranes. Presynaptic inhibitory A1 and facilitatory A2A receptors mediate different modulatory functions on acetylcholine release. This study investigated whether adenosine A1 receptor agonist contributes to the first twitch tension (T1) of train-of-four (TOF) stimulation depression and TOF fade during rocuronium-induced neuromuscular blockade, and sugammadex-induced recovery. Phrenic nerve-diaphragm tissues were obtained from 30 adult Sprague-Dawley rats. Each tissue specimen was randomly allocated to either control group or 2-chloroadenosine (CADO, 10 μM) group. One hour of reaction time was allowed before initiating main experimental data collection. Loading and boost doses of rocuronium were sequentially administered until > 95% depression of the T1 was achieved. After confirming that there was no T1 twitch tension response, 15 min of resting time was allowed, after which sugammadex was administered. Recovery profiles (T1, TOF ratio [TOFR], and recovery index) were collected for 1 h and compared between groups. There were statistically significant differences on amount of rocuronium (actually used during experiment), TOFR changes during concentration-response of rocuronium (P = 0.04), and recovery profiles (P < 0.01) of CADO group comparing with the control group. However, at the initial phase of this experiment, dose-response of rocuronium in each group demonstrated no statistically significant differences (P = 0.12). The adenosine A1 receptor agonist (CADO) influenced the TOFR and the recovery profile. After activating adenosine receptor, sugammadex-induced recovery from rocuronium-induced neuromuscular block was delayed.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

PubMed

Dehuisser, Virginie; Bosmans, Tim; Kitshoff, Adriaan; Duchateau, Luc; de Rooster, Hilde; Polis, Ingeborgh

2017-11-01

To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. Prospective, blinded, randomized, experimental study. A group of 12 intact female dogs. Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Does Intravenous Midazolam Dose Influence the Duration of Recovery Room Stay Following Outpatient Third Molar Surgery?

PubMed

Ettinger, Kyle S; Jacob, Adam K; Viozzi, Christopher F; Van Ess, James M; Fillmore, W Jonathan; Arce, Kevin

2015-12-01

To evaluate the impact of intravenous midazolam dose on the duration of recovery room stay for patients undergoing outpatient third molar surgery. Using a retrospective cohort study design, a sample of patients undergoing outpatient third molar surgery under intravenous sedation at Mayo Clinic from 2010 to 2014 was identified. All patients underwent extraction of all 4 third molars during a single operative procedure and the age range was limited to 14 to 29 years. The primary predictor variable was the total dose of intravenous midazolam administered during sedation. The primary outcome variable was recovery room length of stay (LOS) after completion of surgery. Multiple covariates also abstracted included patient age, gender, American Society of Anesthesiologists (ASA) score, duration of surgical procedure, complexity of surgical procedure, types and dosages of all intravenous medications administered during sedation, and volume of crystalloid fluid administered perioperatively. Univariable and multivariable models were developed to evaluate associations between the primary predictor variable and covariates relative to the primary outcome variable. The study sample was composed of 2,610 patients. Mean age was 18.3 years (SD, 3.0 yr; range, 14 to 29 yr) and gender distribution was 52% female. Mean dosage of midazolam administered was 4.1 mg (SD, 1.1 mg; range, 0.5 to 10.0 mg). Variables predicting shorter LOS at multivariable analysis included older age (P < .001), male gender (P = .004), and administration of larger crystalloid fluid volumes (P < .001). Variables predicting longer LOS included higher ASA score (P < .001), administration of ketamine (P < .001), and administration of ketorolac (P < .001). The dose of midazolam administered during sedation was not found to be significantly associated with prolonged recovery room LOS in univariable or multivariable settings. Dosage of intravenous midazolam does not appear to significantly impact the duration of recovery room stay in the prototypical patients undergoing sedation for outpatient third molar surgery. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Comparison of Levetiracetam Dosing Regimens in End-Stage Renal Disease Patients Undergoing Intermittent Hemodialysis.

PubMed

Shiue, Harn J; Taylor, Maria; Sands, Kara A

2017-10-01

Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels. To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD. Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses. We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group. Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial.

PubMed

González, Raquel; Mombo-Ngoma, Ghyslain; Ouédraogo, Smaïla; Kakolwa, Mwaka A; Abdulla, Salim; Accrombessi, Manfred; Aponte, John J; Akerey-Diop, Daisy; Basra, Arti; Briand, Valérie; Capan, Meskure; Cot, Michel; Kabanywanyi, Abdunoor M; Kleine, Christian; Kremsner, Peter G; Macete, Eusebio; Mackanga, Jean-Rodolphe; Massougbodgi, Achille; Mayor, Alfredo; Nhacolo, Arsenio; Pahlavan, Golbahar; Ramharter, Michael; Rupérez, María; Sevene, Esperança; Vala, Anifa; Zoleko-Manego, Rella; Menéndez, Clara

2014-09-01

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86-1.22; p=0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51-0.96]; p=0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85-0.99]; p=0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52-0.88]; p=0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78-0.95]; p=0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment. Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy. ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary.

Effect of artichoke extract (Cynara scolymus L.) on palmitic-1-14C acid oxidation in rats.

PubMed

Juzyszyn, Zygmunt; Czerny, Boguslaw; Pawlik, Andrzej; Drozdzik, Marek

2008-05-01

Studies on the effect of the artichoke extract (AE) on oxidation of palmitic-1-14C acid administered intravenously to rats at a dose 25 and 50 mg/kg bw demonstrated marked enhancement of both 14CO2 expiration rate and 14CO2 recovery in the expired air. The extract suppressed accumulation of palmitic-1-14C acid in serum lipids and epididymal fat pad tissue as well. The effects of the extract on 14CO2 expiration rate, 14CO2 recovery, as well as accumulation of palmitic-1-14C acid were dose dependent. Total14CO2 recovery in expired air during 60 min was elevated by 17.3% (p < 0.05) and 52.1% (p < 0.001) in rats administered the extract at a dose of 25 and 50 mg/kg, respectively. The rats supplemented with the AE at a dose of 25 and 50 mg/kg bw were characterized by 10.0% (not significant) and 19% (p < 0.05) decrease in( 14)C radioactivity of serum lipids as well as reduction of epididymal fat tissue 14C radioactivity by 8.7 and 17.5% (p < 0.05), respectively, in comparison with the control rats. Thus, the results demonstrate that the AE possess stimulatory properties with respect to oxidation of palmitic acid administered to rats, and provide new information on the mechanism of antilipemic activity of the extract associated with activation of lipid oxidation in the organism.

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.

PubMed

Kalderon, N; Xu, S; Koutcher, J A; Fuks, Z

2001-06-22

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.

Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin

2013-03-15

Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) inmore » the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.« less

GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs.

PubMed

Guerrouahen, Bella S; Hahn, Tobias; Alderman, Zefora; Curti, Brendan; Urba, Walter; Akporiaye, Emmanuel T

2016-03-08

Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer.

Time-lapse changes of P- and S-wave velocities and shear wave splitting in the first year after the 2011 Tohoku earthquake, Japan: shallow subsurface

NASA Astrophysics Data System (ADS)

Sawazaki, Kaoru; Snieder, Roel

2013-04-01

We detect time-lapse changes in P- and S-wave velocities (hereafter, VP and VS, respectively) and shear wave splitting parameters associated with the 2011 Tohoku earthquake, Japan, at depths between 0 and 504 m. We estimate not only medium parameters but also the 95 per cent confidence interval of the estimated velocity change by applying a new least squares inversion scheme to the deconvolution analysis of KiK-net vertical array records. Up to 6 per cent VS reduction is observed at more than half of the analysed KiK-net stations in northeastern Japan with over 95 per cent confidence in the first month after the main shock. There is a considerable correlation between the S-wave traveltime delay and the maximum horizontal dynamic strain (MDS) by the main shock motion when the strain exceeds 5 × 10- 4 on the ground surface. This correlation is not clearly observed for MDS at the borehole bottom. On the contrary, VP and shear wave splitting parameters do not show systematic changes after the Tohoku earthquake. These results indicate that the time-lapse change is concentrated near the ground surface, especially in loosely packed soil layers. We conclude that the behaviour of VP, VS and shear wave splitting parameters are explained by the generation of omnidirectional cracks near the ground surface and by the diffusion of water in the porous subsurface. Recovery of VS should be related to healing of the crack which is proportional to the logarithm of the lapse time after the main shock and/or to decompaction after shaking.

Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting.

PubMed

Helmy, Sally A

2015-01-01

Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after splitting was less than 1.5% for all drugs. Bromazepam, carvedilol, and digoxin showed the highest powdering loss during the tablet-splitting process. Tablet splitting could be safer and easier when drug- and patient-specific criteria have been met. Tablet size, shape, and hardness may also play a role in the decision to split a tablet or not. Tablets containing drugs with a wide therapeutic index and long half-life might be more suitable candidates for division. Dose variation exceeded a proxy USP specification for more than one-third of sampled half tablets of bromazepam, carvedilol, bisoprolol, and digoxin. Drug content variation in half tablets appeared to be attributed to weight variation due to fragment or powder loss during the splitting process.

EFFECT OF $gamma$-RAYS ON THE BIOCHEMICAL PROPERTIES OF WHEAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sosedov, N.I.; Vakar, A.B.

1963-01-01

Progress in the Soviet Union on radiation effects on biochemical and baking properties of wheat is reported. biochemical analysis of the various forms of nitrogenous substances in wheat with moisture contents of 13.4 and 25.8 percent after irradiation with gamma rays shows that the radiation effects on giuten are dependent upon moisture content. Gluten in dry grain exposed to gamma rays became weak, inelastic, and too extensile while that in moist grain became excessively stiff with consequent loss of extensibility and cohesion. In dry irradiated grain increases were found in protein substance solubility and protein splitting, whereas in irradiated grainmore » with a higher moisture content, there was less protein splitting and solubility of protein substances was reduced. When the moisture content was 16.4-percent, radintion damage was least, the two opposite sets of deleterious effects being somewhat (not completely) balanced. The different effects of the same radiation doses on moist and dry grain was corfirmed by spectrophotometric examination. Large gamma doses increase the quantity of reducing sugars and decrease the starch content. These carbohydrate changes are more pronounced with dry than with moist grain. It is concluded that with present knowledge and techniques the method of radiational treatment of grain cannot be recommended for practical use. (H.M.G.)« less

Intrathecal Baclofen Dosing Regimens: A Retrospective Chart Review.

PubMed

Clearfield, Jacob S; Nelson, Mary Elizabeth S; McGuire, John; Rein, Lisa E; Tarima, Sergey

2016-08-01

To examine dosing patterns in patients receiving baclofen via intrathecal baclofen pumps to assess for common patterns by diagnosis, ambulation ability, and affected limbs distribution. This trial study included 25 patients with baclofen pumps selected from the 356 patients enrolled in our center's baclofen pump program. Selection was done by splitting all patients into diagnostic categories of stroke, multiple sclerosis, traumatic/anoxic brain injury, cerebral palsy, and spinal cord injury, and then, five patients were randomly selected from each diagnosis.A systematic chart review was then conducted for each patient from Jan 1, 2008, through September 16, 2013, to look at factors including mean daily dose at end of study, and among those implanted during the study mean initial stable dose and time to initial stable dose. Analysis of mean daily dose across diagnoses found significant differences, with brain injury, cerebral palsy, and spinal cord injury patients having higher doses while multiple sclerosis and stroke patients required lower doses. Nonambulatory patients strongly trended to have higher daily doses than ambulatory patients. Similar trends of mean initial stable dose being higher in a similar pattern as that of end mean daily dose were seen according to diagnoses and ambulatory status, although statistical significance could not be achieved with the small sample size. Significant differences in dosing were found between diagnoses and trended to differ by ambulatory status at the end of the study, and similar trends could be observed in achieving initial stable dose. © 2015 International Neuromodulation Society.

Automated segmentation and dose-volume analysis with DICOMautomaton

NASA Astrophysics Data System (ADS)

Clark, H.; Thomas, S.; Moiseenko, V.; Lee, R.; Gill, B.; Duzenli, C.; Wu, J.

2014-03-01

Purpose: Exploration of historical data for regional organ dose sensitivity is limited by the effort needed to (sub-)segment large numbers of contours. A system has been developed which can rapidly perform autonomous contour sub-segmentation and generic dose-volume computations, substantially reducing the effort required for exploratory analyses. Methods: A contour-centric approach is taken which enables lossless, reversible segmentation and dramatically reduces computation time compared with voxel-centric approaches. Segmentation can be specified on a per-contour, per-organ, or per-patient basis, and can be performed along either an embedded plane or in terms of the contour's bounds (e.g., split organ into fractional-volume/dose pieces along any 3D unit vector). More complex segmentation techniques are available. Anonymized data from 60 head-and-neck cancer patients were used to compare dose-volume computations with Varian's EclipseTM (Varian Medical Systems, Inc.). Results: Mean doses and Dose-volume-histograms computed agree strongly with Varian's EclipseTM. Contours which have been segmented can be injected back into patient data permanently and in a Digital Imaging and Communication in Medicine (DICOM)-conforming manner. Lossless segmentation persists across such injection, and remains fully reversible. Conclusions: DICOMautomaton allows researchers to rapidly, accurately, and autonomously segment large amounts of data into intricate structures suitable for analyses of regional organ dose sensitivity.

Use of split-thickness plantar skin grafts in the management of leg and foot skin defects.

PubMed

Liu, Hung-Hui; Chang, Chun-Kai; Huang, Chih-Han; Wu, Jen-Ru; Chen, Chun-Yu; Huang, Dun-Wei; Chu, Tzi-Shiang; Hsu, Kuo-Feng; Wang, Chi-Yu; Chiang, I-Han; Ou, Kuang-Ling; Wang, Chih-Hsin; Dai, Niann-Tzyy; Chen, Shyi-Gen; Tzeng, Yuan-Sheng

2018-05-24

The basic principle of donor site selection is to take skin from areas that will heal with minimal scarring while balancing the needs of the recipient site. For skin loss from the lower legs and feet, the most common harvest site for split-thickness skin grafts is the anterior or posterior thigh; grafts from the plantar areas have been mostly used to cover the volar aspect of digits and palms. Between September 2015 and September 2017, 42 patients with areas of skin loss on the legs or feet were treated with plantar skin grafts because of their cosmetic benefits and the convenience of the surgical procedure and postoperative wound care. Our technique of harvesting a single layer of split-thickness skin graft (0.014 in. thick) from a non-weight-bearing area of the foot of the injured leg is simple and provided good functional and cosmetic outcomes at both the donor and recipient sites. All patients were very satisfied with the recovery progress and final results. Therefore, in the management of skin defects in the lower legs or feet that comprise less than 1.5% of the total body surface area, our surgical method is a reliable alternative to anterior or posterior thigh skin grafting. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Functional recovery upon human dental pulp stem cell transplantation in a diabetic neuropathy rat model.

PubMed

Datta, Indrani; Bhadri, Naini; Shahani, Pradnya; Majumdar, Debanjana; Sowmithra, Sowmithra; Razdan, Rema; Bhonde, Ramesh

2017-10-01

Diabetic neuropathy (DN) is among the most debilitating complications of diabetes. Here, we investigated the effects of human dental pulp stem cell (DPSC) transplantation in Streptozotocin (STZ)-induced neuropathic rats. Six weeks after STZ injection, DPSCs were transplanted through two routes, intravenous (IV) or intramuscular (IM), in single or two repeat doses. Two weeks after transplantation, a significant improvement in hyperalgesia, grip-strength, motor coordination and nerve conduction velocity was observed in comparison with controls. A rapid improvement in neuropathic symptoms was observed for a single dose of DPSC IV; however, repeat dose of DPSC IV did not bring about added improvement. A single dose of DPSC IM showed steady improvement, and further recovery continued upon repeat IM administration. DPSC single dose IV showed greater improvement than DPSC single dose IM, but IM transplantation brought about better improvement in body weight. A marked reduction in tumor necrosis factor (TNF) α and C-reactive protein (CRP) levels was observed in the blood plasma for all treated groups, as compared with controls. With respect to inflammatory cytokines, repeat dose of DPSC IM showed further improvement, suggesting that a repeat dose is required to maintain the improved inflammatory state. Gene expression of inflammatory markers in liver confirmed amelioration in inflammation. Arachidonic acid level was unaffected by IV DPSC transplantation but showed noticeable increase through IM administration of a repeat dose. These results suggest that DPSC transplantation through both routes and dosage was beneficial for the retrieval of neuropathic parameters of DN; transplantation via the IM route with repeat dose was the most effective. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A new dose of maximal-intensity interval training in hypoxia to improve body composition and hemoglobin and hematocrit levels: a pilot study.

PubMed

Camacho-Cardenosa, Marta; Camacho-Cardenosa, Alba; Martínez Guardado, Ismael; Marcos-Serrano, Marta; Timon, Rafael; Olcina, Guillermo

2017-01-01

This pilot study had the aim to determine the effects of a new dose of maximal-intensity interval training in hypoxia in active adults. Twenty-four university student volunteers were randomly assigned to three groups: hypoxia group, normoxia group or control group. The eight training sessions consisted of 2 sets of 5 repeated sprints of 10 seconds with a recovery of 20 seconds between sprints and a recovery period of 10 minutes between sets. Body composition was measured following standard procedures. A blood sample was taken for an immediate hematocrit (HCT) and hemoglobin (Hb) concentration assessment. An all-out 3-ute test was performed to evaluate ventilation parameters and power. HCT and Hb were significantly higher for the hypoxia group in Post- and Det- (P=0.01; P=0.03). Fat mass percentage was significantly lower for the hypoxia group in both assessments (P=0.05; P=0.05). The hypoxia group underwent a significant increase in mean power after the recovery period. A new dose of 8 sessions of maximal-intensity interval training in hypoxia is enough to decrease the percentage of fat mass and to improve HCT and Hb parameters and mean muscle power in healthy and active adults.

Management of an unusual extreme extension contracture of the wrist: role of a custom-designed exercise program in achieving a good range of movement and prevention of recontraction.

PubMed

Saraiya, Hemant

2003-01-01

An extreme extension contracture of wrist with dorsal contracture of fingers 15 years after burn injury is described. Shortening of extensor tendons, secondary lengthening of flexor tendons, contracted wrist joint capsule, unusual dislocation of carpals, dorsal dislocation of metacarpophalangeal joints of fingers, and provision of sufficient amount of good-quality skin were some of the issues that had to be addressed in treatment. The contracture was released, the carpals and metacarpophalangeal joint dislocations were corrected and fixed with K wires, and the resulting defect was covered with a sheet split-thickness skin graft. An exercise program was designed that consisted of isotonic, isokinetic, and isometric resistance exercises and passive, active, and active-assistive range of motion exercises. These exercises were pursued with the intention of increasing dynamic strength, endurance, and overall functional recovery of the flexor muscles by exploiting the immature nature of early scar tissue. The resultant enhanced flexor muscle power from exercises along with the dynamic splint helped in lengthening of extensor tendons, wrist joint capsule, and split-thickness skin graft. It also helped in resisting the recontracting tendency, with further recovery of good range of wrist and fingers movements, obviating the need of tendon-lengthening surgery and flap coverage. One and half years of follow up didn't show any sign of recontracture, and the patient was able to perform his routine activities. Postburn wrist contractures of such magnitude have been seldom described. Emphasis is put on simple contracture release and a postoperative exercise program.

Dosages of cold-water immersion post exercise on functional and clinical responses: a randomized controlled trial.

PubMed

Machado, A F; Almeida, A C; Micheletti, J K; Vanderlei, F M; Tribst, M F; Netto Junior, J; Pastre, C M

2017-11-01

Cold-water immersion (CWI) is one of the recovery techniques commonly used by athletes for post-exercise recovery. Nevertheless, the effects of CWI using different temperatures and the dose-response relationship of this technique have not yet been investigated. The aims of this study were to compare the effects of two strategies of CWI, using different water temperatures with passive recovery post exercise in the management of some markers of muscle damage, and to observe whether any of the techniques used caused deleterious effects on performance. Sixty healthy male participants performed an eccentric protocol to induce muscle damage and were then randomized to one of three groups (CWI1: 15 min at 9 °C; CWI2: 15 min at 14 °C; CG: control group). Levels of creatine kinase, muscle soreness, pain threshold, perception of recovery, and maximal voluntary isometric contraction were monitored up to 96 h post exercise. A large effect for time for all outcomes was observed [P < 0.001; CK (ES = 0.516), muscle soreness (ES = 0.368); pain threshold (ES = 0.184); perception of recovery (ES = 0.565); MVIC (ES = 0.273)]. CWI groups presented an earlier recovery for muscle soreness with lower ratings immediately post recovery. For delayed effects, the application of CWI2 (15 min at 14 °C) presented earlier recovery compared with CWI1 and control condition for maximal voluntary isometric contraction (P < 0.05). There were no significant group and interaction (Group × Time) effects. CWI groups acted more efficiently for muscle soreness and performance considering the time of recovery was observed. No evidence was found to suggest dose-response relationship and deleterious effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Speed of onset of bronchodilator response to salbutamol inhaled via different devices in asthmatics: a bioassay based on functional antagonism

PubMed Central

Lavorini, Federico; Geri, Pietro; Mariani, Laura; Marmai, Cecilia; Maluccio, Nazzarena Maria; Pistolesi, Massimo; Fontana, Giovanni A

2006-01-01

Aims To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. Methods Eighteen patients inhaled methacholine (MCh) until FEV1 decreased by 35% of control. Following administration of placebo, 200 µg salbutamol or 400 µg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV1 and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. Results For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV1 and volume-adjusted mid-expiratory flow similar to those obtained with 200 µg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) µg, 395 (95% CI 388, 404) µg and 404 (95% CI 393, 415) µg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). Conclusions Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus. PMID:16995861

Evaluation of hematopoietic progenitors in hematopoietic progenitor cell transplants. CD34+ dose effect in marrow recovery. Retrospective analysis in 38 patients.

PubMed

Gabús, R; Magariños, A; Zamora, M; De Lisa, E; Landoni, A I; Martínez, G; Canessa, C; Giordano, H; Bodega, E

1999-08-01

Our main goal was to evaluate the CD34+ dose in patients undergoing haemotopoietic stem celltransplantation and its results in terms of recovery of neutrophile and platelet counts, transfusion requirements, days of fever, antibiotic requirements and length of hospital stay. We studied 38 consecutive patients with haematological malignancies transplanted at our Department, from Feb. 96 through Sept. 98. The CD34+ cell quantification technique was standardized, using a modification of the ISAGHE 96 protocol. Patients were sorted into three groups according to the CD34+ count administered: a) between 3 and 5 x 10(6) cells/kg; b) between 5 and 10 x 10(6) cells/kg; c) > 10 x 10(6) CD34+ cells/kg. As a secondary end point, results were assessed according to the number of aphereses required to arrive at the target count of CD34+, separating those patients that required only 1 or 2 aphereses versus those requiring 3 or more. Finally, an analysis was made of the results of transplantation comparing the different sources of stem cells (PBSC versus PBSC + B.M.). The best results were obtained in the group with cells between 3 and 5 x 10(6) CD34+. No statistically significant advantages were found in the group with cells over 5. The supra-optimal dose of more 10 x 10(6) would yield no additional beneficial results, while they can imply a greater infusion of residual tumor cells. The number of aphereses had no impact on engraftment. Results obtained with PBSC transplants were better than those with BM+PBSC in terms of neutrophile and platelet recovery. The number of CD34+ cells remains the main element in stem cell transplantation to evaluate the haematopoietic recovery after engraftment. Minimum and optimum yields remain unclear. Centers should establish their own optimal dose based on local methodologies and outcomes, maximizing costs and benefits.

Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.

PubMed

Minic, Zeljka; Zhang, Yanhua; Mao, Guangzhao; Goshgarian, Harry G

2016-03-23

Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients. Copyright © 2016 the authors 0270-6474/16/363441-12$15.00/0.

A review of the evidence of zolpidem efficacy in neurological disability after brain damage due to stroke, trauma and hypoxia: A justification of further clinical trials.

PubMed

Sutton, J A; Clauss, R P

2017-01-01

During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions. Then positron emission tomography scans and electroencephalography detected renewed metabolic and neuronal activity. Placebo or a similar, gamma-aminobutyric acid (GABA)-ergic, sedative zopiclone has no such effect. The effect appears only several months after the injury, reflecting recent evidence in mice of substantial differences between the states of GABA receptors in acute and chronic repair phases of recovery. Zolpidem's good safety record and rapid absorption further indicate a need for more clinical trials. List of acronyms: BOLD, Blood-Oxygen-Level Dependent contrast imaging in MRI; CRS, Coma Recovery Scale; CRS-R, Coma Recovery Scale Revised; CSI, Cerebral State Index; CSM, Cerebral State Monitor; DOC, Disorder of Consciousness; EEG, Electro Encephalography; FDG-PET, FluoroDeoxyGlucose-Positron Emission Tomography; FTD, Frontotemporal dementia; GABA, Gamma-Aminobutyric Acid; MCS, Minimally Conscious State; M-EEG, Magneto-Encephalography; MRI, Magnetic Resonance Image; MSN, Median Spiny Neurones; PET, Positron Emission Tomography; PVS, Persistent Vegetative Sate; RLAC, Rancho Los Amigos Cognitive scores; SPECT, Single-photon emission computed tomography; TFES, Tinetti Falls Efficacy Scale; 99mTc HMPAO, Technetium hexamethylpropyleneamine oxime.

Rapid expansion of T cells: Effects of culture and cryopreservation and importance of short-term cell recovery.

PubMed

Sadeghi, Arian; Ullenhag, Gustav; Wagenius, Gunnar; Tötterman, Thomas H; Eriksson, Fredrik

2013-06-01

Successful cell therapy relies on the identification and mass expansion of functional cells for infusion. Cryopreservation of cells is an inevitable step in most cell therapies which also entails consequences for the frozen cells. This study assessed the impact of cryopreservation and the widely used protocol for rapid expansion of T lymphocytes. The effects on cell viability, immunocompetence and the impact on apoptotic and immunosuppressive marker expression were analyzed using validated assays. Cryopreservation of lymphocytes during the rapid expansion protocol did not affect cell viability. Lymphocytes that underwent mass expansion or culture in high dose IL-2 were unable to respond to PHA stimulation by intracellular ATP production immediately after thawing (ATP = 16 ± 11 ng/ml). However, their reactivity to PHA was regained within 48 hours of recovery (ATP = 356 ± 61 ng/ml). Analysis of mRNA levels revealed downregulation of TGF-β and IL-10 at all time points. Culture in high dose IL-2 led to upregulation of p73 and BCL-2 mRNA levels while FoxP3 expression was elevated after culture in IL-2 and artificial TCR stimuli. FoxP3 levels decreased after short-term recovery without IL-2 or stimulation. Antigen specificity, as determined by IFNγ secretion, was unaffected by cryopreservation but was completely lost after addition of high dose IL-2 and artificial TCR stimuli. In conclusion, allowing short-time recovery of mass expanded and cryopreserved cells before reinfusion could enhance the outcome of adoptive cell therapy as the cells regain immune competence and specificity.

Dark recovery of uv-irradiated phage TI. I. A minor recovery effect whose exclusion permits the study of survival kinetics under presumably repairless conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harm, W.

1973-12-01

The survival of uv-irradiated phage Tl is much lower in excision repair- deficient than in excision repair-proficient E.coli cells, due to lack of host ceH reactivation (HCR). sn additional decrease in phage survival occurs when repair-deficient (HCR-) host cells have been exposed to uv doses from 3000 to 10,000 erg mm/-sup 2/ of 254 nm uv radiation prior to infection. The observed effect is attributed to loss of a minor phage recovery process, which requires neither the bacterial excision repair nor the bacterial REC repair system. This type of recovery is little affected by caffeine or acriflavine at concentrations thatmore » preclude HCR completely. Its full inhibition by uv-irradiation of the cells requires on approximately 8 times larger dose than complete inhibition of HCR. In heavily preirradiated cells, the TI burst size is extremely small and multiplicity reactivation is considerably less extensive than in unirradiated cells. Presumably the survival of singly infecting Tl in these cells reflects absence of any type of repair. The observed phage sensitivity and shape of the curve are compatible with the expectation for completely repairless conditions. The mechanism underlying the minor recovery is not known; theoretical considerations make a phage REC repair mechanism seem likely. (auth)« less

The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams.

PubMed

Masunaga, Shin-Ichiro; Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Sanada, Yu; Suzuki, Minoru; Maruhashi, Akira; Ono, Koji

2015-08-01

The aim of the study was to clarify the effect of p53 status of tumor cells on radiosensitivity of solid tumors following accelerated carbon-ion beam irradiation compared with γ-rays or reactor neutron beams, referring to the response of intratumor quiescent (Q) cells. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at a high or reduced dose-rate. Other tumor-bearing mice received reactor thermal or epithermal neutrons at a reduced dose-rate. Immediately or 9 hours after the high dose-rate irradiation (HDRI), or immediately after the reduced dose-rate irradiation (RDRI), the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The difference in radiosensitivity between the total (P + Q) and Q cells after γ-ray irradiation was markedly reduced with reactor neutron beams or carbon-ion beams, especially with a higher linear energy transfer (LET) value. Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. In both total and Q cells within both SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially with a higher LET, showed little recovery capacity through leaving an interval between HDRI and the assay or decreasing the dose-rate. The recovery from radiation-induced damage after γ-ray irradiation was a p53-dependent event, but little recovery was found after carbon-ion beam irradiation. With RDRI, the radiosensitivity to reactor thermal and epithermal neutron beams was slightly higher than that to carbon-ion beams. For tumor control, including intratumor Q-cell control, accelerated carbon-ion beams, especially with a higher LET, and reactor thermal and epithermal neutron beams were very useful for suppressing the recovery from radiation-induced damage irrespective of p53 status of tumor cells.

The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams

PubMed Central

Masunaga, Shin-ichiro; Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Sanada, Yu; Suzuki, Minoru; Maruhashi, Akira; Ono, Koji

2015-01-01

Background The aim of the study was to clarify the effect of p53 status of tumor cells on radiosensitivity of solid tumors following accelerated carbon-ion beam irradiation compared with γ-rays or reactor neutron beams, referring to the response of intratumor quiescent (Q) cells. Methods Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor-bearing mice received 5-bromo-2’-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at a high or reduced dose-rate. Other tumor-bearing mice received reactor thermal or epithermal neutrons at a reduced dose-rate. Immediately or 9 hours after the high dose-rate irradiation (HDRI), or immediately after the reduced dose-rate irradiation (RDRI), the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Results The difference in radiosensitivity between the total (P + Q) and Q cells after γ-ray irradiation was markedly reduced with reactor neutron beams or carbon-ion beams, especially with a higher linear energy transfer (LET) value. Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. In both total and Q cells within both SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially with a higher LET, showed little recovery capacity through leaving an interval between HDRI and the assay or decreasing the dose-rate. The recovery from radiation-induced damage after γ-ray irradiation was a p53-dependent event, but little recovery was found after carbon-ion beam irradiation. With RDRI, the radiosensitivity to reactor thermal and epithermal neutron beams was slightly higher than that to carbon-ion beams. Conclusion For tumor control, including intratumor Q-cell control, accelerated carbon-ion beams, especially with a higher LET, and reactor thermal and epithermal neutron beams were very useful for suppressing the recovery from radiation-induced damage irrespective of p53 status of tumor cells. PMID:28983338

Pharmacodynamics of alfaxalone after single-dose intramuscular administration in red-eared sliders (Trachemys scripta elegans): a comparison of two different doses at two different ambient temperatures.

PubMed

Shepard, Molly K; Divers, Stephen; Braun, Christina; Hofmeister, Erik H

2013-11-01

This study compares the pharmacodynamics of two different doses of alfaxalone administered intramuscularly (IM) to red-eared sliders at two ambient temperatures. Prospective blinded crossover experimental study. Nine adult female sliders (Trachemys scripta elegans). Following a 2-week acclimation at 22-25 °C, nine sliders were randomly assigned to receive alfaxalone, 10 mg kg(-1) (W10), or 20 mg kg(-1) (W20) IM. Each turtle received each dose, with a minimum 7-day washout period. A blinded observer evaluated heart rate (HR), palpebral and corneal reflexes, muscle relaxation, handling, and response to toe pinch at the following points: pre-injection, and 5, 12, 20, 30, 45, 60, and 120 minutes post-injection. Turtles then acclimated to 18-20 °C for 63 days, and the experiment was repeated in this lower-temperature environment, with treatment groups C10 (alfaxalone 10 mg kg(-1)) and C20 (alfaxalone 20 mg kg(-1)) subjected to the same crossover design. C10 and C20 groups had significantly lower intraanesthetic HR than W10 or W20, respectively. C10 and W20 were significantly more relaxed and easier to handle than W10. No significant differences were observed in palpebral reflex, nor responsiveness to the toe pinch stimulus. None of the turtles lost corneal reflex. W20 and C20 had prolonged recoveries, compared to low-dose groups within the same temperature environment. Recovery was also longer at C20 and C10 compared to W10. Turtles given 10 mg kg(-1) were more relaxed and easier to handle in cold than warm conditions. Warm turtles were more relaxed and easier to handle when given 20 mg kg(-1) than those given 10 mg kg(-1). Cold conditions correlated with lower HR and longer recovery time for each dose category. The turtles had dose-dependent and inconsistent responses to alfaxalone. Lower ambient temperature augmented the behavioral effects of this drug. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

PubMed

Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

2016-05-01

Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as shown in (a). Furthermore, the alterations in local spinal blood flow could be significantly alleviated with low dose estrogen therapy. This therapy led to the preservation of the structural integrity of the spinal cord (b), which in turn led to the improved functional recovery as shown (c). © 2016 International Society for Neurochemistry.

ESR analysis of natural and gamma irradiated coriander (Coriandrum sativum L.) seeds

NASA Astrophysics Data System (ADS)

Sezer, M. Özgür; Kaplan, Necati; Sayin, Ulku

2017-12-01

Electron spin resonance (ESR) is a powerful technique to detect radicals trapped in cellulosic food products and has been suggested as a useful method for identification of irradiated herbal foodstuffs. Coriander spice which has important medicinal properties was investigated using ESR spectroscopy. Radicals in natural and irradiated coriander samples were determined at room temperature. ESR spectra of natural sample were characterized by a single central signal with ? value and gamma irradiation produced satellite peaks attributed to cellulose-like radical which is used as a marker for detection of irradiated cellulosic plant products. The spectroscopic splitting values of radicals were determined. Dose dependency and stability of this center were analyzed by dose response and kinetic measurements. The reported results about activation energy, thermal life time and dose response relationship of the cellulose-like radical accurately prove that ESR can be used for identification of irradiated coriander spice seeds.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

PubMed

Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

2017-06-01

In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

Simulations of Dynamics and Transport during the September 2002 Antarctic Major Warming

NASA Technical Reports Server (NTRS)

Manney, Gloria L.; Sabutis, Joseph L.; Allen, Douglas R.; Lahoz, Willian A.; Scaife, Adam A.; Randall, Cora E.; Pawson, Steven; Naujokat, Barbara; Swinbank, Richard

2005-01-01

A mechanistic model simulation initialized on 14 September 2002, forced by 100-hPa geopotential heights from Met Office analyses, reproduced the dynamical features of the 2002 Antarctic major warming. The vortex split on approx.25 September; recovery after the warming, westward and equatorward tilting vortices, and strong baroclinic zones in temperature associated with a dipole pattern of upward and downward vertical velocities were all captured in the simulation. Model results and analyses show a pattern of strong upward wave propagation throughout the warming, with zonal wind deceleration throughout the stratosphere at high latitudes before the vortex split, continuing in the middle and upper stratosphere and spreading to lower latitudes after the split. Three-dimensional Eliassen-Palm fluxes show the largest upward and poleward wave propagation in the 0(deg)-90(deg)E sector prior to the vortex split (coincident with the location of strongest cyclogenesis at the model's lower boundary), with an additional region of strong upward propagation developing near 180(deg)-270(deg)E. These characteristics are similar to those of Arctic wave-2 major warmings, except that during this warming, the vortex did not split below approx.600 K. The effects of poleward transport and mixing dominate modeled trace gas evolution through most of the mid- to high-latitude stratosphere, with a core region in the lower-stratospheric vortex where enhanced descent dominates and the vortex remains isolated. Strongly tilted vortices led to low-latitude air overlying vortex air, resulting in highly unusual trace gas profiles. Simulations driven with several meteorological datasets reproduced the major warming, but in others, stronger latitudinal gradients at high latitudes at the model boundary resulted in simulations without a complete vortex split in the midstratosphere. Numerous tests indicate very high sensitivity to the boundary fields, especially the wave-2 amplitude. Major warmings occurred for initial fields with stronger winds and larger vortices, but not smaller vortices, consistent with the initiation of wind-deceleration by upward-propagating waves near the poleward edge of the region where wave 2 can propagate above the jet core. Thus, given the observed 100-hPa boundary forcing, stratospheric preconditioning is not needed to reproduce a major warming similar to that observed. The anomalously strong forcing in the lower stratosphere can be viewed as the primary direct cause of the major warming.

Characterization and optical studies of 90/10 (wt/wt%) PVA/β-chitin blend irradiated with γ-rays.

PubMed

Abd El-Kader, F H; Gaafer, S A; Abd El-Kader, M F H

2014-10-15

X-ray diffraction, IR spectroscopy and UV/visible spectra were studied as a function of gamma irradiation doses (5-100kGy) for 90/10 (wt/wt%) PVA/β-chitin. A new intense reflection peak at 2θ=21.5° appeared in the X-ray spectrum of the sample irradiated at 50kGy γ-dose. Besides, the band centered at 2931cm(-1) in IR spectrum splits into two clearly separated bands around 2919 and 2941cm(-1) for the sample irradiated at 10kGy γ-dose. The disappearance of the absorption band at 280nm of PVA in the blend sample indicates that the ligand PVA becomes opaque in the UV region and provides evidence for the miscibility between homopolymers. The value of absorbance, in UV/visible range, at 10kGy γ-dose was the highest one compared to the other γ-doses. The location of the γ-doses on the chromaticity diagram was different, indicating the change in the spectral colors of the investigated blend. In addition, the absorption edge, band tail and color parameters values were determined as a function of γ-doses. Copyright © 2014 Elsevier B.V. All rights reserved.

Polyethylene Glycol-3350 (Miralax®)+1.9-L sports drink (Gatorade®)+2 tablets of bisacodyl results in inferior bowel preparation for colonoscopy compared with Polyethylene Glycol-Ascorbic Acid (MoviPrep®).

PubMed

Khan, Maqsood Ahmed; Patel, Kevin B; Nooruddin, Mohammed; Swanson, Garth; Fogg, Louis; Keshavarzian, Ali; Brown, Michael

2018-01-01

Polyethylene glycol (PEG)-3350, approved by Food and Drug Administration (FDA) only for constipation, combined with 1.9 L of sports drink (SD) (GatoradeR) and bisacodyl (B) is commonly used in outpatient practice for bowel preparation due to cited patient satisfaction and tolerability of this specific regimen. We aim to compare PEG-3350 (MiralaxR) with PEG-AA-based (MoviPrepR) in terms of efficacy, patient satisfaction, and the effects of these two regimen on serum electrolytes. This study is a prospective, single-blinded, block randomized trial comparing single-dose PEG-3350+SD+B to split-dose 2-L PEG-AA in the outpatient endoscopy unit in patients undergoing colonoscopy. Basic metabolic profiles were checked on the day of randomization and on the day of procedure. Patients completed a survey on the day of procedure. Bowel preparation quality was assessed using the Boston Bowel Preparation Scale (BBPS) by two endoscopists and a nurse present during the procedure. We randomized 150 patients (74 PEG-3350+SD+B and 76 PEG-AA). The PEG-AA group had significantly higher BBPS scores in the right colon by Endoscopist 1, Nurse, and Endoscopist 2 (p 0.005, <0.000, 0.001) and in the left and transverse colon by Nurse and Endoscopist 2 (p 0.004, 0.26, 0.000, 0.006). There was no statistically significant difference in patient satisfaction or change in serum electrolytes between the two groups. Use of single-dose PEG-3350+SD+B results in inferior bowel preparation for colonoscopy compared with split-dose PEGAA and does not provide any advantage in regards to patient satisfaction. We therefore recommend discontinuing the use of PEG 3350 for bowel preparation.

Laparoscopic cholecystectomy under spinal anesthesia: comparative study between conventional-dose and low-dose hyperbaric bupivacaine

PubMed Central

Imbelloni, Luiz Eduardo; Sant’Anna, Raphael; Fornasari, Marcos; Fialho, José Carlos

2011-01-01

Background Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture. Methods A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg) or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 μg). Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups. Results All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia. Conclusion Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 μg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 μg, causes markedly less hypotension. The low-dose strategy may have an advantage in ambulatory patients because of the earlier recovery of motor and sensory function and earlier discharge. PMID:22915892

Biological Effects of Protracted Exposure to Ionizing Radiation: Review, Analysis, and Model Development

DTIC Science & Technology

1991-11-01

dynamics, physiological changes, morphologi- cal changes, cell/tissue damage and recovery mechanisms, and existing radiobiological injury and recovery...humans and the ferret. The gut injury model (GIM) is a three-compartment hierarchial- type tissue model to simulate radiation-induced changes in the...Prodromal Symptoms Diarrhea Gastrointestinal Symptoms Dose Rate Cell Survival Intestinal Injury Fatigability Cell Damage Cell Repair Cell Proliferation

Oral administration of citrus pulp reduces gasrointestinal recovery of orally dosed Escherichia coli F18 in weaned pigs

USDA-ARS?s Scientific Manuscript database

The effects of citrus pulp (CTP), on the immune and cortisol responses to E. coli F18 inoculation and subsequent E. coli recovery were evaluated in newly weaned pigs (23.3 + 1.8 d of age). Barrows were assigned to 1 of 2 treatment groups; with (CTP; n = 15) and without (Control; n = 15) the in-feed ...

Low dose decitabine in very high risk relapsed or refractory acute myeloid leukaemia in children and young adults.

PubMed

Phillips, Christine L; Davies, Stella M; McMasters, Richard; Absalon, Michael; O'Brien, Maureen; Mo, Jun; Broun, Randall; Moscow, Jeffrey A; Smolarek, Teresa; Garzon, Ramiro; Blum, William; Schwind, Sebastian; Marcucci, Guido; Perentesis, John P

2013-05-01

Low-dose decitabine has encouraging activity and tolerability in adults with acute myeloid leukaemia (AML), but paediatric experience is lacking. We report our retrospective experience with decitabine in eight children and young adults (median age 4 years) with refractory/relapsed AML, who had failed multiple regimens or were not candidates for standard retrieval regimens due to prior toxicities. Three of eight patients (38%) had complete response (CR; 1 each of CR, CR with incomplete platelet recovery and CR with incomplete count recovery). Best responses were observed after a median of 2.5 cycles (range 1-4 cycles). Four patients received subsequent allogeneic stem cell transplant, and two remain in long-term CR. © 2013 Blackwell Publishing Ltd.

The effect of dietary neonicotinoid pesticides on non-flight thermogenesis in worker bumble bees (Bombus terrestris).

PubMed

Potts, Robert; Clarke, Rebecca M; Oldfield, Sophie E; Wood, Lisa K; Hempel de Ibarra, Natalie; Cresswell, James E

2018-01-01

For bumble bees (genus Bombus), the capacity for non-flight thermogenesis is essential for two fundamental processes undertaken by adult workers, namely recovery from torpor after chilling and brood incubation. Farmland bees can be widely exposed to dietary residues of neurotoxic neonicotinoid insecticides that appear in the nectar and pollen of treated bee-attractive crops, which may harm them. An earlier study shows that dietary neonicotinoids cause complex alterations to thermoregulation in honey bees, but their effect on the thermogenic capabilities of individual bumble bees has been untested previously. We therefore conducted laboratory trials involving separate dietary exposures of bumble bees to two neonicotinoids, imidacloprid and thiamethoxam, and we measured their effects on the thoracic temperatures of bees during recovery from chilling. Specifically, we used thermal imaging to measure the rates of rewarming by individual bees after chill-induced torpor and to quantify their equilibrated thoracic temperatures post-recovery. We found that both toxicants caused dose-dependent decreases in the rates of rewarming and in the equilibrated thoracic temperatures. As previously found in honey bees, the dose-response relationship for imidacloprid exhibited a biphasic hormesis with low-dose stimulation and high-dose inhibition, for which we propose a mechanism. Our present study is among the first to detect ecologically relevant effects on bees in neonicotinoid exposures involving dietary concentrations below 5 ppb. If the effects on thoracic temperatures that we observed over a short period were sustained, they could have ecologically significant impacts on farmland bumble bees. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical-grade purification of natural killer cells in haploidentical hematopoietic stem cell transplantation.

PubMed

Meyer-Monard, Sandrine; Passweg, Jakob; Siegler, Uwe; Kalberer, Christian; Koehl, Ulrike; Rovó, Alicia; Halter, Jörg; Stern, Martin; Heim, Dominik; Alois Gratwohl, Johannes Rischewski; Tichelli, André

2009-02-01

Because of a high risk of graft-versus-host disease (GVHD), donor lymphocyte infusions with unmodified lymphapheresis products are not used after haploidentical hematopoietic stem cell transplantation. Natural killer (NK) cells have antitumor activity and may consolidate engraftment without inducing GVHD. Production of NK cells under good manufacturing practice (GMP) conditions in a sufficient number is difficult. Twenty-four apheresis procedures and subsequent NK-cell enrichment from 14 haploidentical donors were performed. NK-cell enrichment was performed using a GMP suitable immunomagnetic procedure. Factors influencing the NK-cell recovery, purity, and NK-cell dose were analyzed. A median number of 4.9 x 10(8) NK cells were obtained and median NK-cell recovery was 58 percent. Median T-cell depletion was 4.32 log. The absolute NK-cell number in the final product after processing significantly correlated with the preharvest NK-cell content of the peripheral blood (p = 0.002, r = 0.867). The NK-cell recovery was inversely correlated to the absolute NK-cell number in the apheresis product (p = 0.01, r = -0.51). The NK-cell dose per kg of body weight of the patient was inversely correlated to the weight of the patient (p = 0.007, r = -0.533). Donors with a high NK-cell count in peripheral blood are likely to provide NK-cell products with the highest cell number. However, maximal NK-cell dose is limited and high NK-cell doses may only be obtained for patients with a low body weight, making children and young adults the best candidates for NK-cell therapy.

Mechanical Behavior of a Low-Cost Ti-6Al-4V Alloy

NASA Astrophysics Data System (ADS)

Casem, D. T.; Weerasooriya, T.; Walter, T. R.

2018-01-01

Mechanical compression tests were performed on an economical Ti-6Al-4V alloy over a range of strain-rates and temperatures. Low rate experiments (0.001-0.1/s) were performed with a servo-hydraulic load frame and high rate experiments (1000-80,000/s) were performed with the Kolsky bar (Split Hopkinson pressure bar). Emphasis is placed on the large strain, high-rate, and high temperature behavior of the material in an effort to develop a predictive capability for adiabatic shear bands. Quasi-isothermal experiments were performed with the Kolsky bar to determine the large strain response at elevated rates, and bars with small diameters (1.59 mm and 794 µm, instrumented optically) were used to study the response at the higher strain-rates. Experiments were also conducted at temperatures ranging from 81 to 673 K. Two constitutive models are used to represent the data. The first is the Zerilli-Armstrong recovery strain model and the second is a modified Johnson-Cook model which uses the recovery strain term from the Zerilli-Armstrong model. In both cases, the recovery strain feature is critical for capturing the instability that precedes localization.

Hurricane Sandy science plan: coastal impact assessments

USGS Publications Warehouse

Stronko, Jakob M.

2013-01-01

Hurricane Sandy devastated some of the most heavily populated eastern coastal areas of the Nation. With a storm surge peaking at more than 19 feet, the powerful landscape-altering destruction of Hurricane Sandy is a stark reminder of why the Nation must become more resilient to coastal hazards. In response to this natural disaster, the U.S. Geological Survey (USGS) received a total of $41.2 million in supplemental appropriations from the Department of the Interior (DOI) to support response, recovery, and rebuilding efforts. These funds support a science plan that will provide critical scientific information necessary to inform management decisions for recovery of coastal communities, and aid in preparation for future natural hazards. This science plan is designed to coordinate continuing USGS activities with stakeholders and other agencies to improve data collection and analysis that will guide recovery and restoration efforts. The science plan is split into five distinct themes: coastal topography and bathymetry, impacts to coastal beaches and barriers, impacts of storm surge, including disturbed estuarine and bay hydrology, impacts on environmental quality and persisting contaminant exposures, impacts to coastal ecosystems, habitats, and fish and wildlife. This fact sheet focuses assessing impacts to coastal beaches and barriers.

Contribution of plastic waste recovery to greenhouse gas (GHG) savings in Spain.

PubMed

Sevigné-Itoiz, Eva; Gasol, Carles M; Rieradevall, Joan; Gabarrell, Xavier

2015-12-01

This paper concentrates on the quantification of greenhouse gas (GHG) emissions of post-consumer plastic waste recovery (material or energy) by considering the influence of the plastic waste quality (high or low), the recycled plastic applications (virgin plastic substitution or non-plastic substitution) and the markets of recovered plastic (regional or global). The aim is to quantify the environmental consequences of different alternatives in order to evaluate opportunities and limitations to select the best and most feasible plastic waste recovery option to decrease the GHG emissions. The methodologies of material flow analysis (MFA) for a time period of thirteen years and consequential life cycle assessment (CLCA) have been integrated. The study focuses on Spain as a representative country for Europe. The results show that to improve resource efficiency and avoid more GHG emissions, the options for plastic waste management are dependent on the quality of the recovered plastic. The results also show that there is an increasing trend of exporting plastic waste for recycling, mainly to China, that reduces the GHG benefits from recycling, suggesting that a new focus should be introduced to take into account the split between local recycling and exporting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of penile rehabilitation with low-dose vardenafil on recovery of erectile function in Japanese men following nerve-sparing radical prostatectomy

PubMed Central

Nakano, Yuzo; Miyake, Hideaki; Chiba, Koji; Fujisawa, Masato

2014-01-01

Erectile dysfunction (ED) is a major complication after radical prostatectomy (RP); however, debate continues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function (EF). This study included a total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 (46.6%) of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation (60.0%) was significantly greater than that in those without penile rehabilitation (38.2%). Of several parameters examined, the preoperative International Index of Erectile Function-5 (IIEF-5) score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP. PMID:24994781

Radiation effects on the resting and proliferating cells in normal tissue of mouse (in Japanese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayashi, S.

1972-10-01

The investigation was planned to compare the radiosensitivity of callus- forming cells in resting phase with that in proliferating phase and to compare the recovery of sublethal damage of callusforming cells in resting phase with that in proliferating phase. Experimental animals were 8-week-old female I.C.R./ J.C.L. mice. The maximum sizes of callus were nearly constant among control mice without irradiation after fracture. They, however, were inhibited with administered doses and seemed to be reflected by the Proliferating ability of callus-forming cells after irradiation. The analysis was performed by C.I.D. 50 (callus inhibition dose 50) or dose that produced a specifiedmore » inhibition of callus size in half of the subjects. The callus-forming cells in adult mice were in resting phase without any stimulations, but they extensively entered into proliferating phase after fracture. The labeling index rose around 6 hrs after fracture and reached 9% of the maximum value at 72 are after fracture. Mice were followed by x-ray projection until 60 days after irradiation to observe the callus sizes, and the maximum sizes of callus for each mouse were examined by planimetry to calculate the C.I.D. 50. The callus-forming cell was more radioresistant in resting phase by a factor of 1.5 to 2.0 than in proliferating phase. The cell in resting phase demonstrated a marked recovery of sublethal damage in 4 hrs after administration of 1.000 rads, and it showed essentially no more changes in recovery with the increased time interval to 24 hrs, while the cell in proliferating phase demonstrated almost full recovery of sublethal damage is 2 hrs after administration of 300 rads and showed a fluctuated pattern of recovery with a dip at 4 hrs of the time interval in two fractions. (auth)« less

Effect of continuous gamma-ray exposure on performance of learned tasks and effect of subsequent fractionated exposures on blood-forming tissue

NASA Technical Reports Server (NTRS)

Spalding, J. F.; Holland, L. M.; Prine, J. R.; Farrer, D. N.; Braun, R. G.

1972-01-01

Sixteen monkeys trained to perform continuous and discrete-avoidance and fixed-ratio tasks with visual and auditory cues were performance-tested before, during, and after 10-day gamma-ray exposures totaling 0, 500, 750, and 1000 rads. Approximately 14 months after the performance-test exposures, surviving animals were exposed to 100-rad gamma-ray fractions at 56-day intervals to observe injury and recovery patterns of blood-forming tissues. The fixed-ratio, food-reward task performance showed a transient decline in all dose groups within 24 hours of the start of gamma-ray exposure, followed by recovery to normal food-consumption levels within 48 to 72 hours. Avoidance tasks were performed successfully by all groups during the 10-day exposure, but reaction times of the two higher dose-rate groups in which animals received 3 and 4 rads per hour or total doses of 750 and 1000 rads, respectively, were somewhat slower.

Single dose intravenous methyl prednisolone versus oral prednisolone in Bell's palsy: A randomized controlled trial

PubMed Central

Giri, Prithvi; Garg, Ravindra Kumar; Singh, Maneesh Kumar; Verma, Rajesh; Malhotra, Hardeep Singh; Sharma, Praveen Kumar

2015-01-01

Objectives: Corticosteroids have been used in the treatment of Bell's palsy and several other postinfectious neurological conditions. We hypothesized that administration of a single dose of intravenous (IV) methylprednisolone might be an effective alternative to oral prednisolone. Materials and Methods: In this open label, randomized trial, patients with acute Bell's palsy were randomized into two groups. One group received single dose (500 mg) of IV methylprednisolone while the other group received 10 days of oral prednisone. Outcome was assessed at 1 and 3 months with House–Brackmann scale. Results: At 3 months, 93 (79.48%) patients had completely recovered. IV methylprednisolone and oral prednisolone groups had similar recovery rates (80% vs. 78.33%, P > 0.05). Patients with Grade 2 and 3 recovered completely. In patients with Grade 6, the recovery rate was 20%. A better outcome was observed if corticosteroids were administered within 3 days of onset of palsy. Conclusion: Intravenous methylprednisolone and oral prednisolone showed equivalent benefit in patients with acute Bell's palsy. PMID:25878371

Multiple use of water in industry--the textile industry case.

PubMed

Rott, Ulrich

2003-08-01

The main aim of this article is to give a review on the state of the art of available processes for the advanced treatment of wastewater from Textile Processing Industry (TPI). After an introduction to the specific wastewater situation of the TPI the article reviews the options of process and production integrated measures. The available unit processes and examples of applied combinations of unit processes are described. A special place is given to the in-plant treatment, the reuse of the treated split flow or mixed wastewater and the recovery of textile auxiliaries and dyes.

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

PubMed

Elias, A D; Ayash, L; Anderson, K C; Hunt, M; Wheeler, C; Schwartz, G; Tepler, I; Mazanet, R; Lynch, C; Pap, S

1992-06-01

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.

Soft switching resonant converter with duty-cycle control in DC micro-grid system

NASA Astrophysics Data System (ADS)

Lin, Bor-Ren

2018-01-01

Resonant converter has been widely used for the benefits of low switching losses and high circuit efficiency. However, the wide frequency variation is the main drawback of resonant converter. This paper studies a new modular resonant converter with duty-cycle control to overcome this problem and realise the advantages of low switching losses, no reverse recovery current loss, balance input split voltages and constant frequency operation for medium voltage direct currentgrid or system network. Series full-bridge (FB) converters are used in the studied circuit in order to reduce the voltage stresses and power rating on power semiconductors. Flying capacitor is used between two FB converters to balance input split voltages. Two circuit modules are paralleled on the secondary side to lessen the current rating of rectifier diodes and the size of magnetic components. The resonant tank is operated at inductive load circuit to help power switches to be turned on at zero voltage with wide load range. The pulse-width modulation scheme is used to regulate output voltage. Experimental verifications are provided to show the performance of the proposed circuit.

Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function.

PubMed

Koshkin, Vadim S; Barata, Pedro C; Rybicki, Lisa A; Zahoor, Haris; Almassi, Nima; Redden, Alicia M; Fergany, Amr F; Kaouk, Jihad; Haber, Georges-Pascal; Stephenson, Andrew J; Ornstein, Moshe C; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian I; Grivas, Petros

2018-02-22

Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC. A retrospective analysis of patients who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR < 60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula were compared to patients with GFR ≥ 60 mL/min for NAC tolerability, pathologic complete and partial response (pPR), and the ability to undergo radical cystectomy. Thirty patients with low GFR (34-59 mL/min) and 94 patients with normal GFR (≥ 60 mL/min) were identified. Low GFR patients were older (median, 71 vs. 65 years), but other demographic and transurethral resection of bladder tumor characteristics were comparable. Low GFR patients more frequently had early NAC discontinuation (30% vs. 13%), NAC modifications (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability or outcomes were noted among low GFR patients receiving split-dose versus standard regimens. No differences were noted between low and normal GFR patients in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to cystectomy, and GFR change from baseline to after NAC. Pathologic complete response was higher among normal GFR patients (24% vs. 14%). Patients with low GFR had more NAC discontinuations and modifications, but most completed planned NAC cycles. For carefully selected patients with GFR < 60 mL/min, cisplatin-based NAC remains a treatment option. Copyright © 2018 Elsevier Inc. All rights reserved.

Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir

PubMed Central

Blanche, P; Rigolet, A; Gombert, B; Ginsburg, C; Salmon, D; Sicard, D

1999-01-01

We report a rare case of ergotism related to a single dose of ergotamine tartrate in a man with AIDS being treated with ritonavir. He was treated with a prostacyclin analogue and made a complete recovery.


Keywords: ergotism; ergotamine tartrate; AIDS; ritonavir; adverse drug reaction; HIV infection PMID:10616689

AS03-Adjuvanted, Very-Low-Dose Influenza Vaccines Induce Distinctive Immune Responses Compared to Unadjuvanted High-Dose Vaccines in BALB/c Mice

PubMed Central

Yam, Karen K.; Gupta, Jyotsana; Winter, Kaitlin; Allen, Elizabeth; Brewer, Angela; Beaulieu, Édith; Mallett, Corey P.; Burt, David S.; Ward, Brian J.

2015-01-01

During the 2009–2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted “high” (3 μg) and low-dose (0.03–0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted “high-dose” vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of “standard” doses of vaccines in pre-clinical vaccine studies. PMID:25972874

Oral administration of citrus pulp reduces gastrointestinal recovery of orally dosed Escherichia coli F18 in weaned pigs

USDA-ARS?s Scientific Manuscript database

The effects of citrus pulp (CTP) on the immune and cortisol responses to E. coli F18 inoculation and subsequent E. coli recovery were evaluated in newly weaned pigs (23.3 + 1.8 d of age). Barrows were assigned to 1 of 2 treatment groups; with (CTP; n = 15) and without (Control; n = 15) the in-feed i...

THE INFLUENCE OF ENDOTOXIN ADMINISTRATION ON THE NUTRITIONAL REQUIREMENTS OF MICE

PubMed Central

Dubos, René; Costello, Richard; Schaedler, Russell W.

1965-01-01

Albino mice lose weight within 24 hours following administration of bacterial endotoxin. The initial weight loss is proportional to the dose of endotoxin injected only when this dose is very small. The loss during the 1st day reaches a maximum with 10 to 30 µg of endotoxin; larger doses increase the duration of the overall effect. The rate at which mice regain weight after administration of endotoxin is markedly influenced by the composition of the diet. Recovery was rapid and complete within a few days when the animals were fed commercial pellets or a semisynthetic diet containing casein. In contrast, recovery was slow and incomplete when wheat gluten was used instead of casein in the diet. The deleterious effect of the gluten diet was less marked in older than in younger animals, probably because the latter have less exacting nutritional requirements. It was postulated that the failure of endotoxin-treated mice to regain weight when fed the gluten diet was due to the fact that this protein is low in certain amino acids. In fact, rapid and complete recovery from the weight loss uniformly occurred when the gluten diet was supplemented with proper amounts of lysine and threonine. The composition of the diet did not influence the extent of the initial loss of weight caused by endotoxin, nor did it prevent the animals from developing tolerance to this substance. PMID:5322368

Preliminary toxicity findings in dogs and rodents given the iron chelator ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) (EDHPA).

PubMed

Rosenkrantz, H; Metterville, J J; Fleischman, R W

1986-02-01

Because of a projected pilot study with EDHPA in Cooley's anemia patients, animal studies with emphasis on reversibility of potential toxic signs were performed. Young dogs were treated iv with 6-18 mg/kg or orally with 30-240 mg/kg for 14 days followed by a 16-day recovery period. Drug-induced emesis, elevated BUN changes in kidney, spleen, and thymus weights diminished during recovery. One deceased dog exhibited nephrotoxicity consisting of tubular necrosis and deposition of the iron-EDHPA complex. The latter was observed in the excreta of survivors but kidney damage was not evident. Atrophy of the spleen and thymus in the deceased dog was consistent with less intense organ weight changes in recovered survivors. In the absence of morphologic changes after recovery, the precise effect on the immune system is unknown. The iv LD50 was 53 mg/kg for rats and mice. No rodent deaths occurred at an oral dose of 6000 mg/kg. An elevated BUN and changes in kidney, spleen, and thymus weights were confirmed in rodents given iv doses of 5-20 mg/kg or oral doses of 150-600 mg/kg for 5 days. It is cautioned that during the use of EDHPA derivatives that the functions of the renal and immune systems be monitored.

Piezosurgery for Sagittal Split Osteotomy: Procedure Duration and Postoperative Sensory Perturbation.

PubMed

Köhnke, Robert; Kolk, Andreas; Kluwe, Lan; Ploder, Oliver

2017-09-01

To evaluate piezosurgery for bilateral sagittal split osteotomy (BSSO) for its duration and inferior alveolar nerve (IAN) perturbation. In this prospective randomized study, the authors evaluated 100 BSSO procedures in 50 patients. Piezoelectric (group I) and conventional (group II) osteotomies were carried out on each side of the mandible of a patient by 2 specialists. The surgeons had at least 1 year of experience using piezosurgery. The period from incision to complete splitting of the mandibular bone was recorded (ie, procedure duration). The intraoperative status (visibility and relocation) of the IAN also was recorded. The neurosensory function of the IAN was measured by the 2-point discrimination threshold and static light touch methods before surgery and postoperatively (1, 3, and 6 weeks and 6 and 12 months). Parameters were compared between the test groups by the paired t, nonparametric Wilcoxon, or χ 2 test. Intergroup comparison showed the mean duration of osteotomy was significantly shorter for group I (17 ± 6 vs 25 ± 9 minutes; P < .001). The rate of intraoperative exposures of the IAN was slightly lower for group I (68%) compared with group II (81%). However, the difference was not relevant. Neurosensory disturbance and recovery of the IAN did not differ between groups. Piezoelectric osteotomy requires considerably less time than conventional mechanical approaches, but shows no advantage in preventing neurosensory perturbation. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

USSR and Eastern Europe Scientific Abstracts Biomedical and Behavioral Sciences No. 64

DTIC Science & Technology

1977-02-17

and the chemical composition of the grain; and yield and grain quality of winter wheat following treatment . The authors found that: 1) the applica...split type) played no part in the effectiveness of the treatment . Increasing the amount of mineral fertilizer applied from 6 up to 8 centners per...such treatment is determined as a function of the timing, doses and repetition of applying the chemical. It is found that the most effective treatment

A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in rats.

PubMed

Breglia, Rudolph; Bui, Quang; Burnett, Donald; Koschier, Francis; Lapadula, Elizabeth; Podhasky, Paula; Schreiner, Ceinwen; White, Russell

2014-01-01

A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

Issues around the Prescription of Half Tablets in Northern Switzerland: The Irrational Case of Quetiapine

PubMed Central

Allemann, Samuel S.; Bornand, Delia; Hug, Balthasar; Hersberger, Kurt E.; Arnet, Isabelle

2015-01-01

Background. Prescription of fragmented tablets is useful for individualisation of dose but includes several drawbacks. Although without score lines, the antipsychotic drug quetiapine was in 2011 the most often prescribed 1/2 tablet in discharge prescriptions at the University Hospital in Basel (USB, 671 beds). We aimed at analysing the prescription patterns of split tablets in general and of quetiapine in particular in Switzerland. Methods. All orders of community pharmacies for unit-of-use soft pouch blisters placed at Medifilm AG, the leader company in Switzerland for repackaging into pouch blisters, were analysed. Results. Out of 4,784,999 tablets that were repacked in 2012 in unit-of-use pouch blisters, 8.5% were fragmented, mostly in half (87.6%), and were predominantly psycholeptics (pipamperone 15.8%). Prescription of half quetiapine appears to be a Basel specificity (highest rates of fragments and half quetiapine). Conclusions. Prescription of fragmented tablet is frequent. It represents a safety issue for the patient, and a pharmaceutical care issue for the pharmacist. In ambulatory care, the patient's cognitive and physical capacities must be clarified, suitability of the splitting of the tablet must be checked, appropriate aids must be offered, like a pill-splitting device in order to improve accuracy, and safe use of the drug must be ensured. PMID:26539514

Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery.

PubMed

Phillips, Andrew J K; Klerman, Elizabeth B; Butler, James P

2017-10-01

Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model's ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules.

Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery

PubMed Central

Phillips, Andrew J. K.

2017-01-01

Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model’s ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules. PMID:29073206

Recovery of shoulder strength and proprioception after open surgery for recurrent anterior instability: a comparison of two surgical techniques.

PubMed

Rokito, Andrew S; Birdzell, Maureen Gallagher; Cuomo, Frances; Di Paola, Matthew J; Zuckerman, Joseph D

2010-06-01

Previous studies have documented a decrease in proprioceptive capacity in the unstable shoulder. The degree to which surgical approach affects recovery of strength and proprioception is unknown. The recovery of strength and proprioception after open surgery for recurrent anterior glenohumeral instability was compared for 2 surgical procedures. A prospective analysis of 55 consecutive patients with posttraumatic unilateral recurrent anterior glenohumeral instability was performed. Thirty patients (group 1) underwent an open inferior capsular shift with detachment of the subscapularis, and 25 (group 2) underwent an anterior capsulolabral reconstruction. Mean preoperative proprioception and strength values were significantly lower for the affected shoulders in both groups. At 6 months after surgery, there were no significant differences for mean strength and proprioception values between the unaffected and operative sides for group 2 patients. In group 1 patients, however, there were still significant deficits in mean position sense and strength values. Complete restoration of proprioception and strength, however, was evident by 12 months in group 1. This study demonstrates that there are significant deficits in both strength and proprioception in patients with posttraumatic, recurrent anterior glenohumeral instability. Although both are completely restored by 1 year after surgery, a subscapularis-splitting approach allows for complete recovery of strength and position sense as early as 6 months postoperatively. Detachment of the subscapularis delays recovery of strength and position sense for up to 12 months after surgery. Copyright 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Multiple-, But Not Single-, Dose of Parecoxib Reduces Shoulder Pain after Gynecologic Laparoscopy

PubMed Central

Zhang, Hufei; Shu, Haihua; Yang, Lu; Cao, Minghui; Zhang, Jingjun; Liu, Kexuan; Xiao, Liangcan; Zhang, Xuyu

2012-01-01

Background: The aim of this study was to investigate effect of single- and multiple-dose of parecoxib on shoulder pain after gynecologic laparoscopy. Methods: 126 patients requiring elective gynecologic laparoscopy were randomly allocated to three groups. Group M (multiple-dose): receiving parecoxib 40mg at 30min before the end of surgery, at 8 and 20hr after surgery, respectively; Group S (single-dose): receiving parecoxib 40mg at 30min before the end of surgery and normal saline at the corresponding time points; Group C (control): receiving normal saline at the same three time points. The shoulder pain was evaluated, both at rest and with motion, at postoperative 6, 24 and 48hr. The impact of shoulder pain on patients' recovery (activity, mood, walking and sleep) was also evaluated. Meanwhile, rescue analgesics and complications were recorded. Results: The overall incidence of shoulder pain in group M (37.5%) was lower than that in group C (61.9%) (difference=-24.4%; 95% CI: 3.4~45.4%; P=0.023). Whereas, single-dose regimen (61.0%) showed no significant reduction (difference with control=-0.9%; 95% CI: -21.9~20.0%; P=0.931). Moreover, multiple-dose regimen reduced the maximal intensity of shoulder pain and the impact for activity and mood in comparison to the control. Multiple-dose of parecoxib decreased the consumption of rescue analgesics. The complications were similar among all groups and no severe complications were observed. Conclusions: Multiple-, but not single-, dose of parecoxib may attenuate the incidence and intensity of shoulder pain and thereby improve patients' quality of recovery following gynecologic laparoscopy. PMID:23136538

Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month toxicity study in dogs.

PubMed

Dahms, Irina; Beilstein, Paul; Bonnette, Kimberly; Salem, Norman

2016-06-01

DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic acid manufactured from the microalgal oil. The objective of the 9-month study was to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000 and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any findings after a 2-month recovery period. DHA-EE was well tolerated at all doses. There were observations of dry flaky skin with occasional reddened areas at doses ≥1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no longer present after the recovery period. There were no toxicologically relevant findings in body weights, body weight gains, food consumption, ophthalmological examinations, and ECG measurements. Test article-related changes in hematology parameters were limited to decreases in reticulocyte count in the high-dose males and considered non-adverse. In clinical chemistry parameters, dose-related decreases in cholesterol and triglycerides levels were observed at all doses in males and females and attributed to the known lipid-lowering effects of DHA. There were no effects on other clinical chemistry, urinalysis or coagulation parameters. There were no abnormal histopathology findings attributed to test article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000 mg/kg bw/day for both genders. Copyright © 2016 Elsevier Ltd. All rights reserved.

A 13-week oral toxicity study of senna in the rat with an 8-week recovery period.

PubMed

Mengs, U; Mitchell, J; McPherson, S; Gregson, R; Tigner, J

2004-05-01

Senna was administered by gavage to Sprague Dawley rats once daily at dose levels of 0, 100, 300, 750 or 1500 mg/kg for up to 13 consecutive weeks followed by an 8-week recovery period for selected animals. Dose- and treatment-related clinical signs included abnormal feces, which were seen to varying degrees from animals at 300 mg/kg per day and more. Animals receiving 750 or 1500 mg/kg per day had significantly reduced body weight gain (males only) and, related to the laxative properties of senna, increased water consumption and notable changes in electrolytes in both serum and urine. At both the terminal and recovery phase necropsy, an increase in absolute and relative kidney weights was seen for male and female animals receiving 750 and/or 1500 mg/kg per day. A dark discoloration of the kidneys was observed at necropsy along with histopathological changes in the kidneys (slight to moderate tubular basophilia and pigment deposits) at 300 mg/kg and above. However, there were no indications in laboratory parameters of any renal dysfunction. In addition, for all treated groups, minimal to slight hyperplasia was recorded in the forestomach and large intestine. Following 8 weeks of recovery, with the exception of the brown pigment in the kidneys, there were no histopathological abnormalities. Thus, the biochemical and morphological changes seen following 13 weeks of treatment of senna significantly reversed following 8 weeks of recovery.

Proportional Recovery From Lower Limb Motor Impairment After Stroke.

PubMed

Smith, Marie-Claire; Byblow, Winston D; Barber, P Alan; Stinear, Cathy M

2017-05-01

In people with preserved corticospinal tract (CST) function after stroke, upper limb impairment resolves by ≈70% within 3 months. This is known as the proportional recovery rule. Patients without CST function do not fit this rule and have worse upper limb outcomes. This study investigated resolution of motor impairment in the lower limb (LL). Patients with stroke and LL weakness were assessed 3 days and 3 months after stroke with the LL Fugl-Meyer. CST integrity was determined in a subset of patients using transcranial magnetic stimulation to test for LL motor-evoked potentials and magnetic resonance imaging to measure CST lesion load. Linear regression analyses were conducted to predict resolution of motor impairment (ΔFugl-Meyer) including factors initial impairment, motor-evoked potential status, CST lesion load, and LL therapy dose. Thirty-two patients completed 3-month follow-up and recovered 74% (95% confidence interval, 60%-88%) of initial LL motor impairment. Initial impairment was the only significant predictor of resolution of motor impairment. There was no identifiable cluster of patients who did not fit the proportional recovery rule. Measures of CST integrity did not predict proportional LL recovery. LL impairment resolves by ≈70% within 3 months after stroke. The absence of a nonfitter group may be because of differences in the neuroanatomical organization of descending motor tracts to the upper limb and LL. Proportional recovery of the LL is not influenced by therapy dose providing further evidence that it reflects a fundamental biological process. © 2017 American Heart Association, Inc.

Rocuronium duration of action under sevoflurane, desflurane or propofol anaesthesia.

PubMed

Maidatsi, P G; Zaralidou, A Th; Gorgias, N K; Amaniti, E N; Karakoulas, K A; Giala, M M

2004-10-01

We conducted a prospective randomized study to evaluate whether the duration of action of a single bolus dose of rocuronium is influenced by maintenance of anaesthesia with sevoflurane, desflurane or propofol infusion. Fifty-seven ASA I-II patients undergoing elective abdominal surgery were enrolled in this study. Anaesthesia was induced with thiopental 3-5 mg kg(-1) or propofol 2.5 mg kg(-1) and fentanyl 5 microg kg(-1) and tracheal intubation was facilitated with rocuronium 0.9 mg kg(-1). Thereafter patients were randomly allocated to three different groups to receive sevoflurane, desflurane or propofol for maintenance of anaesthesia. Recovery of neuromuscular function was monitored by single twitch stimulation of the ulnar nerve and by recording the adductor pollicis response using accelerometry. Intergroup recovery times to 5% of control value of single twitch were analysed using analysis of variance with Bonferroni correction. The mean (95% confidence interval) recovery time to 5% of control value of single twitch during desflurane anaesthesia was 90.18 (86.11-94.25) min. Significantly shorter recovery times were observed during sevoflurane or propofol anaesthesia, 58.86 (54.73-62.99) min and 51.11 (45.47-56.74) min, respectively (P < 0.001). There were also significant differences in the recovery time between groups receiving desflurane vs. sevoflurane (P < 0.001) and desflurane vs. propofol (P < 0.001). Desflurane anaesthesia significantly prolongs the duration of action of rocuronium at 0.9 mg kg(-1) single bolus dose, compared to sevoflurane or propofol anaesthesia maintenance regimens.

Kinetic analysis of IMP split dose method for two consecutive measurement of cerebral blood flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishizawa, S.; Yonekura, Y.; Tanaka, F.

1994-05-01

The split dose method for two consecutive measurements of cerebral blood flow (CBF) with I-123 IMP seems to offer a great merit to the SPECT study of the brain. However, because of complexity of the dynamics of IMP, it is not clear if microsphere (MS) model permits a estimation of CBF for the 2nd dose. We applied kinetic (KN) analysis based on 2 compartment model to the dynamic SPECT scan data, and compared the results with those obtained by MS model. Dynamic SPECT (1-min scans for 50 min) was performed using 3-head SPECT camera in 5 patients to test themore » reproducibility of measured CBF and in 9 patients to test the vascular response to acetazolamide (ACZ). Two doses of IMP (111 MBq each) were injected at the time of, and 25 min after, the scan initiation. ACZ (1g) was administered at 13 min. Arterial blood samples were drawn manually during the scan and an octanol extracted input function was obtained. Dynamic scan data for 22 min was used for CBF by KN analysis (K1), and 4-min scan data at 5 min for CBF by MS model (Km), for each dose. For 2nd CBF by MS model, simple subtraction of brain activity due to the I st dose was done using 4-min scan data just prior to the 2nd dose. Reproducibility of measured CBF by KN analysis was excellent (r=0.949, 1st K1=39.2{plus_minus}5.6 and 2nd K1=38.5{plus_minus}6.6 ml/l00g/min: mean{plus_minus}SD). Vascular response to ACZ was good (1st K1=42.4{plus_minus}7.8 to 2nd K1=67.9{plus_minus}10.0) in areas without ischemia, but poor (1st K1=41.1{plus_minus}8.5 to 2nd K1=46.1{plus_minus}11.1) in ischemic areas. Compared to KN analysis, MS model underestimated 3.5% for the 1st CBF measurement and 12.8% for the 2nd. However, excellent correlation was observed not only between 1st K1 and Km (r=0.993, slope=0.920) but between 2nd K1 and Km (r=0.994, slope=0.814), and the results permitted a reasonable correction for Km.« less

Reversal of neuromuscular blockade by sugammadex in laparoscopic bariatric surgery: In support of dose reduction.

PubMed

Badaoui, Rachid; Cabaret, Aurélie; Alami, Youssef; Zogheib, Elie; Popov, Ivan; Lorne, Emmanuel; Dupont, Hervé

2016-02-01

Sugammadex is the first molecule able to antagonize steroidal muscle relaxants with few adverse effects. Doses are adjusted to body weight and the level of neuromuscular blockade. Sleeve gastrectomy is becoming a very popular form of bariatric surgery. It requires deep muscle relaxation followed by complete and rapid reversal to decrease postoperative and especially post-anaesthetic morbidity. Sugammadex is therefore particularly indicated in this setting. The objective of this study was to evaluate the deep neuromuscular blockade reversal time after administration of various doses of sugammadex (based on real weight or at lower doses). Secondary endpoints were the interval between the sugammadex injection and extubation and transfer from the operating room to the recovery room. We then investigated any complications observed in the recovery room. This pilot, prospective, observational, clinical practice evaluation study was conducted in the Amiens University Hospital. Neuromuscular blockade was induced by rocuronium. At the end of the operation, deep neuromuscular blockade was reversed by sugammadex at the dose of 4mg/kg. Sixty-four patients were included: 31 patients received sugammadex at a dosage based on their real weight (RW) and 33 patients received a lower dose (based on ideal weight [IW]). For identical rocuronium doses calculated based on IBW, sugammadex doses were significantly lower in the IW group: 349 (± 65) mg versus 508 (± 75) mg (P<0.0001). Despite this dose reduction, neuromuscular blockade reversal took 115 (± 69) s in the IW group versus 87 (± 40) s in the RW group, but with no significant difference between the two groups (P=0.08). The intervals between injection of sugammadex and extubation (P=0.07) and transfer from the operating room to the recovery room (P=0.68) were also non-significantly longer in the IW group. The mean dose of sugammadex used by anaesthetists in the IW group was 4mg/kg of ideal weight increased by 35% to 50% (n=20; 351±34mg). No sugammadex adverse effects and no residual neuromuscular blockades were observed. Postoperative nausea and vomiting (PONV) was observed in 19.4% of patients in the real weight group versus 27.3% in the ideal weight group (P=NS). Reversal of deep neuromuscular blockades by sugammadex in obese subjects can be performed at doses of 4mg/kg of ideal weight plus 35-50% with no clinical consequences and no accentuation of adverse effects. Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy.

PubMed

Valiante, Flavio; Bellumat, Angelo; De Bona, Manuela; De Boni, Michele

2013-09-07

To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy.

Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive.

PubMed

O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary

2018-01-01

Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

Ethanol does not delay muscle recovery but decreases testosterone/cortisol ratio.

PubMed

Haugvad, Anders; Haugvad, Lars; Hamarsland, Håvard; Paulsen, Gøran

2014-11-01

This study investigated the effects of ethanol consumption on recovery from traditional resistance exercise in recreationally trained individuals. Nine recreationally trained volunteers (eight males and one female, 26 ± 4 yr, 81 ± 4 kg) conducted four resistance exercise sessions and consumed a low (0.6 (females) and 0.7 (males) g · kg(-1) body mass) or a high dose (1.2 or 1.4 g · kg(-1) body mass) of ethanol 1-2.5 h after exercise on two occasions. The first session was for familiarization with the tests and exercises and was performed without ethanol consumption. As a control trial, alcohol-free drinks were consumed after the exercise session. The sequence of trials, with low and high ethanol doses and alcohol-free drinks (control), was randomized. Maximal voluntary contractions (MVC) (knee extension), electrically stimulated contractions (knee extension), squat jumps, and hand grip strength were assessed 10-15 min and 12 and 24 h after the ethanol/placebo drinks. In addition to a baseline sample, blood was collected 1, 12, and 24 h after the ethanol/placebo drinks. The exercise session comprised 4 × 8 repetition maximum of squats, leg presses, and knee extensions. MVC were reduced by 13%-15% immediately after the exercise sessions (P < 0.01). MVC, electrically stimulated force, and squat jump performance were recovered 24 h after ethanol drinks. MVC was not fully recovered at 24 h in the control trial. Compared with those in the control, cortisol increased and the free testosterone/cortisol ratio were reduced after the high ethanol dose (P < 0.01). Neither a low nor a high dose of ethanol adversely affected recovery of muscle function after resistance exercise in recreationally strength-trained individuals. However, the increased cortisol levels and reduced testosterone/cortisol ratio after the high ethanol dose could translate into long-term negative effects.

In-situ thermal annealing of on-membrane silicon-on-insulator semiconductor-based devices after high gamma dose irradiation.

PubMed

Amor, S; André, N; Kilchytska, V; Tounsi, F; Mezghani, B; Gérard, P; Ali, Z; Udrea, F; Flandre, D; Francis, L A

2017-05-05

In this paper, we investigate the recovery of some semiconductor-based components, such as N/P-type field-effect transistors (FETs) and a complementary metal-oxide-semiconductor (CMOS) inverter, after being exposed to a high total dose of gamma ray radiation. The employed method consists mainly of a rapid, low power and in situ annealing mitigation technique by silicon-on-insulator micro-hotplates. Due to the ionizing effect of the gamma irradiation, the threshold voltages showed an average shift of -580 mV for N-channel transistors, and -360 mV for P-MOSFETs. A 4 min double-cycle annealing of components with a heater temperature up to 465 °C, corresponding to a maximum power of 38 mW, ensured partial recovery but was not sufficient for full recovery. The degradation was completely recovered after the use of a built-in high temperature annealing process, up to 975 °C for 8 min corresponding to a maximum power of 112 mW, which restored the normal operating characteristics for all devices after their irradiation.

In-situ thermal annealing of on-membrane silicon-on-insulator semiconductor-based devices after high gamma dose irradiation

NASA Astrophysics Data System (ADS)

Amor, S.; André, N.; Kilchytska, V.; Tounsi, F.; Mezghani, B.; Gérard, P.; Ali, Z.; Udrea, F.; Flandre, D.; Francis, L. A.

2017-05-01

In this paper, we investigate the recovery of some semiconductor-based components, such as N/P-type field-effect transistors (FETs) and a complementary metal-oxide-semiconductor (CMOS) inverter, after being exposed to a high total dose of gamma ray radiation. The employed method consists mainly of a rapid, low power and in situ annealing mitigation technique by silicon-on-insulator micro-hotplates. Due to the ionizing effect of the gamma irradiation, the threshold voltages showed an average shift of -580 mV for N-channel transistors, and -360 mV for P-MOSFETs. A 4 min double-cycle annealing of components with a heater temperature up to 465 °C, corresponding to a maximum power of 38 mW, ensured partial recovery but was not sufficient for full recovery. The degradation was completely recovered after the use of a built-in high temperature annealing process, up to 975 °C for 8 min corresponding to a maximum power of 112 mW, which restored the normal operating characteristics for all devices after their irradiation.

Diagnostic doses and times for Phlebotomus papatasi and Lutzomyia longipalpis sand flies (Diptera: Psychodidae: Phlebotominae) using the CDC bottle bioassay to assess insecticide resistance.

PubMed

Denlinger, David S; Creswell, Joseph A; Anderson, J Laine; Reese, Conor K; Bernhardt, Scott A

2016-04-15

Insecticide resistance to synthetic chemical insecticides is a worldwide concern in phlebotomine sand flies (Diptera: Psychodidae), the vectors of Leishmania spp. parasites. The CDC bottle bioassay assesses resistance by testing populations against verified diagnostic doses and diagnostic times for an insecticide, but the assay has been used limitedly with sand flies. The objective of this study was to determine diagnostic doses and diagnostic times for laboratory Lutzomyia longipalpis (Lutz & Nieva) and Phlebotomus papatasi (Scopoli) to ten insecticides, including pyrethroids, organophosphates, carbamates, and DDT, that are used worldwide to control vectors. Bioassays were conducted in 1,000-ml glass bottles each containing 10-25 sand flies from laboratory colonies of L. longipalpis or P. papatasi. Four pyrethroids, three organophosphates, two carbamates and one organochlorine, were evaluated. A series of concentrations were tested for each insecticide, and four replicates were conducted for each concentration. Diagnostic doses were determined only during the exposure bioassay for the organophosphates and carbamates. For the pyrethroids and DDT, diagnostic doses were determined for both the exposure bioassay and after a 24-hour recovery period. Both species are highly susceptible to the carbamates as their diagnostic doses are under 7.0 μg/ml. Both species are also highly susceptible to DDT during the exposure assay as their diagnostic doses are 7.5 μg/ml, yet their diagnostic doses for the 24-h recovery period are 650.0 μg/ml for Lu. longipalpis and 470.0 μg/ml for P. papatasi. Diagnostic doses and diagnostic times can now be incorporated into vector management programs that use the CDC bottle bioassay to assess insecticide resistance in field populations of Lu. longipalpis and P. papatasi. These findings provide initial starting points for determining diagnostic doses and diagnostic times for other sand fly vector species and wild populations using the CDC bottle bioassay.

Microarray-based analysis of the lung recovery process after stainless-steel welding fume exposure in Sprague-Dawley rats.

PubMed

Oh, Jung-Hwa; Yang, Mi-jin; Yang, Young-Su; Park, Han-Jin; Heo, Sun Hee; Lee, Eun-Hee; Song, Chang-Woo; Yoon, Seokjoo

2009-02-01

Repeated exposure to welding fumes promotes a reversible increase in pulmonary disease risk, but the molecular mechanisms by which welding fumes induce lung injury and how the lung recovers from such insults are unclear. In the present study, pulmonary function and gene-expression profiles in the lung were analyzed by Affymetrix GeneChip microarray after 30 days of consecutive exposure to manual metal arc welding combined with stainless-steel (MMA-SS) welding fumes, and again after 30 days of recovery from MMA-SS fume exposure. In total, 577 genes were identified as being either up-regulated or down-regulated (over twofold changes, p < 0.05) in the lungs of low-dose or high-dose groups. Differentially expressed genes were classified based on a k-means clustering algorithm and biological functions and molecular networks were further analyzed using Ingenuity Pathways Analysis. Among the genes affected by exposure to or recovery from MMA-SS fumes, the transcriptional changes of 13 genes that were highly altered by treatment were confirmed by quantitative real-time PCR. Notably, Mmp12, Cd5l, Ccl7, Cxcl5, and Spp1 related to the immune response were up-regulated only in the exposure group, whereas Trem2, IgG-2a, Igh-1a, and Igh were persistently up-regulated in both the exposure and recovery groups. In addition, several genes that might play a role in the repair process of the lung were up-regulated exclusively in the recovery group. Collectively, these data may help elucidate the molecular mechanism of the recovery process of the lung after welding fume exposure.

Effect of contrast water therapy duration on recovery of running performance.

PubMed

Versey, Nathan G; Halson, Shona L; Dawson, Brian T

2012-06-01

To investigate whether contrast water therapy (CWT) assists acute recovery from high-intensity running and whether a dose-response relationship exists. Ten trained male runners completed 4 trials, each commencing with a 3000-m time trial, followed by 8 × 400-m intervals with 1 min of recovery. Ten minutes postexercise, participants performed 1 of 4 recovery protocols: CWT, by alternating 1 min hot (38°C) and 1 min cold (15°C) for 6 (CWT6), 12 (CWT12), or 18 min (CWT18), or a seated rest control trial. The 3000-m time trial was repeated 2 h later. 3000-m performance slowed from 632 ± 4 to 647 ± 4 s in control, 631 ± 4 to 642 ± 4 s in CWT6, 633 ± 4 to 648 ± 4 s in CWT12, and 631 ± 4 to 647 ± 4 s in CWT18. Following CWT6, performance (smallest worthwhile change of 0.3%) was substantially faster than control (87% probability, 0.8 ± 0.8% mean ± 90% confidence limit), however, there was no effect for CWT12 (34%, 0.0 ± 1.0%) or CWT18 (34%, -0.1 ± 0.8%). There were no substantial differences between conditions in exercise heart rates, or postexercise calf and thigh girths. Algometer thigh pain threshold during CWT12 was higher at all time points compared with control. Subjective measures of thermal sensation and muscle soreness were lower in all CWT conditions at some post-water-immersion time points compared with control; however, there were no consistent differences in whole body fatigue following CWT. Contrast water therapy for 6 min assisted acute recovery from high-intensity running; however, CWT duration did not have a dose-response effect on recovery of running performance.

Optimal dose of rocuronium bromide undergoing adenotonsillectomy under 5% sevoflurane with fentanyl.

PubMed

Huh, Hyub; Park, Jeong Jun; Kim, Ji Yeong; Kim, Tae Hoon; Yoon, Seung Zhoo; Shin, Hye Won; Lee, Hye-Won; Lim, Hye-Ja; Cho, Jang Eun

2017-10-01

Adenotonsillectomy is a short surgical procedure under general anaesthesia in children. An ideal muscle relaxant for adenotonsillectomy would create an intense neuromuscular block while having a quick recovery time without postoperative morbidity. We compared the effect of different doses of rocuronium for the tracheal intubation in children under 5% sevoflurane and fentanyl. 75 children (aged 3-10 years, ASA I) scheduled for adenotonsillectomy were enrolled. Anaesthesia was induced with propofol 2.5 mg/kg, followed by fentanyl 2 μg/kg. After mask ventilation with 5 vol% sevoflurane in 100% oxygen for 2 min, 2 ml of study drug was administered intravenously, i.e., either normal saline (S Group) or one of two doses (0.15 or 0.3 mg/kg) of rocuronium. We assessed conditions during tracheal intubation and also recorded the surgical condition, the time from discontinuation of sevoflurane to extubation and PAED scale, pain scores in PACU. Rocuronium groups (96% and 100%, respectively; P < 0.01) showed statistically superior clinically acceptable intubating conditions than the saline group (72%). The 0.3 mg/kg rocuronium (80%) treatment clearly resulted in excellent intubating conditions compared with the 0.15 mg/kg group (44%; p = 0.028). There was no significant difference in the time to extubation and surgical condition, and in the postoperative measures of emergence delirium, pain, and recovery time among the three groups. A dose of 0.3 mg/kg rocuronium may provide optimal intubating conditions without delayed recovery in 5% sevoflurane anaesthesia with fentanyl in children undergoing adenotonsillectomy. NCT02467595. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation-epidemiological Study of Cerebrovascular Diseases in the Cohort of Russian Recovery Operation Workers of the Chernobyl Accident.

PubMed

Kashcheev, V V; Chekin, S Yu; Maksioutov, M A; Tumanov, K A; Menyaylo, A N; Kochergina, E V; Kashcheeva, P V; Gorsky, A I; Shchukina, N V; Karpenko, S V; Ivanov, V K

2016-08-01

The paper presents an analysis of the incidence of cerebrovascular diseases (CeVD) in the cohort of Russian workers involved in recovery tasks after the Chernobyl accident. The studied cohort consists of 53,772 recovery operation workers (liquidators) who arrived in the zone of the Chernobyl accident within the first year after this accident (26 April 1986-26 April 1987). The mean external whole body dose in the cohort was 0.161 Gy, while individual doses varied from 0.0001 Gy to 1.42 Gy. During the follow-up period 1986-2012, a total of 23,264 cases of CeVD were diagnosed as a result of annual health examinations. A Poisson regression model was applied for estimation of radiation risks and for an assessment of other risk factors of CeVD. The following factors were considered as risk factors for CeVD: the dose, duration of the liquidators' work in the Chernobyl zone, and the concomitant diseases (hypertension, ischemic heart disease, atherosclerosis, and diabetes). The baseline incidence of CeVD is statistically significantly (p < 0.001) associated with all studied concomitant diseases. The incidence of CeVD has revealed a statistically significant dose response with the lack of a latent period and with the average ERR/Gy = 0.45, 95% CI: (0.28, 0.62), p < 0.001. Radiation risks of CeVD statistically significantly (p = 0.03) varied with the duration of liquidators' stay in the Chernobyl zone; for those who stayed in the Chernobyl zone less than 6 wk, ERR/Gy = 0.64, 95% CI = (0.38; 0.93), p < 0.001. Among studied concomitant diseases, diabetes mellitus statistically significantly (p = 0.002) increases the radiation risk of CeVD: for liquidators with diagnosed diabetes, ERR/Gy = 1.29.

Perioperative systemic steroid for rapid recovery in total knee and hip arthroplasty: a systematic review and meta-analysis of randomized trials.

PubMed

Yue, Chen; Wei, Rong; Liu, Youwen

2017-06-27

Perioperative systemic steroid administration for rapid recovery in total knee and hip arthroplasty (TKA/THA) is an important and controversial topic. We conducted this systematic review and meta-analysis to evaluate the overall benefits and harms of perioperative systemic steroid in patients undergoing TKA and THA. A comprehensive search was performed on PubMed, OVID, and Web of Science databases, and a systematic approach was carried out starting from the PRISMA recommendations. Relevant randomized controlled trials (RCTs) were selected. The risk of bias was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions version. Data were extracted and meta-analyzed or qualitatively synthesized for all the outcomes. Data were extracted from 11 trials involving 774 procedures. Meta-analysis showed that high-dose systemic steroid (dexamethasone > 0.1 mg/kg) rather than low dose is effective to reduce postoperative nausea and vomiting and postoperative acute pain (within 24 h). In addition, systemic steroid is associated within faster functional rehabilitation and greater inflammation control. On the other hand, systemic steroid is associated with a higher level of postoperative serum glucose on the operation day. The complications between groups are similarly low. Our study suggests that by providing lower incidence of postoperative nausea and vomiting and less postoperative acute pain, high-dose systemic steroid plays a critical role in rapid recovery to TKA and THA. The preliminary results also show the superior possibility of systemic steroid in functional rehabilitation and inflammation control. More large, high-quality studies that investigate the safety and dose-response relationship are necessary.

Vivianite as an important iron phosphate precipitate in sewage treatment plants.

PubMed

Wilfert, P; Mandalidis, A; Dugulan, A I; Goubitz, K; Korving, L; Temmink, H; Witkamp, G J; Van Loosdrecht, M C M

2016-11-01

Iron is an important element for modern sewage treatment, inter alia to remove phosphorus from sewage. However, phosphorus recovery from iron phosphorus containing sewage sludge, without incineration, is not yet economical. We believe, increasing the knowledge about iron-phosphorus speciation in sewage sludge can help to identify new routes for phosphorus recovery. Surplus and digested sludge of two sewage treatment plants was investigated. The plants relied either solely on iron based phosphorus removal or on biological phosphorus removal supported by iron dosing. Mössbauer spectroscopy showed that vivianite and pyrite were the dominating iron compounds in the surplus and anaerobically digested sludge solids in both plants. Mössbauer spectroscopy and XRD suggested that vivianite bound phosphorus made up between 10 and 30% (in the plant relying mainly on biological removal) and between 40 and 50% of total phosphorus (in the plant that relies on iron based phosphorus removal). Furthermore, Mössbauer spectroscopy indicated that none of the samples contained a significant amount of Fe(III), even though aerated treatment stages existed and although besides Fe(II) also Fe(III) was dosed. We hypothesize that chemical/microbial Fe(III) reduction in the treatment lines is relatively quick and triggers vivianite formation. Once formed, vivianite may endure oxygenated treatment zones due to slow oxidation kinetics and due to oxygen diffusion limitations into sludge flocs. These results indicate that vivianite is the major iron phosphorus compound in sewage treatment plants with moderate iron dosing. We hypothesize that vivianite is dominating in most plants where iron is dosed for phosphorus removal which could offer new routes for phosphorus recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of ultrasound-assisted emulsification microextraction based on solidification of a floating organic droplet for determination of organochlorine pesticides in water samples.

PubMed

Shu, Bin; Yang, Zhaoguang; Lee, Hsiaowan; Qiu, Bo; Li, Haipu

2016-02-01

An ultrasound-assisted emulsification microextraction based on the solidification of a floating organic droplet followed by gas chromatography with electron capture detection was developed for the simultaneous determination of 13 organochlorine pesticides in water samples. In the proposed method, ultrasound was applied to achieve the emulsification without addition of any dispersive solvent. In consequence, the volume of extraction phase remained unaffected by the ion strength of aqueous phase and high extraction recoveries were obtained. It was also found that dilution of the floating phase with acetone was necessary for preventing peak splitting in chromatogram. Under optimal conditions, the proposed method provided good sensitivity (the detection limits of organochlorine pesticides ranged from 1.3 to 3.9 ng/L) and good repeatability of extraction (below 6.5%, n = 5). The recoveries in reservoir and river water samples were between 75.8% and 96.9%. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

On the Recovery Stress of a Ni50.3Ti29.7Hf20 High Temperature Shape Memory Alloy

NASA Technical Reports Server (NTRS)

Benafan, O.; Noebe, R. D.; Padula, S. A., II; Bigelow, G. S.; Gaydosh, D. J.; Garg, A.; Halsmer, T. J.

2015-01-01

Recovery stress in shape memory alloys (SMAs), also known as blocking stress, is an important property generally obtained during heating under a dimensional constraint as the material undergoes the martensitic phase transformation. This property has been instinctively utilized in most SMA shape-setting procedures, and has been used in numerous applications such as fastening and joining, rock splitting, safety release mechanisms, reinforced composites, medical devices, and many other applications. The stress generation is also relevant to actuator applications where jamming loads (e.g., in case the actuator gets stuck and is impeded from moving) need to be determined for proper hardware sizing. Recovery stresses in many SMA systems have been shown to reach stresses in the order of 800 MPa, achieved via thermo-mechanical training such as pre-straining, heat treatments or other factors. With the advent of high strength, high temperature SMAs, recovery stress data has been rarely probed, and there is no information pertinent to the magnitudes of these stresses. Thus, the purpose of this work is to investigate the recovery stress capability of a precipitation strengthened, Ni50.3Ti29.7Hf20 (at.) high temperature SMA in uniaxial tension and compression. This material has been shown to exhibit outstanding strength and stability during constant-stress, thermal cycling, but no data exists on constant-strain thermal cycling. Several training routines were implemented as part of this work including isothermal pre-straining, isobaric thermal cycling, and isothermal cyclic training routines. Regardless of the training method used, the recovery stress was characterized using constant-strain (strain-controlled condition) thermal cycling between the upper and lower cycle temperatures. Preliminary results indicate recovery stresses in excess of 1.5 GPa were obtained after a specific training routine. This stress magnitude is significantly higher than conventional NiTi stress generation capability.

Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults.

PubMed

Cooper, Curtis; Thorne, Anona; Klein, Marina; Conway, Brian; Boivin, Guy; Haase, David; Shafran, Stephen; Zubyk, Wendy; Singer, Joel; Halperin, Scott; Walmsley, Sharon

2011-03-25

The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy. A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity. 297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 =  31-58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related. Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population. ClinicalTrials.gov NCT00764998.

Incorporating partial shining effects in proton pencil-beam dose calculation

NASA Astrophysics Data System (ADS)

Li, Yupeng; Zhang, Xiaodong; Fwu Lii, Ming; Sahoo, Narayan; Zhu, Ron X.; Gillin, Michael; Mohan, Radhe

2008-02-01

A range modulator wheel (RMW) is an essential component in passively scattered proton therapy. We have observed that a proton beam spot may shine on multiple steps of the RMW. Proton dose calculation algorithms normally do not consider the partial shining effect, and thus overestimate the dose at the proximal shoulder of spread-out Bragg peak (SOBP) compared with the measurement. If the SOBP is adjusted to better fit the plateau region, the entrance dose is likely to be underestimated. In this work, we developed an algorithm that can be used to model this effect and to allow for dose calculations that better fit the measured SOBP. First, a set of apparent modulator weights was calculated without considering partial shining. Next, protons spilled from the accelerator reaching the modulator wheel were simplified as a circular spot of uniform intensity. A weight-splitting process was then performed to generate a set of effective modulator weights with the partial shining effect incorporated. The SOBPs of eight options, which are used to label different combinations of proton-beam energy and scattering devices, were calculated with the generated effective weights. Our algorithm fitted the measured SOBP at the proximal and entrance regions much better than the ones without considering partial shining effect for all SOBPs of the eight options. In a prostate patient, we found that dose calculation without considering partial shining effect underestimated the femoral head and skin dose.

OSL studies of local bricks for retrospective dosimetric application

NASA Astrophysics Data System (ADS)

Singh, A. K.; Menon, S. N.; Kadam, S. Y.; Koul, D. K.; Datta, D.

2016-09-01

Luminescence properties of quartz extracted from bricks has been reported worldwide for its use in dose estimation in case of nuclear or radiological accident. Accordingly, in this study the feasibility of utilizing the optically stimulated luminescence (OSL) emission of quartz extracted from red bricks collected from three different locations in and around Mumbai, India for retrospective dosimetry was explored. Thermoluminescence and OSL characterization of the samples were carried out. The growth curve, thermal stability and equivalent dose plateau of the OSL signal suggested the signals to be well behaving. Subsequently, the dose recovery tests carried for different administered doses, using single aliquot regenerative protocol, demonstrated the feasibility of the OSL emissions of these samples for dose evaluation in retrospective dosimetry.

Staged corrective surgery for complex congenital scoliosis and split cord malformation

PubMed Central

Asad, Ambreen; Pasha, Ibrahim Farooq; Malik, Arslan Sharif; Arlet, Vincent

2009-01-01

Congenital scoliosis associated with split cord malformation raises the issue on how to best manage these patients to avoid neurologic injury while achieving satisfactory correction. We present the case of a 12-year-old girl who first presented when she was 11-year old with such combination but without much physical handicap or neurological deficit. The corrective surgery offered at that time was refused by the family. She again presented after 1 year with documented severe aggravation of the curve resulting in unstable walking and psychological upset. Her imaging studies showed multiple malformations in lower cervical and thoracic spine and a split cord malformation type 2 (fibrous septum with diplomyelia) at the apex of the deformity. A one-stage correction was deemed neurologically too risky. We therefore performed during a first stage a thoracotomy with anterior release. This was followed by skeletal traction with skull tongs and bilateral femoral pins. After gradual increase in traction weights a reasonable correction was achieved without any neurological deficit, over the next 10 days. A second-stage operation was done on the 11th day and a posterior instrumented fusion was performed. Post-operative recovery was uneventful and there were no complications. She was discharged with a Boston Brace to be worn for 3 months. At 2-year follow-up the patient outcome is excellent with excellent balance and correction of the deformity. In this grand round case, we discuss all the different option of treatment of congenital scoliosis associated with split cord malformation. In a medical environment where spinal cord monitoring is lacking, we recommend an initial release followed by skull and bifemoral traction over several days to monitor the neurologic status of the patient. Once optimal correction is achieved with the traction, a posterior instrumentation can be safely done. PMID:19626347

Wavelength dependent recovery of UV-mediated damage: Tying up the loose ends of optical based powdery mildew management.

PubMed

Suthaparan, Aruppillai; Pathak, Ranjana; Solhaug, Knut Asbjørn; Gislerød, Hans Ragnar

2018-01-01

Controlled environment chamber experiments at Petri dish level were conducted to examine the wavelength and dose dependent efficacy of ultraviolet (UV) radiation, the recovery action potential of optical radiation applied concomitantly/subsequently to effective UV treatment, and the lapse time between UV treatment and subsequent exposure to recovery wavelength on germination efficiency of Oidium neolycopersici conidia. Conidia of eight- to nine-day-old colonies were dusted on water agar surface in Petri dishes and exposed to UV treatments (without lid). Immediately after UV treatments, Petri dishes were sealed and incubated in darkness or differing optical environments generated using seven different radiation sources (range 290nm to 780nm). Twenty-four hours after UV treatment, fifty conidia from each sample were assessed for germination. Compared to non-UV controls, <10% of the conidia germinated after 30s of exposure to 254nm or 283nm UV and subsequent dark incubation. Conidia germination was almost negligible if the exposure duration increased to 4min. Germination was about 60% with broad spectrum UV after 1min of exposure, and about 35% after 2 to 4min of exposure. There was no reduction of conidia germination with the exposure of ≤4min with 310nm. With the tested wavelength and dose ranges, germination recovery was effective in the 350nm to 500nm range. Germination efficiency of conidia treated with effective UV was significantly higher (>73%) if incubated subsequently in the 350nm to 500nm range (germination recovery). Furthermore, germination recovery depends on the characteristics of UV treatment (wavelength, and duration of exposure) and the lapse time between UV treatment and subsequent exposure to optical radiation in the recovery range. The findings of this study provide key criteria for wavelength selection, combination and application time in the optical radiation range, enabling improved design of optical based management strategies against powdery mildews. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled. PMID:23635256

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

PubMed

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

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Herpetic keratoconjunctivitis: Therapy with synthetic double-stranded RNA

USGS Publications Warehouse

Friedman, I.; Evans, C.; Meighan, C.W.; Foote, L.J.; Aiello, P.V.; Park, J.H.; Baron, S.

1968-01-01

A study was undertaken in rabbits to determine how late in the course of keratoconjunctivitis caused by herpes simplex recovery could be effected by an inducer of interferon. Interferon was induced by means of synthetic double-stranded RNA copolymer formed with polynosinic acid : polycytidilic acid RNA. Therapy promotes recovery from severe and fully established keratoconjunctivitis for which treatment was begun as late as 3 days after virus inoculation. No drug toxicity was observed in the therapeutic dose range. These findings further support the proposed role of the interferon mechanism in the natural recovery of already established viral infection. They also suggest the usefulness of interferon inducers in viral infections of man.

SolarSyngas: Results from a virtual institute developing materials and key components for solar thermochemical fuel production

NASA Astrophysics Data System (ADS)

Roeb, Martin; Steinfeld, Aldo; Borchardt, Günter; Feldmann, Claus; Schmücker, Martin; Sattler, Christian; Pitz-Paal, Robert

2016-05-01

The Helmholtz Virtual Institute (VI) SolarSynGas brings together expertise from solar energy research and materials science to develop metal oxide based redox materials and to integrate them in a suitable way into related process technologies for two-step thermochemical production of hydrogen and carbon monoxide from water and CO2. One of the foci of experimental investigation was exploring the impact of doping on the feasibility of ceria-based materials - mainly by Zr-doping. The results indicate that a certain Zr-content enhances the reducibility and therefore the splitting performance. Increasing the Zr-content to x = 0.15 improved the specific CO2-splitting performance by 50% compared to pure ceria. This finding agrees with theoretical studies attributing the improvements to lattice modification caused by the introduction of Zr4+. Thermogravimetric relaxation experiments and equilibrium oxygen isotope exchange experiments with subsequent depth profiling analysis were carried out on ceria. As a result the reduction reaction of even dense samples of pure ceria with a grain size of about 20 µm is surface reaction controlled. The structure of the derived expression for the apparent activation energy suggests that the chemical surface exchange coefficient should show only a very weak dependence on temperature for ceria doped with lower valence cations. A solar receiver reactor exhibiting a foam-type reticulated porous ceramics made of ceria was tested. It could be shown that applying dual-scale porosity to those foams with mm-size pores for effective radiative heat transfer during reduction and μm-size pores within its struts for enhanced kinetics during oxidation allows enhancing the performance of the reactor significantly. Also a particle process concept applying solid-solid heat recovery from redox particles in a high temperature solar thermochemical process was analysed that uses ceramic spheres as solid heat transfer medium. This concept can be implemented into any particle reactor and offers sufficiently high heat recovery rates and thus high overall system efficiencies. A detailed model to calculate the performance of the concept in consideration of temperature dependent material data and several other influencing factors was developed. It was found that the molar flow ratio needs to be optimized regarding the contact time and the heat recovery rate only increases slightly over a contact time of τ=10s. The system reaches a heat recovery rate over 70% in case of six stages, connected in a quasi-counter-current principle.

[Infusion of Daratumumab in Combination Therapies - Practical Information for The Outpatient Area].

PubMed

Scheid, Christof; Munder, Markus; Salwender, Hans; Engelhardt, Monika

2018-06-06

Combination therapies such as Dara-Rd and Dara-Vd show significantly higher survival rates after 12 months than the respective therapies without Daratumumab. The initial infusion of Daratumumab is associated with a high incidence of IRR. Dosage and speed of infusion of Daratumumab have to be strictly controlled. Any suspicion of even low IRR requires corrections. Concomitant medication before and after Daratumumab administration is required. For this purpose, various preparations have been tested in everyday clinical practice. Eight hours of infusion may be required. This does not only overwhelm the patient, but also the most ambulant structures. The split-dose concept means to divide the dose into infusions on different days. Again, the dosage is crucial for good compatibility. © Georg Thieme Verlag KG Stuttgart · New York.

Impact of Body Mass Index on Immunogenicity of Pandemic H1N1 Vaccine in Children and Adults

PubMed Central

Callahan, S. Todd; Wolff, Mark; Hill, Heather R.; Edwards, Kathryn M.; Keitel, Wendy; Atmar, Robert; Patel, Shital; Sahly, Hana El; Munoz, Flor; Paul Glezen, W.; Brady, Rebecca; Frenck, Robert; Bernstein, David; Harrison, Christopher; Jackson, Mary Anne; Swanson, Douglas; Newland, Jason; Myers, Angela; Livingston, Robyn A; Walter, Emmanuel; Dolor, Rowena; Schmader, Kenneth; Mulligan, Mark J.; Edupuganti, Srilatha; Rouphael, Nadine; Whitaker, Jennifer; Spearman, Paul; Keyserling, Harry; Shane, Andi; Eckard, Allison Ross; Jackson, Lisa A.; Frey, Sharon E.; Belshe, Robert B.; Graham, Irene; Anderson, Edwin; Englund, Janet A.; Healy, Sara; Winokur, Patricia; Stapleton, Jack; Meier, Jeffrey; Kotloff, Karen; Chen, Wilbur; Hutter, Julia; Stephens, Ina; Wooten, Susan; Wald, Anna; Johnston, Christine; Edwards, Kathryn M.; Buddy Creech, C.; Todd Callahan, S.

2014-01-01

Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses. PMID:24795475

Self-Driven Photoelectrochemical Splitting of H2S for S and H2 Recovery and Simultaneous Electricity Generation.

PubMed

Luo, Tao; Bai, Jing; Li, Jinhua; Zeng, Qingyi; Ji, Youzhi; Qiao, Li; Li, Xiaoyan; Zhou, Baoxue

2017-11-07

A novel, facile self-driven photoelectrocatalytic (PEC) system was established for highly selective and efficient recovery of H 2 S and simultaneous electricity production. The key ideas were the self-bias function between a WO 3 photoanode and a Si/PVC photocathode due to their mismatched Fermi levels and the special cyclic redox reaction mechanism of I - /I 3 - . Under solar light, the system facilitated the separation of holes in the photoanode and electrons in the photocathode, which then generated electricity. Cyclic redox reactions were produced in the photoanode region as follows: I - was transformed into I 3 - by photoholes or hydroxyl radicals, H 2 S was oxidized to S by I 3 - , and I 3 - was then reduced to I - . Meanwhile, H + was efficiently converted to H 2 in the photocathode region. In the system, H 2 S was uniquely oxidized to sulfur but not to polysulfide (S x n- ) because of the mild oxidation capacity of I 3 - . High recovery rates for S and H 2 were obtained up to ∼1.04 mg h -1 cm -1 and ∼0.75 mL h -1 cm -1 , respectively, suggesting that H 2 S was completely converted into H 2 and S. In addition, the output power density of the system reached ∼0.11 mW cm -2 . The proposed PEC-H 2 S system provides a self-sustaining, energy-saving method for simultaneous H 2 S treatment and energy recovery.

Drug interactions: volatile anesthetics and opioids.

PubMed

Glass, P S; Gan, T J; Howell, S; Ginsberg, B

1997-09-01

Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

[BIPADDLED SPLIT PECTORALIS MAJOR MYOCUTANEOUS FLAPS FOR IMMEDIATE RECONSTRUCTION OF ORAL MUCOSAL DEFECTS AND NECK DEFECTS AFTER RESECTION OF RECURRENT ORAL CANCER].

PubMed

Chen, Jie; Jiang, Canhua; Li, Ning; Gao, Zhengyang; Chen, Lichun; Wu, Xiaoshan; Chen, Xinqun; Jian, Xinchun

2015-07-01

To investigate the feasibility of the bipaddled split pectoralis major myocutaneous flap for immediate reconstruction of oral mucosal defects and neck defects after resection of recurrent oral cancer. Six patients with oral mucosal defects combined with neck defects after recurrent oral cancer resection were treated with bipaddled split pectoralis major myocutaneous flap between September 2013 and September 2014. There were 5 males and 1 female with an average age of 54.7 years (range, 45-62 years), including 4 cases of recurrent tongue cancer, 1 case of recurrent mandibular gingival cancer, and 1 case of mouth floor carcinoma. All patients underwent local recurrence at 8 to 14 months after first operation, with no distant metastasis. The defects of the intraoral mucosa was 4.0 cm x 2.5 cm to 6.5 cm x 3.5 cm and the defect of the neck skin was 5.5 cm x 3.5 cm to 7.5 cm x 5.0 cm. The pectoralis major myocutaneous flaps (14.0 cm x 3.5 cm to 17.0 cm x 5.5 cm) were incised at the level of the 3rd to the 4th rib, and then split down along the muscle fiber till about 2 cm away from the thoracoacromial vessels, forming 2 independent skin paddles with 1-2 branch vessels to the pedicles of the distal ones. The distal skin paddles were used for oral reconstruction while the proximal paddles for repair of neck defects. The chest donor sites were sutured directly. Cervical haematoma and infection happened in 1 patient respectively after operation, and were cured after symptomatic treatment. All 6 split pectoralis major myocutaneous flaps with 12 skin paddles completely survived. All patients were followed up 6 to 18 months (mean, 11 months). One patient died of pulmonary metastasis at 8 months after operation and the other 5 survived without relapse or metastasis during follow-up. The intraoral paddles showed good shape with satisfactory speech function and swallowing recovery. The paddles also healed perfectly on the neck with flat outlooks, and all patients obtained full appearance and free movement of the neck. No fistula formed on the submandibular region and neck. The bipaddled split pectoralis major myocutaneous flap can complete simultaneous immediate reconstruction of oral mucosal defect and neck defect. It is very useful in the treatment of recurrent oral cancer.

Treatment of traumatic infra orbital nerve paresthesia

PubMed Central

Lone, Parveen Akhter; Singh, R. K.; Pal, U. S.

2012-01-01

This study was done to find out the role of topiramate therapy in infraorbital nerve paresthesia after miniplate fixation in zygomatic complxex fractures. A total 2 cases of unilateral zygomatic complex fracture, 2-3 weeks old with infra orbital nerve paresthesia were slected. Open reduction and plating was done in frontozygomaticregion. Antiepileptic drug tab topiramate was given in therapeutic doses and dose was increased slowly until functional recovery was noticed. PMID:23833503

Hydronephrosis in mice exposed to TCDD-contaminated breast milk: Identification of the peak period of sensitivity and assessment of potential recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Couture-Haws, L.; Harris, M.W.; McDonald, M.M.

1991-01-01

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of hydronephrosis in mice both pre- and post-natally. To identify the critical period of susceptibility for development of TCDD-induced hydronephrosis in neonatal mice, as well as to characterize the potential for recovery from this renal lesion, dose-response and time-course studies were conducted using lactational exposure. Pregnant C57BL/6N mice were allowed natural delivery. In the dose-response phase of the investigation, mothers were administered 0, 3, 6, or 12 microgram TCDD/kg once by gavage on post natal day (pnd) 1, 4, 8, or 14, and dams and pups were sacrificed on pnd 26.more » In the time-course studies, dams were given a single oral dose of 0 or 9 microgram TCDD/kg on pnd 1, and mothers and litters were subsequently sacrificed on pnd 7, 13, 19, or 26. Neonatal kidneys were examined, and hydronephrotic severity was scored. The incidence and severity of hydronephrosis were significantly elevated above controls at all dose levels on pnd 26 following treatment on pnds 1 and 4, while treatment on pnd 8 or 14 was ineffective at inducing hydronephrosis.« less

Effect of seabuckthorn leaf extracts on circulating energy fuels, lipid peroxidation and antioxidant parameters in rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post stress recovery.

PubMed

Saggu, Shalini; Kumar, Ratan

2008-06-01

The present study was carried out to study mechanism of adaptogenic activity of seabuckthorn leaf extract, administered orally in rats both in single and five doses at a dose of 100mg/kg body weight 30min prior to C-H-R exposure. The efficacy of the extract was studied on circulating energy fuels, lipid peroxidation and anti-oxidant parameters in rats on attaining the T(rec) 23 degrees C during C-H-R exposure and after recovery (T(rec) 37 degrees C) from C-H-R induced hypothermia. Single dose treatment in rats restricted rise in blood malondialdehyde (MDA) levels and decrease in glutathione (GSH) and catalase (CAT) levels. Both single and five doses also restricted the rise in serum free fatty acids (FFA) and lactate dehydrogenase (LDH) levels on attaining T(rec) 23 degrees C during C-H-R exposure, suggesting more efficient utilization of FFA for energy production and better maintained cell membrane permeability. This suggested that the adaptogenic activity of the extract might be due to its anti-oxidative activity, maintained blood glucose levels, better utilization of FFA and improved cell membrane permeability.

Visualization of energy: light dose indicator based on electrochromic gyroid nano-materials

NASA Astrophysics Data System (ADS)

Wei, Di; Scherer, Maik R. J.; Astley, Michael; Steiner, Ullrich

2015-06-01

The typical applications of electrochromic devices do not make use of the charge-dependent, gradual optical response due to their slow voltage-sensitive coloration. However, in this paper we present a design for a reusable, self-powered light dose indicator consisting of a solar cell and a gyroid-structured nickel oxide (NiO) electrochromic display that measures the cumulative charge per se, making use of the efficient voltage-sensitive coloration of gyroid materials. To circumvent the stability issues associated with the standard aqueous electrolyte that is typically accompanied by water splitting and gas evolution, we investigate a novel nano-gyroid NiO electrochromic device based on organic solvents of 1,1,1,3,3,3-hexafluoropropan-2-ol, and room temperature ionic liquid (RTIL) triethylsulfonium bis(trifluoromethylsulfonyl) imide ([SET3][TFSI]) containing lithium bis(trifluoromethylsulfonyl) imide. We show that an effective light dose indicator can be enabled by nano-gyroid NiO with RTIL; this proves to be a reliable device since it does not involve solvent degradation or gas generation.

Hurricane Sandy science plan: coastal topographic and bathymetric data to support hurricane impact assessment and response

USGS Publications Warehouse

Stronko, Jakob M.

2013-01-01

Hurricane Sandy devastated some of the most heavily populated eastern coastal areas of the Nation. With a storm surge peaking at more than 19 feet, the powerful landscape-altering destruction of Hurricane Sandy is a stark reminder of why the Nation must become more resilient to coastal hazards. In response to this natural disaster, the U.S. Geological Survey (USGS) received a total of $41.2 million in supplemental appropriations from the Department of the Interior (DOI) to support response, recovery, and rebuilding efforts. These funds support a science plan that will provide critical scientific information necessary to inform management decisions for recovery of coastal communities, and aid in preparation for future natural hazards. This science plan is designed to coordinate continuing USGS activities with stakeholders and other agencies to improve data collection and analysis that will guide recovery and restoration efforts. The science plan is split into five distinct themes: • Coastal topography and bathymetry • Impacts to coastal beaches and barriers • Impacts of storm surge, including disturbed estuarine and bay hydrology • Impacts on environmental quality and persisting contaminant exposures • Impacts to coastal ecosystems, habitats, and fish and wildlife This fact sheet focuses on coastal topography and bathymetry. This fact sheet focuses on coastal topography and bathymetry.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs.

PubMed

Tamura, Jun; Ishizuka, Tomohito; Fukui, Sho; Oyama, Norihiko; Kawase, Kodai; Miyoshi, Kenjiro; Sano, Tadashi; Pasloske, Kirby; Yamashita, Kazuto

2015-03-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs

PubMed Central

TAMURA, Jun; ISHIZUKA, Tomohito; FUKUI, Sho; OYAMA, Norihiko; KAWASE, Kodai; MIYOSHI, Kenjiro; SANO, Tadashi; PASLOSKE, Kirby; YAMASHITA, Kazuto

2014-01-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone. PMID:25428797

Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non-prescribed drugs.

PubMed

Pedrero-Pérez, Eduardo J; MethaQoL, Grupo

2016-06-14

The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy. Some authors maintain that only doses higher than 50-60 mg/day ought to be considered effective, since only these block all the opioid receptors. But others propose the use of doses adjusted to the needs of the patient, based on their recovery process. Quality of life, satisfaction with treatment, psychopathological symptoms, cognitive performance and additional intake of illegal and unprescribed drugs were evaluated in a representative sample of all patients treated with opioid agonists in the Addiction Institute of Madrid (N = 1898, n = 450) and the Junta de Extremadura (N = 100, n = 65). The results revealed a negative relationship between dose and quality of life, psychopathological symptoms and cognitive performance. Satisfaction with treatment, based on doses negotiated together by doctor and patient, was very high, regardless of the dose. To establish hypothetical causal dependencies among the studied variables structural equation modelling was performed. The results reject the need for high dosage if not required by the patient, and highlight the benefits of other psychosocial interventions that lead to recovery, despite the chronification that could imply the use of high doses. Whereas high dosage programmes provide better indicators of social control, the patient's quality of life must be one of the main indicators of a successful treatment, as in any other health problem.

NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

PubMed Central

Mansky, Patrick J.; Sannes, Timothy S.; Johnson, Laura Lee; Blackman, Marc R.; Grem, Jean L.; Swain, Sandra M.; Monahan, Brian P.

2013-01-01

Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone. PMID:24285980

Merthiolate poisoning

MedlinePlus

... gets medical help, the better the chance for recovery. Kidney dialysis (filtration) through a machine may be needed if the kidneys do not recover after acute mercury poisoning, Kidney failure and death can occur, even with small doses.

Schwann Cells Transplantation Improves Locomotor Recovery in Rat Models with Spinal Cord Injury: a Systematic Review and Meta-Analysis.

PubMed

Yang, Lei; Ge, Yingbin; Tang, Jian; Yuan, Jinxia; Ge, Dawei; Chen, Hongtao; Zhang, Hongxiu; Cao, Xiaojian

2015-01-01

Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI. Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library Medline databases and analyzed by Review Manager 5.2.5. Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemi-sected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding. SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI. © 2015 The Author(s) Published by S. Karger AG, Basel.

Radiotherapy Dose-Volume Effects on Salivary Gland Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

Sugammadex is effective in reversing rocuronium in the presence of antibiotics

PubMed Central

2014-01-01

Background The effectiveness of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in the presence of drugs that may potentiate NMB remains to be fully established. The aim of this post-hoc analysis of data from a Phase III clinical trial (VISTA; NCT00298831) was to investigate the impact of antibiotics on recovery from rocuronium-induced NMB after administration of sugammadex for reversal, and compared the neuromuscular recovery in patients who received antibiotics preoperatively with those who did not. Methods A Phase III, multicenter, open-label study designed to reflect potential use of sugammadex in clinical practice was conducted at 19 sites. Data obtained from patients who received antibiotics were compared with the cohort of patients who underwent the same protocol without antibiotics. Each subject received rocuronium 0.6 mg/kg for muscle relaxation, after which tracheal intubation was performed; patients were also permitted to receive maintenance doses of rocuronium 0.15 mg/kg to maintain the desired level of NMB throughout the operation, as required.. At least 15 min after the last rocuronium dose, patients received sugammadex 4.0 mg/kg for reversal. Neuromuscular monitoring was continued until a train-of-four (TOF) ratio of ≥0.9 was achieved or the anesthetic was discontinued. Results The presence of antibiotics prior to the administration of sugammadex did not affect the recovery time from rocuronium-induced NMB when sugammadex 4.0 mg/kg was administered at least 15 min after the last dose of rocuronium. In the presence of antibiotics, the geometric mean (95% CI) time from administration of sugammadex 4.0 mg/kg to recovery of the TOF ratio to ≥0.9 was 1.6 (1.4–1.9) min (range: 0.7–10.5 min), compared with 2.0 (1.8–2.3) min (range: 0.7–22.3 min) for patients who did not receive antibiotics. Conclusions These findings suggest that prophylactic antibiotic use is unlikely to have a major impact on the recovery time from rocuronium-induced NMB with sugammadex reversal. Trial registration ClinicalTrials.gov Identifier: NCT00298831. PMID:25157214

Sugammadex is effective in reversing rocuronium in the presence of antibiotics.

PubMed

Hudson, Mark E; Rietbergen, Henk; Chelly, Jacques E

2014-01-01

The effectiveness of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in the presence of drugs that may potentiate NMB remains to be fully established. The aim of this post-hoc analysis of data from a Phase III clinical trial (VISTA; NCT00298831) was to investigate the impact of antibiotics on recovery from rocuronium-induced NMB after administration of sugammadex for reversal, and compared the neuromuscular recovery in patients who received antibiotics preoperatively with those who did not. A Phase III, multicenter, open-label study designed to reflect potential use of sugammadex in clinical practice was conducted at 19 sites. Data obtained from patients who received antibiotics were compared with the cohort of patients who underwent the same protocol without antibiotics. Each subject received rocuronium 0.6 mg/kg for muscle relaxation, after which tracheal intubation was performed; patients were also permitted to receive maintenance doses of rocuronium 0.15 mg/kg to maintain the desired level of NMB throughout the operation, as required.. At least 15 min after the last rocuronium dose, patients received sugammadex 4.0 mg/kg for reversal. Neuromuscular monitoring was continued until a train-of-four (TOF) ratio of ≥0.9 was achieved or the anesthetic was discontinued. The presence of antibiotics prior to the administration of sugammadex did not affect the recovery time from rocuronium-induced NMB when sugammadex 4.0 mg/kg was administered at least 15 min after the last dose of rocuronium. In the presence of antibiotics, the geometric mean (95% CI) time from administration of sugammadex 4.0 mg/kg to recovery of the TOF ratio to ≥0.9 was 1.6 (1.4-1.9) min (range: 0.7-10.5 min), compared with 2.0 (1.8-2.3) min (range: 0.7-22.3 min) for patients who did not receive antibiotics. These findings suggest that prophylactic antibiotic use is unlikely to have a major impact on the recovery time from rocuronium-induced NMB with sugammadex reversal. ClinicalTrials.gov Identifier: NCT00298831.

Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Zhonghe; Yan Chao; Zhang Zhiyuan

Purpose: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Methods and Materials: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n = 5 patients) and postoperative (n = 47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGsmore » spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Results: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Conclusions: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.« less

Streptomycin ototoxicity and hair cell regeneration in the adult pigeon utricle

NASA Technical Reports Server (NTRS)

Frank, T. C.; Dye, B. J.; Newlands, S. D.; Dickman, J. D.

1999-01-01

OBJECTIVE: The purpose of this study was to develop a technique to investigate the regeneration of utricular hair cells in the adult pigeon (Columba livia) following complete hair cell loss through administration of streptomycin. STUDY DESIGN: Experimental animal study. METHODS: Animals were divided into four groups. Group 1 received 10 to 15 days of systemic streptomycin injections. Animals in Groups 2 and 3 received a single direct placement of a 1-, 2-, 4-, or 8-mg streptomycin dose into the perilymphatic space. Animals in Groups 1 and 2 were analyzed within 1 week from injection to investigate hair cell destruction, whereas Group 3 was investigated at later dates to study hair cell recovery. Group 4 animals received a control injection of saline into the perilymphatic space. Damage and recovery were quantified by counting hair cells in isolated utricles using scanning electron microscopy. RESULTS: Although systemic injections failed to reliably achieve complete utricular hair cell destruction, a single direct placement of a 2-, 4-, or 8-mg streptomycin dose caused complete destruction within the first week. Incomplete hair cell loss was observed with the 1-mg dose. Over the long term, regeneration of the hair cells was seen with the 2-mg dose but not the 8-mg dose. Control injections of saline into the perilymphatic space caused no measurable hair cell loss. CONCLUSIONS: Direct placement of streptomycin into the perilymph is an effective, reliable method for complete destruction of utricular hair cells while preserving the regenerative potential of the neuroepithelium.

Balanced propofol sedation administered by nonanesthesiologists: The first Italian experience

PubMed Central

Repici, Alessandro; Pagano, Nico; Hassan, Cesare; Carlino, Alessandra; Rando, Giacomo; Strangio, Giuseppe; Romeo, Fabio; Zullo, Angelo; Ferrara, Elisa; Vitetta, Eva; Ferreira, Daniel de Paula Pessoa; Danese, Silvio; Arosio, Massimo; Malesci, Alberto

2011-01-01

AIM: To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies. METHODS: Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected. RESULTS: Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively. CONCLUSION: A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation. PMID:21987624

Reduced somatosensory impairment by piezosurgery during orthognathic surgery of the mandible.

PubMed

Brockmeyer, Phillipp; Hahn, Wolfram; Fenge, Stefan; Moser, Norman; Schliephake, Henning; Gruber, Rudolf Matthias

2015-09-01

This clinical trial aimed to test the hypothesis that piezosurgery causes reduced nerval irritations and, thus, reduced somatosensory impairment when used in orthognathic surgery of the mandible. To this end, 37 consecutive patients with Angle Class II and III malocclusion were treated using bilateral sagittal split osteotomies (BSSO) of the mandible. In a split mouth design, randomized one side of the mandible was operated using a conventional saw, while a piezosurgery device was used on the contralateral side. In order to test the individual qualities of somatosensory function, quantitative sensory testings (QSTs) were performed 1 month, 6 months and 1 year after surgery. A comparison of the data using a two-way analysis of variance (ANOVA) revealed a significant reduction in postoperative impairment in warm detection threshold (WDT) (P = 0.046), a decreased dynamic mechanical allodynia (ALL) (P = 0.002) and a decreased vibration detection threshold (VDT) (P = 0.030) on the piezosurgery side of the mandible as opposed to the conventionally operated control side. In the remaining QSTs, minor deviations from the preoperative baseline conditions and a more rapid regression could be observed. Piezosurgery caused reduced somatosensory impairment and a faster recovery of somatosensory functions in the present investigation.

Comparison of Etomidate, Benzocaine, and MS222 Anesthesia with and without Subsequent Flunixin Meglumine Analgesia in African Clawed Frogs (Xenopus laevis).

PubMed

Smith, Briony D; Vail, Krystal J; Carroll, Gwendolyn L; Taylor, Maggie C; Jeffery, Nicholas D; Vemulapalli, Tracy H; Elliott, James J

2018-03-01

Often few alternative anesthetics for exotic species are available, due to the small numbers of these animals used in research. In this study, we evaluated the depth and duration of anesthesia in Xenopus laevis after their immersion in 3 doses of etomidate (15, 22.5, and 30 mg/L) and in 3 doses of benzocaine (0.1%, 0.5%, and 1%) compared with the 'gold standard,' tricaine methanesulfonate (MS222; 2 g/L). We then chose an optimal dose for each alternative anesthetic according to induction time, duration of surgical plane, and time to complete recovery. The optimal etomidate and benzocaine doses (22.5 mg/L and 0.1%, respectively) as well as the MS222 dose were then used to achieve a surgical plane of anesthesia, with the addition of flunixin meglumine (25 or 50 mg/kg) administered in the dorsal lymph sac at the completion of mock oocyte harvest. Efficacy of the analgesic was assessed at 1, 3, 6, and 24 h postoperatively by using acetic acid testing (AAT). Histology of the liver, kidney, and tissues surrounding the dorsal lymph sac was performed at day 3, 14, and 28 in each group of animals. Mild to moderate myocyte degeneration and necrosis were present in tissues surrounding the dorsal lymph sac at both flunixin meglumine doses after etomidate and benzocaine anesthesia. In addition, the 50-mg/kg dose of flunixin meglumine resulted in the death of 5 of the 12 frogs within 24 h, despite an otherwise uneventful anesthetic recovery. In conclusion, benzocaine and etomidate offer alternative anesthetic regimens, according to typical requirements for an anesthetic event. Flunixin meglumine at the 25-mg/kg dose provided analgesic relief at the latest time point during etomidate dosage and at all time points during benzocaine dosage, but further characterization is warranted regarding long-term or repeated analgesic administration.

A point kernel algorithm for microbeam radiation therapy

NASA Astrophysics Data System (ADS)

Debus, Charlotte; Oelfke, Uwe; Bartzsch, Stefan

2017-11-01

Microbeam radiation therapy (MRT) is a treatment approach in radiation therapy where the treatment field is spatially fractionated into arrays of a few tens of micrometre wide planar beams of unusually high peak doses separated by low dose regions of several hundred micrometre width. In preclinical studies, this treatment approach has proven to spare normal tissue more effectively than conventional radiation therapy, while being equally efficient in tumour control. So far dose calculations in MRT, a prerequisite for future clinical applications are based on Monte Carlo simulations. However, they are computationally expensive, since scoring volumes have to be small. In this article a kernel based dose calculation algorithm is presented that splits the calculation into photon and electron mediated energy transport, and performs the calculation of peak and valley doses in typical MRT treatment fields within a few minutes. Kernels are analytically calculated depending on the energy spectrum and material composition. In various homogeneous materials peak, valley doses and microbeam profiles are calculated and compared to Monte Carlo simulations. For a microbeam exposure of an anthropomorphic head phantom calculated dose values are compared to measurements and Monte Carlo calculations. Except for regions close to material interfaces calculated peak dose values match Monte Carlo results within 4% and valley dose values within 8% deviation. No significant differences are observed between profiles calculated by the kernel algorithm and Monte Carlo simulations. Measurements in the head phantom agree within 4% in the peak and within 10% in the valley region. The presented algorithm is attached to the treatment planning platform VIRTUOS. It was and is used for dose calculations in preclinical and pet-clinical trials at the biomedical beamline ID17 of the European synchrotron radiation facility in Grenoble, France.

Dexmedetomidine in the Supratentorial Craniotomy

PubMed Central

Ilhan, Osman; Koruk, Senem; Serin, Gokcen; Erkutlu, Ibrahim; Oner, Unsal

2010-01-01

Objective: In this double-blind prospective clinical study, we investigated the effects of fentanyl and dexmedetomidine as adjuvant agents in supratentorial craniotomies on the following: hemodynamic changes during perioperative and recovery periods, brain edema perioperatively, recovery times and side effects, such as hypertension, shivering, nausea and vomiting. Materials and Methods: Thirty consenting ASA physical status I–II patients undergoing intracranial tumor surgery were randomly divided in two groups. In group D (n=15), dexmedetomidine was infused as a 1 μg/kg bolus dose 10 minutes before induction of anesthesia and maintained with 0.4–0.5 μg/kg/min during the operation. In group F (n=15), animals were given fentanyl 0.02 μg/kg/min as an infusion for anesthesia maintenance. At induction, fentanyl was given as a 2 μg/kg dose in group D and as a 4 μg/kg dose in group F. Hemodynamic changes, recovery times and postoperative side effects were recorded before induction, during the perioperative period and 24 hours postoperatively. Results: In group D; MAP and HR values after intubation, after skull clamp insertion and after extubation were lower than in group F (p<0.05). In group D, cerebral relaxation scores were also significantly lower. Recovery times were found to be shorter in group D as compared to group F; the same trend was observed for the supplemental opioid requirement. During the postoperative period, there was no shivering, nausea or vomiting in group D, but in group F, 3 patients complained of shivering, and 2 patients experienced nausea and vomiting. Conclusion: In our study, we found that dexmedetomidine controlled the hemodynamic changes better than fentanyl perioperatively, after extubation and during the early postoperative period. Our results suggest that that dexmedetomidine is safer and more effective in controlling hemodynamic changes during surgical stimulation than the standard agents used in neuroanesthesia. PMID:25610125

The effect of a single dose of preemptive pregabalin administered with COX-2 inhibitor: a trial in total knee arthroplasty.

PubMed

Lee, Jin Kyu; Chung, Kyu-Sung; Choi, Choong Hyeok

2015-01-01

We sought to compare a group (Group L) (n=21) of patients that underwent total knee arthroplasty and received a single preoperative dose of pregabalin combined with a COX-2 inhibitor with a control group (Group C) (n=20) that only received a COX-2 inhibitor in terms of (1) acute postoperative pain intensity, (2) analgesic consumption, and (3) functional recovery. Mean cumulative fentanyl consumption during the first 48 hours was lower in Group L than in Group C (P<0.05). The pain scores at rest were lower in Group L at 6 and 12 hours after surgery (P<0.05). No significant intergroup difference was noted in functional recovery. The addition of pregabalin led to an additive reduction in early postoperative pain and analgesic consumption. Copyright © 2014 Elsevier Inc. All rights reserved.

Sustained trilineage recovery and disappearance of abnormal chromosome clone in a patient with myelodysplastic syndrome following combination therapy with cytokines (granulocyte colony-stimulating factor and erythropoietin) and high-dose methylprednisolone.

PubMed

Imai, Y; Fukuoka, T; Nakatani, A; Ohsaka, A; Takahashi, A

1996-04-01

We report a case of hypoplastic myelodyplastic syndrome (MDS) (refractory anemia (RA)) in which sustained trilineage haematological response and persistent disappearance of an abnormal chromosome clone were achieved after treatment with combination therapy of cytokines (granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo)) and methylprednisolone (mPSL) pulse dose. The patient's haematological recovery was rapid and maintained even after cessation of the therapy. In addition, the predominant chromosome clone 13q- in bone marrow cells disappeared in the fourth week. The patient's improved bone marrow haemopoiesis and disappearance of the abnormal chromosome has continued to the present, 13 months after treatment. The occurrence of both trilineage response and abnormal chromosome disappearance in MDS patients treated with cytokine(s) or steroids is rare. Combination therapy might therefore be advantageous in MDS.

The dose-response of time served in prison on mortality: New York State, 1989-2003.

PubMed

Patterson, Evelyn J

2013-03-01

I investigated the differential impact of the dose-response of length of stay on postprison mortality among parolees. Using 1989-2003 New York State parole administrative data from the Bureau of Justice Statistics on state correctional facilities, I employed multinomial logistic regression analyses and formal demographic techniques that used the life table of the populations to deduce changes in life expectancy. Each additional year in prison produced a 15.6% increase in the odds of death for parolees, which translated to a 2-year decline in life expectancy for each year served in prison. The risk was highest upon release from prison and declined over time. The time to recovery, or the lowest risk level, was approximately two thirds of the time served in prison. Incarceration reduces life span. Future research should investigate the pathways to this higher mortality and the possibilities of recovery.

Optimizing a readout protocol for low dose retrospective OSL-dosimetry using household salt.

PubMed

Christiansson, Maria; Mattsson, Sören; Bernhardsson, Christian; Rääf, Christopher L

2012-06-01

The authors' aim has been to find a single aliquot regenerative dose (SAR) protocol that accurately recovers an unknown absorbed dose in the region between 1-250 mGy in household salt. The main investigation has been conducted on a specific mine salt (>98.5% NaCl) intended for household use, using optical stimulation by blue LED (λ = 462 nm). The most accurate dose recovery for this brand of salt is found to be achieved when using Peak Signal Summing (PSS) of the OSL-decay and a preheat temperature of 200°C after the test dose. A SAR protocol for the household salt with preset values of regenerative doses (R1--R5) and a test dose (TED) of 17 mGy is also suggested here. Under laboratory conditions, the suggested protocol recovers unknown absorbed doses in this particular brand within 5% (2 SD) in the dose range between 1-250 mGy. This is a very promising result for low dose applications of household salt as a retrospective dosimeter after a nuclear or radiological event.

Diet composition modifies the toxicity of repeated soman exposure in rats.

PubMed

Langston, Jeffrey L; Myers, Todd M

2011-12-01

It was previously demonstrated that diet potently modulates the toxic effects of an acute lethal dose of the nerve agent soman. The current investigation was undertaken to examine the influence of diet on the cumulative toxicity of repeated soman administration. Rats were fed one of four distinct diets (standard, choline-enriched, glucose-enriched, or ketogenic) for four weeks prior to and throughout a repeated soman dosing and recovery regimen. Each diet group included animals exposed to an equivalent volume of saline that served as negative controls. In exposure Week 1, animals received three consecutive daily doses of 0.4 LD(50) soman. In exposure Week 2, animals received four consecutive daily doses of 0.5 LD(50) soman. In exposure Week 3, animals received five consecutive daily doses of 0.5 LD(50) soman. Week 4 constituted a post-exposure recovery evaluation. Throughout the experiment, behavioral function was assessed by a discriminated avoidance test that required intact sensory and motor function. Survival and body weight changes were recorded daily. Differences in toxicity as a function of diet composition became apparent during the first week. Specifically, rats fed the glucose-enriched diet showed pronounced intoxication during Week 1, resulting in imperfect survival, weight loss, and deteriorated avoidance performance relative to all other groups. All rats fed the glucose-enriched diet died by the end of exposure Week 2. In contrast, only 10% of animals fed the standard diet died by the end of Week 2. Also in Week 2, weight loss and disrupted avoidance performance were apparent for all groups except for those fed the ketogenic diet. This differential effect of diet composition became even more striking in Week 3 when survival in the standard and choline diet groups approximated 50%, whereas survival equaled 90% in the ketogenic diet group. Avoidance performance and weight loss measures corroborated the differential toxicity observed across diet groups. Upon cessation of soman exposure during the final week, recovery of weight and avoidance performance in survivors was comparable across diet groups. These results systematically replicate previous findings demonstrating that diet composition exacerbates or attenuates toxicity in rodents exposed acutely to organophosphorus compounds. Published by Elsevier B.V.

Oxycodone recycling: a novel hypothesis of opioid tolerance development in humans.

PubMed

Linares, Oscar A; Fudin, Jeffrey; Schiesser, William E; Linares, Annemarie Daly; Boston, Raymond C

2014-09-01

We hypothesize that oxycodone (OC) recycling promotes sustained synaptic OC content, which prolongs OC's exposure to local μ-opioid receptors (μORs). In that way, OC recycling gives rise to OC tolerance in humans. To pilot test our hypothesis, we developed a whole-body OC mass transport tolerance recovery model. The model derived quantifiable measure of tolerance is TΩ. TΩ estimates OC's tolerance recovery in days; It is defined as the rate of recovery of OC's pharmacologic response after OC is stopped. We studied a random sample of five opioid intolerant healthy male subjects with no history of opioid or illicit drug use, or comorbidities in silico. Subjects were age 24.5 ± 2.3 yr (all values mean ± SD), weight 93 ± 20 kg, and CYP2D6 EM phenotype. Each subject was studied under two experimental conditions: (1) administration of a single oral dose of OC 12 ± 7 mg; and, after complete washout of OC from the intravascular pool, (2) administration of repetitive oral OC doses every 4h for 5 half-lives (t1/2 = 4.5h)-after which time steady-state was assumed. Repetitive OC dose TΩ fell 61% compared to single OC dose TΩ (5.2 ± 1.1 vs. 3.5 ± 0.7 days, p = 0.001). The fall in TΩ was associated with a significant 3-fold increase in extravascular OC content, which was accompanied by 2-fold increase in OC spillover from the extravascular pool, into the intravascular pool. Thus, the model predicted that a single dose of orally administered OC could give rise to tolerance. This is consistent with the widely held view of acute opioid tolerance. In addition, the dynamic changes accompanying repetitive OC dosing suggested that local unbound OC gave rise to both higher extravascular OC content and increased OC spillover. This reflects that OC stimulated endocytosis of μORs was accompanied by a reduction in the availability OC responsive neuroeffector cell surface μOR binding sites. We conclude that our hypothesis extends current concepts of opioid tolerance development to include OC recycling. OC recycling is a novel hypothesis of OC tolerance development in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reversal of Pipecuronium-Induced Moderate Neuromuscular Block with Sugammadex in the Presence of a Sevoflurane Anesthetic: A Randomized Trial.

PubMed

Tassonyi, Edömér; Pongrácz, Adrienn; Nemes, Réka; Asztalos, László; Lengyel, Szabolcs; Fülesdi, Béla

2015-08-01

Pipecuronium is a steroidal neuromuscular blocking agent. Sugammadex, a relaxant binding γ-cyclodextrin derivative, reverses the effect of rocuronium, vecuronium, and pancuronium. We investigated whether sugammadex reverses moderate pipecuronium-induced neuromuscular blockade (NMB) and the doses required to achieve reversal. This single-center, randomized, double-blind, 5-group parallel-arm study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX) according to international standards. When the NMB recovered spontaneously to train-of-four count 2, patients randomly received 1.0, 2.0, 3.0, or 4.0 mg/kg of sugammadex or placebo. Recovery time from sugammadex injection to normalized train-of-four (TOF) ratio 0.9 was the primary outcome variable. The recovery time from the sugammadex injection to final T1 was the secondary end point. Postoperative neuromuscular functions were also assessed. Each patient who received sugammadex recovered to a normalized TOF ratio of 0.9 within 5.0 minutes (95% lower confidence interval for the lowest dose 70.1%; for all doses 90.8%) and 79% of these patients reached a normalized TOF ratio 0.9 within 2.0 minutes (95% lower confidence interval for the lowest dose 26.7%; for all doses 63.7%). T1 recovered several minutes after the TOF ratio. No residual postoperative NMB was observed. Sugammadex adequately and rapidly reverses pipecuronium-induced moderate NMB during sevoflurane anesthesia. Once the train-of-four count has spontaneously returned to 2 responses following pipecuronium administration, a dose of 2.0 mg/kg of sugammadex is sufficient to reverse the NMB.

Effects of a pre-moistened multilayered breathable fabric in promoting heat loss during recovery after exercise under hot conditions.

PubMed

Foreman, J H; Benson, G J; Foreman, M H

2006-08-01

Horses generate considerable internal heat burdens when exercising. Although common practice for a trainer or groom to place a wet blanket or towel on the dorsum of a hot horse post exercise, there are no data supporting the efficacy of this cooling method. To test the hypothesis that a pre-moistened blanket designed with a multilayered breathable fabric would enhance heat loss in horses post exercise. Eight treadmill-trained horses performed a standardised exercise test (SET) weekly for 3 weeks, with 3 different recovery treatments administered randomly. Pulmonary artery temperature (PAT) was measured via Swan-Ganz catheter. The SET consisted of 10 min at 3.7 m/sec, 3 min at 11.0 m/sec, 25 min at 3.7 m/sec and 20 min of recovery walking at 2.0 m/sec (58 min exercise and recovery under laboratory conditions of 35.0-40.6 degrees C and 27-49% RH). From 3-7 min during recovery, the treadmill was stopped and horses randomly received either: (a) no bath (negative control); (b) a bath consisting of 32 l of 1-4 degrees C water split into 3-4 cycles of bilateral water application (positive control) followed by water removal ('scraping'); or (c) application of a multilayered fabric blanket soaked in 16-19 degrees C water, wrung out, and placed over the dorsum and sides of the horse. PAT was compared using RM ANOVA with the Student Neuman-Keul's test used post hoc to discriminate between treatments at specific points in time. Mean PAT rose with each phase of exercise (P<0.001) and peaked at a mean of 40.2 +/- 0.2 degrees C. During recovery, the cold bath decreased HR and PAT for 9 min after walking resumed (P<0.001-P<0.05). The blanket did not decrease HR or PAT compared to negative control (P>0.05), and both were hotter than the cold bath treatment through 16 min of recovery (P<0.05). A specially-designed cooling blanket failed to reduce PAT when compared to negative control. Cold water bathing decreased HR and PAT but was not effective throughout all of recovery. A specially-designed, pre-moistened multilayered breathable fabric failed to promote evaporative cooling compared to negative control. Cold water baths may need to be repeated throughout recovery to optimise their effect.

Quality and Dose Optimized CT Trauma Protocol - Recommendation from a University Level-I Trauma Center.

PubMed

Kahn, Johannes; Kaul, David; Böning, Georg; Rotzinger, Roman; Freyhardt, Patrick; Schwabe, Philipp; Maurer, Martin H; Renz, Diane Miriam; Streitparth, Florian

2017-09-01

Purpose  As a supra-regional level-I trauma center, we evaluated computed tomography (CT) acquisitions of polytraumatized patients for quality and dose optimization purposes. Adapted statistical iterative reconstruction [(AS)IR] levels, tube voltage reduction as well as a split-bolus contrast agent (CA) protocol were applied. Materials and Methods  61 patients were split into 3 different groups that differed with respect to tube voltage (120 - 140 kVp) and level of applied ASIR reconstruction (ASIR 20 - 50 %). The CT protocol included a native acquisition of the head followed by a single contrast-enhanced acquisition of the whole body (64-MSCT). CA (350 mg/ml iodine) was administered as a split bolus injection of 100 ml (2 ml/s), 20 ml NaCl (1 ml/s), 60 ml (4 ml/s), 40 ml NaCl (4 ml/s) with a scan delay of 85 s to detect injuries of both the arterial system and parenchymal organs in a single acquisition. Both the quantitative (SNR/CNR) and qualitative (5-point Likert scale) image quality was evaluated in parenchymal organs that are often injured in trauma patients. Radiation exposure was assessed. Results  The use of IR combined with a reduction of tube voltage resulted in good qualitative and quantitative image quality and a significant reduction in radiation exposure of more than 40 % (DLP 1087 vs. 647 mGyxcm). Image quality could be improved due to a dedicated protocol that included different levels of IR adapted to different slice thicknesses, kernels and the examined area for the evaluation of head, lung, body and bone injury patterns. In synopsis of our results, we recommend the implementation of a polytrauma protocol with a tube voltage of 120 kVp and the following IR levels: cCT 5mm: ASIR 20; cCT 0.625 mm: ASIR 40; lung 2.5 mm: ASIR 30, body 5 mm: ASIR 40; body 1.25 mm: ASIR 50; body 0.625 mm: ASIR 0. Conclusion  A dedicated adaptation of the CT trauma protocol (level of reduction of tube voltage and of IR) according to the examined body region (head, lung, body, bone) combined with a split bolus CA injection protocol allows for a high-quality CT examination and a relevant reduction of radiation exposure in the examination of polytraumatized patients Key Points   · Dedicated adaption of the CT trauma protocol allows for an optimized examination.. · Different levels of iterative reconstruction, tube voltage and the CA injection protocol are crucial.. · A reduction of radiation exposure of more than 40 % with good image quality is possible.. Citation Format · Kahn J, Kaul D, Böning G et al. Quality and Dose Optimized CT Trauma Protocol - Recommendation from a University Level-I Trauma Center. Fortschr Röntgenstr 2017; 189: 844 - 854. © Georg Thieme Verlag KG Stuttgart · New York.

Assessment of the effectiveness of orange (Citrus reticulata) peel in the recovery of nickel from electroplating wastewater.

PubMed

Hussein, Rim A

2014-12-01

Wastewater discharged from electroplating industry contains different concentrations of heavy metals, which when released into the environment pose a health hazard to human beings. The aim of this study was to assess the effectiveness of orange peel as an adsorbent in the recovery of Nickel (Ni) from electroplating wastewater. The effectiveness of orange peel as an adsorbent was assessed by determining the optimum conditions of adsorption (adsorbent dose, pH, and contact time), calculating the recovery percentage, and characterizing the orange peel sludge resulting from adsorption/desorption process as being hazardous or not. Under optimum conditions for adsorption, orange peel was found to be an effective adsorbent of Ni from electroplating wastewater. It achieved 59.28% removal of the metal from a solution containing 528 mg/l, at a dose of 60 g/l, at pH 7, and for 1-h contact time. The nickel uptake capacity of orange peel was calculated to be 5.2 mg/g. Using HCl for desorption of adsorbed Ni, a recovery of 44.46% of Ni discharged in the wastewater could be reached. Orange peel resulting from the adsorption/desorption process was characterized as being nonhazardous. Orange peel was found to be effective in the recovery of nearly half of the amount of Ni discharged in electroplating wastewater. Further studies are required to determine (a) the impact of the recovered NiCl2 solution on the quality of the plated product, (b) the effect of activation of orange peel on the adsorption process, and (c) the number of cycles during which orange peel can be reused as an effective adsorbent.

A comparison of sugammadex and neostigmine for reversal of rocuronium-induced neuromuscular blockade in children.

PubMed

Ammar, A S; Mahmoud, K M; Kasemy, Z A

2017-04-01

Sugammadex is designed to be a reversal agent for steroidal muscle relaxants. The current trial was aimed to compare between sugammadex and neostigmine concerning the recovery time from neuromuscular blockade. We hypothesised that sugammadex might have shorter recovery time than neostigmine. Sixty paediatric patients aged 2-10 years scheduled for lower abdominal surgeries were randomly assigned into two equal groups to receive 4 mg/kg sugammadex (Group S) or 0.35 mg/kg neostigmine and 0.02 mg/kg atropine (Group N) as a reversal agent for rocuronium at the end of surgery. Primary outcome was the recovery time [time from starting of sugammadex or neostigmine till reaching train of four (TOF) ratio> 0.9] whereas secondary outcomes included number of patients who needed another dose of sugammadex or neostigmine to reach TOF ratio> 0.9, extubation time (time from stoppage of anaesthetic inhalation until the patient fulfilled criteria for safe extubation, post-anaesthesia care unit (PACU) discharge time and post-operative adverse effects. The mean recovery and extubation times were significantly shorter (P = 0.002 and 0.005) in Group S compared with Group N (2.5 and 2.0 min vs. 12.6 min and 4.3 min respectively). In the Group N, eight patients needed another reversal dose compared with one patient in Group S (P = 0.035). PACU discharge time showed no significant difference between both groups. Incidence of nausea, vomiting, tachycardia, and dry mouth were significantly higher in Group N. Sugammadex administration in children resulted in faster recovery and extubation times and lower incidence of adverse events compared with neostigmine. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Advanced oxidative processes and membrane separation for micropollutant removal from biotreated domestic wastewater.

PubMed

Silva, Larissa L S; Sales, Julio C S; Campos, Juacyara C; Bila, Daniele M; Fonseca, Fabiana V

2017-03-01

The presence of micropollutants in sewage is already widely known, as well as the effects caused by natural and synthetic hormones. Thus, it is necessary to apply treatments to remove them from water systems, such as advanced oxidation processes (AOPs) and membrane separation processes, which can oxidize and remove high concentrations of organic compounds. This work investigated the removal of 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and estriol (E3) from biotreated sewage. Reverse osmosis processes were conducted at three recoveries (50, 60, and 70 %). For E2 and EE2, the removals were affected by the recovery. The best results for RO were as follows: the E2 compound removal was 89 % for 60 % recovery and the EE2 compound removal was 57 % for 50 % recovery. The RO recovery did not impact the E3 removal. It was concluded that the interaction between the evaluated estrogens, and the membrane was the major factor for the hormone separation. The AOP treatment using H 2 O 2 /UV was carried out in two sampling campaigns. First, we evaluated the variation of UV doses (24.48, 73.44, 122.4, and 244.8 kJ m -2 ) with 18.8 mg L -1 of H 2 O 2 in the reaction. EE2 showed considerable removals (around 70 %). In order to optimize the results, an experimental design was applied. The best result was obtained with higher UV dose (122.4 kJ m -2 ) and lower H 2 O 2 concentration (4 mg L -1 ), achieving removal of 91 % for E3 and 100 % for E2 and EE2.

Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling.

PubMed

Baek, Sang-Min; Yu, Seung-Young; Son, Youngsook; Hong, Hyun Sook

2016-01-01

Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress. To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3β activation in RPE cells in vitro. H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3β signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells. SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3β signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases.

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial.

PubMed

Rigby-Jones, Ann E; Sneyd, J Robert; Vijn, Peter; Boen, Patrick; Cross, Maurice

2010-06-29

Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy

PubMed Central

Valiante, Flavio; Bellumat, Angelo; De Bona, Manuela; De Boni, Michele

2013-01-01

AIM: To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. METHODS: This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. Interventions: BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. RESULTS: Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). CONCLUSION: BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy. PMID:24023492

Effect of single-dose low-level helium-neon laser irradiation on orthodontic pain: a split-mouth single-blind placebo-controlled randomized clinical trial.

PubMed

Sobouti, Farhad; Khatami, Maziar; Chiniforush, Nasim; Rakhshan, Vahid; Shariati, Mahsa

2015-01-01

Pain is the most common complication of orthodontic treatment. Low-level laser therapy (LLLT) has been suggested as a new analgesic treatment free of the adverse effects of analgesic medications. However, it is not studied thoroughly, and the available studies are quite controversial. Moreover, helium neon (He-Ne) laser has not been assessed before. This split-mouth placebo-controlled randomized clinical trial was performed on 16 male and 14 female orthodontic patients requiring bilateral upper canine retraction. The study was performed at a private clinic in Sari, Iran, in 2014. It was single blind: patients, orthodontist, and personnel were blinded of the allocations, but the laser operator (periodontist) was not blinded. Once canine retractor was activated, a randomly selected maxillary quarter received a single dose of He-Ne laser irradiation (632.8 nm, 10 mw, 6 j/cm(2) density). The other quarter served as the placebo side, treated by the same device but powered off. In the first, second, fourth, and seventh days, blinded patients rated their pain sensed on each side at home using visual analog scale (VAS) questionnaires. There was no harm identified during or after the study. Pain changes were analyzed using two- and one-way repeated-measures ANOVA, Bonferroni, and t-test (α = 0.01, β > 0.99). This trial was not registered. It was self-funded by the authors. Sixteen males and 11 females remained in the study (aged 12-21). Average pain scores sensed in all 4 intervals on control and laser sides were 4.06 ± 2.85 and 2.35 ± 1.77, respectively (t-test P < 0.0001). One-way ANOVA showed significant pain declines over time, in each group (P < 0.0001). Two-way ANOVA showed significant effects for LLLT (P < 0.0001) and time (P = <0.0001). Single-dose He-Ne laser therapy might reduce orthodontic pain caused by retracting maxillary canines.

Cardiac Autonomic Responses during Exercise and Post-exercise Recovery Using Heart Rate Variability and Systolic Time Intervals-A Review.

PubMed

Michael, Scott; Graham, Kenneth S; Davis, Glen M

2017-01-01

Cardiac parasympathetic activity may be non-invasively investigated using heart rate variability (HRV), although HRV is not widely accepted to reflect sympathetic activity. Instead, cardiac sympathetic activity may be investigated using systolic time intervals (STI), such as the pre-ejection period. Although these autonomic indices are typically measured during rest, the "reactivity hypothesis" suggests that investigating responses to a stressor (e.g., exercise) may be a valuable monitoring approach in clinical and high-performance settings. However, when interpreting these indices it is important to consider how the exercise dose itself (i.e., intensity, duration, and modality) may influence the response. Therefore, the purpose of this investigation was to review the literature regarding how the exercise dosage influences these autonomic indices during exercise and acute post-exercise recovery. There are substantial methodological variations throughout the literature regarding HRV responses to exercise, in terms of exercise protocols and HRV analysis techniques. Exercise intensity is the primary factor influencing HRV, with a greater intensity eliciting a lower HRV during exercise up to moderate-high intensity, with minimal change observed as intensity is increased further. Post-exercise, a greater preceding intensity is associated with a slower HRV recovery, although the dose-response remains unclear. A longer exercise duration has been reported to elicit a lower HRV only during low-moderate intensity and when accompanied by cardiovascular drift, while a small number of studies have reported conflicting results regarding whether a longer duration delays HRV recovery. "Modality" has been defined multiple ways, with limited evidence suggesting exercise of a greater muscle mass and/or energy expenditure may delay HRV recovery. STI responses during exercise and recovery have seldom been reported, although limited data suggests that intensity is a key determining factor. Concurrent monitoring of HRV and STI may be a valuable non-invasive approach to investigate autonomic stress reactivity; however, this integrative approach has not yet been applied with regards to exercise stressors.

Cardiac Autonomic Responses during Exercise and Post-exercise Recovery Using Heart Rate Variability and Systolic Time Intervals—A Review

PubMed Central

Michael, Scott; Graham, Kenneth S.; Davis, Glen M.

2017-01-01

Cardiac parasympathetic activity may be non-invasively investigated using heart rate variability (HRV), although HRV is not widely accepted to reflect sympathetic activity. Instead, cardiac sympathetic activity may be investigated using systolic time intervals (STI), such as the pre-ejection period. Although these autonomic indices are typically measured during rest, the “reactivity hypothesis” suggests that investigating responses to a stressor (e.g., exercise) may be a valuable monitoring approach in clinical and high-performance settings. However, when interpreting these indices it is important to consider how the exercise dose itself (i.e., intensity, duration, and modality) may influence the response. Therefore, the purpose of this investigation was to review the literature regarding how the exercise dosage influences these autonomic indices during exercise and acute post-exercise recovery. There are substantial methodological variations throughout the literature regarding HRV responses to exercise, in terms of exercise protocols and HRV analysis techniques. Exercise intensity is the primary factor influencing HRV, with a greater intensity eliciting a lower HRV during exercise up to moderate-high intensity, with minimal change observed as intensity is increased further. Post-exercise, a greater preceding intensity is associated with a slower HRV recovery, although the dose-response remains unclear. A longer exercise duration has been reported to elicit a lower HRV only during low-moderate intensity and when accompanied by cardiovascular drift, while a small number of studies have reported conflicting results regarding whether a longer duration delays HRV recovery. “Modality” has been defined multiple ways, with limited evidence suggesting exercise of a greater muscle mass and/or energy expenditure may delay HRV recovery. STI responses during exercise and recovery have seldom been reported, although limited data suggests that intensity is a key determining factor. Concurrent monitoring of HRV and STI may be a valuable non-invasive approach to investigate autonomic stress reactivity; however, this integrative approach has not yet been applied with regards to exercise stressors. PMID:28611675

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

PubMed Central

Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

2016-01-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

Thermal annealing recovery of fracture toughness in HT9 steel after irradation to high doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byun, Thak Sang; Baek, Jong-Hyuk; Anderoglu, Osman

2013-08-03

The HT9 ferritic/martensitic steel with a nominal chemistry of Fe(bal.)–12%Cr–1%MoVW has been used as a primary core material for fast fission reactors such as FFTF because of its high resistance to radiationinduced swelling and embrittlement. Both static and dynamic fracture test results have shown that the HT9 steel can become brittle when it is exposed to high dose irradiation at a relatively low temperature 430 °C). This article aims at a comprehensive discussion on the thermal annealing recovery of fracture toughness in the HT9 steel after irradiation up to 3–148 dpa at 378–504 °C. A specimen reuse technique has beenmore » established and applied to this study: the fracture specimens were tested Charpy specimens or broken halves of Charpy bars (13 3 4 mm). The post-anneal fracture test results indicated that much of the radiation-induced damage can be recovered by a simple thermal annealing schedule: the fracture toughness was incompletely recovered by 550 °C annealing, while nearly complete or complete recovery occurred after 650 °C annealing. This indicates that thermal annealing is a feasible damage mitigation technique for the reactor components made of HT9 steel. The partial recovery is probably due to the non-removable microstructural damages such as void or gas bubble formation, elemental segregation and precipitation.« less

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Efficacy of alfaxalone for intravascular anesthesia and euthanasia in blue crabs (Callinectes sapidus).

PubMed

Minter, Larry J; Harms, Craig A; Archibald, Kate E; Broadhurst, Heather; Bailey, Kate M; Christiansen, Emily F; Lewbart, Gregory A; Posner, Lysa P

2013-09-01

The objective of this study was to characterize the behavioral effects and changes in heart rate of four doses of alfaxalone delivered by intravascular injection to blue crabs (Callinectes sapidus). Thirty (male, n = 27; female, n = 3) blue crabs were randomly assigned to one of four treatment groups of alfaxalone: eight animals were assigned to each of the 5-, 10-, and 15-mg/kg treatment groups, and the remaining six animals were assigned to the 100-mg/kg group. Times for anesthetic induction and recovery periods were recorded. Righting reflex, defensive posturing, and heart rate were evaluated before, during, and after the anesthetic trial. Anesthesia was induced in all 14 animals consolidated into the high-dosage group (15 mg/kg [n = 8] and 100 mg/kg [n = 6]), which was significantly greater than 8 of 16 animals in the low-dosage group (5 mg/kg [n = 2] and 10 mg/kg [n = 6]). Median anesthesia induction time for all crabs was 0.4 min, with no significant difference in induction time between groups observed. Median recovery time was 9.4 min (n = 2), 6.1 min (n = 5), 11.3 min (n = 8), and 66.1 min (n = 5) for the 5-, 10-, 15-, and 100-mg/kg groups, respectively. Recovery times were significantly longer for crabs exposed to an induction dose of 100 mg/kg compared with the 10- and 15-mg/kg induction doses. A significant decrease in the median heart rate was observed between the baseline value and that observed at both induction and 5 min postinjection in the 100-mg/kg dose trial. Two mortalities were observed during the anesthesia trials (n = 1, 10 mg/kg; n = 1, 100 mg/kg), both associated with the autotomization of limbs. In summary, the intravascular administration of alfaxalone at 15 mg/kg provided rapid and reliable sedation, whereas alfaxalone administered at 100 mg/kg produced rapid and long lasting anesthesia.

Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

NASA Astrophysics Data System (ADS)

Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

2012-07-01

The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

Assessing potential radiological harm to fukushima recovery workers.

PubMed

Scott, Bobby R

2011-01-01

A radiological emergency exists at the Fukushima Daiichi (Fukushima I) nuclear power plant in Japan as a result of the March 11, 2011 magnitude 9.0 earthquake and the massive tsunami that arrived later. News media misinformation related to the emergency triggered enormous social fear worldwide of the radioactivity that is being released from damaged fuel rods. The heroic recovery workers are a major concern because they are being exposed to mostly gamma radiation during their work shifts and life-threatening damage to the radiosensitive bone marrow could occur over time. This paper presents a way in which the bone marrow equivalent dose (in millisieverts), as estimated per work shift, could be used along with the hazard function model previously developed for radiological risk assessment to repeatedly check for potential life-threatening harm (hematopoietic system damage) to workers. Three categories of radiation hazard indication are proposed: 1, life-threatening damage unlikely; 2, life-threatening damage possible; 3, life-threatening damage likely. Categories 2 and 3 would be avoided if the whole body effective dose did not exceed the annual effective dose limit of 250 mSv. For down-wind populations, hormetic effects (activated natural protective processes) are much more likely than are deleterious effects.

Effects of lithium chloride as a potential radioprotective agent on radiation response of DNA synthesis in mouse germinal cells.

PubMed

Bhattacharjee, D; Rajan, R; Krishnamoorthy, L; Singh, B B

1997-06-01

Mouse spermatogonial germ cells are highly sensitive to ionizing radiation. Lithium salts are reported to stimulate the postirradiation recovery of hematopoietic marrow cells. We have, therefore, examined whether administered lithium chloride (LiCl) would also be able to protect the mouse germinal cells against radiation injury. Taking DNA synthesis as an endpoint, our results show that the testicular DNA-specific activity in irradiated mice was higher by 61% on average when they had been pretreated with LiCl both 24 h and 1 h prior to gamma-irradiation (2.0 Gy). It was also observed that the DNA synthetic activity in the germinal cells fully recovered after LiCl pretreatment at doses of 40 mg per kg body weight prior to total body irradiation of 0.05-0.25 Gy, whereas at doses of 0.5-6.0 Gy, following the same procedure of LiCl pretreatment, only an incomplete recovery was observed. The dose reduction factor for LiCl is 1.84. The current findings indicate that pretreatment with LiCl provides considerable protection against radiation damage in mouse spermatogonia.

Determination of dose distributions and parameter sensitivity. Hanford Environmental Dose Reconstruction Project; dose code recovery activities; Calculation 005

DOE Office of Scientific and Technical Information (OSTI.GOV)

Napier, B.A.; Farris, W.T.; Simpson, J.C.

1992-12-01

A series of scoping calculations has been undertaken to evaluate the absolute and relative contribution of different radionuclides and exposure pathways to doses that may have been received by individuals living in the vicinity of the Hanford site. This scoping calculation (Calculation 005) examined the contributions of numerous parameters to the uncertainty distribution of doses calculated for environmental exposures and accumulation in foods. This study builds on the work initiated in the first scoping study of iodine in cow`s milk and the third scoping study, which added additional pathways. Addressed in this calculation were the contributions to thyroid dose ofmore » infants from (1) air submersion and groundshine external dose, (2) inhalation, (3) ingestion of soil by humans, (4) ingestion of leafy vegetables, (5) ingestion of other vegetables and fruits, (6) ingestion of meat, (7) ingestion of eggs, and (8) ingestion of cows` milk from Feeding Regime 1 as described in Calculation 001.« less

COMPARISON OF HYDROCORTISONE 10 MG TABLETS: TABLET HARDNESS OPTIMISED FOR ADULT USE HAS NEGATIVE CONSEQUENCES FOR PAEDIATRIC USE.

PubMed

Saimbi, Sarina; Madden, Valerie; Stirling, Heather; Yahyouche, Asma; Batchelor, Hannah

2016-09-01

Children's medicines are not always readily available as an age appropriate product and manipulation of adult products is often required. Recently the commercial manufacturing process for 10 mg hydrocortisone tablets has changed and the compression force increased due to tablets fracturing on removal from the blister pack. However, this change led to parents of children requiring hydrocortisone reporting that the tablets were more difficult to manipulate.This study evaluated 10 mg hydrocortisone tablets for their suitability for manipulation in order to deliver an appropriate dose to children (2 mg dose). The physical properties of tablets with the old and new compression force were compared as well as the accuracy of obtaining the paediatric dose. The tablets compared were hydrocortisone Auden 10 mg tablets (Brand A, PL16876/002)-these are the newer, harder tablets- and hydrocortisone 10 mg tablets (Brand B, PL17507/0097). Tablet physical properties including friability (Copley FRV200) and tablet hardness (Copley TBF1000) were compared. The accuracy of split doses (halve and quarter tablets) were recorded on a Sartorius analytical balance. The accuracy of the 2 mg paediatric dosing was assessed by crushing the tablet, adding 10 mL of water and extracting 2 mL. The concentration was measured using UV analysis (Jenway Genova Plus) according to a calibration curve (wavelength=246 nm). Two devices were used to crush the tablets: a spoon onto a plate and a commercially available crushing device (Apothecary Ezy Crush Pill Crusher With Ergo Grip). As anticipated Brand A tablets were harder (51.85 ±5.1 N) compared to Brand B (30.99±4.1 N). Brand A tablets passed the friability testing with <1% weight loss whereas Brand B failed as 5 tablets broke during testing.The accuracy of split doses using the score lines to halve and quarter the tablets showed that Brand A were generally better with smaller ranges for both halves (Range for A=41-55%; B=29-70%) and quarters (Range for A=17-35%; B=12-42%) compared to Brand B.The 2 mg dosing accuracy was better for Brand B tablets compared to A and crushing tablets using a commercial device improved the accuracy of dosing for both brands of tablets. When crushing using a spoon the mean dose obtained was 1.3 mg for Brand A and 1.7 mg for Brand B; the commercial crushing device gave values of 1.9 mg for Brand A and 2.1 mg for Brand B. Parents or carers who are required to manipulate 10 mg hydrocortisone tablets to administer a dose to children dispersed in water should be advised to crush the tablet into a fine powder where possible to improve the likelihood of administering an accurate dose. This is particularly important since the introduction of new hydrocortisone Auden tablets which are known to be harder tablets and therefore more force is required to crush these. Some of the experimental work within this project was conducted by Andrew Hackett and Kameron Paul-Thaper whilst at the University of Birmingham on work experience from Arden Sixth Form, Station Rd, Knowle, Solihull, West Midlands, B93 0PT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Postconditioning hormesis put in perspective: an overview of experimental and clinical studies.

PubMed

Wiegant, F A C; Prins, H A B; Van Wijk, R

2011-01-01

A beneficial effect of applying mild stress to cells or organisms, that were initially exposed to a high dose of stress, has been referred to as 'postconditioning hormesis'. The initial high dose of stress activates intrinsic self-recovery mechanisms. Modulation of these endogenous adaptation strategies by administration of a subsequent low dose of stress can confer effects that are beneficial to the biological system. Owing to its potentially therapeutic applications, postconditioning hormesis is subject to research in various scientific disciplines. This paper presents an overview of the dynamics of postconditioning hormesis and illustrates this phenomenon with a number of examples in experimental and clinical research.

A new approach to quantifying physical demand in rugby union.

PubMed

Lacome, Mathieu; Piscione, Julien; Hager, Jean-Philippe; Bourdin, Muriel

2014-01-01

The objective of the study was to describe an original approach to assessing individual workload during international rugby union competitions. The difference between positional groups and between the two halves was explored. Sixty-seven files from 30 French international rugby union players were assessed on a computerised player-tracking system (Amisco Pro(®), Sport Universal Process, Nice, France) during five international games. Each player's action was split up into exercise and recovery periods according to his individual velocity threshold. Exercise-to-recovery (E:R) period ratios and acceleration were calculated. Results indicated that about 65% of exercise periods lasted less than 4 s; half of the E:Rs were less than 1:4, and about one-third ranged between 1 and 1:4 and about 40% of exercise periods were classified as medium intensity. Most acceleration values were less than 3 m·s(-2) and started from standing or walking activity. Back row players showed the highest mean acceleration values over the game (P < 0.05). No significant decrease in physical performance was seen between the first and second halves of the games except for back rows, who showed a significant decrease in mean acceleration (P < 0.05). The analysis of results emphasised the specific activity of back rows and tended to suggest that the players' combinations of action and recovery times were optimal for preventing large decrease in the physical performance.

Fibroma induction in rat skin following single or multiple doses of 1.0 GeV/nucleon 56Fe ions from the Brookhaven Alternating Gradient Synchrotron (AGS)

NASA Technical Reports Server (NTRS)

Burns, F. J.; Zhao, P.; Xu, G.; Roy, N.; Loomis, C.

2001-01-01

Rat skin was exposed to the plateau region of the 1.0 GeV/nucleon 56Fe beam at the Brookhaven AGS. Rats were irradiated or not with single of split doses of 56Fe or argon; some 56Fe-exposed rats were fed 250 ppm retinyl acetate continuously in the lab chow beginning 1 week before irradiation. All lesions were noted, photographed and identified for eventual histological diagnosis. The preponderance of the tumors so far are fibromas. The data show that single doses of 56Fe ions are 2 or 3 fold more effective than argon in producing tumors at 4.5 Gy but are about equally effective at 3.0 Gy and 9.0 Gy. The presence of 250 ppm retinyl acetate in the lab chow reduced the incidence of tumors by about 50-60% in comparison to groups exposed only to the radiation. These are preliminary findings based on only about one-fourth the eventual number of tumors expected.

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

PubMed

Sulkes, A; Benner, S E; Canetta, R M

1998-10-01

This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

A 3D isodose manipulation tool for interactive dose shaping

NASA Astrophysics Data System (ADS)

Kamerling, C. P.; Ziegenhein, P.; Heinrich, H.; Oelfke, U.

2014-03-01

The interactive dose shaping (IDS) planning paradigm aims to perform interactive local dose adaptations of an IMRT plan without compromising already established valuable dose features in real-time. In this work we introduce an interactive 3D isodose manipulation tool which enables local modifications of a dose distribution intuitively by direct manipulation of an isodose surface. We developed an in-house IMRT TPS framework employing an IDS engine as well as a 3D GUI for dose manipulation and visualization. In our software an initial dose distribution can be interactively modified through an isodose surface manipulation tool by intuitively clicking on an isodose surface. To guide the user interaction, the position of the modification is indicated by a sphere while the mouse cursor hovers the isodose surface. The sphere's radius controls the locality of the modification. The tool induces a dose modification as a direct change of dose in one or more voxels, which is incrementally obtained by fluence adjustments. A subsequent recovery step identifies voxels with violated dose features and aims to recover their original dose. We showed a proof of concept study for the proposed tool by adapting the dose distribution of a prostate case (9 beams, coplanar). Single dose modifications take less than 2 seconds on an actual desktop PC.

Estimating Historical Eastern North Pacific Blue Whale Catches Using Spatial Calling Patterns

PubMed Central

Monnahan, Cole C.; Branch, Trevor A.; Stafford, Kathleen M.; Ivashchenko, Yulia V.; Oleson, Erin M.

2014-01-01

Blue whales (Balaenoptera musculus) were exploited extensively around the world and remain endangered. In the North Pacific their population structure is unclear and current status unknown, with the exception of a well-studied eastern North Pacific (ENP) population. Despite existing abundance estimates for the ENP population, it is difficult to estimate pre-exploitation abundance levels and gauge their recovery because historical catches of the ENP population are difficult to separate from catches of other populations in the North Pacific. We collated previously unreported Soviet catches and combined these with known catches to form the most current estimates of North Pacific blue whale catches. We split these conflated catches using recorded acoustic calls from throughout the North Pacific, the knowledge that the ENP population produces a different call than blue whales in the western North Pacific (WNP). The catches were split by estimating spatiotemporal occurrence of blue whales with generalized additive models fitted to acoustic call patterns, which predict the probability a catch belonged to the ENP population based on the proportion of calls of each population recorded by latitude, longitude, and month. When applied to the conflated historical catches, which totaled 9,773, we estimate that ENP blue whale catches totaled 3,411 (95% range 2,593 to 4,114) from 1905–1971, and amounted to 35% (95% range 27% to 42%) of all catches in the North Pacific. Thus most catches in the North Pacific were for WNP blue whales, totaling 6,362 (95% range 5,659 to 7,180). The uncertainty in the acoustic data influence the results substantially more than uncertainty in catch locations and dates, but the results are fairly insensitive to the ecological assumptions made in the analysis. The results of this study provide information for future studies investigating the recovery of these populations and the impact of continuing and future sources of anthropogenic mortality. PMID:24892427

Estimating historical eastern North Pacific blue whale catches using spatial calling patterns.

PubMed

Monnahan, Cole C; Branch, Trevor A; Stafford, Kathleen M; Ivashchenko, Yulia V; Oleson, Erin M

2014-01-01

Blue whales (Balaenoptera musculus) were exploited extensively around the world and remain endangered. In the North Pacific their population structure is unclear and current status unknown, with the exception of a well-studied eastern North Pacific (ENP) population. Despite existing abundance estimates for the ENP population, it is difficult to estimate pre-exploitation abundance levels and gauge their recovery because historical catches of the ENP population are difficult to separate from catches of other populations in the North Pacific. We collated previously unreported Soviet catches and combined these with known catches to form the most current estimates of North Pacific blue whale catches. We split these conflated catches using recorded acoustic calls from throughout the North Pacific, the knowledge that the ENP population produces a different call than blue whales in the western North Pacific (WNP). The catches were split by estimating spatiotemporal occurrence of blue whales with generalized additive models fitted to acoustic call patterns, which predict the probability a catch belonged to the ENP population based on the proportion of calls of each population recorded by latitude, longitude, and month. When applied to the conflated historical catches, which totaled 9,773, we estimate that ENP blue whale catches totaled 3,411 (95% range 2,593 to 4,114) from 1905-1971, and amounted to 35% (95% range 27% to 42%) of all catches in the North Pacific. Thus most catches in the North Pacific were for WNP blue whales, totaling 6,362 (95% range 5,659 to 7,180). The uncertainty in the acoustic data influence the results substantially more than uncertainty in catch locations and dates, but the results are fairly insensitive to the ecological assumptions made in the analysis. The results of this study provide information for future studies investigating the recovery of these populations and the impact of continuing and future sources of anthropogenic mortality.

Protective effects of HemoHIM on immune and hematopoietic systems against γ-irradiation.

PubMed

Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee; Yee, Sung-Tae; Kim, Sung-Ho

2014-02-01

We examined the effect of HemoHIM on the protective efficacy of hematopoietic stem cells and on the recovery of immune cells against sublethal doses of ionizing radiation. Two-month-old mice were exposed to γ-rays at a dose of 8, 6.5, or 5 Gy for a30-day survival study, endogenous spleen colony formation, or other experiments, respectively. HemoHIM was injected intraperitoneally before and after irradiation. Our results showed that HemoHIM significantly decreased the mortality of sublethally irradiated mice. The HemoHIM administration decreased the apoptosis of bone marrow cells in irradiated mice. On the other hand, HemoHIM increased the formation of endogenous spleen colony in irradiated mice. In irradiated mice, the recovery of total leukocytes in the peripheral blood and lymphocytes in the spleen were enhanced significantly by HemoHIM. Moreover, the function of B cells, T cells, and NK cells regenerated in irradiated mice were significantly improved by the administration of HemoHIM. HemoHIM showed an ideal radioprotector for protecting hematopoietic stem cells and for accelerating the recovery of immune cells. We propose HemoHIM as a beneficial supplement drug during radiotherapy to alleviate adverse radiation-induced effects for cancer patients. Copyright © 2013 John Wiley & Sons, Ltd.

Analysis of hematopoietic recovery after autologous transplantation as method of quality control for long-term progenitor cell cryopreservation.

PubMed

Pavlů, J; Auner, H W; Szydlo, R M; Sevillano, B; Palani, R; O'Boyle, F; Chaidos, A; Jakob, C; Kanfer, E; MacDonald, D; Milojkovic, D; Rahemtulla, A; Bradshaw, A; Olavarria, E; Apperley, J F; Pello, O M

2017-12-01

Hematopoietic precursor cells (HPC) are able to restore hematopoiesis after high-dose chemotherapy and their cryopreservation is routinely employed prior to the autologous hematopoietic cell transplantation (AHCT). Although previous studies showed feasibility of long-term HPC storage, concerns remain about possible negative effects on their potency. To study the effects of long-term cryopreservation, we compared time to neutrophil and platelet recovery in 50 patients receiving two AHCT for multiple myeloma at least 2 years apart between 2006 and 2016, using HPC obtained from one mobilization and collection attempt before the first transplant. This product was divided into equivalent fractions allowing a minimum of 2 × 10 6 CD34+ cells/kg recipient's weight. One fraction was used for the first transplant after median storage of 60 days (range, 17-165) and another fraction was used after median storage of 1448 days (range, 849-3510) at the second AHCT. Neutrophil recovery occurred at 14 days (median; range, 11-21) after the first and 13 days (10-20) after the second AHCT. Platelets recovered at a median of 16 days after both procedures. Considering other factors, such as disease status, conditioning and HPC dose, this single institution data demonstrated no reduction in the potency of HPC after long-term storage.

SU-E-T-237: Deformable Image Registration and Deformed Dose Composite for Volumetric Evaluation of Multimodal Gynecological Cancer Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albani, D; Sherertz, T; Ellis, R

2015-06-15

Purpose: Radiotherapy plans for patients with cervical cancer treated with EBRT followed by HDR brachytherapy are optimized by constraining dose to organs at risk (OARs). Risk of treatment related toxicities is estimated based on the dose received to the hottest 2cc (D2cc) of the bladder, bowel, rectum, and sigmoid. To account for intrafractional variation in OAR volume and positioning, a dose deformation method is proposed for more accurate evaluation of dose distribution for these patients. Methods: Radiotherapy plans from five patients who received 50.4Gy pelvic EBRT followed by 30Gy in five fractions of HDR brachytherapy, using split-ring and tandem applicators,more » were retrospectively evaluated using MIM Software version 6.0. Dose accumulation workflows were used for initial deformation of EBRT and HDR planning CTs onto a common HDR planning CT. The Reg Refine tool was applied with user-specified local alignments to refine the deformation. Doses from the deformed images were transferred to the common planning CT. Deformed doses were scaled to the EQD2, following the linear-quadratic BED model (considered α/β ratio for tumor as 10, and 3 for rest of the tissues), and then combined to create the dose composite. MIM composite doses were compared to the clinically-reported plan assessments based upon the American Brachytherapy Society (ABS) guidelines for cervical HDR brachytherapy treatment. Results: Bladder D2cc exhibited significant reduction (−11.4%±3.85%, p< 0.02) when evaluated using MIM deformable dose composition. Differences observed for bowel, rectum, and sigmoid D2cc were not significant (−0.58±7.37%, −4.13%±13.7%, and 8.58%±4.71%, respectively and p>0.05 for all) relative to the calculated values used clinically. Conclusion: Application of deformable dose composite techniques may lead to more accurate total dose reporting and can allow for elevated dose to target structures with the assurance of not exceeding dose to OARs. Further study into deformable dose composition and correlation with clinical outcomes is warranted.« less

Mechanical and microstructural changes in tungsten due to irradiation damage

NASA Astrophysics Data System (ADS)

Uytdenhouwen, I.; Schwarz-Selinger, T.; Coenen, J. W.; Wirtz, M.

2016-02-01

Stress-relieved pure tungsten received three damage levels (0.10, 0.25 and 0.50 dpa) by self-tungsten ion beam irradiation at room temperature. Positron annihilation spectroscopy showed the formation of mono-vacancies and vacancy clusters after ion beam exposure. In the first irradiation step (0-0.10 dpa) some splitting up of large vacancy clusters occurred which became more numerous. For increasing dose to 0.25 dpa, growth of the vacancy clusters was seen. At 0.50 dpa a change in the defect formation seems to occur leading to a saturation in the lifetime signal obtained from the positrons. Nano-indentation on the cross-sections showed a flat damage depth distribution profile. The nano-indentation hardness increased for increasing damage dose without any saturation up to 0.50 dpa. This means that other defects such as dislocation loops and large sized voids seem to contribute.

Effect of hyperthermia on the repair of sublethal radiation damage in normal and membrane fatty acid substituted fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolters, H.; Kelholt, D.; Konings, A.W.

1987-02-01

The interaction of heat and X irradiation was studied in normal and polyunsaturated fatty acid (PUFA) substituted mouse fibroblast LM cells. As a result of the substitution the membranes of the PUFA cells were more fluid than the membranes of the normal cells. Three different heat doses were applied (60 min 42 degrees C, 20 min 43 degrees C, and 10 min 44 degrees C) in combination with single or split doses of X rays. Heat radiosensitization was the largest for the 60 min 42 degrees C treatment. Heat radiosensitization and the heat-induced inhibition of the rate of sublethal damagemore » repair were the same for the normal and the PUFA cells. It is concluded from the experiments reported that the processes of hyperthermic inhibition of SLD repair and hyperthermic radiosensitization are independent of membrane fluidity and membrane fatty acid composition.« less

Rat striatal monoamine oxidase-B inhibition by l-deprenyl and rasagiline: its relationship to 2-phenylethylamine-induced stereotypy and Parkinson's disease.

PubMed

Youdim, M B H; Tipton, K F

2002-03-01

Rats were injected intraperitoneally with varying doses of l-deprenyl (selegiline) followed 2h later by 30 mg kg(-1) 2-phenylethylamine (PEA), administered in the same way, and the stereotypic behavioural response elicited was assessed. l-Deprenyl alone at doses of up to 5 mg kg(-1) caused no significant behavioural response. Administration of PEA without prior l-deprenyl treatment resulted in only a modest increase in stereotypic behaviour and this was not significantly enhanced by the prior administration 1 mg kg(-1) l-deprenyl. When the administered dose of l-deprenyl was increased to 2.5 or 5 mgkg(-1), however, the stereotypic behavioural response to PEA was greatly potentiated and in the latter case persisted for 60 min. A dose of 2.5 mg kg(-1) l-deprenyl and 1 mg kg(-1) rasagiline was shown to result in over 90% inhibition of the monoamine oxidase (MAO)-B from rat liver and striatum, whereas the inhibition of MAO-A was about 60 and 40% in liver and striatum, respectively. The recovery of MAO-B activity in rat striatum and liver following a single i.p. injection of 5 mg kg(-1) l-deprenyl gave first-order rate constants of 1.80 and 7.15 h(-1), respectively, which corresponded to half-lives of 9.23 and 2.33 days. Similar results were obtained with rasagiline. The corresponding indices of stereotypic response to PEA (30 mg kg(-1); i.p.) during recovery from the single dose of l-deprenyl were initially high, but had started to decline by the third day after l-deprenyl treatment and was not significant after day 4. At that time, less than 20% of the striatal monoamine oxidase-B activity had been regained, whereas the recovery of the liver enzyme was about 65%. These data are discussed in terms of the suggested involvement of PEA potentiation in the anti-parkinsonian actions of l-deprenyl and rasagiline and the duration of the 'wash-out' period used in studies on the effects of l-deprenyl on patients with Parkinson's disease. The longer duration of the recovery of brain monoamine oxidase B after its selective inhibition and the corresponding behavioural responses of the animals to PEA at same time points, indicate that PEA may have a major pharmacological role in the mechanism of the antiParkinson action of l-deprenyl and rasagiline. Brain monoamine oxidase B inhibition has previously been shown to significantly increases brain PEA and which is capable of releasing dopamine endogenously or that formed from L-dopa.

Implementation of Monte Carlo Dose calculation for CyberKnife treatment planning

NASA Astrophysics Data System (ADS)

Ma, C.-M.; Li, J. S.; Deng, J.; Fan, J.

2008-02-01

Accurate dose calculation is essential to advanced stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) especially for treatment planning involving heterogeneous patient anatomy. This paper describes the implementation of a fast Monte Carlo dose calculation algorithm in SRS/SRT treatment planning for the CyberKnife® SRS/SRT system. A superposition Monte Carlo algorithm is developed for this application. Photon mean free paths and interaction types for different materials and energies as well as the tracks of secondary electrons are pre-simulated using the MCSIM system. Photon interaction forcing and splitting are applied to the source photons in the patient calculation and the pre-simulated electron tracks are repeated with proper corrections based on the tissue density and electron stopping powers. Electron energy is deposited along the tracks and accumulated in the simulation geometry. Scattered and bremsstrahlung photons are transported, after applying the Russian roulette technique, in the same way as the primary photons. Dose calculations are compared with full Monte Carlo simulations performed using EGS4/MCSIM and the CyberKnife treatment planning system (TPS) for lung, head & neck and liver treatments. Comparisons with full Monte Carlo simulations show excellent agreement (within 0.5%). More than 10% differences in the target dose are found between Monte Carlo simulations and the CyberKnife TPS for SRS/SRT lung treatment while negligible differences are shown in head and neck and liver for the cases investigated. The calculation time using our superposition Monte Carlo algorithm is reduced up to 62 times (46 times on average for 10 typical clinical cases) compared to full Monte Carlo simulations. SRS/SRT dose distributions calculated by simple dose algorithms may be significantly overestimated for small lung target volumes, which can be improved by accurate Monte Carlo dose calculations.

Automatic radiation dose monitoring for CT of trauma patients with different protocols: feasibility and accuracy.

PubMed

Higashigaito, K; Becker, A S; Sprengel, K; Simmen, H-P; Wanner, G; Alkadhi, H

2016-09-01

To demonstrate the feasibility and accuracy of automatic radiation dose monitoring software for computed tomography (CT) of trauma patients in a clinical setting over time, and to evaluate the potential of radiation dose reduction using iterative reconstruction (IR). In a time period of 18 months, data from 378 consecutive thoraco-abdominal CT examinations of trauma patients were extracted using automatic radiation dose monitoring software, and patients were split into three cohorts: cohort 1, 64-section CT with filtered back projection, 200 mAs tube current-time product; cohort 2, 128-section CT with IR and identical imaging protocol; cohort 3, 128-section CT with IR, 150 mAs tube current-time product. Radiation dose parameters from the software were compared with the individual patient protocols. Image noise was measured and image quality was semi-quantitatively determined. Automatic extraction of radiation dose metrics was feasible and accurate in all (100%) patients. All CT examinations were of diagnostic quality. There were no differences between cohorts 1 and 2 regarding volume CT dose index (CTDIvol; p=0.62), dose-length product (DLP), and effective dose (ED, both p=0.95), while noise was significantly lower (chest and abdomen, both -38%, p<0.017). Compared to cohort 1, CTDIvol, DLP, and ED in cohort 3 were significantly lower (all -25%, p<0.017), similar to the noise in the chest (-32%) and abdomen (-27%, both p<0.017). Compared to cohort 2, CTDIvol (-28%), DLP, and ED (both -26%) in cohort 3 was significantly lower (all, p<0.017), while noise in the chest (+9%) and abdomen (+18%) was significantly higher (all, p<0.017). Automatic radiation dose monitoring software is feasible and accurate, and can be implemented in a clinical setting for evaluating the effects of lowering radiation doses of CT protocols over time. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

NASA Technical Reports Server (NTRS)

Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

2014-01-01

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

[Idiopathic sudden deafness: a report of 96 patients].

PubMed

Gabanou, F; Bera, G; Vincent, C

2012-01-01

Evaluation of the management of idiopathic sudden deafness indicating the usefulness of biological assessments and the pronostic factors of hearing recovery. This is a retrospective study of 96 patients with idiopathic sudden deafness referred to a tertiary centre between 2005 and 2009 treated with corticosteroids intravenously at a daily dose of 1 mg/kg. Mean tonal thresholds were assessed (PTA = [500 Hz + 1000 Hz + 2000 Hz + 4000 Hz]/4). Each audiogram was classified as five classes according to its frequency profile. The hearing recovery is significant between D0-D5 and D5-M1 for the frequencies 0.5, 1 and 2 kHz. For 4 kHz, the recovery is significant between 0 and J5. There is no statistically significant correlation between the presence of associated signs (tinnitus, vertigo) and hearing recovery. Hearing recovery according to the five types of audiograms has the same evolution in the follow-up time but with audiograms type E (cophosis or subcophosis) often associated with an hyporeactivity at the videonystagmography. The presence of cardiovascular disease is a predictor of poor hearing recovery. The usefullness of systematic extensive blood tests is low. In sudden deafness, the maximum hearing recovery takes place in the month following the onset of symptoms. The predictors of poor hearing recovery are an initial mean threshold > 70 dB, the existence of an associated cardiovascular disease.

Combinatorial treatments enhance recovery following facial nerve crush.

PubMed

Sharma, Nijee; Moeller, Carl W; Marzo, Sam J; Jones, Kathryn J; Foecking, Eileen M

2010-08-01

To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. Prospective, controlled animal study. After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4-8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. : Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposedmore » lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.« less

A critical test of Drosophila anaesthetics: Isoflurane and sevoflurane are benign alternatives to cold and CO2.

PubMed

MacMillan, Heath A; Nørgård, Mikkel; MacLean, Heidi J; Overgaard, Johannes; Williams, Catherine J A

2017-08-01

Anaesthesia is often a necessary step when studying insects like the model organism Drosophila melanogaster. Most studies of Drosophila and other insects that require anaesthesia use either cold exposure or carbon dioxide exposure to induce a narcotic state. These anaesthetic methods are known to disrupt physiology and behavior with increasing exposure, and thus ample recovery time is required prior to experimentation. Here, we examine whether two halogenated ethers commonly used in vertebrate anaesthesia, isoflurane and sevoflurane, may serve as alternative means of insect anaesthesia. Using D. melanogaster, we generated dose-response curves to identify exposure times for each anaesthetic (cold, CO 2 , isoflurane and sevoflurane) that allow for five-minutes of experimental manipulation of the animals after the anaesthetic was removed (i.e. 5min recovery doses). We then compared the effects of this practical dose on high temperature, low temperature, starvation, and desiccation tolerance, as well as locomotor activity and fecundity of female flies following recovery from anaesthesia. Cold, CO 2 and isoflurane each had significant or near significant effects on the traits measured, but the specific effects of each anaesthetic differed, and effects on stress tolerance generally did not persist if the flies were given 48h to recover from anaesthesia. Sevoflurane had no measureable effect on any of the traits examined. Care must be taken when choosing an anaesthetic in Drosophila research, as the impacts of specific anaesthetics on stress tolerance, behavior and reproduction can widely differ. Sevoflurane may be a practical alternative to cold and CO 2 anaesthesia in insects - particularly if flies are to be used for experiments shortly after anesthesia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

PubMed

Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

2012-03-17

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation.

PubMed

Dempsey, Sean P; Sickman, Amy; Slagle, William Scott

2018-05-01

This case illustrates a novel screening protocol for linezolid-induced toxic optic neuropathy. To present a case report and analysis of linezolid-induced optic neuropathies in adult patients to develop screening recommendations. A case report of optic neuropathy from extended use of linezolid illustrates its potential effects on vision. We conduct a retrospective analysis of 39 reported cases to derive a recommended screening protocol for linezolid-induced toxic optic neuropathy in adult patients. Of 39 reported adult cases, 32 presented with optic neuropathy within 90 to 365 days of treatment. Within this subset, the duration of linezolid dosage to first symptoms is 235 ± 71 days. Seven outliers either experienced optic neuropathy within the first 28 days or between 600 and 1125 days. Of the 33 cases that quantified visual recovery, 30 reported final binocular visual acuity equivalent to 20/40 or better when the medication was discontinued from 0 to 268 days after symptom onset. Recovery potential was reported over a period of 2 weeks to approximately 6 months after cessation. To evaluate the effect of cumulative dose, the data were separated into patients taking 600 mg twice daily and those at 600 mg once daily. At the higher dosage, a mean of 180 ± 96 days with a mean cumulative dosage of 216 ± 115 g was noted at first symptom, whereas at lower dosage, a mean of 201 ± 102 days was noted with a mean cumulative dose of 138 ± 69 g. We recommend screening adult patients within 1 month after initiating linezolid, followed by a subsequent evaluation every 30 to 60 days beginning 3 months from initiation. Substantial visual recovery is reported when linezolid is discontinued. Toxicity appears to be correlated to duration of treatment, rather than cumulative dose.

Impact of Abbreviated Filgrastim Schedule on Survival and Hematopoietic Recovery after Irradiation in Four Mouse Strains with Different Radiosensitivity

PubMed Central

Satyamitra, Merriline; Kumar, Vidya P.; Biswas, Shukla; Cary, Lynnette; Dickson, Leonora; Venkataraman, Srinivasan; Ghosh, Sanchita P.

2017-01-01

Filgrastim (Neupogen®, granulocyte-colony stimulating factor) is among the few countermeasures recommended for management of patients in the event of lethal total-body irradiation. Despite the plethora of studies using filgrastim as a radiation countermeasure, relatively little is known about the optimal dose schedule of filgrastim to mitigate radiation lethality. We evaluated the efficacy of filgrastim in improving 30-day survival of CD2F1 mice irradiated with a lethal dose (LD70/30) in the AFRRI cobalt-60 facility. We tested different schedules of 1, 3, 5,10 or 16 once-daily injections of filgrastim initiated one day after irradiation. Time optimization studies with filgrastim treatment were also performed, beginning 6–48 h postirradiation. Maximum survival was observed with 3 daily doses of 0.17 mg/kg filgrastim. Survival efficacy of the 3-day treatment was compared against the conventional 16-day filgrastim treatment after irradiation in four mouse strains with varying radiation sensitivities: C3H/HeN, C57BL/6, B6C3F1 and CD2F1. Blood indices, bone marrow histopathology and colony forming unit assays were also evaluated. Filgrastim significantly increased 30-day survival (P < 0.001) with a 3-day treatment compared to 16-day treatment. Filgrastim did not prevent cytopenia nadirs, but facilitated faster recovery of white blood cells, neutrophils, red blood cells, platelets, lymphocytes and hematocrits in all four strains. Accelerated hematopoietic recovery was also reflected in faster bone marrow reconstitution and significant increase in hematopoietic progenitors (P < 0.001) in all four mouse strains. These data indicate that prompt and abbreviated filgrastim treatment has potential benefit for triage in the event of a radiological incident for treating acute hematopoietic syndrome. PMID:28362168

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs.

PubMed

Heinonen, J A; Schramko, A A; Skrifvars, M B; Litonius, E; Backman, J T; Mervaala, E; Rosenberg, P H

2017-04-01

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid ® ( n = 7) with Ringer's acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration ( p < 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p < 0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer's acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p < 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.

Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury.

PubMed

Lee, Jee Y; Choi, Hae Y; Yune, Tae Y

2016-10-01

Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hood River Passive House, Hood River, Oregon (Fact Sheet)

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

2014-02-01

The Hood River Passive Project was developed by Root Design Build of Hood River Oregon using the Passive House Planning Package (PHPP) to meet all of the requirements for certification under the European Passive House standards. The Passive House design approach has been gaining momentum among residential designers for custom homes and BEopt modeling indicates that these designs may actually exceed the goal of the U.S. Department of Energy's (DOE) Building America program to "reduce home energy use by 30%-50%" (compared to 2009 energy codes for new homes). This report documents the short term test results of the Shift Housemore » and compares the results of PHPP and BEopt modeling of the project. The design includes high R-Value assemblies, extremely tight construction, high performance doors and windows, solar thermal DHW, heat recovery ventilation, moveable external shutters and a high performance ductless mini-split heat pump. Cost analysis indicates that many of the measures implemented in this project did not meet the BA standard for cost neutrality. The ductless mini-split heat pump, lighting and advanced air leakage control were the most cost effective measures. The future challenge will be to value engineer the performance levels indicated here in modeling using production based practices at a significantly lower cost.« less

[Determination of methyl nonyl ketone in volatile oil from herbs of Houttuynia cordata by GC-MS].

PubMed

Yang, Lixin; Zhang, Yongxin; Yi, Hong; Yang, Hua; Zhang, Qiwei

2010-08-01

To develop a GC-MS method for the determination of methyl nonyl ketone in the volatile oil from the herbs of Houttuynia cordata. The sample was split in the 240 degrees C injection port, with 20:1 split ratio, and separated on a DB-5 (30 m x 0.25 mm, 0.25 microm film thickness) fused silica column with helium as the carrier gas. The temperature program was as follows: 100 degrees C for 2 min, the 5 degrees C x min(-1) to 150 degrees C, then 15 degrees C x min(-1) to 200 degrees C, and kept for 10 min. The MS transfer line temperature was set to 250 degrees C, the MS source temperature was set to 200 degrees C. The ionization mode was electron ionization (EI) and the selective ion monitor mode was used. A good linear relationship was constructed over the injection amount range of 5.5-110 ng of methyl nonyl ketone. The average recovery was 98.9%, and RSD was 2. 2%. The developed method was sensitive, accurate, and can be used for the determination of methyl nonyl ketone in the volatile oil and for the quality control of H. cordata.

New Whole-House Solutions Case Study: Hood River Passive House

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2014-02-01

The Hood River Passive Project was developed by Root Design Build of Hood River Oregon using the Passive House Planning Package (PHPP) to meet all of the requirements for certification under the European Passive House standards. The Passive House design approach has been gaining momentum among residential designers for custom homes and BEopt modeling indicates that these designs may actually exceed the goal of the U.S. Department of Energy's (DOE) Building America program to "reduce home energy use by 30%-50%" (compared to 2009 energy codes for new homes). This report documents the short term test results of the Shift Housemore » and compares the results of PHPP and BEopt modeling of the project. The design includes high R-Value assemblies, extremely tight construction, high performance doors and windows, solar thermal DHW, heat recovery ventilation, moveable external shutters and a high performance ductless mini-split heat pump. Cost analysis indicates that many of the measures implemented in this project did not meet the BA standard for cost neutrality. The ductless mini-split heat pump, lighting and advanced air leakage control were the most cost effective measures. The future challenge will be to value engineer the performance levels indicated here in modeling using production based practices at a significantly lower cost.« less

Distal biceps tendon rupture reconstruction using muscle-splitting double-incision approach

PubMed Central

Tarallo, Luigi; Mugnai, Raffaele; Zambianchi, Francesco; Adani, Roberto; Catani, Fabio

2014-01-01

AIM: To evaluate the clinical and functional results after repair of distal biceps tendon tears, following the Morrey’s modified double-incision approach. METHODS: We retrospectively reviewed 47 patients with distal rupture of biceps brachii treated between 2003 and 2012 in our Orthopedic Department with muscle-splitting double-incision technique. Outcome measures included the Mayo elbow performance, the DASH questionnaire, patient’s satisfaction, elbow and forearm motion, grip strength and complications occurrence. RESULTS: At an average 18 mo follow-up (range, 7 mo-10 years) the average Mayo elbow performance and DASH score were respectively 97.2 and 4.8. The elbow flexion range was 94%, extension was -2°, supination was 93% and pronation 96% compared with the uninjured limb. The mean grip strength, expressed as percentage of respective contralateral limb, was 83%. The average patient satisfaction rating on a Likert scale (from 0 to 10) was 9.4. The following complications were observed: 3 cases of heterotopic ossification (6.4%), one (2.1%) re-rupture of the tendon at the site of reattachment and 2 cases (4.3%) of posterior interosseous nerve palsy. No complication required further surgical treatment. CONCLUSION: This technique allows an anatomic reattachment of distal biceps tendon at the radial tuberosity providing full functional recovery with low complication rate. PMID:25133147

The relationship between session frequency and psychotherapy outcome in a naturalistic setting.

PubMed

Erekson, David M; Lambert, Michael J; Eggett, Dennis L

2015-12-01

The dose-response relationship in psychotherapy has been examined extensively, but few studies have included session frequency as a component of psychotherapy "dose." Studies that have examined session frequency have indicated that it may affect both the speed and the amount of recovery. No studies were found examining the clinical significance of this construct in a naturalistic setting, which is the aim of the current study. Using an archival database of session-by-session Outcome Questionnaire 45 (OQ-45) measures over 17 years, change trajectories of 21,488 university counseling center clients (54.9% female, 85.0% White, mean age = 22.5) were examined using multilevel modeling, including session frequency at the occasion level. Of these clients, subgroups that attended therapy approximately weekly or fortnightly were compared to each other for differences in speed of recovery (using multilevel Cox regression) and clinically significant change (using multilevel logistic regression). Results indicated that more frequent therapy was associated with steeper recovery curves (Cohen's f2 = 0.07; an effect size between small and medium). When comparing weekly and fortnightly groups, clinically significant gains were achieved faster for those attending weekly sessions; however, few significant differences were found between groups in total amount of change in therapy. Findings replicated previous session frequency literature and supported a clinically significant effect, where higher session frequency resulted in faster recovery. Session frequency appears to be an impactful component in delivering more efficient psychotherapy, and it is important to consider in individual treatment planning, institutional policy, and future research. (c) 2015 APA, all rights reserved).

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

PubMed

Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

2015-07-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Impact of Morphine After a Spinal Cord Injury

PubMed Central

Hook, Michelle A.; Liu, Grace T.; Washburn, Stephanie N.; Ferguson, Adam R.; Bopp, Anne C.; Huie, John R.; Grau, James W.

2007-01-01

Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury. PMID:17383022

[Single intravenous tranexamic acid dose to reduce blood loss in primary total knee replacement].

PubMed

Sanz-Reig, J; Parra Ruiz, B; Ferrández Martínez, J; Martínez López, J F

2016-01-01

To evaluate the effectiveness and safety of a single intravenous dose of tranexamic acid in order to reduce blood loss in total knee replacement. Prospective observational study of the administration of tranexamic acid in patients undergoing primary total knee arthroplasty from November 2013 to February 2015, in which an autologous blood recovery system was used. The study included 98 patients, distributed into two groups of 49 patients according to whether or not they received intravenous tranexamic acid. The primary endpoint was the number of patients requiring autologous transfusion from the recovery system autologous blood recovery system. No drop-outs were recorded during follow-up. There were no significant differences between groups as regards the preoperative and hospital variables. The mean preoperative haemoglobin and haematocrit at 24 and 48 hours postoperatively were similar in both groups. The average volume of bleeding in the autologous blood recovery system and estimated average blood loss was lower in patients who had been administered tranexamic acid, with significant differences. No patients in the group that was administered tranexamic acid required blood autotransfusion. The transfusion rate was zero in the two groups. No adverse events related to the administration of tranexamic acid were recorded. Intravenous administration of tranexamic acid, according to the described protocol, has presented a non-autotransfusion or allo-transfusion rate of 100%, with no increased incidence of thrombotic events. Thus, its use in this group of patients is recommended. The indication should be individualized, its use justified in the patient medical records, and informed consent is mandatory. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study.

PubMed

Scheidtmann, K; Fries, W; Müller, F; Koenig, E

2001-09-08

Functional disability is generally caused by hemiplegia after stroke. Physiotherapy used to be the only way of improving motor function in such patients. However, administration of amphetamines in addition to exercise improves motor recovery in animals, probably by increasing the concentration of norepinephrine in the central nervous system. Our aim was to ascertain whether levodopa could enhance the efficacy of physiotherapy after hemiplegia. We did a prospective, randomised, placebo-controlled, double-blind study in which we enrolled 53 primary stroke patients. For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. We quantitatively assessed motor function every week with Rivermead motor assessment (RMA). Six patients were excluded from analyses because of non-neurological complications. Motor recovery was significantly improved after 3 weeks of drug intervention in those on levodopa (RMA improved by 6.4 points) compared with placebo (4.1), and the result was independent of initial degree of impairment (p<0.004). The advantage of the levodopa group was maintained at study endpoint 3 weeks after levodopa was stopped. At the end of the study the total RMA score gain for the levodopa group was 8.2 points compared with 5.7 in the placebo group (p=0.020). A single dose of levodopa is well tolerated and, when given in combination with physiotherapy, enhances motor recovery in patients with hemiplegia. In view of its minimal side-effects, levodopa will be a possible add- on during stroke rehabilitation.

Effect of selected solutes on growth and recovery of a radiation-resistant Moraxella

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruns, M.A.; Maxcy, R.B.

1978-01-01

A highly radiation-resistant Moraxella sp. from beef was more resistant to gamma radiation in frozen beef than Clostridium botulinum 33A spores. Even though the Moraxella sp. was extremely radiation-resistant, its recovery after irradiation was markedly influenced by the plating medium. Fewer colony-forming units were recovered in Tryptic Soy Agar (TSA) than in Plate Count Agar (PCA), and differences in recovery became more pronounced with increasing radiation dose. Growth studies of the nonirradiated Moraxella sp. suggested the presence of dialyzable inhibitory factor(s) in Trypticase Soy Broth (TSB) and TSA. The low (0.5 percent) concentration of NaCl in TSA was shown tomore » be mainly responsible for the slow growth and reduced recovery after irradiation. Reduced recovery was also obtained by plating the Moraxella sp. in PCA plus 0.5 percent NaCl or PCA plus 6 percent glucose after irradiation. It was noted that 2 other highly radiation-resistant isolates identified as Moraxella sp. gave similar results. Sensitivity to low solute concentrations, therefore, appeared to be a general phenomenon for this group.« less

[Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

PubMed

Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

1997-12-01

4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

Effective and rapid treatment of wound botulism, a case report.

PubMed

Schulte, M; Hamsen, U; Schildhauer, T A; Ramczykowski, T

2017-10-26

The latest news shows several cases of contaminated heroin that is found in different parts all over Europe. This information can be helpful for the emergency doctors to find the correct diagnosis of wound botulism in patients who are intravenous drug users. We describe a case of a 40-year-old man who presented to the emergency department in 2016. He suffered from mild dysarthria, diplopia, dysphagia and ptosis since two days. The CT-scan of the cerebrum and the liquor were without any pathological results. We found out that the patient is an intravenous drug user and the clinical examination showed an abscess in the left groin. So we treated him with the suspected diagnosis of wound botulism. In the emergency operation we split the abscess, made a radical debridement and complementary treated him with a high dose of penicillin g and two units of botulism antitoxin. The suspected diagnosis was confirmed a few days later by finding the Toxin B in the abscess and in the patient's serum. In the following days the neurological symptoms decreased and the wound healing was without any complications. The patient left the hospital after nine days; the antibiotic therapy with penicillin g was continued for several days. In a following examination, 14 days after the patient's discharge of the hospital, no further symptoms were found and the abscess was treated successfully without any problems. Because wound botulism is a very rare disease it can be challenging to the attending physician. This case shows a fast treatment with full recovery of the patient without any further disabilities, which can be used for the future.

Inhalation and Ingestion Intakes with Associated Dose Estimates for Level II and Level III Personnel Using Capstone Study Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szrom, Fran; Falo, Gerald A.; Lodde, Gordon M.

2009-03-01

Depleted uranium (DU) intake rates and subsequent dose rates were estimated for personnel entering armored combat vehicles perforated with DU penetrators (level II and level III personnel) using data generated during the Capstone Depleted Uranium (DU) Aerosol Study. Inhalation intake rates and associated dose rates were estimated from cascade impactors worn by sample recovery personnel and from cascade impactors that served as area monitors. Ingestion intake rates and associated dose rates were estimated from cotton gloves worn by sample recovery personnel and from wipe test samples from the interior of vehicles perforated with large caliber DU munitions. The mean DUmore » inhalation intake rate for level II personnel ranged from 0.447 mg h-1 based on breathing zone monitor data (in and around a perforated vehicle) to 14.5 mg h-1 based on area monitor data (in a perforated vehicle). The mean DU ingestion intake rate for level II ranged from 4.8 mg h-1 to 38.9 mg h-1 based on the wipe test data including surface to glove transfer factors derived from the Capstone data. Based on glove contamination data, the mean DU ingestion intake rates for level II and level III personnel were 10.6 mg h-1 was and 1.78 mg h-1, respectively. Effective dose rates and peak kidney uranium concentration rates were calculated based on the intake rates. The peak kidney uranium concentration rate cannot be multiplied by the total exposure duration when multiple intakes occur because uranium will clear from the kidney between the exposures.« less

Remifentanil in combination with ketamine versus remifentanil in spinal fusion surgery--a double blind study.

PubMed

Hadi, B A; Al Ramadani, R; Daas, R; Naylor, I; Zelkó, R

2010-08-01

This study is aimed at conducting a program for two different anesthetic methods used during a spinal fusion surgery to ensure better intra-operative hemodynamic stability and post-operative pain control. A prospective, randomized, double blind study in patients scheduled for spinal fusion surgery, who were randomly allocated to two groups, G1 and G2, (n = 15 per group), class I-II ASA, was carried out. Both groups received pre-operatively midazolam, followed intra-operatively by propofol, sevoflurane, atracurium, and either remifentanil infusion 0.2 microg/kg/min (G1), or the same dose of remifentanil infusion and low doses of ketamine infusion 1 microg/kg/min (G2) anesthetics, antidote medication and post-operative morphine doses. HR, MAP, vital signs, surgical bleeding, urine output, duration of surgery and duration of anesthesia were recorded. In a 24-h recovery period in a post-anesthesia care unit (PACU) the recovery time, the first pain score and analgesic requirements were measured. Intra-operative HR and arterial BP were significantly less (p < 0.05) in G1 as compared to G2. In the PACU the first pain scores were significantly less (p < 0.05) in G2 than in G1. The time for the first patient analgesia demand dose was greater in G2, as also morphine consumption which was greater in G1 than G2 (p < 0.05). Other results were the same. None of the patients had any adverse drug reaction. Adding low doses of ketamine hydrochloride could be a routine therapy to improve the hemodynamic stability and reduce the post-operative morphine consumption during spinal fusion surgery.

Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211–labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation

PubMed Central

Chen, Yun; Kornblit, Brian; Hamlin, Donald K.; Sale, George E.; Santos, Erlinda B.; Wilbur, D. Scott; Storer, Barry E.; Storb, Rainer

2012-01-01

To reduce toxicity associated with external γ-beam radiation, we investigated radioimmunotherapy with an anti-CD45 mAb labeled with the α-emitter, astatine-211 (211At), as a conditioning regimen in dog leukocyte antigen-identical hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated with 100 to 618 μCi/kg 211At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT rescue demonstrated dose-dependent myelosuppression with subsequent autologous recovery, and transient liver toxicity in dogs treated with 211At doses less than or equal to 405 μCi/kg. Higher doses of 211At induced clinical liver failure. Subsequently, 8 dogs were conditioned with 155 to 625 μCi/kg 211At-labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical bone marrow followed by a short course of cyclosporine and mycophenolate mofetil immunosuppression. Neutropenia (1-146 cells/μL), lymphopenia (0-270 cells/μL), and thrombocytopenia (1500-6560 platelets/μL) with prompt recovery was observed. Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1 dog treated with the lowest 211At dose (155 μCi/kg) had low donor mononuclear cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver toxicity and no renal toxicity had been observed. In conclusion, conditioning with 211At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning. PMID:22134165

Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals.

PubMed

Tabor, B; Ikegami, M; Yamada, T; Jobe, A

1990-03-01

Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

Behavioral phenotypes associated with MPTP induction of partial lesions in common marmosets (Callithrix jacchus).

PubMed

Phillips, Kimberley A; Ross, Corinna N; Spross, Jennifer; Cheng, Catherine J; Izquierdo, Alyssa; Biju, K C; Chen, Cang; Li, Senlin; Tardif, Suzette D

2017-05-15

Parkinson's disease is a chronic neurodegenerative disorder with the core motor features of resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms also occur, and include cognitive dysfunction, mood disorders, anosmia (loss of smell), and REM sleep disturbances. As the development of medications and other therapies for treatment of non-motor symptoms is ongoing, it is essential to have animal models that aid in understanding the neural changes underlying non-motor PD symptoms and serve as a testing ground for potential therapeutics. We investigated several non-motor symptoms in 10 adult male marmosets using the MPTP model, with both the full (n=5) and partial (n=5) MPTP dosing regimens. Baseline data in numerous domains were collected prior to dosing; assessments in these same domains occurred post-dosing for 12 weeks. Marmosets given the partial MPTP dose (designed to mimic the early stages of the disease) differed significantly from marmosets given the full MPTP dose in several ways, including behavior, olfactory discrimination, cognitive performance, and social responses. Importantly, while spontaneous recovery of PD motor symptoms has been previously reported in studies of MPTP monkeys and cats, we did not observe recovery of any non-motor symptoms. This suggests that the neurochemical mechanisms behind the non-motor symptoms of PD, which appear years before the onset of symptoms, are independent of the striatal dopaminergic transmission. We demonstrate the value of assessing a broad range of behavioral change to detect non-motor impairment, anosmia, and differences in socially appropriate responses, in the marmoset MPTP model of early PD. Copyright © 2017 Elsevier B.V. All rights reserved.

A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer.

PubMed

Gunawardana, Dishan H; Basser, Russell L; Davis, Ian D; Cebon, Jonathan; Mitchell, Paul; Underhill, Craig; Kilpatrick, Trevor J; Reardon, Katrina; Green, Michael D; Bardy, Peter; Amor, Pene; Crump, David; Ng, Siobhan; Nation, Roger L; Begley, C Glenn

2003-06-01

Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the interleukin 6 family of cytokines. We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer. In stage 1 of the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25-16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2, 40 patients received rhLIF or placebo, either once daily for 14 days commencing the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2). In stage 1, platelet counts increased in most patients, including those who received placebo. Blood progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0 micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2, increases in C reactive protein were seen at higher doses. Several patients developed evidence of autonomic dysfunction, in particular impotence and episodic hypotension. The dose-limiting toxicities were hypotension and rigors. Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of dose. We demonstrated a biological effect of rhLIF on blood progenitor cells, C reactive protein levels, and hemopoietic recovery after chemotherapy.

How are different neural networks related to consciousness?

PubMed

Qin, Pengmin; Wu, Xuehai; Huang, Zirui; Duncan, Niall W; Tang, Weijun; Wolff, Annemarie; Hu, Jin; Gao, Liang; Jin, Yi; Wu, Xing; Zhang, Jianfeng; Lu, Lu; Wu, Chunping; Qu, Xiaoying; Mao, Ying; Weng, Xuchu; Zhang, Jun; Northoff, Georg

2015-10-01

We aimed to investigate the roles of different resting-state networks in predicting both the actual level of consciousness and its recovery in brain injury patients. We investigated resting-state functional connectivity within different networks in patients with varying levels of consciousness: unresponsive wakefulness syndrome (UWS; n = 56), minimally conscious state (MCS; n = 29), and patients with brain lesions but full consciousness (BL; n = 48). Considering the actual level of consciousness, we compared the strength of network connectivity among the patient groups. We then checked the presence of connections between specific regions in individual patients and calculated the frequency of this in the different patient groups. Considering the recovery of consciousness, we split the UWS group into 2 subgroups according to recovery: those who emerged from UWS (UWS-E) and those who remained in UWS (UWS-R). The above analyses were repeated on these 2 subgroups. Functional connectivity strength in salience network (SN), especially connectivity between the supragenual anterior cingulate cortex (SACC) and left anterior insula (LAI), was reduced in the unconscious state (UWS) compared to the conscious state (MCS and BL). Moreover, at the individual level, SACC-LAI connectivity was more present in MCS than in UWS. Default-mode network (DMN) connectivity strength, especially between the posterior cingulate cortex (PCC) and left lateral parietal cortex (LLPC), was reduced in UWS-R compared with UWS-E. Furthermore, PCC-LLPC connectivity was more present in UWS-E than in UWS-R. Our findings show that SN (SACC-LAI) connectivity correlates with behavioral signs of consciousness, whereas DMN (PCC-LLPC) connectivity instead predicts recovery of consciousness. © 2015 American Neurological Association.

Understanding N timing in corn yield and fertilizer N recovery: An insight from an isotopic labeled-N determination

PubMed Central

de Almeida, Rodrigo Estevam Munhoz; Pierozan Junior, Clovis; Lago, Bruno Cocco; Trivelin, Paulo Cesar Ocheuze

2018-01-01

Early fertilizer nitrogen (N) application on cover crops or their residues during the off-season is a practice adopted in Brazil subtropical conditions under no-tillage corn (Zea mays L.) systems. However, the effect of early N application on yield, plant N content, and N recovery efficiency (NRE) for corn is not yet well documented. Five fertilizer N timings in an oat-corn system were evaluated in two studies utilizing an isotopic-labeled N determination, 15N isotope. The N fertilization timings were: (i) oat tillering, (ii) 15 days before corn planting time, over the oat residues, (iii) at corn planting time, (iv) in-season at the three-leaf growth stage (V3), and (v) in-season split application at V3 and six-leaf (V6) growth stages. Based on the statistical analysis, the N fertilization timings were separated into three groups: 1) N-OATS, designated to N applied at oat; 2) N-PLANT, referred to pre-plant and planting N applications; and 3) N-CORN, designated to in-season corn N applications. Corn yield was not affected by the N fertilization timing. However, the N-CORN N fertilization timings enhanced NRE by 17% and 35% and final N recovery system (plant plus soil) by 16% and 24% all relative to N-OATS and N-PLANT groups, respectively. Overall, N-OATS resulted in the largest N derived from fertilizer (NDFF) amount in the deeper soil layer, in overall a delta of 10 kg N ha-1 relative to the rest of the groups. Notwithstanding corn yield was not affected, early N fertilization under subtropical conditions is not a viable option since NRE was diminished and the non-recovery N increased relative to the in-season N applications. PMID:29462178

Frozen chips: an unusual cause of severe frostbite injury

PubMed Central

Graham, C.; Stevenson, J.

2000-01-01

A case of severe frostbite injury to the right foot is presented. This was caused by the inappropriate application of a bag of frozen chips to the foot in an attempt to ease non-specific pain. No specific acute traumatic injury was identified. As the patient was a teacher of physical education, the pain had initially been assumed to originate from a minor musculoskeletal injury. Full recovery ensued after surgical excision of necrotic tissue and split skin grafting. The danger of inappropriate overenthusiastic use of ice packs or other frozen material to treat soft tissue injuries is emphasised. The need for education to prevent similar future injuries is discussed. Key Words: cold injury; frostbite; ice pack; skin; necrosis PMID:11049150

Fast, accurate photon beam accelerator modeling using BEAMnrc: A systematic investigation of efficiency enhancing methods and cross-section data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fragoso, Margarida; Kawrakow, Iwan; Faddegon, Bruce A.

In this work, an investigation of efficiency enhancing methods and cross-section data in the BEAMnrc Monte Carlo (MC) code system is presented. Additionally, BEAMnrc was compared with VMC++, another special-purpose MC code system that has recently been enhanced for the simulation of the entire treatment head. BEAMnrc and VMC++ were used to simulate a 6 MV photon beam from a Siemens Primus linear accelerator (linac) and phase space (PHSP) files were generated at 100 cm source-to-surface distance for the 10x10 and 40x40 cm{sup 2} field sizes. The BEAMnrc parameters/techniques under investigation were grouped by (i) photon and bremsstrahlung cross sections,more » (ii) approximate efficiency improving techniques (AEITs), (iii) variance reduction techniques (VRTs), and (iv) a VRT (bremsstrahlung photon splitting) in combination with an AEIT (charged particle range rejection). The BEAMnrc PHSP file obtained without the efficiency enhancing techniques under study or, when not possible, with their default values (e.g., EXACT algorithm for the boundary crossing algorithm) and with the default cross-section data (PEGS4 and Bethe-Heitler) was used as the ''base line'' for accuracy verification of the PHSP files generated from the different groups described previously. Subsequently, a selection of the PHSP files was used as input for DOSXYZnrc-based water phantom dose calculations, which were verified against measurements. The performance of the different VRTs and AEITs available in BEAMnrc and of VMC++ was specified by the relative efficiency, i.e., by the efficiency of the MC simulation relative to that of the BEAMnrc base-line calculation. The highest relative efficiencies were {approx}935 ({approx}111 min on a single 2.6 GHz processor) and {approx}200 ({approx}45 min on a single processor) for the 10x10 field size with 50 million histories and 40x40 cm{sup 2} field size with 100 million histories, respectively, using the VRT directional bremsstrahlung splitting (DBS) with no electron splitting. When DBS was used with electron splitting and combined with augmented charged particle range rejection, a technique recently introduced in BEAMnrc, relative efficiencies were {approx}420 ({approx}253 min on a single processor) and {approx}175 ({approx}58 min on a single processor) for the 10x10 and 40x40 cm{sup 2} field sizes, respectively. Calculations of the Siemens Primus treatment head with VMC++ produced relative efficiencies of {approx}1400 ({approx}6 min on a single processor) and {approx}60 ({approx}4 min on a single processor) for the 10x10 and 40x40 cm{sup 2} field sizes, respectively. BEAMnrc PHSP calculations with DBS alone or DBS in combination with charged particle range rejection were more efficient than the other efficiency enhancing techniques used. Using VMC++, accurate simulations of the entire linac treatment head were performed within minutes on a single processor. Noteworthy differences ({+-}1%-3%) in the mean energy, planar fluence, and angular and spectral distributions were observed with the NIST bremsstrahlung cross sections compared with those of Bethe-Heitler (BEAMnrc default bremsstrahlung cross section). However, MC calculated dose distributions in water phantoms (using combinations of VRTs/AEITs and cross-section data) agreed within 2% of measurements. Furthermore, MC calculated dose distributions in a simulated water/air/water phantom, using NIST cross sections, were within 2% agreement with the BEAMnrc Bethe-Heitler default case.« less

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

PubMed Central

Santos, Daniel; Gonzalez-Perez, Francisco; Navarro, Xavier

2016-01-01

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo. PMID:27867665

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2004-01-01

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

Comparison of cobinamide to hydroxocobalamin in reversing cyanide physiologic effects in rabbits using diffuse optical spectroscopy monitoring

NASA Astrophysics Data System (ADS)

Brenner, Matthew; Mahon, Sari B.; Lee, Jangwoen; Kim, Jae; Mukai, David; Goodman, Seth; Kreuter, Kelly A.; Ahdout, Rebecca; Mohammad, Othman; Sharma, Vijay S.; Blackledge, William; Boss, Gerry R.

2010-01-01

Our purpose is to compare cobinamide to hydroxocobalamin in reversing cyanide (CN)-induced physiologic effects in an animal model using diffuse optical spectroscopy (DOS). Cyanide poisoning is a major threat worldwide. Cobinamide is a novel molecule that can bind two molecules of cyanide, has a much higher binding affinity than hydroxocobalamin, and is more water soluble. We investigated the ability of equimolar doses of cobinamide and hydroxocobalamin to reverse the effects of cyanide exposure in an animal model monitored continuously by DOS. Cyanide toxicity was induced in 16 New Zealand white rabbits by intravenous infusion. Animals were divided into three groups: controls (n=5) received saline following cyanide, hydroxocobalamin (N=6) following cyanide, and cobinamide (N=5) following cyanide. Cobinamide caused significantly faster and more complete recovery of oxy- and deoxyhemoglobin concentrations in cyanide-exposed animals than hydroxocobalamin- or saline-treated animals, with a recovery time constant of 13.8+/-7.1 min compared to 75.4+/-25.1 and 76.4+/-42.7 min, for hydroxocobalamin- and saline-treated animals, respectively (p<0.0001). This study indicates that cobinamide more rapidly and completely reverses the physiologic effects of cyanide than equimolar doses of cobalamin at the dose used in this study, and CN effects and response can be followed noninvasively using DOS.

N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.

PubMed

Norwood, Daniel L; Mullis, James O; Feinberg, Thomas N; Davis, Letha K

2009-01-01

N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.

A nanoremediation strategy for the recovery of an As-polluted soil.

PubMed

Gil-Díaz, M; Diez-Pascual, S; González, A; Alonso, J; Rodríguez-Valdés, E; Gallego, J R; Lobo, M C

2016-04-01

The present study investigates the impact of the nanoremediation treatment on soil recovery as evaluated by the development of barley plants. Highly As-polluted brownfield soil was treated with nanoscale zero-valent iron (nZVI) commercial suspension at two doses (1% and 10%). Barley plants were cultivated in treated and untreated soils in a growth chamber, and the As, Fe, and nutrients uptake were determined. The efficacy of As immobilization was evaluated according to the toxicity characteristics leaching procedure (TCLP) as well as using a sequential extraction procedure. The application of nZVI reduced the amount of As in the more available fractions and increased the amount of As in the residual fraction. The best immobilization results were obtained for the highest dose of nZVI (10%). In turn, the lower availability of As in nZVI-treated soils, particularly at the dose of 10%, stimulated the development of the barley plants and decreased the As uptake. Neither an important increase of available Fe nor negative impact on soil physico-chemical and biological properties were observed. Thus, our results show that the use of nZVI could be an adequate strategy to recover the land use in As polluted soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

NASA Technical Reports Server (NTRS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2004-01-01

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs.

PubMed

Johnson, William D; Muzzio, Miguel; Detrisac, Carol J; Kapetanovic, Izet M; Kopelovich, Levy; McCormick, David L

2011-11-18

CP-31398 (N'-[2-[2-(4-methoxyphenyl)ethenyl]-4-quinazolinyl]-N,N-dimethyl-1,3-propanediamine dihydrochloride) is a styrylquinazoline that stabilizes the DNA binding conformation of p53, thereby maintaining the activity of p53 as a transcription factor and tumor suppressor. In consideration of the potential use of p53 stabilizers for cancer prevention and therapy, 28-day studies (with recovery) were performed to characterize the toxicity of CP-31398 in rats and dogs. In the rat study, groups of 15 CD rats/sex received daily gavage exposure to CP-31398 at 0, 40, 80, or 160mg/kg/day (0, 240, 480, or 960mg/m(2)/day). In the dog study, groups of five beagle dogs received daily gavage exposure to CP-31398 at 0, 10, 20, or 40mg/kg/day (0, 200, 400, or 800mg/m(2)/day). The high dose of CP-31398 induced mortality in both species: seven male rats and four female rats died as a result of hepatic infarcts, and two female dogs died as a result of hepatic necrosis without evidence of thrombosis. No deaths were seen in the mid- or low-dose groups in either species. In dogs, sporadic emesis was seen in the high dose and mid dose groups, and reductions in body weight gain were observed in all drug-exposed groups. CP-31398 induced mild anemia in both species; clinical pathology data also demonstrated hepatic toxicity, renal toxicity, inflammatory reactions, and coagulopathies in rats in the high dose and mid dose groups. Treatment-related microscopic changes in high dose and mid dose rats were identified in the liver, kidney, heart, bone marrow, lung, adrenals, spleen, thymus, skeletal muscle, and ovary; microscopic changes in the liver, heart, lung, and adrenals persisted through the recovery period. In dogs, microscopic changes were identified in the central nervous system, lung, and liver; changes in all tissues remained at the end of the recovery period. The liver is the primary site of limiting toxicity for CP-31398 in rats, and is also a key site of toxicity in dogs. The maximum tolerated dose (MTD) for subchronic oral administration of CP-31398 is 80mg/kg/day (480mg/m(2)/day) in rats and 20mg/kg/day (400mg/m(2)/day) in dogs. Although only modest and apparently reversible toxicities (microscopic changes in rats; reductions in body weight gain and alterations in red cell parameters in dogs) were seen in the low dose groups, no observed adverse effect levels (NOAELs) for CP-31398 could not be established for either species. The toxicity of CP-31398 suggests that this agent may not be suitable for use in cancer prevention. However, should in vivo antitumor efficacy be achievable at doses that do not induce limiting toxicity, CP-31398 may have utility as a cancer therapeutic. Modification of the primary sites of CP-31398 metabolism (N-demethylation of the alkyl side chain; hydroxylation and O-demethylation of the styryl benzene group) may result in the development of CP-31398 analogs with comparable pharmacologic activity and reduced toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs

PubMed Central

Johnson, William D.; Muzzio, Miguel; Detrisac, Carol J.; Kapetanovic, Izet M.; Kopelovich, Levy; McCormick, David L.

2011-01-01

CP-31398 (N′-[2-[2-(4-methoxyphenyl)ethenyl]-4-quinazolinyl]-N,N-dimethyl-1,3-propanediamine dihydrochloride) is a styrylquinazoline that stabilizes the DNA binding conformation of p53, thereby maintaining the activity of p53 as a transcription factor and tumor suppressor. In consideration of the potential use of p53 stabilizers for cancer prevention and therapy, 28-day studies (with recovery) were performed to characterize the toxicity of CP-31398 in rats and dogs. In the rat study, groups of 15 CD rats/sex received daily gavage exposure to CP-31398 at 0, 40, 80, or 160 mg/kg/day (0, 240, 480, or 960 mg/m2/day). In the dog study, groups of five beagle dogs received daily gavage exposure to CP-31398 at 0, 10, 20, or 40 mg/kg/day (0, 200, 400, or 800 mg/m2/day). The high dose of CP-31398 induced mortality in both species: seven male rats and four female rats died as a result of hepatic infarcts, and two female dogs died as a result of hepatic necrosis without evidence of thrombosis. No deaths were seen in the mid- or low dose groups in either species. In dogs, sporadic emesis was seen in the high dose and mid dose groups, and reductions in body weight gain were observed in all drug-exposed groups. CP-31398 induced mild anemia in both species; clinical pathology data also demonstrated hepatic toxicity, renal toxicity, inflammatory reactions, and coagulopathies in rats in the high dose and mid dose groups. Treatment-related microscopic changes in high dose and mid dose rats were identified in the liver, kidney, heart, bone marrow, lung, adrenals, spleen, thymus, skeletal muscle, and ovary; microscopic changes in the liver, heart, lung, and adrenals persisted through the recovery period. In dogs, microscopic changes were identified in the central nervous system, lung, and liver; changes in all tissues remained at the end of the recovery period. The liver is the primary site of limiting toxicity for CP-31398 in rats, and is also a key site of toxicity in dogs. The Maximum Tolerated Dose (MTD) for subchronic oral administration of CP-31398 is 80 mg/kg/day (480 mg/m2/day) in rats and 20 mg/kg/day (400 mg/m2/day) in dogs. Although only modest and apparently reversible toxicities (microscopic changes in rats; reductions in body weight gain and alterations in red cell parameters in dogs) were seen in the low dose groups, No Observed Adverse Effect Levels (NOAELs) for CP-31398 could not be established for either species. The toxicity of CP-31398 suggests that this agent may not be suitable for use in cancer prevention. However, should in vivo antitumor efficacy be achievable at doses that do not induce limiting toxicity, CP-31398 may have utility as a cancer therapeutic. Modification of the primary sites of CP-31398 metabolism (N-demethylation of the alkyl side chain; hydroxylation and O-demethylation of the styryl benzene group) may result in the development of CP-31398 analogs with comparable pharmacologic activity and reduced toxicity. PMID:21864638

Citrulline as a Biomarker for Gastrointestinal-Acute Radiation Syndrome: Species Differences and Experimental Condition Effects.

PubMed

Bujold, K; Hauer-Jensen, M; Donini, O; Rumage, A; Hartman, D; Hendrickson, H P; Stamatopoulos, J; Naraghi, H; Pouliot, M; Ascah, A; Sebastian, M; Pugsley, M K; Wong, K; Authier, S

2016-07-01

Animal models of hematopoietic and gastrointestinal acute radiation syndromes (ARS) have been characterized to develop medical countermeasures. Acute radiation-induced decrease of intestinal absorptive function has been correlated to a decrease in the number of intestinal crypt cells resulting from apoptosis and enterocyte mass reduction. Citrulline, a noncoded amino acid, is produced almost exclusively by the enterocytes of the small intestine. Citrullinemia has been identified as a simple, sensitive and suitable biomarker for radiation-induced injury associated with gastrointestinal ARS (GI-ARS). Here we discuss the effect of radiation on plasma citrulline levels in three different species, C57BL/6 mice, Göttingen minipigs and rhesus nonhuman primates (NHPs), measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). The effects of experimental study conditions such as feeding and anesthesia were also examined on plasma citrulline levels in the NHPs. Both the mice and Göttingen minipigs were partial-body irradiated (PBI) with doses from 13-17 Gy and 8-16 Gy, respectively, whereas NHPs were total-body irradiated (TBI) with doses from 6.72-13 Gy. Blood samples were taken at different time points and plasma citrulline levels were measured in the three species at baseline and after irradiation. Basal plasma citrulline concentrations (mean ± SEM) in mice and minipigs were 57.8 ± 2.8 μM and 63.1 ± 2.1 μM, respectively. NHPs showed a basal plasma citrulline concentration of 32.6 ± 0.7 μM, very similar to that of humans (∼40 μM). Plasma citrulline progressively decreased after irradiation, reaching nadir values between day 3.5 and 7. The onset of citrulline recovery was observed earlier at lower radiation doses, while only partial citrulline recovery was noted at higher radiation doses in minipigs and NHPs, complete recovery was noted in mice at all doses. Plasma citrulline levels in NHPs anesthetized with ketamine and acepromazine significantly decreased by 35.5% (P = 0.0017), compared to unanesthetized NHPs. In the postprandial state, citrulline concentrations in NHPs were slightly but significantly decreased by 12.2% (P = 0.0287). These results suggest that plasma citrulline is affected by experimental conditions such as anesthesia and feeding.

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases.

PubMed

Keever-Taylor, Carolyn A; Heimfeld, Shelly; Steinmiller, Kaitlyn C; Nash, Richard A; Sullivan, Keith M; Czarniecki, Christine W; Granderson, Tomeka C; Goldstein, Julia S; Griffith, Linda M

2017-09-01

To ensure comparable grafts for autologous hematopoietic cell transplantation (HCT) in the National Institute of Allergy and Infectious Diseases-sponsored Investigational New Drug protocols for multiple sclerosis (HALT-MS) and systemic sclerosis (SCOT), a Drug Master File approach to control manufacture was implemented, including a common Master Production Batch Record and site-specific standard operating procedures with "Critical Elements." We assessed comparability of flow cytometry and controlled rate cryopreservation among sites and stability of cryopreserved grafts using hematopoietic progenitor cells (HPCs) from healthy donors. Hematopoietic Progenitor Cells, Apheresis-CD34+ Enriched, for Autologous Use (Auto-CD34 + HPC) graft specifications included ≥70% viable CD34 + cells before cryopreservation. For the 2 protocols, 110 apheresis collections were performed; 121 lots of Auto-CD34 + HPC were cryopreserved, and 107 of these (88.4%) met release criteria. Grafts were infused at a median of 25 days (range, 17 to 68) post-apheresis for HALT-MS (n = 24), and 25 days (range, 14 to 78) for SCOT (n = 33). Subjects received precryopreservation doses of a median 5.1 × 10 6 viable CD34 + cells/kg (range, 3.9 to 12.8)  for HALT-MS and 5.6 × 10 6 viable CD34 + cells/kg (range, 2.6 to 10.2) for SCOT. Recovery of granulocytes occurred at a median of 11 days (range, 9 to 15) post-HCT for HALT-MS and 10 days (range, 8 to 12) for SCOT, independent of CD34 + cell dose. Subjects received their last platelet transfusion at a median of 9 days (range, 6 to 16) for HALT-MS and 8 days (range, 6 to 23) for SCOT; higher CD34 + /kg doses were associated with faster platelet recovery. Stability testing of cryopreserved healthy donor CD34 + HPCs over 6 months of vapor phase liquid nitrogen storage demonstrated consistent 69% to 73% recovery of viable CD34 + cells. Manufacturing of Auto-CD34 + HPC for the HALT-MS and SCOT protocols was comparable across all sites and supportive for timely recovery of granulocytes and platelets. Published by Elsevier Inc.

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2016-04-01

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min-1 for conventional fractionation.

Dose-response effects of corneal anesthetics.

PubMed

Polse, K A; Keener, R J; Jauregui, M J

1978-01-01

With double-masking procedures, the dose-response curves for 0.1, 0.2, and 0.4% benoxinate and 0.125, 0.25, and 0.50% proparacaine hydrochloride were determined by monitoring changes in corneal touch threshold after applying each anesthetic. The level of corneal anesthesia necessary for applanation tonometry was also determined. The maximum increase in threshold that could be measured following instillation of 50 microliter of the drug was 200 mg/mm2 All 6 anesthetic solutions produced this amount of decreased corneal sensitivity. Recovery from the anesthetic was exponential for all concentrations; however, the lower doses had the shortest duration. For applanation tonometry, the corneal threshold for touch must be 75 mg/mm2 or higher. We conclude that a quarter to a half of the commonly used anesthetic dose is sufficient for routine tonometric evaluation.

Recovery of cholinesterase activity in five avian species exposed to dicrotophos, an organophosphorus pesticide

USGS Publications Warehouse

Fleming, W.J.; Grue, C.E.

1981-01-01

The responses of brain and plasma cholinesterase (ChE) activities were examined in mallard ducks, bobwhite quail, barn owls, starlings, and common grackles given oral doses of dicrotophos, an organophosphorus insecticide. Up to an eightfold difference in response of brain ChE activity to dicrotophos was found among these species. Brain ChE activity recovered to within 2 SD of normal within 26 days after being depressed 55 to 64%. Recovery of brain ChE activity was similar among species and followed the model Y = a + b (log10X).

Complete recovery after severe myxoedema coma complicated by status epilepticus

PubMed Central

Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

2015-01-01

We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. PMID:25809434

Complete recovery after severe myxoedema coma complicated by status epilepticus.

PubMed

Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

2015-03-25

We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. 2015 BMJ Publishing Group Ltd.

Development of a preprototype hyperfiltration wash water recovery subsystem

NASA Technical Reports Server (NTRS)

1981-01-01

The use of hyperfiltration as a mode of reclamation of waste water on board an extended mission spacecraft was investigated. Two basic approaches are considered with respect to hyperfiltration of wash water recovery. The initial approach involves the use of a hollow fiber permeator and a tubular module, operating at ambient temperature. In this system, relatively large doses of biocides are used to control microbial activity. Since biocides require a long contact time, and many have adverse dematological effects as well as many interact with membrane material, a second approach is considered which involves operating at pasturization temperature.

Testing of selected pharmacological agents for capturing waterfowl [Annual Progress Report

USGS Publications Warehouse

Cline, D.R.

1970-01-01

The response of game-farm mallards (Frost strain) to seven pharmacological immobilizing agents was evaluated in Phase I of a planned four-phase study. A limited amount of testing was also done with wild mallards. Single dosages were administered to determine the mean effective dose (ED50) and mean lethal dose (LD50), The therapeutic index, or safety factor (LD50/ED50), and palatability were also established. Optimum dosage rates of compounds administered orally on baits were not considered in this phase of the study. Compounds were-administered by intubation and calculated in terms of mg/kg. All except one compound produced narcosis within 5 minutes at the effective dose rate.Immobilization periods for the seven compounds ranged from 7-24 minutes, and recovery periods from 1.0-6.5 hours. Such wide variations in actions of the compounds can be attributed to a compound's rate of absorption, the ease with which it passes the blood-brain barrier, its solubility in tissues, and its rate of metabolism in the liver and kidneys. Length of both the immobilization and recovery periods were extended when dosages were increased. There was no delayed mortality among survivors with any of the seven compounds at either the ED50 or LD50. Females were generally more sensitive to the anesthetizing agents than males. The ED50 for wild mallards was substantially higher than that for the experimental game-farm birds for the two compounds on which this was tested.Tribromoethanol (Avertin of Winthrop Laboratories) satisfied all test criteria an Phase I and will be subjected to more intensive investigation in ensuing tests. Thiopental sodium (Pentothal of Amdal Company) and pentobarbital sodium (Nembutal of Abbott Laboratories) were judged to be marginal. Although their therapeutic indexes were good (5.00), recovery periods were prolonged and toxic convulsions occurred at medium to high dose rates as the LD50 was approached.Alpha-chloralose (Fisher Scientific) proved least promising of the seven compounds, mainly because of its unacceptable therapeutic index (2.25) and because it possesses prolonged induction and recovery periods. Two new experimental drugs, methoxymol and metomidate (Pitman-Moore), appeared effective and safe when administered by intubation but produced a taste aversion when added to bait. Rejection because of taste was also a problem with secobarbital (Seconal of Elanco Products), and its therapeutic index of 2.75 was unacceptable. Monitoring of heart and respiratory rates, and body temperature by telemetry showed promise as a technique for determining physiological response to drug action.

SU-E-T-317: The Development of a DIBH Technique for Left Sided Breast Patients Undergoing Radiation Therapy Utilizing Varians RPM System in a Community Hospital

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasson, B; Young, M; Workie, D

2014-06-01

Purpose: To develop and implement a Deep Inhalation Breath Hold program (DIBH) for treatment of patients with Left-sided breast cancer in a community hospital. Methods: All patients with left sided breast cancer underwent a screening free breathing CT. Evaluation of the conventional tangent treatment fields and the heart was conducted. If the heart would not be excluded using tangents, the patient then received DIBH breathe coaching. The patients returned for a 4D CT simulation. The patients breathing cycle was monitored using the Varian Real-Time position ManagementTM (RPM) system to assess duration of DIBH, amplitude, phase and recovery time to normalmore » breathing. Then a DIBH CT was obtained at the desired amplitude. Duplicate plans were developed for both free breathing and DIBH on the Eclipse planning system and comparison DVH's were created. The plan that provided the prescribed treatment coverage and the least doses to the OAR (heart, Lt. Lung) was determined. Those patients selected to receive treatment with DIBH were set up for treatment, and breathing was monitored using the RPM system. Practice trials were used to confirm that the amplitude, phase and recovery were consistent with findings from simulation. Results: 10 patients have been treated using the DIBH procedure in our clinic. The DIBH patients had an average increase of 80% lung volume on DIBH, decreased lung volume receiving 50% of the dose, and decreases in the V20 dose. Significant reduction in the maximum and mean dose to the heart, as well as the dose to 1CC of the volume for the DIBH plans. Conclusion: Using the RPM system already available in the clinic, staff training, and patient coaching a simple DIBH program was setup. The use of DIBH has shown promise in reducing doses to the critical organs while maintaining PTV coverage for left sided breast treatments.« less

Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding

PubMed Central

Dynlacht, Joseph R.; Garrett, Joy; Joel, Rebecca; Lane, Katharina; Mendonca, Marc S.; Orschell, Christie M.

2017-01-01

There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer to this approach as “protective wounding”. In this article, we report on our efforts to further optimize, characterize and demonstrate the validity of the protective wounding response by comparing the response of female and male mice, varying the radiation dose, the size of the wound, and the timing of wounding with respect to administration of the radiation dose. Both male and female mice that received a subcutaneous incision after irradiation were significantly protected from radiation lethality. We observed that the extent of protection against lethality after an LD50/30 X-ray dose was independent of the size of the subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing the survival of mice exposed to a broad range of radiation doses (LD15–LD100). Over the range of 6.2–6.7 Gy, the increase in survival observed in mice that received an incision was associated with an enhanced recovery of hematopoiesis. The enhanced rate of recovery of hematopoiesis was preceded by an increase in the production of a select group of cytokines. Thus, a thorough knowledge of the timing of the cytokine cascade after wounding could aid in the development of novel pharmacological radiation countermeasures that can be administered several days after the actual radiation exposure. PMID:28437188

The efficacy of alfaxalone for immersion anesthesia in koi carp (Cyprinus carpio).

PubMed

Minter, Larry J; Bailey, Kate M; Harms, Craig A; Lewbart, Gregory A; Posner, Lysa P

2014-07-01

To characterize the physiologic and behavioral effects of a single induction dose and two maintenance doses of alfaxalone delivered by water immersion in the anesthesia of koi (Cyprinus carpio). Prospective, within-subject complete crossover design. Six adult koi (Cyprinus carpio) with a median body weight of 344.5 g (range 292.0-405.0 g). Koi were immersed in water containing 10 mg L(-1) alfaxalone until immobile and then maintained with alfaxalone at either 1 or 2.5 mg L(-1) via a recirculating water system. Times for anesthetic induction and recovery periods were recorded. Physiologic and blood gas parameters were evaluated before, during and after the anesthetic trial. Response to noxious stimuli was also assessed. Median anesthesia induction time for all fish was 5.4 minutes. Median recovery time was 11.8 and 26.4 minutes in the 1.0 and 2.5 mg L(-1) doses, respectively, which were significantly different (p = 0.04). Cessation of opercular movement occurred in 0/6 and 4/6 fish exposed to 1.0 and 2.5 mg L(-1) dose respectively. No difference was observed in median heart rate over the duration of the anesthetic events. Response to noxious stimulation was 4/6 and 0/6 in the 1.0 and 2.5 mg L(-1) doses respectively. Oxygenation and ventilation did not change during the experiment, but there was a significant decrease in blood pH along with an increase in blood lactate concentration. Administration of alfaxalone, via water immersion, as an induction and maintenance anesthesia agent provided rapid and reliable anesthesia of koi with no mortality. The maintenance dose of 2.5 mg L(-1) was sufficient to prevent response to noxious stimuli but was associated with a clinically relevant depression in opercular rate. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Prolonged Perioperative Low-Dose Ketamine Does Not Improve Short and Long-term Outcomes After Pediatric Idiopathic Scoliosis Surgery.

PubMed

Perelló, Marina; Artés, David; Pascuets, Cristina; Esteban, Elisabeth; Ey Batlle, Ana M

2017-03-01

A randomized, double-blind, placebo-controlled study, with a six-month follow-up period. The aim of this study was to test the hypothesis that a 72-hour dose of subanesthetic ketamine in this surgical procedure reduces postoperative morphine use and to assess whether there are fewer adverse effects, if postoperative recovery is faster, if there is less peri-incisional hyperalgesia, or if there is lower incidence of persistent postsurgical pain. Tissue injury and high opioid requirements following posterior spinal fusion surgery produce central sensitization, which can in turn be associated with hyperalgesia and chronic pain. Clinical trials involving this type of procedure using subanesthetic ketamine doses have assessed pain and morphine requirements with contradictory results. The effects of prolonged subanesthetic ketamine doses on postoperative recovery, mechanical hyperalgesia, and the incidence of chronic pain are unknown. A total of 48 pediatric patients between 10 and 18 years diagnosed with idiopathic scoliosis were randomized to receive perioperative low-dose ketamine or placebo for 72 hours. They received general anesthesia, intraoperative remifentanil, and morphine postoperatively (patient-controlled analgesia). We measured morphine consumption, pain at rest and during movement (coughing), undesirable effects, and sedation during morphine treatment. The onset of oral intake, ambulation, and hospital stay were recorded. The extent of the peri-incisional hyperalgesia was measured at 72 hours and pain controls were conducted postsurgery. Primary endpoint results (total cumulative morphine consumption while admitted) were obtained in 44 patients. Results were 2.72 (SD 1.13) in the placebo group and 3.13 (SD 1.13) in the study group (P = 0.2903), with no significant differences. Moreover, differences were not found between the experimental group and the placebo group in the secondary endpoints analyzed. Our findings do not support the routine combining of prolonged subanesthetic ketamine doses with opioids in posterior fusion surgery in children with idiopathic scoliosis. 2.

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies.

PubMed

Herring, William Joseph; Woo, Tiffany; Assaid, Christopher A; Lupinacci, Robert J; Lemmens, Hendrikus J; Blobner, Manfred; Khuenl-Brady, Karin S

2017-09-01

To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations. Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies. Operating room. 1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB. Sugammadex (2.0mg/kg at second twitch reappearance [T 2 ; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo. Time to recovery of the train-of-four (TOF) ratio to 0.9. Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T 2 after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan). Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Accelerated hematopoietic recovery with angiotensin-(1-7) after total body radiation.

PubMed

Rodgers, Kathleen E; Espinoza, Theresa; Roda, Norma; Meeks, Christopher J; Hill, Colin; Louie, Stan G; Dizerega, Gere S

2012-06-01

Angiotensin (1-7) [A(1-7)] is a component of the renin angiotensin system (RAS) that stimulates hematopoietic recovery after myelosuppression. In a Phase I/IIa clinical trial, thrombocytopenia after chemotherapy was reduced by A(1-7). In this study, the ability of A(1-7) to improve recovery after total body irradiation (TBI) is shown with specific attention to radiation-induced hematopoietic injury. Mice were exposed to TBI (doses of 2-7 Gray [Gy]) of cesium 137 gamma rays, followed by treatment with A(1-7), typical doses were 100-1000 μg/kg given once or once daily for a specified number of days depending on the study. Animals are injected subcutaneously via the nape of the neck with 0.1 ml drug in saline. The recovery of blood and bone marrow cells was determined. Effects of TBI and A(1-7) on survival and bleeding time was also evaluated. Daily administration of A(1-7) after radiation exposure improved survival (from 60% to 92-97%) and reduced bleeding time at day 30 after TBI. Further, A(1-7) increased early mixed progenitors (3- to 5-fold), megakaryocyte (2- to 3-fold), myeloid (3- to 6-fold) and erythroid (2- to 5-fold) progenitors in the bone marrow and reduced radiation-induced thrombocytopenia (RIT) (up to 2-fold). Reduction in the number of treatments to 3 per week also improved bone marrow recovery and reduced RIT. As emergency responder and healthcare systems in case of nuclear accident or/and terrorist attack may be overwhelmed, the consequence of delayed initiation of treatment was ascertained. Treatment with A(1-7) can be delayed up to 5 days and still be effective in the reduction of RIT or acceleration of bone marrow recovery. The data presented in this paper indicate that A(1-7) reduces the consequences of critical radiation exposure and can be initiated well after initial exposure with maximal effects on early responding hematopoietic progenitors when treatment is initiated 2 days after exposure and 5 days after exposure for the later responding progenitors and reduced thrombocytopenia. There was some effect of A(1-7) even when given days after radiation exposure.

Safety and Immune Responses in Children After Concurrent or Sequential 2009 H1N1 and 2009–2010 Seasonal Trivalent Influenza Vaccinations

PubMed Central

Frey, Sharon E.; Bernstein, David I.; Gerber, Michael A.; Keyserling, Harry L.; Munoz, Flor M.; Winokur, Patricia L.; Turley, Christine B.; Rupp, Richard E.; Hill, Heather; Wolff, Mark; Noah, Diana L.; Ross, Allison C.; Cress, Gretchen; Belshe, Robert B.

2012-01-01

Background. Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Methods. Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results. All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Conclusions. Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. Clinical Trials Registration. NCT00943202. PMID:22802432

Evaluating the dose effects of a longitudinal micro-CT study on pulmonary tissue in C57BL/6 mice

NASA Astrophysics Data System (ADS)

Detombe, Sarah A.; Dunmore-Buyze, Joy; Petrov, Ivailo E.; Drangova, Maria

2012-03-01

Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study. Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung volume or lung density between the control group and the irradiated group. Similarly, there were no significant differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung tissue also showed no evidence of inflammation or fibrosis in the irradiated group. Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro- CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.

Determination of the spatial resolution required for the HEDR dose code. Hanford Environmental Dose Reconstruction Project: Dose code recovery activities, Calculation 007

DOE Office of Scientific and Technical Information (OSTI.GOV)

Napier, B.A.; Simpson, J.C.

1992-12-01

A series of scoping calculations has been undertaken to evaluate the doses that may have been received by individuals living in the vicinity of the Hanford site. This scoping calculation (Calculation 007) examined the spatial distribution of potential doses resulting from releases in the year 1945. This study builds on the work initiated in the first scoping calculation, of iodine in cow`s milk; the third scoping calculation, which added additional pathways; the fifth calculation, which addressed the uncertainty of the dose estimates at a point; and the sixth calculation, which extrapolated the doses throughout the atmospheric transport domain. A projectionmore » of dose to representative individuals throughout the proposed HEDR atmospheric transport domain was prepared on the basis of the HEDR source term. Addressed in this calculation were the contributions to iodine-131 thyroid dose of infants from (1) air submersion and groundshine external dose, (2) inhalation, (3) ingestion of soil by humans, (4) ingestion of leafy vegetables, (5) ingestion of other vegetables and fruits, (6) ingestion of meat, (7) ingestion of eggs, and (8) ingestion of cows` milk from-Feeding Regime 1 as described in scoping calculation 001.« less

Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials.

PubMed

Sewell, Fiona; Chapman, Kathryn; Baldrick, Paul; Brewster, David; Broadmeadow, Alan; Brown, Paul; Burns-Naas, Leigh Ann; Clarke, Janet; Constan, Alex; Couch, Jessica; Czupalla, Oliver; Danks, Andy; DeGeorge, Joseph; de Haan, Lolke; Hettinger, Klaudia; Hill, Marilyn; Festag, Matthias; Jacobs, Abby; Jacobson-Kram, David; Kopytek, Stephan; Lorenz, Helga; Moesgaard, Sophia Gry; Moore, Emma; Pasanen, Markku; Perry, Rick; Ragan, Ian; Robinson, Sally; Schmitt, Petra M; Short, Brian; Lima, Beatriz Silva; Smith, Diane; Sparrow, Sue; van Bekkum, Yvette; Jones, David

2014-10-01

An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk. They are included on toxicology studies to assess whether effects observed during dosing persist or reverse once treatment ends. The group devised a questionnaire to collect information on the use of recovery animals in general regulatory toxicology studies to support first-in-human studies. Questions focused on study design, the rationale behind inclusion or exclusion and the impact this had on internal and regulatory decisions. Data on 137 compounds (including 53 biologicals and 78 small molecules) from 259 studies showed wide variation in where, when and why recovery animals were included. An analysis of individual study and programme design shows that there are opportunities to reduce the use of recovery animals without impacting drug development. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Optimizing the combination insulin bolus split for a high-fat, high-protein meal in children and adolescents using insulin pump therapy.

PubMed

Lopez, P E; Smart, C E; McElduff, P; Foskett, D C; Price, D A; Paterson, M A; King, B R

2017-10-01

To determine the optimum combination bolus split to maintain postprandial glycaemia with a high-fat and high-protein meal in young people with Type 1 diabetes. A total of 19 young people (mean age 12.9 ± 6.7 years) participated in a randomized, repeated-measures trial comparing postprandial glycaemic control across six study conditions after a high-fat and high-protein meal. A standard bolus and five different combination boluses were delivered over 2 h in the following splits: 70/30 = 70% standard /30% extended bolus; 60/40=60% standard/40% extended bolus; 50/50=50% standard/50% extended bolus; 40/60=40% standard/60% extended bolus; and 30/70=30% standard/70% extended bolus. Insulin dose was determined using the participant's optimized insulin:carbohydrate ratio. Continuous glucose monitoring was used to assess glucose excursions for 6 h after the test meal. Standard bolus and combination boluses 70/30 and 60/40 controlled the glucose excursion up to 120 min. From 240 to 300 min after the meal, the glucose area under the curve was significantly lower for combination bolus 30/70 compared with standard bolus (P=0.004). High-fat and high-protein meals require a ≥60% insulin:carbohydrate ratio as a standard bolus to control the initial postprandial rise. Additional insulin at an insulin:carbohydrate ratio of up to 70% is needed in the extended bolus for a high fat and protein meal to prevent delayed hyperglycaemia. © 2017 Diabetes UK.

Scram recoveries---C Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constable, D.W.; Pierce, J.R.; Wood, S.A.

1962-04-26

The purpose of this report is to discuss the observations made on two equilibrium scram recovery startups (April 5 and April 16). Normally, the two startups would have little significance but unusual ruptures were experienced in the top near section of the reactor shortly after both startups, which indicates that some similarity could exist between the two. The ruptures were unusual in that the two tubes involved both had multiple ruptures. One tube contained two E{sup 2} ruptures and the other tube contained three overbore metal ruptures. The overbore tube also contained three incipient ruptures (uranium split under the can).more » The initial rise to power on both startups appeared to be normal with the flux peaking on the near side as expected. On the April 16 startup the maximum level reached was 1050 at which time a rupture in overbore tube 3062 caused on increase in pressure resulting in a high trip on the Panellit gauge. A level of 1600 was reached on the April 5 startup which was held for approximately 14 hours at which time the reactor was shut down due to rupture indications on row 29.« less

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats

PubMed Central

2013-01-01

Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus. PMID:24131855

Results of a Community-based, Randomized Study Comparing a Clear Liquid Diet With a Low-residue Diet Using a Magnesium Citrate Preparation for Screening and Surveillance Colonoscopies.

PubMed

Thukral, Chandrashekhar; Tewani, Sumeet K; Lake, Adam J; Shiels, Aaron J; Geissler, Kathy; Popejoy, Sara; Stafford, Megan; Vicari, Joseph J

2017-11-03

Current bowel preparations for colonoscopy include a clear liquid diet (CLD) along with consumption of a laxative. This dietary restriction along with large volume bowel preparations are barriers to compliance and willingness among patients in scheduling screening examinations. The aim of our study was to compare the efficacy and tolerability of a low-volume split dose magnesium citrate bowel preparation in patients on a low-residue diet (LRD) with those on a CLD. In this single center, single blinded, randomized controlled trial, patients scheduled for outpatient colonoscopies were assigned to either a CLD or a LRD 1 day before the examination. Both groups received a split dose magnesium citrate preparation. The quality of the preparation was rated using the Boston Bowel Preparation Scale (BBPS). Patient satisfaction and side effects were evaluated using a questionnaire. We were unable to detect a significant difference in the BBPS scores between the LRD and CLD groups (P=0.581). A significantly higher percentage of patients in the LRD group rated the diet as easy compared with the CLD group (P<0.001). Satisfaction scores were significantly higher in the LRD group, compared with the CLD group (P<0.001). The side effect profiles of both arms were similar. There was no significant difference between LRD and CLD in patients using a magnesium citrate bowel preparation for screening and surveillance colonoscopies. Patient satisfaction scores were higher with a LRD compared with a CLD. We believe the LRD should be the recommended diet in patients using a standard bowel preparation for screening and surveillance colonoscopy.

Educational strategies for colonoscopy bowel prep overcome barriers against split-dosing: A randomized controlled trial

PubMed Central

Andrealli, Alida; Paggi, Silvia; Amato, Arnaldo; Rondonotti, Emanuele; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Spinzi, Giancarlo; Radaelli, Franco

2018-01-01

Background A split-dose (SD) regimen is crucial for colonoscopy quality. Compliance with SD for early morning colonoscopy is generally poor. The present study evaluated whether pre-colonoscopy counselling, in addition to a dedicated leaflet, might increase SD uptake. Methods Consecutive 50–69-year-old patients undergoing screening colonoscopy before 10 a.m. were randomized to either receive written information only on bowel preparation (Written Group, WG) or written and oral instructions (Written and Oral Group, WaOG). The leaflet strongly encouraged SD adoption. The primary endpoint was the number of patients adopting SD in each group. The secondary endpoints were predictors of SD uptake, compliance with preparation schemes and cleansing adequacy. Results A total of 286 patients (143 WG, 143 WaOG) were enrolled (mean age 59.6 ± 6.1 years, men 49.3%). SD was adopted by 114 and 125 patients in the WG and WaOG, respectively (79.7% versus 87.4%, p = 0.079). No significant differences were observed for the proportion of patients with full compliance with preparation scheme (97.9% versus 97.2%, p = 0.99) and of procedures with adequate bowel cleansing (95.6% versus 95.1%, p = 0.77). At multivariate analysis, a > 1 h travel time to the endoscopy service was inversely correlated with SD uptake (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09–0.98). Conclusions Our leaflet guaranteed satisfactory uptake of SD and excellent adherence to the preparation scheme for early morning colonoscopy. Its use might marginalize the need for additional oral instructions, particularly in open-access settings. PMID:29511558

Antibody response after a single dose of an AS03-adjuvanted split-virion influenza A (H1N1) vaccine in heart transplant recipients.

PubMed

Meyer, Sven; Adam, Matti; Schweiger, Brunhilde; Ilchmann, Corina; Eulenburg, Christine; Sattinger, Edgar; Runte, Hendrik; Schlüter, Michael; Deuse, Tobias; Reichenspurner, Hermann; Costard-Jäckle, Angelika

2011-05-15

Influenza A (H1N1) has emerged as a considerable threat for recipients of organ transplants. Vaccination against the novel influenza A (H1N1) virus has generally been advocated. There is limited experience with AS03-adjuvanted A/H1N1 pandemic influenza vaccines in immunosuppressed patients. We conducted an observational, nonrandomized single-center study to assess antibody response and vaccine-related adverse effects in 47 heart transplant recipients (44 men; age, 56±13 years). The AS03-adjuvanted, inactivated split-virion A/California/7/2009 H1N1v pandemic vaccine was administered. Antibody titers were measured using hemagglutination inhibition; immunoglobulin G (IgG) response was assessed using a new pandemic influenza A IgG enzyme-linked immunosorbent assay (ELISA) test kit and compared with hemagglutination-inhibition titers. Adverse effects of vaccination were assessed by a questionnaire. Postvaccination antibody titers of greater than or equal to 1:40 were found in only 15 patients, corresponding to a seroprotection rate of 32% (95% confidence interval, 19%-47%). Sensitivity, specificity, positive predictive value, and negative predictive value of ELISA testing were 80.0%, 68.8%, 54.5%, and 88.0%, respectively. Age, time posttransplantation, and immunosuppressive regimen did not impact antibody response. Vaccination was well tolerated. Single-dose administration of an AS03-adjuvanted vaccine against the novel influenza A (H1N1) virus did not elicit seroprotective antibody concentrations in a substantial proportion of heart transplant recipients; the new pandemic influenza A IgG ELISA test kit proved to be of limited clinical use.

SU-F-T-370: A Fast Monte Carlo Dose Engine for Gamma Knife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, T; Zhou, L; Li, Y

2016-06-15

Purpose: To develop a fast Monte Carlo dose calculation algorithm for Gamma Knife. Methods: To make the simulation more efficient, we implemented the track repeating technique on GPU. We first use EGSnrc to pre-calculate the photon and secondary electron tracks in water from two mono-energy photons of 60Co. The total photon mean free paths for different materials and energies are obtained from NIST. During simulation, each entire photon track was first loaded to shared memory for each block, the incident original photon was then splitted to Nthread sub-photons, each thread transport one sub-photon, the Russian roulette technique was applied formore » scattered and bremsstrahlung photons. The resultant electrons from photon interactions are simulated by repeating the recorded electron tracks. The electron step length is stretched/shrunk proportionally based on the local density and stopping power ratios of the local material. Energy deposition in a voxel is proportional to the fraction of the equivalent step length in that voxel. To evaluate its accuracy, dose deposition in a 300mm*300mm*300mm water phantom is calculated, and compared to EGSnrc results. Results: Both PDD and OAR showed great agreements (within 0.5%) between our dose engine result and the EGSnrc result. It only takes less than 1 min for every simulation, being reduced up to ∼40 times compared to EGSnrc simulations. Conclusion: We have successfully developed a fast Monte Carlo dose engine for Gamma Knife.« less

Linear Energy Transfer Painting With Proton Therapy: A Means of Reducing Radiation Doses With Equivalent Clinical Effectiveness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fager, Marcus, E-mail: Marcus.Fager@UPHS.UPenn.edu; Medical Radiation Physics, Stockholm University, Stockholm; Toma-Dasu, Iuliana

Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LET{sub d}) while keeping the radiobiologically weighted dose (D{sub RBE}) to the target the same. Methods and Materials: The target is painted with LET{sub d} by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LET{sub d} within the target increases with increasing number of fields, D decreases to maintain the D{sub RBE} the same as the conventional treatment planning method by using beams treatingmore » the full target (full target planning [FTP]). Results: The LET{sub d} increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LET{sub d} led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP. Conclusions: LET{sub d} painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment.« less

The financial and service implications of splitting fixed-dose antiretroviral drugs - a case study.

PubMed

Taylor, R; Carlin, E; Sadique, Z; Ahmed, I; Adams, E J

2015-02-01

In 2010/2011, regional commissioners withdrew payment for the fixed-dose combination Combivir, forcing a switch to component drugs. This was deemed clinically acceptable and annual savings of £44 k expected. We estimated the true costs of switching and examined patient outcomes. Information for 46 patients using Combivir was extracted from case notes for each clinical contact in the 12 months pre- and post-switch (clinician seen, tests, antiretrovirals). Post-switch care costs £93/patient more annually versus pre-switch (95% CI £424 to £609), yielding £4278/year more post-switch for all patients. Drug and pathology costs were more expensive post-switch and extra clinical visits required. None of these results were statistically significant. Forty-two per cent of patients switched directly or in the subsequent year to an alternative fixed-dose combination rather than generics. Costs in this group were significantly higher post-switch driven by drug cost. Six patients (13%) reported problems with the switch including confusion around dosing and new side effects. As less-expensive generic antiretroviral drugs become available, it may appear cheaper to switch from fixed-dose combinations to component drugs. However, the additional clinical costs involved may outweigh the initial cost savings of the drugs and switching may cause confusion for some patients, risking loss of adherence. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas

PubMed Central

Queiroz-Williams, Patricia; Doherty, Thomas J.; da Cunha, Anderson F.; Leonardi, Claudia

2016-01-01

This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery. PMID:27127341

Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas.

PubMed

Queiroz-Williams, Patricia; Doherty, Thomas J; da Cunha, Anderson F; Leonardi, Claudia

2016-04-01

This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery.

Reversal of progressive necrotizing vasculitis with intravenous pulse cyclophosphamide and methylprednisolone.

PubMed

Fort, J G; Abruzzo, J L

1988-09-01

We describe a patient with polyarteritis nodosa who, despite therapy with daily doses of oral prednisone and cyclophosphamide, developed acute renal failure. Renal histopathologic examination demonstrated crescentic glomerulonephritis. Treatment with intravenous pulse cyclophosphamide and methylprednisolone resulted in clinical improvement and significant recovery of renal function.

Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets

USDA-ARS?s Scientific Manuscript database

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolis...

Education's Shot in the Arm

ERIC Educational Resources Information Center

Butler, Kevin

2009-01-01

The federal stimulus package provides badly needed aid to school districts, allowing them to avoid massive staff and teacher layoffs and injecting them with a healthy dose of funds for many programs ranging from technology to renovation work. The American Recovery and Reinvestment Act (ARRA), which President Barack Obama signed on Feb.17, provides…

Neuroleptic-Induced Dementia Documented in Four Adults with Mental Retardation.

ERIC Educational Resources Information Center

Gedye, A.

1998-01-01

Describes four case studies of neuroleptic-induced dementia in four adults with mental retardation. The neuroleptic-induced dementia occurred while the individuals were on a low dose of either loxapine, thioridazine, haloperidol, or pimozide. The individuals showed full recovery after the offending medication was withdrawn. (Author/CR)

Splitting the mind within the individual, nation and economy: reflections on the struggle for integration in post-war Germany.

PubMed

Plänkers, Tomas

2015-02-01

With respect to theorisations of psychical splitting, this paper explores the psychical mechanisms that underlie different forms of social splitting. The paper first outlines Freud's and Kleins different theorisations of the psychical mechanisms of splitting, where the good is split from the bad, the inside split from the outside, and the painful disavowed. I then consider the psychical mechanisms of splitting that underlie ideological supports of certain social systems, specifically that of National Socialist Germany, East Germany during the Cold War period, and neoliberal capitalism. Here, I consider ideological splits between good and evil, the relation between external and internal splits, the relation between geographical, social and internal splitting, as well as splitting as disavowal of the other. Copyright © 2015 Institute of Psychoanalysis.

SU-F-T-273: Using a Diode Array to Explore the Weakness of TPS DoseCalculation Algorithm for VMAT and Sliding Window Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Lu, B; Yan, G

Purpose: To identify the weakness of dose calculation algorithm in a treatment planning system for volumetric modulated arc therapy (VMAT) and sliding window (SW) techniques using a two-dimensional diode array. Methods: The VMAT quality assurance(QA) was implemented with a diode array using multiple partial arcs that divided from a VMAT plan; each partial arc has the same segments and the original monitor units. Arc angles were less than ± 30°. Multiple arcs delivered through consecutive and repetitive gantry operating clockwise and counterclockwise. The source-toaxis distance setup with the effective depths of 10 and 20 cm were used for a diodemore » array. To figure out dose errors caused in delivery of VMAT fields, the numerous fields having the same segments with the VMAT field irradiated using different delivery techniques of static and step-and-shoot. The dose distributions of the SW technique were evaluated by creating split fields having fine moving steps of multi-leaf collimator leaves. Calculated doses using the adaptive convolution algorithm were analyzed with measured ones with distance-to-agreement and dose difference of 3 mm and 3%.. Results: While the beam delivery through static and step-and-shoot techniques showed the passing rate of 97 ± 2%, partial arc delivery of the VMAT fields brought out passing rate of 85%. However, when leaf motion was restricted less than 4.6 mm/°, passing rate was improved up to 95 ± 2%. Similar passing rate were obtained for both 10 and 20 cm effective depth setup. The calculated doses using the SW technique showed the dose difference over 7% at the final arrival point of moving leaves. Conclusion: Error components in dynamic delivery of modulated beams were distinguished by using the suggested QA method. This partial arc method can be used for routine VMAT QA. Improved SW calculation algorithm is required to provide accurate estimated doses.« less

Disposition, metabolism and mass balance of delafloxacin in healthy human volunteers following intravenous administration.

PubMed

McEwen, Andrew; Lawrence, Laura; Hoover, Randy; Stevens, Lloyd; Mair, Stuart; Ford, Gill; Williams, Dylan; Wood, Stuart

2015-01-01

1. The pharmacokinetics and disposition of delafloxacin was investigated following a single intravenous (300 mg, 100 µCi) dose to healthy male subjects. 2. Mean Cmax, AUC0-∞, Tmax and t1/2 values for delafloxacin were 8.98 µg/mL, 21.31 µg h/mL, 1 h and 2.35 h, respectively, after intravenous dosing. 3. Radioactivity was predominantly excreted via the kidney with 66% of the radioactive dose recovered in the urine. Approximately 29% of the radioactivity was recovered in the faeces, giving an overall mean recovery of 94% administered radioactivity. 4. The predominant circulating components were identified as delafloxacin and a direct glucuronide conjugate of delafloxacin.

SCHISTOSOMIASIS: AGE OF SNAILS AND SUSCEPTIBILITY TO X-IRRADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szumlewicz, A.P.

1964-04-17

Studies on sensitivity of Australorbis glabratus to x rays have defined the chronological and physiological age at which the snail is most sensitive to radiation damage. Results showed that the dose producing 50-percent mortality at 30 days after irradiation increased with age but that at 90 days it was practically constant from 2 to 210 days of age. In view of the avaiIable data on recovery from radiation damage caused by doses from 6000 to 9000 roentgens it is suggested that doses above those causing 50% lethality at 60 days but below those causing 50% lethality for 30 days shouldmore » be considered in setting up radiation barriers to cortrol snails in water-distribution systems. (auth)« less

Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: A study with entropy analysis

PubMed Central

Patel, Chirag Ramanlal; Engineer, Smita R; Shah, Bharat J; Madhu, S

2012-01-01

Background: Dexmedetomidine, an α2 agonist, when used as an adjuvant in general anaesthesia attenuates stress response to various noxious stimuli, maintains perioperative haemodynamic stability and provides sedation without significant respiratory depression postoperatively. Methods: Sixty patients were randomly divided into two groups of 30 each. In group A, fentanyl 2 μg/kg and in group B dexmedetomidine were given intravenously as loading dose of 1 μg/kg over 10 min prior to induction. After induction with thiopentone, in group B, dexmedetomidine was given as infusion at a dose of 0.2–0.8 μg/kg. Sevoflurane was used as inhalation agent in both groups. Haemodynamic variables and entropy (response entropy and state entropy) were recorded continuously. Postoperative sedation and recovery were assessed by sedation score and modified Aldrete's score, respectively. Results: Dexmedetomidine significantly attenuates stress response at intubation with lesser increase in heart rate (10% vs. 17%), systolic blood pressure (6% vs. 23%) and diastolic blood pressure (7% vs. 20%) as compared to the control group (P<0.05). Intraoperatively, an average of 8% fall in systolic blood pressure and 8.16% fall in diastolic pressure in the test group as compared to 3.6% rise in systolic and 3.3% in diastolic pressure of the control group was observed. Postoperatively, the test group showed significant sedation at 2 h as compared to the control group (P=0.00) and recovery was better in the control group for the first 2 h post extubation. Conclusion: Dexmedetomidine attenuates various stress responses during surgery and maintains the haemodynamic stability when used as an adjuvant in general anaesthesia. Also, the sedative action of dexmedetomidine delays recovery for the first few hours post extubation. PMID:23325938