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Sample records for kaplan-meier method toxicity

  1. The analysis of competing events like cause-specific mortality--beware of the Kaplan-Meier method

    NARCIS (Netherlands)

    Verduijn, Marion; Grootendorst, Diana C.; Dekker, Friedo W.; Jager, Kitty J.; le Cessie, Saskia

    2011-01-01

    Kaplan-Meier analysis is a popular method used for analysing time-to-event data. In case of competing event analyses such as that of cardiovascular and non-cardiovascular mortality, however, the Kaplan-Meier method profoundly overestimates the cumulative mortality probabilities for each of the

  2. The Kaplan-Meier Theatre

    Science.gov (United States)

    Gerds, Thomas A.

    2016-01-01

    Survival is difficult to estimate when observation periods of individuals differ in length. Students imagine sailing the Titanic and then recording whether they "live" or "die." A clever algorithm is performed which results in the Kaplan-Meier estimate of survival.

  3. Modified Weighted Kaplan-Meier Estimator

    Directory of Open Access Journals (Sweden)

    Mohammad Shafiq

    2007-01-01

    Full Text Available In many medical studies majority of the study subjects do not reach to the event of interest during the study period. In such situations survival probabilities can be estimated for censored observation by Kaplan Meier estimator. However in case of heavy censoring these estimates are biased and over estimate the survival probabilities. For heavy censoring a new method was proposed (Bahrawar Jan, 2005 to estimate the survival probabilities by weighting the censored observations by non-censoring rate. But the main defect in this weighted method is that it gives zero weight to the last censored observation. To over come this difficulty a new weight is proposed which also gives a non-zero weight to the last censored observation.

  4. The Kaplan-Meier theatre

    DEFF Research Database (Denmark)

    Gerds, Thomas Alexander

    2016-01-01

    Survival probabilities are not straightforward toobtain when observation periods of individuals differ in length. The Kaplan–Meier theatre is a classroom activity, which starts by a data collection exercise where students imagine sailing on the Titanic. Several students ‘fall in the water’ where....... The Kaplan–Meier method assumes that censored individuals have the same survival chances as the individuals who are still observed. During the Kaplan–Meier theatre, students perform a clever algorithm (Efron 1967), which translates the assumption into action and results in the Kaplan–Meier estimate...

  5. Understanding survival analysis: Kaplan-Meier estimate.

    Science.gov (United States)

    Goel, Manish Kumar; Khanna, Pardeep; Kishore, Jugal

    2010-10-01

    Kaplan-Meier estimate is one of the best options to be used to measure the fraction of subjects living for a certain amount of time after treatment. In clinical trials or community trials, the effect of an intervention is assessed by measuring the number of subjects survived or saved after that intervention over a period of time. The time starting from a defined point to the occurrence of a given event, for example death is called as survival time and the analysis of group data as survival analysis. This can be affected by subjects under study that are uncooperative and refused to be remained in the study or when some of the subjects may not experience the event or death before the end of the study, although they would have experienced or died if observation continued, or we lose touch with them midway in the study. We label these situations as censored observations. The Kaplan-Meier estimate is the simplest way of computing the survival over time in spite of all these difficulties associated with subjects or situations. The survival curve can be created assuming various situations. It involves computing of probabilities of occurrence of event at a certain point of time and multiplying these successive probabilities by any earlier computed probabilities to get the final estimate. This can be calculated for two groups of subjects and also their statistical difference in the survivals. This can be used in Ayurveda research when they are comparing two drugs and looking for survival of subjects.

  6. A review and comparison of methods for recreating individual patient data from published Kaplan-Meier survival curves for economic evaluations: a simulation study.

    Science.gov (United States)

    Wan, Xiaomin; Peng, Liubao; Li, Yuanjian

    2015-01-01

    In general, the individual patient-level data (IPD) collected in clinical trials are not available to independent researchers to conduct economic evaluations; researchers only have access to published survival curves and summary statistics. Thus, methods that use published survival curves and summary statistics to reproduce statistics for economic evaluations are essential. Four methods have been identified: two traditional methods 1) least squares method, 2) graphical method; and two recently proposed methods by 3) Hoyle and Henley, 4) Guyot et al. The four methods were first individually reviewed and subsequently assessed regarding their abilities to estimate mean survival through a simulation study. A number of different scenarios were developed that comprised combinations of various sample sizes, censoring rates and parametric survival distributions. One thousand simulated survival datasets were generated for each scenario, and all methods were applied to actual IPD. The uncertainty in the estimate of mean survival time was also captured. All methods provided accurate estimates of the mean survival time when the sample size was 500 and a Weibull distribution was used. When the sample size was 100 and the Weibull distribution was used, the Guyot et al. method was almost as accurate as the Hoyle and Henley method; however, more biases were identified in the traditional methods. When a lognormal distribution was used, the Guyot et al. method generated noticeably less bias and a more accurate uncertainty compared with the Hoyle and Henley method. The traditional methods should not be preferred because of their remarkable overestimation. When the Weibull distribution was used for a fitted model, the Guyot et al. method was almost as accurate as the Hoyle and Henley method. However, if the lognormal distribution was used, the Guyot et al. method was less biased compared with the Hoyle and Henley method.

  7. About an adaptively weighted Kaplan-Meier estimate.

    Science.gov (United States)

    Plante, Jean-François

    2009-09-01

    The minimum averaged mean squared error nonparametric adaptive weights use data from m possibly different populations to infer about one population of interest. The definition of these weights is based on the properties of the empirical distribution function. We use the Kaplan-Meier estimate to let the weights accommodate right-censored data and use them to define the weighted Kaplan-Meier estimate. The proposed estimate is smoother than the usual Kaplan-Meier estimate and converges uniformly in probability to the target distribution. Simulations show that the performances of the weighted Kaplan-Meier estimate on finite samples exceed that of the usual Kaplan-Meier estimate. A case study is also presented.

  8. The Kaplan-Meier Integral in the Presence of Covariates

    DEFF Research Database (Denmark)

    Gerds, Thomas A.; Beyersmann, Jan; Starkopf, Liis

    2017-01-01

    In a series of papers, Winfried Stute introduced and studied the Kaplan-Meier integral as an estimator of parameters of the joint distribution of survival times and covariates based on right censored survival times. We present a review of this work and show that his estimator has an inverse...... probability of censoring weighting (IPCW) representation. We further investigate large sample bias and efficiency. As a central application in a biostatistical context, Kaplan-Meier integrals are used to estimate transition probabilities in a non-Markov illness-death model. We extend already existing...

  9. Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis.

    Science.gov (United States)

    Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter D; Ghali, William A; Marshall, Deborah A

    2015-11-01

    Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown. We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks? We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and

  10. Competing risk bias was common in Kaplan-Meier risk estimates published in prominent medical journals.

    Science.gov (United States)

    van Walraven, Carl; McAlister, Finlay A

    2016-01-01

    Risk estimates from Kaplan-Meier curves are well known to medical researchers, reviewers, and editors. In this study, we determined the proportion of Kaplan-Meier analyses published in prominent medical journals that are potentially biased because of competing events ("competing risk bias"). We randomly selected 100 studies that had at least one Kaplan-Meier analysis and were recently published in prominent medical journals. Susceptibility to competing risk bias was determined by examining the outcome and potential competing events. In susceptible studies, bias was quantified using a previously validated prediction model when the number of outcomes and competing events were given. Forty-six studies (46%) contained Kaplan-Meier analyses susceptible to competing risk bias. Sixteen studies (34.8%) susceptible to competing risk cited the number of outcomes and competing events; in six of these studies (6/16, 37.5%), the outcome risk from the Kaplan-Meier estimate (relative to the true risk) was biased upward by 10% or more. Almost half of Kaplan-Meier analyses published in medical journals are susceptible to competing risk bias and may overestimate event risk. This bias was found to be quantitatively important in a third of such studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Biostatistics with emphasis on life table survival rate calculations (including Kaplan Meier) and the logrank test

    International Nuclear Information System (INIS)

    Mould, Richard F.

    1995-01-01

    Purpose/Objective: To explain some of the most useful statistical calculation procedures which are relevant to radiation oncologists and to provide insights on what tests and procedures should be used in various situations such as when survival rates and their associated standard errors have to be determined. To describe some of the problems and pitfalls in clinical trial designs which have to be overcome if a trial is to have the possibility of reaching a successful conclusion. To review methods of computing criteria to quantitatively describe criteria of success (eg. quality of life, long-term survival, cure) of radiation oncology and to suggest possible future statistical improvements in this area. Chi-Squared Test: The chi-squared test is probably the most useful of the tests of statistical significance for the radiation oncologist. Applications will be described, including goodness of fit tests and 2x2 contingency tables which are the simplest of the generalized nxm contingency tables. Degrees of Freedom and P<0.05 for Significance Testing: An Introduction will be given to the meaning of P<0.05 in relation to significance testing and the use of tables of critical values of a test statistic (eg. chi-squared) which are given as a function of degrees of freedom and P-values. Survival Rate Calculations for Grouped and Ungrouped Data: The life-table method (sometimes termed the actuarial method) will be explained for both grouped data (eg. survival times grouped in annual intervals for patients who have died and for those who are still alive or lost to follow-up) and for ungrouped data (when individual survival times are used). The method for ungrouped data is variously termed the Kaplan-Meier or Product Limit method. Logrank Test: This is the most useful test for comparison of the survival experience of two groups of patients and its use will be explained. In part the computation is similar to that for the Kaplan-Meier/Product Limit method

  12. Biostatistics with emphasis on life table survival rate calculations (including Kaplan Meier) and the logrank test

    Energy Technology Data Exchange (ETDEWEB)

    Mould, Richard F

    1995-07-01

    Purpose/Objective: To explain some of the most useful statistical calculation procedures which are relevant to radiation oncologists and to provide insights on what tests and procedures should be used in various situations such as when survival rates and their associated standard errors have to be determined. To describe some of the problems and pitfalls in clinical trial designs which have to be overcome if a trial is to have the possibility of reaching a successful conclusion. To review methods of computing criteria to quantitatively describe criteria of success (eg. quality of life, long-term survival, cure) of radiation oncology and to suggest possible future statistical improvements in this area. Chi-Squared Test: The chi-squared test is probably the most useful of the tests of statistical significance for the radiation oncologist. Applications will be described, including goodness of fit tests and 2x2 contingency tables which are the simplest of the generalized nxm contingency tables. Degrees of Freedom and P<0.05 for Significance Testing: An Introduction will be given to the meaning of P<0.05 in relation to significance testing and the use of tables of critical values of a test statistic (eg. chi-squared) which are given as a function of degrees of freedom and P-values. Survival Rate Calculations for Grouped and Ungrouped Data: The life-table method (sometimes termed the actuarial method) will be explained for both grouped data (eg. survival times grouped in annual intervals for patients who have died and for those who are still alive or lost to follow-up) and for ungrouped data (when individual survival times are used). The method for ungrouped data is variously termed the Kaplan-Meier or Product Limit method. Logrank Test: This is the most useful test for comparison of the survival experience of two groups of patients and its use will be explained. In part the computation is similar to that for the Kaplan-Meier/Product Limit method.

  13. Kaplan-Meier survival analysis overestimates cumulative incidence of health-related events in competing risk settings: a meta-analysis.

    Science.gov (United States)

    Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter; Ghali, William A; Marshall, Deborah A

    2018-01-01

    Kaplan-Meier survival analysis overestimates cumulative incidence in competing risks (CRs) settings. The extent of overestimation (or its clinical significance) has been questioned, and CRs methods are infrequently used. This meta-analysis compares the Kaplan-Meier method to the cumulative incidence function (CIF), a CRs method. We searched MEDLINE, EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies for studies estimating cumulative incidence using the Kaplan-Meier method and CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs) comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random effects models. We performed stratified meta-analyses by clinical area, rate of CRs (CRs/events of interest), and follow-up time. Of 2,192 identified abstracts, we included 77 studies in the systematic review and meta-analyzed 55. The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. The Kaplan-Meier method overestimated the cumulative incidence across 10 clinical areas. Using CRs methods will ensure accurate results inform clinical and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves

    Directory of Open Access Journals (Sweden)

    Guyot Patricia

    2012-02-01

    Full Text Available Abstract Background The results of Randomized Controlled Trials (RCTs on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios with statistics based on repeated reconstructions by multiple observers. Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. Conclusion The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

  15. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.

    Science.gov (United States)

    Guyot, Patricia; Ades, A E; Ouwens, Mario J N M; Welton, Nicky J

    2012-02-01

    The results of Randomized Controlled Trials (RCTs) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios) with statistics based on repeated reconstructions by multiple observers. The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

  16. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    International Nuclear Information System (INIS)

    Grybaeck, P.; Naeslund, E.; Hellstroem, P.M.; Jacobsson, H.; Backman, L.

    1996-01-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs

  17. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    Energy Technology Data Exchange (ETDEWEB)

    Grybaeck, P. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden); Naeslund, E. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden); Hellstroem, P.M. [Department of Internal Medicine, Karolinska Hospital, Stockholm (Sweden); Jacobsson, H. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden)]|[Department of Nuclear Medicine, Karolinska Hospital, Stockholm (Sweden); Backman, L. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden)

    1996-12-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs.

  18. Application of Kaplan-Meier analysis in reliability evaluation of products cast from aluminium alloys

    OpenAIRE

    J. Szymszal; A. Gierek; J. Kliś

    2010-01-01

    The article evaluates the reliability of AlSi17CuNiMg alloys using Kaplan-Meier-based technique, very popular as a survival estimation tool in medical science. The main object of survival analysis is a group (or groups) of units for which the time of occurrence of an event (failure) taking place after some time of waiting is estimated. For example, in medicine, the failure can be patient’s death. In this study, the failure was the specimen fracture during a periodical fatigue test, while the ...

  19. KMWin--a convenient tool for graphical presentation of results from Kaplan-Meier survival time analysis.

    Science.gov (United States)

    Gross, Arnd; Ziepert, Marita; Scholz, Markus

    2012-01-01

    Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.

  20. KMWin – A Convenient Tool for Graphical Presentation of Results from Kaplan-Meier Survival Time Analysis

    Science.gov (United States)

    Gross, Arnd; Ziepert, Marita; Scholz, Markus

    2012-01-01

    Background Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. Results On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. Conclusions We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups. PMID:22723912

  1. KMWin--a convenient tool for graphical presentation of results from Kaplan-Meier survival time analysis.

    Directory of Open Access Journals (Sweden)

    Arnd Gross

    Full Text Available BACKGROUND: Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav, SAS export (xpt or text file (dat, which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. RESULTS: On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. CONCLUSIONS: We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.

  2. A versatile test for equality of two survival functions based on weighted differences of Kaplan-Meier curves.

    Science.gov (United States)

    Uno, Hajime; Tian, Lu; Claggett, Brian; Wei, L J

    2015-12-10

    With censored event time observations, the logrank test is the most popular tool for testing the equality of two underlying survival distributions. Although this test is asymptotically distribution free, it may not be powerful when the proportional hazards assumption is violated. Various other novel testing procedures have been proposed, which generally are derived by assuming a class of specific alternative hypotheses with respect to the hazard functions. The test considered by Pepe and Fleming (1989) is based on a linear combination of weighted differences of the two Kaplan-Meier curves over time and is a natural tool to assess the difference of two survival functions directly. In this article, we take a similar approach but choose weights that are proportional to the observed standardized difference of the estimated survival curves at each time point. The new proposal automatically makes weighting adjustments empirically. The new test statistic is aimed at a one-sided general alternative hypothesis and is distributed with a short right tail under the null hypothesis but with a heavy tail under the alternative. The results from extensive numerical studies demonstrate that the new procedure performs well under various general alternatives with a caution of a minor inflation of the type I error rate when the sample size is small or the number of observed events is small. The survival data from a recent cancer comparative study are utilized for illustrating the implementation of the process. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Applying Kaplan-Meier to Item Response Data

    Science.gov (United States)

    McNeish, Daniel

    2018-01-01

    Some IRT models can be equivalently modeled in alternative frameworks such as logistic regression. Logistic regression can also model time-to-event data, which concerns the probability of an event occurring over time. Using the relation between time-to-event models and logistic regression and the relation between logistic regression and IRT, this…

  4. Effect and toxicity of endoluminal high-dose-rate (HDR) brachytherapy in centrally located tumors of the upper respiratory tract

    International Nuclear Information System (INIS)

    Harms, W.; Wannenmacher, M.; Becker, H.; Herth, F.; Fritz, P.

    2000-01-01

    Aim: To assess effect an toxicity of high-dose-rate afterloading (HDR) alone or in combination with external beam radiotherapy (EBRT) in centrally located tumors of the upper respiratory tract. Patients and Methods: From 1987 to 1996, 55 patients were treated. Twenty-one patients (group A1: 17 non-small-cell lung cancer [NSCLC], A2: 4 metastases from other malignancies) were treated using HDR alone due to a relapse after external beam irradiation. In 34 previously untreated and inoperable patients (group B1: 27 NSCLC, B2: 7 metastases from other malignancies) HDR was given as a boost after EBRT (30 to 60 Gy, median 50). HDR was carried out with a 192 Ir source (370 GBq). The brachytherapy dose (group A: 5 to 27 Gy, median 20; B: 10 to 20 Gy, median 15) was prescribed to 1 cm distance from the source axis. A distanciable applicator was used in 39/55 patients. Results: In group A1, a response rate (CR, PR) of 53% (group B1: 77%) was reached. The median survival (Kaplan-Meier) was 5 months in group A1 (B1: 20 months). The 1-, 3- and 5-year local progression free survival rates (Kaplan-Meier) were 66% (15%), 52% (0%), and 37% (0%) in group B1 (group A1). Prognostic favorable factors in group B1 were a tumor diameter 70. Grade-1 or 2 toxicity (RTOG/EORTC) occurred in 0% in group A and in 6% in group B. We observed no Grad-3 or 4 toxicity. Complications caused by persistent or progressive local disease occurred in 3 patients in goup A (fatal hemorrhage, tracheomediastinal fistula, hemoptysis) and in 2 patients in group B (fatal hemorrhage, hemoptysis). Conclusions: HDR brachytherapy is an effective treatment with moderate side effects. In combination with external beam irradiation long-term remissions can be reached in one third of the patients. (orig.) [de

  5. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    International Nuclear Information System (INIS)

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-01-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  6. Etanercept therapy for toxic epidermal necrolysis.

    Science.gov (United States)

    Paradisi, Andrea; Abeni, Damiano; Bergamo, Fabio; Ricci, Francesco; Didona, Dario; Didona, Biagio

    2014-08-01

    Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. To describe a case series of patients with TEN treated with a single dose of etanercept. We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan-Meier method. All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. This is a small, uncontrolled case series. These preliminary results suggest the possibility that tumor necrosis factor-alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  7. Bias and precision of methods for estimating the difference in restricted mean survival time from an individual patient data meta-analysis

    Directory of Open Access Journals (Sweden)

    Béranger Lueza

    2016-03-01

    Full Text Available Abstract Background The difference in restricted mean survival time ( rmstD t ∗ $$ rmstD\\left({t}^{\\ast}\\right $$ , the area between two survival curves up to time horizon t ∗ $$ {t}^{\\ast } $$ , is often used in cost-effectiveness analyses to estimate the treatment effect in randomized controlled trials. A challenge in individual patient data (IPD meta-analyses is to account for the trial effect. We aimed at comparing different methods to estimate the rmstD t ∗ $$ rmstD\\left({t}^{\\ast}\\right $$ from an IPD meta-analysis. Methods We compared four methods: the area between Kaplan-Meier curves (experimental vs. control arm ignoring the trial effect (Naïve Kaplan-Meier; the area between Peto curves computed at quintiles of event times (Peto-quintile; the weighted average of the areas between either trial-specific Kaplan-Meier curves (Pooled Kaplan-Meier or trial-specific exponential curves (Pooled Exponential. In a simulation study, we varied the between-trial heterogeneity for the baseline hazard and for the treatment effect (possibly correlated, the overall treatment effect, the time horizon t ∗ $$ {t}^{\\ast } $$ , the number of trials and of patients, the use of fixed or DerSimonian-Laird random effects model, and the proportionality of hazards. We compared the methods in terms of bias, empirical and average standard errors. We used IPD from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC and its updated version MAC-NPC2 for illustration that included respectively 1,975 and 5,028 patients in 11 and 23 comparisons. Results The Naïve Kaplan-Meier method was unbiased, whereas the Pooled Exponential and, to a much lesser extent, the Pooled Kaplan-Meier methods showed a bias with non-proportional hazards. The Peto-quintile method underestimated the rmstD t ∗ $$ rmstD\\left({t}^{\\ast}\\right $$ , except with non-proportional hazards at t ∗ $$ {t}^{\\ast } $$ = 5 years. In the presence of treatment effect

  8. Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson; Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A.; Dong, Lei; Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E.; Lee, Andrew K.

    2013-01-01

    Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a

  9. Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Burri, Ryan J.; Stone, Nelson N.; Unger, Pam; Stock, Richard G.

    2010-01-01

    Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with 103 Pd or 125 I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade ≥2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

  10. Late toxicity and five year outcomes after high-dose-rate brachytherapy as a monotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Ghadjar, Pirus; Oesch, Sebastian L; Rentsch, Cyrill A; Isaak, Bernhard; Cihoric, Nikola; Manser, Peter; Thalmann, George N; Aebersold, Daniel M

    2014-01-01

    To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy. Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses. The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V 120 (urethral volume receiving ≥120% of the PD; p = 0.0005) after multivariate Cox regression. After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V 120 . GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent

  11. LCIA selection methods for assessing toxic releases

    DEFF Research Database (Denmark)

    Larsen, Henrik Fred; Birkved, Morten; Hauschild, Michael Zwicky

    2002-01-01

    the inventory that contribute significantly to the impact categories on ecotoxicity and human toxicity to focus the characterisation work. The reason why the selection methods are more important for the chemical-related impact categories than for other impact categories is the extremely high number......Characterization of toxic emissions in life cycle impact assessment (LCIA) is in many cases severely limited by the lack of characterization factors for the emissions mapped in the inventory. The number of substances assigned characterization factors for (eco)toxicity included in the dominating LCA....... The methods are evaluated against a set of pre-defined criteria (comprising consistency with characterization and data requirement) and applied to case studies and a test set of chemicals. The reported work is part of the EU-project OMNIITOX....

  12. Intensity-modulated radiotherapy vs. parotid-sparing 3D conformal radiotherapy. Effect on outcome and toxicity in locally advanced head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lambrecht, M.; Nevens, D.; Nuyts, S. [University Hospitals Leuven (Belgium). Dept. of Radiation Oncology

    2013-03-15

    Background and purpose: Intensity-modulated radiotherapy (IMRT) has rapidly become standard of care in the management of locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, our aim was to retrospectively investigate the effect of the introducing IMRT on outcome and treatment-related toxicity compared to parotid-sparing 3D conformal radiotherapy (3DCRT). Material and methods: A total of 245 patients with stage III and IV HNSCC treated with primary radiotherapy between January 2003 and December 2010 were included in this analysis: 135 patients were treated with 3DCRT, 110 patients with IMRT. Groups were compared for acute and late toxicity, locoregional control (LRC), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analysis and compared using a log-rank test. Acute toxicity was analyzed according to the Common Terminology Criteria for Adverse Events v3.0 and late toxicity was scored using the RTOG/EORTC late toxicity scoring system. Results: Median follow-up was 35 months in the IMRT group and 68 months in the 3DCRT group. No significant differences were found in 3-year LRC and OS rates between the IMRT group and 3DCRT group. Significantly less acute mucositis {>=} grade 3 was observed in the IMRT group (32% vs. 44%, p = 0.03). There was significantly less late xerostomia {>=} grade 2 in the IMRT group than in the 3DCRT group (23% vs. 68%, p < 0.001). After 24 months, there was less dysphagia {>=} grade 2 in the IMRT group although differences failed to reach statistical significance. Conclusion: The introduction of IMRT in the radiotherapeutic management of locally advanced head and neck cancer significantly improved late toxicity without compromising tumor control compared to a parotid-sparing 3D conformal radiotherapy technique. (orig.)

  13. Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response

    International Nuclear Information System (INIS)

    Skwarchuk, Mark W.; Jackson, Andrew; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Cowen, Didier M.; Levegruen, Sabine; Burman, Chandra M.; Fuks, Zvi; Leibel, Steven A.; Ling, C. Clifton

    2000-01-01

    Purpose: The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis. Methods and Materials: Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.0 Gy. The 5-year actuarial rate of late rectal toxicity was assessed using Kaplan-Meier statistics. A retrospective dosimetric analysis was performed for patients treated to 70.2 Gy (52 patients) or 75.6 Gy (119 patients) who either exhibited late rectal bleeding (RTOG Grade 2/3) within 30 months after treatment (i.e., 70.2 Gy--13 patients, 75.6 Gy--36 patients) or were nonbleeding for at least 30 months (i.e., 70.2 Gy--39 patients, 75.6 Gy--83 patients). Univariate and multivariate logistic regression was performed to correlate late rectal bleeding with several anatomic, dosimetric, and clinical variables. Results: A dose response for ≥ Grade 2 late rectal toxicity was observed. By multivariate analysis, the following factors were significantly correlated with ≥ Grade 2 late rectal bleeding for patients prescribed 70.2 Gy: 1) enclosure of the outer rectal contour by the 50% isodose on the isocenter slice (i.e., Iso50) (p max (p max

  14. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H., E-mail: ccrane@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

  15. Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Krema, Hatem, E-mail: htmkrm19@yahoo.com [Department of Ocular Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Heydarian, Mostafa [Department of Radiation Medicine, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Beiki-Ardakani, Akbar [Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Weisbrod, Daniel [Department of Ocular Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Xu, Wei [Department of Biostatistics, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Laperriere, Normand J.; Sahgal, Arjun [Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada)

    2013-07-01

    Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

  16. Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

    Science.gov (United States)

    Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

    2016-01-01

    The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Evaluation of the efficacy and toxicity of protocol cisplatin, 5-fluorouracil, leucovorin compared to protocol fluorouracil, doxorubicin and mitomycin C in locally advanced and metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Andrić Zoran

    2012-01-01

    Full Text Available Introduction. Still there is no consensus on the choice of the most efficient and the least toxic chemotherapy regimen in the treatment of advanced gastric cancer. Nowadays few therapy protocols are available for treating this disease. Objective. Study was conducted to compare the efficacy and toxicity of FAM (flurouracil, doxorubicin, mitomycin C with CDDP and FU/FA (cisplatin, 5-fluorouracil, leucovorin protocols in patients with locally advanced and metastatic gastric cancer. Methods. This randomized study involved a group of 50 patients with locally advanced or metastatic gastric cancer, who had not previously undergone chemotherapy treatment. Progression free survival, overall survival and drug toxicity were evaluated. For statistical analysis chi-square test, Kaplan-Meier curve and the log rank test were used. Results. The overall response rate was 20% in the group treated with FAM and 24% in the group treated with CDDP, FU/FA (4% of patients from each group had complete response, but without significant statistical difference. Median survival was 10.9 months in the FAM group and 11.8 months in CDDP, FU/FA group, with no statistically significant difference. Non-haematological and haematological toxicities of CDDP, FU/FA were considerably less frequent than of FAM, and there was no treatment related deaths in any of the groups. Conclusion. Both investigated regimens demonstrated moderate efficacy. The study shows in favour of justified application of both protocols, while in regard to toxicity CDDP and FU/FA can be recommended as preferable treatment for locally advanced and metastatic gastric cancer. New strategies should be considered for better efficacy in the treatment of advanced gastric cancer. New strategies are necessary with the goal to achieve a better therapeutic effect.

  18. Hypofractionated conformal radiotherapy (HCRT) for primary and metastatic lung cancers with small dimension. Efficacy and toxicity

    International Nuclear Information System (INIS)

    Mirri, Maria Alessandra; Arcangeli, Giorgio; Pinzi, Valentina; Benassi, Marcello; D'Angelo, Annelisa; Strigari, Lidia; Caterino, Mauro; Rinaldi, Massimo; Ceribelli, Anna

    2009-01-01

    Purpose: to report on the clinical outcome of hypofractionated conformal radiotherapy (HCRT) for medically inoperable stage I non-small cell lung carcinoma (NSCLC) or limited pulmonary metastases ≤ 5 cm in diameter. Patients and methods: from June 2003 to March 2007, 40 patients (42 lesions) underwent HCRT consisting of 40 Gy in five fractions over 2.5 weeks received by at least 95% of planning target volume. All patients underwent CT simulation and treatment under free shallow breathing. To evaluate target displacement under respiratory activity, two additional CT scans were performed with breath-holding during the expiratory and inspiratory phases. Of all patients enrolled, those with a follow-up ≥ 4 months were considered suitable for analysis. Local response was evaluated with CT imaging 4 months after the end of HCRT and every 3 months thereafter. Local relapse-free survival (LRFS) and overall survival (OS) were calculated with the Kaplan-Meier method. Results: local response to the treatment was complete response, partial response, no change, and progressive disease as seen in 29%, 43%, 14%, and 7% of tumors, respectively. LRFS at 1 year and 3 years was 76% and 63%, respectively. Lung toxicities ≥ grade 2 were observed in 4/40 patients, but no grade 4. Pericardial effusion occurred in one patient. In stage I NSCLC patients (n = 15) with a median follow-up of 25 months, the 1-year LRFS and OS rates were 88% and 81%, respectively, and the 3-year rates 72% and 61%, respectively. Conclusion: HCRT is an effective and low-toxic treatment for medically inoperable early-stage lung cancers and pulmonary metastases for all clinicians lacking the aid of a dedicated stereotactic system. (orig.)

  19. Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Larissa J. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

    2012-12-01

    Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure

  20. Toxicity identification evaluation methods for identification of toxicants in refinery effluents

    International Nuclear Information System (INIS)

    Barten, K.A.; Mount, D.R.; Hackett, J.R.

    1993-01-01

    During the last five years, the authors have used Toxicity Identification Evaluation (TIE) methods to characterize and identify the source(s) of toxicity in effluents from dozens of municipal and industrial facilities. In most cases, specific chemicals responsible for toxicity have been identified. Although generally successful, the initial experience was that for several refinery effluents, they were able only to qualitatively characterize the presence of organic toxicants; standard toxicant identification procedures were not able to isolate specific organic chemicals. They believe that organic toxicity in these refinery effluents is caused by multiple organic compounds rather than by just a few; evidence for this includes an inability to isolate toxicity in a small number of fractions using liquid chromatography and the presence of very large numbers of compounds in isolated fractions. There is also evidence that the toxicant(s) may be ionic, in that the toxicity of whole effluent and isolated fractions often show increasing toxicity with decreasing pH. Finally, positive-pressure filtration has also reduced toxicity in some samples. In this presentation the authors summarize their experiences with refinery effluents, focusing on typical patterns they have observed and alternative procedures they have used to better understand the nature of these toxicants

  1. Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

    International Nuclear Information System (INIS)

    Kachnic, Lisa A.; Tsai, Henry K.; Coen, John J.; Blaszkowsky, Lawrence S.; Hartshorn, Kevan; Kwak, Eunice L.; Willins, John D.; Ryan, David P.; Hong, Theodore S.

    2012-01-01

    Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs ≤3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6–43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2–24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.

  2. Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org [Department of Radiation Oncology, Boston Medical Center, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Tsai, Henry K. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA (United States); Coen, John J. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Blaszkowsky, Lawrence S. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Hartshorn, Kevan [Department of Medicine, Boston Medical Center, Boston, MA (United States); Kwak, Eunice L. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Willins, John D. [Department of Radiation Oncology, Boston Medical Center, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Ryan, David P. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Hong, Theodore S. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2012-01-01

    Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs {<=}3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.

  3. Oropharyngeal squamous cell carcinoma with known human papillomavirus status treated with definitive chemoradiotherapy: patterns of failure and toxicity outcomes

    International Nuclear Information System (INIS)

    Bledsoe, Trevor J; Koyfman, Shlomo A; Noble, Anisha R; Hunter, Grant K; Rybicki, Lisa A; Hoschar, Aaron; Chute, Deborah J; Saxton, Jerrold P; Greskovich, John F; Adelstein, David J

    2013-01-01

    Tumor human papillomavirus (HPV) status has emerged as one of the most powerful prognostic factors for disease control and survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). We reviewed our experience in patients with OPSCC and known tumor HPV status treated with definitive chemoradiotherapy (CRT). Patients with stage III-IVb OPSCC and known tumor HPV status treated with CRT between 2006 and 2011 were identified from an IRB approved registry for this retrospective review. Outcomes were estimated using the Kaplan-Meier method and compared between HPV-positive and negative patients using the log-rank test. Of the 121 pts (89% male, 93% Caucasian) included in this study, median age was 57 (range: 40–73) and median follow-up was 21 months (range: 6–63). Ninety-seven (80%) patients were HPV-positive and 24 (20%) were HPV-negative. Primary site was base of tongue (55%), tonsil (44%), and oropharyngeal wall (2%). Two year rates of locoregional recurrence (3% vs. 26%; p = 0.002), disease free survival (93% vs. 64%; p = 0.001) and overall survival (94% vs 73%; p = 0.002) were superior in HPV-positive patients, while rates of distant recurrence were similar (3% vs. 5%; p = 0.98). While acute toxicities were similar between both groups, patients with HPV-positive disease were more likely to resume a normal diet (90% vs. 65%; p = 0.017) at last follow up. Also, no HPV-positive patient required a feeding tube beyond 6 months after treatment, compared with 24% of HPV-negative patients. Definitive CRT produces excellent rates of disease control with minimal late toxicity for patients with HPV-positive OPSCC. Studies of OPSCC should account for tumor HPV status when identifying factors prognostic for outcome

  4. Association of TGF-β1 and XPD polymorphisms with severe acute radiation-induced esophageal toxicity in locally advanced lung cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Zhang Li; Yang Ming; Bi Nan; Ji Wei; Wu Chen; Tan Wen; Zhao Lujun; Yu Dianke; Lin Dongxin; Wang Luhua

    2010-01-01

    Purpose: Radiation-induced esophageal toxicity (RIET) is a dose-limiting toxicity in lung cancer patients receiving radiotherapy. Accumulating evidence indicates that DNA repair and the cytokine pathways play essential roles in radiation-induced diseases. Genetic polymorphisms of genes in these pathways may affect gene function and/or gene expression and lead to different treatment-related esophageal toxicity. Materials and methods: This study investigated the association of 21 polymorphisms in 14 genes, with the occurrence of ≥grade 2 acute RIET. Genotypes were analyzed among 213 stage III lung cancer patients receiving radiotherapy. Results: We used Cox proportional hazard model to examine the effects of genotypes on ≥grade 2 acute RIET risk and Kaplan-Meier estimator to compare effects of different genotypes on such risk. Multivariate analysis showed that CT or TT genotype of TGF-β1-509C/T polymorphism was associated with a significantly higher RIET risk (adjusted hazard ratio [HR] = 2.47; 95% confidence interval (CI) = 1.17-5.24; P = 0.018, or HR = 3.86; 95% CI = 1.50-9.92; P = 0.005), respectively, compared with the CC genotype. Moreover, Lys/Gln+Gln/Gln genotypes of XPD Lys751Gln polymorphism were also associated with a significantly decreased RIET risk (adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.030). Conclusions: This report, for the first time, examined the influence of inherited variation in the DNA repair and the cytokine pathways on RIET.

  5. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

    Directory of Open Access Journals (Sweden)

    Thaler Josef

    2012-09-01

    Full Text Available Abstract Background Integument-related toxicities are common during epidermal growth factor receptor (EGFR-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Methods Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. Results 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59; most (98% experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]. Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56% compared with those with grade 0/1 (29%. Mean overall EQ-5D health state index scores (0.81 vs. 0.78, health rating scores (72.5 vs. 71.0 and QLQ-C30 global health status scores (65.8 vs. 66.7 were comparable at baseline vs. safety follow-up (8 weeks after completion, respectively and appeared unaffected by skin toxicity severity. Conclusions First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument

  6. Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Pollack, Alan; Levy, Larry; Starkschall, George; Lei Dong; Rosen, Isaac; Kuban, Deborah A.

    2002-01-01

    Purpose: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74-78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24-102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity. Results: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p 3 of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p=0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p<0.05 for all comparisons). Conclusion: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications

  7. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-01-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; ≥6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. ≥6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  8. Marine Biotoxins: Occurrence, Toxicity, and Detection Methods

    Science.gov (United States)

    Asakawa, M.

    2017-04-01

    This review summarizes the role of marine organisms as vectors of marine biotoxins, and discusses the need for surveillance to protect public health and ensure the quality of seafood. I Paralytic shellfish poison (PSP) and PSP-bearing organisms-PSP is produced by toxic dinoflagellates species belonging to the genera Alexandrium, Gymnodinium, and Pyrodinium. Traditionally, PSP monitoring programs have only considered filter-feeding molluscs that concentrate these toxic algae, however, increasing attention is now being paid to higher-order predators that carry PSP, such as carnivorous gastropods and crustaceans. II. Tetrodotoxin (TTX) and TTX-bearing organisms - TTX is the most common natural marine toxin that causes food poisonings in Japan, and poses a serious public health risk. TTX was long believed to be present only in pufferfish. However, TTX was detected in the eggs of California newt Taricha torosa in 1964, and since then it has been detected in a wide variety of species belonging to several different phyla. In this study, the main toxic components in the highly toxic ribbon worm Cephalothrix simula and the greater blue-ringed octopus Hapalochlaena lunulata from Japan were purified and analysed.

  9. Analytical methods for toxic gases from thermal degradation of polymers

    Science.gov (United States)

    Hsu, M.-T. S.

    1977-01-01

    Toxic gases evolved from the thermal oxidative degradation of synthetic or natural polymers in small laboratory chambers or in large scale fire tests are measured by several different analytical methods. Gas detector tubes are used for fast on-site detection of suspect toxic gases. The infrared spectroscopic method is an excellent qualitative and quantitative analysis for some toxic gases. Permanent gases such as carbon monoxide, carbon dioxide, methane and ethylene, can be quantitatively determined by gas chromatography. Highly toxic and corrosive gases such as nitrogen oxides, hydrogen cyanide, hydrogen fluoride, hydrogen chloride and sulfur dioxide should be passed into a scrubbing solution for subsequent analysis by either specific ion electrodes or spectrophotometric methods. Low-concentration toxic organic vapors can be concentrated in a cold trap and then analyzed by gas chromatography and mass spectrometry. The limitations of different methods are discussed.

  10. Adenocarcinoma of the esophagogastric junction. Neoadjuvant radiochemotherapy and radical surgery. Early results and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Leibl, Bernhard J. [Klinikum Coburg (Germany). Dept. of Surgery; Coburg Cancer Center, Coburg (Germany); Vitz, Stephanie; Schaefer, Wolfgang; Alfrink, Martin; Grabenbauer, Gerhard G. [DiCura Coburg, Coburg (Germany). Dept. of Radiation Oncology; Coburg Cancer Center, Coburg (Germany); Geschwendtner, Andreas [Klinikum Coburg (Germany). Dept. of Pathology; Coburg Cancer Center, Coburg (Germany)

    2011-04-15

    Purpose: To retrospectively evaluate treatment results and toxicity following a combined approach consisting of neoadjuvant radiochemotherapy and radical surgery in advanced adenocarcinoma of the esophagus and gastroesophageal junction. Patients and Methods: Between 2005 and 2009, a total of 41 consecutive patients with newly diagnosed nonmetastatic adenocarcinoma of the esophagus and the esophagogastric junction were evaluated, of whom 23 received neoadjuvant radiochemo-therapy (RCT). A total dose of 50.4 Gy with 2 cycles of simultaneous cisplatin/5-fluorouracil (FU) or Taxol/FU-chemotherapy were applied. A radical transthoracic subtotal esophageal and proximal gastric resection through a right thoracoabdominal laparotomy with intrathoracic anastomosis was performed 6-8 weeks following RCT. This was combined with a two-field lymphadenectomy of mediastinal and abdominal lymph nodes. Standard histopathological evaluation included the application of regression grading according to Werner and Hoefler. Toxicity was recorded on the basis of CTC criteria; survival curves were calculated according to Kaplan-Meier. V10, V15, and V20 data were correlated with pulmonary toxicity. Results: Overall survival for all 23 patients was 61% at 3 years. Of the original 23 patients, 18 (78%) patients proceeded to radical surgery. Reasons for no surgery included advanced age of 79, 82, and 86 years (n = 3), severe comorbidity (n = 1), and progression during radiochemotherapy (n = 1). Surgical morbidity (grade 3-4) and mortality rates were 35% and 6%, respectively. Resurgery was necessary in 3 cases (18%). Clear resection margins were achieved in 17 of 18 patients (94%). Twelve of 18 (67%) patients initially diagnosed with T3 tumors and 3 of 3 patients with T4 tumors experienced downstaging. The ypN0 rate was 12 of 18 patients (67%). Out of a total of 18 patients, regression grading revealed < 10% viable cells in 8 (44%) including 3 cases (17%) with complete regression, 10-50% viable

  11. Toxicity of methods of implant material sterilization on corneal endothelium

    Energy Technology Data Exchange (ETDEWEB)

    Singh, G.; Boehnke, Mv.; von Domarus, D.; Draeger, J.

    1985-11-01

    The toxicity of different procedures utilized for the sterilization of intraocular implant material was assessed on the endothelium of organ-cultured porcine corneas. Polymethylmethacrylate lenses sterilized by treatment with sodium hydroxide (NaOH), ethylene oxide, formaldehyde, and gamma radiation were added to a culture medium containing normal porcine corneas. Considering the viability of endothelial cells, appearance of intracellular degenerative vacuoles, and denudation of corneal Descemet's membrane as criterion for the evaluation of toxicity of different methods of sterilization, the NaOH-treated lenses were found to be the least toxic to porcine corneal endothelium. Phase-contrast microscopy and vital staining of the endothelium permitted direct viewing of the endothelium aiding in the assessment of toxicity.

  12. Outcomes and Toxicity for Hypofractionated and Single-Fraction Image-Guided Stereotactic Radiosurgery for Sarcomas Metastasizing to the Spine

    Energy Technology Data Exchange (ETDEWEB)

    Folkert, Michael R. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark H. [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Tom, Ashlyn K. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Oh, Jung Hun [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Laufer, Ilya [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Tap, William D. [Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yamada, Yoshiya, E-mail: yamadaj@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Purpose: Conventional radiation treatment (20-40 Gy in 5-20 fractions, 2-5 Gy per fraction) for sarcoma metastatic to the spine provides subtherapeutic doses, resulting in poor durable local control (LC) (50%-77% at 1 year). Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) may provide a more effective means of managing these lesions. Methods and Materials: Patients with pathologically proven high-grade sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. LC and overall survival (OS) were analyzed by the use of Kaplan-Meier statistics. Univariate and multivariate analyses were performed by the use of Cox regression with competing-risks analysis; all confidence intervals are 95%. Toxicities were assessed according to Common Terminology Criteria for Adverse Events, version 4.0. Results: From May 2005 to November 11, 2012, 88 patients with 120 discrete metastases received HF (3-6 fractions; median dose, 28.5 Gy; n=52, 43.3%) or SF IG-SRS (median dose, 24 Gy; n=68, 56.7%). The median follow-up time was 12.3 months. At 12 months, LC was 87.9% (confidence interval [CI], 81.3%-94.5%), OS was 60.6% (CI, 49.6%-71.6%), and median survival was 16.9 months. SF IG-SRS demonstrated superior LC to HF IG-SRS (12-month LC of 90.8% [CI, 83%-98.6%] vs 84.1% [CI, 72.9%-95.3%] P=.007) and retained significance on multivariate analysis (P=.030, hazard ratio 0.345; CI, 0.132-0.901]. Treatment was well tolerated, with 1% acute grade 3 toxicity, 4.5% chronic grade 3 toxicity, and no grade >3 toxicities. Conclusions: In the largest series of metastatic sarcoma to the spine to date, IG-SRS provides excellent LC in the setting of an aggressive disease with low radiation sensitivity and poor prognosis. Single-fraction IG-SRS is associated with the highest rates of LC with minimal toxicity.

  13. Contemporary Toxicity Profile of Breast Brachytherapy Versus External Beam Radiation After Lumpectomy for Breast Cancer

    International Nuclear Information System (INIS)

    Huo, Jinhai; Giordano, Sharon H.; Smith, Benjamin D.; Shaitelman, Simona F.; Smith, Grace L.

    2016-01-01

    Purpose: We compared toxicities after brachytherapy versus external beam radiation therapy (EBRT) in contemporary breast cancer patients. Methods and Materials: Using MarketScan healthcare claims, we identified 64,112 women treated from 2003 to 2012 with lumpectomy followed by radiation (brachytherapy vs EBRT). Brachytherapy was further classified by multichannel versus single-channel applicator approach. We identified the risks and predictors of 1-year infectious and noninfectious postoperative adverse events using logistic regression and temporal trends using Cochran-Armitage tests. We estimated the 5-year Kaplan-Meier cumulative incidence of radiation-associated adverse events. Results: A total of 4522 (7.1%) patients received brachytherapy (50.2% multichannel vs 48.7% single-channel applicator). The overall risk of infectious adverse events was higher after brachytherapy than after EBRT (odds ratio [OR] = 1.21; 95% confidence interval [CI] 1.09-1.34, P<.001). However, over time, the frequency of infectious adverse events after brachytherapy decreased, from 17.3% in 2003 to 11.6% in 2012, and was stable after EBRT at 9.7%. Beyond 2007, there were no longer excess infections with brachytherapy (P=.97). The overall risk of noninfectious adverse events was higher after brachytherapy than after EBRT (OR=2.27; 95% CI 2.09-2.47, P<.0001). Over time, the frequency of noninfectious adverse events detected increased: after multichannel brachytherapy, from 9.1% in 2004 to 18.9% in 2012 (Ptrend = .64); single-channel brachytherapy, from 12.8% to 29.8% (Ptrend<.001); and EBRT, from 6.1% to 10.3% (Ptrend<.0001). The risk was significantly higher with single-channel than with multichannel brachytherapy (hazard ratio = 1.32; 95% CI 1.03-1.69, P=.03). Of noninfectious adverse events, 70.9% were seroma. Seroma significantly increased breast pain risk (P<.0001). Patients with underlying diabetes, cardiovascular disease, and treatment with chemotherapy had increased

  14. Contemporary Toxicity Profile of Breast Brachytherapy Versus External Beam Radiation After Lumpectomy for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Huo, Jinhai [Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Giordano, Sharon H. [Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Benjamin D. [Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shaitelman, Simona F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Grace L., E-mail: glsmith@mdanderson.org [Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-03-15

    Purpose: We compared toxicities after brachytherapy versus external beam radiation therapy (EBRT) in contemporary breast cancer patients. Methods and Materials: Using MarketScan healthcare claims, we identified 64,112 women treated from 2003 to 2012 with lumpectomy followed by radiation (brachytherapy vs EBRT). Brachytherapy was further classified by multichannel versus single-channel applicator approach. We identified the risks and predictors of 1-year infectious and noninfectious postoperative adverse events using logistic regression and temporal trends using Cochran-Armitage tests. We estimated the 5-year Kaplan-Meier cumulative incidence of radiation-associated adverse events. Results: A total of 4522 (7.1%) patients received brachytherapy (50.2% multichannel vs 48.7% single-channel applicator). The overall risk of infectious adverse events was higher after brachytherapy than after EBRT (odds ratio [OR] = 1.21; 95% confidence interval [CI] 1.09-1.34, P<.001). However, over time, the frequency of infectious adverse events after brachytherapy decreased, from 17.3% in 2003 to 11.6% in 2012, and was stable after EBRT at 9.7%. Beyond 2007, there were no longer excess infections with brachytherapy (P=.97). The overall risk of noninfectious adverse events was higher after brachytherapy than after EBRT (OR=2.27; 95% CI 2.09-2.47, P<.0001). Over time, the frequency of noninfectious adverse events detected increased: after multichannel brachytherapy, from 9.1% in 2004 to 18.9% in 2012 (Ptrend = .64); single-channel brachytherapy, from 12.8% to 29.8% (Ptrend<.001); and EBRT, from 6.1% to 10.3% (Ptrend<.0001). The risk was significantly higher with single-channel than with multichannel brachytherapy (hazard ratio = 1.32; 95% CI 1.03-1.69, P=.03). Of noninfectious adverse events, 70.9% were seroma. Seroma significantly increased breast pain risk (P<.0001). Patients with underlying diabetes, cardiovascular disease, and treatment with chemotherapy had increased

  15. The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma

    International Nuclear Information System (INIS)

    Kleinberg, Lawrence; Grossman, Stuart A.; Piantadosi, Steven; Zeltzman, Michel; Wharam, Moody

    1999-01-01

    Purpose: To determine the effects of sequential versus concurrent administration of cranial radiotherapy and cisplatin/carmustine (BCNU) chemotherapy on survival and toxicity in newly diagnosed high-grade astrocytomas. Methods and Materials: From 1988 to 1996, 101 patients were treated on 2 therapeutic protocols for malignant glioma that used the identical chemotherapy regimen but differed in the timing of cranial radiotherapy. The eligibility criteria for the 2 protocols were identical. In the first protocol (1988-1991, 52 patients), cisplatin 120 mg/BCNU 120 mg i.v. over 72 h, was given for 3 monthly cycles prior to cranial radiotherapy. After a response rate of 42%, with a median survival of 13 months was achieved with this sequential regimen, a successor protocol (1992-1996, 49 patients) was developed in which cranial radiotherapy began concurrently with the start of the identical chemotherapy regimen. Chemotherapy was delayed but not discontinued if prolonged grade III/IV hematologic toxicity was experienced, but protocol therapy was discontinued if disease progression or thromboembolic events occurred. Survival outcome and hematologic toxicity were compared for the patients treated on these protocols. Results: Seventy-seven percent of sequentially-treated patients and 68% of concurrently-treated patients completed all planned therapy. Kaplan-Meier survival was similar to concurrent or sequential administration of chemotherapy and radiotherapy (median 12.8 months vs. 13.8 months, respectively). Hematologic toxicity was significantly less in sequentially- versus concurrently-treated patients, with median nadir per cycle (2.9 vs. 1.8 x 10 3 /mm 3 ) (p < 0.001), and incidence of grade 3/4 leukopenia 40% versus 77% (p = 0.002). There was also an increase in platelet transfusion requirements in concurrently-treated patients, but no significant worsening of anemia. We postulate that the worsened leukopenia results from the effects of concurrent radiotherapy on

  16. A SEDIMENT TOXICITY METHOD USING LEMNA MINOR, DUCKWEED

    Science.gov (United States)

    We developed a Lemna minor sediment toxicity test method to assess sediment contaminants which may affect plants. This 96-hour test used 15 ml of sediment and 2 ml of overlying water which was renewed after 48 hours. Sand was used as the control sediment and also to dilute test ...

  17. NEW METHOD FOR DETERMINING EFFLUENT TOXICITY USING DUCKWEED (LEMNA MINOR)

    Science.gov (United States)

    Duckweed (Lemna minor), a small vascular plant, grows rapidly, is sensitive to a wide variety of toxicants and is easy to culture. ethod is described that measures duckweed frond growth and chlorophyll levels as indicators of growth inhibition. he method requires a small testing ...

  18. Diagnosis of toxic alcohols: limitations of present methods.

    Science.gov (United States)

    Kraut, Jeffrey A

    2015-01-01

    Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxications are associated with cellular dysfunction and an increased risk of death. Adverse effects can develop quickly; thus, there is a need for methods for rapidly detecting their presence. To examine the value and limitations of present methods to diagnose patients with possible toxic alcohol exposure. I searched MEDLINE for articles published between 1969 and 2014 using the terms: toxic alcohols, serum osmolality, serum osmol gap, serum anion gap, metabolic acidosis, methanol, ethylene glycol, diethylene glycol, propylene glycol, and fomepizole. Each article was reviewed for additional references. The diagnosis of toxic alcohol exposure is often made on the basis of this history and physical findings along with an increase in the serum osmol and anion gaps. However, an increase in the osmol and/or anion gaps is not always present. Definitive detection in blood requires gas or liquid chromatography, laborious and expensive procedures which are not always available. Newer methods including a qualitative colorimetric test for detection of all alcohols or enzymatic tests for a specific alcohol might allow for more rapid diagnosis. Exposure to toxic alcohols is associated with cellular dysfunction and increased risk of death. Treatment, if initiated early, can markedly improve outcome, but present methods of diagnosis including changes in serum osmol and anion gap, and use of gas or liquid chromatography have important limitations. Development of more rapid and effective tests for detection of these intoxications is essential for optimal care of patients.

  19. A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (1) -survival and toxicity

    International Nuclear Information System (INIS)

    Su Shengfa; Lu Bing; Zhang Bo; Hu Yinyang; Ouyang Weiwei; Li Huiqin; Wang Gang; Long Jinhua

    2011-01-01

    Objective: To evaluate the overall survival and safety among patients for stage IV non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT). Methods: From Jan. 2003 to July 2010, 201 patients with stage IV NSCLC were included. All patients were treated with CCTTRT. Those patients who received only one cycle chemotherapy were not included in survival analysis,but analysis of toxicity. One hundred and eighty-two patients were eligible for survival analysis. All patients received platinum-based two-drug chemotherapy. The median number of cycles was 4. The median dose to planning target volume of primary tumor (DT PTV ) was 63 Gy. Treatment-related gastrointestinal and hematological toxicity were scored according to WHO criteria. Radiation-related pneumonitis and esophagitis were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) version 3.0. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model was used to examine the effect of CCTTRT on overall survival. Results: The follow-up rate of 201 patients was 97.5%. with 201, 170 and 134 patients finished 2 =10.10, P =0.001). For patients eligible for survival analysis and received 4 - 5 cycles of systemic chemotherapy, MST of patients treated with DT PTV ≥63 Gy was significantly longer than those treated with DT PTV 2 =20.48, P =0.000) and 16.1 months vs.8.8 months (χ 2 =11.75, P =0.001)]. For patients with single organ metastasis, MST was 16 months for those treated with DT PTV ≥63 Gy and 9 months for those with DT PTV 2 =10.51, P=0.000); for patients with multiple organ metastasis, it was 11 months and 7 months, respectively (χ 2 =7.90, P =0.005). Multivariate analysis showed that concurrent 4 - 5 cycles chemotherapy and DTPTV ≥63 Gy (β =0.243, P=0.019) and improved KPS (β =1.268, P=0.000) were independent factors for survival. For the whole

  20. Collection and cultivation methods of Acartia tonsa for toxicity testing

    International Nuclear Information System (INIS)

    Hood, C.A.; Mayo, R.R.

    1995-01-01

    Acartia tonsa were located and collected from Galveston Bay, Texas in June 1995, using plankton nets and transported to the laboratory for culture. After literature searching and laboratory experimentation. A simple reliable method was designed to culture A. tonsa. This method requires a minimum of glassware and supplies. Adult A. tonsa are placed in one gallon bell jars filled with natural seawater. The jars are then maintained in a water bath at a constant temperature. Water changes are conducted twice weekly and organisms are fed daily with a mixture of algae, Skeletonema costatum, isocrysis galbana, and Thalassiosira sp. Gravid females are then isolated in generators for 24 hours to obtain known age neonates. The neonates are maintained up to a specific age and then are used in toxicity tests such as the ''Determination of the Acute Lethal Toxicity to Marine Copepods,'' required in the United Kingdom for all chemicals used for offshore drilling fluid applications

  1. "Cold combustion" as a new method of toxic waste destruction

    Directory of Open Access Journals (Sweden)

    Екатерина Юрьевна Ткаченко

    2015-05-01

    Full Text Available This article describes a promising new method for the destruction of toxic industrial waste, obsolete pesticides and military poisons and explosives. The proposed method can be used to create mobile modular units that will produce the destruction of the "field", to clean the soil and water containing low concentrations of a pollutant, to solve the problem of disposal of explosives, which is often accompanied by the destruction of uncontrolled detonation. The proposed method is environmentally friendly, using ice as the working body

  2. Randomized Phase III Trial to Test Accelerated Versus Standard Fractionation in Combination With Concurrent Cisplatin for Head and Neck Carcinomas in the Radiation Therapy Oncology Group 0129 Trial: Long-Term Report of Efficacy and Toxicity

    Science.gov (United States)

    Nguyen-Tan, Phuc Felix; Zhang, Qiang; Ang, K. Kian; Weber, Randal S.; Rosenthal, David I.; Soulieres, Denis; Kim, Harold; Silverman, Craig; Raben, Adam; Galloway, Thomas J.; Fortin, André; Gore, Elizabeth; Westra, William H.; Chung, Christine H.; Jordan, Richard C.; Gillison, Maura L.; List, Marcie; Le, Quynh-Thu

    2014-01-01

    Purpose We tested the efficacy and toxicity of cisplatin plus accelerated fractionation with a concomitant boost (AFX-C) versus standard fractionation (SFX) in locally advanced head and neck carcinoma (LA-HNC). Patients and Methods Patients had stage III to IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Radiation therapy schedules were 70 Gy in 35 fractions over 7 weeks (SFX) or 72 Gy in 42 fractions over 6 weeks (AFX-C). Cisplatin doses were 100 mg/m2 once every 3 weeks for two (AFX-C) or three (SFX) cycles. Toxicities were scored by using National Cancer Institute Common Toxicity Criteria 2.0 and the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. Overall survival (OS) and progression-free survival (PFS) rates were estimated by using the Kaplan-Meier method and were compared by using the one-sided log-rank test. Locoregional failure (LRF) and distant metastasis (DM) rates were estimated by using the cumulative incidence method and Gray's test. Results In all, 721 of 743 patients were analyzable (361, SFX; 360, AFX-C). At a median follow-up of 7.9 years (range, 0.3 to 10.1 years) for 355 surviving patients, no differences were observed in OS (hazard ratio [HR], 0.96; 95% CI, 0.79 to 1.18; P = .37; 8-year survival, 48% v 48%), PFS (HR, 1.02; 95% CI, 0.84 to 1.24; P = .52; 8-year estimate, 42% v 41%), LRF (HR, 1.08; 95% CI, 0.84 to 1.38; P = .78; 8-year estimate, 37% v 39%), or DM (HR, 0.83; 95% CI, 0.56 to 1.24; P = .16; 8-year estimate, 15% v 13%). For oropharyngeal cancer, p16-positive patients had better OS than p16-negative patients (HR, 0.30; 95% CI, 0.21 to 0.42; P < .001; 8-year survival, 70.9% v 30.2%). There were no statistically significant differences in the grade 3 to 5 acute or late toxicities between the two arms and p-16 status. Conclusion When combined with cisplatin, AFX-C neither improved outcome nor increased late toxicity in patients with LA-HNC. Long-term high survival

  3. Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chance, William W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rice, David C. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsao, Anne S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fontanilla, Hiral P. [Princeton Radiation Oncology, Monroe Township, New Jersey (United States); Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza J. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-01-01

    Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

  4. Marine Biotoxins: Occurrence, Toxicity, Regulatory Limits and Reference Methods

    Directory of Open Access Journals (Sweden)

    Pierina Visciano

    2016-07-01

    Full Text Available Harmful algal blooms are natural phenomena caused by the massive growth of phytoplankton that may contain highly toxic chemicals, the so-called marine biotoxins causing illness and even death to both aquatic organisms and humans. Their occurrence has been increased in frequency and severity, suggesting a worldwide public health risk. Marine biotoxins can accumulate in bivalve molluscs and regulatory limits have been set for some classes according to European Union legislation. These compounds can be distinguished in water- and fat-soluble molecules. The first group involves those of Paralytic Shellfish Poisoning and Amnesic Shellfish Poisoning, whereas the toxins soluble in fat can cause Diarrheic Shellfish Poisoning and Neurotoxic Shellfish Poisoning. Due to the lack of long-term toxicity studies, establishing tolerable daily intakes for any of these marine biotoxins was not possible, but an acute reference dose can be considered more appropriate, because these molecules show an acute toxicity. Dietary exposure assessment is linked both to the levels of marine biotoxins present in bivalve molluscs and the portion that could be eaten by consumers. Symptoms may vary from a severe gastrointestinal intoxication with diarrhea, nausea, vomiting, and abdominal cramps to neurological disorders such as ataxia, dizziness, partial paralysis, and respiratory distress. The official method for the detection of marine biotoxins is the mouse bioassay (MBA showing some limits due to ethical restrictions and insufficient specificity. For this reason, the liquid chromatography–mass spectrometry method has replaced MBA as the reference technique. However, the monitoring of algal blooms producing marine biotoxins should be regularly assessed in order to obtain more reliable, accurate estimates of bloom toxicity and their potential impacts.

  5. An evaluation of the whole effluent toxicity test method

    International Nuclear Information System (INIS)

    Osteen, D.V.

    1999-01-01

    Whole effluent toxicity (WET) testing has become increasingly more important to the Environmental Protection Agency (EPA) and the States in the permitting of wastewater discharges from industry and municipalities. The primary purpose of the WET test is to protect aquatic life by predicting the effect of an effluent on the receiving stream. However, there are both scientific and regulatory concerns that using WET tests to regulate industrial effluents may result in either false positives and/or false negatives. In order to realistically predict the effect of an effluent on the receiving stream, the test should be as representative as possible of the conditions in the receiving stream. Studies (Rand and Petrocelli 1985) suggested several criteria for an ideal aquatic toxicity test organism, one of which is that the organism be indigenous to, or representative of, the ecosystem receiving the effluent. The other component needed in the development of a predictive test is the use of the receiving stream water or similar synthetic water as the control and dilution water in the test method. Use of an indigenous species and receiving water in the test should help reduce the variability in the method and allow the test to predict the effect of the effluent on the receiving stream. The experience with toxicity testing at the Savannah River Site (SRS) has yielded inconclusive data because of the inconsistency and unreliability of the results. The SRS contention is that the WET method in its present form does not adequately mimic actual biological/chemical conditions of the receiving streams and is neither reasonable nor accurate. This paper discusses the rationale for such a position by SRS on toxicity testing in terms of historical permitting requirements, outfall effluent test results, standard test method evaluation, scientific review of alternate test species, and concerns over the test method expressed by other organizations. This paper presents the Savannah River Site

  6. Long term toxicity and prognostic factors of radiation therapy for secreting and non-secreting pituitary adenomas

    International Nuclear Information System (INIS)

    Rieken, Stefan; Habermehl, Daniel; Welzel, Thomas; Mohr, Angela; Lindel, Katja; Debus, Jürgen; Combs, Stephanie E

    2013-01-01

    Radiotherapy is controversially discussed in the management of benign disorders for fear of late sequelae such as tumor induction. This study was initiated to investigate long-term toxicity, treatment outcome and prognostic factors after radiotherapy (RT) in patients with pituitary adenomas. 92 patients with pituitary adenomas were included in this analysis. RT was conducted using either 3D conformal (16%) or fractionated stereotactic techniques (83%) in a postoperative adjuvant setting (16%), as second-line treatment for recurring tumors (78%) or as primary treatment (6%). Postoperatively, RT was offered to patients with residual tumor tissue or in case of locally extensive adenomas, in whom early recurrence was deemed likely. Patients were followed for a median time of 152.5 months, and analysed for overall and local progression-free survival (OS and LPFS). Multiple factors were analysed for prognostic impact. Patients were contacted with an institutional questionnaire about qualiy of life (QOL). Statistical analysis was performed using the log-rank test and the Kaplan-Meier method using a software tool (SPSS 19.0). Median follow-up was 152.5 months. Before treatment, 2% of all patients were diagnosed with adenoma-related hypopituitarism. Following surgery, 68% suffered from new pituitary deficits. RT was associated with mild toxicity, including visual deficits (5.4%) and hypopituitarism (10.9%). In particular, no radiation-induced brain necrosis or malignancy was observed. QOL was reported to be stable or improved in 92% of all patients, and RT was perceived to not compromise but increase QOL in the vast majority of patients (95%). OS after RT was 93.3% and 61.0% at 120 and 240 months. LPFS following RT was 90.4 and 75.5% at 120 and 240 months. Early initiation of RT after surgery instead of reserving it for recurring adenomas predisposed for improved outcome. RT for pituitary adenomas is safe and and self-reported QOL is stable or improved by almost all

  7. Inventory of LCIA selection methods for assessing toxic releases. Methods and typology report part B

    DEFF Research Database (Denmark)

    Larsen, Henrik Fred; Birkved, Morten; Hauschild, Michael Zwicky

    method(s) in Work package 8 (WP8) of the OMNIITOX project. The selection methods and the other CRS methods are described in detail, a set of evaluation criteria are developed and the methods are evaluated against these criteria. This report (Deliverable 11B (D11B)) gives the results from task 7.1d, 7.1e......This report describes an inventory of Life Cycle Impact Assessment (LCIA) selection methods for assessing toxic releases. It consists of an inventory of current selection methods and other Chemical Ranking and Scoring (CRS) methods assessed to be relevant for the development of (a) new selection...... and 7.1f of WP 7 for selection methods. The other part of D11 (D11A) is reported in another report and deals with characterisation methods. A selection method is a method for prioritising chemical emissions to be included in an LCIA characterisation of toxic releases, i.e. calculating indicator scores...

  8. Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gunther, Jillian R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michelle A. [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akhtari, Mani [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, The University of Texas Medical Branch at Galveston, Galveston, Texas (United States); Smith, Grace L.; Pinnix, Chelsea C.; Milgrom, Sarah A.; Yehia, Zeinab Abou; Allen, Pamela K.; Osborne, Eleanor M. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-09-01

    Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.

  9. Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

    International Nuclear Information System (INIS)

    Gunther, Jillian R.; Fanale, Michelle A.; Reddy, Jay P.; Akhtari, Mani; Smith, Grace L.; Pinnix, Chelsea C.; Milgrom, Sarah A.; Yehia, Zeinab Abou; Allen, Pamela K.; Osborne, Eleanor M.; Mawlawi, Osama; Dabaja, Bouthaina S.

    2016-01-01

    Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.

  10. Testing of toxicity based methods to develop site specific clean up objectives - phase 1: Toxicity protocol screening and applicability

    International Nuclear Information System (INIS)

    Hamilton, H.; Kerr, D.; Thorne, W.; Taylor, B.; Zadnik, M.; Goudey, S.; Birkholz, D.

    1994-03-01

    A study was conducted to develop a cost-effective and practical protocol for using bio-assay based toxicity assessment methods for remediation of decommissioned oil and gas production, and processing facilities. The objective was to generate site-specific remediation criteria for contaminated sites. Most companies have used the chemical-specific approach which, however, did not meet the ultimate land use goal of agricultural production. The toxicity assessment method described in this study dealt with potential impairment to agricultural crop production and natural ecosystems. Human health concerns were not specifically addressed. It was suggested that chemical-specific methods should be used when human health concerns exist. . Results showed that toxicity tests will more directly identify ecological stress caused by site contamination than chemical-specific remediation criteria, which can be unnecessarily protective. 11 refs., 7 tabs., 6 figs

  11. Acute toxicity and efficacy of postoperative combined modality therapy for adenocarcinoma of the pancreas

    International Nuclear Information System (INIS)

    Davis, Brian J.; Raben, Adam; Casper, Ephraim; Minsky, Bruce D.

    1996-01-01

    PURPOSE: To examine the acute toxicity and outcome in patients (pts) treated with combined modality therapy following resection of adenocarcinoma of the pancreas. MATERIALS AND METHODS: From 2/88 to 2/96, 34 pts (M:20, F:14) received postoperative combined modality therapy following a pancreatic resection. Tumor location included; head only: 28, head and ampulla: 1, ampulla only: 1, body and tail: 2, and tail only: 2. Postoperative stages included: stage I: 7 (21%) and stage III: 27 (79%). Pts were referred for combined modality therapy based on surgeon preference. In general, pts were treated who had one or more adverse prognostic factors. These included positive local/regional lymph nodes (79%), positive margins (50%) or disease invasive into adjacent structures (85 %). Radiation fields included the original primary tumor bed (based on preoperative CT scans) and peri-pancreatic and para-aortic lymph nodes adjacent to vertebral bodies T10 through L3. No attempt was made to include the entire pancreas in the radiation field. Patients received 5040 cGy at 180 cGy/day using a 3 or 4 field technique and CT-based treatment planning. Concurrent bolus 5-FU (375-500 mg/m 2 ) was delivered on the first three and last three days of radiation. Post-radiation maintenance bolus 5-FU was given to 7 patients for a median of 6 cycles. A toxicity assessment using the NCI toxicity criteria was performed at each weekly visit and 4 weeks following the completion of combined modality therapy. The median follow-up was 13 months (range: 2-36 months). Patterns of failure as a component of failure were assessed by radiographic criteria and, in 2 pts, by intraoperative evaluation for symptomatic progression of disease. Local/regional failure was defined as recurrence within the radiation field. Distant failure included liver, peritoneal seeding, and extra-abdominal sites. Actuarial survival was calculated from the time of surgery using the Kaplan-Meier method. RESULTS: The only grade 3

  12. Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.

    Science.gov (United States)

    Schlussel Markovic, Emily; Buckstein, Michael; Stone, Nelson N; Stock, Richard G

    2018-05-01

    To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer. A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan-Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes. A total of 902 patients were identified, with a median follow-up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040). Brachytherapy monotherapy results in equal biochemical and distant control in both patients with

  13. In silico toxicology: computational methods for the prediction of chemical toxicity

    KAUST Repository

    Raies, Arwa B.; Bajic, Vladimir B.

    2016-01-01

    Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models.

  14. In silico toxicology: computational methods for the prediction of chemical toxicity

    KAUST Repository

    Raies, Arwa B.

    2016-01-06

    Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models.

  15. CYTOTOXICITY AND MUTAGENESIS METHODS FOR EVALUATING TOXICITY REMOVAL FROM WASTEWATERS

    Science.gov (United States)

    This project was a feasibility study of the effectiveness of a mammalian cell cytotoxicity assay and a mammalian cell mutagenesis assay for monitoring the toxicity and mutagenicity of influent and effluent wastewater at treatment plants. In the cytotoxicity assay, ambient samples...

  16. Novel ceramic processing method for substitution of toxic plasticizers

    DEFF Research Database (Denmark)

    Foghmoes, Søren Preben Vagn; Teocoli, Francesca; Brodersen, K.

    2016-01-01

    A systematic screening of plasticisers for a polyvinyl butyral based binder system revealed that dibutyl maleate, dibutyl adipate and Pycal 94 are promising and less toxic alternatives to the very harmful but frequently used dibutyl phthalate. Pycal 94 seems especially promising as it unlike...

  17. Microbial Hydrocarbon and ToxicPollutant Degradation Method

    Energy Technology Data Exchange (ETDEWEB)

    Schlueter, Dietrich [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Janabi, Mustafa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); O' Neil, James [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Budinger, Thomas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-08-16

    The goal of this project is to determine optimum conditions for bacterial oxidation of hydrocarbons and long-chain alkanes that are representative of petroleum contamination of the environment. Polycyclic Aromatic Hydrocarbons (PAHs) are of concern because of their toxicity, low volatility, and resistance to microbial degradation, especially under anaerobic conditions. The uniqueness of our approach is to use carbon-11 in lieu of the traditional use of carbon-14.

  18. Evaluation and modeling of the parameters affecting fluoride toxicity level in aquatic environments by bioassay method

    Directory of Open Access Journals (Sweden)

    Hamid Reza Shamsollahi

    2014-04-01

    Full Text Available Background: Fluoride exists in various forms in nature and water resources. , The rising level of fluoride in water resources due to discharge of industrial effluents can cause toxicity in aquatic organisms. To prevent toxicity, it is necessary to determine maximum fluoride toxicity as well as effluent discharge limits. The aim of this study was to determine the maximum fluoride toxicity and the factors affecting fluoride toxicity to provide a model in order to determine the effluent discharge limits. Methods: Daphnia magna bioassay in the absence of confounding factors was used to determine the maximum level of fluoride toxicity. Then, bioassay was repeated in the presence of the confounding factors (hardness, temperature and exposure time to determine their effects. Results: In the absence of intervening factors, fluoride LC50 levels determined after 24, 48 and 72 hours exposure were 4.9, 46.5 and 38.7 mg/l, respectively.. Also, the influence of confounding factors on LC50 values was reported significant by Minitab software. Conclusion: Increasing the water hardness reduced fluoride toxicity, and increasing the water temperature and exposure time increased fluoride toxicity in aquatic environments. Therefore, while determining the wastewater discharge limit in terms of fluoride concentration, it is essential to take the effect of confounding factors on fluoride toxicity into account in order to prevent toxicity in the open water resources.

  19. Arsenic: A Review of the Element's Toxicity, Plant Interactions, and Potential Methods of Remediation.

    Science.gov (United States)

    Hettick, Bryan E; Cañas-Carrell, Jaclyn E; French, Amanda D; Klein, David M

    2015-08-19

    Arsenic is a naturally occurring element with a long history of toxicity. Sites of contamination are found worldwide as a result of both natural processes and anthropogenic activities. The broad scope of arsenic toxicity to humans and its unique interaction with the environment have led to extensive research into its physicochemical properties and toxic behavior in biological systems. The purpose of this review is to compile the results of recent studies concerning the metalloid and consider the chemical and physical properties of arsenic in the broad context of human toxicity and phytoremediation. Areas of focus include arsenic's mechanisms of human toxicity, interaction with plant systems, potential methods of remediation, and protocols for the determination of metals in experimentation. This assessment of the literature indicates that controlling contamination of water sources and plants through effective remediation and management is essential to successfully addressing the problems of arsenic toxicity and contamination.

  20. Effect of soil contaminant extraction method in determining toxicity using the Microtox(reg.) assay

    International Nuclear Information System (INIS)

    Harkey, G.A.; Young, T.M.

    2000-01-01

    This project examined the influence of different extraction methods on the measured toxicity of contaminated soils collected from manufactured gas plant (MGP) sites differing in soil composition and contaminant concentration. Aged soils from a number of MGP sites were extracted using a saline solution, supercritical fluid extraction (SFE), and Soxhlet extraction. Toxicity was assessed using two forms of Microtox tests: acute aqueous tests on saline and SFE soil extracts and solid-phase tests (SPTs) on soil particles. Microtox SPTs were performed on soils before and after SFE to determine resulting toxicity reduction. Three hypotheses were tested: (1) Toxicity of soil extracts is related to contaminant concentrations of the extracts, (2) measured toxicity significantly decreases with less vigorous methods of extraction, and (3) supercritical fluid extractability correlates with measured toxicity. The EC50s for SPTs performed before and after SFE were not different for some soils but were significantly greater after extraction for other soils tested. The most significant toxicity reductions were observed for soils exhibiting the highest toxicity in both preextraction SPTs and acute aqueous tests. Acute Microtox tests performed on SFE extracts showed significantly lower EC50s than those reported from saline-based extraction procedures. Toxicity of the soils measured by Microtox SPTs was strongly correlated with both SFE efficiency and measures of contaminant aging. Data from this project provide evidence of sequestration and reduced availability of polycyclic aromatic hydrocarbons (PAHs) from soils extracted via physiologically based procedures compared to vigorous physical extraction protocols

  1. In silico toxicology: comprehensive benchmarking of multi-label classification methods applied to chemical toxicity data

    KAUST Repository

    Raies, Arwa B.

    2017-12-05

    One goal of toxicity testing, among others, is identifying harmful effects of chemicals. Given the high demand for toxicity tests, it is necessary to conduct these tests for multiple toxicity endpoints for the same compound. Current computational toxicology methods aim at developing models mainly to predict a single toxicity endpoint. When chemicals cause several toxicity effects, one model is generated to predict toxicity for each endpoint, which can be labor and computationally intensive when the number of toxicity endpoints is large. Additionally, this approach does not take into consideration possible correlation between the endpoints. Therefore, there has been a recent shift in computational toxicity studies toward generating predictive models able to predict several toxicity endpoints by utilizing correlations between these endpoints. Applying such correlations jointly with compounds\\' features may improve model\\'s performance and reduce the number of required models. This can be achieved through multi-label classification methods. These methods have not undergone comprehensive benchmarking in the domain of predictive toxicology. Therefore, we performed extensive benchmarking and analysis of over 19,000 multi-label classification models generated using combinations of the state-of-the-art methods. The methods have been evaluated from different perspectives using various metrics to assess their effectiveness. We were able to illustrate variability in the performance of the methods under several conditions. This review will help researchers to select the most suitable method for the problem at hand and provide a baseline for evaluating new approaches. Based on this analysis, we provided recommendations for potential future directions in this area.

  2. In silico toxicology: comprehensive benchmarking of multi-label classification methods applied to chemical toxicity data

    KAUST Repository

    Raies, Arwa B.; Bajic, Vladimir B.

    2017-01-01

    One goal of toxicity testing, among others, is identifying harmful effects of chemicals. Given the high demand for toxicity tests, it is necessary to conduct these tests for multiple toxicity endpoints for the same compound. Current computational toxicology methods aim at developing models mainly to predict a single toxicity endpoint. When chemicals cause several toxicity effects, one model is generated to predict toxicity for each endpoint, which can be labor and computationally intensive when the number of toxicity endpoints is large. Additionally, this approach does not take into consideration possible correlation between the endpoints. Therefore, there has been a recent shift in computational toxicity studies toward generating predictive models able to predict several toxicity endpoints by utilizing correlations between these endpoints. Applying such correlations jointly with compounds' features may improve model's performance and reduce the number of required models. This can be achieved through multi-label classification methods. These methods have not undergone comprehensive benchmarking in the domain of predictive toxicology. Therefore, we performed extensive benchmarking and analysis of over 19,000 multi-label classification models generated using combinations of the state-of-the-art methods. The methods have been evaluated from different perspectives using various metrics to assess their effectiveness. We were able to illustrate variability in the performance of the methods under several conditions. This review will help researchers to select the most suitable method for the problem at hand and provide a baseline for evaluating new approaches. Based on this analysis, we provided recommendations for potential future directions in this area.

  3. A comparison of sediment toxicity test methods at three Great Lake Areas of Concern

    Science.gov (United States)

    Burton, G. Allen; Ingersoll, Christopher G.; Burnett, LouAnn C.; Henry, Mary; Hinman, Mark L.; Klaine, Stephen J.; Landrum, Peter F.; Ross, Phillipe; Tuchman, Marc

    1996-01-01

    The significance of sediment contamination is often evaluated using sediment toxicity (bioassay) testing. There are relatively few “standardized” test methods for evaluating sediments. Popular sediment toxicity methods examine the extractable water (elutriate), interstitial water, or whole (bulk) sediment phases using test species spanning the aquatic food chain from bacteria to fish. The current study was designed to evaluate which toxicity tests were most useful in evaluations of sediment contamination at three Great Lake Areas of Concern. Responses of 24 different organisms including fish, mayflies, amphipods, midges, cladocerans, rotifers, macrophytes, algae, and bacteria were compared using whole sediment or elutriate toxicity assays. Sediments from several sites in the Buffalo River, Calumet River (Indiana Harbor), and Saginaw River were tested, as part of the U.S. Environmental Protection Agency's (USEPA) Assessment and Remediation of Contaminated Sediments (ARCS) Project. Results indicated several assays to be sensitive to sediment toxicity and able to discriminate between differing levels of toxicity. Many of the assay responses were significantly correlated to other toxicity responses and were similar based on factor analysis. For most applications, a test design consisting of two to three assays should adequately detect sediment toxicity, consisting of various groupings of the following species: Hyalella azteca, Ceriodaphnia dubia, Chironomus riparius, Chironomus tentans, Daphnia magna, Pimephales promelas, Hexagenia bilineata, Diporeia sp., Hydrilla verticillata, or Lemna minor.

  4. Toxicity of some formation fluids and methods of rehabilitation subsequent to their spillage

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, D R

    1976-01-01

    This paper deals with the effects that formation fluids have on animal and plant life. Crude oil is a mixture--not only of hydrocarbons, but of suspended salts and of sulfur compounds. The toxicity of some of the hydrocarbons and some of the sulfur compounds is discussed, as is the toxicity of salt. Consideration is also given to the complexity of the hydrocarbon components and the influence of refining methods on toxicity. Some mechanisms by which an animal system may attempt to overcome injurious effects are outlined. Finally, methods of aiding recovery are suggested. 26 references.

  5. Evaluation of the Treatment Process of Landfill Leachate Using the Toxicity Assessment Method

    Directory of Open Access Journals (Sweden)

    Aifeng Qiu

    2016-12-01

    Full Text Available Landfill leachate is composed of a complex composition with strong biological toxicity. The combined treatment process of coagulation and sedimentation, anaerobics, electrolysis, and aerobics was set up to treat landfill leachate. This paper explores the effect of different operational parameters of coagulation and sedimentation tanks and electrolytic cells, while investigating the combined process for the removal efficiency of physicochemical indices after processing the landfill leachate. Meanwhile, a battery of toxicity tests with Vibrio fischeri, zebrafish larvae, and embryos were conducted to evaluate acute toxicity and calculated the toxicity reduction efficiency after each treatment process. The combined treatment process resulted in a 100% removal efficiency of Cu, Cd and Zn, and a 93.50% and an 87.44% removal efficiency of Ni and Cr, respectively. The overall removal efficiency of chemical oxygen demand (COD, ammonium nitrogen (NH4+-N, and total nitrogen (TN were 93.57%, 97.46% and 73.60%, respectively. In addition, toxicity test results showed that the acute toxicity of landfill leachate had also been reduced significantly: toxicity units (TU decreased from 84.75 to 12.00 for zebrafish larvae, from 82.64 to 10.55 for zebrafish embryos, and from 3.41 to 0.63 for Vibrio fischeri. The combined treatment process was proved to be an efficient treatment method to remove heavy metals, COD, NH4+-N, and acute bio-toxicity of landfill leachate.

  6. Evaluation of the Treatment Process of Landfill Leachate Using the Toxicity Assessment Method.

    Science.gov (United States)

    Qiu, Aifeng; Cai, Qiang; Zhao, Yuan; Guo, Yingqing; Zhao, Liqian

    2016-12-21

    Landfill leachate is composed of a complex composition with strong biological toxicity. The combined treatment process of coagulation and sedimentation, anaerobics, electrolysis, and aerobics was set up to treat landfill leachate. This paper explores the effect of different operational parameters of coagulation and sedimentation tanks and electrolytic cells, while investigating the combined process for the removal efficiency of physicochemical indices after processing the landfill leachate. Meanwhile, a battery of toxicity tests with Vibrio fischeri , zebrafish larvae, and embryos were conducted to evaluate acute toxicity and calculated the toxicity reduction efficiency after each treatment process. The combined treatment process resulted in a 100% removal efficiency of Cu, Cd and Zn, and a 93.50% and an 87.44% removal efficiency of Ni and Cr, respectively. The overall removal efficiency of chemical oxygen demand (COD), ammonium nitrogen (NH₄⁺-N), and total nitrogen (TN) were 93.57%, 97.46% and 73.60%, respectively. In addition, toxicity test results showed that the acute toxicity of landfill leachate had also been reduced significantly: toxicity units (TU) decreased from 84.75 to 12.00 for zebrafish larvae, from 82.64 to 10.55 for zebrafish embryos, and from 3.41 to 0.63 for Vibrio fischeri . The combined treatment process was proved to be an efficient treatment method to remove heavy metals, COD, NH₄⁺-N, and acute bio-toxicity of landfill leachate.

  7. Bioassay method for toxicity studies of insecticide formulations to Tuta absoluta (meyrick, 1917)

    OpenAIRE

    Galdino, Tarcísio Visintin da Silva; Picanço, Marcelo Coutinho; Morais, Elisangela Gomes Fidelis de; Silva, Nilson Rodrigues; Silva, Geverson Aelton Rezende da; Lopes, Mayara Cristina

    2011-01-01

    Chemical control is the main method for controlling the tomato leafminer, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae). Reported techniques for the evaluation of insecticide toxicity to the tomato leafminer are not in agreement with field conditions and do not allow us to verify whether doses used in the field are efficient for control. Thus, the objective of this work was to develop a bioassay methodology to study the toxicity of insecticide formulations to T. absoluta that repre...

  8. Bioassay method for toxicity studies of insecticide formulations to tuta absoluta (meyrick, 1917).

    OpenAIRE

    GALDINO, T. V. da S.; PICANÇO, M. C.; MORAIS, E. G. F. de; SILVA, N. R.; SILVA, G. A. R da; LOPES, M. C.

    2014-01-01

    Chemical control is the main method for controlling the tomato leafminer, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae). Reported techniques for the evaluation of insecticide toxicity to the tomato leafminer are not in agreement with field conditions and do not allow us to verify whether doses used in the field are efficient for control. Thus, the objective of this work was to develop a bioassay methodology to study the toxicity of insecticide formulations to T. absoluta that repre...

  9. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

    Science.gov (United States)

    Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

    2018-02-01

    For a drug, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  10. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

    Directory of Open Access Journals (Sweden)

    Hongbin Yang

    2018-02-01

    Full Text Available During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  11. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts.

    Science.gov (United States)

    Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

    2018-01-01

    During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  12. Toxicity detection of sodium nitrite, borax and aluminum potassium sulfate using electrochemical method.

    Science.gov (United States)

    Yu, Dengbin; Yong, Daming; Dong, Shaojun

    2013-04-01

    Based on the inhibition effect on the respiratory chain activity of microorganisms by toxicants, an electrochemical method has been developed to measure the current variation of a mediator in the presence of microorganisms contacted with a toxicant. Microelectrode arrays were adopted in this study, which can accelerate the mass transfer rate of an analyte to the electrode and also increase the total current signal, resulting in an improvement in detection sensitivity. We selected Escherichia coli as the testee and the standard glucose-glutamic acid as an exogenous material. Under oxygen restriction, the experiments in the presence of toxicant were performed at optimum conditions (solution pH 7.0, 37 degrees C and reaction for 3 hr). The resulting solution was then separated from the suspended microorganisms and was measured by an electrochemical method, using ferricyanide as a mediator. The current signal obtained represents the reoxidation of ferrocyanide, which was transformed to inhibiting efficiency, IC50, as a quantitative measure of toxicity. The IC50 values measured were 410, 570 and 830 mg/L for sodium nitrite, borax and aluminum potassium sulfate, respectively. The results show that the toxicity sequence for these three food additives is consistent with the value reported by other methods. Furthermore, the order of damage degree to the microorganism was also observed to be: sodium nitrite > borax > aluminum potassium sulfate > blank, according to the atomic force microscopy images of E. coli after being incubated for 3 hr with the toxic compound in buffer solutions. The electrochemical method is expected to be a sensitive and simple alternative to toxicity screening for chemical food additives.

  13. Bias Correction Methods Explain Much of the Variation Seen in Breast Cancer Risks of BRCA1/2 Mutation Carriers.

    Science.gov (United States)

    Vos, Janet R; Hsu, Li; Brohet, Richard M; Mourits, Marian J E; de Vries, Jakob; Malone, Kathleen E; Oosterwijk, Jan C; de Bock, Geertruida H

    2015-08-10

    Recommendations for treating patients who carry a BRCA1/2 gene are mainly based on cumulative lifetime risks (CLTRs) of breast cancer determined from retrospective cohorts. These risks vary widely (27% to 88%), and it is important to understand why. We analyzed the effects of methods of risk estimation and bias correction and of population factors on CLTRs in this retrospective clinical cohort of BRCA1/2 carriers. The following methods to estimate the breast cancer risk of BRCA1/2 carriers were identified from the literature: Kaplan-Meier, frailty, and modified segregation analyses with bias correction consisting of including or excluding index patients combined with including or excluding first-degree relatives (FDRs) or different conditional likelihoods. These were applied to clinical data of BRCA1/2 families derived from our family cancer clinic for whom a simulation was also performed to evaluate the methods. CLTRs and 95% CIs were estimated and compared with the reference CLTRs. CLTRs ranged from 35% to 83% for BRCA1 and 41% to 86% for BRCA2 carriers at age 70 years width of 95% CIs: 10% to 35% and 13% to 46%, respectively). Relative bias varied from -38% to +16%. Bias correction with inclusion of index patients and untested FDRs gave the smallest bias: +2% (SD, 2%) in BRCA1 and +0.9% (SD, 3.6%) in BRCA2. Much of the variation in breast cancer CLTRs in retrospective clinical BRCA1/2 cohorts is due to the bias-correction method, whereas a smaller part is due to population differences. Kaplan-Meier analyses with bias correction that includes index patients and a proportion of untested FDRs provide suitable CLTRs for carriers counseled in the clinic. © 2015 by American Society of Clinical Oncology.

  14. Method and apparatus for the treatment of radioactive or toxic waste waters

    Energy Technology Data Exchange (ETDEWEB)

    Hofstaetter, K; Glock, J; Jakusch, H

    1976-05-26

    A method is described which proposes to store radioactive or toxic waste water in a binder, e.g. bitumen, for disposal. First of all, the liquid contained in the waste water is evaporated so that the radioactive or toxic part remains in solid form. This solid, whose specific gravity must be higher than that of the binder, is put on the surface of the binder, e.g. bitumen. Due to gravity it is embedded by sedimentation and completely covered by the binder. An apparatus with two variants to carry out the process is described, with particular emphasis on the advantages as compared to conventional methods.

  15. Toxicity of ionic liquids: Database and prediction via quantitative structure–activity relationship method

    International Nuclear Information System (INIS)

    Zhao, Yongsheng; Zhao, Jihong; Huang, Ying; Zhou, Qing; Zhang, Xiangping; Zhang, Suojiang

    2014-01-01

    Highlights: • A comprehensive database on toxicity of ionic liquids (ILs) was established. • Relationship between structure and toxicity of IL has been analyzed qualitatively. • Two new QSAR models were developed for predicting toxicity of ILs to IPC-81. • Accuracy of proposed nonlinear SVM model is much higher than the linear MLR model. • The established models can be explored in designing novel green agents. - Abstract: A comprehensive database on toxicity of ionic liquids (ILs) is established. The database includes over 4000 pieces of data. Based on the database, the relationship between IL's structure and its toxicity has been analyzed qualitatively. Furthermore, Quantitative Structure–Activity relationships (QSAR) model is conducted to predict the toxicities (EC 50 values) of various ILs toward the Leukemia rat cell line IPC-81. Four parameters selected by the heuristic method (HM) are used to perform the studies of multiple linear regression (MLR) and support vector machine (SVM). The squared correlation coefficient (R 2 ) and the root mean square error (RMSE) of training sets by two QSAR models are 0.918 and 0.959, 0.258 and 0.179, respectively. The prediction R 2 and RMSE of QSAR test sets by MLR model are 0.892 and 0.329, by SVM model are 0.958 and 0.234, respectively. The nonlinear model developed by SVM algorithm is much outperformed MLR, which indicates that SVM model is more reliable in the prediction of toxicity of ILs. This study shows that increasing the relative number of O atoms of molecules leads to decrease in the toxicity of ILs

  16. Toxicity assessment of chemical contaminants;transition from in vitromethods to novel in vitro methods

    Directory of Open Access Journals (Sweden)

    A.A. Farshad

    2007-04-01

    Full Text Available Exposure to occupational and environmental contaminants is a major contributor to human health problems. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there areapproximately 80, 000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from ethical, economical and scientific perspectives. Therefore, increasing the number of available industrial chemicals andnew products has created a demand for alternatives to animal methods for better safety evaluation. Recent toxicity studies have demonstrated that in vitro methods are capable of rapidly providing toxicity information. In this review, current toxicity test methods for risk evaluation of industrial chemical contaminants are presented. To evaluate the potential applications of  more recent test methods developed for toxicity testing of chemical contaminants are discussed. Although  to be considered more broadly for risk assessment of human chemical exposures. In vitro methods,in vitro toxicology methods cannot exactly mimic the biodynamics of the whole body, in vitro  relationships (QSARs and physiologically based toxicokinetic (PBTK models have a potentialtest systems in combination with the knowledge of quantitative structure activity.

  17. Inhalation method for delivery of nanoparticles to the Drosophila respiratory system for toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Posgai, Ryan; Ahamed, Maqusood [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Hussain, Saber M. [Applied Biotechnology Branch, Human Effectiveness Directorate Air Force Research Laboratory/RHBP, Wright-Patterson Air Force Base, OH, 45433 (United States); Rowe, John J. [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Nielsen, Mark G., E-mail: Mark.Nielsen@notes.udayton.edu [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States)

    2009-12-20

    The growth of the nanotechnology industry and subsequent proliferation of nanoparticle types present the need to rapidly assess nanoparticle toxicity. We present a novel, simple and cost-effective nebulizer-based method to deliver nanoparticles to the Drosophila melanogaster respiratory system, for the purpose of toxicity testing. FluoSpheres (registered) , silver, and CdSe/ZnS nanoparticles of different sizes were effectively aerosolized, showing the system is capable of functioning with a wide range of nanoparticle types and sizes. Red fluorescent CdSe/ZnS nanoparticles were successfully delivered to the fly respiratory system, as visualized by fluorescent microscopy. Silver coated and uncoated nanoparticles were delivered in a toxicity test, and induced Hsp70 expression in flies, confirming the utility of this model in toxicity testing. This is the first method developed capable of such delivery, provides the advantage of the Drosophila health model, and can serve as a link between tissue culture and more expensive mammalian models in a tiered toxicity testing strategy.

  18. Inhalation method for delivery of nanoparticles to the Drosophila respiratory system for toxicity testing

    International Nuclear Information System (INIS)

    Posgai, Ryan; Ahamed, Maqusood; Hussain, Saber M.; Rowe, John J.; Nielsen, Mark G.

    2009-01-01

    The growth of the nanotechnology industry and subsequent proliferation of nanoparticle types present the need to rapidly assess nanoparticle toxicity. We present a novel, simple and cost-effective nebulizer-based method to deliver nanoparticles to the Drosophila melanogaster respiratory system, for the purpose of toxicity testing. FluoSpheres (registered) , silver, and CdSe/ZnS nanoparticles of different sizes were effectively aerosolized, showing the system is capable of functioning with a wide range of nanoparticle types and sizes. Red fluorescent CdSe/ZnS nanoparticles were successfully delivered to the fly respiratory system, as visualized by fluorescent microscopy. Silver coated and uncoated nanoparticles were delivered in a toxicity test, and induced Hsp70 expression in flies, confirming the utility of this model in toxicity testing. This is the first method developed capable of such delivery, provides the advantage of the Drosophila health model, and can serve as a link between tissue culture and more expensive mammalian models in a tiered toxicity testing strategy.

  19. Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

    Science.gov (United States)

    Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

    2010-09-17

    Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows.

    Science.gov (United States)

    Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Rawlings, Jane M; Belanger, Scott E; Oris, James T

    2014-11-01

    An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. © 2014 SETAC.

  1. A NEW APPROACH FOR CULTURING LEMNA MINOR (DUCKWEED) AND STANDARDIZED METHOD FOR USING ATRAZINE AS A REFERENCE TOXICANT

    Science.gov (United States)

    Lemna minor (Duckweed) is commonly used in aquatic toxicity investigations. Methods for culturing and testing with reference toxicants, such as atrazine, are somewhat variable among researchers. Our goal was to develop standardized methods of culturing and testing for use with L....

  2. [Investigation of potential toxic factors for fleece-flower root: from perspective of processing methods evolution].

    Science.gov (United States)

    Cui, He-Rong; Bai, Zhao-Fang; Song, Hai-Bo; Jia, Tian-Zhu; Wang, Jia-Bo; Xiao, Xiao-He

    2016-01-01

    In recent years, the rapid growth of reports on fleece-flower root-caused liver damages has drawn wide attention of both at home and abroad, however, there were rare literature on toxicology of fleece-flower root in ancient Chinese medicine. But why there are so many reports on toxicology of fleece-flower root now compared with the ancient literature? As a typical tonic medicine, the clinical utility of fleece-flower root was largely limited by its standardization and reliability of processing methods in ancient Chinese medicine. The ancient processing methods of fleece-flower root emphasized nine times of steaming and nine times of drying, while the modern processes have been simplified into one time of steaming. Whether the differences between ancient and modern processing methods are the potential cause of the increased events of fleece-flower root-caused liver damages. We will make deep analysis and provide new clues and perspectives for the research on its toxicity. This article, therefore, would discuss the affecting factors and key problems in toxicity attenuation of fleece-flower root on the basis of sorting out the processing methods of fleece-flower root in ancient medical books and modern standards, in order to provide the reference for establishing specification for toxicity attenuation of fleece-flower root. Copyright© by the Chinese Pharmaceutical Association.

  3. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs

    Science.gov (United States)

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty

    2016-01-01

    Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used

  4. A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay

    International Nuclear Information System (INIS)

    Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

    2010-01-01

    The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle ≤ 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC 50 values for cadmium for automated measurements (176-192 μM) were comparable to those previously reported for a 72-h exposure using manual counting (151 μM). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms.

  5. A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone

    International Nuclear Information System (INIS)

    Hatch, G.E.; Koren, H.; Aissa, M.

    1989-01-01

    Present models for predicting the pulmonary toxicity of O 3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O 3 mass balance and species comparisons of mechanisms that protect tissue against O 3 . The goal of the study described was to identify a method to directly compare O 3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O 3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18 O-labeled O 3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O 3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O 3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18 O 3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O 3 to alveoli of animals or humans

  6. Characterization and toxicity studies of bioglass by Sol-gel method for prostate cancer therapy

    International Nuclear Information System (INIS)

    Roberto, Wanderley S.; Veloso, Gabriela A.; Silva, Luciana; Campos, Tarcísio P.R.

    2017-01-01

    One of the most advanced methods for the treatment of prostate cancer in the initial stage is brachytherapy, which uses titanium seeds, incorporated with 125 I, which is radioactive, and which is implanted in the prosthetic volume. In recent studies, we investigated the possibility of applying the Sol-Gel (SG) method for the production of bioactive seeds, incorporated with radioactive Sm in silica glasses for the treatment of cancer. In this project three compositions of the glasses of the SiO 2 -CaO system were synthesized using the SG method. The chemical and physical composition of the seeds were analyzed by X-ray diffraction and Atomic Absorption Analysis. A pilot study of in vivo and in vitro toxicity was conducted in rabbit and PC-3 lineage cells. The results showed that the ceramic matrices in the SiO 2 - CaO - Sm system present no toxicity in the in vivo model presenting no post-implant inflammatory process. None restriction of in vitro cell growth was found. In conclusion, there is no toxicity in seeds and the radiotoxicity will occur only in the period in which the seeds present activity coming from 153 Sm

  7. BAYESIAN DATA AUGMENTATION DOSE FINDING WITH CONTINUAL REASSESSMENT METHOD AND DELAYED TOXICITY

    Science.gov (United States)

    Liu, Suyu; Yin, Guosheng; Yuan, Ying

    2014-01-01

    A major practical impediment when implementing adaptive dose-finding designs is that the toxicity outcome used by the decision rules may not be observed shortly after the initiation of the treatment. To address this issue, we propose the data augmentation continual re-assessment method (DA-CRM) for dose finding. By naturally treating the unobserved toxicities as missing data, we show that such missing data are nonignorable in the sense that the missingness depends on the unobserved outcomes. The Bayesian data augmentation approach is used to sample both the missing data and model parameters from their posterior full conditional distributions. We evaluate the performance of the DA-CRM through extensive simulation studies, and also compare it with other existing methods. The results show that the proposed design satisfactorily resolves the issues related to late-onset toxicities and possesses desirable operating characteristics: treating patients more safely, and also selecting the maximum tolerated dose with a higher probability. The new DA-CRM is illustrated with two phase I cancer clinical trials. PMID:24707327

  8. The analysis of toxic connections content in water by spectral methods

    Science.gov (United States)

    Plotnikova, I. V.; Chaikovskaya, O. N.; Sokolova, I. V.; Artyushin, V. R.

    2017-08-01

    The current state of ecology means the strict observance of measures for the utilization of household and industrial wastes that is connected with very essential expenses of means and time. Thanks to spectroscopic devices usage the spectral methods allow to carry out the express quantitative and qualitative analysis in a workplace and field conditions. In a work the application of spectral methods by studying the degradation of toxic organic compounds after preliminary radiation of various sources is shown. Experimental data of optical density of water at various influences are given.

  9. Different rectal toxicity tolerance with and without simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving hypofractionated prostate radiotherapy

    International Nuclear Information System (INIS)

    McDonald, Andrew M; Baker, Christopher B; Popple, Richard A; Shekar, Kiran; Yang, Eddy S; Jacob, Rojymon; Cardan, Rex; Kim, Robert Y; Fiveash, John B

    2014-01-01

    To investigate added morbidity associated with the addition of pelvic elective nodal irradiation (ENI) to hypofractionated radiotherapy to the prostate. Two-hundred twelve patients, treated with hypofractionated radiotherapy to the prostate between 2004 and 2011, met the inclusion criteria for the analysis. All patients received 70 Gy to the prostate delivered over 28 fractions and 103 (49%) received ENI consisting of 50.4 Gy to the pelvic lymphatics delivered simultaneously in 1.8 Gy fractions. The mean dose-volume histograms were compared between the two subgroups defined by use of ENI, and various dose-volume parameters were analyzed for effect on late lower gastrointestinal (GI) and genitourinary (GU) toxicity. Acute grade 2 lower GI toxicity occurred in 38 (37%) patients receiving ENI versus 19 (17%) in those who did not (p = 0.001). The Kaplan-Meier estimate of grade ≥ 2 lower GI toxicity at 3 years was 15.3% for patients receiving ENI versus 5.3% for those who did not (p = 0.026). Each rectal isodose volume was increased for patients receiving ENI up to 50 Gy (p ≤ 0.021 for each 5 Gy increment). Across all patients, the absolute V 70 of the rectum was the only predictor of late GI toxicity. When subgroups, defined by the use of ENI, were analyzed separately, rectal V 70 was only predictive of late GI toxicity for patients who received ENI. For patients receiving ENI, V 70 > 3 cc was associated with an increased risk of late GI events. Elective nodal irradiation increases the rates of acute and late GI toxicity when delivered simultaneously with hypofractioanted prostate radiotherapy. The use of ENI appears to sensitize the rectum to hot spots, therefore we recommend added caution to minimize the volume of rectum receiving 100% of the prescription dose in these patients

  10. Different rectal toxicity tolerance with and without simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving hypofractionated prostate radiotherapy.

    Science.gov (United States)

    McDonald, Andrew M; Baker, Christopher B; Popple, Richard A; Shekar, Kiran; Yang, Eddy S; Jacob, Rojymon; Cardan, Rex; Kim, Robert Y; Fiveash, John B

    2014-06-03

    To investigate added morbidity associated with the addition of pelvic elective nodal irradiation (ENI) to hypofractionated radiotherapy to the prostate. Two-hundred twelve patients, treated with hypofractionated radiotherapy to the prostate between 2004 and 2011, met the inclusion criteria for the analysis. All patients received 70 Gy to the prostate delivered over 28 fractions and 103 (49%) received ENI consisting of 50.4 Gy to the pelvic lymphatics delivered simultaneously in 1.8 Gy fractions. The mean dose-volume histograms were compared between the two subgroups defined by use of ENI, and various dose-volume parameters were analyzed for effect on late lower gastrointestinal (GI) and genitourinary (GU) toxicity. Acute grade 2 lower GI toxicity occurred in 38 (37%) patients receiving ENI versus 19 (17%) in those who did not (p = 0.001). The Kaplan-Meier estimate of grade ≥ 2 lower GI toxicity at 3 years was 15.3% for patients receiving ENI versus 5.3% for those who did not (p = 0.026). Each rectal isodose volume was increased for patients receiving ENI up to 50 Gy (p ≤ 0.021 for each 5 Gy increment). Across all patients, the absolute V70 of the rectum was the only predictor of late GI toxicity. When subgroups, defined by the use of ENI, were analyzed separately, rectal V70 was only predictive of late GI toxicity for patients who received ENI. For patients receiving ENI, V70 > 3 cc was associated with an increased risk of late GI events. Elective nodal irradiation increases the rates of acute and late GI toxicity when delivered simultaneously with hypofractioanted prostate radiotherapy. The use of ENI appears to sensitize the rectum to hot spots, therefore we recommend added caution to minimize the volume of rectum receiving 100% of the prescription dose in these patients.

  11. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance

    NARCIS (Netherlands)

    de Win, Maartje M. L.; Jager, Gerry; Vervaeke, Hylke K. E.; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C.; den Heeten, Gerard J.; Ramsey, Nick F.; Korf, Dirk J.; van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin

  12. Evaluation and modeling of the parameters affecting fluoride toxicity level in aquatic environments by bioassay method

    OpenAIRE

    Hamid Reza Shamsollahi; Hadi asady; Amir Hossein Mahvi; Zahra zolghadr

    2014-01-01

    Background: Fluoride exists in various forms in nature and water resources. , The rising level of fluoride in water resources due to discharge of industrial effluents can cause toxicity in aquatic organisms. To prevent toxicity, it is necessary to determine maximum fluoride toxicity as well as effluent discharge limits. The aim of this study was to determine the maximum fluoride toxicity and the factors affecting fluoride toxicity to provide a model in order to determine the effluent discha...

  13. Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Kahn, Rachel S; Niemierko, Andrzej; Delaney, Thomas F; Russell, Anthony H

    2013-01-01

    To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38–80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach

  14. An easy, rapid and inexpensive method to monitor tributyltin (TBT) toxicity in the laboratory.

    Science.gov (United States)

    Cruz, Andreia; Moreira, Rafael; Mendo, Sónia

    2014-05-01

    Tributyltin (TBT) contamination remains a major problem worldwide. Many laboratories are committed to the development of remediation methodologies that could help reduce the negative impact of this compound in the environment. Furthermore, it is important to have at hand simple methodologies for evaluating TBT toxicity in the laboratory, besides the use of complex and costly analytical instrumentation. With that purpose, a method was adapted that is based on the inhibition of growth of an indicator strain, Micrococcus luteus ATCC 9341, under TBT. Different types of matrices, of TBT concentrations and sample treatments were tested. The results herein reported show that the bioassay method can be applied for both aqueous and soil samples and also for a high range of TBT concentrations (at least up to 500 μmol/L). Besides being cheap and easy to perform, it can be performed in any laboratory. Additionally, one possible application of the method to monitor TBT degradation is presented as an example.

  15. Different Chromatographic Methods for Simultaneous Determination of Mefenamic Acid and Two of Its Toxic Impurities.

    Science.gov (United States)

    Morcoss, Martha M; Abdelwahab, Nada S; Ali, Nouruddin W; Elsaady, Mohammed T

    2017-08-01

    Two sensitive, accurate and precise chromatographic methods mentioned as TLC-densitometric method and RP-HPLC-DAD method, were developed and validated for the simultaneous determination of mefenamic acid (MEF) and its two toxic impurities, benzoic acid (BA) and 2,3-dimethylaniline (DMA). In the proposed TLC-densitometric method a developing system consisting of chloroform:acetone:acetic acid:ammonia solution(70:30:2:2, v/v/v/v) was used, TLC aluminum plates 60 F254 was used as a stationary phase and the separated bands were UV-scanned at 225 nm. While the proposed RP-HPLC-DAD method depended on chromatographic separation on C18 column using 0.05 M KH2PO4 buffer: acetonitrile (40:60, v/v) as a mobile phase at constant flow rate of 1 mL/min with UV detection at 225 nm. Linear relationships were obtained in the ranges of 0.3-2, 0.3-2 and 0.3-1.8 μg/band (for TLC-densitometric method) and in the ranges of 7-50, 10-50 and 7-50 μg/mL (for HPLC-DAD method) for MEF, BA and DMA, respectively. Factors affecting the developed methods have been studied and optimized. Moreover ,the proposed methods were successfully applied for determination of the studied drug in its pharmaceutical dosage form. The methods showed no significance difference when compared with the reported method using F-test and Student's-t test. The low of detection and quantization limits of the proposed methods get them suitable for quality control and stability studies of MEF in pharmaceutical formulation. The developed methods have advantages of being more selective and sensitive than the published methods. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model -

    Directory of Open Access Journals (Sweden)

    Himanshu R Gupta

    2016-12-01

    Full Text Available Objectives: Advancements in nanotechnology have led to nanoparticle (NP use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio. Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED. For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and

  17. Comparison of methods for conducting marine and estuarine sediment porewater toxicity tests—extraction, storage, and handling techniques

    Science.gov (United States)

    Carr, R.S.; Chapman, D.C.

    1995-01-01

    A series of studies was conducted to compare different porewater extraction techniques and to evaluate the effects of sediment and porewater storage conditions on the toxicity of pore water, using assays with the sea urchin Arbacia punctulata. If care is taken in the selection of materials, several different porewater extraction techniques (pressurized squeezing, centrifugation, vacuum) yield samples with similar toxicity. Where the primary contaminants of concern are highly hydrophobic organic compounds, centrifugation is the method of choice for minimizing the loss of contaminants during the extraction procedure. No difference was found in the toxicity of pore water obtained with the Teflon® and polyvinyl chloride pressurized extraction devices. Different types of filters in the squeeze extraction devices apparently adsorbed soluble contaminants to varying degrees. The amount of fine suspended particulate material remaining in the pore water after the initial extraction varied among the methods. For most of the sediments tested, freezing and thawing did not affect the toxicity of porewater samples obtained by the pressurized squeeze extraction method. Pore water obtained by other methods (centrifugation, vacuum) and frozen without additional removal of suspended particulates by centrifugation may exhibit increased toxicity compared with the unfrozen sample.The toxicity of pore water extracted from refrigerated (4°C) sediments exhibited substantial short-term (days, weeks) changes. Similarly, sediment pore water extracted over time from a simulated amphipod solid-phase toxicity test changed substantially in toxicity. For the sediments tested, the direction and magnitude of change in toxicity of pore water extracted from both refrigerated and solid-phase test sediments was unpredictable.

  18. Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review.

    Science.gov (United States)

    Bakand, S; Winder, C; Khalil, C; Hayes, A

    2005-12-01

    Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.

  19. A method for measuring sulfide toxicity in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Livshits, Leonid; Gross, Einav

    2017-01-01

    Cysteine catabolism by gut microbiota produces high levels of sulfide. Excessive sulfide can interfere with colon function, and therefore may be involved in the etiology and risk of relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide. Therefore, it is crucial to understand how cells/animals regulate the detoxification of sulfide generated by bacterial cysteine catabolism in the gut. Here we describe a simple and cost-effective way to explore the mechanism of sulfide toxicity in the nematode Caenorhabditis elegans ( C. elegans ). •A rapid cost-effective method to quantify and study sulfide tolerance in C. elegans and other free-living nematodes.•A cost effective method to measure the concentration of sulfide in the inverted plate assay.

  20. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs: - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model.

    Science.gov (United States)

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty; Thakur, Mansee

    2016-12-01

    model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

  1. Methods for the calculation of derived working limits for surface contamination by low-toxicity radionuclides

    International Nuclear Information System (INIS)

    Gibson, J.A.B.; Wrixon, A.D.

    1979-01-01

    Surface contamination is often measured as an indication of the general spread of radioactive contamination in a particular place. Derived working limits, (DWLs) for surface contamination provide figures against which to assess the significance of measurements. Derived working limits for surface contamination were first established for use in the nuclear energy industry. They were designed to cope with a wide range of unspecified radionuclides and were therefore based on the assumption that the contamination was due to the presence of the most hazardous radionuclides, e.g. 90 Sr, 210 Pb, 226 Ra and 239 Pu. While this assumption may still be appropriate when the radionuclide mixture is unknown, there are now many specialized uses of particular low-toxicity radionuclides in universities, hospitals and general industry. If it is known that only a particular radionuclide is present, the general DWL can be replaced by a more specific value. The methods for calculating DWLs for some of the more commonly employed low-toxicity radionuclides are described. The exposure pathways considered are (a) external radiation of the skin and inhalation of airborne material from contaminated surfaces in active areas; (b) external irradiation of the skin and ingestion from contaminated skin. Some consideration is given to the effect of the revised dose equivalent limits in the most recent recommendations of ICRP. (author)

  2. Toxicity of potassium chloride to veliger and byssal stage dreissenid mussels related to water quality

    Science.gov (United States)

    Moffitt, Christine M.; Stockton-Fiti, Kelly A.; Claudi, Renata

    2016-01-01

    Natural resource managers are seeking appropriate chemical eradication and control protocols for infestations of zebra mussels, Dreissena polymorpha (Pallas, 1769), and quagga mussels. D. rostiformis bugensis (Andrusov, 1897) that have limited effect on non-target species. Applications of low concentrations of potassium salt (as potash) have shown promise for use where the infestation and treatment can be contained or isolated. To further our understanding of such applications and obtain data that could support a pesticide registration, we conducted studies of the acute and chronic toxicity of potassium chloride to dreissenid mussels in four different water sources from infested and non-infested locations (ground water from northern Idaho, surface water from the Snake River, Idaho, USA, surface water from Lake Ontario, Ontario, Canada, and surface water from the Colorado River, Arizona, USA). We found short term exposure of veligers (29 d) at concentrations of 100 and 200 mg/L KCl. Rapid mortality occurred within 10 d of exposure to concentrations of 200 mg/L KCl, regardless of water source. Kaplan-Meier estimates of mean survival of byssal mussels in 100 mg/L KCl prepared in surface water from Idaho and Lake Ontario were 4.9 or 6.9 d, respectively; however, mean survival of mussels tested in the Colorado River water was > 23 d. The sodium content of the Colorado River water was nearly three times that measured in waters from the other locations, and we hypothesized sodium concentrations may affect mussel survival. To test our hypothesis, we supplemented Snake River and Lake Ontario water with NaCl to equivalent conductivity as the Colorado River, and found mussel survival increased to levels observed in tests of veliger and byssal mussels in Colorado River water. We recommend KCl disinfection and eradication protocols must be developed to carefully consider the water quality characteristics of treatment locations.

  3. Comparative analysis of the toxic effects of natural toxins and harmful substances produced by conventional processing methods or by irradiation and of toxicity tests

    International Nuclear Information System (INIS)

    Dahlhelm, H.; Arndt, K.; Groeger, G.; Schreiber, G.A.; Boegl, K.W.

    1994-01-01

    In this review, tasks and methods of food toxicology as well as the application of the different toxicity tests for the risk assessment of food ingredients are described. Particular reference is made to short-term genotoxicity tests. Enzymatic digestion and extraction methods for complex foodstuffs which are used in the toxicological testing of foods in in vitro systems are described. Radiolytic products which result from irradiation of foods or components of foodstuffs and corresponding results of toxicity testing are reviewed. Foodstuffs irradiated with doses of up to 10 kGy are regarded as toxicologically safe. A survey of the toxicologically tested irradiated foodstuffs as well as the applied maximum doses are given in tables at the end of chapter 8. Among the great number of toxicological studies of irradiated foods those are especially mentioned which have given rise to discussions on the health risks involved. In addition, the difficulties associated with the testing of toxicity of irradiated foodstuffs in feeding experiments are discussed. Short-term tests used to establish the benotoxicity of irradiated foods and essential results of toxicological testing are also presented in tables. An overview is given of the occurrence, frequency and health risks of natural toxins in foods and harmful substances produced by conventional methods of cooking and preservation, in order to enable a comparison with the health risks of irradiated foods. The relevance of animal experiments and in vitro investigations for the prediction of toxic effects of harmful substances of foodstuffs in man is discussed in the final chapter. (VHE) [de

  4. A highly efficient nonchemical method for isolating live nematodes (Caenorhabditis elegans) from soil during toxicity assays.

    Science.gov (United States)

    Kim, Shin Woong; Moon, Jongmin; An, Youn-Joo

    2015-01-01

    The success of soil toxicity tests using Caenorhabditis elegans may depend in large part on recovering the organisms from the soil. However, it can be difficult to learn the International Organization for Standardization/ASTM International recovery process that uses the colloidal silica flotation method. The present study determined that a soil-agar isolation method provides a highly efficient and less technically demanding alternative to the colloidal silica flotation method. Test soil containing C. elegans was arranged on an agar plate in a donut shape, a linear shape, or a C curve; and microbial food was placed outside the soil to encourage the nematodes to leave the soil. The effects of ventilation and the presence of food on nematode recovery were tested to determine the optimal conditions for recovery. A linear arrangement of soil on an agar plate that was sprinkled with microbial food produced nearly 83% and 90% recovery of live nematodes over a 3-h and a 24-h period, respectively, without subjecting the nematodes to chemical stress. The method was tested using copper (II) chloride dihydrate, and the resulting recovery rate was comparable to that obtained using colloidal silica flotation. The soil-agar isolation method portrayed in the present study enables live nematodes to be isolated with minimal additional physicochemical stress, making it a valuable option for use in subsequent sublethal tests where live nematodes are required. © 2014 SETAC.

  5. In silico prediction of Tetrahymena pyriformis toxicity for diverse industrial chemicals with substructure pattern recognition and machine learning methods.

    Science.gov (United States)

    Cheng, Feixiong; Shen, Jie; Yu, Yue; Li, Weihua; Liu, Guixia; Lee, Philip W; Tang, Yun

    2011-03-01

    There is an increasing need for the rapid safety assessment of chemicals by both industries and regulatory agencies throughout the world. In silico techniques are practical alternatives in the environmental hazard assessment. It is especially true to address the persistence, bioaccumulative and toxicity potentials of organic chemicals. Tetrahymena pyriformis toxicity is often used as a toxic endpoint. In this study, 1571 diverse unique chemicals were collected from the literature and composed of the largest diverse data set for T. pyriformis toxicity. Classification predictive models of T. pyriformis toxicity were developed by substructure pattern recognition and different machine learning methods, including support vector machine (SVM), C4.5 decision tree, k-nearest neighbors and random forest. The results of a 5-fold cross-validation showed that the SVM method performed better than other algorithms. The overall predictive accuracies of the SVM classification model with radial basis functions kernel was 92.2% for the 5-fold cross-validation and 92.6% for the external validation set, respectively. Furthermore, several representative substructure patterns for characterizing T. pyriformis toxicity were also identified via the information gain analysis methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Method to prepare essentially organic waste liquids containing radioactive or toxic materials

    International Nuclear Information System (INIS)

    Baehr, W.; Drobnik, S.H.; Hild, W.; Kroebel, R.; Meyer, A.; Naumann, G.

    1976-01-01

    Waste solutions occuring in nuclear technology containing radioactive or toxic materials can be solidified by mixing with a polymerisable mixture with subsequent polymerization. An improvement of this method, especially for liquids in which the radioactive components are present as organic compounds is achieved by adding a mixture of at least one monomeric vinyl compound, at least one polyvinyl compound and appropriate catalysts and by polymerizing at temperatures between 15 and 150 0 C. Should the waste liquid contain mineral acid, this is first neutralized by the addition of CaO or MgO. In processing oils or soaps, the addition of swelling agent for polystyrol resins is advantageous. 16 examples illustrate the invention. (UWI) [de

  7. Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

    Science.gov (United States)

    Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

    2018-02-01

    Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon ® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC. © 2017 SETAC.

  8. Development of a suitable test method for evaluating the toxicity of contaminated soils to earthworms in Canada

    Energy Technology Data Exchange (ETDEWEB)

    Stephenson, G.L. [Univ. of Guelph, Ontario (Canada); Scroggins, R. [Environment Canada, Gloucester, Ontario (Canada). Method Development and Application Section

    1995-12-31

    Environment Canada has embarked on a five year program to develop, standardize, and validate a battery of soil toxicity tests which can be used to assess the relative toxicity of contaminants in soils to terrestrial organisms. These tests must be applicable to soil conditions typically found in Canadian environments and the test species must be representative of the species of soil invertebrates or plants inhabiting soil ecosystems in Canada. One of the toxicity tests being developed is designed to assess the toxicity of contaminated soils to earthworms. Five of the potential test species belong to the Lumbricidae family and include the Canadian worm (Allobophora calignosa/Aporrectodea tuberculate), the European bark worm (Dendrodtilus rubidus (rubida)), the pink soil worm (Eisenia rosea), the red marsh worm (Lumbricus rubellus), and the Canadian night crawler or dew worm (Lumbricus terrestris). The sixth species, the white pot worm (Enchytraeus albidus), belongs to the Enchytraeidae family. Further assessment reduced the number of representative species to three. Most earthworm test methods have been developed to assess the toxicity of chemically-spiked artificial soils to Eisenia fetida or E. andrei. Test methods have also been developed to assess the relative toxicity of contaminated soils from hazardous waste sites. Comparative acute toxicity data for three species of earthworm exposed to a hydrocarbon contamination will be presented. Comparative toxicity data for the same three species of earthworm will also be presented using test procedures and conditions that have been modified to accommodate biological differences among the species of earthworm. Recommendations regarding test design, methods, and conditions optimal for each test species will be summarized and discussed with respect to the precision of test results.

  9. Comparison of the common spatial interpolation methods used to analyze potentially toxic elements surrounding mining regions.

    Science.gov (United States)

    Ding, Qian; Wang, Yong; Zhuang, Dafang

    2018-04-15

    The appropriate spatial interpolation methods must be selected to analyze the spatial distributions of Potentially Toxic Elements (PTEs), which is a precondition for evaluating PTE pollution. The accuracy and effect of different spatial interpolation methods, which include inverse distance weighting interpolation (IDW) (power = 1, 2, 3), radial basis function interpolation (RBF) (basis function: thin-plate spline (TPS), spline with tension (ST), completely regularized spline (CRS), multiquadric (MQ) and inverse multiquadric (IMQ)) and ordinary kriging interpolation (OK) (semivariogram model: spherical, exponential, gaussian and linear), were compared using 166 unevenly distributed soil PTE samples (As, Pb, Cu and Zn) in the Suxian District, Chenzhou City, Hunan Province as the study subject. The reasons for the accuracy differences of the interpolation methods and the uncertainties of the interpolation results are discussed, then several suggestions for improving the interpolation accuracy are proposed, and the direction of pollution control is determined. The results of this study are as follows: (i) RBF-ST and OK (exponential) are the optimal interpolation methods for As and Cu, and the optimal interpolation method for Pb and Zn is RBF-IMQ. (ii) The interpolation uncertainty is positively correlated with the PTE concentration, and higher uncertainties are primarily distributed around mines, which is related to the strong spatial variability of PTE concentrations caused by human interference. (iii) The interpolation accuracy can be improved by increasing the sample size around the mines, introducing auxiliary variables in the case of incomplete sampling and adopting the partition prediction method. (iv) It is necessary to strengthen the prevention and control of As and Pb pollution, particularly in the central and northern areas. The results of this study can provide an effective reference for the optimization of interpolation methods and parameters for

  10. Different Spectrophotometric and Chromatographic Methods for Determination of Mepivacaine and Its Toxic Impurity.

    Science.gov (United States)

    Abdelwahab, Nada S; Fared, Nehal F; Elagawany, Mohamed; Abdelmomen, Esraa H

    2017-09-01

    Stability-indicating spectrophotometric, TLC-densitometric, and ultra-performance LC (UPLC) methods were developed for the determination of mepivacaine HCl (MEP) in the presence of its toxic impurity, 2,6-dimethylanaline (DMA). Different spectrophotometric methods were developed for the determination of MEP and DMA. In a dual-wavelength method combined with direct spectrophotometric measurement, the absorbance difference between 221.4 and 240 nm was used for MEP measurements, whereas the absorbance at 283 nm was used for measuring DMA in the binary mixture. In the second-derivative method, amplitudes at 272.2 and 232.6 nm were recorded and used for the determination of MEP and DMA, respectively. The developed TLC-densitometric method depended on chromatographic separation using silica gel 60 F254 TLC plates as a stationary phase and methanol-water-acetic acid (9 + 1 + 0.1, v/v/v) as a developing system, with UV scanning at 230 nm. The developed UPLC method depended on separation using a C18 column (250 × 4.6 mm id, 5 μm particle size) as a stationary phase and acetonitrile-water (40 + 60, v/v; pH 4 with phosphoric acid) as a mobile phase at a flow rate of 0.4 mL/min, with UV detection at 215 nm. The chromatographic run time was approximately 1 min. The proposed methods were validated with respect to International Conference on Harmonization guidelines regarding precision, accuracy, ruggedness, robustness, and specificity.

  11. Dredged Material Evaluations: Review of Zooplankton Toxicity Test Methods for Marine Water Quality Evaluations

    Science.gov (United States)

    2016-09-01

    term impacts of the DM while settling through the water column (elutriate toxicity tests), and long-term toxicity (whole sediment toxicity tests) and...elutriates are prepared according to guidance (USEPA/USACE 1991; 1998) by mixing sediment and site water and allowing settling for prescribed periods...of water and waste water . 17th ed. Washington, DC: APHA. Arnold, W. R., R. L. Diamond, and D. S. Smith. 2010a. The effects of salinity, pH, and

  12. Application of mercurometric analysis methods to radioactive (and/or toxic) samples: Pycnometry and porosimetry

    International Nuclear Information System (INIS)

    Sannen, L.

    1991-01-01

    The analytical tools and methods used in the laboratory of High and Medium Activity of the Nuclear Research Centre in Mol to determine the density and the open porosity of radioactive (and/or toxic) samples are described. The density is determined by a vacuum pycnometer with plunger displacement. This home-made apparatus has been automated up to a high degree so that operation is easily performed in the remote handling conditions of a hot cell environment. The amount of mercury displaced by the sample is measured. The accuracy is better than 0.2 %. The porosimeter is a commercial apparatus which was modified to improve the hot cell compatibility and to provide fast processing of the data. The open porosity and its pore size distribution are determined from the measurement of the amount of mercury intruded into the sample under increasing pressure. The paper describes both instruments and the working methods. Also included are some examples of measurement results. (author). 5 figs

  13. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

    International Nuclear Information System (INIS)

    Thaler, Josef; Köhne, Claus-Henning; Karthaus, Meinolf; Mineur, Laurent; Greil, Richard; Letocha, Henry; Hofheinz, Ralf; Fernebro, Eva; Gamelin, Erick; Baños, Ana

    2012-01-01

    Integument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity. First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. ClinicalTrials.gov NCT00508404

  14. Quantitative Characterization of the Toxicities of Cd-Ni and Cd-Cr Binary Mixtures Using Combination Index Method

    Directory of Open Access Journals (Sweden)

    Lingyun Mo

    2016-01-01

    Full Text Available Direct equipartition ray design was used to construct Cd-Ni and Cd-Cr binary mixtures. Microplate toxicity analysis was used to evaluate the toxicity of individual substance and the Cd-Ni and Cd-Cr mixtures on Chlorella pyrenoidosa and Selenastrum capricornutum. The interacting toxicity of the mixture was analyzed with concentration addition (CA model. In addition, combination index method (CI was proposed and used to quantitatively characterize the toxicity of the binary mixtures of Cd-Ni and Cd-Cr observed in experiment and find the degree of deviation from the predicted outcome of the CA model, that is, the intensity of interacting toxicity. Results indicate that most of the 20 binary mixtures exhibit enhancing and synergistic effect, and only Cd-Cr-R4 and Cd-Cr-R5 mixtures have relatively high antagonistic effects against C. pyrenoidosa. Based on confidence interval, CI can compare the intensities of interaction of the mixtures under varying levels of effect. The characterization methods are applicable for analyzing binary mixture with complex interaction.

  15. Determination of Antioxidant Activity and Toxicity of Sambucus nigra Fruit Extract Using Alternative Methods

    Directory of Open Access Journals (Sweden)

    Elena Doroftei

    2012-01-01

    Full Text Available The aim of the study is to measure the in vitro antioxidant activity of elderberry (Sambucus nigra fruit extract and to study its toxicity in a plant model system with regard to its possible application in food and agricultural industry. The antioxidant capacity of Sambucus nigra fruit powder was quantified by a photochemiluminescence method. The study of phytotoxicity of aqueous solutions of powder extract was performed using Allium cepa as a test organism. Photochemiluminescence determinations showed a very high antioxidant capacity of the product but also revealed its cytotoxic effect, along with mitodepressive activity and even inhibiton of mitosis at the preprophase stage when the fruit extract was used at higher concentrations. Aqueous solutions of the fruit powder have a reasonably expressed mutagenic activity in vivo on the radicles of Allium cepa, especially when they are used at a concentration of 1 g/dL for a prolonged time (48 h. At lower concentrations (0.1 g/dL, however, the mutagenic effect was not observed any more. The conclusion of our study is that Sambucus nigra fruit extract powder has a very high in vitro antioxidant activity and no mutagenic effects at low concentrations, which makes it recommendable for applications in the food industry.

  16. Toxicity and bioaccumulation of sediment-associated contaminants using freshwater invertebrates: A review of methods and applications

    Science.gov (United States)

    Ingersoll, C.G.; Ankley, G.T.; Benoit, D.A.; Brunson, E.L.; Burton, G.A.; Dwyer, F.J.; Hoke, R.A.; Landrum, P.F.; Norberg-King, T. J.; Winger, P.V.

    1995-01-01

    This paper reviews recent developments in methods for evaluating the toxicity and bioaccumulation of contaminants associated with freshwater sediments and summarizes example case studies demonstrating the application of these methods. Over the past decade, research has emphasized development of more specific testing procedures for conducting 10-d toxicity tests with the amphipod Hyalella azteca and the midge Chironomus tentans. Toxicity endpoints measured in these tests are survival for H. azteca and survival and growth for C. tentans. Guidance has also been developed for conducting 28-d bioaccumulation tests with the oligochaete Lumbriculus variegatus, including determination of bioaccumulation kinetics for different compound classes. These methods have been applied to a variety of sediments to address issues ranging from site assessments to bioavailability of organic and inorganic contaminants using field-collected and laboratory-spiked samples. Survival and growth of controls routinely meet or exceed test acceptability criteria. Results of laboratory bioaccumulation studies with L. variegatus have been confirmed with comparisons to residues (PCBs, PAHs, DDT) present from synoptically collected field populations of oligochaetes. Additional method development is currently underway to develop chronic toxicity tests and to provide additional data-confirming responses observed in laboratory sediment tests with natural benthic populations.

  17. Evaluation and improvements of a mayfly, Neocloeon (Centroptilum) triangulifer (Ephemeroptera: Baetidae) toxicity test method - SETAC Europe 2016

    Science.gov (United States)

    A recently published test method for Neocloeon triangulifer assessed the survival and growth of larval mayflies exposed to several reference toxicants (NaCl, KCl, and CuSO4). Results were not able to be replicated in subsequent experiments. To identify potential sources of variab...

  18. A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing

    Science.gov (United States)

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...

  19. UNDERSTANDING AND ACCOUNTING FOR METHOD VARIABILITY IN WHOLE EFFLUENT TOXICITY APPLICATIONS UNDER THE NPDES PROGRAM

    Science.gov (United States)

    This chapter provides a brief introduction to whole effluent toxicity (WET) testing and describes the regulatory background and context of WET testing. This chapter also describes the purpose of this document and outlines the issues addressed in each chapter.

  20. What Food and Feeding Rates are Optimum for the Chironomus dilutus Sediment Toxicity Test Method?

    Science.gov (United States)

    Laboratory tests with benthic macroinvertebrates are commonly used to assess the toxicity of both contaminated sediments and individual chemicals. Among the standard procedures for benthic macroinvertebrates are 10-d, 20-d, and life cycle exposures using the midge, Chironomus ...

  1. COMPUTER-BASED PREDICTION OF TOXICITY USING THE ELECTRON-CONFORMATIONAL METHOD. APPLICATION TO FRAGRANCE ALLERGENS AND OTHER ENVIRONMENTAL POLLUTANTS

    Directory of Open Access Journals (Sweden)

    Natalia N. Gorinchoy

    2012-06-01

    Full Text Available The electron-conformational (EC method is employed for the toxicophore (Tph identification and quantitative prediction of toxicity using the training set of 24 compounds that are considered as fragrance allergens. The values of a=LD50 in oral exposure of rats were chosen as a measure of toxicity. EC parameters are evaluated on the base of conformational analysis and ab initio electronic structure calculations (including solvent influence. The Tph consists of four sites which in this series of compounds are represented by three carbon and one oxygen atoms, but may be any other atoms that have the same electronic and geometric features within the tolerance limits. The regression model taking into consideration the Tph flexibility, anti-Tph shielding, and influence of out-of-Tph functional groups predicts well the experimental values of toxicity (R2 = 0.93 with a reasonable leaveone- out cross-validation.

  2. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

    Science.gov (United States)

    Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

  3. Evaluation of zinc toxicity in soils by means of the CaCl/sub 2/ method

    Energy Technology Data Exchange (ETDEWEB)

    Merkel, D; Koester, W

    1976-01-01

    Soils in the valleys of the rivers Innerste and Oker, north of the Harz mountains, are seriously contaminated by heavy metals. Above all high zinc contents cause severe plant damages. They are like injuries caused by air pollution in the environment of smelting-houses. Usually the heavy metal content of the soil is estimated by extraction with diluted acids, e.g., 0.43 N HNO/sub 3/. In this way nearly the whole zinc store is recorded. For an evaluation of the plant available zinc content we extracted contaminated soils with 0.025 N CaCl/sub 2/. This procedure records the influence of soil properties on the plant availability of the zinc like pH value and clay content. With 0.43 NHNO/sub 3/ 260-7500 ppM zinc were estimated. The maximum content of the CaCl/sub 2/ solution was 109 ppM. Cereals at stage of shooting contained 68-1210 ppM (DM), sugar beet leaves 72-812 ppM (DM). The CaCl/sub 2/ method brought about a closer relationship between soils and plants compared with the HNO/sub 3/ method. Beyond it these method permits the establishment of a preliminary toxicity limit which is supposed in the range of 1 ppM. The percent quota of Zn-CaCl/sub 2/ on Zn-HNO/sub 3/ as a measure of the zinc availability was closely related to the pH value of the soil. The relationship was closer the more soils with lower pH values were present, but there was an essential relationship even at pH levels above 7.0. In the environment of a smelting-house the zinc content of plants was closer related to Zn-HNO/sub 3/ compared with Zn-CaCl/sub 2/. In this case the zinc content of the plants was partly caused by the zinc pollution. But at increasing pH value of the soil even here the availability of the soil zinc decreased too. 33 references.

  4. Development of an accelerated leaching method for incineration bottom ash correlated to toxicity characteristic leaching protocol.

    Science.gov (United States)

    Lin, Shengxuan; Zhou, Xuedong; Ge, Liya; Ng, Sum Huan; Zhou, Xiaodong; Chang, Victor Wei-Chung

    2016-10-01

    Heavy metals and some metalloids are the most significant inorganic contaminants specified in toxicity characteristic leaching procedure (TCLP) in determining the safety of landfills or further utilization. As a consequence, a great deal of efforts had been made on the development of miniaturized analytical devices, such as Microchip Electrophoresis (ME) and μTAS for on-site testing of heavy metals and metalloids to prevent spreading of those pollutants or decrease the reutilization period of waste materials such as incineration bottom ash. However, the bottleneck lied in the long and tedious conventional TCLP that requires 18 h of leaching. Without accelerating the TCLP process, the on-site testing of the waste material leachates was impossible. In this study, therefore, a new accelerated leaching method (ALM) combining ultrasonic assisted leaching with tumbling was developed to reduce the total leaching time from 18 h to 30 min. After leaching, the concentrations of heavy metals and metalloids were determined with ICP-MS or ICP-optical emission spectroscopy. No statistical significance between ALM and TCLP was observed for most heavy metals (i.e., cobalt, manganese, mercury, molybdenum, nickel, silver, strontium, and tin) and metalloids (i.e., arsenic and selenium). For the heavy metals with statistical significance, correlation factors derived between ALM and TCLP were 0.56, 0.20, 0.037, and 0.019 for barium, cadmium, chromium, and lead, respectively. Combined with appropriate analytical techniques (e.g., ME), the ALM can be applied to rapidly prepare the incineration bottom ash samples as well as other environmental samples for on-site determination of heavy metals and metalloids. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. An efficient and reproducible method for improving growth of a soil alga (Chlorococcum infusionum) for toxicity assays.

    Science.gov (United States)

    Nam, Sun-Hwa; An, Youn-Joo

    2015-12-01

    This study evaluated five methods of soil inoculation using the soil alga Chlorococcum infusionum to determine the most efficient and reproducible method for promoting the growth of soil algae for toxicity testing. The five techniques included application of C. infusionum in a circle on top of the soil, to a central spot on top of the soil, to a central spot in the subsoil, to one side on top of the soil, and application divided between a circle and a central spot on top of the soil. Of these, the first method generated the greatest amount of chlorophyll fluorescence and was the method with the best reproducibility. We evaluated the applicability of this method in an assessment of the toxicity of copper and nickel to C. infusionum in two representative standard soils. Copper (20-75 mg/kg for OECD soil and 20-60 mg/kg Lufa 2.2 soil) and nickel (400-500 mg/kg for OECD soil and 60-100 mg/kg Lufa 2.2 soil) reduced the chlorophyll fluorescence of C. infusionum when the inoculation was delivered in a circle on top of both soil types. To our knowledge, this is the first study to assess the suitability of different soil algal inoculation methods for terrestrial toxicity testing. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Long-Term Outcome and Toxicities of Intraoperative Radiotherapy for High-Risk Neuroblastoma

    International Nuclear Information System (INIS)

    Gillis, Amy M.; Sutton, Elizabeth; DeWitt, Kelly D.; Matthay, Katherine K.; Weinberg, Vivian; Fisch, Benjamin M.; Chan, Albert; Gooding, Charles; Daldrup-Link, Heike; Wara, William M.; Farmer, Diana L.; Harrison, Michael R.; Haas-Kogan, Daphne

    2007-01-01

    Purpose: To review a historical cohort of consecutively accrued patients with high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to determine the therapeutic effect and late complications of this treatment. Methods and Materials: Between 1986 and 2002, 31 patients with newly diagnosed high-risk neuroblastoma were treated with IORT as part of multimodality therapy. Their medical records were reviewed to determine the outcome and complications. Kaplan-Meier probability estimates of local control, progression-free survival, and overall survival at 36 months after diagnosis were recorded. Results: Intraoperative radiotherapy to the primary site and associated lymph nodes achieved excellent local control at a median follow-up of 44 months. The 3-year estimate of the local recurrence rate was 15%, less than that of most previously published series. Only 1 of 22 patients who had undergone gross total resection developed recurrence at the primary tumor site. The 3-year estimate of local control, progression-free survival, and overall survival was 85%, 47%, and 60%, respectively. Side effects attributable to either the disease process or multimodality treatment were observed in 7 patients who developed either hypertension or vascular stenosis. These late complications resulted in the death of 2 patients. Conclusions: Intraoperative radiotherapy at the time of primary resection offers effective local control in patients with high-risk neuroblastoma. Compared with historical controls, IORT achieved comparable control and survival rates while avoiding many side effects associated with external beam radiotherapy in young children. Although complications were observed, additional analysis is needed to determine the relative contributions of the disease process and specific components of the multimodality treatment to these adverse events

  7. Determination of Toxic Elements in Cigarettes Smoke, Using Neutron Activation Method

    International Nuclear Information System (INIS)

    Mellawati, J; Chichester D

    1996-01-01

    The purpose of the experiments was to get information of the toxic elements content in cigarettes smoke which could be used to estimate the cigarettes smoke contribution in air pollution. The sample were cigarette smoke from the mixture of 7 popular brand cigarettes collected by The Centre Cigarettes Research, University of kentucky, USA. Neutron activation was done in the Hoger Onderwijs Reactor, IRI Delft Netherlands, using thermal neutron flux 4.8 x 10 16n cm-2 second-1 for 4 hours. Result of the analysis showed that the cigarettes smoke contained Cd, As, Sb, and Br which are toxic elements

  8. [Survival analysis with competing risks: estimating failure probability].

    Science.gov (United States)

    Llorca, Javier; Delgado-Rodríguez, Miguel

    2004-01-01

    To show the impact of competing risks of death on survival analysis. We provide an example of survival time without chronic rejection after heart transplantation, where death before rejection acts as a competing risk. Using a computer simulation, we compare the Kaplan-Meier estimator and the multiple decrement model. The Kaplan-Meier method overestimated the probability of rejection. Next, we illustrate the use of the multiple decrement model to analyze secondary end points (in our example: death after rejection). Finally, we discuss Kaplan-Meier assumptions and why they fail in the presence of competing risks. Survival analysis should be adjusted for competing risks of death to avoid overestimation of the risk of rejection produced with the Kaplan-Meier method.

  9. METHOD EVALUATION TO MEASURE PERSISTENT BIOACCUMULATIVE TOXIC POLLUTANTS IN COW MILK

    Science.gov (United States)

    It is important to understand the persistent and bioaccumulative toxic (PBT) levels in milk, as milk fat may be one of the highest dietary sources of PBT exposure. Analysis of milk also allows the opportunity to investigate geographic variability, as milk is produced and distrib...

  10. Development of stable solidification methods for toxic lead oxide in radioactive wastes

    International Nuclear Information System (INIS)

    Hitoshi Mimura; Shingo Ikeda; Yuichi Niibori

    2009-01-01

    The objective of this study is to develop the advanced solidification methods for the toxic lead oxide contained in radioactive wastes and to examine their chemical durability in terms of leachability and surface alteration; the solidification characteristics and leachability for the following three kinds of solidified products immobilizing lead were examined, and the experimental results were summarized as follows. (a) Mineral solidified products: A-zeolite or fly ash (FA) was used as a binder, and NaAlO 2 and Na 2 SiO 3 were mixed as additives. The leachability of lead ions in pure water was considerably lowered by the heat treatment at higher temperature (1,000 degree C), and the concentration of lead ions leached was under criterion value of 0.3 mg/l. The products prepared by mixing A-zeolite and fly ash also had low leachability under 0.3 mg/l even in the saturated Ca(OH)2 solution. (b) Melted solidified products: A-zeolite or fly ash was used as a binder and glass-forming reagents of B 2 O 3 and NaH 2 PO 4 were used as additives. The XRD peaks assigned PbO were not observed in all products. The products for the mixtures of FA:NaH 2 PO 4 :PbO (2:2:1 and 3:1:1) had low leachability under criterion value in both leachants of deionized water and saturated Ca(OH) 2 solution. (c) Phosphate ceramics products: the chemically bonded phosphate ceramics were produced by using MgKPO 4 , MgHPO 4 , Zr(HPO 4 ) 2 , potassium iron phosphate and sodium iron phosphate, and FA was used as additives. In particular, by using MgHPO 4 , the leachability of the products was lowered less than 0.3 mg/l in both leachants. The phosphate ceramics products and melted solidified products are favorable as the waste solid forms immobilizing lead. In particular, novel ceramics products have advantages in the simple solidification procedure similarly to the cement products. As for mineral solidification, natural zeolites and FA as binder also useful from the viewpoint of cost efficiency

  11. Overview of toxicity data and risk assessment methods for evaluating the chemical effects of depleted uranium compounds

    International Nuclear Information System (INIS)

    Hartmann, H.M.; Monette, F.A.; Avci, H.I.

    2000-01-01

    In the United States, depleted uranium is handled or used in several chemical forms by both governmental agencies and private industry (primarily companies producing and machining depleted uranium metal for military applications). Human exposure can occur as a result of handling these compounds, routine low-level effluent releases to the environment from processing facilities, or materials being accidentally released from storage locations or during processing or transportation. Exposure to uranium can result in both chemical and radiological toxicity, but in most instances chemical toxicity is of greater concern. This article discusses the chemical toxic effects from human exposure to depleted uranium compounds that are likely to be handled during the long-term management and use of depleted uranium hexafluoride (UF 6 ) inventories in the United States. It also reviews representative publications in the toxicological literature to establish appropriate reference values for risk assessments. Methods are described for evaluating chemical toxicity caused by chronic low-level exposure and acute exposure. Example risk evaluations are provided for illustration. Preliminary results indicate that chemical effects of chronic exposure to uranium compounds under normal operating conditions would be negligibly small. Results also show that acute exposures under certain accident conditions could cause adverse chemical effects among the populations exposed.

  12. Environmental labeling of car tires--toxicity to Daphnia magna can be used as a screening method.

    Science.gov (United States)

    Wik, Anna; Dave, Göran

    2005-02-01

    Car tires contain several water-soluble compounds that can leach into water and have toxic effects on aquatic organisms. Due to tire wear, 10,000 tonnes of rubber particles end up along the Swedish roads every year. This leads to a diffuse input of emissions of several compounds. Emissions of polyaromatic hydrocarbons (PAHs) are of particular concern. PAHs are ingredients of the high aromatic oil (HA oil) that is used in the rubber as a softener and as a filler. The exclusion of HA oils from car tires has started, and an environmental labeling of tires could make HA oils obsolete. The toxicity to Daphnia magna from 12 randomly selected car tires was tested in this study. Rubber from the tread of the tires was grated into small pieces, to simulate material from tire wear, and the rubber was equilibrated with dilution water for 72 h before addition of test organisms. The 24-h EC50s of the rubber pieces ranged from 0.29 to 32 gl-1, and the 48-h EC50s ranged from 0.0625 to 2.41 gl-1. Summer tires were more toxic than winter tires. After the 48-h exposure, the daphnids were exposed to UV-light for 2 h, to determine if the tires contained compounds that were phototoxic. After UV-activation the EC50s ranged from 0.0625 to 0.38 gl-1. Four of the 12 tires had a very distinct photoactivation, with a toxicity increase of >10 times. This study has shown that the used method for toxicity testing with Daphnia magna according to ISO 6341 could be used as a basis for environmental labeling of car tires.

  13. Análisis de supervivencia en presencia de riesgos competitivos: estimadores de la probabilidad de suceso Survival analysis with competing risks: estimating failure probability

    Directory of Open Access Journals (Sweden)

    Javier Llorca

    2004-10-01

    Full Text Available Objetivo: Mostrar el efecto de los riesgos competitivos de muerte en el análisis de supervivencia. Métodos: Se presenta un ejemplo sobre la supervivencia libre de rechazo tras un trasplante cardíaco, en el que la muerte antes de desarrollar el rechazo actúa como riesgo competitivo. Mediante una simulación se comparan el estimador de Kaplan-Meier y el modelo de decrementos múltiples. Resultados: El método de Kaplan-Meier sobrestima el riesgo de rechazo. A continuación, se expone la aplicación del modelo de decrementos múltiples para el análisis de acontecimientos secundarios (en el ejemplo, la muerte tras el rechazo. Finalmente, se discuten las asunciones propias del método de Kaplan-Meier y las razones por las que no puede ser aplicado en presencia de riesgos competitivos. Conclusiones: El análisis de supervivencia debe ajustarse por los riesgos competitivos de muerte para evitar la sobrestimación del riesgo de fallo que se produce con el método de Kaplan-Meier.Objective: To show the impact of competing risks of death on survival analysis. Method: We provide an example of survival time without chronic rejection after heart transplantation, where death before rejection acts as a competing risk. Using a computer simulation, we compare the Kaplan-Meier estimator and the multiple decrement model. Results: The Kaplan-Meier method overestimated the probability of rejection. Next, we illustrate the use of the multiple decrement model to analyze secondary end points (in our example: death after rejection. Finally, we discuss Kaplan-Meier assumptions and why they fail in the presence of competing risks. Conclusions: Survival analysis should be adjusted for competing risks of death to avoid overestimation of the risk of rejection produced with the Kaplan-Meier method.

  14. Quantification of inhaled aerosol particles composed of toxic household disinfectant using radioanalytical method.

    Science.gov (United States)

    Shim, Ha Eun; Lee, Jae Young; Lee, Chang Heon; Mushtaq, Sajid; Song, Ha Yeon; Song, Lee; Choi, Seong-Jin; Lee, Kyuhong; Jeon, Jongho

    2018-05-25

    To assess the risk posed by a toxic chemical to human health, it is essential to quantify its uptake in a living subject. This study aims to investigate the biological distribution of inhaled polyhexamethylene guanidine (PHMG) aerosol particle, which is known to cause severe pulmonary damage. By labeling with indium-111 ( 111 In), we quantified the uptake of PHMG for up to 7 days after inhalation exposure in rats. The data demonstrate that PHMG is only slowly cleared, with approximately 74% of inhaled particles persisting in the lungs after 168 h. Approximately 5.3% of inhaled particles were also translocated to the liver after 168 h, although the level of redistribution to other tissues, including the kidneys and spleen, was minimal. These observations suggest that large uptake and slow clearance may underlie the fatal inhalation toxicity of PHMG in humans. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

    Science.gov (United States)

    Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

    2003-05-01

    The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC

  16. Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

    Science.gov (United States)

    Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

    2002-01-01

    The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

  17. Parallel comparative studies on toxicity of quantum dots synthesized and surface engineered with different methods in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Liu F

    2017-07-01

    Full Text Available Fengjun Liu1,* Wen Ye1,* Jun Wang2 Fengxiang Song1 Yingsheng Cheng3 Bingbo Zhang21Department of Radiology, Shanghai Public Health Clinical Center, 2Institute of Photomedicine, Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, 3Department of Radiology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China *These authors contributed equally to this work Abstract: Quantum dots (QDs have been considered to be promising probes for biosensing, bioimaging, and diagnosis. However, their toxicity issues caused by heavy metals in QDs remain to be addressed, in particular for their in vivo biomedical applications. In this study, a parallel comparative investigation in vitro and in vivo is presented to disclose the impact of synthetic methods and their following surface modifications on the toxicity of QDs. Cellular assays after exposure to QDs were conducted including cell viability assessment, DNA breakage study in a single cellular level, intracellular reactive oxygen species (ROS receptor measurement, and transmission electron microscopy to evaluate their toxicity in vitro. Mice experiments after QD administration, including analysis of hemobiological indices, pharmacokinetics, histological examination, and body weight, were further carried out to evaluate their systematic toxicity in vivo. Results show that QDs fabricated by the thermal decomposition approach in organic phase and encapsulated by an amphiphilic polymer (denoted as QDs-1 present the least toxicity in acute damage, compared with those of QDs surface engineered by glutathione-mediated ligand exchange (denoted as QDs-2, and the ones prepared by coprecipitation approach in aqueous phase with mercaptopropionic acid capped (denoted as QDs-3. With the extension of the investigation time of mice respectively injected with QDs, we found that the damage caused by QDs to the organs can be

  18. Radioisotopic methods - determination of action of toxic chemicals to food - digestion organs

    International Nuclear Information System (INIS)

    Saitmuratova, O.H.; Tursunov, E.A.

    2004-01-01

    Full text: It is known that poison chemicals used for agriculture enter in an organism of human and animal by various ways and affect key processes in cells and tissues. These processes are investigated insufficiently, nevertheless, investigating actions of chemicals on bodies and tissues it, is possible to define a degree of its toxicity. In the present work influence of defoliant drop and insecticide buldok on protein synthetic ability (PSA) of cells of digestive bodies (a liver, a stomach and duodenal gut) is investigated. Experiments carried out on white not purebred rats - males in weight 160-180 g, which entered drop in doze of 1/5 IC 50 5350 mg/kg, buldok 1/5 IC 50 400 mg/kg and 14 C-glutamine acid with the general activity 1 mk Curie (2.2*106 imp/min) in one hour up to slaughter. A control animal in parallel entered a physiological solution. In animals hammered in one hour and investigated inclusion 14 C- glutamine acids in structure of synthesized proteins of a liver, a stomach and duodenal gut. Action of preparations checked in 1, 24 and 72 hours after introduction. As have shown the received data drop suppresses PSA in cells of a liver on 14 % and 45 % in 24 and 72 hours accordingly; in a stomach - on 32 % and 34 %; in duodenal gut - on 39 % and 48 %. PSA it is more suppressed in a stomach. Further process is gradually restored in all bodies. Buldok in the same terms suppresses PSA in a liver on 4 % and 25 %; in a stomach of 4 % and 16 % and in duodenal gut on the contrary are raised with formation of protein on 27 %. The next day there is restoration PSA in all investigated bodies. From the received data it is visible, that defoliant drop as well as insecticide buldok influence on PSA cells, but action of drop is stronger, than buldok. It will be coordinated to earlier received data on change of morphological structures under influence of these pesticides. Though drop and buldok differ on dynamics of action on PSA digestive bodies, they are not strongly

  19. Influence of the method of fluoride administration on toxicity and fluoride concentrations in Japanese quail

    Science.gov (United States)

    Fleming, W.J.; Schuler, C.A.

    1988-01-01

    Young Japanese quail (Coturnix japonica) were administered NaF for 16 d either in their diet or by esophageal intubation. Based on the total fluoride ion (Emg F-) intake over the l6-d experimental period, fluoride administered by intubation was at least six times more toxic than that fed in the diet. Dietary concentrations of 1,000 ppm F- (Emg F- for 16 d = approx. 144) produced no mortality, whereas intubated doses produced 73% or greater mortality in all groups administered 54 mg F- /kg/d or more (Emg F- for 16 d _ approx. 23 mg). GraphIc companson of the regression of log F- ppm in femurs/mg F- intake showed that fluoride levels in the femurs of quail administered fluoride by intubation were higher than in those administered fluoride in the diet.

  20. Modern methods for evaluating the workability of cement used as a binder for the stabilization and solidification of toxic wastes

    Energy Technology Data Exchange (ETDEWEB)

    De Angelis, Giorgio [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1997-10-01

    The workability of cement pastes has a great influence on the final properties of the solidified products, like mechanical strength, stability density and durability. This is quite relevant in the field of stabilization / solidification of toxic and hazardous wastes. Hence considerable importance attaches to having reliable control over the fresh concrete properties, especially its early stiffening behaviour. This paper discussers measuring methods of the stiffening of two different types of cement pastes, prepared with different water / cement ratios, and examines the possible consequences of the early stiffening of cement pastes on their set times and bleeding.

  1. Rationale for methods of prevention and treatment of toxic infections complications of combined radiation and thermal injuries

    International Nuclear Information System (INIS)

    Bodugov, R.S.; Nesterenko, V.S.; Makarov, G.F.; Ul'yanova, L.P.; Khlopovskaya, E.I.

    1992-01-01

    Analysis of the results of experimental studies on the pathogenesis of combined radiation and thermal injuries (CRTI) helped single out the factors aggravating the outcomes of such injuries. Potentiation of the hepatotoxic effects of bacterial enteroendotoxicosis and early toxemia associated with burns is the principal factor augmenting the disorders in the reactivity of radiosensitive systems in CRTI. The authors' findings evidence the efficacy of enterosorption, of methods enhancing the gastrointestinal motoricity, and of a number of modifiers of biologic reactions and heterologous immunoglobulins for the prevention and treatment of toxic infectious complications of CRTI

  2. Overview of Provisional Peer-Reviewed Toxicity Values (PPRTVs), Alternative Methods in Human Health Risk Assessment, and the RapidTox Dashboard

    Science.gov (United States)

    This poster provides an overview of three key lines of ongoing work at EPA/ORD/NCEA-CIN: Provisional Peer-Reviewed Toxicity Values (PPRTVs), Alternative Methods in Human Health Risk Assessment, and the RapidTox Dashboard collaboration.

  3. A simple and low-toxic method of preparing small specimens of bacteria, flagellates and their likes for Scanning Electron Microscopy

    DEFF Research Database (Denmark)

    Møller, O. S.; Buchman, K.; Dalsgaard, Inger

    2013-01-01

    The preparation of samples of bacteria and other very small organisms (Electron Microscopy is often complex and intricate, which typically involve the use of specialized filter systems, complex handling and toxic chemicals. Based on the methods described in the literature...

  4. Comparison of sample preparation methods for the determination of essential and toxic elements in important indigenous medicinal plant Aloe barbadensis

    International Nuclear Information System (INIS)

    Sahito, S.R.; Kazi, T.G.; Kazi, G.H.; Jakhrani, M.A.; Wattoo, M.H.S.

    2002-01-01

    The role of elements particularly traces elements in health and disease is now well established. In this paper we investigate the presence of various elements in very important herb Aloe barbadensis, it is commonly used in different ailments especially of elementary tract. We used four extraction methods for the determination of total elements in Aloe barbadensis. The procedure, which is found to be more efficient and decompose the biological material, is nitric acid and 30% hydrogen peroxide as compared to other method. The sample of plants was collected from surrounding of Hyderabad; Sindh University and vouches specimens were prepared following the standard herbarium techniques. Fifteen essential, trace and toxic elements such as Zn, Cr, K, Mg, Ca, Na, Fe, Pb, Al, Ba, Mn, Co, Ni and Cd were determined in plant and in its decoction. Using Flame Atomic Absorption Spectrophotometer Hitachi Model 180-50. It is noted that, level of essential elements was found high as compare to the level of toxic elements. (author)

  5. Direct method for impact assessment of environmental pollutants and toxicants causing health hazards

    International Nuclear Information System (INIS)

    Fazal-ur-Rehman; Adil, A.; Abdullah, A.; Masood, S.R.; Agha, A.

    1997-01-01

    Industrial waste pollutants and toxicants are released in three forms i.e. gas, liquid, solid or their admixtures, causing atmospheric , hydro spheric and lithospheric pollutions. Gaseous wastes pollute the surrounding air before entering the waste-cycle and bio-cycle through vegetation/ forestation(i.e., plant kingdom). Liquid wastes enter the water-cycle directly and speedily whereas solid wastes enter the water-cycle indirectly and slowly. All these wastes, as it is well known later on enter plant and animal kingdoms which ultimately effect the human health and make different body parts sick/malignant. Therefore, the regular monitoring of elemental composition of these body parts becomes imperative. The above mentioned format of impact assessment has been followed during different joint studies (carried out in collaboration with university of the Punjab, INMOL and other Departments) which are based on the analytical data collected during the period of last five years. These samples include specimens of blood serum, cancer tissues, drinking and running water, industrial wastes and effluents etc. The comparison, of analysis of samples of unaffected (healthy) and malignant body parts, leads to the direct assessment of environmental pollutants and the inhabitants. (author)

  6. Continuous flow bioassay method to evaluate the effects of outboard motor exhausts and selected aromatic toxicants on fish. [Carassius auratus

    Energy Technology Data Exchange (ETDEWEB)

    Brenniman, G. (Univ. of Illinois, Chicago); Hartung, R.; Weber, W.J. Jr.

    1976-01-01

    A continuous flow bioassay system was designed to measure the effects of outboard motor exhaust (OME) emissions and selected volatile and evaporative aromatic toxicants on goldfish (Carassius auratus). Continuous flow bioassays were run for 24, 48, 72, 96, and 720 h to determine lethal concentrations for 50 percent of individuals (LC 50's) for leaded OME, non-leaded OME, toluene, xylene, and 1,3,5 trimethylbenzene, the three individual compounds having been identified as significant aromatic components of OME. The 96 h LC-50's for these substances were found to be 171, 168, 23, 17, and 13 ppm, respectively. The values of 171 and 168 ppm for the two OME's are given in terms of gallons of fuel burned per million gallons of water. The continuous flow bioassay method was demonstrated to be a more reliable indicator of the effects of OME pollutants on aquatic organisms than is the static bioassay method.

  7. Microalgae based biorefinery: evaluation of oil extraction methods in terms of efficiency, costs, toxicity and energy in lab-scale

    Directory of Open Access Journals (Sweden)

    Ángel Darío González-Delgado

    2013-06-01

    Full Text Available Several alternatives of microalgal metabolites extraction and transformation are being studied for achieving the total utilization of this energy crop of great interest worldwide. Microalgae oil extraction is a key stage in microalgal biodiesel production chains and their efficiency affects significantly the global process efficiency. In this study, a comparison of five oil extraction methods in lab-scale was made taking as additional parameters, besides extraction efficiency, the costs of method performing, energy requirements, and toxicity of solvents used, in order to elucidate the convenience of their incorporation to a microalgae-based topology of biorefinery. Methods analyzed were Solvent extraction assisted with high speed homogenization (SHE, Continuous reflux solvent extraction (CSE, Hexane based extraction (HBE, Cyclohexane based extraction (CBE and Ethanol-hexane extraction (EHE, for this evaluation were used the microalgae strains Nannochloropsis sp., Guinardia sp., Closterium sp., Amphiprora sp. and Navicula sp., obtained from a Colombian microalgae bioprospecting. In addition, morphological response of strains to oil extraction methods was also evaluated by optic microscopy. Results shows that although there is not a unique oil extraction method which excels in all parameters evaluated, CSE, SHE and HBE appears as promising alternatives, while HBE method is shown as the more convenient for using in lab-scale and potentially scalable for implementation in a microalgae based biorefinery

  8. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    Directory of Open Access Journals (Sweden)

    Gui Mi Ko

    2010-06-01

    Full Text Available In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme of the Federal University of São Paulo (UNIFESP: 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995, 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for acute dermal toxicity, and 2 for irritation of mucous membrane. The following agents were tested: cosmetics and related substances (42.0%, chemicals used in industry (32.9%, plastics, rubber, and other polymers (15.9%, agrotoxics (4.0%, medicines (2.7%, and vaccines (2.5%. In the present description, emphasis was given to tests of dermal irritability and sensitization. This work was conducted entirely in animal facilities, according to our general belief that animal facilities at universities, while considering ethic principles and sanitary, genetic, nutritional, and pathophysiological controls, also require laboratories specialized in areas such as transgenics, cryopreservation, ambiental physiology, functional genomics, alternative models, and mainly activities and research on methods in toxicology, as focused in this study.Descrevemos os testes usados em ensaios biológicos de curta duração para estudo de toxicidade e inocuidade de cosméticos, fármacos e outras substâncias químicas, feitos no Biotério Central/Cedeme da Unifesp, de 1986 a 2000. Testamos 602 amostras nos seguintes ensaios: 385 de irritação cutânea, 90 de irritação ocular (até 1995, 31 de toxicidade sistêmica por injeção, 26 de toxicidade oral aguda, 15 de toxicidade por aplicação intracutânea, 15 de sensibilização da pele, 15 de toxicidade de soros e vacinas de uso humano, 14 de toxicidade por implantação intramuscular, 7 de pirogênio, 2 de toxicidade dérmica aguda e

  9. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance.

    Science.gov (United States)

    De Win, Maartje M L; Jager, Gerry; Vervaeke, Hylke K E; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C; Den Heeten, Gerard J; Ramsey, Nick F; Korf, Dirk J; Van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin axons, but most of these studies have serious methodological limitations. The current study is a combination of different approaches with three substudies: (1) a crosssectional substudy among heavy ecstasy users and controls with variation in drug use, which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs; (2) a prospective cohort substudy in ecstasy-naive subjects with high risk for future ecstasy use, which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity, and (3) a retrospective cohort substudy in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population. Neurotoxicity is studied using (a) different imaging techniques (beta-CIT SPECT, 1H-MR spectroscopy, diffusion tensor imaging, perfusion weighted imaging and functional magnetic resonance imaging), and (b) neuropsychological and psychiatric assessments of memory, depression, and personality. The combined results will lead to conclusions that can be used in prevention messages, clinical decision making, and the development of an (inter)national ecstasy policy.

  10. A Tutorial for Analysing the Cost-effectiveness of Alternative Methods for Assessing Chemical Toxicology: The Case of Acute Oral Toxicity Prediction

    NARCIS (Netherlands)

    Norlen, H.; Worth, A.P.; Gabbert, S.G.M.

    2014-01-01

    Compared with traditional animal methods for toxicity testing, in vitro and in silico methods are widely considered to permit a more cost-effective assessment of chemicals. However, how to assess the cost-effectiveness of alternative methods has remained unclear. This paper offers a user-oriented

  11. Comparison of a specific HPLC determination of toxic aconite alkaloids in processed Radix aconiti with a titration method of total alkaloids.

    Science.gov (United States)

    Csupor, Dezso; Borcsa, Botond; Heydel, Barbara; Hohmann, Judit; Zupkó, István; Ma, Yan; Widowitz, Ute; Bauer, Rudolf

    2011-10-01

    In traditional Chinese medicine, Aconitum (Ranunculaceae) roots are only applied after processing. Nevertheless, several cases of poisoning by improperly processed aconite roots have been reported. The aim of this study was to develop a reliable analytical method to assess the amount of toxic aconite alkaloids in commercial aconite roots, and to compare this method with the commonly used total alkaloid content determination by titration. The content of mesaconitine, aconitine, and hypaconitine in 16 commercial samples of processed aconite roots was determined by an HPLC method and the total alkaloid content by indirect titration. Five samples were selected for in vivo toxicological investigation. In most of the commercial samples, toxic alkaloids were not detectable, or only traces were found. In four samples, we could detect >0.04% toxic aconite alkaloids, the highest with a content of 0.16%. The results of HPLC analysis were compared with the results obtained by titration, and no correlation was found between the two methods. The in vivo results reassured the validity of the HPLC determination. Samples with mesaconitine, aconitine, and hypaconitine content below the HPLC detection limit still contained up to 0.2% alkaloids determined by titration. Since titration of alkaloids gives no information selectively on the aconitine-type alkaloid content and toxicity of aconite roots this method is not appropriate for safety assessment. The HPLC method developed by us provides a quick and reliable assessment of toxicity and should be considered as a purity test in pharmacopoeia monographs.

  12. A LITERATURE REVIEW OF WIPE SAMPLING METHODS FOR CHEMICAL WARFARE AGENTS AND TOXIC INDUSTRIAL CHEMICALS

    Science.gov (United States)

    Wipe sampling is an important technique for the estimation of contaminant deposition in buildings, homes, or outdoor surfaces as a source of possible human exposure. Numerousmethods of wipe sampling exist, and each method has its own specification for the type of wipe, we...

  13. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer.

    Science.gov (United States)

    Tremblay, Gabriel; Livings, Christopher; Crowe, Lydia; Kapetanakis, Venediktos; Briggs, Andrew

    2016-01-01

    Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.

  14. Toxicity and Detoxification Effects of Herbal Caowu via Ultra Performance Liquid Chromatography/Mass Spectrometry Metabolomics Analyzed using Pattern Recognition Method

    Science.gov (United States)

    Yan, Yan; Zhang, Aihua; Dong, Hui; Yan, Guangli; Sun, Hui; Wu, Xiuhong; Han, Ying; Wang, Xijun

    2017-01-01

    Background: Caowu (Radix Aconiti kusnezoffii, CW), the root of Aconitum kusnezoffii Reichb., has widely used clinically in rheumatic arthritis, painful joints, and tumors for thousands of years. However, the toxicity of heart and central nervous system induced by CW still limited the application. Materials and Methods: Metabolomics was performed to identify the sensitive and reliable biomarkers and to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity, and the detoxification by combinatorial intervention of CW with Gancao (Radix Glycyrrhizae) (CG), Baishao (Radix Paeoniae Alba) (CB), and Renshen (Radix Ginseng) (CR) was also analyzed by pattern recognition methods. Results: As a result, the metabolites were characterized and responsible for pentose and glucuronate interconversions, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, fructose and mannose metabolism, and starch and sucrose metabolism, six networks of which were the same to the metabolic pathways of Chuanwu (Radix Aconiti, CHW) group. The ascorbate and aldarate metabolism was also characterized by CW group. The urinary metabolomics also revealed CW-induced serious toxicity to heart and liver. Thirteen significant metabolites were identified and had validated as phenotypic toxicity biomarkers of CW, five biomarkers of which were commonly owned in Aconitum. The changes of toxicity metabolites obtained from combinatorial intervention of CG, CB, and CR also were analyzed to investigate the regulation degree of toxicity biomarkers adjusted by different combinatorial interventions at 6th month. Conclusion: Metabolomics analyses coupled with pattern recognition methods in the evaluation of drug toxicity and finding detoxification methods were highlighted in this work. SUMMARY Metabolomics was performed to characterize the biochemical potential mechanisms of Caowu toxicityThirteen significant metabolites

  15. A comparison of methods used to calculate normal background concentrations of potentially toxic elements for urban soil

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, Katherine A., E-mail: k.rothwell@ncl.ac.uk; Cooke, Martin P., E-mail: martin.cooke@ncl.ac.uk

    2015-11-01

    To meet the requirements of regulation and to provide realistic remedial targets there is a need for the background concentration of potentially toxic elements (PTEs) in soils to be considered when assessing contaminated land. In England, normal background concentrations (NBCs) have been published for several priority contaminants for a number of spatial domains however updated regulatory guidance places the responsibility on Local Authorities to set NBCs for their jurisdiction. Due to the unique geochemical nature of urban areas, Local Authorities need to define NBC values specific to their area, which the national data is unable to provide. This study aims to calculate NBC levels for Gateshead, an urban Metropolitan Borough in the North East of England, using freely available data. The ‘median + 2MAD’, boxplot upper whisker and English NBC (according to the method adopted by the British Geological Survey) methods were compared for test PTEs lead, arsenic and cadmium. Due to the lack of systematically collected data for Gateshead in the national soil chemistry database, the use of site investigation (SI) data collected during the planning process was investigated. 12,087 SI soil chemistry data points were incorporated into a database and 27 comparison samples were taken from undisturbed locations across Gateshead. The SI data gave high resolution coverage of the area and Mann–Whitney tests confirmed statistical similarity for the undisturbed comparison samples and the SI data. SI data was successfully used to calculate NBCs for Gateshead and the median + 2MAD method was selected as most appropriate by the Local Authority according to the precautionary principle as it consistently provided the most conservative NBC values. The use of this data set provides a freely available, high resolution source of data that can be used for a range of environmental applications. - Highlights: • The use of site investigation data is proposed for land contamination studies

  16. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    International Nuclear Information System (INIS)

    Ahmed, Awad A.; Egleston, Brian; Alcantara, Pino; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2013-01-01

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P 68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored

  17. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    International Nuclear Information System (INIS)

    Embry, Michelle R.; Belanger, Scott E.; Braunbeck, Thomas A.; Galay-Burgos, Malyka; Halder, Marlies; Hinton, David E.; Leonard, Marc A.; Lillicrap, Adam; Norberg-King, Teresa; Whale, Graham

    2010-01-01

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  18. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    Energy Technology Data Exchange (ETDEWEB)

    Embry, Michelle R., E-mail: membry@ilsi.org [ILSI Health and Environmental Sciences Institute, 1156 15th Street, NW, Suite 200, Washington, DC 20005 (United States); Belanger, Scott E., E-mail: belanger.se@pg.com [Procter and Gamble, Central Product Safety, PO Box 538707, Miami Valley Innovation Center, Cincinnati, OH 45253-8707 (United States); Braunbeck, Thomas A., E-mail: braunbeck@zoo.uni-heidelberg.de [University of Heidelberg, Im Neuenheimer Feld 230, Heidelberg D -69120 (Germany); Galay-Burgos, Malyka, E-mail: malyka.galay-burgos@ecetoc.org [European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 4 Avenue E. Van Nieuwenhuyse B-1160, Brussels (Belgium); Halder, Marlies, E-mail: marlies.halder@jrc.ec.europa.eu [European Commission, Joint Research Centre, Institute for Health and Consumer Protection, In-Vitro Methods Unit TP-580 Ispra 21027 (Italy); Hinton, David E., E-mail: dhinton@duke.edu [Duke University, Nicholas School of the Environment, PO Box 90328, Durham, NC 27708, Unites States (United States); Leonard, Marc A., E-mail: mleonard@rd.loreal.com [L' Oreal Recherche Avancee, Unite d' Ecotoxicologie, 1 av. E. Schueller, 93601 Aulnay sous bois (France); Lillicrap, Adam, E-mail: Adam.lillicrap@niva.no [AstraZeneca, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Norberg-King, Teresa, E-mail: norberg-king.teresa@epa.gov [U.S. EPA, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804-1636 (United States); Whale, Graham, E-mail: graham.whale@shell.com [Shell Global Solutions, Analytical Technology, P.O. Box 1, Chester CH1 3SH (United Kingdom)

    2010-04-15

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  19. Development of radiochemical separation method for determination of toxic elements in biological samples

    International Nuclear Information System (INIS)

    Maihara, V.A.; Vasconcellos, M.B.A.; Favaro, D.I.T.; Armelin, M.J.A.

    1990-01-01

    In order to determine Hg, Sb, As and Se in biological materials by neutron activation analysis, a radiochemical separation was developed. The chemical separation procedure used was based on the digestion of the irradiated sample in a mixture of H NO 3 and H 2 SO 4 in a teflon bomb, at 130 0 C for 1 to 4 hours. After the dissolution of organic matter, Hg and Sb were retained by a Dowex 2-X8 resin column in 6 M HCl. The effluent was passed through a TDO, tin dioxide column which retains As and Se in 3 M HCl medium. Radioactive tracers of these elements were used to determine the yields of the separation process. Certified reference materials were analyzed to check the precision and accuracy of the method. (author)

  20. Development of a radiochemical separation method for toxic elements determination from biologic samples

    International Nuclear Information System (INIS)

    Malhara, V.A.; Vasconcellos, M.B.A.; Favaro, D.I.T.; Armelin, M.J.A.

    1990-01-01

    In order to determine Hg, Sb, As and Se in biological materials by neutron activation analysis, a radiochemical separation was developed. The chemical separation procedure used was based on the digestion of the irradiated sample in a mixture of HNO 3 and H 2 SO 4 in a teflon bomb, at 130 0 C for 1 to 4 hours. After the dissolution of organic matter, Hg and Sb were retained by a Dowex 2-XB resin column in 6M HCI. The efluent was passed through a TDO, tin dioxide column which retains As and Se in 3M HCI medium. Radioactive tracers of these elements were used to determine the yields of the separation process. Certified reference materials were analyzed to check the precision and accuracy of the method. (author)

  1. Testing contamination risk assessment methods for toxic elements from mine waste sites

    Science.gov (United States)

    Abdaal, A.; Jordan, G.; Szilassi, P.; Kiss, J.; Detzky, G.

    2012-04-01

    Major incidents involving mine waste facilities and poor environmental management practices have left a legacy of thousands of contaminated sites like in the historic mining areas in the Carpathian Basin. Associated environmental risks have triggered the development of new EU environmental legislation to prevent and minimize the effects of such incidents. The Mine Waste Directive requires the risk-based inventory of all mine waste sites in Europe by May 2012. In order to address the mining problems a standard risk-based Pre-selection protocol has been developed by the EU Commission. This paper discusses the heavy metal contamination in acid mine drainage (AMD) for risk assessment (RA) along the Source-Pathway-Receptor chain using decision support methods which are intended to aid national and regional organizations in the inventory and assessment of potentially contaminated mine waste sites. Several recognized methods such as the European Environmental Agency (EEA) standard PRAMS model for soil contamination, US EPA-based AIMSS and Irish HMS-IRC models for RA of abandoned sites are reviewed, compared and tested for the mining waste environment. In total 145 ore mine waste sites have been selected for scientific testing using the EU Pre-selection protocol as a case study from Hungary. The proportion of uncertain to certain responses for a site and for the total number of sites may give an insight of specific and overall uncertainty in the data we use. The Pre-selection questions are efficiently linked to a GIS system as database inquiries using digital spatial data to directly generate answers. Key parameters such as distance to the nearest surface and ground water bodies, to settlements and protected areas are calculated and statistically evaluated using STATGRAPHICS® in order to calibrate the RA models. According to our scientific research results, of the 145 sites 11 sites are the most risky having foundation slope >20o, 57 sites are within distance 66 (class VI

  2. Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment.

    Science.gov (United States)

    Doskocz, Marek; Marchewka, Zofia; Jeż, Magdalena; Passowicz-Muszyńska, Ewa; Długosz, Anna

    2015-01-01

    Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p≤0.05, p≤0.01). There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program.

  3. Prediction of Acute Mammalian Toxicity Using QSAR Methods: A Case Study of Sulfur Mustard and Its Breakdown Products

    Directory of Open Access Journals (Sweden)

    John Wheeler

    2012-07-01

    Full Text Available Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR, has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance’s database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD50 for determining relative toxicity of a number of substances. In general, the smaller the LD50 value, the more toxic the chemical, and the larger the LD50 value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s of interest, during emergency responses, LD50 values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD50 models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD50 values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

  4. Trends in study design and the statistical methods employed in a leading general medicine journal.

    Science.gov (United States)

    Gosho, M; Sato, Y; Nagashima, K; Takahashi, S

    2018-02-01

    Study design and statistical methods have become core components of medical research, and the methodology has become more multifaceted and complicated over time. The study of the comprehensive details and current trends of study design and statistical methods is required to support the future implementation of well-planned clinical studies providing information about evidence-based medicine. Our purpose was to illustrate study design and statistical methods employed in recent medical literature. This was an extension study of Sato et al. (N Engl J Med 2017; 376: 1086-1087), which reviewed 238 articles published in 2015 in the New England Journal of Medicine (NEJM) and briefly summarized the statistical methods employed in NEJM. Using the same database, we performed a new investigation of the detailed trends in study design and individual statistical methods that were not reported in the Sato study. Due to the CONSORT statement, prespecification and justification of sample size are obligatory in planning intervention studies. Although standard survival methods (eg Kaplan-Meier estimator and Cox regression model) were most frequently applied, the Gray test and Fine-Gray proportional hazard model for considering competing risks were sometimes used for a more valid statistical inference. With respect to handling missing data, model-based methods, which are valid for missing-at-random data, were more frequently used than single imputation methods. These methods are not recommended as a primary analysis, but they have been applied in many clinical trials. Group sequential design with interim analyses was one of the standard designs, and novel design, such as adaptive dose selection and sample size re-estimation, was sometimes employed in NEJM. Model-based approaches for handling missing data should replace single imputation methods for primary analysis in the light of the information found in some publications. Use of adaptive design with interim analyses is increasing

  5. Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

    Science.gov (United States)

    Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

    2018-06-01

    Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results

  6. Review on toxicity testing with marine macroalgae and the need for method standardization--exemplified with copper and phenol.

    Science.gov (United States)

    Eklund, Britta T; Kautsky, Lena

    2003-02-01

    Toxic effects on macroalgae have been compiled. Eighty-two articles have been found in literature during 1959-2000. A total of 120 substances were investigated using 65 different macroalgae species. About one-third of the tested compounds were organic substances (33%), another third metal-organic substances (35%), and the last third were oils (14%), metals (8%), detergents (7.5%) and other inorganic chemicals (2.5%). Half of the substances were only tested once on a single species. Likewise, toxicity data has only been reported for one chemical tested on a single occasion for about half of the 65 species. Thus little is known about the toxic effects on marine macroalgae. The objectives of the previous studies undertaken varied and therefore the toxicity data was presented in numerous ways, e.g. using different exposure times, temperature, light intensity, light regime, salinity, and nutrients, which makes a direct comparison of the data difficult. This review also shows that many stages in the lifecycle of macroalgae are often more sensitive to toxic substances than other aquatic organisms. Consequently, tests using macroalgae may discover toxicity earlier, which would in turn also protect the fauna. If toxic compounds have a negative affect on the distribution and growth of structurally and functionally dominating macroalgae, there may indirectly be a large and harmful influence on the whole marine coastal ecosystem. For this reason tests on macroalgae should be included in control programs along the coasts.

  7. Introducing Toxics

    OpenAIRE

    David C. Bellinger

    2013-01-01

    With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present ...

  8. Estimation of toxicity using the Toxicity Estimation Software Tool (TEST)

    Science.gov (United States)

    Tens of thousands of chemicals are currently in commerce, and hundreds more are introduced every year. Since experimental measurements of toxicity are extremely time consuming and expensive, it is imperative that alternative methods to estimate toxicity are developed.

  9. Determining the bioavailability and toxicity of lead contamination to earthworms requires using a combination of physicochemical and biological methods

    International Nuclear Information System (INIS)

    Luo, Wei; Verweij, Rudo A.; Gestel, Cornelis A.M. van

    2014-01-01

    This study aimed at assessing the bioavailability and toxicity of lead to Eisenia andrei in shooting range soils representing different land uses (forest, grassland, bullet plot). Soils contained 47–2398 mg Pb/kg dry weight (dw), but also had different pH-CaCl 2 (3.2–6.8) and organic matter contents (3.8–13%). Therefore artificial soils with different pH and organic matter contents and two natural soils were included as control soils. Earthworms were exposed for 28 days and toxicity and uptake of Pb were related to total, water and 0.01 M CaCl 2 extractable and porewater Pb concentrations as well as to soil characteristics. Pb uptake in the earthworms linearly increased with increasing soil concentrations. At >2000 mg Pb/kg dw and pH 3.3–3.5, high earthworm mortality with significant weight loss and complete inhibition of reproduction were recorded. At <1000 mg/kg dw, earthworm reproduction was more related to differences in pH and other soil characteristics than to Pb. -- Highlights: • Availability and earthworm toxicity of Pb determined in field-contaminated soils. • Earthworm toxicity of most-polluted soils explained from available Pb levels. • Earthworm response in less polluted soils mainly determined by soil pH. • Earthworm toxicity correlated with Pb uptake from the soil. • Soil properties explained differences in earthworm Pb uptake and effects. -- Combination of physicochemical and biological assays helped explaining Pb toxicity in shooting range soils from available Pb concentrations and soil characteristics

  10. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    NARCIS (Netherlands)

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as

  11. Building up a QSAR model for toxicity toward Tetrahymena pyriformis by the Monte Carlo method: A case of benzene derivatives.

    Science.gov (United States)

    Toropova, Alla P; Schultz, Terry W; Toropov, Andrey A

    2016-03-01

    Data on toxicity toward Tetrahymena pyriformis is indicator of applicability of a substance in ecologic and pharmaceutical aspects. Quantitative structure-activity relationships (QSARs) between the molecular structure of benzene derivatives and toxicity toward T. pyriformis (expressed as the negative logarithms of the population growth inhibition dose, mmol/L) are established. The available data were randomly distributed three times into the visible training and calibration sets, and invisible validation sets. The statistical characteristics for the validation set are the following: r(2)=0.8179 and s=0.338 (first distribution); r(2)=0.8682 and s=0.341 (second distribution); r(2)=0.8435 and s=0.323 (third distribution). These models are built up using only information on the molecular structure: no data on physicochemical parameters, 3D features of the molecular structure and quantum mechanics descriptors are involved in the modeling process. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    OpenAIRE

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds esp...

  13. Progress in the development of short term chronic toxicity testing methods for crude oil and commercial bioremediation agents

    International Nuclear Information System (INIS)

    Cavender, R.C.; Cherry, D.S.; Dobbs, M.G.; Bidwell, J.R.; Yeager, M.M.

    1995-01-01

    Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan (NCP) have prompted examinations of the methodology used in toxicity testing of the water soluble fraction of oil, commercial bioremediation agents (CBA), and a combination of the two. The specific concerns addressed by this research are the use of unweathered Alaska North Slope (ANS) crude oil instead of the more expensive, less environmentally realistic distillate ANS-521, and the appropriate laboratory preparation methodology for the water soluble fraction (WSF) used in testing. Seven-day chronic tests exposing the inland silverside (Menidia beryllina) and estuarine mysid (Mysidopsis bahia) to the water soluble fraction of unweathered ANS and ANS-521 showed that mysids responded similarly to the two types of oils while silversides were more sensitive to unweathered ANS. In the presence of a CBA and WSF, the mortality of the organisms and the mysid growth were similar in both types of oil. The NOEC for silverside growth, however, was lower in the combined exposure of a CBA with ANS-521 WSF than it was in the CBA-WSF unweathered ANS. Testing is underway to determine if the stirring time length effects the toxicity of the WSF, or the WSF and CBA combination. In chronic tests using both the silverside and mysid there were no differences in growth and mortality of the organisms tested in WSF prepared from 10 and 20 hours of stirring, however, the 5 hour stirring exposure is less toxic to both organisms

  14. Using combined bio-omics methods to evaluate the complicated toxic effects of mixed chemical wastewater and its treated effluent

    International Nuclear Information System (INIS)

    Zhang, Yan; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang

    2014-01-01

    Highlights: • Mice exposed to mixed chemical wastewater and its treated effluent for 90 days. • Hepatic transcriptomic alterations were analyzed by digital gene expression. • Serum metabolomic alterations were analyzed by proton nuclear magnetic resonance. • The water samples induced disruption of lipid metabolism and hepatotoxicity. • Omics approaches are valuable to evaluate the complicated toxicity of wastewater. - Abstract: Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures of trace contaminants, which cannot be effectively removed by wastewater treatment plants (WWTP) and have become an unignored threat to ambient environment. However, limited information is available to evaluate the complicated toxic effects of MCWW and its effluent from wastewater treatment plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed to the MCWW and WTPE for 90 days and distinct differences in the hepatic transcriptome and serum metabolome were analyzed by digital gene expression (DGE) and proton nuclear magnetic resonance ( 1 H-NMR) spectra, respectively. Our results indicated that disruption of lipid metabolism in liver and hepatotoxicity were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the environment, which is in need of more attention. Furthermore, we demonstrated the potential ability of bio-omics approaches for evaluating toxic effects of MCWW and WTPE

  15. Using combined bio-omics methods to evaluate the complicated toxic effects of mixed chemical wastewater and its treated effluent

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang, E-mail: hqren@nju.edu.cn

    2014-05-01

    Highlights: • Mice exposed to mixed chemical wastewater and its treated effluent for 90 days. • Hepatic transcriptomic alterations were analyzed by digital gene expression. • Serum metabolomic alterations were analyzed by proton nuclear magnetic resonance. • The water samples induced disruption of lipid metabolism and hepatotoxicity. • Omics approaches are valuable to evaluate the complicated toxicity of wastewater. - Abstract: Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures of trace contaminants, which cannot be effectively removed by wastewater treatment plants (WWTP) and have become an unignored threat to ambient environment. However, limited information is available to evaluate the complicated toxic effects of MCWW and its effluent from wastewater treatment plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed to the MCWW and WTPE for 90 days and distinct differences in the hepatic transcriptome and serum metabolome were analyzed by digital gene expression (DGE) and proton nuclear magnetic resonance ({sup 1}H-NMR) spectra, respectively. Our results indicated that disruption of lipid metabolism in liver and hepatotoxicity were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the environment, which is in need of more attention. Furthermore, we demonstrated the potential ability of bio-omics approaches for evaluating toxic effects of MCWW and WTPE.

  16. Rapid bioassessment methods for assessing vegetation toxicity at the Savannah River Site - germination tests and root elongation trials

    Energy Technology Data Exchange (ETDEWEB)

    Specht, W.L.; Klaine, S.J.; Hook, D.D. [and others

    1996-01-01

    Plants form the basis of all ecosystems including wetlands. Although they are the most abundant life form and are the primary producers for all other organisms, they have received the least attention when it comes to environmental matters. Higher plants have rarely been used in ecotoxicity testing and may not respond in the same manner as algae, which have been used more frequently. The introduction of hazardous waste materials into wetland areas has the potential to alter and damage the ecological processes in these ecosystems. Measuring the impact of these contaminants on higher plants is therefore important and needs further research. Higher plants are useful for detecting both herbicidal toxicity and heavy metal toxicity. For phytotoxicity tests to be practical they must be simple, inexpensive, yet sensitive to a variety of contaminants. A difference between seed germination and root elongation tests is that seed germination tests measure toxicity associated with soils directly, while root elongation tests consider the indirect effects of water-soluble constituents that may be present in site samples.

  17. An assessment of the toxicity of crude oils in soils using earthworms, Microtox reg-sign Solid-Phase and early plant growth methods

    International Nuclear Information System (INIS)

    Vipond, T.E.; Dorn, P.B.; Salanitro, J.P.; Huesemann, M.H.; Wisniewski, H.L.; Moore, K.O.

    1993-01-01

    The qualitative assessment of soil quality resulting from a chemical or oil spill and/or remediation effort may be obtained by evaluating the toxicity to soil organisms. To enhance the authors understanding of the soil quality resulting from oil spill remediation, they have begun a program to assess three soil toxicity test methods. A heavy, medium and light crude oil were spiked into a sandy soil and a topsoil in the laboratory. The earthworm (Eisenia foetida) 14-d lethality assay, the modified Microbics Microtox Solid-Phase method, and the 14-d agricultural plant seed germination rate and plant growth assay were exposed to combinations of crude oils and soils. Earthworms were 1.4 to 14 times more sensitive than the Microtox and 1.3 to >77 times more sensitive than the plants to the oily soils. Light crude oil in sandy soil was the most toxic to the earthworms. Six percent heavy crude oil in topsoil showed little effect on the three organisms with LC50's ranging from 6.7--7.3 for earthworms to no effects on plants. These bioassay techniques are shown to be sensitive indicators of soil quality and may be used to evaluate the soil quality of remediated oil soils

  18. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors to h...

  19. INTRAPERITONEAL AEROSOL CHEMOTHERAPY UNDER PRESSURE (IACUP – AN INNOVATIVE METHOD OF TREATMENT OF PATIENTS WITH PERITONEAL CARCINOMATOSIS

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

    Full Text Available Widespread peritoneal carcinomatosis in gastric cancer, in fact, is the end-stage of the disease. The survival median of patients is no more than 3–6 months. Development of various methods of intraperitoneal chemotherapy can improve the prognosis of this category of patients.Objective. To evaluate the efficacy and safety of intraperitoneal aerosol chemotherapy under pressure (IACUP in patients with gastric cancer with peritoneal carcinomatosis.Materials and methods. The treatment Protocol consisted of a laparotomy or laparoscopy for the staging of the tumor process, 3–4 courses of systemic chemotherapy scheme XELOX followed by conducting at least 3 sessions of intraperitoneal aerosol chemotherapy under pressure (IACUP with an interval of 6 weeks on the background of chemotherapy. In the case of progression the patient was excluded from the study. Currently, the study included 27 patients with disseminated gastric cancer who underwent 46 procedures of IACUP. There were 8 men and 19 women. The average age of patients was 50.6 years.Results. In the framework of the safety assessment of IACUP there were 3 cases of adverse effects. Two patients (7,4% noted nausea for the first 2 days after running the session of IACUP. In one patient the iatrogenic perforation of the diaphragm during biopsy of the peritoneum with the development of carbonetworks occurred. The survival median was 11 months. One-year survival rate (by KaplanMeier was 50.7%. 14 patients are alive and continue to participate in the study during the first year of observation.Conclusion. Intraperitoneal aerosol chemotherapy under pressure (IACUP is a simple, minimally invasive and safe method for the palliative treatment of patients with disseminated carcinomatosis of gastric cancer. We developed the treatment Protocol that allows us to achieve one-year survival of more than half of patients.

  20. Introducing Toxics

    Directory of Open Access Journals (Sweden)

    David C. Bellinger

    2013-04-01

    Full Text Available With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present their work in as much detail as they wish. Toxics will publish original research papers, conventional reviews, meta-analyses, short communications, theoretical papers, case reports, commentaries and policy perspectives, and book reviews (Book reviews will be solicited and should not be submitted without invitation. Toxins and toxicants concern individuals from a wide range of disciplines, and Toxics is interested in receiving papers that represent the full range of approaches applied to their study, including in vitro studies, studies that use experimental animal or non-animal models, studies of humans or other biological populations, and mathematical modeling. We are excited to get underway and look forward to working with authors in the scientific and medical communities and providing them with a novel venue for sharing their work. [...

  1. Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models.

    Science.gov (United States)

    Pal, Shipra; Sadhu, Arpita Sengupta; Patra, Swarup; Mukherjea, Kalyan K

    2008-11-12

    CDDP for 10 days. Our comparative studies with normal and drug treated animals reveal that the drug does not affect the body weight of the drug treated animals significantly. The biochemical parameters like ALT and AST levels are also within normal limits which rules out hepatotoxicity. The detailed histological studies by SEM reveal that the hepatic, kidney and spleen tissues are not adversely affected by the drug. Comparison of biochemical parameters with the CDDP treated animals show that Pt-ATP is not at all toxic like the CDDP. The Kaplan-Meier analysis of the survival data of Set I has shown promising results with a significance of p < 0.0001. Set I results are promising and indicating antineoplastic efficacy of the synthesized drug with increased life span of the animals. Biochemical analysis, hematological and SEM studies revealed that the drug was neither nephrotoxic nor hepato-spleeno-toxic under the experimental set up.

  2. Antimony Toxicity

    Directory of Open Access Journals (Sweden)

    Shyam Sundar

    2010-12-01

    Full Text Available Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically.

  3. Antimony Toxicity

    OpenAIRE

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The...

  4. Oxygen toxicity

    Directory of Open Access Journals (Sweden)

    C. A. van der Westhuizen

    1990-07-01

    Full Text Available Oxygen has been discovered about 200 years ago. Since then the vital physiological involvement of oxygen in various biologi­cal processes, mainly energy production, has been established. However, in the body molecular oxygen can be converted to toxic oxygen metabolites such as superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These toxic metabolites are produced mainly in the mitochondria, plasma membranes and endoplasmic reticulum.

  5. Post-disposal safety assessment of toxic and radioactive waste: waste types, disposal practices, disposal criteria, assessment methods and post-disposal impacts

    International Nuclear Information System (INIS)

    Torres, C.; Simon, I.; Little, R.H.; Charles, D.; Grogan, H.A.; Smith, G.M.; Sumerling, T.J.; Watkins, B.M.

    1993-01-01

    The need for safety assessments of waste disposal stems not only from the implementation of regulations requiring the assessment of environmental effects, but also from the more general need to justify decisions on protection requirements. As waste-disposal methods have become more technologically based, through the application of more highly engineered design concepts and through more rigorous and specific limitations on the types and quantities of the waste disposed, it follows that assessment procedures also must become more sophisticated. It is the overall aim of this study to improve the predictive modelling capacity for post-disposal safety assessments of land-based disposal facilities through the development and testing of a comprehensive, yet practicable, assessment framework. This report records all the work which has been undertaken during Phase 1 of the study. Waste types, disposal practices, disposal criteria and assessment methods for both toxic and radioactive waste are reviewed with the purpose of identifying those features relevant to assessment methodology development. Difference and similarities in waste types, disposal practices, criteria and assessment methods between countries, and between toxic and radioactive wastes are highlighted and discussed. Finally, an approach to identify post-disposal impacts, how they arise and their effects on humans and the environment is described

  6. Menacalc, a quantitative method of metastasis assessment, as a prognostic marker for axillary node-negative breast cancer

    International Nuclear Information System (INIS)

    Forse, Catherine L.; Agarwal, Seema; Pinnaduwage, Dushanthi; Gertler, Frank; Condeelis, John S.; Lin, Juan; Xue, Xiaonan; Johung, Kimberly; Mulligan, Anna Marie; Rohan, Thomas E.; Bull, Shelley B.; Andrulis, Irene L.

    2015-01-01

    Mena calc is an immunofluorescence-based, quantitative method in which expression of the non-invasive Mena protein isoform (Mena11a) is subtracted from total Mena protein expression. Previous work has found a significant positive association between Mena calc and risk of death from breast cancer. Our goal was to determine if Mena calc could be used as an independent prognostic marker for axillary node-negative (ANN) breast cancer. Analysis of the association of Mena calc with overall survival (death from any cause) was performed for 403 ANN tumors using Kaplan Meier survival curves and the univariate Cox proportional hazards (PH) model with the log-rank or the likelihood ratio test. Cox PH models were used to estimate hazard ratios (HRs) for the association of Mena calc with risk of death after adjustment for HER2 status and clinicopathological tumor features. High Mena calc was associated with increased risk of death from any cause (P = 0.0199, HR (CI) = 2.18 (1.19, 4.00)). A similarly elevated risk of death was found in the subset of the Mena calc cohort which did not receive hormone or chemotherapy (n = 142) (P = 0.0052, HR (CI) = 3.80 (1.58, 9.97)). There was a trend toward increased risk of death with relatively high Mena calc in the HER2, basal and luminal molecular subtypes. Mena calc may serve as an independent prognostic biomarker for the ANN breast cancer patient population. The online version of this article (doi:10.1186/s12885-015-1468-6) contains supplementary material, which is available to authorized users

  7. Separations chemistry of toxic metals

    International Nuclear Information System (INIS)

    Smith, P.; Barr, M.; Barrans, R.

    1996-01-01

    Sequestering and removing toxic metal ions from their surroundings is an increasingly active area of research and is gaining importance in light of current environmental contamination problems both within the DOE complex and externally. One method of separating metal ions is to complex them to a molecule (a ligand or chelator) which exhibits specific binding affinity for a toxic metal, even in the presence of other more benign metals. This approach makes use of the sometimes subtle differences between toxic and non-toxic metals resulting from variations in size, charge and shape. For example, toxic metals such as chromium, arsenic, and technetium exist in the environment as oxyanions, negatively charged species with a characteristic tetrahedral shape. Other toxic metals such as actinides and heavy metals are positively charged spheres with specific affinities for particular donor atoms such as oxygen (for actinides) and nitrogen (for heavy metals). In most cases the toxic metals are found in the presence of much larger quantities of less toxic metals such as sodium, calcium and iron. The selectivity of the chelators is critical to the goal of removing the toxic metals from their less toxic counterparts. The approach was to build a ligand framework that complements the unique characteristics of the toxic metal (size, charge and shape) while minimizing interactions with non-toxic metals. The authors have designed ligands exhibiting specificity for the target metals; they have synthesized, characterized and tested these ligands; and they have shown that they exhibit the proposed selectivity and cooperative binding effects

  8. Pediatric Toxic Shock Syndrome

    Directory of Open Access Journals (Sweden)

    Jennifer Yee

    2017-09-01

    Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

  9. Separation of toxic rhodamine B from aqueous solution using an efficient low-cost material, Azolla pinnata, by adsorption method.

    Science.gov (United States)

    Kooh, Muhammad Raziq Rahimi; Lim, Linda B L; Lim, Lee Hoon; Dahri, Muhammad Khairud

    2016-02-01

    This study investigated the potential of untreated Azolla pinnata (AP) to remove toxic rhodamine B (RB) dye. The effects of adsorbent dosage, pH, ionic strength, contact time, and concentration were studied. Experiments involving the effects of pH and ionic strength indicated that hydrophobic-hydrophobic interactions might be the dominant force of attraction for the RB-AP adsorption system. The kinetics modelling of the kinetics experiment showed that pseudo-second-order best represented the adsorption process. The Weber-Morris intraparticle diffusion model showed that intraparticle diffusion is not the rate-limiting step, while the Boyd model suggested that film diffusion might be rate-limiting. The adsorption isotherm model, Langmuir, best represented the adsorption process, and the maximum adsorption capacity was predicted to be 72.2 and 199.7 mg g(-1) at 25 and 65 °C, respectively. Thermodynamics study indicates spontaneity, endothermic and physisorption-dominant adsorption process. The adsorbents were regenerated to satisfactory level with distilled water, HNO3 and NaOH. Pre-treatment of adsorbent with oxalic acid, citric acid, NaOH, HCl and phosphoric acid was investigated but the adsorption capacity was less than the untreated AP.

  10. Investigation of the toxic effect of cadmium on Candida humicola and Bacillus subtilis using a microcalorimetric method

    International Nuclear Information System (INIS)

    Chen Haiyan; Yao Jun; Zhou Yong; Chen Huilun; Wang Fei; Gai Nan; Zhuang Rensheng; Ceccanti, Brunello; Maskow, Thomas; Zaray, Gyula

    2008-01-01

    In this study, the technique of microcalorimetry based on heat-output by aerobic bacterial respiration was explored to evaluate the toxic effect of cadmium on Candida humicola, Bacillus subtilis, singularly or in a mixture of both. Power-time curves of the growth metabolism of C. humicola and B. subtilis and the effect of Cd 2+ were studied using the TAM III (the third generation thermal activity monitor) multi-channel microcalorimetric system, isothermal mode, at 28 deg. C. The differences in shape of the power-time curves and the thermodynamic and kinetic characteristics of microorganisms growth were compared. The effect of cadmium added into microorganism would significantly reduce the life cycle and change the thermal effect of microbial metabolic process with different concentrations of Cd 2+ . The experimental results revealed that at the same concentration, the sequence of inhibitory ratio (I) and maximum thermal power (P max ) of the Cd 2+ was: mixed microorganisms > C. humicola > B. subtilis. The sequence of total thermal effect (Q total ) and growth rate constant (k) is mixed microorganisms > B. subtilis > C. humicola. These results are important to further studies of the physiology and pharmacology of C. humicola and B. subtilis and may support the theory of restoring contaminated soil

  11. Evaluation of the mobility and pollution index of selected essential/toxic metals in paddy soil by sequential extraction method.

    Science.gov (United States)

    Hasan, Maria; Kausar, Dilshad; Akhter, Gulraiz; Shah, Munir H

    2018-01-01

    Comparative distribution and mobility of selected essential and toxic metals in the paddy soil from district Sargodha, Pakistan was evaluated by the modified Community Bureau of Reference (mBCR) sequential extraction procedure. Most of the soil samples showed slightly alkaline nature while the soil texture was predominantly silty loam in nature. The metal contents were quantified in the exchangeable, reducible, oxidisable and residual fractions of the soil by flame atomic absorption spectrophotometry and the metal data were subjected to the statistical analyses in order to evaluate the mutual relationships among the metals in each fraction. Among the metals, Ca, Sr and Mn were found to be more mobile in the soil. A number of significant correlations between different metal pairs were noted in various fractions. Contamination factor, geoaccumulation index and enrichment factor revealed extremely severe enrichment/contamination for Cd; moderate to significant enrichment/contamination for Ni, Zn, Co and Pb while Cr, Sr, Cu and Mn revealed minimal to moderate contamination and accumulation in the soil. Multivariate cluster analysis showed significant anthropogenic intrusions of the metals in various fractions. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Using an interlaboratory study to revise methods for conducting 10-d to 42-d water or sediment toxicity tests with Hyalella azteca

    Science.gov (United States)

    Ivey, Chris D.; Ingersoll, Christopher G.; Brumbaugh, William G.; Hammer, Edward J.; Mount, David R.; Hockett, J. Russell; Norberg-King, Teresa J.; Soucek, Dave; Taylor, Lisa

    2016-01-01

    Studies have been conducted to refine US Environmental Protection Agency, ASTM International, and Environment Canada standard methods for conducting 42-d reproduction tests with Hyalella azteca in water or in sediment. Modifications to the H. azteca method include better-defined ionic composition requirements for exposure water (i.e., >15 mg/L of chloride and >0.02 mg/L of bromide) and improved survival, growth, and reproduction with alternate diets provided as increased rations over time in water-only or whole-sediment toxicity tests. A total of 24 laboratories volunteered to participate in the present interlaboratory study evaluating the performance of H. azteca in 42-d studies in control sand or control sediment using the refined methods. Improved growth and reproduction of H. azteca was observed with 2 alternate diets of 1) ramped diatoms (Thalassiosira weissflogii) + ramped Tetramin or 2) yeast–cerophyll–trout chow (YCT) + ramped Tetramin, especially when compared with results from the traditional diet of 1.8 mg YCT/d. Laboratories were able to meet proposed test acceptability criteria and in most cases had lower variation in growth or reproduction compared with previous interlaboratory studies using the traditional YCT diet. Laboratory success in conducting 42-d H. azteca exposures benefited from adherence to several key requirements of the detailed testing, culturing, and handling methods. Results from the present interlaboratory study are being used to help revise standard methods for conducting 10-d to 42-d water or sediment toxicity exposures with H. azteca.

  13. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

  14. Radionuclide toxicity

    International Nuclear Information System (INIS)

    Galle, P.

    1982-01-01

    The aim of this symposium was to review the radionuclide toxicity problems. Five topics were discussed: (1) natural and artificial radionuclides (origin, presence or emission in the environment, human irradiation); (2) environmental behaviour of radionuclides and transfer to man; (3) metabolism and toxicity of radionuclides (radioiodine, strontium, rare gas released from nuclear power plants, ruthenium-activation metals, rare earths, tritium, carbon 14, plutonium, americium, curium and einsteinium, neptunium, californium, uranium) cancerogenous effects of radon 222 and of its danghter products; (4) comparison of the hazards of various types of energy; (5) human epidemiology of radionuclide toxicity (bone cancer induction by radium, lung cancer induction by radon daughter products, liver cancer and leukaemia following the use of Thorotrast, thyroid cancer; other site of cancer induction by radionuclides) [fr

  15. Short-term Clinical Course of Knee Pain in Children and Adolescents: A Feasibility Study Using Electronic Methods of Data Collection.

    Science.gov (United States)

    Swain, Michael S; Kamper, Steven J; Maher, Chris G; Latimer, Jane; Broderick, Carolyn; McKay, Damien; Henschke, Nicholas

    2017-10-01

    Musculoskeletal disorders, such as knee pain, are common in children and adolescents, but there is a lack of high quality research that evaluates the clinical course of these conditions. The objective of this study was to evaluate the feasibility of conducting a prospective study of children and adolescents with knee pain using electronic methods of data collection. Children and adolescents with knee pain that presented to primary care physiotherapy clinics were enrolled and followed-up on a weekly basis via short messaging service (SMS) until their knee pain had recovered (i.e. two consecutive weeks of no pain). Feasibility was assessed in terms of recruitment, retention and response rates to SMS and an online questionnaire. Baseline and 6-month follow-up measures included pain, disability, physical function, physical activity and health related quality of life. Kaplan-Meier survival analysis was used to estimate the median time to knee pain recovery. Thirty participants (mean age 13.0 ± 2.2 years, 53% boys) were recruited over 26 months. The overall response rate to weekly SMS follow-up was 71.3% (809 received/1135 sent). One third of participants stopped responding to SMS prior to recovery, and these participants typically had a much lower response rate during the time they remained in the study. At 6-month follow-up, 80% of the cohort completed the final online questionnaire, and 29% of participants still reported current knee pain (≥1/10 VAS). The median time for knee pain recovery was 8 weeks (95%CI: 5, 10). Electronic data collection alone seems insufficient to track pain recovery in young people and may need to be supplemented with more traditional data collection methods. Researchers should consider further measures to address slow recruitment rates and high attrition when designing large prospective studies of children and adolescents in the future. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Cheap non-toxic non-corrosive method of glass cleaning evaluated by contact angle, AFM, and SEM-EDX measurements.

    Science.gov (United States)

    Dey, Tania; Naughton, Daragh

    2017-05-01

    Glass surface cleaning is the very first step in advanced coating deposition and it also finds use in conserving museum objects. However, most of the wet chemical methods of glass cleaning use toxic and corrosive chemicals like concentrated sulfuric acid (H 2 SO 4 ), piranha (a mixture of concentrated sulfuric acid and 30% hydrogen peroxide), and hydrogen fluoride (HF). On the other hand, most of the dry cleaning techniques like UV-ozone, plasma, and laser treatment require costly instruments. In this report, five eco-friendly wet chemical methods of glass cleaning were evaluated in terms of contact angle (measured by optical tensiometer), nano-scale surface roughness (measured by atomic force microscopy or AFM), and elemental composition (measured by energy dispersive x-ray spectroscopy or SEM-EDX). These glass cleaning methods are devoid of harsh chemicals and costly equipment, hence can be applied in situ in close proximity with plantation such as greenhouse or upon subtle objects such as museum artifacts. Out of these five methods, three methods are based on the chemical principle of chelation. It was found that the citric acid cleaning method gave the greatest change in contact angle within the hydrophilic regime (14.25° for new glass) indicating effective cleansing and the least surface roughness (0.178 nm for new glass) indicating no corrosive effect. One of the glass sample showed unique features which were traced backed to the history of the glass usage.

  17. The use of hogdahl convention k0 neutron activation analysis (NAA) standardization method and atomic absortion spectroscopy (ASS) for determination of toxic elements in foodstuffs

    International Nuclear Information System (INIS)

    Ahiamadie, H.

    2008-06-01

    Copper, cadmium, tin, chromium, arsenic, antimony, vanadium and mercury contents were determined in various foodstuffs (Mussa paradisiaca (plantains), Manihot esculentus (cassavas), Vantosoma sagittifolium (cocoyam). Vantosoma sagittifolium leaves (kontomire), Lycopersicum esculentus (tomatoes), Capsicum species (peppers), Solanum melongena (garden eggs), Nbelmoschus esculentus (okro), and Colocasia esculenta (kooko or taro)) produced in the Wassa West District, Ghana. These plants are the basis of human nutrition in the study area. These elements were determined using Hogdahl convention k 0 Instrumental Neutron Activation Analysis (NAA) Standardization Method and Atomic Absorption Spectroscopy (AAS). The elements in the various foodstuffs and their concentration ranges were Cu (16.87-180.06) mg/kg, As (2.68-9.84) µg/g, Cd (0.63-5.64) µg/g, Hg (0.01-67) ng/g, Cr (0.03-3.66) µg/g, Sb (1.1- 18.6) ng/g, Sn (3.4-58.4) ng/g, and V (12-99) ng/g. The study showed that there are high levels of toxic elements in the foodstuffs grown in the mining areas as compared to that of the non-mining area (i.e., control area). This could be attributed to gold mines pollution. Compared to the World Health Organization (WHO) permissible levels of toxic elements in foods, Cu, Cr and Hg were above the permissible levels whereas the concentrations of As, Cd. Sb, Sn and V fall within the permissible levels. (au)

  18. Thyroid cancer in toxic and non-toxic multinodular goiter

    Directory of Open Access Journals (Sweden)

    Cerci C

    2007-01-01

    Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

  19. A proposal for a test method for assessment of hazard property HP 12 ("Release of an acute toxic gas") in hazardous waste classification - Experience from 49 waste.

    Science.gov (United States)

    Hennebert, Pierre; Samaali, Ismahen; Molina, Pauline

    2016-12-01

    A stepwise method for assessment of the HP 12 is proposed and tested with 49 waste samples. The hazard property HP 12 is defined as "Release of an acute toxic gas": waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact with water or an acid. When a waste contains a substance assigned to one of the following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, 2014b). When the substances with the cited hazard statement codes react with water or an acid, they can release HCl, Cl 2 , HF, HCN, PH 3 , H 2 S, SO 2 (and two other gases very unlikely to be emitted, hydrazoic acid HN 3 and selenium oxide SeO 2 - a solid with low vapor pressure). Hence, a method is proposed:For a set of 49 waste, water addition did not produce gas. Nearly all the solid waste produced a gas in contact with hydrochloric acid in 5 min in an automated calcimeter with a volume >0.1L of gas per kg of waste. Since a plateau of pressure is reached only for half of the samples in 5 min, 6 h trial with calorimetric bombs or glass flasks were done and confirmed the results. Identification of the gases by portable probes showed that most of the tested samples emit mainly CO 2 . Toxic gases are emitted by four waste: metallic dust from the aluminum industry (CO), two air pollution control residue of industrial waste incinerator (H 2 S) and a halogenated solvent (organic volatile(s) compound(s)). HF has not been measured in these trials started before the present definition of HP 12. According to the definition of HP 12, only the H 2 S emission of substances with hazard statement EUH031 is accounted for. In view of the calcium content of the two air pollution control residue, the presence of calcium sulphide (EUH031) can be assumed. These two waste are therefore classified potentially hazardous for HP 12, from a total of 49 waste. They are also classified as hazardous for other properties (HP 7

  20. Bioassay method for toxicity studies of insecticide formulations to Tuta absoluta (meyrick, 1917) Metodologia de bioensaio para estudos de toxicidade de formulações comerciais de inseticidas a Tuta absoluta (Meyrick, 1917)

    OpenAIRE

    Tarcísio Visintin da Silva Galdino; Marcelo Coutinho Picanço; Elisangela Gomes Fidelis de Morais; Nilson Rodrigues Silva; Geverson Aelton Rezende da Silva; Mayara Cristina Lopes

    2011-01-01

    Chemical control is the main method for controlling the tomato leafminer, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae). Reported techniques for the evaluation of insecticide toxicity to the tomato leafminer are not in agreement with field conditions and do not allow us to verify whether doses used in the field are efficient for control. Thus, the objective of this work was to develop a bioassay methodology to study the toxicity of insecticide formulations to T. absoluta that repre...

  1. Toxic Cyanobacteria in Svalbard: Chemical Diversity of Microcystins Detected Using a Liquid Chromatography Mass Spectrometry Precursor Ion Screening Method

    Directory of Open Access Journals (Sweden)

    Julia Kleinteich

    2018-04-01

    Full Text Available Cyanobacteria synthesize a large variety of secondary metabolites including toxins. Microcystins (MCs with hepato- and neurotoxic potential are well studied in bloom-forming planktonic species of temperate and tropical regions. Cyanobacterial biofilms thriving in the polar regions have recently emerged as a rich source for cyanobacterial secondary metabolites including previously undescribed congeners of microcystin. However, detection and detailed identification of these compounds is difficult due to unusual sample matrices and structural congeners produced. We here report a time-efficient liquid chromatography-mass spectrometry (LC-MS precursor ion screening method that facilitates microcystin detection and identification. We applied this method to detect six different MC congeners in 8 out of 26 microbial mat samples of the Svalbard Archipelago in the Arctic. The congeners, of which [Asp3, ADMAdda5, Dhb7] MC-LR was most abundant, were similar to those reported in other polar habitats. Microcystins were also determined using an Adda-specific enzyme-linked immunosorbent assay (Adda-ELISA. Nostoc sp. was identified as a putative toxin producer using molecular methods that targeted 16S rRNA genes and genes involved in microcystin production. The mcy genes detected showed highest similarities to other Arctic or Antarctic sequences. The LC-MS precursor ion screening method could be useful for microcystin detection in unusual matrices such as benthic biofilms or lichen.

  2. Hydrophobic Sand Is a Non-Toxic Method of Urine Collection, Appropriate for Urinary Metal Analysis in the Rat

    Directory of Open Access Journals (Sweden)

    Jessica F. Hoffman

    2017-10-01

    Full Text Available Hydrophobic sand is a relatively new method of urine collection in the rodent, comparable to the established method using a metabolic cage. Urine samples are often used in rodent research, especially for biomarkers of health changes after internal contamination from embedded metals, such as in a model of a military shrapnel wound. However, little research has been done on the potential interference of hydrophobic sand with urine metal concentrations either by contamination from the sand particulate, or adsorption of metals from the urine. We compare urine collected from rats using the metabolic cage method and the hydrophobic sand method for differences in metal concentration of common urinary metals, and examine physical properties of the sand material for potential sources of contamination. We found minimal risk of internal contamination of the rat by hydrophobic sand, and no interference of the sand with several common metals of interest (cobalt, strontium, copper, and manganese, although we advise caution in studies of aluminum in urine.

  3. An innovative, simple, fast, and less toxic high-performance liquid chromatographic method for determination of prednisone in capsules

    Directory of Open Access Journals (Sweden)

    Pedro Henrique Reis da Silva

    2017-06-01

    Full Text Available ABSTRACT Prednisone is an anti-inflammatory steroid drug widely used in clinical practice. However, no high-performance liquid chromatographic (HPLC method has been described in the literature for the determination of prednisone in capsules until now. Thus, an HPLC method was developed using a C18 (250x4.0, 5 µm column, with methanol:water (70:30 as mobile phase at a flow rate of 1 mL/min and detection at 240 nm. The developed method was validated following current Brazilian legislation. Additionally, linearity was assessed by evaluating the assumptions of normality, homoscedasticity, and independency of residuals, and the fit to the linear model. The method showed linearity (r2>0.99 over the range of 14.0-26.0 µg/mL, selectivity, precision (RSD<2.0%, robustness, and accuracy (average recovery of 100.05%. The chromatographic procedure was applied for assay and uniformity content determination of three different batches of prednisone capsules, showing to be suitable for their quality control.

  4. Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

    International Nuclear Information System (INIS)

    Barney, Brandon M.; Petersen, Ivy A.; Dowdy, Sean C.; Bakkum-Gamez, Jamie N.; Haddock, Michael G.

    2012-01-01

    Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORT dose was 12.5 Gy (range, 10–20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20–62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11–203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.

  5. Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Barney, Brandon M., E-mail: barney.brandon@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Dowdy, Sean C.; Bakkum-Gamez, Jamie N. [Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota (United States); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2012-05-01

    Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORT dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.

  6. Studies by nuclear and physico-chemical methods of tissue's metallic contamination located around biomaterials. Toxicity measurements of several biomaterials residual radioactivity

    International Nuclear Information System (INIS)

    Guibert, Geoffroy

    2004-01-01

    Implants used as biomaterials fulfill conditions of functionality, compatibility and occasionally bio-activity. There are four main families of biomaterials: metals and metal alloys, polymers, bio-ceramics and natural materials. Because of corrosion and friction in the human body, implants generate debris. These debris develop different problems: toxicity, inflammatory reactions, prosthetic unsealing by osseous dissolution. Nature, size, morphology and amount of debris are the parameters which have an influence on tissue response. We characterize metallic contamination coming from knee prosthesis into surrounding capsular tissue by depth migration, in vivo behaviours, content, size and nature of debris. The PIXE-RBS and STEM-EDXS methods, that we used, are complementary, especially about characterization scale. Debris contamination distributed in the whole articulation is very heterogeneous. Debris migrate on several thousands μm in tissue. Solid metallic particles, μm, are found in the most polluted samples, for both kinds of alloys TA6V and CrCoMo. In the mean volume analysed by PIXE, the in vivo mass ratios [Ti]/[V] and [Co]/[Cr] confirm the chemical stability of TA6V debris and chemical evolution of CrCoMo debris. Complementary measures of TA6V grains, on a nano-metric scale by STEM-EDXS, show a dissolution of coarse grain (μm) in smaller grains (nm). Locally, TA6V grains of a phase are detected and could indicate a preferential dissolution of β phase (grain boundaries) with dropping of Al and V, both toxic and carcinogenic elements. A thin target protocol development correlates PIXE and histological analysis on the same zone. This protocol allows to locate other pathologies in relationship with weaker metal contamination, μg/g, thanks to the great sensitivity of PIXE method. Harmlessness with respect to the residual radioactivity of several natural or synthetic biomaterials is established, using ultra low background noise γ detection system. (author)

  7. An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results.

    Science.gov (United States)

    Andresen, H; Aydin, B E; Mueller, A; Iwersen-Bergmann, S

    2011-09-01

    Abuse of gamma-hydroxybutyric acid (GHB) has been known since the early 1990's, but is not as widespread as the consumption of other illegal drugs. However, the number of severe intoxications with fatal outcomes is comparatively high; not the least of which is brought about by the consumption of the currently legal precursor substances gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). In regards to previous assumptions, addiction to GHB or its analogues can occur with severe symptoms of withdrawal. Moreover, GHB can be used for drug-facilitated sexual assaults. Its pharmacological effects are generated mainly by interaction with both GABA(B) and GHB receptors, as well as its influence on other transmitter systems in the human brain. Numerous analytical methods for determining GHB using chromatographic techniques were published in recent years, and an enzymatic screening method was established. However, the short window of GHB detection in blood or urine due to its rapid metabolism is a challenge. Furthermore, despite several studies addressing this problem, evaluation of analytical results can be difficult: GHB is a metabolite of GABA (gamma-aminobutyric acid); a differentiation between endogenous and exogenous concentrations has to be made. Apart from this, in samples with a longer storage interval and especially in postmortem specimens, higher levels can be measured due to GHB generation during this postmortem interval or storage time. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Toxic metal levels in cocoa powder and chocolate by ICP-MS method after microwave-assisted digestion.

    Science.gov (United States)

    Lo Dico, Gianluigi Maria; Galvano, Fabio; Dugo, Giacomo; D'ascenzi, Carlo; Macaluso, Andrea; Vella, Antonio; Giangrosso, Giuseppe; Cammilleri, Gaetano; Ferrantelli, Vincenzo

    2018-04-15

    The Commission Regulation (EC) Regulation N. 488/2014, established the concentration limits for cadmium in specific products based on cocoa and chocolate products as from January 2019. Based on this information there is a need to determine ultratrace levels of elements that might be presents in cocoa and chocolate products. In this work, the concentrations of Arsenic, Antimony, Cadmium, Chromium, Lead, Selenium and Vanadium were evaluated in cocoa powder and chocolate by the validation of an ICP-MS method. Good selectivity/specificity, recovery, repeatability and within-laboratory reproducibility, LOD, LOQ, range of linearity, standard measurement uncertainty parameters for method validation were achieved, in accordance with Commission Regulation. The cocoa powder revealed the maximum metal concentrations of 0.303 ± 0.035 mg/kg for cadmium, 1.228 ± 0.146 mg/kg for lead and 0.094 ± 0.013 mg/kg for arsenic. A significant difference was found between cocoa powder and chocolate samples (p < .05). Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Toxic Leadership in Educational Organizations

    Science.gov (United States)

    Green, James E.

    2014-01-01

    While research on the traits and skills of effective leaders is plentiful, only recently has the phenomenon of toxic leadership begun to be investigated. This research report focuses on toxic leadership in educational organizations--its prevalence, as well as the characteristics and early indicators. Using mixed methods, the study found four…

  10. New methods for estimating follow-up rates in cohort studies

    Directory of Open Access Journals (Sweden)

    Xiaonan Xue

    2017-12-01

    Full Text Available Abstract Background The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the “Percentage Method”, defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark’s Completeness Index (CCI also have limitations. Methods We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR, which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset. Results Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%. Conclusions The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and

  11. An ultrasound-assisted digestion method for the determination of toxic element concentrations in ash samples by inductively coupled plasma optical emission spectrometry

    International Nuclear Information System (INIS)

    Ilander, Aki; Vaeisaenen, Ari

    2007-01-01

    A method of ultrasound-assisted digestion followed by inductively coupled plasma optical emission spectrometry (ICP-OES) used for the determination of toxic element concentrations (arsenic, barium, cobalt, copper, lead, nickel, strontium, vanadium and zinc) in ash samples was developed. All the measurements were performed in robust plasma conditions which were tested by measuring the Mg(II) 280.270 nm/Mg(I) 285.213 nm line intensity ratios. The highest line intensity ratios were observed when a nebulizer gas flow of 0.6 L min -1 , auxiliary gas flow of 0.2 L min -1 and plasma power of 1400 W were used for radially viewed plasma. The analysis of SRM 1633b showed that the ultrasound-assisted method developed is highly comparable with the microwave digestion method standardized by the United States Environmental Protection Agency (EPA-3052). The ultrasound-assisted digestion with a digestion solution of aqua regia and hydrofluoric acid (HF) resulted in recovery rates of over 81%. One exception is arsenic which resulted in recoveries of about 60% only; however, it could be digested with good recovery (>90%) using a digestion solution of 5 mL of water and 5 mL of aqua regia. The major advantage of the ultrasound-assisted digestion over microwave digestion is the high treatment rate (30 samples simultaneously with a sonication time of 18 min)

  12. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  13. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    all chemicals and impact pathways characterizes the contribution of each factor to the total variation of 10–12 orders of magnitude in impacts per kg across all chemicals. This large variation between characterisation factors for different chemicals as well as the 3 orders of magnitude uncertainty....... As a whole, the assessment of toxicity in LCA has progressed on a very sharp learning curve during the past 20 years. This rapid progression is expected to continue in the coming years, focusing more on direct exposure of workers to chemicals during manufacturing and of consumers during product use...

  14. A comparison of four porewater sampling methods for metal mixtures and dissolved organic carbon and the implications for sediment toxicity evaluations.

    Science.gov (United States)

    Cleveland, Danielle; Brumbaugh, William G; MacDonald, Donald D

    2017-11-01

    Evaluations of sediment quality conditions are commonly conducted using whole-sediment chemistry analyses but can be enhanced by evaluating multiple lines of evidence, including measures of the bioavailable forms of contaminants. In particular, porewater chemistry data provide information that is directly relevant for interpreting sediment toxicity data. Various methods for sampling porewater for trace metals and dissolved organic carbon (DOC), which is an important moderator of metal bioavailability, have been employed. The present study compares the peeper, push point, centrifugation, and diffusive gradients in thin films (DGT) methods for the quantification of 6 metals and DOC. The methods were evaluated at low and high concentrations of metals in 3 sediments having different concentrations of total organic carbon and acid volatile sulfide and different particle-size distributions. At low metal concentrations, centrifugation and push point sampling resulted in up to 100 times higher concentrations of metals and DOC in porewater compared with peepers and DGTs. At elevated metal levels, the measured concentrations were in better agreement among the 4 sampling techniques. The results indicate that there can be marked differences among operationally different porewater sampling methods, and it is unclear if there is a definitive best method for sampling metals and DOC in porewater. Environ Toxicol Chem 2017;36:2906-2915. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

  15. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. ... The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab ...

  16. Survival of Root-filled Teeth in the Swedish Adult Population

    DEFF Research Database (Denmark)

    Fransson, Helena; Dawson, Victoria S; Frisk, Fredrik

    2016-01-01

    INTRODUCTION: The aim was to assess survival in the Swedish population of teeth treated by nonsurgical root canal treatment during 2009. METHODS: Data from the Swedish Social Insurance Agency were analyzed by Kaplan-Meier analysis to assess cumulative tooth survival during a period of 5-6 years o...

  17. STAT3 inhibitor enhances chemotherapy drug efficacy by ...

    African Journals Online (AJOL)

    Immunohistochemistry and Kaplan-Meier method of survival analysis were used to determine chemoresistance trends in patients. STAT3 inhibitor treatment, RNAi or ectopic overexpression of STAT3 or MUC1 in NSCLC cells were used to determine their inter-molecular relation and for modulating stemness-related genes.

  18. Survival analysis II: Cox regression

    NARCIS (Netherlands)

    Stel, Vianda S.; Dekker, Friedo W.; Tripepi, Giovanni; Zoccali, Carmine; Jager, Kitty J.

    2011-01-01

    In contrast to the Kaplan-Meier method, Cox proportional hazards regression can provide an effect estimate by quantifying the difference in survival between patient groups and can adjust for confounding effects of other variables. The purpose of this article is to explain the basic concepts of the

  19. Modelling the survivorship of Nigeria children in their first 10 years of ...

    African Journals Online (AJOL)

    Fagbamigbe

    Conflict of Interest: Authors declared no conflict of interest ... Keywords: Survivorship, Nigeria, children mortality, Kaplan Meier, Brass Indirect method, Prediction ... variables or sex of older siblings, post- neonatal mortality is 12% higher and 2nd ... Relationship between maternal education and child survival in developing ...

  20. The influence of obesity on response to tumour necrosis factor-α inhibitors in psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Glintborg, Bente; Kristensen, Lars Erik

    2016-01-01

    OBJECTIVES: To investigate the impact of obesity on response to the first TNF-α inhibitor (TNFI) treatment course in patients with PsA followed in routine care. METHODS: We performed an observational cohort study based on the Danish and Icelandic biologics registries. Kaplan-Meier plots, Cox and ...

  1. Application of the standard lymphadenectomy in gastric adenocarcinoma

    International Nuclear Information System (INIS)

    Aguirre Fernandez, Roberto Eduardo; LLera Dominguez, Gerardo de la; Pennon Guerra, Maria; Alvarez Perez, Alvaro

    2011-01-01

    The 5-years postoperative survival of 132 patients operated on due to gastric adenocarcinoma that underwent lymphadenectomy of the two first ganglionic levels. The results of the epidemiological parameters were determined and the survival by Kaplan-Meier method was defined

  2. Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir

    DEFF Research Database (Denmark)

    Kirk, O; Mocroft, A; Pradier, C

    2001-01-01

    -up within the EuroSIDA study. METHODS: Changes in plasma viral load (pVL) and CD4 cell count from baseline were compared between treatment groups. Time to new AIDS-defining events and death were compared in Kaplan--Meier models, and Cox models were established to further assess differences in clinical...

  3. Enhanced toxic cloud knockdown spray system for decontamination applications

    Science.gov (United States)

    Betty, Rita G [Rio Rancho, NM; Tucker, Mark D [Albuquerque, NM; Brockmann, John E [Albuquerque, NM; Lucero, Daniel A [Albuquerque, NM; Levin, Bruce L [Tijeras, NM; Leonard, Jonathan [Albuquerque, NM

    2011-09-06

    Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

  4. Phase II Study of Paclitaxel Given Once per Week Along With Trastuzumab and Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

    Science.gov (United States)

    Dang, Chau; Iyengar, Neil; Datko, Farrah; D'Andrea, Gabriella; Theodoulou, Maria; Dickler, Maura; Goldfarb, Shari; Lake, Diana; Fasano, Julie; Fornier, Monica; Gilewski, Theresa; Modi, Shanu; Gajria, Devika; Moynahan, Mary Ellen; Hamilton, Nicola; Patil, Sujata; Jochelson, Maxine; Norton, Larry; Baselga, Jose; Hudis, Clifford

    2015-01-01

    Purpose The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients and Methods Patients with metastatic human epidermal growth factor receptor 2–positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m2 once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. Results From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Conclusion Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy. PMID:25547504

  5. A proposal for a test method for assessment of hazard property HP 12 (“Release of an acute toxic gas”) in hazardous waste classification - Experience from 49 waste

    OpenAIRE

    Hennebert , Pierre; Samaali , Ismahen; Molina , Pauline

    2016-01-01

    International audience; A stepwise method for assessment of the HP 12 is proposed and tested with 49 waste samples. The hazard property HP 12 is defined as “Release of an acute toxic gas”: waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact with water or an acid. When a waste contains a substance assigned to one of the following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, ...

  6. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

    Science.gov (United States)

    Dang, Chau; Iyengar, Neil; Datko, Farrah; D'Andrea, Gabriella; Theodoulou, Maria; Dickler, Maura; Goldfarb, Shari; Lake, Diana; Fasano, Julie; Fornier, Monica; Gilewski, Theresa; Modi, Shanu; Gajria, Devika; Moynahan, Mary Ellen; Hamilton, Nicola; Patil, Sujata; Jochelson, Maxine; Norton, Larry; Baselga, Jose; Hudis, Clifford

    2015-02-10

    The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients with metastatic human epidermal growth factor receptor 2-positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m(2) once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy. © 2014 by American Society of Clinical Oncology.

  7. Toxicity of pyrolysis gases from polyether sulfone

    Science.gov (United States)

    Hilado, C. J.; Olcomendy, E. M.

    1979-01-01

    A sample of polyether sulfone was evaluated for toxicity of pyrolysis gases, using the toxicity screening test method developed at the University of San Francisco. Animal response times were relatively short at pyrolysis temperatures of 600 to 800 C, with death occurring within 6 min. The principal toxicant appeared to be a compound other than carbon monoxide.

  8. Building a developmental toxicity ontology.

    Science.gov (United States)

    Baker, Nancy; Boobis, Alan; Burgoon, Lyle; Carney, Edward; Currie, Richard; Fritsche, Ellen; Knudsen, Thomas; Laffont, Madeleine; Piersma, Aldert H; Poole, Alan; Schneider, Steffen; Daston, George

    2018-04-03

    As more information is generated about modes of action for developmental toxicity and more data are generated using high-throughput and high-content technologies, it is becoming necessary to organize that information. This report discussed the need for a systematic representation of knowledge about developmental toxicity (i.e., an ontology) and proposes a method to build one based on knowledge of developmental biology and mode of action/ adverse outcome pathways in developmental toxicity. This report is the result of a consensus working group developing a plan to create an ontology for developmental toxicity that spans multiple levels of biological organization. This report provide a description of some of the challenges in building a developmental toxicity ontology and outlines a proposed methodology to meet those challenges. As the ontology is built on currently available web-based resources, a review of these resources is provided. Case studies on one of the most well-understood morphogens and developmental toxicants, retinoic acid, are presented as examples of how such an ontology might be developed. This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity. © 2018 Wiley Periodicals, Inc.

  9. TU-AB-202-12: A Novel Method to Map Endoscopic Video to CT for Treatment Planning and Toxicity Analysis in Radiation Therapy

    International Nuclear Information System (INIS)

    Ingram, W; Yang, J; Beadle, B; Wendt, R; Rao, A; Court, L

    2016-01-01

    Purpose: Endoscopic examinations are routine procedures for head-and-neck cancer patients. Our goal is to develop a method to map the recorded video to CT, providing valuable information for radiotherapy treatment planning and toxicity analysis. Methods: We map video frames to CT via virtual endoscopic images rendered at the real endoscope’s CT-space coordinates. We developed two complementary methods to find these coordinates by maximizing real-to-virtual image similarity:(1)Endoscope Tracking: moves the virtual endoscope frame-by-frame until the desired frame is reached. Utilizes prior knowledge of endoscope coordinates, but sensitive to local optima. (2)Location Search: moves the virtual endoscope along possible paths through the volume to find the desired frame. More robust, but more computationally expensive. We tested these methods on clay phantoms with embedded markers for point mapping and protruding bolus material for contour mapping, and we assessed them qualitatively on three patient exams. For mapped points we calculated 3D-distance errors, and for mapped contours we calculated mean absolute distances (MAD) from CT contours. Results: In phantoms, Endoscope Tracking had average point error=0.66±0.50cm and average bolus MAD=0.74±0.37cm for the first 80% of each video. After that the virtual endoscope got lost, increasing these values to 4.73±1.69cm and 4.06±0.30cm. Location Search had point error=0.49±0.44cm and MAD=0.53±0.28cm. Point errors were larger where the endoscope viewed the surface at shallow angles<10 degrees (1.38±0.62cm and 1.22±0.69cm for Endoscope Tracking and Location Search, respectively). In patients, Endoscope Tracking did not make it past the nasal cavity. However, Location Search found coordinates near the correct location for 70% of test frames. Its performance was best near the epiglottis and in the nasal cavity. Conclusion: Location Search is a robust and accurate technique to map endoscopic video to CT. Endoscope

  10. ["That flesh, pink and perishable": analysis of disease-free survival analysis in breast cancer in Gipuzkoa (Spain) in the presence of competing risks].

    Science.gov (United States)

    Martínez-Camblor, Pablo; Larrañaga, Nerea; Sarasqueta, Cristina; Mitxelena, María José; Basterretxea, Mikel

    2009-01-01

    To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied. Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

  11. Impact of reconstruction methods and pathological factors on survival after pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Salah Binziad

    2013-01-01

    Full Text Available Background: Surgery remains the mainstay of therapy for pancreatic head (PH and periampullary carcinoma (PC and provides the only chance of cure. Improvements of surgical technique, increased surgical experience and advances in anesthesia, intensive care and parenteral nutrition have substantially decreased surgical complications and increased survival. We evaluate the effects of reconstruction type, complications and pathological factors on survival and quality of life. Materials and Methods: This is a prospective study to evaluate the impact of various reconstruction methods of the pancreatic remnant after pancreaticoduodenectomy and the pathological characteristics of PC patients over 3.5 years. Patient characteristics and descriptive analysis in the three variable methods either with or without stent were compared with Chi-square test. Multivariate analysis was performed with the logistic regression analysis test and multinomial logistic regression analysis test. Survival rate was analyzed by use Kaplan-Meier test. Results: Forty-one consecutive patients with PC were enrolled. There were 23 men (56.1% and 18 women (43.9%, with a median age of 56 years (16 to 70 years. There were 24 cases of PH cancer, eight cases of PC, four cases of distal CBD cancer and five cases of duodenal carcinoma. Nine patients underwent duct-to-mucosa pancreatico jejunostomy (PJ, 17 patients underwent telescoping pancreatico jejunostomy (PJ and 15 patients pancreaticogastrostomy (PG. The pancreatic duct was stented in 30 patients while in 11 patients, the duct was not stented. The PJ duct-to-mucosa caused significantly less leakage, but longer operative and reconstructive times. Telescoping PJ was associated with the shortest hospital stay. There were 5 postoperative mortalities, while postoperative morbidities included pancreatic fistula-6 patients, delayed gastric emptying in-11, GI fistula-3, wound infection-12, burst abdomen-6 and pulmonary infection-2. Factors

  12. Reporting of loss to follow-up information in randomised controlled trials with time-to-event outcomes: a literature survey

    Directory of Open Access Journals (Sweden)

    Bender Ralf

    2011-09-01

    Full Text Available Abstract Background To assess the reporting of loss to follow-up (LTFU information in articles on randomised controlled trials (RCTs with time-to-event outcomes, and to assess whether discrepancies affect the validity of study results. Methods Literature survey of all issues of the BMJ, Lancet, JAMA, and New England Journal of Medicine published between 2003 and 2005. Eligible articles were reports of RCTs including at least one Kaplan-Meier plot. Articles were classified as "assessable" if sufficient information was available to assess LTFU. In these articles, LTFU information was derived from Kaplan-Meier plots, extracted from the text, and compared. Articles were then classified as "consistent" or "not consistent". Sensitivity analyses were performed to assess the validity of study results. Results 319 eligible articles were identified. 187 (59% were classified as "assessable", as they included sufficient information for evaluation; 140 of 319 (44% presented consistent LTFU information between the Kaplan-Meier plot and text. 47 of 319 (15% were classified as "not consistent". These 47 articles were included in sensitivity analyses. When various imputation methods were used, the results of a chi2-test applied to the corresponding 2 × 2 table changed and hence were not robust in about half of the studies. Conclusions Less than half of the articles on RCTs using Kaplan-Meier plots provide assessable and consistent LTFU information, thus questioning the validity of the results and conclusions of many studies presenting survival analyses. Authors should improve the presentation of both Kaplan-Meier plots and LTFU information, and reviewers of study publications and journal editors should critically appraise the validity of the information provided.

  13. Anaerobic biodegradability and toxicity of complex or toxicant wastewater

    International Nuclear Information System (INIS)

    Wills Betancur, B.A.

    1995-01-01

    As a first approximation to wastewater classification in susceptibility terms to treatment by anaerobic biological system, anaerobic biodegradability trials are accomplished to leached of sanitary landfill, to wastewater of coffee grain wet treatment plant and to wastewater of fumaric acid recuperation plant. In the last Plant, anaerobic toxicity trials and lethal toxicity on the Daphnia pulex micro-crustacean are made too. Anaerobic biological trials are made continuing the Wageningen University (Holland) Methodology (1.987). Lethal toxicity biological trials are made following the Standard Methods for the Examination of Water and Wastewater(18th edition, 1992). In development of this investigation project is found that fumaric acid recuperation plant leached it has a low anaerobic biodegradability, a high anaerobic toxicity and a high lethal toxicity over Daphnia pulex, for such reasons this leached is cataloged as complex and toxic wastewater. The other hand, wastewater of coffee grain wet treatment plant and wastewater of sanitary landfill they are both highly biodegradability and not-toxic, for such reasons these wastewaters are cataloged as susceptible to treatment by anaerobic biological system

  14. Comparison of Results according to the treatment Method in Maxillary Sinus Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Ki; Jo, Jae Sik; Ahn, Sung Ja; Nam, Taek Keun; Nah, Byung Sik [Chonnam National University College of Medicine, Kwangju (Korea, Republic of); Park, Seung Jin [Gyeongsang National Univ., Jinju (Korea, Republic of)

    1995-03-15

    Purpose : A retrospective analysis was performed to investigate the proper management of maxillary sinus carcinoma. Materials and Methods : Authors analysed 33 patients of squamous cell carcinoma of maxillary sinus treated at Chonnam University Hospital from January 1986 to December 1992. There were 24 men and 9 women with median age of 55 years. According to AJCC TNM system of 1988, a patient of T2, 10 patients of T3 and 22 patients of T4 were available, respectively. Cervical lymph node metastases was observed in 5 patients(N1;4/33, N2b;1/33). Patients were classified as 3 groups according to management method. The first group, named as 'FAR' (16 patients), was consisted of preoperative intra-arterial chemotherapy with 5-fluorouracil(5-FU;mean of total dosage;3078mg) through the superficial temporal artery with concurrent radiation(mean dose delivered;3433cGy, daily 180-200cGy) and vitamin A(50,000 IU daily), and followed by total maxillectomy and postoperative radiation therapy(mean dose;2351cGy). The second group, named as 'SR'(7 patients), was consisted of total maxillectomy followed by postoperative radiation therapy(mean dose 5920 cGy). Her third group, named as 'R'(6 patients), was treated with radiation alone(mean dose;7164cGy). Kaplan-Meier product limit method was used for survival analysis and Mantel-Cox test was performed for significance of survival difference between two groups. Results : Local recurrence free survival rate in the end of 2 year was 100%, 5-% and 0% in FAR, SR and R group, respectively. Disease free survival rate in 2 years was 88.9%, 40% and 50% in Far, SR and R group, respectively. There were statistically significant difference between FAR and SR or FAR and R group in their local recurrence free, disease free and overall survival rates. But difference of each survival rate between SR and R group was not significant. Conclusion : In this study FAR group revealed better results that SR or R group. In the

  15. Comparison of Results according to the treatment Method in Maxillary Sinus Carcinoma

    International Nuclear Information System (INIS)

    Chung, Woong Ki; Jo, Jae Sik; Ahn, Sung Ja; Nam, Taek Keun; Nah, Byung Sik; Park, Seung Jin

    1995-01-01

    Purpose : A retrospective analysis was performed to investigate the proper management of maxillary sinus carcinoma. Materials and Methods : Authors analysed 33 patients of squamous cell carcinoma of maxillary sinus treated at Chonnam University Hospital from January 1986 to December 1992. There were 24 men and 9 women with median age of 55 years. According to AJCC TNM system of 1988, a patient of T2, 10 patients of T3 and 22 patients of T4 were available, respectively. Cervical lymph node metastases was observed in 5 patients(N1;4/33, N2b;1/33). Patients were classified as 3 groups according to management method. The first group, named as 'FAR' (16 patients), was consisted of preoperative intra-arterial chemotherapy with 5-fluorouracil(5-FU;mean of total dosage;3078mg) through the superficial temporal artery with concurrent radiation(mean dose delivered;3433cGy, daily 180-200cGy) and vitamin A(50,000 IU daily), and followed by total maxillectomy and postoperative radiation therapy(mean dose;2351cGy). The second group, named as 'SR'(7 patients), was consisted of total maxillectomy followed by postoperative radiation therapy(mean dose 5920 cGy). Her third group, named as 'R'(6 patients), was treated with radiation alone(mean dose;7164cGy). Kaplan-Meier product limit method was used for survival analysis and Mantel-Cox test was performed for significance of survival difference between two groups. Results : Local recurrence free survival rate in the end of 2 year was 100%, 5-% and 0% in FAR, SR and R group, respectively. Disease free survival rate in 2 years was 88.9%, 40% and 50% in Far, SR and R group, respectively. There were statistically significant difference between FAR and SR or FAR and R group in their local recurrence free, disease free and overall survival rates. But difference of each survival rate between SR and R group was not significant. Conclusion : In this study FAR group revealed better results that SR or R group. In the future prospective randomized

  16. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  17. Portable, accurate toxicity testing

    International Nuclear Information System (INIS)

    Sabate, R.W.; Stiffey, A.V.; Dewailly, E.L.; Hinds, A.A.; Vieaux, G.J.

    1994-01-01

    Ever tightening environmental regulations, severe penalties for non-compliance, and expensive remediation costs have stimulated development of methods to detect and measure toxins. Most of these methods are bioassays that must be performed in the laboratory; none previously devised has been truly portable. The US Army, through the Small Business Innovative Research program, has developed a hand-held, field deployable unit for testing toxicity of battlefield water supplies. This patented system employs the measurable quenching, in the presence of toxins, of the natural bioluminescence produced by the marine dinoflagellate alga Pyrocystis lunula. The procedure's inventor used it for years to measure toxicity concentrations of chemical warfare agents actually, their simulants, primarily in the form of pesticides and herbicides plus assorted toxic reagents, waterbottom samples, drilling fluids, even blood. While the procedure is more precise, cheaper, and faster than most bioassays, until recently it was immobile. Now it is deployable in the field. The laboratory apparatus has been proven to be sensitive to toxins in concentrations as low as a few parts per billion, repeatable within a variation of 10% or less, and unlike some other bioassays effective in turbid or colored media. The laboratory apparatus and the hand-held tester have been calibrated with the EPA protocol that uses the shrimplike Mysidopsis bahia. The test organism tolerates transportation well, but must be rested a few hours at the test site for regeneration of its light-producing powers. Toxicity now can be measured confidently in soils, water columns, discharge points, and many other media in situ. Most significant to the oil industry is that drilling fluids can be monitored continuously on the rig

  18. Survival chance in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method

    International Nuclear Information System (INIS)

    Esik, Olga; Tusnady, Gabor; Daubner, Kornel; Nemeth, Gyoergy; Fuezy, Marton; Szentirmay, Zoltan

    1997-01-01

    Purpose: The typically benign, but occasionally rapidly fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to a given patient. Materials and methods: A retrospective study was performed on 400 papillary thyroid cancer patients with a median follow-up time of 7.1 years to establish a clinical database for uni- and multivariate analysis of the prognostic factors related to survival (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, the effect of the most important clinical events were then investigated on the basis of a Markov renewal model. The basic concept of this approach is that each patient has an individual disease course which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses). On the supposition that these events and the cause-specific death are influenced by the same biological processes, the parameters of transient survival probability characterizing the speed of the course of the disease for each clinical event and their sequence were determined. The individual survival curves for each patient were calculated by using these parameters and the independent significant clinical variables selected from multivariate studies, summation of which resulted in a mean cause-specific survival function valid for the entire group. On the basis of this Markov model, prediction of the cause-specific survival probability is possible for extrastudy cases, if it is supposed that the clinical events occur within new patients in the same manner and with the similar probability as within the study population. Results: The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumor size and extent (pT), the external irradiation dosage and the degree of TSH suppression proved to be

  19. SU-D-204-03: Comparison of Patient Positioning Methods Through Modeling of Acute Rectal Toxicity in Intensity Modulated Radiation Therapy for Prostate Cancer. Does Quality of Data Matter More Than the Quantity?

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X; Fatyga, M; Vora, S; Wong, W; Schild, S; Schild, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Herman, M [Mayo Clinic, Rochester, MN (United States); Li, J; Wu, T [Arizona State University, Tempe, AZ (United States)

    2016-06-15

    Purpose: To determine if differences in patient positioning methods have an impact on the incidence and modeling of grade >=2 acute rectal toxicity in prostate cancer patients who were treated with Intensity Modulated Radiation Therapy (IMRT). Methods: We compared two databases of patients treated with radiation therapy for prostate cancer: a database of 79 patients who were treated with 7 field IMRT and daily image guided positioning based on implanted gold markers (IGRTdb), and a database of 302 patients who were treated with 5 field IMRT and daily positioning using a trans-abdominal ultrasound system (USdb). Complete planning dosimetry was available for IGRTdb patients while limited planning dosimetry, recorded at the time of planning, was available for USdb patients. We fit Lyman-Kutcher-Burman (LKB) model to IGRTdb only, and Univariate Logistic Regression (ULR) NTCP model to both databases. We perform Receiver Operating Characteristics analysis to determine the predictive power of NTCP models. Results: The incidence of grade >= 2 acute rectal toxicity in IGRTdb was 20%, while the incidence in USdb was 54%. Fits of both LKB and ULR models yielded predictive NTCP models for IGRTdb patients with Area Under the Curve (AUC) in the 0.63 – 0.67 range. Extrapolation of the ULR model from IGRTdb to planning dosimetry in USdb predicts that the incidence of acute rectal toxicity in USdb should not exceed 40%. Fits of the ULR model to the USdb do not yield predictive NTCP models and their AUC is consistent with AUC = 0.5. Conclusion: Accuracy of a patient positioning system affects clinically observed toxicity rates and the quality of NTCP models that can be derived from toxicity data. Poor correlation between planned and clinically delivered dosimetry may lead to erroneous or poorly performing NTCP models, even if the number of patients in a database is large.

  20. Hydrophobic lapatinib encapsulated dextran-chitosan nanoparticles using a toxic solvent free method: fabrication, release property & in vitro anti-cancer activity

    Energy Technology Data Exchange (ETDEWEB)

    Mobasseri, Rezvan [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Karimi, Mahdi [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Tian, Lingling, E-mail: lingling_tian@nus.edu.sg [Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Naderi-Manesh, Hossein, E-mail: naderman@modares.ac.ir [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ramakrishna, Seeram [Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632 (China)

    2017-05-01

    Dextran sulfate-chitosan (DS-CS) nanoparticles, which possesses properties such as nontoxicity, biocompatibility and biodegradability have been employed as drug carriers in cancer therapy. In this study, DS-CS nanoparticles were synthesized and their sizes were controlled by a modification of the divalent cations cross-linkers (Ca{sup 2+}, Zn{sup 2+} or Mg{sup 2+}). Based on the optimized processing parameters, lapatinib encapsulated nanoparticles were developed and characterized by Dynamics Light Scattering (DLS) measurements, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). Calcium chloride (CaCl{sub 2}) facilitated the formation of bare (100.3 ± 0.80 nm) and drug-loaded nanoparticles (134.3 ± 1.3 nm) with narrow size distributions being the best cross-linker. The surface potential of drug-loaded nanoparticles was − 16.8 ± 0.47 mV and its entrapment and loading efficiency were 76.74 ± 1.73% and 47.36 ± 1.27%, respectively. Cellular internalization of nanoparticles was observed by fluorescence microscopy and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay was used to determine cytotoxicity of bare and drug-loaded nanoparticles in comparison to the free drug lapatinib. The MTT assay showed that drug-loaded nanoparticles had comparable anticancer activity to free drug within a duration of 48 h. The aforementioned results showed that the DS-CS nanoparticles were able to entrap, protect and release the hydrophobic drug, lapatinib in a controlled pattern and could further serve as a suitable drug carrier for cancer therapy. - Highlights: • The best condition to prepare best size (about 100 nm) dextran-chitosan nanoparticles is proposed. • Divalent cationic cross-linker can act as hardener and compress the particles. • Drug/dextran mixing in a toxic solvent free method provides hydrophobic drug encapsulation within a hydrophilic system. • High entrapment efficiency of Lapatinib in polymeric

  1. Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: The Mayo Clinic experience

    International Nuclear Information System (INIS)

    Miller, Robert C.; Lachance, Daniel H.; Lucchinetti, Claudia F.; Keegan, B. Mark; Gavrilova, Ralitza H.; Brown, Paul D.; Weinshenker, Brian G.; Rodriguez, Moses

    2006-01-01

    Purpose: The aim of this study was a retrospective assessment of neurotoxicity in patients with multiple sclerosis (MS) receiving external beam radiotherapy (EBRT) to the brain. Methods and Materials: We studied 15 consecutively treated patients with MS who received brain EBRT. Neurologic toxicity was assessed with the Common Toxicity Criteria v.3.0. Results: Median follow-up for the 5 living patients was 6.0 years (range, 3.3-27.4 years). No exacerbation of MS occurred in any patient during EBRT. Five patients had Grade 4 neurologic toxicity and 1 had possible Grade 5 toxicity. Kaplan-Meier estimated risk of neurotoxicity greater than Grade 4 at 5 years was 57% (95% confidence interval, 27%-82%). Toxicity occurred at 37.5 to 54.0 Gy at a median of 1.0 year (range, 0.2-4.3 years) after EBRT. Univariate analysis showed an association between opposed-field irradiation of the temporal lobes, central white matter, and brainstem and increased risk of neurotoxicity (p < 0.04). Three of 6 cases of toxicity occurred in patients treated before 1986. Conclusions: External beam radiotherapy of the brain in patients with MS may be associated with an increased risk of neurotoxicity compared with patients without demyelinating illnesses. However, this risk is associated with treatment techniques that may not be comparable to modern, conformal radiotherapy

  2. Multiple bio-analytical methods to reveal possible molecular mechanisms of developmental toxicity in zebrafish embryos/larvae exposed to tris(2-butoxyethyl) phosphate

    International Nuclear Information System (INIS)

    Han, Zhihua; Wang, Qiangwei; Fu, Jie; Chen, Hongshan; Zhao, Ye; Zhou, Bingsheng; Gong, Zhiyuan; Wei, Si; Li, Jun; Liu, Hongling; Zhang, Xiaowei; Liu, Chunsheng; Yu, Hongxia

    2014-01-01

    Highlights: • TBEP exposure decreased the survival of zebrafish embryos/larvae. • TBEP exposure led to its bioconcentration in zebrafish lavare. • TBEP caused developmental toxicity by inhibiting the degradation and utilization of nutrients. • TBEP exposure caused developmental toxicity by inducing apoptosis. - Abstract: The flame retardant tris(2-butoxyethyl) phosphate (TBEP) is a frequently detected contaminant in the environment, wildlife and human milk. The potentially toxic effects of TBEP and their underlying molecular mechanisms have not been elucidated. Here, zebrafish embryos were exposed to different concentrations of TBEP from 4 hours of post-fertilization (hpf) to 120 hpf, and effects on embryonic development and global protein expression patterns examined. Our results demonstrate that treatment with TBEP (0.8–100 mg/L) causes a concentration- and time-dependent decrease in embryonic survival and the hatching percentage. The median lethal concentration was 10.7 mg/L at 120 hpf. Furthermore, exposure to 150 or 800 μg/L TBEP inhibited the degradation and utilization of vitellogenins and down-regulated the expression of proteins related to cation binding, and lipid transport, uptake and metabolism, accompanied by a decrease in heart rate and body length. Exposure to TBEP (150 or 800 μg/L) also decreased the expression of proteins involved in cell proliferation and DNA repair, and led to an increased number of apoptotic cells in the tail region. Collectively, our results suggest that exposure to TBEP causes toxicity in the developing zebrafish by inhibiting the degradation and utilization of nutrients from the mother and inducing apoptosis

  3. Multiple bio-analytical methods to reveal possible molecular mechanisms of developmental toxicity in zebrafish embryos/larvae exposed to tris(2-butoxyethyl) phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Han, Zhihua [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Wang, Qiangwei [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Fu, Jie [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Chen, Hongshan [State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of the Environment, Northeast Normal University, Changchun 130024 (China); Department of Biological Sciences, National University of Singapore (Singapore); Zhao, Ye [Department of Biological Sciences, National University of Singapore (Singapore); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Gong, Zhiyuan [Department of Biological Sciences, National University of Singapore (Singapore); Wei, Si; Li, Jun; Liu, Hongling; Zhang, Xiaowei [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Liu, Chunsheng, E-mail: liuchunshengidid@126.com [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Department of Biological Sciences, National University of Singapore (Singapore); College of Fisheries, Huazhong Agricultural University, Wuhan 430070 (China); Yu, Hongxia, E-mail: yuhx@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China)

    2014-05-01

    Highlights: • TBEP exposure decreased the survival of zebrafish embryos/larvae. • TBEP exposure led to its bioconcentration in zebrafish lavare. • TBEP caused developmental toxicity by inhibiting the degradation and utilization of nutrients. • TBEP exposure caused developmental toxicity by inducing apoptosis. - Abstract: The flame retardant tris(2-butoxyethyl) phosphate (TBEP) is a frequently detected contaminant in the environment, wildlife and human milk. The potentially toxic effects of TBEP and their underlying molecular mechanisms have not been elucidated. Here, zebrafish embryos were exposed to different concentrations of TBEP from 4 hours of post-fertilization (hpf) to 120 hpf, and effects on embryonic development and global protein expression patterns examined. Our results demonstrate that treatment with TBEP (0.8–100 mg/L) causes a concentration- and time-dependent decrease in embryonic survival and the hatching percentage. The median lethal concentration was 10.7 mg/L at 120 hpf. Furthermore, exposure to 150 or 800 μg/L TBEP inhibited the degradation and utilization of vitellogenins and down-regulated the expression of proteins related to cation binding, and lipid transport, uptake and metabolism, accompanied by a decrease in heart rate and body length. Exposure to TBEP (150 or 800 μg/L) also decreased the expression of proteins involved in cell proliferation and DNA repair, and led to an increased number of apoptotic cells in the tail region. Collectively, our results suggest that exposure to TBEP causes toxicity in the developing zebrafish by inhibiting the degradation and utilization of nutrients from the mother and inducing apoptosis.

  4. Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

    Science.gov (United States)

    Nendza, Monika; Müller, Martin; Wenzel, Andrea

    2017-03-22

    Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

  5. Toxicity alarm: Case history

    International Nuclear Information System (INIS)

    Hogan, D.; Retallack, J.

    1993-01-01

    In late fall 1991, the Novacor petrochemical plant near Joffre, Alberta experienced a toxicity alarm, the first since its startup 14 years ago. Fish exposed to a normal toxicity test were stressed within 2 h and showed 100% mortality after 24 h. A history of the events leading up to, during, and after the toxicity alarm is presented. The major effluent sources were three cooling water systems. Although these sources are well characterized, the event causes were not immediately clear. Initial toxic screening indicated that one was very toxic, another moderately toxic, and the third not toxic at all. All three systems utilized the same chemical treatment program to avoid fouling: stabilized phosphates with minor variants. The most toxic of the cooling systems operated at 10-12 cycles, had three chemicals for biocide control, and had three makeup streams. Toxic and nontoxic system characteristics were compared. An in-depth modified toxicity identification and evaluation program was then performed to identify and evaluate the cause of the toxicity alarm for future prevention. The most probable causes of toxicity were identified by elimination. The combination of high numbers of cycles, hydrocarbons in the makeup water, and bromine added as an antifoulant resulted in formation of aromatic bromamines which are capable of causing the toxic condition experienced. 2 tabs

  6. Toxic substances handbook

    Science.gov (United States)

    Junod, T. L.

    1979-01-01

    Handbook, published in conjunction with Toxic Substances Alert Program at NASA Lewis Research Center, profiles 187 toxic chemicals in their relatively pure states and include 27 known or suspected carcinogens.

  7. Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks

    Directory of Open Access Journals (Sweden)

    Anne Hansen Ree

    2014-12-01

    Full Text Available Organ toxicity in cancer therapy is likely caused by an underlying disposition for given pathophysiological mechanisms in the individual patient. Mechanistic data on treatment toxicity at the patient level are scarce; hence, probabilistic and translational linkages among different layers of data information, all the way from cellular targets of the therapeutic exposure to tissues and ultimately the patient’s organ systems, are required. Throughout all of these layers, untoward treatment effects may be viewed as perturbations that propagate within a hierarchically structured network from one functional level to the next, at each level causing disturbances that reach a critical threshold, which ultimately are manifested as clinical adverse reactions. Advances in bioinformatics permit compilation of information across the various levels of data organization, presumably enabling integrated systems biology-based prediction of treatment safety. In view of the complexity of biological responses to cancer therapy, this communication reports on a “top-down” strategy, starting with the systematic assessment of adverse effects within a defined therapeutic context and proceeding to transcriptomic and proteomic analysis of relevant patient tissue samples and computational exploration of the resulting data, with the ultimate aim of utilizing information from functional connectivity networks in evaluation of patient safety in multimodal cancer therapy.

  8. A biological method for in-situ synthesis of hydroxyapatite-coated magnetite nanoparticles using Enterobacter aerogenes: Characterization and acute toxicity assessments.

    Science.gov (United States)

    Ahmadzadeh, Elham; Talebnia Rowshan, Farid; Hosseini, Morteza

    2017-04-01

    Hydroxyapatite (HA)-coated magnetite nanoparticles (MNPs) are being widely investigated for various applications in medical engineering and wastewater treatment. In this work, the MNPs were thoroughly coated by bacterial synthesized HA nanoparticles during biomineralization process using Enterobacter aerogenes. The resulting bacterial-induced precipitate was then calcined at 600°C and investigated with respect to structural characteristics, particle size and magnetic strength by XRD, FT-IR, SEM, EDS, TEM and VSM analyses. The effects of MNPs and HA-coated MNPs (HA-MNPs) on the viability of human MCF-7 cell lines were also investigated via mitochondrial activity test (MTT) and lactate dehydrogenase (LDH) assays. The powder characterization results showed appropriate structural properties for HA-MNPs samples. The particles diameter size of the MNPs and HA-MNPs were in the range of 3-25nm and 20-80nm, respectively. The biologically-synthesized HA-MNPs formed a stable suspension in water while keeping their magnetic property. The saturation magnetization (Ms) of HA-MNPs was measured at ~10emug -1 which was in good agreement with the structural composition of this sample. Finally, the results of the cell lines viability indicated that coating of toxic MNPs via biomineralization was a promising approach in order to synthesize bio-compatible magnetic nanoparticles with suitable physical and chemical structural characteristics. The toxicity level of MNPs was reduced by 10 fold when coated by bacterial-synthesized HA. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Multiple bio-analytical methods to reveal possible molecular mechanisms of developmental toxicity in zebrafish embryos/larvae exposed to tris(2-butoxyethyl) phosphate.

    Science.gov (United States)

    Han, Zhihua; Wang, Qiangwei; Fu, Jie; Chen, Hongshan; Zhao, Ye; Zhou, Bingsheng; Gong, Zhiyuan; Wei, Si; Li, Jun; Liu, Hongling; Zhang, Xiaowei; Liu, Chunsheng; Yu, Hongxia

    2014-05-01

    The flame retardant tris(2-butoxyethyl) phosphate (TBEP) is a frequently detected contaminant in the environment, wildlife and human milk. The potentially toxic effects of TBEP and their underlying molecular mechanisms have not been elucidated. Here, zebrafish embryos were exposed to different concentrations of TBEP from 4 hours of post-fertilization (hpf) to 120 hpf, and effects on embryonic development and global protein expression patterns examined. Our results demonstrate that treatment with TBEP (0.8-100mg/L) causes a concentration- and time-dependent decrease in embryonic survival and the hatching percentage. The median lethal concentration was 10.7 mg/L at 120 hpf. Furthermore, exposure to 150 or 800 μg/L TBEP inhibited the degradation and utilization of vitellogenins and down-regulated the expression of proteins related to cation binding, and lipid transport, uptake and metabolism, accompanied by a decrease in heart rate and body length. Exposure to TBEP (150 or 800 μg/L) also decreased the expression of proteins involved in cell proliferation and DNA repair, and led to an increased number of apoptotic cells in the tail region. Collectively, our results suggest that exposure to TBEP causes toxicity in the developing zebrafish by inhibiting the degradation and utilization of nutrients from the mother and inducing apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Rapid bioassessment methods for assessing the toxicity of terrestrial waste sites at the Savannah River Site using the earthworm, Eisenia foetida

    International Nuclear Information System (INIS)

    Specht, W.L.

    1995-08-01

    Studies were conducted to assess the feasibility of using the earthworm, Eisenia foetida, to evaluate the toxicity of contaminated soils at the Savannah River Site. Survival was assessed in several uncontaminated soils, including sandy loams and clayey loams, as well as in soils contaminated with coal fines, ash, diesel fuel, and heavy metals. In addition, behavior responses, changes in biomass, and bioaccumulation of heavy metals were assessed as sublethal indicators of toxicity. The results indicate excellent survival of Eisenia foetida in uncontaminated sandy and clayey soils. No amendment of these uncontaminated soils or addition of food was necessary to sustain the worms for the 14-day test period. In contaminated soils, no significant mortality was observed, except in soils which have very low pH (< 3). However, sublethal responses were observed in earthworms exposed to several of the contaminated soils. These responses included worms clumping on the surface of the soil, worms clumping between the sides of the test container and the soil, increased burrowing times, reductions in biomass, and elevated concentrations of heavy metals in worm tissue

  11. Retention in Care among HIV-Infected Adults in Ethiopia, 2005- 2011: A Mixed-Methods Study.

    Directory of Open Access Journals (Sweden)

    Yordanos M Tiruneh

    Full Text Available Poor retention in HIV care challenges the success of antiretroviral therapy (ART. This study assessed how well patients stay in care and explored factors associated with retention in the context of an initial ART rollout in Sub-Saharan Africa.We conducted a mixed-methods study at a teaching hospital in Addis Ababa, Ethiopia. A cohort of 385 patients was followed for a median of 4.6 years from ART initiation to lost-to-follow-up (LTFU-missing appointments for more than three months after last scheduled visit or administrative censoring. We used Kaplan-Meier plots to describe LTFU over time and Cox-regression models to identify factors associated with being LTFU. We held six focus group discussions, each with 6-11 patients enrolled in care; we analyzed data inductively informed by grounded theory.Patients in the cohort were predominantly female (64% and the median age was 34 years. Thirty percent were LTFU by study's end; the median time to LTFU was 1,675 days. Higher risk of LTFU was associated with baseline CD4 counts 200 cells/μL (HR = 1.62; 95% CI:1.03-2.55; and HR = 2.06; 95% CI:1.15-3.70, respectively, compared with patients with baseline CD4 counts of 100-200 cells/μL. Bedridden participants at ART initiation (HR = 2.05; 95% CIs [1.11-3.80] and those with no or only primary education (HR = 1.50; 95% CIs [1.00-2.24] were more likely to be LTFU. Our qualitative data revealed that fear of stigma, care dissatisfaction, use of holy water, and economic constraints discouraged retention in care. Social support and restored health and functional ability motivated retention.Complex socio-cultural, economic, and health-system factors inhibit optimum patient retention. Better tracking, enhanced social support, and regular adherence counseling addressing stigma and alternative healing options are needed. Intervention strategies aimed at changing clinic routines and improving patient-provider communication could address many of the identified barriers.

  12. Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

    Directory of Open Access Journals (Sweden)

    King Christopher R

    2011-01-01

    Full Text Available Abstract Purpose Hypofractionated, stereotactic body radiotherapy (SBRT is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Method and Materials Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method and RTOG toxicity outcomes were assessed. Results At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%. Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusion Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.

  13. Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma - A prospective randomized trial

    International Nuclear Information System (INIS)

    Singh, Niveditha B.; Lakier, Roy H.; Donde, Bernard

    2008-01-01

    Purpose: To compare a conventional fractionation regimen with a hypofractionated regimen in the treatment of Epidemic Kaposi sarcoma with radiation therapy. Materials and methods: Sixty patients were randomized to receive a standard regimen of 24 Gy in 12 fractions (ARM A) or the study regimen of 20 Gy in five fractions (ARM B). Radiation technique was individualized. Treatment response, local control and toxicity were recorded. Results: Thirty five sites were treated in ARM A and 30 sites in ARM B. Treatment arms were similar for gender, ECOG performance score, treated site, antiretroviral therapy usage, T stage, I stage and S stage. The overall survival using the Kaplan Meier method was 37% at 1 year. Complete responses were recorded at 28 sites (13 Arm A, 15 Arm B), partial responses at 19 sites (8 Arm A, 11 Arm B) and stable disease at three sites (2 Arm A, 1 Arm B). The mean time to maximum objective response was 3 months (range: 1-14 months). Response rates and local control were equal in the two arms (p = 0.73 and 0.77, respectively, log rank test). Acute skin toxicity (p = 0.77) and late skin toxicity (p = 0.24) were equal in the two arms. Conclusion: The two treatment regimens produced equivalent results for treatment response, local recurrence-free survival and toxicity

  14. Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials.

    Science.gov (United States)

    Strehlau, Jenny; Weber, Till; Lürenbaum, Constantin; Bornhorst, Julia; Galla, Hans-Joachim; Schwerdtle, Tanja; Winter, Martin; Nowak, Sascha

    2017-10-01

    A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9%. It could be shown that no matrix effects were present and recovery rates between 98 and 104% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place. Graphical abstract Schematic setup for the investigation of toxicity of lithium ion battery electrolytes.

  15. Estimation of Toxicity Equivalent Concentration (TEQ) of ...

    African Journals Online (AJOL)

    Estimation of Toxicity Equivalent Concentration (TEQ) of carcinogenic polycyclic aromatic hydrocarbons in soils from Idu Ekpeye playground and University of Port ... Effective soil remediation and detoxification method like Dispersion by chemical reaction technology should be deployed to clean-up sites to avoid soil toxicity ...

  16. Method for aquatic multiple species toxicant testing: acute toxicity of 10 chemicals to 5 vertebrates and 2 invertebrates. [Pimephales promelas; Carassius auratus; Ictalurus punctatus; Lepomis macrochirus; Salmo gairdneri; Orconectes immunis; Aplexa hypnorum

    Energy Technology Data Exchange (ETDEWEB)

    Phipps, G.L.; Holcombe, G.W.

    1985-01-01

    A method was developed to simultaneously ascertain 96 h LC/sub 50/ values for seven freshwater species in a single flow through test with measured concentrations. It allows interspecific comparisons, easy determination of the most sensitive species, and cuts cost of labor, materials and chemical analysis for measured concentration tests. Species tested included fathead minnows Pimephales promelas, goldfish Carassius auratus, channel catfish Ictalurus punctatus, bluegill Lepomis macrochirus, rainbow trout Salmo gairdneri, crayfish Orconectes immunis and snails Aplexa hypnorum. Compounds tested were pentachlorophenol, 2-chloroethanol, 2,4-pentanedione, hexachloroethane, ..cap alpha..-bromo-2',5'-dimethoxyacetophenone, benzaldehyde, 1,3-dichloro-4,6-dinitro-benzene, dursban, sevin and cadmium chloride. The LC/sub 50/ values from these multiple species tests compared favourably with those determined using single species tests at this laboratory, usually within 20%.

  17. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Minatel, Emilio; Durofil, Elena [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Polesel, Jerry [Department of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Avanzo, Michele [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Aviano, Pordenone (Italy); Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G. [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy)

    2014-04-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.

  18. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Trovo, Marco; Minatel, Emilio; Durofil, Elena; Polesel, Jerry; Avanzo, Michele; Baresic, Tania; Bearz, Alessandra; Del Conte, Alessandro; Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G.

    2014-01-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern

  19. Antioxidant activity and acute toxicity of Neoglaziovia variegata ...

    African Journals Online (AJOL)

    The total phenolics content of the extracts was determined by the Folin-Ciocalteu method. Total flavonoid was also determined. The most ... of low toxicity. Keywords: Antioxidant activity, acute toxicity, Neoglaziovia variegata, Bromeliaceae ...

  20. Novel view on predicting acute toxicity: Decomposing toxicity data in species vulnerability and chemical potency.

    NARCIS (Netherlands)

    Jager, D.T.; Posthuma, L.; Zwart, D.D.; van de Meent, D.

    2007-01-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We

  1. Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis.

    Science.gov (United States)

    Ost, Piet; Jereczek-Fossa, Barbara Alicja; As, Nicholas Van; Zilli, Thomas; Muacevic, Alexander; Olivier, Kenneth; Henderson, Daniel; Casamassima, Franco; Orecchia, Roberto; Surgo, Alessia; Brown, Lindsay; Tree, Alison; Miralbell, Raymond; De Meerleer, Gert

    2016-01-01

    The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival. Copyright © 2015. Published by Elsevier B.V.

  2. Toxic metals in the atmosphere

    International Nuclear Information System (INIS)

    Munoz-Ribadeneira, F.J.; Mo, T.; Canoy, M.J.

    1975-05-01

    Methods used in Puerto Rico for monitoring toxic metals in the atmosphere are described. Air sampling machines are placed at heights from 15 to 25 ft above the surface and the tapes are subjected to neutron activation and γ spectroscopy. The concentrations of up to 33 elements can be determined with precision and sensitivity without destroying the tapes, which can then be used for analysis by other methods. (U.S.)

  3. Methods of analysis in terms of effects and their application to toxic organic constituents of industrial waste water; Methoden und Anwendung der wirkungsbezogenen Analytik auf toxische organische Inhaltsstoffe in industriellen Abwaessern

    Energy Technology Data Exchange (ETDEWEB)

    Reemtsma, T.; Putschew, A.; Jekel, M. [Technische Univ. Berlin (Germany). Fachgebiet Wasserreinhaltung

    1999-07-01

    Coupling biological action detection with chemical sewage analysis opens up a broad spectrum of methods involving diverse amounts of effort, whose results can range from hints to ways of eliminating a toxic effect to the identification and quantification of individual toxic constituents even in complex waste water. These methods help recognizing problems with effluent quality and enhancing treatment concepts. As possible biological effects of sewage discharges into receiving bodies of water (including sublethal effects) are meeting with increasing attention, the importance of sewage analysis in terms of effects will acquire even greater weight. Automated and miniaturized processes can cut down the involved effort substantially in the future. (orig.) [German] Die Kopplung der biologischen Wirkungsdetektion mit chemischer Abwasseranalytik eroeffnet ein breites Spektrum unterschiedlich aufwendiger Methoden, deren Ergebnisse von Hinweisen auf Methoden zur Entfernung einer toxischen Wirkung bis zur Identifizierung und Quantifizierung einzelner toxischer Inhaltsstoffe auch in komplexer Abwaessern reichten koennen. Diese Methoden helfen beim Erkennen von Problemen in der Ablaufqualitaet und unterstuetzen bei der Verbesserung von Behandlungskonzepten. Mit steigender Beachtung moeglicher biologischer Wirkungen von Abwassereinleitungen im Vorfluter (unter Einbeziehung sublethaler Effekte) wird die Bedeutung der wirkungsbezogenen Abwasseranalytik noch zunehmen. Automatisierte und miniaturisierte Verfahren koennen zukuenftig den dabei zu treibenden Aufwand wesentlich vermindern. (orig.)

  4. Toxic substances alert program

    Science.gov (United States)

    Junod, T. L.

    1978-01-01

    A toxicity profile is provided, of 187 toxic substances procured by NASA Lewis Research Center during a 3 1/2 year period, including 27 known or suspected carcinogens. The goal of the program is to assure that the center's health and safety personnel are aware of the procurement and use of toxic substances and to alert and inform the users of these materials as to the toxic characteristics and the control measures needed to ensure their safe use. The program also provides a continuing record of the toxic substances procured, who procured them, what other toxic substances the user has obtained in the past, and where similar materials have been used elsewhere at the center.

  5. Isonychia spp. and macroinvertebrate community responses to stressors in streams utilizing the benthic in situ toxicity identification evaluation (BiTIE) method

    Energy Technology Data Exchange (ETDEWEB)

    Custer, Kevin W. [Department of Earth and Environmental Sciences, Wright State University, 127 Allyn Hall, 3640 Colonel Glenn Highway, Dayton, OH 45435 (United States)], E-mail: custer.4@wright.edu; Burton, G. Allen [Department of Earth and Environmental Sciences, Wright State University, 127 Allyn Hall, 3640 Colonel Glenn Highway, Dayton, OH 45435 (United States)

    2008-01-15

    Exposures of caged organisms in situ have proven to be a useful way to improve exposure realism and link to stressor effects in aquatic assessments of hazard or risk. A novel cage system, the benthic in situ toxicity identification evaluation (BiTIE), was developed for benthic macroinvertebrates (surrogate species, resident populations and communities) to separate low and high flow effects, and major chemical classes of stressors in streams. Three resin types were used to separate the chemical stressors in the streams Honey Creek and Little Beavercreek, Ohio, USA: Dowex{sup TM} Optipore{sup TM} (non-polar organics), zeolite (ammonia), and polywool (control). Isonychia spp. sensitivity was compared to Chironomus tentans, and no significant differences were found (p > 0.05). Isonychia spp. growth (length) showed a stressor response in the zeolite treatments, and community testing revealed improved metric responses in the Dowex{sup TM} treatments. The BiTIE chamber system demonstrated stressor-response relationships using sublethal and multimetric endpoints. - Use of an indigenous aquatic insect and benthic macroinvertebrate communities allows for discerning the stressors in low and high flows with an in situ TIE approach.

  6. Isonychia spp. and macroinvertebrate community responses to stressors in streams utilizing the benthic in situ toxicity identification evaluation (BiTIE) method

    International Nuclear Information System (INIS)

    Custer, Kevin W.; Burton, G. Allen

    2008-01-01

    Exposures of caged organisms in situ have proven to be a useful way to improve exposure realism and link to stressor effects in aquatic assessments of hazard or risk. A novel cage system, the benthic in situ toxicity identification evaluation (BiTIE), was developed for benthic macroinvertebrates (surrogate species, resident populations and communities) to separate low and high flow effects, and major chemical classes of stressors in streams. Three resin types were used to separate the chemical stressors in the streams Honey Creek and Little Beavercreek, Ohio, USA: Dowex TM Optipore TM (non-polar organics), zeolite (ammonia), and polywool (control). Isonychia spp. sensitivity was compared to Chironomus tentans, and no significant differences were found (p > 0.05). Isonychia spp. growth (length) showed a stressor response in the zeolite treatments, and community testing revealed improved metric responses in the Dowex TM treatments. The BiTIE chamber system demonstrated stressor-response relationships using sublethal and multimetric endpoints. - Use of an indigenous aquatic insect and benthic macroinvertebrate communities allows for discerning the stressors in low and high flows with an in situ TIE approach

  7. Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

    Science.gov (United States)

    Tinkle, Christopher L; Fernandez-Pineda, Israel; Sykes, April; Lu, Zhaohua; Hua, Chia-Ho; Neel, Michael D; Bahrami, Armita; Shulkin, Barry L; Kaste, Sue C; Pappo, Alberto; Spunt, Sheri L; Krasin, Matthew J

    2017-11-15

    Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. Preoperative chemoradiotherapy for locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Pepek Joseph M

    2013-01-01

    Full Text Available Abstract Background To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT for gastric cancer. Methods Patients with gastroesophageal (GE junction (Siewert type II and III or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS, local control (LC and disease-free survival (DFS were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Results Forty-eight patients were included. Most (73% had proximal (GE junction, cardia and fundus tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75% underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

  9. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  10. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Y. E.; Hanson, W. R.; Bharucha, J.; Ainsworth, E. J.; Jaroslow, B.

    1977-01-01

    The antitumor drug Actinomycin D is effective against the growth of some human solid tumors but its use is limited by its extreme toxicity. The development of a method of administering Act. D to reduce its systemic toxicity by incorporating the drug within liposomes reduced its toxicity but its tumoricidal activity was retained.

  11. Baltimore Air Toxics Study (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, D.A. [Sullivan Environmental Consulting, Inc., Alexandria, VA (United States)

    1996-12-31

    The Baltimore Air Toxics Study is one of the three urban air toxics initiatives funded by EPA to support the development of the national air toxics strategy. As part of this project, the Air Quality Integrated Management System (AIMS) is under development. AIMS is designed to bring together the key components of urban air quality management into an integrated system, including emissions assessment, air quality modeling, and air quality monitoring. Urban area source emissions are computed for a wide range of pollutants and source categories, and are joined with existing point source emissions data. Measured air quality data are used to evaluate the adequacy of the emissions data and model treatments as a function of season, meteorological parameters, and daytime/nighttime conditions. Based on tested model performance, AIMS provides the potential to improve the ability to predict air quality benefits of alternative control options for criteria and toxic air pollutants. This paper describes the methods used to develop AIMS, and provides examples from its application in the Baltimore metropolitan area. The use of AIMS in the future to enhance environmental management of major industrial facilities also will be addressed in the paper.

  12. Preoperative chemoradiotherapy for locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Pepek, Joseph M; Chino, Junzo P; Willett, Christopher G; Palta, Manisha; Blazer III, Dan G; Tyler, Douglas S; Uronis, Hope E; Czito, Brian G

    2013-01-01

    To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated

  13. Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules.

    Science.gov (United States)

    Di Santo, Sara; Trignani, Marianna; Neri, Matteo; Milano, Angelo; Innocenti, Paolo; Taraborrelli, Maria; Augurio, Antonietta; Vinciguerra, Annamaria; Di Tommaso, Monica; Ursini, Lucia Anna; Di Pilla, Angelo; Di Nicola, Marta; Genovesi, Domenico

    2015-01-01

    Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.

  14. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    labeled as toxic, can he or she be rehabilitated?; Are there leadership styles that can be promoted to combat toxic leadership?; and Are the senior...examines leadership styles that are favorable for female leaders, and offers Transformational/Adaptive leadership as a style promising rehabilitative tools

  15. USE OF POWDERED COCONUT CHARCOAL AS A TOXICITY IDENTIFICATION AND EVALUATION MANIPULATION FOR ORGANIC TOXICANTS IN MARINE SEDIMENTS

    Science.gov (United States)

    We report on a procedure using powdered coconut charcoal to sequester organic contaminants and reduce toxicity in sediments as part of a series of toxicity identification and evaluation (TIE) methods. Powdered coconut charcoal (PCC) was effective in reducing the toxicity of endos...

  16. Measuring survival time: a probability-based approach useful in healthcare decision-making.

    Science.gov (United States)

    2011-01-01

    In some clinical situations, the choice between treatment options takes into account their impact on patient survival time. Due to practical constraints (such as loss to follow-up), survival time is usually estimated using a probability calculation based on data obtained in clinical studies or trials. The two techniques most commonly used to estimate survival times are the Kaplan-Meier method and the actuarial method. Despite their limitations, they provide useful information when choosing between treatment options.

  17. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  18. Ecological toxicity estimation of solid waste products of Tekely Ore Mining and Processing Enterprise of OJSC 'Kaztsink' using biological testing methods

    International Nuclear Information System (INIS)

    Vetrinskaya, N.I.; Goldobina, E.A.; Kosmukhambetov, A.R.; Kulikova, O.V.; Ismailova, Zh.B.; Gurikova, N.D.; Kozlova, N.V.

    2001-01-01

    Results are examined of solid waste products estimation using methods of biological testing at testing-objects of different phylogenetic development levels (simple aqua animals, algae, supreme water plants). Correlation is found between lead and zinc content in the extract of leaching out and exact reaction of all under-test objects. Conclusion is made that performing of the complex express economical analysis is necessary using methods of biological testing of industrial waste products monitoring and other man-made pollutants. (author)

  19. Challenges in risk estimation using routinely collected clinical data: The example of estimating cervical cancer risks from electronic health-records.

    Science.gov (United States)

    Landy, Rebecca; Cheung, Li C; Schiffman, Mark; Gage, Julia C; Hyun, Noorie; Wentzensen, Nicolas; Kinney, Walter K; Castle, Philip E; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Sasieni, Peter D; Katki, Hormuzd A

    2018-06-01

    Electronic health-records (EHR) are increasingly used by epidemiologists studying disease following surveillance testing to provide evidence for screening intervals and referral guidelines. Although cost-effective, undiagnosed prevalent disease and interval censoring (in which asymptomatic disease is only observed at the time of testing) raise substantial analytic issues when estimating risk that cannot be addressed using Kaplan-Meier methods. Based on our experience analysing EHR from cervical cancer screening, we previously proposed the logistic-Weibull model to address these issues. Here we demonstrate how the choice of statistical method can impact risk estimates. We use observed data on 41,067 women in the cervical cancer screening program at Kaiser Permanente Northern California, 2003-2013, as well as simulations to evaluate the ability of different methods (Kaplan-Meier, Turnbull, Weibull and logistic-Weibull) to accurately estimate risk within a screening program. Cumulative risk estimates from the statistical methods varied considerably, with the largest differences occurring for prevalent disease risk when baseline disease ascertainment was random but incomplete. Kaplan-Meier underestimated risk at earlier times and overestimated risk at later times in the presence of interval censoring or undiagnosed prevalent disease. Turnbull performed well, though was inefficient and not smooth. The logistic-Weibull model performed well, except when event times didn't follow a Weibull distribution. We have demonstrated that methods for right-censored data, such as Kaplan-Meier, result in biased estimates of disease risks when applied to interval-censored data, such as screening programs using EHR data. The logistic-Weibull model is attractive, but the model fit must be checked against Turnbull non-parametric risk estimates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. "I Couldn't Wait to Leave the Toxic Environment": A Mixed Methods Study of Women Faculty Satisfaction and Departure from One Research Institution

    Science.gov (United States)

    Gardner, Susan K.

    2012-01-01

    A mixed methods analysis of women faculty departure at one research institution was conducted using Hagedorn's model of faculty job satisfaction. Findings from an institution-wide survey and interviews with women faculty who had left the institution resulted in several themes: (a) a lack of resources to support faculty work, (b) a lack of…

  1. A gas chromatography-mass spectrometry (GC-MS) method for the detection and quantitation of monofluoroacetate in plants toxic to livestock

    Science.gov (United States)

    Monofluoroacetate (MFA) is a potent toxin that occurs in over 50 plant species in Africa, Australia, and South America and is responsible for significant livestock deaths in these regions. A gas chromatography–mass spectrometry (GC-MS) method for the analysis of MFA in plants based on the derivatiza...

  2. Methods for regionalization of impacts of non-toxic air pollutants in life-cycle assessments often tell a consistent story

    DEFF Research Database (Denmark)

    Djomo, Sylvestre Njakou; Knudsen, Marie Trydeman; Andersen, Mikael Skou

    2017-01-01

    There is an ongoing debate regarding the influence of the source location of pollution on the fate of pollutants and their subsequent impacts. Several methods have been developed to derive site-dependent characterization factors (CFs) for use in life-cycle assessment (LCA). Consistent, precise, a...

  3. Cardiovascular Risk Factors and 5-year Mortality in the Copenhagen Stroke Study

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Olsen, Tom Skyhøj

    2005-01-01

    population. METHODS: We studied 905 ischemic stroke patients from the community-based Copenhagen Stroke Study. Patients had a CT scan and stroke severity was measured by the Scandinavian Stroke Scale on admission. A comprehensive evaluation was performed by a standardized medical examination...... and questionnaire for cardiovascular risk factors, age, and sex. Follow-up was performed 5 years after stroke, and data on mortality were obtained for all, except 6, who had left the country. Five-year mortality was calculated by the Kaplan-Meier procedure and the influence of multiple predictors was analyzed...... by Cox proportional hazards analyses adjusted for age, gender, stroke severity, and risk factor profile. RESULTS: In Kaplan-Meier analyses atrial fibrillation (AF), ischemic heart disease, diabetes, and previous stroke were associated with increased mortality, while smoking and alcohol intake were...

  4. Cardiovascular risk factors and 5-year mortality in the Copenhagen Stroke Study

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Olsen, Tom Skyhøj

    2005-01-01

    population. METHODS: We studied 905 ischemic stroke patients from the community-based Copenhagen Stroke Study. Patients had a CT scan and stroke severity was measured by the Scandinavian Stroke Scale on admission. A comprehensive evaluation was performed by a standardized medical examination...... and questionnaire for cardiovascular risk factors, age, and sex. Follow-up was performed 5 years after stroke, and data on mortality were obtained for all, except 6, who had left the country. Five-year mortality was calculated by the Kaplan-Meier procedure and the influence of multiple predictors was analyzed...... by Cox proportional hazards analyses adjusted for age, gender, stroke severity, and risk factor profile. RESULTS: In Kaplan-Meier analyses atrial fibrillation (AF), ischemic heart disease, diabetes, and previous stroke were associated with increased mortality, while smoking and alcohol intake were...

  5. Treatment of primary tracheal carcinoma. The role of external and endoluminal radiotherapy

    International Nuclear Information System (INIS)

    Harms, W.; Wannenmacher, M.; Becker, H.; Herth, F.; Gagel, B.

    2000-01-01

    Background and Purpose: In a retrospective study the role of radiation therapy for the treatment of primary tracheal carcinoma was investigated. Patients and Methods: Between 1984 and 1997, 25 patients with primary tracheal carcinoma were treated with external beam radiotherapy (17 squamous-cell carcinoma [SCC], 8 adenoid cystic carcinoma [ACC], median dose SCC 60 Gy, ACC 55 Gy). An additional brachytherapy boost was carried out in 10/25 patients (median dose SCC 18 Gy, ACC 15 Gy). Ten patients underwent operative treatment. Results: The median survival (Kaplan-Meier) for patients with SCC was 33 months (ACC 94.2). The 1-, 2- and 5-year survival rates (Kaplan-Meier) for patients with SCC were 64.7% (ACC 85.7%), 64.7% (ACC 85.7%), and 26% (ACC 85.7%). Patients with ACC and patients with a complete remission after treatment had a significantly better survival probability (log rank test, p [de

  6. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b

    DEFF Research Database (Denmark)

    Kyndi, M.; Sorensen, F.B.; Alsner, J.

    2008-01-01

    -Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue microarray......, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots...

  7. Electronic Cigarette Toxicity.

    Science.gov (United States)

    Payne, J Drew; Michaels, David; Orellana-Barrios, Menfil; Nugent, Kenneth

    2017-04-01

    Electronic cigarettes (e-cigarettes) are often advertised as a healthier product when compared with traditional cigarettes. Currently, there are limited data to support this and only a threat of federal regulation from the US Food and Drug Administration. Calls to poison control centers about e-cigarette toxicity, especially in children, and case reports of toxic exposures have increased over the past 3 years. This research letter reports the frequency of hazardous exposures to e-cigarettes and characterizes the reported adverse health effects associated with e-cigarette toxicity.

  8. The toxicity of plutonium

    International Nuclear Information System (INIS)

    Ramsden, D.; Johns, T.F.

    1977-01-01

    Reference is made to recent publications concerned with the radiotoxicity of inhaled insoluble Pu compounds. The publications are a paper by Thorne and Vennart (Nature 263:555 (1976)), a report entitled 'The Toxicity of Plutonium', (London (HMSO), 1975), and the 'Sixth Report of the Royal Commission on Environmental Pollution', (Cmnd. 6618, London (HMSO), 1976). Thorne and Vennart concluded that the previously accepted value for the maximum permissible annual intake (MPAI) of such compounds may be too high by a factor of about five, and a similar conclusion was reached in the other two publications. It is thought by the present authors that the methods which have been used to suggest new values for the MPAI are unduly pessimistic for high-fired PuO 2 ; calculations have been based on the lung model of ICRP Publication 19 'The Metabolism of Compounds of Plutonium and the Other Actinides', (International Commission of Radiological Protection, 1972). This involves concluding that the risks to bone and liver are comparable to those for lung. This is discussed and it is thought that the previously established idea that the lung is the critical organ remains substantially correct for the case of high-fired PuO 2 . (U.K.)

  9. Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

    Science.gov (United States)

    Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

    2005-04-01

    The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

  10. Melanoma Patients with Unknown Primary Site or Nodal Recurrence after Initial Diagnosis Have a Favourable Survival Compared to Those with Synchronous Lymph Node Metastasis and Primary Tumour

    OpenAIRE

    Weide, Benjamin; Faller, Christine; Els?sser, Margrit; B?ttner, Petra; Pflugfelder, Annette; Leiter, Ulrike; Eigentler, Thomas Kurt; Bauer, J?rgen; Meier, Friedegund; Garbe, Claus

    2013-01-01

    BACKGROUND: A direct comparison of prognosis between patients with regional lymph node metastases (LNM) detected synchronously with the primary melanoma (primary LNM), patients who developed their first LNM subsequently (secondary LNM) and those with initial LNM in melanoma with unknown primary site (MUP) is missing thus far. PATIENTS AND METHODS: Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression ...

  11. Syncytin immunoreactivity in colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Julie Mou; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2009-01-01

    monoclonal syncytin antibody we have assessed syncytin expression in a retrospective series of 140 colorectal cancer patients. Variable degrees of syncytin expression were detected in both colonic and rectal tumors and the prognostic impact of such expression was analysed with the Kaplan-Meier method...... and the Cox proportional hazard model. Interestingly, increased syncytin expression was associated with decreased overall survival in rectal but not in colonic cancer patients. Thus, the prognostic impact of syncytin expression appears to vary with the tumor type....

  12. Survival of Patients With Cervical Cancer in Rural India

    OpenAIRE

    Vinoda Thulaseedharan, Jissa; Malila, Nea; Swaminathan, Rajaraman; Esmy Pulikottil, Okuru; Hakama, Matti; Muwonge, Richard; Sankaranarayanan, Rengaswamy

    2015-01-01

    Background: Patients’ survival after diagnosis of cervical cancer is indirectly influenced by socio-economic factors. We evaluated this survival and its socio-economic determinants in a rural population in south India. Methods: We assessed 165 women diagnosed with cervical cancer from the routine care control arm of a randomized screening trial conducted in rural south India. Kaplan-Meier curves were plotted to illustrate the observed survival of cancer patients. The effect of socio-econom...

  13. Cetuximab Concomitant with Second-Line Radiation Therapy in Patients with Locally Advanced Recurrent Squamous Cell Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Muge Akmansu

    2010-12-01

    Full Text Available We presented 9 recurrent head and neck carcinoma patients. Priorly all of them had received radiochemotherapy. We used cetuximab and irradiation concomitantly. Overall survival analysis of the patients was performed using the Kaplan-Meier method on SPSS version 15.0. Based on this calculation, mean follow-up duration is 12.8 months. Mean survival time is 19.8 months and annual mean survival rate is 59.3%.

  14. Application of Enlisted Force Retention Levels and Career Field Stability

    Science.gov (United States)

    2017-03-23

    APPLICATION OF ENLISTED FORCE RETENTION LEVELS AND CAREER FIELD STABILITY THESIS Presented to the Faculty Department of Operational Sciences ...Fulfillment of the Requirements for the Degree of Master of Science in Operations Research Jamie T. Zimmermann, MS, BS Captain, USAF March 2017...Appendix B. The function proc lifetest is a nonparametric estimate of the survivor function using either the Kaplan-Meier method or the actuarial

  15. High income, employment, postgraduate education, and marriage. A suicidal cocktail among psychiatric patients

    DEFF Research Database (Denmark)

    Agerbo, Esben

    2007-01-01

    longitudinal data on income, labor market affiliation, educational attainment, and marital and cohabitational status (96,369 patients, 256,619 admissions, and 2727 suicides). MAIN OUTCOME MEASURES: Suicide risks after hospital discharge were depicted using Kaplan-Meier product-limit methods. Hazard ratios (HRs...... is generally associated with low income, unemployment, educational underachievement, and singleness, but this study suggests that the opposite is true among psychiatric patients. However, loss of income, labor market status, and marriage increase the suicide risk....

  16. Toxicity Estimation Software Tool (TEST)

    Science.gov (United States)

    The Toxicity Estimation Software Tool (TEST) was developed to allow users to easily estimate the toxicity of chemicals using Quantitative Structure Activity Relationships (QSARs) methodologies. QSARs are mathematical models used to predict measures of toxicity from the physical c...

  17. Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes

    International Nuclear Information System (INIS)

    Sole, Claudio V.; Calvo, Felipe A.; Polo, Alfredo; Cambeiro, Mauricio; Gonzalez, Carmen; Desco, Manuel; Martinez-Monge, Rafael

    2015-01-01

    Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates

  18. Toxic Anterior Segment Syndrome (TASS

    Directory of Open Access Journals (Sweden)

    Özlem Öner

    2011-12-01

    Full Text Available Toxic anterior segment syndrome (TASS is a sterile intraocular inflammation caused by noninfectious substances, resulting in extensive toxic damage to the intraocular tissues. Possible etiologic factors of TASS include surgical trauma, bacterial endotoxin, intraocular solutions with inappropriate pH and osmolality, preservatives, denatured ophthalmic viscosurgical devices (OVD, inadequate sterilization, cleaning and rinsing of surgical devices, intraocular lenses, polishing and sterilizing compounds which are related to intraocular lenses. The characteristic signs and symptoms such as blurred vision, corneal edema, hypopyon and nonreactive pupil usually occur 24 hours after the cataract surgery. The differential diagnosis of TASS from infectious endophthalmitis is important. The main treatment for TASS formation is prevention. TASS is a cataract surgery complication that is more commonly seen nowadays. In this article, the possible underlying causes as well as treatment and prevention methods of TASS are summarized. (Turk J Oph thal mol 2011; 41: 407-13

  19. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    International Nuclear Information System (INIS)

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-01-01

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  20. Competing approaches to analysis of failure times with competing risks.

    Science.gov (United States)

    Farley, T M; Ali, M M; Slaymaker, E

    2001-12-15

    For the analysis of time to event data in contraceptive studies when individuals are subject to competing causes for discontinuation, some authors have recently advocated the use of the cumulative incidence rate as a more appropriate measure to summarize data than the complement of the Kaplan-Meier estimate of discontinuation. The former method estimates the rate of discontinuation in the presence of competing causes, while the latter is a hypothetical rate that would be observed if discontinuations for the other reasons could not occur. The difference between the two methods of analysis is the continuous time equivalent of a debate that took place in the contraceptive literature in the 1960s, when several authors advocated the use of net (adjusted or single decrement life table rates) rates in preference to crude rates (multiple decrement life table rates). A small simulation study illustrates the interpretation of the two types of estimate - the complement of the Kaplan-Meier estimate corresponds to a hypothetical rate where discontinuations for other reasons did not occur, while the cumulative incidence gives systematically lower estimates. The Kaplan-Meier estimates are more appropriate when estimating the effectiveness of a contraceptive method, but the cumulative incidence estimates are more appropriate when making programmatic decisions regarding contraceptive methods. Other areas of application, such as cancer studies, may prefer to use the cumulative incidence estimates, but their use should be determined according to the application. Copyright 2001 John Wiley & Sons, Ltd.

  1. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  2. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  3. Censoring: a new approach for detection limits in total-reflection X-ray fluorescence

    International Nuclear Information System (INIS)

    Pajek, M.; Kubala-Kukus, A.; Braziewicz, J.

    2004-01-01

    It is shown that the detection limits in the total-reflection X-ray fluorescence (TXRF), which restrict quantification of very low concentrations of trace elements in the samples, can be accounted for using the statistical concept of censoring. We demonstrate that the incomplete TXRF measurements containing the so-called 'nondetects', i.e. the non-measured concentrations falling below the detection limits and represented by the estimated detection limit values, can be viewed as the left random-censored data, which can be further analyzed using the Kaplan-Meier (KM) method correcting for nondetects. Within this approach, which uses the Kaplan-Meier product-limit estimator to obtain the cumulative distribution function corrected for the nondetects, the mean value and median of the detection limit censored concentrations can be estimated in a non-parametric way. The Monte Carlo simulations performed show that the Kaplan-Meier approach yields highly accurate estimates for the mean and median concentrations, being within a few percent with respect to the simulated, uncensored data. This means that the uncertainties of KM estimated mean value and median are limited in fact only by the number of studied samples and not by the applied correction procedure for nondetects itself. On the other hand, it is observed that, in case when the concentration of a given element is not measured in all the samples, simple approaches to estimate a mean concentration value from the data yield erroneous, systematically biased results. The discussed random-left censoring approach was applied to analyze the TXRF detection-limit-censored concentration measurements of trace elements in biomedical samples. We emphasize that the Kaplan-Meier approach allows one to estimate the mean concentrations being substantially below the mean level of detection limits. Consequently, this approach gives a new access to lower the effective detection limits for TXRF method, which is of prime interest for

  4. Construction of Bimetallic ZIF-Derived Co-Ni LDHs on the Surfaces of GO or CNTs with a Recyclable Method: Toward Reduced Toxicity of Gaseous Thermal Decomposition Products of Unsaturated Polyester Resin.

    Science.gov (United States)

    Hou, Yanbei; Qiu, Shuilai; Hu, Yuan; Kundu, Chanchal Kumar; Gui, Zhou; Hu, Weizhao

    2018-05-16

    This work proposed an idea of recycling in preparing Co-Ni layered double hydroxide (LDH)-derived flame retardants. A novel and feasible method was developed to synthesize CO-Ni LDH-decorated graphene oxide (GO) and carbon nanotubes (CNTs), by sacrificing bimetal zeolitic imidazolate frameworks (ZIFs). Organic ligands that departed from ZIFs were recyclable and can be reused to synthesize ZIFs. ZIFs, as transitional objects, in situ synthesized on the surfaces of GO or CNTs directly suppressed the re-stacking of the carbides and facilitated the preparation of GO@LDHs and CNTs@LDHs. As-prepared hybrids catalytically reduced toxic CO yield during the thermal decomposition of unsaturated polyester resin (UPR). What is more, the release behaviors of aromatic compounds were also suppressed during the pyrolysis process of UPR composites. The addition of GO@LDHs and CNTs@LDHs obviously inhibited the heat release and smoke emission behaviors of the UPR matrix during combustion. Mechanical properties of the UPR matrix also improved by inclusion of the carbides derivatives. This work paved a feasible method to prepare well-dispersed carbides@Co-Ni LDH nanocomposites with a more environmentally friendly method.

  5. A novel ultra-performance liquid chromatography hyphenated with quadrupole time of flight mass spectrometry method for rapid estimation of total toxic retronecine-type of pyrrolizidine alkaloids in herbs without requiring corresponding standards.

    Science.gov (United States)

    Zhu, Lin; Ruan, Jian-Qing; Li, Na; Fu, Peter P; Ye, Yang; Lin, Ge

    2016-03-01

    Nearly 50% of naturally-occurring pyrrolizidine alkaloids (PAs) are hepatotoxic, and the majority of hepatotoxic PAs are retronecine-type PAs (RET-PAs). However, quantitative measurement of PAs in herbs/foodstuffs is often difficult because most of reference PAs are unavailable. In this study, a rapid, selective, and sensitive UHPLC-QTOF-MS method was developed for the estimation of RET-PAs in herbs without requiring corresponding standards. This method is based on our previously established characteristic and diagnostic mass fragmentation patterns and the use of retrorsine for calibration. The use of a single RET-PA (i.e. retrorsine) for construction of calibration was based on high similarities with no significant differences demonstrated by the calibration curves constructed by peak areas of extract ion chromatograms of fragment ion at m/z 120.0813 or 138.0919 versus concentrations of five representative RET-PAs. The developed method was successfully applied to measure a total content of toxic RET-PAs of diversified structures in fifteen potential PA-containing herbs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Eco-Friendly Synthesis of Silver Nanoparticles Through Economical Methods and Assessment of Toxicity Through Oxidative Stress Analysis in the Labeo Rohita.

    Science.gov (United States)

    Khan, Muhammad Saleem; Qureshi, Naureen Aziz; Jabeen, Farhat; Asghar, Muhammad Saleem; Shakeel, Muhammad; Fakhar-E-Alam, Muhammad

    2017-04-01

    The physicochemical and biological properties of metals change as the particles are reduced to nanoscale. This ability increases the application of nanoparticles in commercial and medical industry. Keeping in view this importance, Silver nanoparticles (Ag-NPs) were synthesized by reduction methods using formaldehyde as reducing agent in the chemical route and lemon extracts in the biological route. The scanning electron microscope (SEM) images of nanoparticles suggested that the particles were either agglomerated or spherical in shape with mean diameter of 16.59 nm in the chemical route and 42.93 nm in the biological route. The particles were between 5 and 80 nm with maximum frequency between 5 and 20 nm in the chemical route and between 5 and 100 nm with maximum frequency between 15 and 50 nm in the biological method. In the second phase of the study, the effect of Ag-NPs on the oxidative stress was studied. For this purpose, Labeo rohita (20 ± 2.5 g in weight and 12 ± 1.4 cm in length) were involved. Six treatments were applied in three replicates having five fishes in each replicate. The first treatment was used as control group, and the other five treatments were exposed to either 10 or 20 or 30 or 45 or 55 mg L -1 of Ag-NPs for 28 days. The treatment of Ag-NPs caused oxidative stress in the liver and gill tissues, which induced alterations in the activities of antioxidant enzymes. The level of catalase (CAT) was decreased in response to Ag-NPs concentration in dose-dependent manner. Ag-NPs treatment stimulated the liver and gill tissues to significantly increase the level of superoxide dismutase (SOD), which might be due to synthesis of SOD and addition in the pre-existing SOD level. The level decreases again due to depletion of SOD level. There was a sharp decline in the activities of glutathione S-transferase (GST) in both gills and liver tissues even at lower concentration, and this decrease in the GST activity was significantly

  7. Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Francis, Jasmine H., E-mail: francij1@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gobin, Y. Pierre; Marr, Brian P. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States); Brodie, Scott E. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mount Sinai School of Medicine, New York, New York (United States); Dunkel, Ira J.; Abramson, David H. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States)

    2013-11-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.

  8. Outcomes of Therasphere Radioembolization for Colorectal Metastases.

    Science.gov (United States)

    Abbott, Andrea M; Kim, Richard; Hoffe, Sarah E; Arslan, Bulent; Biebel, Ben; Choi, Junsung; El-Haddad, Ghassan; Kis, Bela; Sweeney, Jennifer; Meredith, Kenneth L; Almhanna, Khaldoun; Strosberg, Jonathan; Shibata, David; Fulp, William J; Shridhar, Ravi

    2015-09-01

    The liver is the most common site for colorectal cancer (CRC) metastases. Radioembolization with yttrium-90 (Y90) represents an alternative approach in the management of unresectable hepatic colorectal metastases. The objective of this study was to evaluate outcomes after treatment with Y90. A retrospective review of patients undergoing Y90 glass microsphere treatment for metastatic CRC from 2009 to 2013 was conducted. Multivariable analysis (MVA) of factors related to overall survival (OS) was performed using the Cox proportional hazard and OS estimates were calculated using the Kaplan-Meier method. We identified 68 patients. Median and 2-year OS were 11.6 months and 34%. For patients with ≤ 25% hepatic burden of disease (HBD) and 1 chemotherapy regimen, 2-year OS was 63%. Median and 2-year OS for patients with ≤ 25% versus > 25% HBD were 19.6 months and 42% versus 3.4 months and 0% (P 25% HBD, ≥ 3 lines of chemotherapy, and higher CEA were independently prognostic for increased mortality, and resected status of the primary tumor was associated with decreased mortality. The presence of extrahepatic metastases was not prognostic. Toxicities were mild and only 5 patients experienced Grade 3/4 biochemical toxicity. Yttrium-90 was associated with acceptable OS with minimal morbidity in this series. Minimal exposure to chemotherapy and low HBD were found to be associated with better OS, however, even patients with chemotherapy-refractory disease received a benefit from treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

    International Nuclear Information System (INIS)

    Francis, Jasmine H.; Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil; Gobin, Y. Pierre; Marr, Brian P.; Brodie, Scott E.; Dunkel, Ira J.; Abramson, David H.

    2013-01-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG

  10. Evaluation of a carbon paste electrode modified with Strontium substituted bismuth and titanium oxide nanoparticles in the toxic metal chromium (VI determination potentiometric method

    Directory of Open Access Journals (Sweden)

    Atefeh Badri

    2016-09-01

    Full Text Available Strontium substituted bismuth and titanium oxide nanoparticles with aurivillius morphology synthesized by chemical co-precipitation method and were characterized using XRD. The nanopartcles were used in the composition of the carbon paste to improve conductivity and transduction of chemical signal to electrical signal. A procedure for the determination of chromium is described based on pre-concentration of the dichromate anion at a carbon paste electrode modified. A novel potentiometric Cr6+carbon paste electrode incorporating Strontium substituted bismuth and titanium oxide nanoparticles (SSBTO. Ina acetate buffer solution of pH 5, the sensor displays a rapid and linear response for Cr6+ over the concentration range 1.0×10-5 to 1.0×10-1mol L-1 M with an anionic slope of 54.8± 0.2 mV decade ’ and a detection limit of the order of0.002 /µg ml ‘. The sensor is used for determination of Cr6+ by direct monitoring of Cr6+.The average recoveries of Cr6+at concentration levels of 0.5~40 pg/ml ’is 98.3. The electrode has a short response time (<6s and can be used for at least twenty days without any considerable divergence in potentials and the working pH range was 4.5-6.5. The proposed electrode was successfully used as an indicator for potentiometric determination of Cr6+in water sample.

  11. Determination of toxic and trace elements in human hair and sediment samples by reactor neutron activation analysis technique based-on the k-zero method

    International Nuclear Information System (INIS)

    Ho Manh Dung; Nguyen Mong Sinh; Nguyen Thanh Binh; Cao Dong Vu; Nguyen Thi Si

    2004-01-01

    The analysis of human hair can evaluate the degree of environmental pollutants exposure to human body, intakes of food and metabolism. Also, the analysis of sediment can aid in reconstructing the history of changes, understanding human impact on the ecosystem, and suggesting possible remedial strategies. The k o -standardization method of neutron activation analysis (k o -NAA) on research reactor is capable to play an important role as a main analytical technique with the advantages of sensitivity, precision, accuracy, multielement and routine for the sample object. Therefore, the project's aim is to build the k o -NAA procedures on the Dalat research reactor for the analysis of human hair and sediment samples. The K o -NAA procedure on the Dalat research reactor is able to determine of multielement: Ag, Al, As, Br, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K Mg, Mn, Na, S, Sb, Se, Sr, Ti, V and Zn in The human hair; and of multielement: As, Co, Cr, Cs, Fe, Hf, K, La, Mn, Na Rb, Sb, Sc, Yb and Zn in the sediment. (author)

  12. Use of zeolite for removing ammonia and ammonia-caused toxicity in marine toxicity identification evaluations.

    Science.gov (United States)

    Burgess, R M; Perron, M M; Cantwell, M G; Ho, K T; Serbst, J R; Pelletier, M C

    2004-11-01

    Ammonia occurs in marine waters including effluents, receiving waters, and sediment interstitial waters. At sufficiently high concentrations, ammonia can be toxic to aquatic species. Toxicity identification evaluation (TIE) methods provide researchers with tools for identifying aquatic toxicants. For identifying ammonia toxicity, there are several possible methods including pH alteration and volatilization, Ulva lactuca addition, microbial degradation, and zeolite addition. Zeolite addition has been used successfully in freshwater systems to decrease ammonia concentrations and toxicity for several decades. However, zeolite in marine systems has been used less because ions in the seawater interfere with zeolite's ability to adsorb ammonia. The objective of this study was to develop a zeolite method for removing ammonia from marine waters. To accomplish this objective, we performed a series of zeolite slurry and column chromatography studies to determine uptake rate and capacity and to evaluate the effects of salinity and pH on ammonia removal. We also assessed the interaction of zeolite with several toxic metals. Success of the methods was also evaluated by measuring toxicity to two marine species: the mysid Americamysis bahia and the amphipod Ampelisca abdita. Column chromatography proved to be effective at removing a wide range of ammonia concentrations under several experimental conditions. Conversely, the slurry method was inconsistent and variable in its overall performance in removing ammonia and cannot be recommended. The metals copper, lead, and zinc were removed by zeolite in both the slurry and column treatments. The zeolite column was successful in removing ammonia toxicity for both the mysid and the amphipod, whereas the slurry was less effective. This study demonstrated that zeolite column chromatography is a useful tool for conducting marine water TIEs to decrease ammonia concentrations and characterize toxicity.

  13. Clinical Significance of Preoperative Albumin and Globulin Ratio in Patients with Gastric Cancer Undergoing Treatment

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    Min-jie Mao

    2017-01-01

    Full Text Available Background. The pretreatment albumin and globulin ratio (AGR was an inflammation-associated factor which was related to the overall survival in various malignancies. The aim of this study was to evaluate the prognostic value of AGR in patients with gastric cancer. Method. This retrospective study included 862 cases pathologically diagnosed with gastric cancer. All patients were randomly divided into the testing group (431 cases and validation group (431 cases. The relationships of AGR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing group, the median overall survival was 26.90 months and the cutoff value of AGR was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was correlated with poorer overall survival. Multivariate analysis demonstrated that AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI = 0.351–0.973, and p = 0.039. In the validation group, the median overall survival was 24.10 months. Lower AGR (≤1.50 also had a significantly poorer overall survival by Kaplan-Meier analysis. According to multivariate analysis, the AGR was also confirmed to be an independent prognostic factor for overall survival (HR: 0.578, 95% CI = 0.373–0.897, and p = 0.015. Conclusions. Our study suggested that the pretreatment AGR could be a prognostic biomarker for overall survival in patients with gastric cancer.

  14. The development of a new algorithm to calculate a survival function in non-parametric ways

    International Nuclear Information System (INIS)

    Ahn, Kwang Won; Kim, Yoon Ik; Chung, Chang Hyun; Kim, Kil Yoo

    2001-01-01

    In this study, a generalized formula of the Kaplan-Meier method is developed. The idea of this algorithm is that the result of the Kaplan-Meier estimator is the same as that of the redistribute-to-the right algorithm. Hence, the result of the Kaplan-Meier estimator is used when we redistribute to the right. This can be explained as the following steps, at first, the same mass is distributed to all the points. At second, when you reach the censored points, you must redistribute the mass of that point to the right according to the following rule; to normalize the masses, which are located to the right of the censored point, and redistribute the mass of the censored point to the right according to the ratio of the normalized mass. Until now, we illustrate the main idea of this algorithm.The meaning of that idea is more efficient than PL-estimator in the sense that it decreases the mass of after that area. Just like a redistribute to the right algorithm, this method is enough for the probability theory

  15. Developmental toxicity of organotin compounds in animals

    Directory of Open Access Journals (Sweden)

    Lijiao eWu

    2014-09-01

    Full Text Available Organotin compounds (OTs have been used as biocides in antifouling paints and agriculture. The IMO introduced a global ban on the use of OTs in antifouling systems in 2001 due to their high toxicity. However, OTs have still been detected in the environment and pose a threat to the ecosystem. Several research groups have summarized the analytical methods, environmental fate, biochemistry, reproductive toxicity and mechanisms of actions of OTs. Here, we reviewed the developmental toxicity of OTs in various organisms such as sea urchin, ascidian, mussel and fish. The differences in sensitivity to OT exposure exist not only in different species but also at different stages in the same species. Though some hypotheses have been proposed to explain the developmental toxicity of OTs, the solid evidences are greatly in need.

  16. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

  17. Assay for the developmental toxicity of safflower (Carthamus tinctorius L. to zebrafish embryos/larvae

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    Qing Xia

    2017-01-01

    Conclusion: Safflower exhibits developmental toxicity for zebrafish embryos/larvae. The developing heart was speculated as the target organ of toxicity. Oxidative stress and increased apoptosis have roles in the developmental toxicity of safflower. This article provides a novel method to research the teratogenicity and possible mechanisms of toxicity of traditional Chinese medicines that are prohibited or contraindicated in pregnant women.

  18. Bioassay method for toxicity studies of insecticide formulations to Tuta absoluta (meyrick, 1917 Metodologia de bioensaio para estudos de toxicidade de formulações comerciais de inseticidas a Tuta absoluta (Meyrick, 1917

    Directory of Open Access Journals (Sweden)

    Tarcísio Visintin da Silva Galdino

    2011-10-01

    Full Text Available Chemical control is the main method for controlling the tomato leafminer, Tuta absoluta (Meyrick, 1917 (Lepidoptera: Gelechiidae. Reported techniques for the evaluation of insecticide toxicity to the tomato leafminer are not in agreement with field conditions and do not allow us to verify whether doses used in the field are efficient for control. Thus, the objective of this work was to develop a bioassay methodology to study the toxicity of insecticide formulations to T. absoluta that represent field conditions for fast-acting insecticides (neurotoxics and inhibitors of respiration and slow-acting insecticides (Bacillus thuringiensis and insect growth regulators. The leaf-dip method was the most efficient method for toxicity studies of insecticides formulations to T. absoluta. We verified that bioassays with fast-acting insecticides should be performed with glass Petri dishes containing one tomato foliole from the 4th leaf from the plant apex infested with 10 larvae of 3rd instar and these bioassays can last 48 hours. Conversely, bioassays with slow-acting insecticides should be performed with two-liter transparent PET bottles containing the 4th leaf from the plant apex, with their petioles immersed in a glass bottle containing 120 mL of water, and this leaf should be infested with 10 larvae of 2nd instar and this bioassays can last seven days.O principal método utilizado no controle da traça-do-tomateiro Tuta absoluta (Meyrick, 1917 (Lepidoptera: Gelechiidae é a aplicação de inseticidas. As técnicas atuais de avaliação da toxicidade de inseticidas sobre essa praga não simulam a situação de campo e não possibilitam a verificação se as doses usadas no campo são eficientes no seu controle. Assim, neste trabalho, objetivou-se desenvolver uma metodologia que represente as condições de campo para inseticidas de ação rápida (neurotóxicos e inibidores respiratórios e de ação lenta (Bacillus thuringiensis e reguladores de

  19. Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    King, Christopher R.; Brooks, James D.; Gill, Harcharan; Presti, Joseph C.

    2012-01-01

    Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 ± 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%–102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.

  20. Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, Christopher R., E-mail: crking@mednet.ucla.edu [Departments of Radiation Oncology and Urology, University of California Los Angeles School of Medicine, Los Angeles, CA (United States); Brooks, James D.; Gill, Harcharan; Presti, Joseph C. [Department of Urology, Stanford University School of Medicine, Stanford, CA (United States)

    2012-02-01

    Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 {+-} 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.

  1. Quality of Life after Post-Prostatectomy Intensity Modulated Radiation Therapy: Pelvic Nodal Irradiation Is Not Associated with Worse Bladder, Bowel, or Sexual Outcomes.

    Directory of Open Access Journals (Sweden)

    James M Melotek

    Full Text Available Limited data exist regarding toxicity and quality of life (QOL after post-prostatectomy intensity modulated radiation therapy (IMRT and whether pelvic nodal RT influences these outcomes.118 men were treated with curative-intent RT after radical prostatectomy. 69 men (58% received pelvic nodal RT. QOL data and physician-assigned toxicity were prospectively collected. Changes in QOL from baseline were assessed with Wilcoxon signed-rank tests and risk factors associated with each domain were identified with generalized estimating equation (GEE models. Late freedom from (FF toxicity was estimated by the Kaplan-Meier method and comparisons were tested using the log-rank test.Urinary irritation/obstruction, bowel, and sexual domain scores declined at 2 months (all P ≤ 0.01 but were no different than baseline at subsequent visits through 4 years of follow-up. At 4 years, FF grade 2+ GI toxicity was 90% and FF grade 2+ GU toxicity was 89%. On GEE analysis, pelvic nodal RT was associated with decreased bowel function (P = 0.09 and sexual function (P = 0.01. On multivariate analysis, however, there was no significant association with either decreased bowel (P = 0.31 or sexual (P = 0.84 function. There was also no association with either FF grade 2+ GI toxicity (P = 0.24 or grade 2+ GU toxicity (P = 0.51.Receipt of pelvic nodal RT was not associated with inferior QOL or toxicity compared to prostate bed alone RT. For the entire cohort, RT was associated with only temporary declines in patient-reported urinary, bowel, or sexual QOL.

  2. The toxicity of plutonium

    International Nuclear Information System (INIS)

    Crouse, P.L.

    1994-01-01

    Shipments of plutonium occasionally pass around the Cape coastal waters on its way to Japan from Europe. This invariably leads to a great deal of speculation of the dangers involved and of the extreme toxicity of plutonium, with the media and environmental groups claiming that (a) plutonium is the most toxic substance known to man, and that (b) a few kilograms of plutonium ground finely and dispersed in the atmosphere could kill every human being on earth. Comparisons with other poisons are drawn, e.g. common inorganic chemicals and biological agents. The original scare around the extraordinary toxicity of Pu seems to have started in 1974 with the claims of Tamplin and Cochran's hot particle theory about plutonium lodging in the sensitive portions of the lungs in small concentrated aggregates where they are much more effective in producing cancers. This theory, however, is regarded as thoroughly discredited by the experts in the field of radiotoxicity. 8 refs

  3. Iron metabolism and toxicity

    International Nuclear Information System (INIS)

    Papanikolaou, G.; Pantopoulos, K.

    2005-01-01

    Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

  4. A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

    International Nuclear Information System (INIS)

    Asher, Anthony L.; Burri, Stuart H.; Wiggins, Walter F.; Kelly, Renee P.; Boltes, Margaret O.; Mehrlich, Melissa; Norton, H. James; Fraser, Robert W.

    2014-01-01

    Purpose: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong

  5. A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Asher, Anthony L., E-mail: asher@cnsa.com [Department of Neurosurgery, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States); Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (United States); Burri, Stuart H. [Department of Radiation Oncology, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States); Wiggins, Walter F. [Wake Forest School of Medicine MD/PhD Program, Winston-Salem, North Carolina (United States); Kelly, Renee P. [Brain Tumor Fund for the Carolinas, Charlotte, North Carolina (United States); Boltes, Margaret O.; Mehrlich, Melissa [Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (United States); Norton, H. James [Department of Biostatistics, Carolinas Medical Center, Charlotte, North Carolina (United States); Fraser, Robert W. [Department of Radiation Oncology, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States)

    2014-03-15

    Purpose: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong

  6. Intensity modulated radiotherapy with concurrent chemotherapy for larynx preservation of advanced resectable hypopharyngeal cancer

    Directory of Open Access Journals (Sweden)

    Chao Hsing-Lung

    2010-05-01

    Full Text Available Abstract Background To analyze the rate of larynx preservation in patients of locally advanced hypopharyngeal cancer treated with intensity modulated radiotherapy (IMRT plus concurrent chemotherapy, and compare the results with patients treated with primary surgery. Methods Between January 2003 and November 2007, 14 patients were treated with primary surgery and 33 patients were treated with concurrent chemoradiotherapy (CCRT using IMRT technique. Survival rate, larynx preservation rate were calculated with the Kaplan-Meier method. Multivariate analysis was conducted for significant prognostic factors with Cox-regression method. Results The median follow-up was 19.4 months for all patients, and 25.8 months for those alive. The 5-year overall survival rate was 33% and 44% for primary surgery and definitive CCRT, respectively (p = 0.788. The 5-year functional larynx-preservation survival after IMRT was 40%. Acute toxicities were common, but usually tolerable. The rates of treatment-related mucositis (≥ grade 2 and pharyngitis (≥ grade 3 were higher in the CCRT group. For multivariate analysis, treatment response and cricoid cartilage invasion strongly correlated with survival. Conclusions IMRT plus concurrent chemotherapy may preserve the larynx without compromising survival. Further studies on new effective therapeutic agents are essential.

  7. Immunotoxicity, genotoxicity and epigenetic toxicity of nanomaterials: New strategies for toxicity testing?

    Science.gov (United States)

    Dusinska, Maria; Tulinska, Jana; El Yamani, Naouale; Kuricova, Miroslava; Liskova, Aurelia; Rollerova, Eva; Rundén-Pran, Elise; Smolkova, Bozena

    2017-11-01

    The unique properties of nanomaterials (NMs) are beneficial in numerous industrial and medical applications. However, they could also induce unintended effects. Thus, a proper strategy for toxicity testing is essential in human hazard and risk assessment. Toxicity can be tested in vivo and in vitro; in compliance with the 3Rs, alternative strategies for in vitro testing should be further developed for NMs. Robust, standardized methods are of great importance in nanotoxicology, with comprehensive material characterization and uptake as an integral part of the testing strategy. Oxidative stress has been shown to be an underlying mechanism of possible toxicity of NMs, causing both immunotoxicity and genotoxicity. For testing NMs in vitro, a battery of tests should be performed on cells of human origin, either cell lines or primary cells, in conditions as close as possible to an in vivo situation. Novel toxicity pathways, particularly epigenetic modification, should be assessed along with conventional toxicity testing methods. However, to initiate epigenetic toxicity screens for NM exposure, there is a need to better understand their adverse effects on the epigenome, to identify robust and reproducible causal links between exposure, epigenetic changes and adverse phenotypic endpoints, and to develop improved assays to monitor epigenetic toxicity. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Tomotherapy for prostate adenocarcinoma: A report on acute toxicity

    International Nuclear Information System (INIS)

    Keiler, Louis; Dobbins, Donald; Kulasekere, Ravi; Einstein, Douglas

    2007-01-01

    Background and purpose: To analyze the impact of Tomotherapy (TOMO) intensity modulated radiotherapy (IMRT) on acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer. Materials and methods: The records of 55 consecutively treated TOMO patients were reviewed. Additionally a well-matched group of 43 patients treated with LINAC-based step and shoot IMRT (LINAC) was identified. Acute toxicity was scored according to Radiation Therapy Oncology Group acute toxicity criterion. Results: The grade 2-3 acute GU toxicity rates for the TOMO vs. LINAC groups were 51% vs. 28% (p = 0.001). Acute grade 2 GI toxicity was 25% vs. 40% (p = 0.024), with no grade 3 GI toxicity in either group. In univariate analysis, androgen deprivation, prostate volume, pre-treatment urinary toxicity, and prostate dose homogeneity correlated with acute GI and GU toxicity. With multivariate analysis use of Tomotherapy, median bladder dose and bladder dose homogeneity remained significantly correlated with GU toxicity. Conclusions: Acute GI toxicity for prostate cancer is improved with Tomotherapy at a cost of increased acute GU toxicity possibly due to differences in bladder and prostate dose distribution

  9. External radiation toxicity

    International Nuclear Information System (INIS)

    Fritz, T.E.

    1979-01-01

    The section contains summaries of research on neutron and gamma-ray toxicity in rodents, late effects of low-dose rate, whole-body, protracted exposure to 60 Co gamma rays on young adult beagles, and the effects of protracted, low-dose rate exposure to 60 Co gamma rays on preclinical leukemic phase-related changes in the granulopoietic system of beagles

  10. Local anaesthetic toxicity

    African Journals Online (AJOL)

    Local anaesthetic toxicity has been known since the introduction of local anaesthetic drugs into anaesthetic practice more than a hundred ... was the first to think of cocaine as a narcotic. ..... anaesthetics act as Na+ channel-blocking agents, they slow down .... all neurons, leading to global CNS depression, slowing and.

  11. Toxicity of lunar dust

    NARCIS (Netherlands)

    Linnarsson, D.; Carpenter, J.; Fubini, B.; Gerde, P.; Loftus, D.; Prisk, K.; Staufer, U.; Tranfield, E.; van Westrenen, W.

    2012-01-01

    The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of

  12. Uranium: biokinetics and toxicity

    International Nuclear Information System (INIS)

    Menetrier, F.; Renaud-Salis, V.; Flury-Herard, A.

    2000-01-01

    This report was achieved as a part of a collaboration with the Fuel Cycle Direction. Its aim was to give the state of the art about: the behaviour of uranium in the human organism (biokinetics) after ingestion, its toxicity (mainly renal) and the current regulation about its incorporation. Both in the upstream and in the downstream of the fuel cycle, uranium remains, quantitatively, the first element in the cycle which is, at the present time, temporarily disposed or recycled. Such a considerable quantity of uranium sets the problem of its risk on the health. In the long term, the biosphere may be affected and consequently the public may ingest water or food contaminated with uranium. In this way, radiological and chemical toxicity risk may be activated. This report emphasizes: the necessity of confirming some experimental and epidemiological biokinetic data used or not in the ICRP models. Unsolved questions remain about the gastrointestinal absorption according to chemical form (valency state, mixtures...), mass and individual variations (age, disease) further a chronic ingestion of uranium. It is well established that uranium is mainly deposited in the skeleton and the kidney. But the skeleton kinetics following a chronic ingestion and especially in some diseases has to be more elucidated; the necessity of taking into account uranium at first as a chemical toxic, essentially in the kidney and determining the threshold of functional lesion. In this way, it is important to look for some specific markers; the problem of not considering chemical toxicity of uranium in the texts regulating its incorporation

  13. How toxic is ibogaine?

    NARCIS (Netherlands)

    Litjens, Ruud P. W.; Brunt, Tibor M.

    2016-01-01

    Ibogaine is a psychoactive indole alkaloid found in the African rainforest shrub Tabernanthe Iboga. It is unlicensed but used in the treatment of drug and alcohol addiction. However, reports of ibogaine's toxicity are cause for concern. To review ibogaine's pharmacokinetics and pharmacodynamics,

  14. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    The brain is reportedly sensitive to monosodium glutamate (MSG) toxicity via oxidative stress. Sida acuta leaf ethanolic .... wherein the right hemisphere, was preserved for histology and fixed in 10% ... Biochemical Assays: The left hemisphere of the brain samples was ...... development in male and female rats. Exp Physiol.

  15. Nanomaterials and Retinal Toxicity

    Science.gov (United States)

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  16. Toxic Hazards in Aviation.

    Science.gov (United States)

    1981-04-01

    Pasteur, Lillm,FRANCE. (2) CONISH H.H., EARTH M.L.& IANNi F.L, "Comparative Toxicology of Platics during Thar-modecoqiorition Intsw-re8posium on...Pyrolysnis and Combustion of Materials" Firm and Materials (1976).1, 29-35 (8) ALAAIE Y."Toxicity of Platic dacomposition ProductsŖd Annu~al Progress

  17. Field experiments of Anopheles gambiae attraction to local fruits/seedpods and flowering plants in Mali to optimize strategies for malaria vector control in Africa using attractive toxic sugar bait methods

    Directory of Open Access Journals (Sweden)

    Bah Sekou

    2010-09-01

    Full Text Available Abstract Background Based on recent studies in Israel demonstrating that attractive toxic sugar bait (ATSB methods can be used to decimate local anopheline and culicine mosquito populations, an important consideration is whether the same methods can be adapted and improved to attract and kill malaria vectors in Africa. The ATSB approach uses fruit or flower scent as an attractant, sugar solution as a feeding stimulant, and an oral toxin. The ATSB solutions are either sprayed on vegetation or suspended in simple bait stations, and the mosquitoes ingesting the toxic solutions are killed. As such, this approach targets sugar-feeding female and male mosquitoes. This study examines the attractiveness of African malaria vectors to local fruits/seedpods and flowering plants, key biological elements of the ATSB approach for mosquito control. Methods Three field experiments were conducted at sites in Mali. The attraction of Anopheles gambiae s.l. to 26 different local fruits and seedpods was determined at a site in the semi-arid Bandiagara District of Mali. Wire mesh glue traps with fruits/seedpods suspended on skewers inside were set along a seasonal lagoon. Seven replicates of each fruit/seedpod species were tested, with a water-soaked sponge and a sugar-soaked sponge as controls. The attraction of An. gambiae s.l. to 26 different types of flowering plants was determined at a site near Mopti in Mali. The flowering plants held in a water-filled buried container were tested using the same glue traps, with controls including water only and sugar solution. Six replicates of each selected plant type were tested on transects between rice paddies. Additional studies using CDC light traps were done to determine the relative densities and periodicity of An. gambiae s.l. attraction to branches of the most highly attractive flowering plant, branches without flowers, human odor, and candescent light. Results Of the 26 fruits and seedpods tested, 6 were attractive

  18. Late toxicity in breast cancer radiotherapy

    International Nuclear Information System (INIS)

    Gonzalez Coletti, F.; Rafailovici, L.; Filomia, M.L.; Chiozza, J.; Dosoretz, B.

    2008-01-01

    Full text: The aim of this study is to describe and classify chronic complications due to radiotherapy in breast cancer. Also the impact of radiotherapy on the quality of life of patients is evaluated. Materials and methods: 50 patients with breast cancer at early stages (78% in situ, 22% I and II) treated with radiotherapy in breast volume plus boost (45/50 Gy + 18/20 Gy) with a follow up over 5 years. Acute toxicities were found retrospectively and chronic toxicities were assessed though physical examination and review of complementary studies. To facilitate data collection, pre printed forms were used. Bibliographic searches were made. Results: 10% received chemotherapy and 64% tamoxifen. The predominant chronic toxicity were found in skin (66%), although grade I and II (hyperpigmentation 26%, dryness 22%, telangiectasia 10% fibrosis, 4%, other 4%). A 50% of the patients showed hypoesthesia in ipsilateral upper limb. The other toxicities were presented in low rate and magnitude: mastodynia 16%; actinic pneumonitis 4%, pyrosis 4%, Tachycardia 2%, among others. Of the patients with acute toxicity, only 30% were grade III. The 70% of the patients had a positive impact of radiotherapy on quality of life. Conclusions: We found low rates and degrees of late toxicity. It was noticed a relationship between acute and chronic toxicity, because those who presented adverse effects during treatment developed late effects. It reflects the importance of integrating monitoring as part of radiation treatment. It should be adopted a single score of late toxicity measurement to unify data from different series. (authors) [es

  19. Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, Sebastien, E-mail: sebastien.clavel@umontreal.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen, David H.A.; Fortin, Bernard [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Despres, Philippe [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Khaouam, Nader [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Donath, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Soulieres, Denis [Department of Medical Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Guertin, Louis [Department of Head and Neck Surgery, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen-Tan, Phuc Felix [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada)

    2012-02-01

    Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

  20. Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Clavel, Sébastien; Nguyen, David H.A.; Fortin, Bernard; Després, Philippe; Khaouam, Nader; Donath, David; Soulières, Denis; Guertin, Louis; Nguyen-Tan, Phuc Felix

    2012-01-01

    Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

  1. Uterine Carcinosarcoma Confined to the Pelvis: A Retrospective Review and Outcome Analysis

    International Nuclear Information System (INIS)

    Li, H.; TenNapel, M.J.; Bhatia, S.K.; Ahmed, A.; Lin, L.; Jacobson, G.

    2014-01-01

    Objective. We compared the treatments of uterine carcinosarcoma at our institution and evaluated their impact on survival. Methods. A retrospective analysis was performed on 60 eligible patients with carcinosarcoma limited to the pelvis. Subjects were divided into four categories: surgery, surgery plus chemotherapy, surgery plus radiation therapy, and a combination of surgery, chemotherapy, and RT. The most commonly used chemotherapy was cisplatin and/or carboplatin and taxol. Radiotherapy included external beam radiation therapy (EBRT) alone or with high dose rate (HDR) brachytherapy or HDR brachytherapy alone. Survival probability data were computed using the Kaplan-Meier method. The differences between groups were compared using the log-rank test. Results. The combination of surgery and radiation therapy with or without chemotherapy is seen to improve overall survival (OS) compared to surgery alone (Ρ =0.044 and Ρ =0.028 resp.). Brachytherapy involving three HDR vaginal cylinder fractions shows an equally effective reduction in local recurrence compared to EBRT. Conclusion. Our study of a relatively large number of carcinosarcoma patients suggests that adjuvant radiation therapy improves OS compared to surgery alone. Brachytherapy with 3 HDR vaginal cylinder fractions is preferred because of its time-saving, better tolerance, low toxicity and equivalent OS, and local control compared to EBRT.

  2. Field experiments of Anopheles gambiae attraction to local fruits/seedpods and flowering plants in Mali to optimize strategies for malaria vector control in Africa using attractive toxic sugar bait methods.

    Science.gov (United States)

    Müller, Günter C; Beier, John C; Traore, Sekou F; Toure, Mahamoudou B; Traore, Mohamed M; Bah, Sekou; Doumbia, Seydou; Schlein, Yosef

    2010-09-20

    Based on recent studies in Israel demonstrating that attractive toxic sugar bait (ATSB) methods can be used to decimate local anopheline and culicine mosquito populations, an important consideration is whether the same methods can be adapted and improved to attract and kill malaria vectors in Africa. The ATSB approach uses fruit or flower scent as an attractant, sugar solution as a feeding stimulant, and an oral toxin. The ATSB solutions are either sprayed on vegetation or suspended in simple bait stations, and the mosquitoes ingesting the toxic solutions are killed. As such, this approach targets sugar-feeding female and male mosquitoes. This study examines the attractiveness of African malaria vectors to local fruits/seedpods and flowering plants, key biological elements of the ATSB approach for mosquito control. Three field experiments were conducted at sites in Mali. The attraction of Anopheles gambiae s.l. to 26 different local fruits and seedpods was determined at a site in the semi-arid Bandiagara District of Mali. Wire mesh glue traps with fruits/seedpods suspended on skewers inside were set along a seasonal lagoon. Seven replicates of each fruit/seedpod species were tested, with a water-soaked sponge and a sugar-soaked sponge as controls. The attraction of An. gambiae s.l. to 26 different types of flowering plants was determined at a site near Mopti in Mali. The flowering plants held in a water-filled buried container were tested using the same glue traps, with controls including water only and sugar solution. Six replicates of each selected plant type were tested on transects between rice paddies. Additional studies using CDC light traps were done to determine the relative densities and periodicity of An. gambiae s.l. attraction to branches of the most highly attractive flowering plant, branches without flowers, human odor, and candescent light. Of the 26 fruits and seedpods tested, 6 were attractive to An. gambiae s.l. females and males, respectively

  3. Development and validation of a multiresidue method for the simultaneous determination of organophosphorus insecticides and their toxic metabolites in sugarcane juice and refined sugar by gas chromatography with flame photometric detection.

    Science.gov (United States)

    Ramasubramanian, Thirumalaiandi; Paramasivam, Mariappan

    2016-06-01

    A multiresidue method has been developed and validated for the simultaneous determination of organophosphorus insecticides and their toxic metabolites in sugarcane juice and refined sugar by gas chromatography with flame photometric detection. Limits of quantification of the method varied between 0.007 and 0.01 μg/g. Ethyl acetate based extraction followed by dispersive solid-phase extraction cleanup with primary secondary amine yielded internationally acceptable recoveries of acephate, chlorpyrifos, dichlorvos, monocrotophos, malathion, malaoxon, phorate, phorate-sulfoxide, phorate-oxon, phorate-sulfone, and quinalphos from selected matrices. The recoveries of target analytes from cane juice were 75.55 ± 0.5-102.57 ± 4.2, 77.45 ± 4.7-103.33 ± 3.3, and 80.55 ± 6.6-105.82 ± 9.8% at 0.01, 0.02, and 0.1 μg/g levels of fortification, respectively. The recoveries from cane sugar were 73.24 ± 3.5-104.47 ± 1.9, 75.23 ± 1.5-116.10 ± 3.7, and 70.75 ± 5.7-110.15 ± 2.7%, respectively at 0.01, 0.02, and 0.1 μg/g levels of fortification. Matrix effect and measurement uncertainty were within the permissible limit (less than 20%) as prescribed for pesticide residue analysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Differential toxicity and influence of salinity on acute toxicity of ...

    African Journals Online (AJOL)

    Differential toxicity and influence of salinity on acute toxicity of copper sulphate and lead nitrate against Oreochromis niloticus. KA Bawa-Allah, F Osuala, J Effiong. Abstract. This study investigated the salinity-tolerance of Oreochromis niloticus and the influence of salinity changes on the acute toxicities of copper sulphate ...

  5. Biological control of toxic cyanobacteri

    CSIR Research Space (South Africa)

    Ndlela, Luyanda L

    2017-05-01

    Full Text Available . Ecotoxicity studies: is toxicity reduced? (Testing on daphnids, fish and human cell lines) Resulting impacts on cyanotoxins (Toxin conformation changes, ELISA detection) Competition assays against toxic cyanobacteria (Can Bacillus etc. outcompete...

  6. Allegheny County Toxics Release Inventory

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  7. Toxic waste liquor disposal

    International Nuclear Information System (INIS)

    Burton, W.R.

    1985-01-01

    Toxic waste liquors, especially radio active liquors, are disposed in a sub-zone by feeding down a bore hole a first liquid, then a buffer liquid (e.g. water), then the toxic liquors. Pressure variations are applied to the sub-zone to mix the first liquid and liquors to form gels or solids which inhibit further mixing and form a barrier between the sub-zone and the natural waters in the environment of the sub-zone. In another example the location of the sub-zone is selected so that the environement reacts with the liquors to produce a barrier around the zone. Blind bore holes are used to monitor the sub-zone profile. Materials may be added to the liquor to enhance barrier formation. (author)

  8. Lead toxicity: current concerns.

    OpenAIRE

    Goyer, R A

    1993-01-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has be...

  9. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  10. Kombucha--toxicity alert.

    Science.gov (United States)

    The Kombucha mushroom, also known as Manchurian mushroom, is a mail-order product touted to lower blood pressure and raise T-cell counts. No controlled trials have been conducted to test these claims. Aspergillus, a mold that may grow on the Kombucha mushroom, attacks the brain and may be fatal to persons with weakened immune systems. Reported toxicity reactions have included stomach problems and yeast infections. Taking Kombucha in combination with other drugs may affect the drugs potency.

  11. Toxicity of nitrogen pentoxide

    Energy Technology Data Exchange (ETDEWEB)

    Diggle, W M; Gage, J C

    1954-01-01

    Two ppM N/sub 2/O/sub 5/ for 4 h or 1 ppM, 4 h/day for 12 days produced acute pulmonary edema in rats. Ten daily 4-h exposures to 0.5 ppM produced no edema but respiratory distress. NO/sub 2/ produced no edema (some hemorrhage) at 80 mg/m/sup 3/. Nitric acid vapor (63 mg/m/sup 3/) had no obvious toxic effect.

  12. Reirradiation with alternating docetaxel-based chemotherapy for recurrent head and neck squamous cell carcinoma. Update of a single-center prospective phase II protocol

    International Nuclear Information System (INIS)

    Berger, Bernhard; Weinmann, Martin; Bamberg, Michael; Belka, Claus; Budach, Wilfried; Hehr, Thomas

    2010-01-01

    Purpose: to report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy. Patients and methods: chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m 2 day 1 and cisplatin 15 mg/m 2 days 2-5 (first cohort). From 2002 onward, 30 consecutively treated patients received a late-course concomitant boost to 49.6 Gy (second cohort). In July 2008, the survival outcome was analyzed separately for both cohorts and the entire collective (n = 57). Results: the Kaplan-Meier estimates for 1- and 2-year overall survival (OS) were 52% and 24%, respectively (median OS 13.4 months). The median time of locoregional control was 9.6 months, and the actuarial 2-year freedom from distant metastasis rate was 55%. The re-RT dose escalation led to a significant improvement of the median OS (17.4 vs. 9.4 months; p = 0.039). Irrespective of the cohort, severe treatment-related toxicities occurred in about one third of patients. Conclusion: the treatment results confirm the efficacy and the safety of escalated re-RT doses in this chemoreirradiation protocol. (orig.)

  13. Intra-arterial cis-platinum infusion with sodium thiosulfate protection and angiotensin II induced hypertension for treatment of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Onohara, S.; Kobayashi, H.; Itoh, Y.; Shinohara, S.

    Cis-diamminedichloroplatinum II (CDDP; 52-169 mg/m/sup 2/) mixed with angiotensin II (1.5-10 ..mu..g/min) was infused into the hepatic artery in 33 patients with hepatocellular carcinoma. Simultaneously, sodium thiosulfate (10-50 g) was administered intravenously in order to reduce the systemic toxicity of CDDP. Over 50% reduction in tumor size was obtained in 18 patients (55%). Complete response was achieved in 4 patients (12%). Serum alpha-fetoprotein (AFP) levels decreased by more than 75% in 10 of 18 patients in whom the previous AFP level was more than 200 mg/ml. The one year survival rate was estimated at 61% by the Kaplan-Meier method. Alimentary symptoms (nausea, vomiting) were mild or non-existent in nearly 90 per cent of treatments. Peptic ulcer and abdominal pain were manifested in small numbers. Severe changes in the laboratory data were not observed. High dosage arterial infusion of CDDP and angiotensin II and intravenous injection of sodium thiosulfate was well tolerated and gave effective therapy in hepatocellular carcinoma.

  14. [Determinants of survival in HIV patients receiving antiretroviral therapy in Goma, Democratic Republic of Congo].

    Science.gov (United States)

    Akilimali, P Z; Mutombo, P B; Kayembe, P K; Kaba, D K; Mapatano, M A

    2014-06-01

    The study aimed to identify factors associated with the survival of patients receiving antiretroviral therapy. A historic cohort of HIV patients from two major hospitals in Goma (Democratic Republic of Congo) was followed from 2004 to 2012. The Kaplan-Meier method was used to describe the probability of survival as a function of time since inclusion into the cohort. The log-rank test was used to compare survival curves based on determinants. The Cox regression model identified the determinants of survival since treatment induction. The median follow-up time was 3.56 years (IQR=2.22-5.39). The mortality rate was 40 deaths per 1000 person-years. Male gender (RR: 2.56; 95 %CI 1.66-4.83), advanced clinical stage (RR: 2.12; 95 %CI 1.15-3.90), low CD4 count (CD4 < 50) (RR: 2.05; 95 %CI : 1.22-3.45), anemia (RR: 3.95; 95 %CI 2.60-6.01), chemoprophylaxis with cotrimoxazole (RR: 4.29, 95 % CI 2.69-6.86) and period of treatment initiation (2010-2011) (RR: 3.34; 95 %CI 1.24-8.98) were statistically associated with short survival. Initiation of treatment at an early stage of the disease with use of less toxic molecules and an increased surveillance especially of male patients are recommended to reduce mortality. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

    International Nuclear Information System (INIS)

    Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon

    2014-01-01

    To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

  16. RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

    Science.gov (United States)

    2010-01-01

    Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial. PMID:21047402

  17. RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2010-11-01

    Full Text Available Abstract Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%; 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial.

  18. Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM).

    Science.gov (United States)

    Demiral, Selcuk; Dincoglan, Ferrat; Sager, Omer; Gamsiz, Hakan; Uysal, Bora; Gundem, Esin; Elcim, Yelda; Dirican, Bahar; Beyzadeoglu, Murat

    2016-11-01

    While microsurgical resection plays a central role in the management of ACMs, extensive surgery may be associated with substantial morbidity particularly for tumors in intimate association with critical structures. In this study, we evaluated the use of HFSRT in the management of ACM. A total of 22 patients with ACM were treated using HFSRT. Frameless image guided volumetric modulated arc therapy (VMAT) was performed with a 6 MV linear accelerator (LINAC). The total dose was 25 Gy delivered in five fractions over five consecutive treatment days. Local control (LC) and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Common Terminology Criteria for Adverse Events, version 4.0 was used in toxicity grading. Out of the total 22 patients, outcomes of 19 patients with at least 36 months of periodic follow-up were assessed. Median patient age was 40 years old (range 24-77 years old). Median follow-up time was 53 months (range 36-63 months). LC and PFS rates were 100 and 89.4 % at 1 and 3 years, respectively. Only two patients (10.5 %) experienced clinical deterioration during the follow-up period. LINAC-based HFSRT offers high rates of LC and PFS for patients with ACMs.

  19. Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon [Dept.of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

    2014-09-15

    To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

  20. [Significance of three-dimensional reconstruction as a method of preoperative planning of laparoscopic radiofrequency ablation].

    Science.gov (United States)

    Zhang, W W; Wang, H G; Shi, X J; Chen, M Y; Lu, S C

    2016-09-01

    To discuss the significance of three-dimensional reconstruction as a method of preoperative planning of laparoscopic radiofrequency ablation(LRFA). Thirty-two cases of LRFA admitted from January 2014 to December 2015 in Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital were analyzed(3D-LRFA group). Three-dimensional(3D) reconstruction were taken as a method of preoperative planning in 3D-LRFA group.Other 64 LRFA cases were paired over the same period without three-dimensional reconstruction before the operation (LRFA group). Hepatobiliary system contrast enhanced CT scan of 3D-RFA patients were taken by multi-slice spiral computed tomography(MSCT), and the DICOM data were processed by IQQA(®)-Liver and IQQA(®)-guide to make 3D reconstruction.Using 3D reconstruction model, diameter and scope of tumor were measured, suitable size (length and radiofrequency length) and number of RFA electrode were chosen, scope and effect of radiofrequency were simulated, reasonable needle track(s) was planed, position and angle of laparoscopic ultrasound (LUS) probe was designed and LUS image was simulated.Data of operation and recovery were collected and analyzed. Data between two sets of measurement data were compared with t test or rank sum test, and count data with χ(2) test or Fisher exact probability test.Tumor recurrence rate was analyzed with the Kaplan-Meier survival curve and Log-rank (Mantel-Cox) test. Compared with LRFA group ((216.8±66.2) minutes, (389.1±183.4) s), 3D-LRFA group ((173.3±59.4) minutes, (242.2±90.8) s) has shorter operation time(t=-3.138, P=0.002) and shorter mean puncture time(t=-2.340, P=0.021). There was no significant difference of blood loss(P=0.170), ablation rate (P=0.871) and incidence of complications(P=1.000). Compared with LRFA group ((6.3±3.9)days, (330±102)U/L, (167±64)ng/L), 3D-LRFA group ((4.3±3.1) days, (285±102) U/L, (139±43) ng/L) had shorter post-operative stay(t=-2.527, P=0.016), less

  1. Compatibility of hydroxypropyl-β-cyclodextrin with algal toxicity bioassays

    International Nuclear Information System (INIS)

    Fai, Patricia Bi; Grant, Alastair; Reid, Brian J.

    2009-01-01

    Numerous reports have indicated that hydrophobic organic compound bioaccessibility in sediment and soil can be determined by extraction using aqueous hydroxypropyl-β-cyclodextrin (HPCD) solutions. This study establishes the compatibility of HPCD with Selenastrum capricornutum and assesses whether its presence influences the toxicity of reference toxicants. Algal growth inhibition (72 h) showed no significant (P > 0.05) difference at HPCD concentrations up to and including 20 mM. HPCD presence did not influence the toxicity of the inorganic reference toxicant (ZnSO 4 ), with IC50 values of 0.82 μM and 0.85 μM, in the presence and absence of HPCD (20 mM), respectively. However, HPCD presence (20 mM) reduced the toxicity of 2,4-dichlorophenol and the herbicides diuron and isoproturon. These reductions were attributed to inclusion complex formation between the toxicants and the HPCD cavity. Liberation of complexed toxicants, by sample manipulation prior to toxicity assessment, is proposed to provide a sensitive, high throughput, bioassay that reflects compound bioaccessibility. - Compatibility of the biomimetic HPCD extraction method with algal cell growth inhibition bioassays to assess toxicity of reference toxicants and environmental relevant herbicides

  2. Compatibility of hydroxypropyl-{beta}-cyclodextrin with algal toxicity bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Fai, Patricia Bi; Grant, Alastair [School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ (United Kingdom); Reid, Brian J. [School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ (United Kingdom)], E-mail: b.reid@uea.ac.uk

    2009-01-15

    Numerous reports have indicated that hydrophobic organic compound bioaccessibility in sediment and soil can be determined by extraction using aqueous hydroxypropyl-{beta}-cyclodextrin (HPCD) solutions. This study establishes the compatibility of HPCD with Selenastrum capricornutum and assesses whether its presence influences the toxicity of reference toxicants. Algal growth inhibition (72 h) showed no significant (P > 0.05) difference at HPCD concentrations up to and including 20 mM. HPCD presence did not influence the toxicity of the inorganic reference toxicant (ZnSO{sub 4}), with IC50 values of 0.82 {mu}M and 0.85 {mu}M, in the presence and absence of HPCD (20 mM), respectively. However, HPCD presence (20 mM) reduced the toxicity of 2,4-dichlorophenol and the herbicides diuron and isoproturon. These reductions were attributed to inclusion complex formation between the toxicants and the HPCD cavity. Liberation of complexed toxicants, by sample manipulation prior to toxicity assessment, is proposed to provide a sensitive, high throughput, bioassay that reflects compound bioaccessibility. - Compatibility of the biomimetic HPCD extraction method with algal cell growth inhibition bioassays to assess toxicity of reference toxicants and environmental relevant herbicides.

  3. Modern toxic antipersonnel projectiles.

    Science.gov (United States)

    Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

    2014-12-01

    In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

  4. Simple test guidelines for screening oilspill sorbents for toxicity

    International Nuclear Information System (INIS)

    Blenkinsopp, S.A.; Sergy, G.; Doe, K.; Jackman, P.; Huybers, A.

    1998-01-01

    Environment Canada's Emergencies Science Division has established a program to develop a standard test method suitable for evaluating the toxicity of common sorbent materials. Sorbents are used to absorb or adsorb spilled oil and other hazardous materials. They vary widely in composition and packaging. They are often treated with oleophilic and hydrophobic compounds to improve performance and have been used in large quantities during oil spills. Until now, their potential toxicity has never been considered. Three tests have been evaluated to determine how appropriate they are in screening the toxicity of sorbents. Seven toxicity test recommendations for sorbents were presented. 7 refs., 3 tabs., 2 figs

  5. A review of acrylamide toxicity and its mechanism

    Directory of Open Access Journals (Sweden)

    Ehsan Zamani

    2017-05-01

    Full Text Available Acrylamide (AA is an important industrial chemical agent that is mainly used in the production of polymers and copolymers. Recently it has been attention because of its production in the diet at high-temperature (>120 ºC processes such as cooking, frying, toasting, roasting or baking of high carbohydrate foods. According to high exposure to acrylamide, recognition of its toxic effect is necessary. Neurotoxicity, reproductive toxicity and immunotoxicity of AA were observed in several studies. There isn’t a clear mechanism that justifies this toxicity. In this study we reviewed the mechanisms of AA toxicity especially oxidative stress and apoptosis. AA can cause neurotoxicity, reproductive toxicity and genotoxicity on animal models. It showed neurotoxicity in human. We suggested the oxidative stress is the main factor for inducing of acrylamide toxicities. We advised that modifying of food processing methods can be as a good way for decreasing of AA production in foods.

  6. Comparison of the mouse Embryonic Stem cell Test, the rat Whole Embryo Culture and the Zebrafish Embryotoxicity Test as alternative methods for developmental toxicity testing of six 1,2,4-triazoles

    International Nuclear Information System (INIS)

    Jong, Esther de; Barenys, Marta; Hermsen, Sanne A.B.; Verhoef, Aart; Ossendorp, Bernadette C.; Bessems, Jos G.M.; Piersma, Aldert H.

    2011-01-01

    The relatively high experimental animal use in developmental toxicity testing has stimulated the search for alternatives that are less animal intensive. Three widely studied alternative assays are the mouse Embryonic Stem cell Test (EST), the Zebrafish Embryotoxicity Test (ZET) and the rat postimplantation Whole Embryo Culture (WEC). The goal of this study was to determine their efficacy in assessing the relative developmental toxicity of six 1,2,4-triazole compounds, flusilazole, hexaconazole, cyproconazole, triadimefon, myclobutanil and triticonazole. For this purpose, we analyzed effects and relative potencies of the compounds in and among the alternative assays and compared the findings to their known in vivo developmental toxicity. Triazoles are antifungal agents used in agriculture and medicine, some of which are known to induce craniofacial and limb abnormalities in rodents. The WEC showed a general pattern of teratogenic effects, typical of exposure to triazoles, mainly consisting of reduction and fusion of the first and second branchial arches, which are in accordance with the craniofacial malformations reported after in vivo exposure. In the EST all triazole compounds inhibited cardiomyocyte differentiation concentration-dependently. Overall, the ZET gave the best correlation with the relative in vivo developmental toxicities of the tested compounds, closely followed by the EST. The relative potencies observed in the WEC showed the lowest correlation with the in vivo developmental toxicity data. These differences in the efficacy between the test systems might be due to differences in compound kinetics, in developmental stages represented and in the relative complexity of the alternative assays.

  7. Acute toxicity of tobacco ( Nicotiana tobaccum ) leaf dust on ...

    African Journals Online (AJOL)

    Experiments were conducted using dry tobacco (Nicotiana tobaccum) leaves aqueous extract to determine the acute toxicity and sub lethal effects on some haematological indices of Oreochromis niloticus using static renewable bioassay method. The extract was found to be toxic with a 48-h LC50 value of 109.6 mg/l.

  8. Toxicity of Neatex (industrial detergent) and Norust CR 486 ...

    African Journals Online (AJOL)

    Populations of indigenous epigeic adult earthworms, Aporrectodea longa, were exposed to varying concentrations of two chemicals (industrial detergent and corrosion inhibitor) in natural soil to determine the acute toxicity of the chemicals. Earthworm acute toxicity test (OECD) 207 method was employed. After two weeks of ...

  9. Assessment of the Developmental Toxicity of Epidermal Growth ...

    African Journals Online (AJOL)

    Purpose: To determine whether epidermal growth factor (EGF) is involved in reproductive developmental toxicity, using the embryonic stem cell test (EST), as well as ascertain how EGF influences embryonic development. Methods: To predict developmental toxicity on the basis of reducing cell viability and inhibition of ...

  10. Corneal Toxicity Following Exposure to Asclepias Tuberosa

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas

    2017-01-01

    PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small...... epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. RESULTS: The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa, whose latex contains cardenolides...... that inhibit the Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. CONCLUSION: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity...

  11. Method

    Directory of Open Access Journals (Sweden)

    Ling Fiona W.M.

    2017-01-01

    Full Text Available Rapid prototyping of microchannel gain lots of attention from researchers along with the rapid development of microfluidic technology. The conventional methods carried few disadvantages such as high cost, time consuming, required high operating pressure and temperature and involve expertise in operating the equipment. In this work, new method adapting xurography method is introduced to replace the conventional method of fabrication of microchannels. The novelty in this study is replacing the adhesion film with clear plastic film which was used to cut the design of the microchannel as the material is more suitable for fabricating more complex microchannel design. The microchannel was then mold using polymethyldisiloxane (PDMS and bonded with a clean glass to produce a close microchannel. The microchannel produced had a clean edge indicating good master mold was produced using the cutting plotter and the bonding between the PDMS and glass was good where no leakage was observed. The materials used in this method is cheap and the total time consumed is less than 5 hours where this method is suitable for rapid prototyping of microchannel.

  12. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

    International Nuclear Information System (INIS)

    Garin, E.; Lenoir, L.; Edeline, J.; Laffont, S.; Mesbah, H.; Poree, P.; Sulpice, L.; Boudjema, K.; Mesbah, M.; Guillygomarc'h, A.; Quehen, E.; Pracht, M.; Raoul, J.L.; Clement, B.; Rolland, Y.; Boucher, E.

    2013-01-01

    To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with 90 Y-loaded glass microspheres (TheraSphere registered). TheraSphere registered was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). The response rate was 78.8 %. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p 205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD 205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83 % and overall accuracy of 97 %. Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved. (orig.)

  13. High-Dose and Extended-Field Intensity Modulated Radiation Therapy for Early-Stage NK/T-Cell Lymphoma of Waldeyer's Ring: Dosimetric Analysis and Clinical Outcome

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Xi-Wen; Li, Ye-Xiong, E-mail: yexiong@yahoo.com; Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong

    2013-12-01

    Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.

  14. Treatment Results of PDR Brachytherapy Combined With External Beam Radiotherapy in 106 Patients With Intermediate- to High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Pieters, Bradley R.; Geijsen, Elisabeth D.; Koedooder, Kees; Blank, Leo E.C.M.; Rezaie, Elisa; Grient, Johan N.B. van der; Reijke, Theo M. de; Koning, Caro C.E.

    2011-01-01

    Purpose: To evaluate treatment outcome of pulsed dose-rate brachytherapy (PDR) combined with external-beam radiotherapy (EBRT) for the treatment of prostate cancer. Methods and Materials: Between 2002 and 2007, 106 patients were treated by EBRT combined with PDR and followed prospectively. Two, 38, and 66 patients were classified as low-, intermediate-, and high-risk disease respectively according to the National Comprehensive Cancer Network criteria. EBRT dose was 46 Gy in 2.0-Gy fractions. PDR dose was increased stepwise from 24.96 to 28.80 Gy. Biochemical disease free survival and overall survival were determined by the Kaplan-Meier method. Cumulative incidence of late gastrointestinal (GI) and genitourinary (GU) toxicity were scored, according to the Common Terminology Criteria for Adverse Events. Results: The 3- and 5-year biochemical nonevidence of disease (bNED) were 92.8% (95% confidence interval [CI], 87.1-98.5) and 89.5% (95% CI, 85.2-93.8), respectively. Overall survival at 3 and 5 years was 99% (95% CI, 96-100) and 96% (95% CI, 90-100), respectively. The 3- and 5-year Grade 2 GI toxicity was 5.3% (95% CI, 0-10.6) and 12.0% (95% CI, 1.4-22.6), respectively. No Grade 3 or higher GI toxicity was observed. The 3- and 5-year Grade 2 or higher GU toxicity was 18.7% (95% CI, 10.3-27.1) and 26.9% (95% CI, 15.1-38.7), respectively. Conclusion: Results on tumor control and late toxicity of EBRT combined with PDR are good and comparable to results obtained with EBRT combined with high-dose-rate brachytherapy for the treatment of prostate cancer.

  15. Clinical Outcomes of Intensity-Modulated Pelvic Radiation Therapy for Carcinoma of the Cervix

    International Nuclear Information System (INIS)

    Hasselle, Michael D.; Rose, Brent S.; Kochanski, Joel D.; Nath, Sameer K.; Bafana, Rounak; Yashar, Catheryn M.; Hasan, Yasmin; Roeske, John C.; Mundt, Arno J.; Mell, Loren K.

    2011-01-01

    Purpose: To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). Methods and Materials: We included all patients with Stage I-IVA cervical carcinoma treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. Results: The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively. Conclusions: Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques.

  16. No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

    Energy Technology Data Exchange (ETDEWEB)

    Stanic, Sinisa, E-mail: sinisa.stanic@carle.com [Carle Cancer Center and University of Illinois College of Medicine, Urbana, Illinois (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Timmerman, Robert D. [University of Texas Southwestern, Dallas, Texas (United States); Michalski, Jeff M. [Washington University, St. Louis, Missouri (United States); Barriger, Robert B. [Indiana University, Indianapolis, Indiana (United States); Bezjak, Andrea [Princess Margaret Cancer Center, Toronto, Ontario (Canada); Videtic, Gregory M.M. [Cleveland Clinic Foundation, Cleveland, Ohio (United States); Bradley, Jeffrey [Washington University, St. Louis, Missouri (United States)

    2014-04-01

    Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

  17. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept.

    Science.gov (United States)

    Garin, E; Lenoir, L; Edeline, J; Laffont, S; Mesbah, H; Porée, P; Sulpice, L; Boudjema, K; Mesbah, M; Guillygomarc'h, A; Quehen, E; Pracht, M; Raoul, J L; Clement, B; Rolland, Y; Boucher, E

    2013-07-01

    To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with (90)Y-loaded glass microspheres (TheraSphere®). TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). The response rate was 78.8%. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p 205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD 205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83% and overall accuracy of 97%. Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.

  18. No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

    International Nuclear Information System (INIS)

    Stanic, Sinisa; Paulus, Rebecca; Timmerman, Robert D.; Michalski, Jeff M.; Barriger, Robert B.; Bezjak, Andrea; Videtic, Gregory M.M.; Bradley, Jeffrey

    2014-01-01

    Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT

  19. Prediction of toxicity and comparison of alternatives using WebTEST (Web-services Toxicity Estimation Software Tool)

    Science.gov (United States)

    A Java-based web service is being developed within the US EPA’s Chemistry Dashboard to provide real time estimates of toxicity values and physical properties. WebTEST can generate toxicity predictions directly from a simple URL which includes the endpoint, QSAR method, and ...

  20. Is LSD toxic?

    Science.gov (United States)

    Nichols, David E; Grob, Charles S

    2018-03-01

    LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200μg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Toxic potential of palytoxin.

    Science.gov (United States)

    Patocka, Jiří; Gupta, Ramesh C; Wu, Qing-hua; Kuca, Kamil

    2015-10-01

    This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.

  2. Animal data on plutonium toxicity

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1975-01-01

    Animal data are necessary in the assessment of plutonium toxicity since it is unlikely that the necessary information on effects from humans will be obtained. Experiments on animals must be designed to provide understanding of the mechanisms at work if the results are to be applied to man since it is a statistical impossibility to design experiments to measure directly the low levels of risk that are of concern. Cancer induction appears to be the risk of greatest concern with the lung and bone apparently the most susceptible organs, depending upon the method of administration. Current limitations on these organs do not appear to have the safety margin formerly believed and there are some uncertainties in the extrapolation from animal data to man. (author)

  3. Metal metabolism and toxicity

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Whelton, B.D.; Moretti, E.S.; Peterson, D.P.; Oldham, R.D.

    1985-01-01

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  4. Control of air toxics

    International Nuclear Information System (INIS)

    Livengood, C.D.

    1995-01-01

    For more than 10 years, Argonne National Laboratory has supported the US DOE's Flue Gas Cleanup Program objective by developing new or improved environmental controls for industries that use fossil fuels. Argonne's pollutant emissions research has ranged from experiments in the basic chemistry of pollution-control systems, through laboratory-scale process development and testing, to pilot-scale field tests of several technologies. The work on air toxics is currently divided into two components: Investigating measures to improve the removal of mercury in existing pollution-control systems applied to coal combustion; and, Developing sensors and control techniques for emissions found in the textile industry

  5. method

    Directory of Open Access Journals (Sweden)

    L. M. Kimball

    2002-01-01

    Full Text Available This paper presents an interior point algorithm to solve the multiperiod hydrothermal economic dispatch (HTED. The multiperiod HTED is a large scale nonlinear programming problem. Various optimization methods have been applied to the multiperiod HTED, but most neglect important network characteristics or require decomposition into thermal and hydro subproblems. The algorithm described here exploits the special bordered block diagonal structure and sparsity of the Newton system for the first order necessary conditions to result in a fast efficient algorithm that can account for all network aspects. Applying this new algorithm challenges a conventional method for the use of available hydro resources known as the peak shaving heuristic.

  6. The classification and application of toxic Chinese materia medica.

    Science.gov (United States)

    Liu, Xinmin; Wang, Qiong; Song, Guangqing; Zhang, Guangping; Ye, Zuguang; Williamson, Elizabeth M

    2014-03-01

    Many important drugs in the Chinese materia medica (CMM) are known to be toxic, and it has long been recognized in classical Chinese medical theory that toxicity can arise directly from the components of a single CMM or may be induced by an interaction between combined CMM. Traditional Chinese Medicine presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting, and these techniques contribute to reducing toxicity as well as enhancing efficacy. The current classification of toxic CMM drugs, traditional methods for processing toxic CMM and the prohibited use of certain combinations, is based on traditional experience and ancient texts and monographs, but accumulating evidence increasingly supports their use to eliminate or reduce toxicity. Modern methods are now being used to evaluate the safety of CMM; however, a new system for describing the toxicity of Chinese herbal medicines may need to be established to take into account those herbs whose toxicity is delayed or otherwise hidden, and which have not been incorporated into the traditional classification. This review explains the existing classification and justifies it where appropriate, using experimental results often originally published in Chinese and previously not available outside China. Copyright © 2013 John Wiley & Sons, Ltd.

  7. DO TIE LABORATORY BASED ASSESSMENT METHODS REALLY PREDICT FIELD EFFECTS?

    Science.gov (United States)

    Sediment Toxicity Identification and Evaluation (TIE) methods have been developed for both porewaters and whole sediments. These relatively simple laboratory methods are designed to identify specific toxicants or classes of toxicants in sediments; however, the question of whethe...

  8. DO TIE LABORATORY BASED METHODS REALLY REFLECT FIELD CONDITIONS

    Science.gov (United States)

    Sediment Toxicity Identification and Evaluation (TIE) methods have been developed for both interstitial waters and whole sediments. These relatively simple laboratory methods are designed to identify specific toxicants or classes of toxicants in sediments; however, the question ...

  9. Long-acting reversible contraceptive acceptability and unintended pregnancy among women presenting for short-acting methods: a randomized patient preference trial.

    Science.gov (United States)

    Hubacher, David; Spector, Hannah; Monteith, Charles; Chen, Pai-Lien; Hart, Catherine

    2017-02-01

    Measures of contraceptive effectiveness combine technology and user-related factors. Observational studies show higher effectiveness of long-acting reversible contraception compared with short-acting reversible contraception. Women who choose long-acting reversible contraception may differ in key ways from women who choose short-acting reversible contraception, and it may be these differences that are responsible for the high effectiveness of long-acting reversible contraception. Wider use of long-acting reversible contraception is recommended, but scientific evidence of acceptability and successful use is lacking in a population that typically opts for short-acting methods. The objective of the study was to reduce bias in measuring contraceptive effectiveness and better isolate the independent role that long-acting reversible contraception has in preventing unintended pregnancy relative to short-acting reversible contraception. We conducted a partially randomized patient preference trial and recruited women aged 18-29 years who were seeking a short-acting method (pills or injectable). Participants who agreed to randomization were assigned to 1 of 2 categories: long-acting reversible contraception or short-acting reversible contraception. Women who declined randomization but agreed to follow-up in the observational cohort chose their preferred method. Under randomization, participants chose a specific method in the category and received it for free, whereas participants in the preference cohort paid for the contraception in their usual fashion. Participants were followed up prospectively to measure primary outcomes of method continuation and unintended pregnancy at 12 months. Kaplan-Meier techniques were used to estimate method continuation probabilities. Intent-to-treat principles were applied after method initiation for comparing incidence of unintended pregnancy. We also measured acceptability in terms of level of happiness with the products. Of the 916

  10. Toxicity of tritium

    International Nuclear Information System (INIS)

    Dobson, R.L.

    1979-01-01

    Among radionuclides of importance in atomic energy, 3 H has relatively low toxicity. The main health and environmental worry is the possibility that significant biological effects may follow from protracted exposure to low concentrations in water. To examine this possible hazard and measure toxicity at low tritium concentrations, chronic exposure studies were done on mice and monkeys. During vulnerable developmental periods animals were exposed to 3 HOH, and mice were exposed also to 60 Co gamma irradiation and energy-related chemical agents. The biological endpoint measured was the irreversible loss of female germ cells. Effects from tritium were observed at surprisingly low concentrations where 3 H was found more damaging than previously thought. Comparisons between tritium and gamma radiation showed the relative biological effectiveness (RBE) to be greater than 1 and to reach approximately 3 at very low exposures. For perspective, other comparisons were made: between radiation and chemical agents, which revealed parallels in action on germ cells, and between pre- and postnatal exposure, which warn of possible special hazard to the fetus from both classes of energy-related byproducts

  11. Toxic compounds in honey.

    Science.gov (United States)

    Islam, Md Nazmul; Khalil, Md Ibrahim; Islam, Md Asiful; Gan, Siew Hua

    2014-07-01

    There is a wealth of information about the nutritional and medicinal properties of honey. However, honey may contain compounds that may lead to toxicity. A compound not naturally present in honey, named 5-hydroxymethylfurfural (HMF), may be formed during the heating or preservation processes of honey. HMF has gained much interest, as it is commonly detected in honey samples, especially samples that have been stored for a long time. HMF is a compound that may be mutagenic, carcinogenic and cytotoxic. It has also been reported that honey can be contaminated with heavy metals such as lead, arsenic, mercury and cadmium. Honey produced from the nectar of Rhododendron ponticum contains alkaloids that can be poisonous to humans, while honey collected from Andromeda flowers contains grayanotoxins, which can cause paralysis of limbs in humans and eventually leads to death. In addition, Melicope ternata and Coriaria arborea from New Zealand produce toxic honey that can be fatal. There are reports that honey is not safe to be consumed when it is collected from Datura plants (from Mexico and Hungary), belladonna flowers and Hyoscamus niger plants (from Hungary), Serjania lethalis (from Brazil), Gelsemium sempervirens (from the American Southwest), Kalmia latifolia, Tripetalia paniculata and Ledum palustre. Although the symptoms of poisoning due to honey consumption may differ depending on the source of toxins, most common symptoms generally include dizziness, nausea, vomiting, convulsions, headache, palpitations or even death. It has been suggested that honey should not be considered a completely safe food. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Thallium toxicity in humans.

    Science.gov (United States)

    Cvjetko, Petra; Cvjetko, Ivan; Pavlica, Mirjana

    2010-03-01

    Thallium is a naturally occurring trace element, widely distributed in the earth's crust, but at very low concentrations. It does not have a known biological use and does not appear to be an essential element for life. It has been considered one of the most toxic heavy metals.Occasionally, there are reports on thallium poisoning as results of suicide or murder attempt or accident. The main threat to humans is through occupational exposure, environmental contamination, and accumulation in food, mainly in vegetables grown on contaminated soil. Increasing use in emerging new technologies and demanding high-tech industry constantly raise concern about exposure risk to all living organisms. Thallium is considered a cumulative poison that can cause adverse health effects and degenerative changes in many organs. The effects are the most severe in the nervous system. The exact mechanism of thallium toxicity still remains unknown, although impaired glutathione metabolism, oxidative stress, and disruption of potassium-regulated homeostasis may play a role. The lack of data about mutagenic, carcinogenic, or teratogenic effects of thallium compounds in humans calls for further research.

  13. Molecular toxicity of nanomaterials.

    Science.gov (United States)

    Chang, Xue-Ling; Yang, Sheng-Tao; Xing, Gengmei

    2014-10-01

    With the rapid developments in the fields of nanoscience and nanotechnlogy, more and more nanomaterials and their based consumer products have been used into our daily life. The safety concerns of nanomaterials have been well recognized by the scientific community and the public. Molecular mechanism of interactions between nanomaterials and biosystems is the most essential topic and final core of the biosafety. In the last two decades, nanotoxicology developed very fast and toxicity phenomena of nanomaterials have been reported. To achieve better understanding and detoxication of nanomaterials, thorough studies of nanotoxicity at molecular level are important. The interactions between nanomaterials and biomolecules have been widely investigated as the first step toward the molecular nanotoxicology. The consequences of such interactions have been discussed in the literature. Besides this, the chemical mechanism of nanotoxicology is gaining more attention, which would lead to a better design of nontoxic nanomaterials. In this review, we focus on the molecular nanotoxicology and explore the toxicity of nanomaterials at molecular level. The molecular level studies of nanotoxicology are summarized and the published nanotoxicological data are revisited.

  14. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging.

    Science.gov (United States)

    Lewandowski, Robert J; Thurston, Kenneth G; Goin, James E; Wong, Ching-Yee O; Gates, Vanessa L; Van Buskirk, Mark; Geschwind, Jean-Francois H; Salem, Riad

    2005-12-01

    The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate. Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method. Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention. TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.

  15. Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

    International Nuclear Information System (INIS)

    Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

    2014-01-01

    To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

  16. Major ion toxicity in effluents: A review with permitting recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Goodfellow, W.L.; Ausley, L.W.; Burton, D.T.; Denton, D.L.; Dorn, P.B.; Grothe, D.R.; Heber, M.A.; Norberg-King, T.J.; Rodgers, J.H. Jr.

    2000-01-01

    Effluent toxicity testing methods have been well defined, but for the most part, these methods do not attempt to segregate the effects of active ionic concentrations and ion imbalances upon test and species performances. The role of various total dissolved solids in effluents on regulatory compliance has emerged during the last few years and has caused confusion in technical assessment and in permitting and compliance issues. This paper assesses the issue of ionic strength and ion imbalance, provides a brief summary of applicable data, presents several case studies demonstrating successful tools to address toxicity resulting from salinity and ion imbalance, and provides recommendations for regulatory and compliance options to manage discharges with salinity/ion imbalance issues. Effluent toxicity resulting from inorganic ion imbalance and the ion concentration of the effluent is pervasive in permitted discharge from many industrial process and municipal discharges where process streams are concentrated, adjusted, or modified. This paper discusses procedures that use weight-of-evidence approaches to identify ion imbalance toxicity, including direct measurement, predictive toxicity models for freshwater, exchange resins, mock effluents, and ion imbalance toxicity with tolerant/susceptible test species. Cost-effective waste treatment control options for a facility whose effluent is toxic because of total dissolved solids (TDS) or because of specific ion(s) are scarce at best. Depending on the discharge situation, TDS toxicity may not be viewed with the same level of concern as other, more traditional, toxicants. These discharge situations often do not require the conservative safety factors required by other toxicants. Selection of the alternative regulatory solutions discussed in this paper may be beneficial, especially because they do not require potentially expensive or high-energy-using treatment options that may be ineffective control options. The information

  17. Wild lettuce (Lactuca virosa) toxicity

    OpenAIRE

    Besharat, Sima; Besharat, Mahsa; Jabbari, Ali

    2009-01-01

    Wild lettuce (Lactuca virosa) can cause toxic effects when eaten. Wild lettuce grows in the north of Iran and some natives consume it unaware of its adverse side effects. We describe eight patients with manifestations of wild lettuce toxicity, admitted to a general hospital affiliated to the Golestan University of Medical Sciences. All the patients recovered (although one had to spend 48 h in the intensive care unit) and no chronic complications were reported. A clinical suspicion of toxicity...

  18. Tracking pyrethroid toxicity in surface water samples: Exposure dynamics and toxicity identification tools for laboratory tests with Hyalella azteca (Amphipoda).

    Science.gov (United States)

    Deanovic, Linda A; Stillway, Marie; Hammock, Bruce G; Fong, Stephanie; Werner, Inge

    2018-02-01

    Pyrethroid insecticides are commonly used in pest control and are present at toxic concentrations in surface waters of agricultural and urban areas worldwide. Monitoring is challenging as a result of their high hydrophobicity and low toxicity thresholds, which often fall below the analytical methods detection limits (MDLs). Standard daphnid bioassays used in surface water monitoring are not sensitive enough to protect more susceptible invertebrate species such as the amphipod Hyalella azteca and chemical loss during toxicity testing is of concern. In the present study, we quantified toxicity loss during storage and testing, using both natural and synthetic water, and presented a tool to enhance toxic signal strength for improved sensitivity of H. azteca toxicity tests. The average half-life during storage in low-density polyethylene (LDPE) cubitainers (Fisher Scientific) at 4 °C of 5 pyrethroids (permethrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, and esfenvalerate) and one organophosphate (chlorpyrifos; used as reference) was 1.4 d, and piperonyl butoxide (PBO) proved an effective tool to potentiate toxicity. We conclude that toxicity tests on ambient water samples containing these hydrophobic insecticides are likely to underestimate toxicity present in the field, and mimic short pulse rather than continuous exposures. Where these chemicals are of concern, the addition of PBO during testing can yield valuable information on their presence or absence. Environ Toxicol Chem 2018;37:462-472. © 2017 SETAC. © 2017 SETAC.

  19. Identification of Chemical Toxicity Using Ontology Information of Chemicals

    Directory of Open Access Journals (Sweden)

    Zhanpeng Jiang

    2015-01-01

    Full Text Available With the advance of the combinatorial chemistry, a large number of synthetic compounds have surged. However, we have limited knowledge about them. On the other hand, the speed of designing new drugs is very slow. One of the key causes is the unacceptable toxicities of chemicals. If one can correctly identify the toxicity of chemicals, the unsuitable chemicals can be discarded in early stage, thereby accelerating the study of new drugs and reducing the R&D costs. In this study, a new prediction method was built for identification of chemical toxicities, which was based on ontology information of chemicals. By comparing to a previous method, our method is quite effective. We hope that the proposed method may give new insights to study chemical toxicity and other attributes of chemicals.

  20. Cyclophosphamide-induced pulmonary toxicity

    International Nuclear Information System (INIS)

    Siemann, D.W.; Macler, L.; Penney, D.P.

    1986-01-01

    Unlike radiation effects, pulmonary toxicity following drug treatments may develop soon after exposure. The dose-response relationship between Cyclophosphamide and lung toxicity was investigated using increased breathing frequency assays used successfully for radiation induced injury. The data indicate that release of protein into the alveolus may play a significant role in Cy induced pulmonary toxicity. Although the mechanism responsible for the increased alveolar protein is as yet not identified, the present findings suggest that therapeutic intervention to inhibit protein release may be an approach to protect the lungs from toxic effects. (UK)

  1. Prospective Validation of 18F-FDG Brain PET Discriminant Analysis Methods in the Diagnosis of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Van Weehaeghe, Donatienne; Ceccarini, Jenny; Delva, Aline; Robberecht, Wim; Van Damme, Philip; Van Laere, Koen

    2016-08-01

    nearly identical and not separable on an individual basis. Extensive frontotemporal hypometabolism was predictive for a lower survival using a Kaplan-Meier survival analysis (P < 0.001). On the basis of a previously acquired training set, (18)F-FDG PET with advanced discriminant analysis methods is able to accurately distinguish ALS from controls and aids in assessing individual prognosis. Further validation on multicenter datasets and ALS-mimicking disorders is needed to fully assess the general applicability of this approach. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. Amiodarone pulmonary toxicity: Case report

    Directory of Open Access Journals (Sweden)

    Vasić Nada

    2014-01-01

    Full Text Available Introduction. Amiodarone, an antiarrhythmic drug, which contains iodine compound, has a tendency to accumulate in some organs including the lungs. This is age, drug dosage and therapy duration dependent. Case Outline. We present a case of a 73-year-old man, a smoker, who was admitted as emergency case due to severe dyspnea, tachypnea with signs of cyanosis and respiratory insufficiency. Chest x-ray revealed bilateral diffuse pulmonary shadows in the middle and upper parts of the lungs, similar to those in tuberculosis. His illness history showed chronic obstructive pulmonary disease, arterial hypertension, and atrial fibrillation which has been treated with amiodarone for six years. Sputum smears were negative for mycobacteria, and by the diagnostic elimination method for specific, non-specific and malignant disease the diagnosis of amiodarone pulmonary toxicity was made. Fiberoptic bronchoscopy and pathohistological findings of bronchiolitis obliterans organizing pneumonia confirmed the diagnosis. As the first therapeutic approach, amiodarone therapy was stopped. Then, systemic therapy with methylprednisolone 21 (sodium succinate 40 mg i.v. daily during the first two weeks was initiated and continued with daily dose of methylprednisolone 30 mg orally during the next three months. The patient showed a marked subjective improvement during the first week, which was followed by the improvement of respiratory function and withdrawal of pulmonary changes with complete radiographic and CT resolution after eight months. Conclusion. Amiodarone pulmonary toxicity should be taken into consideration, especially in elderly patients with respiratory symptoms and pulmonary changes, even if only a low dose of amiodarone is administred over a longer time period.

  3. Electrocardiographic Manifestations of Benzodiazepine Toxicity

    Directory of Open Access Journals (Sweden)

    Nahid Kazemzadeh

    2014-11-01

    Full Text Available Background: The aim of this study was to evaluate and compare the clinical and electrocardiographic (ECG manifestations of benzodiazepines (BZs. Methods: In this retrospective study, all BZ-poisoned patients hospitalized at Loghman Hakim Hospital between September 2010 and March 2011 were evaluated. Patients’ information including age, sex, time elapsed between the ingestion and presentation, and type of the BZ used were extracted from the patients' charts and recorded. ECGs on presentation to the emergency department (ED were evaluated and parameters such as PR interval, QRS duration, corrected QT, amplitude of S wave in lead I, height of R wave and R/S ratio in the lead aVR were also measured and recorded. Results: Oxazepam, chlordiazepoxide, lorazepam, alprazolam, diazepam, and clonazepam were ingested by 9 (3%, 13 (4.4%, 29 (9.9%, 105 (35.8%, 65 (22.2%, and 72 (24.6% patients, respectively. Mean PR interval was reported to be 0.16 ± 0.03 sec and PR interval of greater than 200 msec was detected in 12 (4.5% patients. Mean QRS duration was 0.07 ± 0.01sec and QRS≥120 msec was observed in 7 (2.6% cases. Conclusion: Diazepam is the only BZ that does not cause QRS widening and oxazepam is the only one not causing PR prolongation. It can be concluded that if a patient refers with a decreased level of consciousness and accompanying signs of BZ toxicity, QRS widening in ECG rules out diazepam, whereas PR prolongation rules out oxazepam toxicity.

  4. Erlotinib in the Second/Third Line Treatment of Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yilong WU

    2009-05-01

    Full Text Available Background and objective Erlotinib is a targeted drug for non-small cell lung cancer (NSCLC. The aim of this study is to evaluate the efficacy, influencing factors and toxicity of erlotinib in patients with NSCLC. Methods Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapyreceived 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier methods was used to analyze the survival rate. Cox regression was used to define the predictive factors. Results Forty-eight patients were enrolled into the study from Dec, 2005 to Sep, 2006. We followed up these patients until 08.Dec.2008. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 7 days. Partial response 33.4% (16/48, stable disease 22.9% (11/48, and progressive disease 43.7% (21/48. Response rate was 33.4% (16/48. Disease control rate was 56.3% (27/48. One and two-year progression-free survival rates and overall survival rates were 25%(events 36, 8.3% (events 40 and 43.8% (death 27, 20.8% (death 38; three-year overall survival 5.6%. The median progression-free survival time and median overall survival time was 5 months and 8 months, respectively. Performance status was the only predictor for overall survival in the Cox model (P <0.001. Skin toxicity(grade 1 to 3 was found in 93.7% patients. One patient discontinued erlotinib because of perianal abscess. Conclusion Erlotinib is another effective drug for patients with previously chemotherapy advanced NSCLC and accepted toxicity profile.

  5. Age is not a limiting factor for radical radiotherapy in pelvic malignancies

    International Nuclear Information System (INIS)

    Pignon, T.; Horiot, J.C.; Bolla, M.; Poppel, H. van; Bartelink, H.; Roelofsen, F.; Pene, F.; Gerard, A.; Einhorn, N.; Nguyen, T.D.; Vanglabbeke, M.; Scalliet, P.

    1997-01-01

    Background and purpose: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. Material and methods: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. Results: Survival was comparable in each age group for prostate (P=0.18), uterus (0.41), anal canal cancer (P=0.6) and slightly better for the younger group of rectum cancer (P=0.04). A total of 1722 acute and 514 late grade ≥1 were recorded. Acute nausea/vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P=0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P=0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P=0.79). For the grade >2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P=0.06) nor trend (P=0.13) between age-groups. Conclusion: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies

  6. Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

    International Nuclear Information System (INIS)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Lieberson, Robert E.; Soltys, Scott G.

    2012-01-01

    Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  7. Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

    International Nuclear Information System (INIS)

    Fukada, Junichi; Shigematsu, Naoyuki; Takeda, Atsuya; Ohashi, Toshio; Tomita, Toshiki; Shiotani, Akihiro; Kunieda, Etsuo; Kawaguchi, Osamu; Fujii, Masato; Kubo, Atsushi

    2010-01-01

    Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m 2 ]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade ≥3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

  8. E-Cigarette Toxicity?

    Science.gov (United States)

    Tegin, Gulay; Mekala, Hema Madhuri; Sarai, Simrat Kaur; Lippmann, Steven

    2018-01-01

    Tobacco smoking is the most preventable cause of morbidity and mortality. In just a few short years, electronic cigarettes (e-cigarettes) have become increasingly popular, especially for younger individuals. Many people believe that e-cigarettes are safe. The inhaled aerosols of e-cigarettes contain numerous potential toxicities, some of which could be dangerous for health with long-term use. The safety of prolonged aerosol exposure is not known. The use of e-cigarettes as a harm-reduction tool at stopping tobacco smoking is not uniformly successful. E-cigarettes may be safer than tobacco products, but repeated prolonged exposure to their aerosols has its own considerable potential risk. The long-term health consequences of their use remain to be established. Physicians should vigorously discourage the use of e-cigarettes and tobacco products, with special emphasis on abstinence for younger people and during pregnancy or lactation.

  9. Discriminating modes of toxic action in mice using toxicity in BALB/c mouse fibroblast (3T3) cells.

    Science.gov (United States)

    Huang, Tao; Yan, Lichen; Zheng, Shanshan; Wang, Yue; Wang, Xiaohong; Fan, Lingyun; Li, Chao; Zhao, Yuanhui; Martyniuk, Christopher J

    2017-12-01

    The objective of this study was to determine whether toxicity in mouse fibroblast cells (3T3 cells) could predict toxicity in mice. Synthesized data on toxicity was subjected to regression analysis and it was observed that relationship of toxicities between mice and 3T3 cells was not strong (R 2  = 0.41). Inclusion of molecular descriptors (e.g. ionization, pKa) improved the regression to R 2  = 0.56, indicating that this relationship is influenced by kinetic processes of chemicals or specific toxic mechanisms associated to the compounds. However, to determine if we were able to discriminate modes of action (MOAs) in mice using the toxicities generated from 3T3 cells, compounds were first classified into "baseline" and "reactive" guided by the toxic ratio (TR) for each compound in mice. Sequence, binomial and recursive partitioning analyses provided strong predictions of MOAs in mice based upon toxicities in 3T3 cells. The correct classification of MOAs based on these methods was 86%. Nearly all the baseline compounds predicted from toxicities in 3T3 cells were identified as baseline compounds from the TR in mice. The incorrect assignment of MOAs for some compounds is hypothesized to be due to experimental uncertainty that exists in toxicity assays for both mice and 3T3 cells. Conversely, lack of assignment can also arise because some reactive compounds have MOAs that are different in mice compared to 3T3 cells. The methods developed here are novel and contribute to efforts to reduce animal numbers in toxicity tests that are used to evaluate risks associated with organic pollutants in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Characterization and toxicity studies of bioglass by Sol-gel method for prostate cancer therapy; Caracterização e estudos de toxicidade de biovidro produzido pelo método Sol-gel para o tratamento do câncer de próstata

    Energy Technology Data Exchange (ETDEWEB)

    Roberto, Wanderley S.; Veloso, Gabriela A.; Silva, Luciana; Campos, Tarcísio P.R., E-mail: wanderley@des.cefetmg.br, E-mail: gabrielaveloso.engmateriais@gmail.com [Departamento de F´ısica e Matem´atica, Centro de Engenharia Biom´edica (CENEB), Centro Federal de Educação Tecnol´gica de Minas Gerais, Belo Horizonte, MG (Brazil)

    2017-07-01

    One of the most advanced methods for the treatment of prostate cancer in the initial stage is brachytherapy, which uses titanium seeds, incorporated with {sup 125} I, which is radioactive, and which is implanted in the prosthetic volume. In recent studies, we investigated the possibility of applying the Sol-Gel (SG) method for the production of bioactive seeds, incorporated with radioactive Sm in silica glasses for the treatment of cancer. In this project three compositions of the glasses of the SiO{sub 2}-CaO system were synthesized using the SG method. The chemical and physical composition of the seeds were analyzed by X-ray diffraction and Atomic Absorption Analysis. A pilot study of in vivo and in vitro toxicity was conducted in rabbit and PC-3 lineage cells. The results showed that the ceramic matrices in the SiO{sub 2} - CaO - Sm system present no toxicity in the in vivo model presenting no post-implant inflammatory process. None restriction of in vitro cell growth was found. In conclusion, there is no toxicity in seeds and the radiotoxicity will occur only in the period in which the seeds present activity coming from {sup 153}Sm.

  11. Children's Ability to Recognise Toxic and Non-Toxic Fruits

    Science.gov (United States)

    Fancovicova, Jana; Prokop, Pavol

    2011-01-01

    Children's ability to identify common plants is a necessary prerequisite for learning botany. However, recent work has shown that children lack positive attitudes toward plants and are unable to identify them. We examined children's (aged 10-17) ability to discriminate between common toxic and non-toxic plants and their mature fruits presented in…

  12. Toxic and trace elements in foodstuffs in Japan

    International Nuclear Information System (INIS)

    Muramatsu, Y.; Sumiya, M.; Ohmomo, Y.

    1988-01-01

    From the viewpoint of environmental safety assessment it is important to have information on the levels of toxic and trace elements in foodstuffs. It is also essential to develop suitable analytical methods for these elements in order to obtain accurate analytical data. In this paper, two analytical methods were used, inductively-coupled plasma atomic emission spectrometry (ICP-AES) and neutron activation analysis (NAA), for analysing toxic and trace elements in several food samples. 3 tabs

  13. Evaluation of levels of select toxic metals in commonly used herbal ...

    African Journals Online (AJOL)

    Even at low concentrations or levels of exposure, toxic metals have also been reported to pose health risks to man. Aim: To ... Materials/Methods :Herbal medicines (n=8) were purchased from on-the-street vendors and evaluated for levels of five toxic metals (Lead, Nickel, Mercury, Cadmium and Arsenic).Analysis of toxic ...

  14. Acute Inhalation Toxicity and Blood Absorption of 2,4-Dinitroanisole (DNAN) in Rats

    Science.gov (United States)

    2015-03-17

    light/dark cycle. A certified pesticide -free rodent chow (Harlan Teklad ® , 8728C Certified Rodent Diet) and drinking quality water were available ad...respiration, toxicity, blood, concentration, alternative, welfare, method, model, in vitro, pain, distress, simulate, video , computer, replacement, refinement...Prevention, Pesticides , and Toxic Substances. December 2002. Health Effects Test Guidelines: OPPTS 870.1000, Acute Toxicity Testing - Background. EPA

  15. Radiation treatment of toxic chemicals

    International Nuclear Information System (INIS)

    Lee, M.J.; Jung, I.H.; Jo, S.K.

    2010-01-01

    Polychlorinated biphenyls (PCBs) were commercially produced from 1920s as complex mixtures containing multiple isomers for a variety of applications. They are very toxic, chemically stable and resist microbial, photochemical, chemical, and thermal degradation. The public, legal, and scientific concerns about PCBs arose from research indicating they were environmental contaminants that had a potential to adversely impact the environment, and, therefore, were undesirable as commercial products. Eventually, most producers reduced or stopped production of PCBs in the 1970s. Stockholm convention on POPs (Persistent Organic Pollutants), which was effective on May 2004 and 151 nations including Korea were joined on June 2005, asked to dispose of PCBs by 2028 with environmental friendly methods. Korean government also has declared to conduct by 2015. According to the Environmental law of Korea, over 2 ppm of PCBs has to be decomposed by legal methods of incineration and thermal destruction. But those are inapplicable owing to the environmental groups. KAERI(Korea Atomic Energy Research Institute) has recently developed a remarkable technology for radiation treatment of toxic chemicals including chlorides using an electron beam accelerator. Electron beam accelerator of 2.5 MeV energy and 100 kW power capacity was used to decompose of PCBs having been used as a commercial transformer oil for more than 30 years. The oil were irradiated with ∼ 0.1 percent of TEA (Triethyl Amin) to make chloride ion aparted off from the PCBs into precipitate at the conditions of normal temperature and pressure. The concentrations of PCBs were measured by GC (Gas Chromatography) with ECD (Electron Capture Detector) following the KS (Korean Standard) test procedure. Electron beam should be a useful tool for environmental conservation. Residual concentrations of PCBs after irradiation were depended on the absorption dose of electron beam energy. Advantages comparing to other methods such as

  16. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  17. Toxic Elements in Food: Occurrence, Binding, and Reduction Approaches

    DEFF Research Database (Denmark)

    Hajeb, P.; Sloth, Jens Jørgen; Shakibazadeh, Sh

    2014-01-01

    Toxic elements such as mercury, arsenic, cadmium, and lead, sometimes called heavy metals, can diminish mental and central nervous system function; elicit damage to blood composition as well as the kidneys, lungs, and liver; and reduce energy levels. Food is considered one of the main routes...... of their entry into the human body. Numerous studies have been performed to examine the effects of common food processing procedures on the levels of toxic elements in food. While some studies have reported negative effects of processing, several have shown that processing practices may have a positive effect...... on the reduction of toxic elements in foodstuffs. A number of studies have also introduced protocols and suggested chemical agents that reduce the amount of toxic elements in the final food products. In this review, the reported methods employed for the reduction of toxic elements are discussed with particular...

  18. Toxicity research of boron-nitrogen modifiers of wooden surface

    Directory of Open Access Journals (Sweden)

    Klyachenkova Ol'ga Aleksandrovna

    2014-07-01

    Full Text Available Boron-nitrogen compounds (BNC have been successfully used to create bio- and fire-protective compositions for wood. Within the framework of this study, our aim was to assess the toxicity of the boron-nitrogen compounds by bioluminescent method with the use of environmental control device "Biotox-10M" and highly sensitive biosensor "Ecolum". We also defined toxicological parameters EC20 and EC50 and concluded, that all the wood preservation compounds are highly toxic, whereby, it is advisable to use them for external protection of wooden structures. As a result of BNC toxicity assessment, it is necessary to consider that any effective bio- and fireprotectives, will be highly toxic. Our researches stated, that BNC protective compositions are highly toxic and, therefore, it is possible to conclude their applicability for external wood processing.

  19. Toxicity of compounds with endocrine activity in the OECD 421 reproductive toxicity screening test

    NARCIS (Netherlands)

    Piersma AH; Verhoef A; Elvers LH; Wester PW; LEO; LPI

    1998-01-01

    The issue of endocrine disruption has, in view of human risk assessment, raised the question on whether more sensitive test methods are needed to detect the reproductive toxic properties of xenobiotic compounds with endocrine properties. We studied six known and alleged endocrine disruptors in an

  20. Hydroxycut-induced Liver Toxicity

    African Journals Online (AJOL)

    hanumantp

    Annals of Medical and Health Sciences Research | Jan-Feb 2014 | Vol 4 ... supplements can be responsible for documented or undocumented adverse drug effects. The ... Keywords: Hydroxycut, Liver toxicity, Nutritional supplements ... Caffeine anhydrous: 200 mg* ... series and review of liver toxicity from herbal weight loss.

  1. One Health and Toxic Cyanobacteria

    Science.gov (United States)

    One Health and toxic cyanobacteria Blooms of toxic freshwater blue-green algae or cyanobacteria (HABs) have been in the news after HABs associated with human and animal health problems have been reported in Florida, California and Utah during 2016. HABs occur in warm, slow moving...

  2. Polish Toxic Currency Options

    Directory of Open Access Journals (Sweden)

    Waldemar Gontarski

    2009-06-01

    Full Text Available Toxic currency options are defined on the basis of the opposition to the nature (essence of an option contract, which is justified in terms of norms founded on the general law clause of characteristics (nature of a relation (which represents an independent premise for imposing restrictions on the freedom of contracts. So-understood toxic currency options are unlawful. Indeed they contravene iuris cogentis regulations. These include for instance option contracts, which are concluded with a bank, if the bank has not informed about option risk before concluding the contract; or the barrier options, which focus only on the protection of bank’s interests. Therefore, such options may appear to be invalid. Therefore, performing contracts for toxic currency options may be qualified as a criminal mismanagement. For the sake of security, the manager should then take into consideration filing a claim for stating invalidity (which can be made in a court verdict. At the same time, if the supervisory board member in a commercial company, who can also be a subject to mismanagement offences, commits an omission involving lack of reaction (for example, if he/she fails to notify of the suspected offence committed by the management board members acting to the company’s detriment when the management board makes the company conclude option contracts which are charged with absolute invalidity the supervisory board member so acting may be considered to act to the company’s detriment. In the most recent Polish jurisprudence and judicature the standard of a “good host” is treated to be the last resort for determining whether the manager’s powers resulting from criminal regulations were performed. The manager of the exporter should not, as a rule, issue any options. Issuing options always means assuming an obligation. In the case of currency put options it is an absolute obligation to purchase a given amount in euro at exchange rate set in advance. On the

  3. Corneal Toxicity Following Exposure to Asclepias Tuberosa

    OpenAIRE

    Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; G?l, Cigdem Altuntas; Heegaard, Steffen

    2017-01-01

    PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa.METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine.RESULTS: The corneal ...

  4. Toxic releases from power plants

    International Nuclear Information System (INIS)

    Rubin, E.S.

    1999-01-01

    Beginning in 1998, electric power plants burning coal or oil must estimate and report their annual releases of toxic chemicals listed in the Toxics Release Inventory (TRI) published by the US Environmental Protection Agency (EPA). This paper identifies the toxic chemicals of greatest significance for the electric utility sector and develops quantitative estimates of the toxic releases reportable to the TRI for a representative coal-fired power plant. Key factors affecting the magnitude and types of toxic releases for individual power plants also are discussed. A national projection suggests that the magnitude of electric utility industry releases will surpass those of the manufacturing industries which current report to the TRI. Risk communication activities at the community level will be essential to interpret and provide context for the new TRI results

  5. VARIATIONS IN REPRODUCTIVE TOXICANT IDENTIFICATION

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, F

    2008-05-13

    Reproductive toxicants are a very important class of compounds. They present unique hazards to those of child bearing ages, perform their 'dirty work' using a wide variety of mechanisms on a number of different organs, and are regulatorily important. Because of all of this, properly identifying reproductive toxicants is important, but fraught with difficulty. In this paper we will describe types or reproductive toxicants, their importance, and both mistakes and good practices that people who are not experts in reproductive toxicology may use in their attempts to identify them. Additionally, this paper will focus on chemical reproductive toxicants and will not address biological agents that could affect reproductive toxicity although many principles outlined here could be applied to that endeavor.

  6. Application of Toxic Chinese Medicine in Chinese Pharmacopoeia

    Science.gov (United States)

    Zhao, Hui; Feng, Yu; Mao, Mingsan

    2018-01-01

    Objective: Explore the application characteristics of proprietary Chinese medicine prescriptions containing toxic herbs in pharmacopoeia. Methods: In this paper, according to the clinical application of pharmacopoeia proprietary Chinese medicine is divided into table agent, Qushu agent, diarrhea agent, heat agent, Wen Li agent, cough and asthma agents, resuscitation agent, Gutian agent, Fuzheng agent, Anshen agent, hemostatic agent, The traditional Chinese medicine prescription and the clinical application of the Chinese herbal medicine containing the toxic Chinese medicine were analyzed and sorted out., Summed up the compatibility of toxic herbs and application characteristics. Results: Toxic Chinese herbal medicine in the cure of traditional Chinese medicine to play a long-standing role, through the overall thinking, dialectical thinking, and thinking of toxic Chinese medicine in the analysis of Chinese medicine that [2], toxic Chinese medicine in the application of proprietary Chinese medicine can not lack. Conclusion: Pharmacopoeia included proprietary Chinese medicine not only in the clinical treatment of good, but also the application of its toxic traditional Chinese medicine and its understanding of the enrichment of the toxic characteristics of traditional Chinese medicine and treatment-related disease pathology between the points of contact for patients with clinical applications Based on and theoretical guidance of Chinese medicine [3].

  7. Toxic Mixtures in Time-The Sequence Makes the Poison.

    Science.gov (United States)

    Ashauer, Roman; O'Connor, Isabel; Escher, Beate I

    2017-03-07

    "The dose makes the poison". This principle assumes that once a chemical is cleared out of the organism (toxicokinetic recovery), it no longer has any effect. However, it overlooks the other process of re-establishing homeostasis, toxicodynamic recovery, which can be fast or slow depending on the chemical. Therefore, when organisms are exposed to two toxicants in sequence, the toxicity can differ if their order is reversed. We test this hypothesis with the freshwater crustacean Gammarus pulex and four toxicants that act on different targets (diazinon, propiconazole, 4,6-dinitro-o-cresol, 4-nitrobenzyl chloride). We found clearly different toxicity when the exposure order of two toxicants was reversed, while maintaining the same dose. Slow toxicodynamic recovery caused carry-over toxicity in subsequent exposures, thereby resulting in a sequence effect-but only when toxicodynamic recovery was slow relative to the interval between exposures. This suggests that carry-over toxicity is a useful proxy for organism fitness and that risk assessment methods should be revised as they currently could underestimate risk. We provide the first evidence that carry-over toxicity occurs among chemicals acting on different targets and when exposure is several days apart. It is therefore not only the dose that makes the poison but also the exposure sequence.

  8. Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: Use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors

    International Nuclear Information System (INIS)

    Shah, Jinesh N.; Ennis, Ronald D.

    2006-01-01

    Purpose: To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. Methods and Materials: We analyzed 135 patients treated with brachytherapy ± hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. Results: Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a 25 (percent of rectal volume receiving 25% of prescribed prostate dose) ≤ 25% vs. 60% for %V 25 > 25% (p 1 ≤ 40% vs. 44% for %V 1 > 40% (p = 0.007). Conclusions: A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V 25 > 25% and %V 1 > 40% predicted worse late diarrhea and maximum toxicity, respectively

  9. Toxic epidermal necrolysis.

    Science.gov (United States)

    Pereira, Frederick A; Mudgil, Adarsh Vijay; Rosmarin, David M

    2007-02-01

    Toxic epidermal necrolysis (TEN) is an unpredictable, life-threatening drug reaction associated with a 30% mortality. Massive keratinocyte apoptosis is the hallmark of TEN. Cytotoxic T lymphocytes appear to be the main effector cells and there is experimental evidence for involvement of both the Fas-Fas ligand and perforin/granzyme pathways. Optimal treatment for these patients remains to be clarified. Discontinuation of the offending drug and prompt referral to a burn unit are generally agreed upon steps. Beyond that, however, considerable controversy exists. Evidence both pro and con exists for the use of IVIG, systemic corticosteroid, and other measures. There is also evidence suggesting that combination therapies may be of value. All the clinical data, however, is anecdotal or based on observational or retrospective studies. Definitive answers are not yet available. Given the rarity of TEN and the large number of patients required for a study to be statistically meaningful, placebo controlled trials are logistically difficult to accomplish. The absence of an animal model further hampers research into this condition. This article reviews recent data concerning clinical presentation, pathogenesis and treatment of TEN. At the conclusion of this learning activity, participants should have acquired a more comprehensive knowledge of our current understanding of the classification, clinical presentation, etiology, pathophysiology, prognosis, and treatment of TEN.

  10. Characterizing toxicity of metal-contaminated sediments from mining areas

    International Nuclear Information System (INIS)

    Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.

    2015-01-01

    Highlights: • We review methods for testing toxicity of sediments affected by metals. • Toxicity testing provides site-specific assessment of impacts on resident biota. • Goals are to document extent of toxicity and associations with metal exposure. • Need to characterize bioavailability of metals in sediment and pore water. • Toxicity data is basis for guidelines used to predict hazards of metal toxicity. - Abstract: This paper reviews methods for testing the toxicity of metals associated with freshwater sediments, linking toxic effects with metal exposure and bioavailability, and developing sediment quality guidelines. The most broadly applicable approach for characterizing metal toxicity is whole-sediment toxicity testing, which attempts to simulate natural exposure conditions in the laboratory. Standard methods for whole-sediment testing can be adapted to test a wide variety of taxa. Chronic sediment tests that characterize effects on multiple endpoints (e.g., survival, growth, and reproduction) can be highly sensitive indicators of adverse effects on resident invertebrate taxa. Methods for testing of aqueous phases (pore water, overlying water, or elutriates) are used less frequently. Analysis of sediment toxicity data focuses on statistical comparisons between responses in sediments from the study area and responses in one or more uncontaminated reference sediments. For large or complex study areas, a greater number of reference sediments is recommended to reliably define the normal range of responses in uncontaminated sediments – the ‘reference envelope’. Data on metal concentrations and effects on test organisms across a gradient of contamination may allow development of concentration-response models, which estimate metal concentrations associated with specified levels of toxic effects (e.g. 20% effect concentration or EC20). Comparisons of toxic effects in laboratory tests with measures of impacts on resident benthic invertebrate

  11. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    International Nuclear Information System (INIS)

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    1995-01-01

    Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO 2 and by observing the disappearance of test substance with gas chromatography. Additional BOD 5 and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicity tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population

  12. Research methods of ″18 incompatible medicaments″incompatibilitytoxicitycharacterizationoftraditional Chinese medicine based on early evaluation of overall toxicity%基于毒性整体早期评价的“十八反”中药配伍禁忌毒性表征的研究思路及方法

    Institute of Scientific and Technical Information of China (English)

    李遇伯; 局亮; 邓皓月; 张振珠; 王磊; 侯治国; 尹佳; 张艳军

    2015-01-01

    Currently,the toxicity study of traditional Chinese medicine is faced with the following problems. Firstly,the evaluation in vitro cannot fully reflect the true state of the body. Secondly,the traditional method is not sensitive enough to the early toxicity. Lastly,the toxicity evaluation indexes cannot determine whether the compatibility of traditional Chinese medicine produces toxicity or increases toxicity systematically. The paper proposed a synthesized early evaluation research method for target organ toxicity induced by traditional Chinese medicine:screening,validation,optimization and application. This method mainly inoolves early target organ toxicity biomarkers in screening,optimi⁃zation,validation,biological significance explanation,and application to the traditional Chinese medicine incompatibility based on the metabolic dynamic fingerprint spectrum in order to obtain biomarkers of target organ toxicity that are sensitive and precede conventional biochemical indices for early evaluation . We attempted to analyze the pattern of chang of the biomarkers for animals acted by″18 incompatible medicaments″compatibility combination. We found that Radix Aconiti Lateralis Preparata with cardiotoxicity were compatible with Rhizoma Pinelliae,and that Trichosanthes kirilowii Maxim,Fritillaria,Ampelopsis Radix and Bletilla striata without non-cardiotoxicity produced and increased cardiotoxicity systematically.%鉴于目前中药毒性研究主要存在的体外评价不能全面真实地反映机体状态、传统的检查方法对毒性早期评价不敏感和毒性评价指标不能综合判断中药配伍是否致毒、增毒的问题,本文通过构建“毒性整体早期评价筛选-验证及优化-应用”的中药靶器官毒性早期评价的研究方法,主要包括基于代谢动态指纹谱对靶器官毒性整体早期评价生物标志物的筛选、优化和验证、生物学意义的阐释以及在中药配伍禁忌中的应用等研究内

  13. Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers

    International Nuclear Information System (INIS)

    Lee, Nancy Y.; O'Meara, William; Chan, Kelvin; Della-Bianca, Cesar; Mechalakos, James G.; Zhung, Joanne; Wolden, Suzanne L.; Narayana, Ashwatha; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2007-01-01

    Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser

  14. Cervical Lymph Node Metastases From Unknown Primary Cancer: A Single-Institution Experience With Intensity-Modulated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, Hugo, E-mail: hugo.villeneuve@umontreal.ca [Department of Radiation Oncology, Centre hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Despres, Philippe; Fortin, Bernard; Filion, Edith; Donath, David [Department of Radiation Oncology, Centre hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Soulieres, Denis [Department of Medical Oncology, Centre hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Guertin, Louis; Ayad, Tarek; Christopoulos, Apostolos [Department of Head and Neck Surgery, Centre hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen-Tan, Phuc Felix [Department of Radiation Oncology, Centre hospitalier de l' Universite de Montreal, Montreal, QC (Canada)

    2012-04-01

    Purpose: To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. Methods and Materials: Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. Results: With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. Conclusion: In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities.

  15. Long-Term Clinical Outcome of Intensity-Modulated Radiotherapy for Inoperable Non-Small Cell Lung Cancer: The MD Anderson Experience

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Zhiqin [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai (China); Yang Kunyu [Cancer Centre, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Komaki, Ritsuko; Wei Xiong [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Zhuang Yan; Martel, Mary K.; Vedam, Sastray; Balter, Peter [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Zhu Guangying [Department of Radiation Oncology, Peking University School of Oncology, Beiijng Cancer Hospital and Institute, Beijing (China); Gomez, Daniel [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Lu, Charles [Department of Thoracic Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Liao Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-05-01

    Purpose: In 2007, we published our initial experience in treating inoperable non-small-cell lung cancer (NSCLC) with intensity-modulated radiation therapy (IMRT). The current report is an update of that experience with long-term follow-up. Methods and Materials: Patients in this retrospective review were 165 patients who began definitive radiotherapy, with or without chemotherapy, for newly diagnosed, pathologically confirmed NSCLC to a dose of {>=}60 Gy from 2005 to 2006. Early and late toxicities assessed included treatment-related pneumonitis (TRP), pulmonary fibrosis, esophagitis, and esophageal stricture, scored mainly according to the Common Terminology Criteria for Adverse Events 3.0. Other variables monitored were radiation-associated dermatitis and changes in body weight and Karnofsky performance status. The Kaplan-Meier method was used to compute survival and freedom from radiation-related acute and late toxicities as a function of time. Results: Most patients (89%) had Stage III to IV disease. The median radiation dose was 66 Gy given in 33 fractions (range, 60-76 Gy, 1.8-2.3 Gy per fraction). Median overall survival time was 1.8 years; the 2-year and 3-year overall survival rates were 46% and 30%. Rates of Grade {>=}3 maximum TRP (TRP{sub max}) were 11% at 6 months and 14% at 12 months. At 18 months, 86% of patients had developed Grade {>=}1 maximum pulmonary fibrosis (pulmonary fibrosis{sub max}) and 7% Grade {>=}2 pulmonary fibrosis{sub max}. The median times to maximum esophagitis (esophagitis{sub max}) were 3 weeks (range, 1-13 weeks) for Grade 2 and 6 weeks (range, 3-13 weeks) for Grade 3. A higher percentage of patients who experienced Grade 3 esophagitis{sub max} later developed Grade 2 to 3 esophageal stricture. Conclusions: In our experience, using IMRT to treat NSCLC leads to low rates of pulmonary and esophageal toxicity, and favorable clinical outcomes in terms of survival.

  16. Molecular toxicity mechanism of nanosilver

    Directory of Open Access Journals (Sweden)

    Danielle McShan

    2014-03-01

    Full Text Available Silver is an ancient antibiotic that has found many new uses due to its unique properties on the nanoscale. Due to its presence in many consumer products, the toxicity of nanosilver has become a hot topic. This review summarizes recent advances, particularly the molecular mechanism of nanosilver toxicity. The surface of nanosilver can easily be oxidized by O2 and other molecules in the environmental and biological systems leading to the release of Ag+, a known toxic ion. Therefore, nanosilver toxicity is closely related to the release of Ag+. In fact, it is difficult to determine what portion of the toxicity is from the nano-form and what is from the ionic form. The surface oxidation rate is closely related to the nanosilver surface coating, coexisting molecules, especially thiol-containing compounds, lighting conditions, and the interaction of nanosilver with nucleic acids, lipid molecules, and proteins in a biological system. Nanosilver has been shown to penetrate the cell and become internalized. Thus, nanosilver often acts as a source of Ag+ inside the cell. One of the main mechanisms of toxicity is that it causes oxidative stress through the generation of reactive oxygen species and causes damage to cellular components including DNA damage, activation of antioxidant enzymes, depletion of antioxidant molecules (e.g., glutathione, binding and disabling of proteins, and damage to the cell membrane. Several major questions remain to be answered: (1 the toxic contribution from the ionic form versus the nano-form; (2 key enzymes and signaling pathways responsible for the toxicity; and (3 effect of coexisting molecules on the toxicity and its relationship to surface coating.

  17. Evaluation of genetic diversity between toxic and non toxic Jatropha ...

    African Journals Online (AJOL)

    Massimo

    Indian varieties and a non-toxic variety of Mexican origin by means of about 400 RAPD ... evaluate the level of polymorphism and the capacity to discriminate between the ..... Population genetic software for teaching and research. Mol. Ecol.

  18. Toxicity of pyrolysis gases from some cellular polymers

    Science.gov (United States)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Various samples of cellular polymers were evaluated for toxicity of pyrolysis gases, using the screening test method developed at the University of San Francisco. The cellular polymer samples included polyimide, polymethacrylimide, polybismaleimide, polyurethane, polyisocyanurate, polyethylene, polychloroprene, polyvinyl chloride, polystyrene, polysiloxane, and polyphosphazene. The cellular polymers exhibited varying levels of toxicity under these test conditions. Among the rigid cellular polymers, times to death were shortest with the imide type foams and longest with polyvinyl chloride and polystyrene. Among the flexible cellular polymers, times to death were shortest with polyimide and polyester, and longest with polychloroprene and polysiloxane. Increased char yield was not necessarily associated with reduced toxicity.

  19. Toxicity of Uranium Adsorbent Materials using the Microtox Toxicity Test

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jiyeon [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jeters, Robert T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gill, Gary A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kuo, Li-Jung [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bonheyo, George T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-10-01

    The Marine Sciences Laboratory at the Pacific Northwest National Laboratory evaluated the toxicity of a diverse range of natural and synthetic materials used to extract uranium from seawater. The uranium adsorbent materials are being developed as part of the U. S. Department of Energy, Office of Nuclear Energy, Fuel Resources Program. The goal of this effort was to identify whether deployment of a farm of these materials into the marine environment would have any toxic effects on marine organisms.

  20. Toxicity of medicinal plants used in traditional medicine in Northern Peru.

    Science.gov (United States)

    Bussmann, R W; Malca, G; Glenn, A; Sharon, D; Nilsen, B; Parris, B; Dubose, D; Ruiz, D; Saleda, J; Martinez, M; Carillo, L; Walker, K; Kuhlman, A; Townesmith, A

    2011-09-01

    The plant species reported here are traditionally used in Northern Peru for a wide range of illnesses. Most remedies are prepared as ethanol or aqueous extracts and then ingested. The aim of this study was to evaluate the potential toxicity of these extracts. The toxicity of ethanolic and water extracts of 341 plant species was determined using a brine-shrimp assay. Overall 24% of the species in water extract and 76% of the species in alcoholic extract showed elevated toxicity levels to brine-shrimp. Although in most cases multiple extracts of the same species showed very similar toxicity values, in some cases the toxicity of different extracts of the same species varied from non-toxic to highly toxic. Traditional preparation methods take different toxicity levels in aqueous and ethanol extracts into account when choosing the appropriate solvent for the preparation of a remedy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. A COMPREHENSIVE REVIEW OF TOXIC LEADERSHIP

    Science.gov (United States)

    2016-02-05

    characteristics of a toxic leader , but labels the characteristics - leader types.  Deceptive  Autocratic  Egotistic  Incompetent  Ignorant...3 Characteristics of a Toxic Leader ...5 Table 2: Toxic Leader Characteristics

  2. National Air Toxic Assessments (NATA) Results

    Data.gov (United States)

    U.S. Environmental Protection Agency — The National Air Toxics Assessment was conducted by EPA in 2002 to assess air toxics emissions in order to identify and prioritize air toxics, emission source types...

  3. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... period. Chamber concentration may be measured using gravimetric or analytical methods as appropriate. If...) Conventional acute toxicity test—(1) Principle of the test method. Several groups of experimental animals are... practicable, monitored continuously or intermittently depending on the method of analysis, and recorded at...

  4. «Esa corporeidad mortal y rosa»: análisis del tiempo libre de enfermedad del cáncer de mama en Gipuzkoa en presencia de riesgos competitivos "That deadly and pink corporeity": Analysis of disease-free survival analysis in breast cancer in Gipuzkoa (Spain in the presence of competing risks

    Directory of Open Access Journals (Sweden)

    Pablo Martínez-Camblor

    2009-12-01

    sobrestimación tanto de la probabilidad de recidiva como de la mortalidad debida a la enfermedad.Objective: To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. Methods: All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival were also studied. Results: Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Conclusions: Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

  5. Toxic and fire hazard of flooring

    Directory of Open Access Journals (Sweden)

    Illarionova L. V.

    2017-12-01

    Full Text Available polymer materials have become widespread in the modern construction industry due to their cheapness and variety. With regard to their popularity at the present time there can appear the issues of their toxic and fire danger. The work has studied the samples of two floor synthetic building materials. The results of the determination of the fire hazard indicators of materials (combustibility, flammability, smoke ratio showed their compliance with the current certificates. The authors have studied the properties of gaseous combustion products of samples by the method of thermal analysis and FTIR analysis. The results of chloride ions analysis according the formula of Maxwell-Mohr in thermolysis products indicate the toxicity of the materials studied.

  6. Effectiveness of the Dader Method for Pharmaceutical Care on Patients with Bipolar I Disorder: Results from the EMDADER-TAB Study.

    Science.gov (United States)

    Salazar-Ospina, Andrea; Amariles, Pedro; Hincapié-García, Jaime A; González-Avendaño, Sebastián; Benjumea, Dora M; Faus, Maria José; Rodriguez, Luis F

    2017-01-01

    Bipolar I disorder (BD-I) is a chronic illness characterized by relapses alternating with periods of remission. Pharmacists can contribute to improved health outcomes in these patients through pharmaceutical care in association with a multidisciplinary health team; however, more evidence derived from randomized controlled trials (RCTs) is needed to demonstrate the effect of pharmaceutical care on patients with BD-I. To assess the effectiveness of a pharmaceutical intervention using the Dader Method on patients with BD-I, measured by the decrease in the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits from baseline through 1 year of follow-up. This study is based on the EMDADER-TAB trial, which was an RCT designed to compare pharmaceutical care with the usual care given to outpatients with BD-I in a psychiatric clinic. The main outcome was the use of health care services, using Kaplan-Meier methods and Cox regression. The trial protocol was registered in ClinicalTrials.gov (Identifier NCT01750255). 92 patients were included in the EMDADER-TAB study: 43 pharmaceutical care patients (intervention group) and 49 usual care patients (control group). At baseline, no significant differences in demographic and clinical characteristics were found across the 2 groups. After 1 year of follow-up, the risk of hospitalizations and emergencies was higher for the control group than for the intervention group (HR = 9.03, P = 0.042; HR = 3.38, P = 0.034, respectively); however, the risk of unscheduled outpatient visits was higher for the intervention group (HR = 4.18, P = 0.028). There was no "placebo" treatment, and patients in the control group might have produced positive outcomes and reduced the magnitude of dif