WorldWideScience

Sample records for survival dfs toxicity

  1. Relation of body mass index (BMI) to disease free (DFS) and distant disease free survivals (DDFS) among Turkish women with operable breast carcinoma.

    Science.gov (United States)

    Demirkan, Binnaz; Alacacioglu, Ahmet; Yilmaz, Ugur

    2007-04-01

    The correlation between body mass index (BMI) and patient and tumor characteristics related to prognosis has not been well explored and may help to elucidate the mechanisms involved in the carcinogenesis. Because of the equivocal, inconsistent and uncertain research results as well as racial and ethnic differences, we aimed to evaluate the prognostic significance of high BMI in Turkish women with operable breast carcinoma. Two hundred and sixty-six patients who had operable invasive breast carcinoma diagnosed from 2000 through 2004 in a single institution were evaluated for their demographic features, BMI, histopathological/immunohistochemical examinations and treatments. Quetelet BMI [weight (kg)/height (m)2] categories were selected according to the World Health Organization definition. Disease free survival (DSF) as well as distant disease free survival (DDSF) analyses were performed to identify independent prognostic factors. Post-menopausal patients were significantly in the higher quartile of BMI than pre-menopausal patients (P = 0.003). While post-menopausal obese patients had worse DSF and DDFS (P = 0.001), vascular invasion was the independent prognostic factor for both survival indices (P = 0.031). Post-menopausal obese Turkish women are at increased risk of developing breast tumors with aggressive phenotype and obesity is a strong predictor of poor DSF and DDFS. Preventive strategies to reduce not only the prevalence of obesity and breast cancer but also the mortality must be recognized as the cost-effective public-health policy for Turkey.

  2. The significance of anti-DFS70 antibodies in the diagnosis of autoimmune disorders

    Directory of Open Access Journals (Sweden)

    Barbara Nieradko-Iwanicka

    2017-06-01

    Full Text Available Background . Anti-DFS70 antibodies are a subgroup of antinuclear antibodies (ANA. They are connected with the dense fine speckled autoantigen of 70 kD, known as the lens epithelium-derived growth factor p75. Objectives. The objective of the review is to present the role of anti-DFS70 antibodies in the diagnosis of autoimmune diseases on the basis of recent publications. Material and methods . The authors searched for articles in the Pubmed database using the key words: anti-DFS70 antibodies, systemic autoimmune rheumatic diseases and autoimmune disorders. Results . Anti-DFS70 antibodies can be detected in eye diseases, atopic diseases, alopecia areata, fibromyalgia, asthma, chronic fatigue syndrome, tumors, Hashimoto’s disease, Graves’ disease, Behcet’s disease, inflammatory bowel diseases, neoplasms and in infectious diseases. These antibodies are sometimes detected in patients with ANA-associated rheumatic diseases (AARD . Up to 20% of serum samples from healthy individuals (HI are ANA-positive. This is probably due to the presence of monospecific anti-DFS70 antibodies. Monospecific anti-DFS70 antibodies are not associated with AARD , but mixed anti-DFS70 can be found in AARD . Conclusions . Family physicians usually do not order ANA, extractable nuclear antigens (ENA or anti-DFS70 antibodies, but they should be aware that anti-DFS70 antibodies are biomarkers that can discriminate AARD from non-AARD , save patients from unnecessary, potentially toxic treatment and save finances typically spent on retesting and visits to specialists.

  3. Thrombophilia Associated with Anti-DFS70 Autoantibodies.

    Directory of Open Access Journals (Sweden)

    Julien Marlet

    Full Text Available Anti-DFS70 antibodies are the most frequent antinuclear antibodies (ANA found in healthy individuals. We assessed the clinical significance of the presence of anti-DFS70 antibodies.We defined a group of patients (n = 421 with anti-DFS70 antibodies and a group of patients (n = 63 with a history of idiopathic arterial and/or venous thrombotic disease and/or obstetric complication (i.e. ≥ 3 miscarriages, fetal death or premature birth with eclampsia. Anti-DFS70 antibodies prevalence was also assessed in a cohort of 300 healthy blood donors.The prevalence of thrombotic disease and/or obstetric complication in the 421 patients with anti-DFS70 antibodies was 13.1% (n = 55 and the prevalence of connective tissue disease was 19% (n = 80. Among the 63 patients with a history of thrombosis and/or obstetric complications, 7 (11.1% had anti-DFS70 antibodies and among the latter, 5 had no common thrombophilic factor. In contrast, the prevalence of anti-DFS70 antibodies was of 3.0% (9 out of 300 in healthy donors. Finally, the Activated Partial Thromboplastin Time (aPTT ratio of patients with a history of thrombosis and anti-DFS70 antibodies was lower than the aPTT ratio of other patients, suggesting that thrombotic patients with anti-DFS70 antibodies may have a hypercoagulable state.We described here for the first time an immune procoagulant state involving anti-DFS70 antibodies.

  4. Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

    2015-01-01

    Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...

  5. Toxicity, Growth And Survival Of Clarias Gariepinus Juveniles ...

    African Journals Online (AJOL)

    Studies were carried out on the toxicity, growth and survival of Clarias gariepinus juveniles exposed to different concentrations of oil-polluted water. Thirty-nine aerated aquaria (60 × 30 × 30 cm3), arranged in a 4 × 3 Complete Randomized Block Design were used for the study. Three oil types: the Bonny light crude oil ...

  6. Protecting your files on the DFS file system

    CERN Multimedia

    Computer Security Team

    2011-01-01

    The Windows Distributed File System (DFS) hosts user directories for all NICE users plus many more data.    Files can be accessed from anywhere, via a dedicated web portal (http://cern.ch/dfs). Due to the ease of access to DFS with in CERN it is of utmost importance to properly protect access to sensitive data. As the use of DFS access control mechanisms is not obvious to all users, passwords, certificates or sensitive files might get exposed. At least this happened in past to the Andrews File System (AFS) - the Linux equivalent to DFS) - and led to bad publicity due to a journalist accessing supposedly "private" AFS folders (SonntagsZeitung 2009/11/08). This problem does not only affect the individual user but also has a bad impact on CERN's reputation when it comes to IT security. Therefore, all departments and LHC experiments agreed recently to apply more stringent protections to all DFS user folders. The goal of this data protection policy is to assist users in pro...

  7. Toxic effects on survival and reproduction, a process oriented approach

    Energy Technology Data Exchange (ETDEWEB)

    Bedaux, J.J.M.; Kooijman, S.A.L.M. [Vrije Univ., Amsterdam (Netherlands). Dept. of Theoretical Biology

    1995-12-31

    The authors present a new analysis of survival and reproduction data from toxicity tests. The analysis is based on the Dynamic Energy Budget theory for feeding, growth and reproduction, and a one-compartment kinetics for the toxic compound. The toxic effect size depends on the internal concentration. Effects on survival occur via the hazard rate, which is set equal to the killing rate times the internal concentration that exceeds a threshold value. Effects on reproduction depend on the mode of action of the toxicant: direct effects (mortality during oogenesis or energy costs per egg), or indirect effects (via growth, maintenance or assimilation). The effects on energetic parameters are quantified by the ratio between the internal concentration that exceeds a threshold value, and the tolerance concentration. The process-based models quantify effects as functions of exposure time and (external) concentration on a mechanistic basis. The parameters (no effect concentration, killing rate, tolerance concentration and elimination rate) are independent from the chosen exposure time of the toxicity test. The standard log-logistic models are purely descriptive, have more parameters and are sensitive to the chosen exposure time. The estimation of no-effect concentrations (NOEC`s as well as parametric NEC`S) in standard statistical analyses is problematic. Application to ring test data for chronic tests on Daphnia magna and other toxicity data reveals that these problems do not occur with the analysis, due to the absence of free gradient parameters. It is possible to obtain estimates for the standard model parameters from the new parameters, but not vice versa. The authors believe that the analysis provides a better basis for risk assessment and QSAR studies than the standard one.

  8. Levels of PBDEs, TBBPA, TBPs, PCDDs/DFs, PXDDs/DFs and PBDDs/DFs in human milk of nursing women and dairy milk products in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, S.; Okumura, T.; Nishimura, H.; Nakao, T.; Aozasa, O.; Miyata, H. [Setsunan Univ., Hirakata (Japan); Shimizu, Y.; Ochiai, F. [Shizuoka Prefecture Inst. of Univ., Shizuoka (Japan)

    2004-09-15

    Many consumer products in modern life contain brominated flame-retardant (BFR) chemicals for the purpose of fire protection. Polybrominated diphenyl ethers (PBDEs), Tetrabromobisphenol A (TBBPA) and Tribromophenol (TBPs) are used in large quantities for many applications such as television sets, computers, paints, and textiles etc. In Japan, the annual consumption of flameretardants in 2002 was 164,000 tons, and the rate of BFRs for total consumption was 39% (31,000 tons/yr). Further, that of DecaBDE,TBBPA and TBPs in 2002 was 2,200, 31,000 and 3800 tons, respectively. As a result, there is growing evidence that the large amounts of such BFRs in the environment are due to released during the manufacturing of these chemicals or consumer products containing these chemicals. In addition, there is sufficient evidence that the incineration of consumer products or manufacturing process of plastic materials containing such flame-retardant chemicals results in the formation of polybrominated/chlorinated dibenzo-p-dioxins (PXDDs) and -furans (PXDFs), polybrominated dibenzo-p-dioxins (PBDDs) and -furans (PBDFs). These chemicals, as well as the BFRs, have been found to occur throughout the environment. And the intake of these contaminants from food, air and water is suspected to be the primary route of human. At present, little is known about human pollution of the above brominated compounds in Japan. In this study, in order to generally evaluate Japanese body burden and future adverse effects of newborn infant by PBDEs, TBBPA, TBPs, PCDDs/DFs, PXDDs/DFs and PBDDs/DFs, we investigated the pollution levels of above contaminants in Japanese Breast milk. As similar purpose, it was also investigated the contamination levels in some dairy milk products like cow's milk and powdered milk.

  9. Dirty Money: A Matter of Bacterial Survival, Adherence, and Toxicity.

    Science.gov (United States)

    Vriesekoop, Frank; Chen, Jing; Oldaker, Jenna; Besnard, Flavien; Smith, Reece; Leversha, William; Smith-Arnold, Cheralee; Worrall, Julie; Rufray, Emily; Yuan, Qipeng; Liang, Hao; Scannell, Amalia; Russell, Cryn

    2016-11-23

    In this study we report the underlying reasons to why bacteria are present on banknotes and coins. Despite the use of credit cards, mobile phone apps, near-field-communication systems, and cryptocurrencies such as bitcoins which are replacing the use of hard currencies, cash exchanges still make up a significant means of exchange for a wide range of purchases. The literature is awash with data that highlights that both coins and banknotes are frequently identified as fomites for a wide range of microorganisms. However, most of these publications fail to provide any insight into the extent to which bacteria adhere and persist on money. We treated the various currencies used in this study as microcosms, and the bacterial loading from human hands as the corresponding microbiome. We show that the substrate from which banknotes are produced have a significant influence on both the survival and adherence of bacteria to banknotes. Smooth, polymer surfaces provide a poor means of adherence and survival, while coarser and more fibrous surfaces provide strong bacterial adherence and an environment to survive on. Coins were found to be strongly inhibitory to bacteria with a relatively rapid decline in survival on almost all coin surfaces tested. The inhibitory influence of coins was demonstrated through the use of antimicrobial disks made from coins. Despite the toxic effects of coins on many bacteria, bacteria do have the ability to adapt to the presence of coins in their environment which goes some way to explain the persistent presence of low levels of bacteria on coins in circulation.

  10. Toxicity of benthic dinoflagellates on grazing, behavior and survival of the brine shrimp Artemia salina

    Science.gov (United States)

    Neves, Raquel A. F.; Fernandes, Tainá; dos Santos, Luciano Neves; Nascimento, Silvia M.

    2017-01-01

    Harmful algae may differently affect their primary grazers, causing sub-lethal effects and/or leading to their death. The present study aim to compare the effects of three toxic benthic dinoflagellates on clearance and grazing rates, behavioral changes, and survival of Artemia salina. Feeding assays consisted in 1-h incubations of brine shrimps with the toxic Prorocentrum lima, Gambierdiscus excentricus and Ostreopsis cf. ovata and the non-toxic Tetraselmis sp. Brine shrimps fed unselectively on all toxic and non-toxic algal preys, without significant differences in clearance and ingestion rates. Acute toxicity assays were performed with dinoflagellate cells in two growth phases during 7-h to assess differences in cell toxicity to A. salina. Additionally, exposure to cell-free medium was performed to evaluate its effects on A. salina survival. The behavior of brine shrimps significantly changed during exposure to the toxic dinoflagellates, becoming immobile at the bottom by the end of the trials. Dinoflagellates significantly affected A. salina survival with 100% mortality after 7-h exposure to cells in exponential phase (all treatments) and to P. lima in stationary phase. Mortality rates of brine shrimps exposed to O. cf. ovata and G. excentricus in stationary phase were 91% and 75%, respectively. However, incubations of the brine shrimps with cell-free medium did not affect A. salina survivorship. Significant differences in toxic effects between cell growth phases were only found in the survival rates of A. salina exposed to G. excentricus. Acute exposure to benthic toxic dinoflagellates induced harmful effects on behavior and survival of A. salina. Negative effects related to the toxicity of benthic dinoflagellates are thus expected on their primary grazers making them more vulnerable to predation and vectors of toxins through the marine food webs. PMID:28388672

  11. Toxicity of benthic dinoflagellates on grazing, behavior and survival of the brine shrimp Artemia salina.

    Directory of Open Access Journals (Sweden)

    Raquel A F Neves

    Full Text Available Harmful algae may differently affect their primary grazers, causing sub-lethal effects and/or leading to their death. The present study aim to compare the effects of three toxic benthic dinoflagellates on clearance and grazing rates, behavioral changes, and survival of Artemia salina. Feeding assays consisted in 1-h incubations of brine shrimps with the toxic Prorocentrum lima, Gambierdiscus excentricus and Ostreopsis cf. ovata and the non-toxic Tetraselmis sp. Brine shrimps fed unselectively on all toxic and non-toxic algal preys, without significant differences in clearance and ingestion rates. Acute toxicity assays were performed with dinoflagellate cells in two growth phases during 7-h to assess differences in cell toxicity to A. salina. Additionally, exposure to cell-free medium was performed to evaluate its effects on A. salina survival. The behavior of brine shrimps significantly changed during exposure to the toxic dinoflagellates, becoming immobile at the bottom by the end of the trials. Dinoflagellates significantly affected A. salina survival with 100% mortality after 7-h exposure to cells in exponential phase (all treatments and to P. lima in stationary phase. Mortality rates of brine shrimps exposed to O. cf. ovata and G. excentricus in stationary phase were 91% and 75%, respectively. However, incubations of the brine shrimps with cell-free medium did not affect A. salina survivorship. Significant differences in toxic effects between cell growth phases were only found in the survival rates of A. salina exposed to G. excentricus. Acute exposure to benthic toxic dinoflagellates induced harmful effects on behavior and survival of A. salina. Negative effects related to the toxicity of benthic dinoflagellates are thus expected on their primary grazers making them more vulnerable to predation and vectors of toxins through the marine food webs.

  12. Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia

    DEFF Research Database (Denmark)

    Løhmann, Ditte J A; Abrahamsson, Jonas; Ha, Shau-Yin

    2016-01-01

    Treatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first...

  13. Surviving streptococcal toxic shock syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Madhusudhan Thayur R

    2007-10-01

    Full Text Available Abstract Streptococcal toxic shock syndrome and associated myositis caused by group A beta-hemolytic streptococcus pyogenes generally have a poor outcome despite aggressive operative treatment. Frequently the diagnosis is missed initially as the clinical features are non-specific. The progression to a toxic state is rapid and unless definitive treatment measures are initiated early, the end result can be catastrophic. We report a previously healthy patient who had features of toxic shock syndrome due to alpha haemolytic (viridans streptococcus mitis which was treated successfully with antibiotics, aggressive intensive care support including the use of a 'sepsis care bundle', monitoring and continuous multidisciplinary review. Life and limb threatening emergencies due to streptococcus mitis in an immune-competent person are rare and to our knowledge, have not previously been described in the English scientific literature. Successful outcome is possible provided a high degree of suspicion is maintained and the patient is intensively monitored.

  14. Properties of Lewis Lung Carcinoma Cells Surviving Curcumin Toxicity

    Directory of Open Access Journals (Sweden)

    Dejun Yan, Michael E. Geusz, Roudabeh J. Jamasbi

    2012-01-01

    Full Text Available The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 μM for 30 hours. Because of the high cell loss at 60 μM, this dose was chosen to select for surviving cells that were then used to establish a new cell line. The resulting line had approximately 20% slower growth than the original LLC cell line and based on ELISA contained less of two markers, NF-κB and ALDH1A, used to identify more aggressive cancer cells. We also injected cells from the original and surviving lines subcutaneously into syngeneic C57BL/6 mice and monitored tumor development over three weeks and found that the curcumin surviving-line remained tumorigenic. Because curcumin has been reported to kill cancer cells more effectively when administered with light, we examined this as a possible way of enhancing the efficacy of curcumin against LLC cells. When LLC cells were exposed to curcumin and light from a fluorescent lamp source, cell loss caused by 20 μM curcumin was enhanced by about 50%, supporting a therapeutic use of curcumin in combination with white light. This study is the first to characterize a curcumin-surviving subpopulation among lung cancer cells. It shows that curcumin at a high concentration either selects for an intrinsically less aggressive cell subpopulation or generates these cells. The findings further support a role for curcumin as an adjunct to traditional chemical or radiation therapy of lung and other cancers.

  15. The toxic effect of Cymbush pesticide on growth and survival of ...

    African Journals Online (AJOL)

    Toxicant effects of cymbush pesticide on growth, and survival levels of Clarias gariepinus fingerlings were studied. Results showed that mortality increased with increase in concentrations. The 96hLC50 was 4.17mgl-1 while the threshold value was 4.15mgl-1. In acute concentrations, there were dark patches on the ...

  16. Survival Trends and Long-Term Toxicity in Pediatric Patients with Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Melanie M. Hagleitner

    2012-01-01

    Full Text Available Background. This study was conducted to investigate the clinical characteristics and treatment results of osteosarcoma in pediatric patients during the past 30 years. Trends in survival rates and long-term toxicity were analyzed. Procedure. 130 pediatric patients under the age of 20 years with primary localized or metastatic high-grade osteosarcoma were analyzed regarding demographic, treatment-related variables, long-term toxicity, and survival data. Results. Comparison of the different time periods of treatment showed that the 5-year OS improved from 58.6% for children diagnosed during 1979–1983 to 78.6% for those diagnosed during 2003–2008 (P=0.13. Interestingly, the basic treatment agents including cisplatin, doxorubicin, and methotrexate remained the same. Treatment reduction due to acute toxicity was less frequent in patients treated in the last era (7.1% versus 24.1% in patients treated in 1979–1983; P=0.04. Furthermore, late cardiac effects and secondary malignancies can become evident many years after treatment. Conclusion. We elucidate the prevalence of toxicity to therapy of patients with osteosarcoma over the past 30 years. The overall improvement in survival may in part be attributed to improved supportive care allowing regimens to be administered to best advantage with higher tolerance of chemotherapy and therefore less chemotherapy-related toxicity.

  17. Toxicity of organoclays to microbial processes and earthworm survival in soils.

    Science.gov (United States)

    Sarkar, Binoy; Megharaj, Mallavarapu; Shanmuganathan, Devarajan; Naidu, Ravi

    2013-10-15

    Organoclays have wide spread application in environmental remediation and nanocomposites synthesis. Some of the quaternary ammonium compounds (QACs) commonly used to prepare organoclays are toxic to biota. However, information on the toxicity of organoclays is rarely available in the literature. This study assessed the toxicity of three laboratory prepared bentonite organoclays on the soil microbially mediated processes (such as dehydrogenase activity and potential nitrification) and soil inhabiting animals, such as earthworms. Toxicity to both microbial processes and earthworm followed the order: hexadecyltrimethyl ammonium modified bentonite>octadecyltrimethyl ammonium modified bentonite>arquad modified bentonite>unmodified bentonite. The organoclays were able to cause slight improvement (up to 25%) in the potential nitrification in some soils when they were added at low application rates up to 5%, but caused reduction (3-86%) in the dehydrogenase activity in all the soils irrespective of loading rates. The organoclays were extremely toxic to the survival and vigour of the earthworms. The average body weight loss of the worms reached as high as 62% in hexadecyltrimethyl ammonium modified bentonite treated soil even at 1% loading. This study holds utmost importance in assessing the toxicity of organoclays to soil microbially mediated processes and earthworms. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Tomas Pascual

    Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

  19. Efficacy and toxicity of pegylated liposomal doxorubicin-based chemotherapy in early-stage breast cancer: a multicenter retrospective case-control study.

    Science.gov (United States)

    Yang, Fu Ou; Hsu, Nicholas C; Moi, Sin-Hua; Lu, Yin-Che; Hsieh, Chia-Ming; Chang, King-Jen; Chen, Dar-Ren; Tu, Chi-Wen; Wang, Hwei-Chung; Hou, Ming-Feng

    2017-10-18

    PEGylated liposomal doxorubicin (PLD) has comparable efficacy and differing toxicity from conventional anthracyclines used to treat advanced breast cancer. This study compared disease-free survival and toxicity between PLD-based and conventional anthracycline-based regimens as adjuvant treatments for early-stage breast cancer. We analyzed disease-free survival (DFS) rates, and adverse events in 102 women with early-stage (I-IIIa) breast cancer who received adjuvant PLD-based chemotherapy from 2002 to 2008. Each patient was matched for age, stage at diagnosis, HER-2 expression and hormone therapy use to a patient treated with an epirubicin-based regimen. Fisher's exact and Pearson's chi-square tests were used for categorical data analysis. Kaplan-Meier analysis and Cox regression models were used to analyze DFS. DFS at 5 years was 81.3% for PLD-based regimen and 82.3% for epirubicin-based regimen. This difference was not significant (p = 0.939). Stage IIIa disease was associated with a shorter DFS in univariate analysis (p = 0.048). In multivariate analysis that controlled for adjuvant treatment, age at diagnosis, stage, HER-2 expression, type of surgery and hormone and radiation therapy, stage IIIa disease (P = 0.023) and lack of hormone therapy (P = 0.024) were each independently associated with shorter DFS. Adverse events were evaluated, and with the exception of hand-foot syndrome, more grade 3 and 4 toxicities occurred in patients who received epirubicin-based regimens than in those given PLD-based regimens. For patients with early-stage breast cancer who received PLD-based adjuvant chemotherapy, 5-year DFS was comparable and toxicity was acceptable, yet different from those of patients who received epirubicin-based regimens. © 2017 John Wiley & Sons Australia, Ltd.

  20. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  1. Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

    Science.gov (United States)

    Fettiplace, Michael R; McCabe, Daniel J

    2017-08-01

    The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

  2. Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

    Science.gov (United States)

    Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

    In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  3. Toxicity of four veterinary pharmaceuticals on the survival and reproduction of Folsomia candida in tropical soils.

    Science.gov (United States)

    Zortéa, Talyta; Segat, Julia C; Maccari, Ana Paula; Sousa, José Paulo; Da Silva, Aleksandro S; Baretta, Dilmar

    2017-04-01

    This study aimed to evaluate the effect of veterinary pharmaceuticals (VPs) used to control endo- and ectoparasites in ruminants, on the survival and reproduction of the collembolan species Folsomia candida. Standard ecotoxicological tests were conducted in Tropical Artificial Soil and the treatments consisted of increasing dosages of four commercial products with different active ingredients: ivermectin, fipronil, fluazuron and closantel. Ecotoxicological effects were related to the class and mode of action of the different compounds. Fipronil and ivermectin were the most toxic compounds causing a significant reduction in the number of juveniles at the lowest doses tested (LOECreprod values of 0.3 and 0.2 mg kg-1 of dry soil, respectively) and similar low EC50 values (fipronil: 0.19 mg kg-1 dry soil, CL95% 0.16-0.22; ivermectin: 0.43 mg kg-1 dry soil, CL95% 0.09-0.77), although the effects observed in the former compound were possibly related to a low adult survival (LC50 of 0.62 mg kg-1 dry soil; CL95%: 0.25-1.06). For the latter compound no significant lethal effects were observed. Fluazuron caused an intermediate toxicity (EC50 of 3.07 mg kg-1 dry soil, CL95%: 2.26-3.87), and also here a decrease in adult survival could explain the effects observed at reproduction. Closantel, despite showing a significant reduction on the number of juveniles produced, no dose-response relationship nor effects higher than 50% were observed. Overall, all tested compounds, especially ivermectin, when present in soil even at sub-lethal concentrations, can impair the reproduction of collembolans and possibly other arthropods. However, the actual risk to arthropod communities should be further investigated performing tests under a more realistic exposure (e.g., by testing the dung itself as the contaminated matrix) and by deriving ecotoxicologically relevant exposure concentration in soil derived from the presence of cattle dung. Copyright © 2017 Elsevier Ltd. All rights

  4. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

    Science.gov (United States)

    Nafar, F; Clarke, J P; Mearow, K M

    2017-05-01

    Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aβ was rescued compared to cultures exposed only to Aβ. Here we investigated treatment with Aβ for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aβ exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aβ for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aβ exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aβ amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted

  5. Improved survival for elderly married glioblastoma patients. Better treatment delivery, less toxicity, and fewer disease complications

    Energy Technology Data Exchange (ETDEWEB)

    Putz, Florian; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany); Putz, Tobias [University of Bamberg, Professorship of Demography, Bamberg (Germany); Eyuepoglu, Ilker; Roessler, Karl [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

    2016-11-15

    Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m{sup 2} vs. 33.1 mg/m{sup 2}; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies. (orig.) [German] Fuer verheiratete Patienten mit malignen Gliomen ist ein verbessertes Gesamtueberleben gut beschrieben. Die zugrunde liegenden Mechanismen konnten bislang jedoch in den verfuegbaren bevoelkerungsbezogenen Arbeiten nicht erklaert werden. Eine Serie von 57 aelteren Patienten mit

  6. Selenium toxicity to honey bee (Apis mellifera L.) pollinators: effects on behaviors and survival.

    Science.gov (United States)

    Hladun, Kristen R; Smith, Brian H; Mustard, Julie A; Morton, Ray R; Trumble, John T

    2012-01-01

    We know very little about how soil-borne pollutants such as selenium (Se) can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER) and taste perception to determine if the presence of Se affected the gustatory response of honey bee (Apis mellifera L., Hymenoptera: Apidae) foragers. Antennae and proboscises were stimulated with both organic (selenomethionine) and inorganic (selenate) forms of Se that commonly occur in Se-accumulating plants. Methionine was also tested. Each compound was dissolved in 1 M sucrose at 5 concentrations, with sucrose alone as a control. Antennal stimulation with selenomethionine and methionine reduced PER at higher concentrations. Selenate did not reduce gustatory behaviors. Two hours after being fed the treatments, bees were tested for sucrose response threshold. Bees fed selenate responded less to sucrose stimulation. Mortality was higher in bees chronically dosed with selenate compared with a single dose. Selenomethionine did not increase mortality except at the highest concentration. Methionine did not significantly impact survival. Our study has shown that bees fed selenate were less responsive to sucrose, which may lead to a reduction in incoming floral resources needed to support coworkers and larvae in the field. If honey bees forage on nectar containing Se (particularly selenate), reductions in population numbers may occur due to direct toxicity. Given that honey bees are willing to consume food resources containing Se and may not avoid Se compounds in the plant tissues on which they are foraging, they may suffer similar adverse effects as seen in other insect guilds.

  7. Selenium toxicity to honey bee (Apis mellifera L. pollinators: effects on behaviors and survival.

    Directory of Open Access Journals (Sweden)

    Kristen R Hladun

    Full Text Available We know very little about how soil-borne pollutants such as selenium (Se can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER and taste perception to determine if the presence of Se affected the gustatory response of honey bee (Apis mellifera L., Hymenoptera: Apidae foragers. Antennae and proboscises were stimulated with both organic (selenomethionine and inorganic (selenate forms of Se that commonly occur in Se-accumulating plants. Methionine was also tested. Each compound was dissolved in 1 M sucrose at 5 concentrations, with sucrose alone as a control. Antennal stimulation with selenomethionine and methionine reduced PER at higher concentrations. Selenate did not reduce gustatory behaviors. Two hours after being fed the treatments, bees were tested for sucrose response threshold. Bees fed selenate responded less to sucrose stimulation. Mortality was higher in bees chronically dosed with selenate compared with a single dose. Selenomethionine did not increase mortality except at the highest concentration. Methionine did not significantly impact survival. Our study has shown that bees fed selenate were less responsive to sucrose, which may lead to a reduction in incoming floral resources needed to support coworkers and larvae in the field. If honey bees forage on nectar containing Se (particularly selenate, reductions in population numbers may occur due to direct toxicity. Given that honey bees are willing to consume food resources containing Se and may not avoid Se compounds in the plant tissues on which they are foraging, they may suffer similar adverse effects as seen in other

  8. Psychometric properties of Greek versions of the Modified Corah Dental Anxiety Scale (MDAS and the Dental Fear Survey (DFS

    Directory of Open Access Journals (Sweden)

    Patrikiou Antonis

    2008-09-01

    Full Text Available Abstract Background A growing body of literature describes the performance of dental fear questionnaires in various countries. We describe the psychometric properties of Greek versions of the Modified Dental Anxiety Scale (MDAS and the Dental Fear Survey (DFS in adult Greek patients. Methods Greek versions of the MDAS and DFS were administered to two samples of adult dental patients. In the first sample, 195 patients attending one of three private practice dental offices in a large city in Greece completed the questionnaires in the waiting room before dental treatment. After treatment, their dentists (who did not know how the patients had answered the questionnaire rated their anxiety during dental treatment. In the second sample, 41 patients attending a Greek university dental school clinic completed the questionnaire twice at two separate visits, in order to provide test-retest data. Cronbach's alpha was used to compute the internal consistencies, while Spearman's rho was used to compute the test-retest reliabilities. Construct validity was assessed by correlating the responses to the MDAS and DFS by Spearman's rho. Spearman's rho was also used to examine the criterion validities, by comparing the questionnaire responses with the dentists' ratings of anxiety. Results The internal consistencies for the MDAS were 0.90 and 0.92 in the two samples; for the DFS, the internal consistencies were 0.96 in both samples. The test-retest reliabilities were 0.94 for the MDAS and 0.95 for the DFS. The correlation between the two questionnaires was 0.89. The patients' responses to both questionnaires were significantly related to the dentists' ratings of their anxiety during dental treatment (both p values Conclusion The results indicate that the Greek versions of the MDAS and DFS have good internal consistencies and test-retest reliabilities, as well as good construct and criterion validities. The psychometric properties of the Greek versions of these

  9. The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Choi, M. Y.; Clarke, A. E.; St Pierre, Y.

    2017-01-01

    , clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate...

  10. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-year Disease-free Survival and Toxicity Observations

    Directory of Open Access Journals (Sweden)

    Donald Blake Fuller

    2014-11-01

    Full Text Available PURPOSEProstate stereotactic body radiotherapy (SBRT may substantially recapitulate the dose distribution of high-dose-rate (HDR brachytherapy, representing an externally delivered Virtual HDR treatment method. Herein we present 5-year outcomes from a cohort of consecutively treated Virtual HDR SBRT prostate cancer patients.METHODSSeventy-nine patients were treated from 2006 - 2009, 40 low-risk and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in 4 fractions. The planning target volume (PTV included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered > 95% of the PTV (V100 >= 95%, with a minimum 150% PTV dose escalation to create HDR-like PTV dose distribution.RESULTSMedian pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70% but only 3 of them subsequently relapsed, Biochemical-relapse-free survival was 100% and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98% and 92% by Phoenix definition. Local relapse did not occur, distant metastasis-free survival was 100% and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10% and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0% and 1%, respectively, with no grade 3 or higher toxicity. Of patients potent pre-SBRT, 65% remained so at 5 years.CONCLUSIONSVirtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

  11. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  12. Effects of functionalized fullerenes on bifenthrin and tribufos toxicity to Daphnia magna: Survival, reproduction, and growth rate.

    Science.gov (United States)

    Brausch, Kathryn A; Anderson, Todd A; Smith, Philip N; Maul, Jonathan D

    2010-11-01

    Incorporation of carbon nanomaterials into industrial and consumer products is increasing, yet their impact on aquatic ecosystems alone and in chemical mixtures is largely unknown. Carbon nanomaterials may be found in the aquatic environment as mixtures with pesticides because of their proposed use in agriculture as smart delivery systems and nanosensors. The interaction effects of a functionalized fullerene ([1,2-methanofullerene C₆₀]-61-carboxylic acid) (fC₆₀) at 52.8 µg/L and the hydrophobic pesticides bifenthrin and tribufos were examined. The test organism was Daphnia magna, and response variables included 48-h survival, reproduction (bifenthrin, 70-d; tribufos, 21-d), and 10-d growth. Both pesticides reduced D. magna survival and reproduction (p Fullerenes significantly increased bifenthrin acute toxicity but did not significantly affect chronic endpoints or growth (p > 0.05). Median lethal concentrations (LC50s), median inhibition concentrations (IC50s) for days surviving, and IC50s for reproduction were 0.86, 0.55, and 0.49 µg/L for bifenthrin; 0.22, 0.39, and 0.77 µg/L for fC₆₀-bifenthrin mix; 6.63, 9.89, and 5.79 µg/L for tribufos; and 9.17, 8.17, and 6.59 µg/L for fC₆₀-tribufos mix. Mixtures did not affect instantaneous growth rate (p > 0.05). These results suggest that fC₆₀ had little effect on pesticide chronic toxicity but influenced acute toxicity. Given the widespread application of nanotechnology, the influence of nanomaterials on environmental contaminants is an important consideration. Thus, our results may be useful in the development and use of nanotechnology in agricultural practices. © 2010 SETAC.

  13. A tundra of sickness: the uneasy relationship between toxic waste, TEK, and cultural survival.

    Science.gov (United States)

    Cassady, Joslyn

    2007-01-01

    In 1992 an abandoned federal radioactive waste dump was discovered in Arctic Alaska. The discovery of this site, a byproduct of the Atomic Energy Commission program known as Project Chariot, sent shockwaves throughout Iñupiaq communities and ignited a heated controversy over the health effects of subsisting on a "tundra of sickness." Drawing on thirty months of ethnographic research in Arctic Alaska, this paper explores a host of environmental, social, and moral uncertainties sparked by toxic waste. Anthropological claims regarding the extent to which "traditional ecological knowledge" will empower local communities and foster self-determination are challenged. Ultimately the paper argues that TEK has been conceived in such restrictive terms that it misrepresents the dynamic, emerging, and at times contradictory responses to toxic waste in the Arctic today. Moreover, there is dire need for a more materialist, as opposed to discourse-based, approach that acknowledges the very real threat of toxic waste to physical, and therefore, cultural reproduction.

  14. Comprehensive Survival Analysis of a Cohort of Patients with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis

    NARCIS (Netherlands)

    Sekula, Peggy; Dunant, Ariane; Mockenhaupt, Maja; Naldi, Luigi; Bavinck, Jan Nico Bouwes; Halevy, Sima; Kardaun, Sylvia; Sidoroff, Alexis; Liss, Yvonne; Schumacher, Martin; Roujeau, Jean-Claude

    Stevens Johnson syndrome and toxic epidermal necrolysis are severe cutaneous adverse reactions that are of major concern because of high mortality rates. On the basis of data collected in the RegiSCAR study, the aim was to assess risk factors (including modalities of patient management) for

  15. Meiotic segregation and sperm DNA fragmentation in Tunisian men with dysplasia of the fibrous sheath (DFS) associated with head abnormalities.

    Science.gov (United States)

    Ghedir, H; Mehri, A; Mehdi, M; Brahem, S; Saad, A; Ibala-Romdhane, S

    2014-09-01

    Dysplasia of the Fibrous Sheath (DFS) is a primitive flagellar pathology for which a broad spectrum of ultrastructural flagellar abnormalities has been described responsible for a severe to total asthenozoospermia. To this phenotype other morphological abnormalities including cephalic and abnormalities in nuclear structure can be associated that could compromise embryonic development in case of use of Assisted Reproductive Technology (ART). The aim of this study was to evaluate the level of DNA fragmentation and aneuploidy rate in ejaculated spermatozoa of Tunisian men presented with DFS sperm defect associated to high percentage of head abnormalities and to compare the results with those from fertile men. Sperm DNA fragmentation was evaluated by the terminal desoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick-end labelling (TUNEL) assay. The study of meiotic segregation was performed by Fluorescence in situ hybridization (FISH) for chromosomes X, Y and 18. The mean DNA fragmentation index was significantly higher in patients compared to the control group. FISH revealed a significantly higher incidence of sperm aneuploidies compared with controls. All patients showed elevated frequencies of sex chromosomes disomy, disomy 18 and diploidy. In some cases of syndromic teratozoospermia due to sperm tail structural abnormalities, such as DFS, other morphological cephalic abnormalities may be associated. In these cases we have demonstrated impaired sperm nuclear quality which will affect the results in ICSI. Hence the interest of a thorough study of the sperm nucleus in these forms of infertility in order to predict the chances of success in ART.

  16. Lethal and Sublethal Toxicity Comparison of BFRs to Three Marine Planktonic Copepods: Effects on Survival, Metabolism and Ingestion.

    Directory of Open Access Journals (Sweden)

    Wenjing Gong

    Full Text Available The estuarine planktonic copepods have a wide geographical distribution and commendable tolerance to various kinds of contaminants. The primary aim of the present study was to contrast the impacts of model POPs (TBBPA and HBCD on three common estuarine planktonic copepods (Oithona similis, Acartia pacifica and Pseudodiaptomus inopinus and establish a protocol for the assessment of acute toxicity of marine organic pollutants. We first quantified the 96h-LC50 (0.566, 0.04 and 0.257 mg/L of TBBPA to the three subjects above respectively and 0.314 mg/L of HBCD to P. inopinus; all reported concentrations are nominal values. In the sub-lethal toxicity tests, it was turned out that the effects of copepods exposed to TBBPA could product different influences on the energy ingestion and metabolism. Different type of pollutions, meanwhile, could also bring varying degree effect on the target copepods. In general, the indicators (the rate of oxygen consumption, ammonia excretion, food ingestion and filtration in higher concentration groups showed marked significant difference compared with controls as well a dose-effect relationship. The study also extended the research on the joint toxicity of TBBPA and HBCD based on the survival rate of P.inopinus. Whether 1:1 concentration or 1:1 toxic level, the research showed synergy effect relative to single exposure conditions. The result indicated that current single ecological testing used for environmental protection activities may underestimate the risk for copepods. It was also demonstrated that short-term sub-lethal experiment could be a standard to evaluate the sensitivity of copepods to POPs.

  17. Survival and Toxicity in Patients With Disseminated Germ CellCancer Aged 40 Years and Older

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Bandak, Mikkel; Thomsen, Maria F

    2014-01-01

    , etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. All patients were...... followed until death or October 1, 2011. RESULTS: The cumulated doses of BEP were comparable between the two groups, however, more patients aged ≥40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P = 0.03). No differences between...

  18. Toxic metals in aquatic plants surviving in surface water polluted by copper mining industry.

    Science.gov (United States)

    Samecka-Cymerman, A; Kempers, A J

    2004-09-01

    Concentrations of the metals Al, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn, as well as the macronutrients N, P, K, Ca, Mg, and S were measured in water, sediments, and the aquatic macrophytes Potamogeton pectinatus and Myriophyllum spicatum, growing in surface water receiving sewages and solid wastes from a copper smelter and a copper ore processing factory located in the Legnica-Glogow copper district in Southwest Poland. The deposition of mineral wastes in this area belong to the largest repository in Europe. The plants were able to survive at heavily contaminated sites. The concentrations of Cd (up to 0.6-1.7 microg/L in water and up to 10.1-12.9 mg/kg in sediments), Cu (up to 29-48 microg/L in water and up to 4.6-5.6g/kg in sediments), Pb (up to 1.5-2.2 g/kg in sediments), and Zn (up to 167-200 microg/L in water and up to 1.4-1.8 g/kg in sediments) seriously exceeded background values. P. pectinatus was able to survive tissue concentrations (in mg/kg) of up to 920 Cu, 6240 Mn, 98 Co, and 59 Ni, while M. spicatum survived tissue concentrations up to 1040 Cu, 6660 Mn, and 57 Co for. Enrichment ratios of elements in plant tissue and in water were much higher than those between plant tissue and sediments. Copyright 2003 Elsevier Inc.

  19. The effect of amiodarone pretreatment on survival of mice with cocaine toxicity.

    Science.gov (United States)

    DeWitt, Christopher R; Cleveland, Nathan; Dart, Richard C; Heard, Kennon

    2005-12-01

    Cocaine is a common drug of abuse and use has been associated with ventricular dysrhythmias. Published guidelines suggest that amiodarone is the first line antidysrhythmic for ventricular tachycardia and fibrillation. However, the effects amiodarone in the setting of cocaine toxicity are unknown and unstudied. The purpose of this study was to evaluate the safety and efficacy of amiodarone pretreatment in a murine model of acute cocaine toxicity. This was a randomized, blinded, placebo controlled investigation using male CF-1 mice weighing 29-37 g. First, the safety of an intraperitoneal dose of amiodarone (40 mg/kg) was confirmed in 5 mice. Second, based on preliminary investigations, an approximate intraperitoneal LD50 dose of cocaine (110 mg/kg) was identified and used as the cocaine dose in this study. Animals were then randomized to 2 groups. The control group received 0.5 mL of intraperitoneal 0.9% saline 30 minutes before cocaine. The study group received 40 mg/kg of intraperitoneal amiodarone (40 mg/kg) 30 minutes before cocaine. A blinded observer monitored mice for 2 hours after cocaine administration. No mice in the amiodarone-only group developed any signs of toxicity or died. In the saline + cocaine group 31/32 (96.9%; 95% CI 83.8 to 99.9) mice seized with a median time to seizure of 2.5 minutes, and 23/32 (71.9%; 95% CI 52.3 to 86.3) died with a median time to death of 5.5 minutes. In the amiodarone + cocaine group 31/33 (93.9%; 95% CI 79.0 to 99.3) mice seized with a median time to seizure of 2.0 minutes, and 24/33 (72.7%; 95% CI 54.5 to 86.7) died with a median time to death of 6.0 minutes. All animals that died did so within 9 minutes. The difference in the proportion of animals dying in the amiodarone + cocaine group compared to the saline + cocaine group was 0.008 (-21 to 22%). In this study, pretreatment with amiodarone in cocaine poisoned mice resulted in no change in seizure incidenceor mortality. However, definite conclusions about the reason

  20. The Effect of Various Species of Macroalgae on the Growth, Survival, and Toxicity of Karenia brevis

    Science.gov (United States)

    Gardner, K. G.; Lovko, V. J.; Henry, M. S.

    2016-02-01

    Harmful algal blooms (HABs) caused by the dinoflagellate Karenia brevis produce toxins that result in negative impacts to both humans and the environment. Little is known about the termination stages of these blooms, and few viable control mechanisms have been suggested. Natural, algae derived compounds have been proposed as a way to limit bloom growth and reduce brevetoxins in the water column. The work presented here examines the ability of macroalgae to inhibit the growth or survival of K. brevis, similar to what has been demonstrated with other red tide species. Additionally, we attempted to determine if macroalgae decreases water column brevetoxins which, to our knowledge, has not been tested with macroalgae but has been demonstrated in other studies with microalgal species. The macroalgae species Dictyota sp. and Gracilaria sp. caused 100% mortality of K. brevis in under 24 hours. Compared to the control, 7 other species significantly decreased the growth rate of K. brevis. The Dictyota treatments showed significant toxin reduction and increase of the antitoxin brevanol. These results indicate that some combination of compounds produced by macroalgae inhibit growth and survival of K. brevis and possibly limit their toxin production. Future studies will attempt to isolate and identify these compounds and test their effects on other marine organisms such as diatoms. Determining the interactions between HAB species K. brevis and macroalgal species will provide insights on the mechanism of bloom termination and a potential control method.

  1. Three dimensional conformal radiation therapy in prostate adenocarcinoma: Survival and rectal toxicity

    Directory of Open Access Journals (Sweden)

    Kannan V

    2005-01-01

    Full Text Available Technological advances in radiation beam planning and linear accelerator based radiation delivery have led to the development of three dimensional conformal radiation therapy (3D-CRT. The 3D-CRT clinical treatment in our hospital was started in September 1998 and till December 2002, 51 patients with M0 stage prostate carcinoma were treated. Treatment method consisted of pelvis and leg immobilization, planning CT scan, marking of planning target volume and organs at risk and 3D beam plan using multileaf collimated beam shaping through beam′s eye view display. Network controlled 3D conformal radiation therapy was delivered with portal image verification. The median 3D-CRT dose was 72 Gy. Of the 51 patients, 35 were followed-up till December 2002 (minimum follow-up 2 years in whom 32 were disease free and 3 had progressive disease. Eleven patients died, 8 of progressive disease, one due to second malignancy and two of intercurrent illness. Five patients were lost for follow up during 0 - 29 months period, after 3D-CRT. The acute rectal reaction (RTOG criteria in 51 patients was grade 0 in 4, grade I in 31 and grade II in 16. None had greater than grade II rectal toxicity. The late rectal toxicity in 49 patients who had a minimum 6 months follow-up was grade 0 in 41, grade I in 3 and grade II in 5. Our experience suggests that a dose of 72 Gy by 3D-CRT can be safely delivered to the prostate and gastrointestinal tolerance during treatment and follow-up period was excellent.

  2. Effects of Toxic Leachate from Commercial Plastics on Larval Survival and Settlement of the Barnacle Amphibalanus amphitrite.

    Science.gov (United States)

    Li, Heng-Xiang; Getzinger, Gordon J; Ferguson, P Lee; Orihuela, Beatriz; Zhu, Mei; Rittschof, Daniel

    2016-01-19

    Plastic pollution represents a major and growing global problem. It is well-known that plastics are a source of chemical contaminants to the aquatic environment and provide novel habitats for marine organisms. The present study quantified the impacts of plastic leachates from the seven categories of recyclable plastics on larval survival and settlement of barnacle Amphibalanus (=Balanus) amphitrite. Leachates from plastics significantly increased barnacle nauplii mortality at the highest tested concentrations (0.10 and 0.50 m(2)/L). Hydrophobicity (measured as surface energy) was positively correlated with mortality indicating that plastic surface chemistry may be an important factor in the effects of plastics on sessile organisms. Plastic leachates significantly inhibited barnacle cyprids settlement on glass at all tested concentrations. Settlement on plastic surfaces was significantly inhibited after 24 and 48 h, but settlement was not significantly inhibited compared to the controls for some plastics after 72-96 h. In 24 h exposure to seawater, we found larval toxicity and inhibition of settlement with all seven categories of recyclable commercial plastics. Chemical analysis revealed a complex mixture of substances released in plastic leachates. Leaching of toxic compounds from all plastics should be considered when assessing the risks of plastic pollution.

  3. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

  4. A retrospective study comparing the outcomes and toxicities of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy for the treatment of children and adolescent nasopharyngeal carcinoma.

    Science.gov (United States)

    Qiu, Wen-Ze; Peng, Xing-Si; Xia, Hai-Qun; Huang, Pei-Yu; Guo, Xiang; Cao, Ka-Jia

    2017-08-01

    To compare the clinical outcomes and toxicities of two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated radiotherapy (IMRT) for the treatment of children and adolescent nasopharyngeal carcinoma (NPC). A total of 176 children with non-metastatic NPC treated at Sun Yat-sen University Cancer Center between October 2003 and September 2013 were included in this study. Of the 176 patients, 74 received 2D-CRT and 102 were treated with IMRT. The clinical outcomes and acute and late toxicities were determined and compared. The IMRT group achieved significantly higher overall survival (OS) (90.4% vs. 76.1% at 5 year, P = 0.007) and disease-free survival (DFS) (85.7% vs. 71.2%, P = 0.029) mainly due to an improvement in locoregional relapse-free survival (LRRFS) (97.9 vs. 88.3%, P = 0.049). After stratification by disease stage, IMRT provided significant benefits for patients with stage III-IV disease in terms of OS, LRRFS and DFS. Multivariate analyses indicated that the treatment group (2D-CRT vs. IMRT) was a prognostic factor for OS, LRRFS and DFS. A significant reduction in Grade 2-4 xerostomia (52.7 vs. 34.3%, P = 0.015) and hearing loss (40.5 vs. 22.5%, P = 0.010) was observed in patients treated by IMRT. IMRT provides better locoregional relapse-free survival and overall survival, especially in late-stage children and adolescent NPC patients, and is associated with a lower incidence of Grade 2-4 xerostomia as well as hearing loss compared with 2D-CRT. Distant metastasis remains a challenge in the treatment of children and adolescent NPC.

  5. NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction.

    Science.gov (United States)

    Wennberg, Berit M; Baumann, Pia; Gagliardi, Giovanna; Nyman, Jan; Drugge, Ninni; Hoyer, Morten; Traberg, Anders; Nilsson, Kristina; Morhed, Elisabeth; Ekberg, Lars; Wittgren, Lena; Lund, Jo-Åsmund; Levin, Nina; Sederholm, Christer; Lewensohn, Rolf; Lax, Ingmar

    2011-05-01

    In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction α/β = 3 Gy was used and the USC parameters used were: α/β = 3 Gy, D(0) = 1.0 Gy, [Formula: see text] = 10, α = 0.206 Gy(-1) and d(T) = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether "high doses to small volumes" or "low doses to large volumes" are most important for lung toxicity. NTCP analysis with the LKB-model using parameters m = 0.4, D(50) = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D(50) = 20 Gy n = 0.93 with LQ correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling.

  6. Glomeromycota communities survive extreme levels of metal toxicity in an orphan mining site.

    Science.gov (United States)

    Sánchez-Castro, I; Gianinazzi-Pearson, V; Cleyet-Marel, J C; Baudoin, E; van Tuinen, D

    2017-11-15

    Abandoned tailing basins and waste heaps of orphan mining sites are of great concern since extreme metal contamination makes soil improper for any human activity and is a permanent threat for nearby surroundings. Although spontaneous revegetation can occur, the process is slow or unsuccessful and rhizostabilisation strategies to reduce dispersal of contaminated dust represent an option to rehabilitate such sites. This requires selection of plants tolerant to such conditions, and optimization of their fitness and growth. Arbuscular mycorrhizal fungi (AMF) can enhance metal tolerance in moderately polluted soils, but their ability to survive extreme levels of metal contamination has not been reported. This question was addressed in the tailing basin and nearby waste heaps of an orphan mining site in southern France, reaching in the tailing basin exceptionally high contents of zinc (ppm: 97,333 total) and lead (ppm: 31,333 total). In order to contribute to a better understanding of AMF ecology under severe abiotic stress and to identify AMF associated with plants growing under such conditions, that may be considered in future revegetation and rhizostabilisation of highly polluted areas, nine plant species were sampled at different growing seasons and AMF root colonization was determined. Glomeromycota diversity was monitored in mycorrhizal roots by sequencing of the ribosomal LSU. This first survey of AMF in such highly contaminated soils revealed the presence of several AMF ribotypes, belonging mainly to the Glomerales, with some examples from the Paraglomerales and Diversisporales. AMF diversity and root colonization in the tailing basin were lower than in the less-contaminated waste heaps. A Paraglomus species previously identified in a polish mining site was common in roots of different plants. Presence of active AMF in such an environment is an outstanding finding, which should be clearly considered for the design of efficient rhizostabilisation processes

  7. Treatment Challenges and Survival Analysis of Human Epidermal Growth Factor Receptor 2-positive Breast Cancer in Real World.

    Science.gov (United States)

    Adusumilli, Praveen; Konatam, Meher Lakshmi; Gundeti, Sadashivudu; Bala, Stalin; Maddali, Lakshmi Srinivas

    2017-01-01

    Advent of trastuzumab has brought tremendous changes in the survival of human epidermal growth factor receptor 2 (Her2)-positive breast cancer patients. Despite the availability of the drug, it is still out of reach for many patients. There is very limited real world data regarding treatment challenges and survival analysis of these patients. Primary objective is disease-free survival (DFS) and secondary objective is overall survival (OS) and toxicity profile. Statistical analysis is done using GraphPad Prism 7.02. This is a retrospective study of all patients diagnosed with Her2-positive (Her2+) nonmetastatic invasive breast cancer from January 2007 to December 2013. In the period of this study, 885 patients are diagnosed with carcinoma breast, of which 212 are Her2/neu positive (23.9%). Of the 212 patients, only 76 (35.8%) patients received trastuzumab along with chemotherapy. Patients receiving trastuzumab with chemotherapy have longer 5-year DFS compared to those receiving chemotherapy alone, 92% and 52.6%, respectively (P = 0.0001). Five-year OS is 90.5% and 41.7% in those patients who received chemotherapy with and without trastuzumab, respectively (P = 0.0001). Seven patients (9.45%) developed Grade II reversible diastolic dysfunction. Grade II/III peripheral neuropathy due to paclitaxel is the main adverse effect seen in 21 patients. In spite of improvement in DFS and OS with trastuzumab, the number of patient receiving targeted therapy is very low due to financial constraints which need to be addressed to bridge the gap in survival of Her2+ patients.

  8. Intensity-modulated radiotherapy following null-margin resection is associated with improved survival in the treatment of intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Jia, Angela Y; Wu, Jian-Xiong; Zhao, Yu-Ting; Li, Ye-Xiong; Wang, Zhi; Rong, Wei-Qi; Wang, Li-Ming; Jin, Jing; Wang, Shu-Lian; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Wang, Wen-Qing; Liu, Xin-Fan; Yu, Zi-Hao; Wang, Wei-Hu

    2015-04-01

    The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection. Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS). At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy. The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels.

  9. Analysis of trans-2,6-difluoro-4'-(N,N-dimethylamino)stilbene (DFS) in biological samples by liquid chromatography-tandem mass spectrometry: metabolite identification and pharmacokinetics.

    Science.gov (United States)

    Yeo, Samuel Chao Ming; Sviripa, Vitaliy M; Huang, Meng; Kril, Liliia; Watt, David S; Liu, Chunming; Lin, Hai-Shu

    2015-09-01

    The metabolism of a promising antineoplastic agent, trans-2,6-difluoro-4'-(N,N-dimethylamino)stilbene (DFS), was studied in mouse, rat, and human liver microsomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with the multiple reaction monitoring-information-dependent acquisition-enhanced product ion scan (MRM-IDA-EPI) method. Ten putative metabolites were identified and the structures of four metabolites were confirmed using authentic standards. Since trans-2,6-difluoro-4'-(N-methylamino)stilbene (DMDFS, M1) was present in all species as metabolite and displayed in vitro growth inhibition superior to DFS, its pharmacokinetic profiles were examined in Sprague-Dawley rats using DFS as a comparator. A reliable LC-MS/MS multiple reaction monitoring (MRM) method was subsequently developed and validated for the simultaneous quantification of both DFS and DMDFS in rat plasma for this purpose. Upon intravenous administration (4 mg/kg), DFS had a moderate clearance (Cl = 62.7 ± 23.2 mL/min/kg), terminal elimination half-life (t 1/2 λZ  = 299 ± 73 min), and mean transit time (MTT = 123 ± 14 min) with demethylation metabolism accounting for about 10 % of its total clearance. DMDFS possessed an intravenous pharmacokinetic profile similar to DFS. During oral dosing (10 mg/kg) where both DFS and DMDFS were absorbed rapidly, the oral bioavailability of DFS was approximately 2-fold greater than that of DMDFS (DFS: F = 42.1 ± 12.8 %; DMDFS: F = 18.7 ± 3.9 %). Interestingly, the DMDFS exposure after oral dosing of DFS (10 mg/kg) was comparable to that after oral administration of DMDFS (10 mg/kg) alone. As DFS displayed potent anticancer activities and excellent pharmacokinetic profiles, it appears to be a favorable candidate for further pharmaceutical development.

  10. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

    Science.gov (United States)

    Imhof, Anna; Brunner, Philippe; Marincek, Nicolas; Briel, Matthias; Schindler, Christian; Rasch, Helmut; Mäcke, Helmut R; Rochlitz, Christoph; Müller-Brand, Jan; Walter, Martin A

    2011-06-10

    To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.

  11. Single- versus Triple-Drug Chemoembolization for Hepatocellular Carcinoma: Comparing Outcomes by Toxicity, Imaging Response, and Survival.

    Science.gov (United States)

    Mouli, Samdeep K; Hickey, Ryan; Thornburg, Bartley; Sato, Kent T; Desai, Kush; Gabr, Ahmed; Kallini, Joseph R; Niemeri, Halla; Kircher, Sheetal; Mulcahy, Mary F; Benson Iii, Al B; Gupta, Ramona; Salem, Riad; Lewandowski, Robert J

    2016-09-01

    To determine the efficacy of single- versus triple-drug chemoembolization for the treatment of hepatocellular carcinoma, as measured by toxicity, tumor response, time to progression (TTP), and overall survival (OS). A single-center retrospective review was performed on 337 patients who underwent chemoembolization over a 14-year period; 172 patients underwent triple-drug conventional transarterial chemoembolization, and 165 patients underwent single-agent doxorubicin chemoembolization. Imaging characteristics and clinical follow-up after conventional transarterial chemoembolization were evaluated to determine TTP. Imaging response was determined per World Health Organization and European Association for the Study of Liver criteria. OS from time of first chemoembolization was calculated. Median TTP was similar between groups: 7.9 months (95% confidence interval [CI], 7.1-9.4) and 6.8 months (95% CI, 4.6-8.6) for triple- and single-drug regimens, respectively (P > .05). For single-agent conventional transarterial chemoembolization, median OS varied significantly by Barcelona Clinic for Liver Cancer (BCLC) stage: A, 40.8 months; B, 36.4 months; C, 10.9 months (P < .01). Median OS for triple-drug therapy also varied significantly by BCLC: A, 28.9 months; B, 18.1 months; C, 9.0 months (P < .01). Single-drug conventional transarterial chemoembolization demonstrated longer median OS compared with triple-drug therapy (P < .05) for BCLC A/B patients. Single-agent chemoembolization with doxorubicin and ethiodized oil demonstrates acceptable efficacy as measured by TTP and OS. Results compare favorably with traditional triple-drug therapy. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  12. Baseline chronic kidney disease is associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Pfister, Christian; Defortescu, Guillaume; Giwerc, Anthony; Charbit, David; Gouerant, Sophie; Sabourin, Jean-Christophe; Di Fiore, Frédéric

    2015-09-01

    To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m. Patients with GFR less than 60 were more likely to encounter severe (grade 3-4) TT-induced toxicities (79 vs. 32%, Prenal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67-13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.

  13. Toxicity Tests of Whole Sediment Samples Using the Hyallella (H. azteca) Survival and Growth Tests (ASTM E 1283-93)

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — 10-day toxicity tests using Hyalella azteca were conducted with sediment samples collected by the U.S. Fish & Wildlife Service, Bloomington, Indiana facility to...

  14. Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study.

    Science.gov (United States)

    Ballal, Sanjana; Yadav, Madhav P; Damle, Nishikant A; Sahoo, Ranjit K; Bal, Chandrasekhar

    2017-11-01

    The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors. One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-DOTANOC PET/CT scans. Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively. There was no significant difference in the hemoglobin levels after Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/μL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression. Addition of capecitabine therapy with Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.

  15. Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery

    Directory of Open Access Journals (Sweden)

    Sarah E. Sinnett

    2017-06-01

    Full Text Available Intravenous administration of adeno-associated virus serotype 9 (AAV9/hMECP2 has been shown to extend the lifespan of Mecp2−/y mice, but this delivery route induces liver toxicity in wild-type (WT mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM. AAV9/hMECP2 (1 × 1012 viral genomes [vg]; ICM extended Mecp2−/y survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of Mecp2−/y mice. Thus, ICM delivery of this vector is impractical as a treatment for Rett syndrome (RTT. To improve the safety of MeCP2 gene therapy, the gene expression cassette was modified to include more endogenous regulatory elements believed to modulate MeCP2 expression in vivo. In Mecp2−/y mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes. In WT mice, these same doses of the modified vector had no adverse effects on survival or neurological phenotypes. In summary, we identified limitations of the original vector and demonstrated that an improved vector design extends Mecp2−/y survival, without apparent toxicity.

  16. Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Gréen, Henrik; Andersen, Charlotte Brasch

    2011-01-01

    Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindiv......Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia...

  17. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  18. Prediction of physico-chemical properties for PCs/DFs using the UNIFAC model with an alternative approximation for group assignment.

    Science.gov (United States)

    Kuramochi, Hidetoshi; Ohsako, Masahiro; Maeda, Kouji; Sakai, Shinichi

    2002-10-01

    The original-type UNIFAC model was used to predict the environmentally important physico-chemical properties of PCDDs/DFs, such as aqueous solubility, Henry's law constant, and 1-octanol/water partition coefficient, through the UNIFAC-derived infinite dilution activity coefficient. In this application, we suggest an alternative approximation that the aromatic ether group AC-O in PCDD/DF molecules is replaced with the aliphatic ether group CH-O, because the AC-O group is not available in the conventional UNIFAC model. With this approximation, the ability of the UNIFAC model to predict those properties was examined by comparing with experimental data. The UNIFAC model provided comparatively good estimation results. From these results, it is shown that the alternative approximation is useful for the UNIFAC estimation of physico-chemical properties for PCDDs/DFs. Furthermore, the predicted solubilities of 2,3,7,8-T4CDD and O8CDD in organic solvents and the co-solvency effect on solubility of PCDDs in methanol/water mixture indicate that the UNIFAC calculation presented here could well predict the physico-chemical properties of PCDDs/DFs in various solution conditions.

  19. Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome.

    Science.gov (United States)

    Kim, Hani; Darwish, Ilyse; Monroy, Maria-Fernanda; Prockop, Darwin J; Liles, W Conrad; Kain, Kevin C

    2014-01-14

    Toxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS. Effects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 μg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 μg) in HLA-DR4 transgenic mice. Despite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS. Our results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than IL-2, IL-6 and TNF are likely to play

  20. Comparison of efficacy and toxicity of traditional Chinese medicine (TCM herbal mixture LQ and conventional chemotherapy on lung cancer metastasis and survival in mouse models.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available Unlike Western medicine that generally uses purified compounds and aims to target a single molecule or pathway, traditional Chinese medicine (TCM compositions usually comprise multiple herbs and components that are necessary for efficacy. Despite the very long-time and wide-spread use of TCM, there are very few direct comparisons of TCM and standard cytotoxic chemotherapy. In the present report, we compared the efficacy of the TCM herbal mixture LQ against lung cancer in mouse models with doxorubicin (DOX and cyclophosphamide (CTX. LQ inhibited tumor size and weight measured directly as well as by fluorescent-protein imaging in subcutaneous, orthotopic, spontaneous experimental metastasis and angiogenesis mouse models of lung cancer. LQ was efficacious against primary and metastatic lung cancer without weight loss and organ toxicity. In contrast, CTX and DOX, although efficacious in the lung cancer models caused significant weight loss, and organ toxicity. LQ also had anti-angiogenic activity as observed in lung tumors growing in nestin-driven green fluorescent protein (ND-GFP transgenic nude mice, which selectively express GFP in nascent blood vessels. Survival of tumor-bearing mice was also prolonged by LQ, comparable to DOX. In vitro, lung cancer cells were killed by LQ as observed by time-lapse imaging, comparable to cisplatinum. LQ was more potent to induce cell death on cancer cell lines than normal cell lines unlike cytotoxic chemotherapy. The results indicate that LQ has non-toxic efficacy against metastatic lung cancer.

  1. A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Sayan, Mutlay; Nelson, Carl; Gagne, Havaleh; Rubin, Deborah; Heimann, Ruth [Dept. of Radiation Oncology, University of Vermont Medical Center, Burlington (United States); Wilson, Karen [University of Vermont Cancer Center, Burlington (United States)

    2017-03-15

    Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

  2. Influence of pH on the toxicity and survival of total cells and spores of Bacillus thuringiensis.

    Science.gov (United States)

    Dias, S C; Sagardoy, M A

    1998-01-01

    B. thuringiensis (Bt) is one of the most important microorganism among those studied because of their entomopathogenic potential against insect plagues and vectors. In this work, the pathogenicity and survival of total cells and spores of three autochthonous strains of B. thuringiensis isolated from Argentine soils (A61, A27 and A68) and the commercial strain HD-1 were studied at different ion hidrogen concentrations (pH = 4.4; 5.4; 7.4; 8.4; 9.4 and 10.4) under laboratory conditions. The greatest antimicrobial effect on the number of spores and total cells was observed at pH 4.4 with a great decrease after 72 hours' growth. Comparing the survival percentage of total cells and spores; pH 5.4 was the one which allowed the higher relative tolerance (survival) among the studied strains. No decrease in pathogenicity was observed in the investigated serotypes at different pHs in bioassays against Cydia pomonella. Two soil strains of Bt (A61/A27) and the Bt (HD-1) of commercial origin caused the highest mortality of the target insect. The sotto serotype (A68), however, did not produce this effect.

  3. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study

    DEFF Research Database (Denmark)

    Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M

    2011-01-01

    Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged...

  4. Extension of the biotic ligand model of acute toxicity to a physiologically-based model of the survival time of rainbow trout (Oncorhynchus mykiss) exposed to silver.

    Science.gov (United States)

    Paquin, Paul R; Zoltay, Viktoria; Winfield, Richard P; Wu, Kuen Benjamin; Mathew, Rooni; Santore, Robert C; Di Toro, Dominic M

    2002-09-01

    Chemical speciation controls the bioavailability and toxicity of metals in aquatic systems and regulatory agencies are recognizing this as they develop updated water quality criteria (WQC) for metals. The factors that affect bioavailability may be quantitatively evaluated with the biotic ligand model (BLM). Within the context of the BLM framework, the 'biotic ligand' is the site where metal binding results in the manifestation of a toxic effect. While the BLM does account for the speciation and complexation of dissolved metal in solution, and competition among the free metal ion and other cations for binding sites at the biotic ligand, it does not explicitly consider either the physiological effects of metals on aquatic organisms, or the direct effect of water chemistry parameters such as pH, Ca(2+)and Na(+) on the physiological state of the organism. Here, a physiologically-based model of survival time is described. In addition to incorporating the effects of water chemistry on metal availability to the organism, via the BLM, it also considers the interaction of water chemistry on the physiological condition of the organism, independent of its effect on metal availability. At the same time it explicitly considers the degree of interaction of these factors with the organism and how this affects the rate at which cumulative damage occurs. An example application of the model to toxicity data for rainbow trout exposed to silver is presented to illustrate how this framework may be used to predict survival time for alternative exposure durations. The sodium balance model (SBM) that is described herein, a specific application of a more generic ion balance model (IBM) framework, adds a new physiological dimension to the previously developed BLM. As such it also necessarily adds another layer of complexity to this already useful predictive framework. While the demonstrated capability of the SBM to predict effects in relation to exposure duration is a useful feature of this

  5. 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

  6. Bcl-2 confers survival in cisplatin treated cervical cancer cells: circumventing cisplatin dose-dependent toxicity and resistance.

    Science.gov (United States)

    Leisching, Gina; Loos, Benjamin; Botha, Matthys; Engelbrecht, Anna-Mart

    2015-10-16

    Cisplatin is the main chemotherapeutic drug for the treatment of cervical cancers, however resistance to cisplatin is increasingly common and therefore has limited the efficacy and use of this drug in the clinic. Dose-dependent toxicity poses an additional challenge since patients suffer long-term and often permanent side-effects after treatment. Bcl-2 up-regulation has been implicated in the resistance to cisplatin in a variety of cancer cell lines, however its role in cervical cancer is confounding. A low, non-cytotoxic concentration of cisplatin was used in the treatment of HeLa and CaSki cells. Bcl-2 expression was determined through Western blotting and immunocytochemistry before and after treatment with cisplatin. To assess the reliance of the cervical cancer cells on Bcl-2 in the presence of cisplatin, Bcl-2 knock-down was achieved through RNA interference, where after apoptosis was assessed through PARP cleavage (Western blotting), Caspase activity (Caspase-Glo(©)) and PI inclusion analysis (Flow cytometry). Finally, pre-malignant and malignant cervical tissue was analysed for the presence of Bcl-2 through Western blotting and immunofluorescence. Cervical cancer cells upregulate Bcl-2 when treated with a non-cytotoxic concentration of cisplatin, which when silenced, effectively enhanced cisplatin sensitivity, and therefore significantly induced apoptosis. Analysis of the expression profile of Bcl-2 in cervical tissue revealed its up-regulation in cervical carcinoma, which agrees with results obtained from the in vitro data. Our data strongly suggest that utilising a lower dose of cisplatin is feasible when combined with Bcl-2 silencing as an adjuvant treatment, thereby improving both the dose-dependent toxicity, as well as cervical cancer resistance.

  7. Dietary exposure of three passerine species to PCDD/DFs from the Chippewa, Tittabawassee, and Saginaw River floodplains, Midland, Michigan, USA.

    Science.gov (United States)

    Fredricks, Timothy B; Giesy, John P; Coefield, Sarah J; Seston, Rita M; Haswell, Melissa M; Tazelaar, Dustin L; Bradley, Patrick W; Moore, Jeremy N; Roark, Shaun A; Zwiernik, Matthew J

    2011-01-01

    Dietary exposure of house wrens (Troglodytes aedon), tree swallows (Tachycineta bicolor), and eastern bluebirds (Sialia sialis) to polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) near Midland, Michigan (USA) was evaluated based on site-specific data, including concentrations of residues in bolus samples and individual invertebrate orders and dietary compositions by study species. Site-specific dietary compositions for the three species were similar to those reported in the literature, but differed in their relative proportions of some dietary items. Oligocheata (non-depurated) and Brachycera (Diptera) contained the greatest average concentrations of ΣPCDD/DFs of the major site-specific dietary items collected via food web-based sampling. Average ingestion values of ΣPCDD/DFs from site-specific bolus-based and food web-based dietary concentrations for nestlings at study areas (SAs) were 6- to 20-fold and 2- to 9-fold greater than at proximally located reference areas (RAs), respectively. Average ingestion values of total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ(WHO - Avian)) from site-specific bolus-based and food web-based dietary concentrations for nestlings at SAs were 31- to 121-fold and 9- to 64-fold greater than at proximally located RAs, respectively. Estimates of ΣPCDD/DFs and TEQ(WHO - Avian) tissue concentrations based on nestling dietary exposures were greater than those measured. Plausible explanations include nestling metabolism of 2,3,7,8-tetrachlorodibenzofuran and assimilation rates of less than the 70% assumed to occur over the nestling growth period. Profiles of the relative concentrations of individual PCDD/DF congeners in samples of invertebrates and bolus at SAs on the Tittabawassee River downstream of the source of contamination were dominated by 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (22% to 44%) and 2,3,7,8-tetrachlorodibenzofuran (18% to 50%).

  8. Acute toxicity of cadmium in Anisops sardeus (Heteroptera:Notonectidae): Effects on adult and nymphal survival and swimming behavior.

    Science.gov (United States)

    Memtombi Chanu, Chongtham; Gupta, Susmita; Gupta, Abhik

    2017-11-01

    Adult female and male, and final instar nymph of Anisops sardeus (Heteroptera: Notonectidae) were exposed to graded concentrations of cadmium in 96h static-with-renewal acute toxicity tests, which were conducted in dry (March) and wet (May-June) seasons. The 96h LC50 values for instar V nymph, adult female and male were found to be 0.9, 0.59 and 0.51mgL-1 Cd, respectively, in wet season, while these were 26.7 and 20.2mgL-1 Cd for adult female and male, respectively, in dry season. Adult males were most sensitive to Cd, followed by females in both seasons, while highest tolerance in wet season was observed in instar V nymph. There was a steep decline in LC50 values from 24 to 96h in wet season. Besides mortality at higher concentrations of Cd, sublethal effects in terms of reduced 'velocity magnitude' (swimming speed) and mostly increased 'rotation angle' (turning angle) could be discerned at concentrations as low as 0.03mgL-1. The swimming pattern of Cd-exposed nymph and adults were also affected. Based on the bioaccumulation factor (BAF) values, A. sardeus could be designated as a macroconcentrator of Cd (BAF > 2), with highest Cd accumulation in instar V nymph, followed by that in female, and with lowest Cd accumulation in male. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Assessment of a simple, non-toxic Alamar blue cell survival assay to monitor tomato cell viability.

    Science.gov (United States)

    Byth, H A; Mchunu, B I; Dubery, I A; Bornman, L

    2001-01-01

    The Alamar Blue (AB) assay, which incorporates a medox indicator that changes colour or fluorescence in response to metabolic activity, is commonly used to assess quantitatively the viability and/or proliferation of mammalian cells and micro-organisms. In this study the AB assay was adapted for the determination of the viability of plant cells. Cell suspension cultures of tomato, Lycopersicon esculentum, L., with differing viabilities, served as the experimental model for a comparison of the AB assay with the conventional 2,3,5-triphenyltetrazolium chloride (TTC) viability assay. The AB assay showed a sigmoidal relationship between cell viability and AB reduction (as quantified by spectrofluorometry or spectrophotometry), which was similar to that obtained using the TTC assay. Both assays detected a significant reduction in cell viability after 48 h exposure to virulent Ralstonia solanacearum (biovar III), while the TTC assay, in addition, revealed cell proliferation in control cells from 24 to 72 h. The TTC assay detected cell proliferation over a wider range of cell densities, while the AB assay was more rapid and versatile whilst being non-toxic and thus allowing subsequent cell analysis.

  10. Survival and Toxicity After Cisplatin Plus Etoposide Versus Carboplatin Plus Etoposide for Extensive-Stage Small-Cell Lung Cancer in Elderly Patients.

    Science.gov (United States)

    Hatfield, Laura A; Huskamp, Haiden A; Lamont, Elizabeth B

    2016-07-01

    Elderly patients with cancer are under-represented in clinical trials and risk greater toxicity from chemotherapy. These patients and their physicians need better evidence to decide among guideline-recommended regimens. We test whether patients with extensive-stage small-cell lung cancer (ES SCLC) have noninferior survival and less hospital-based health care after carboplatin/etoposide compared with cisplatin/etoposide. We analyzed SEER-Medicare data for beneficiaries with ES SCLC diagnosed at age 67 years and older between 1995 and 2009. Among patients treated with first-line chemotherapy in the ambulatory setting, 831 received cisplatin/etoposide and 2,846 received carboplatin/etoposide. Propensity score matching (2:1 ratio) yielded 778 cisplatin/etoposide and 1,502 carboplatin/etoposide patients. Survival was nearly identical in the two groups: 35.7 weeks for cisplatin/etoposide and 35.9 weeks for carboplatin/etoposide. The hazard ratio of 1 (95% CI, 0.91 to 1.09) excluded our prespecified threshold, indicating noninferiority. Mortality at 6 months was indistinguishable: 35% for cisplatin/etoposide and 34% for carboplatin/etoposide. After carboplatin/etoposide, patients were less likely to be admitted to a hospital (80% v 86%, P < .001) and had fewer hospitalizations (median 1 v 2, odds ratio 0.76, 95% CI, 0.65 to 0.9), ED visits (median 1 v 2, odds ratio 0.82, 95% CI, 0.7 to 0.96), and ICU stays (median 0 v 0, odds ratio 0.82, 95% CI, 0.69 to 0.99). First-line carboplatin/etoposide is associated with similar survival and less subsequent hospital-based health care use than cisplatin/etoposide among elderly patients with ES SCLC treated in ambulatory settings. Copyright © 2016 by American Society of Clinical Oncology.

  11. Salvage surgery in recurrent head and neck squamous cell carcinoma: Oncologic outcome and predictors of disease free survival

    OpenAIRE

    Hamoir, Marc; Holvoet, Emma; Ambroise, Jérôme; Lengelé, Benoît; Schmitz, Sandra

    2017-01-01

    Objective Salvage surgery in recurrent SCCHN is associated with poor outcomes. This study aimed to better identify suitable surgical candidates and those at high risk of new recurrence. Materials and methods Single-center retrospective analysis of 109 patients undergoing salvage surgery for recurrent SCCHN. Univariate and multivariate analyses were used to identify prognostic factors affecting disease-free survival (DFS). Results The following factors showed a significant impact on DFS: Disea...

  12. Postoperative radiotherapy of patients with thymic epithelial tumors (TET). A retrospective analysis of outcome and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Haefner, Matthias Felix; Roeder, Falk; Sterzing, Florian; Krug, David; Koerber, Stefan A.; Debus, Juergen [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (dkfz), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Kappes, Jutta [University of Heidelberg, Department of Pneumology, Thoraxklinik Heidelberg, Heidelberg (Germany); Hoffmann, Hans [University of Heidelberg, Department of Thoracic Surgery, Thoraxklinik Heidelberg, Heidelberg (Germany); Slynko, Alla [German Cancer Research Center (dkfz), Biostatistics, Heidelberg (Germany); Bischof, Marc [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); SLK-Kliniken Heilbronn, Department of Radiation Oncology, Heilbronn (Germany)

    2014-08-26

    The purpose of this study was to evaluate postoperative radiotherapy regarding outcome and toxicity in patients with thymic epithelial tumors (TET) after surgery. We retrospectively analyzed medical records of 41 patients with TET treated with postoperative radiotherapy at our institution between 1995 and 2012. The impact of prognostic factors (e.g., Masaoka stage, histological subtype) was investigated and radiation-related toxicity was assessed. Median age was 59.8 years and median follow-up was 61 months. In 24.4 %, TETs were associated with paraneoplastic syndromes. The 5-year overall survival (OS) was 89.5 % and the 5-year disease-free survival (DFS) was 88.9 %. Masaoka stage had a significant impact on OS (p = 0.007). Locally limited stages I + II had a 5-year OS of 100 % compared to 80 % for stage III and 66.7 % for stage IV. The 5-year DFS was excellent with 100 % for both WHO groups A/AB/B1 and B2, respectively, and significantly (p = 0.005) differed from B3/C-staged patients with a 5-year DFS of 63.6 %. Resection status, paraneoplastic association, radiation dose, or tumor size did not influence survival. There were no high-grade acute or late side effects caused by radiotherapy. Masaoka stage has a significant impact on OS as WHO type has on DFS in patients with TETs after surgery and adjuvant irradiation. Postoperative radiotherapy with doses around 50 Gy is safe and not likely to cause high-grade toxicity. Further prospective trials are necessary to separate patient subgroups that benefit from radiotherapy from those that do not. (orig.) [German] Die vorliegende Studie hatte zum Ziel, die postoperative Radiotherapie von Patienten nach Resektion einer Thymusneoplasie epithelialen Ursprungs (Thymom, Thymuskarzinom, ''thymic epithelial tumors'', TET) hinsichtlich prognostischer Relevanz und Nebenwirkungsprofil zu beurteilen. Wir analysierten retrospektiv die medizinischen Krankenakten von 41 Patienten mit TET, die zwischen 1995 und

  13. Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer.

    Science.gov (United States)

    Xie, Wanling; Regan, Meredith M; Buyse, Marc; Halabi, Susan; Kantoff, Philip W; Sartor, Oliver; Soule, Howard; Clarke, Noel W; Collette, Laurence; Dignam, James J; Fizazi, Karim; Paruleker, Wendy R; Sandler, Howard M; Sydes, Matthew R; Tombal, Bertrand; Williams, Scott G; Sweeney, Christopher J

    2017-09-20

    Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Results Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall's τ correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R(2) was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects-measured by log hazard ratios-for the surrogates and OS were well correlated ( R(2), 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). Conclusion MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.

  14. Number of negative lymph nodes is associated with disease-free survival in patients with breast cancer.

    Science.gov (United States)

    Wu, San-Gang; Sun, Jia-Yuan; Zhou, Juan; Li, Feng-Yan; Lin, Qin; Lin, Huan-Xin; Guan, Xun-Xing; He, Zhen-Yu

    2015-02-07

    The aim of this study was to evaluate the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients after mastectomy. 2,455 breast cancer patients who received a mastectomy between January 1998 and December 2007 were retrospectively reviewed. The prognostic impact of the number of NLNs with respect to disease-free survival (DFS) was analyzed. The median follow-up time was 62.0 months, and the 5-year and 10-year DFS was 87.1% and 74.3%, respectively. The DFS of patients with >10 NLNs was significantly higher than that of patents with ≤10 NLNs, and the 5-year DFS rates were 87.5% and 69.5%, respectively (P patients with a higher number of NLNs had a better DFS (HR = 0.977, 95% CI: 0.958-0.997, P = 0.022). Subgroup analysis showed that the NLN count had a prognostic value in patients at different pT stages and pN positive patients (log-rank P patients (log-rank P = 0.684). The number of NLNs is an independent prognostic factor of DFS in breast cancer patients after mastectomy, and patients with a higher number of NLNs have a better DFS.

  15. Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

    Directory of Open Access Journals (Sweden)

    Nikol Snoeren

    Full Text Available BACKGROUND AND OBJECTIVES: This study was designed to identify and validate gene signatures that can predict disease free survival (DFS in patients undergoing a radical resection for their colorectal liver metastases (CRLM. METHODS: Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France and the University Medical Center Utrecht (The Netherlands. Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort. RESULT: No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort. CONCLUSIONS: No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.

  16. Volumetric intensity-modulated arc therapy vs. 3-dimensional conformal radiotherapy for primary chemoradiotherapy of anal carcinoma. Effects on treatment-related side effects and survival

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Hanne Elisabeth; Droege, Leif Hendrik; Hennies, Steffen; Herrmann, Markus Karl; Wolff, Hendrik Andreas [University Medical Center Goettingen, Dept. of Radiotherapy and Radiooncology, Goettingen (Germany); Gaedcke, Jochen [University Medical Center Goettingen, Dept. of General Surgery, Goettingen (Germany)

    2015-11-15

    Primary chemoradiotherapy (CRT) is the standard treatment for locally advanced anal carcinoma. This study compared volumetric intensity-modulated arc therapy (VMAT) to 3-dimensional conformal radiotherapy (3DCRT) in terms of treatment-related side effects and survival. From 1992-2014, 103 consecutive patients with anal carcinoma UICC stage I-III were treated. Concomitant CRT consisted of whole pelvic irradiation, including the iliac and inguinal lymph nodes, with 50.4 Gy (1.8 Gy per fractions) by VMAT (n = 17) or 3DCRT (n = 86) as well as two cycles of 5-fluorouracil and mitomycin C. Acute organ and hematological toxicity were assessed according to the Common Terminology Criteria (CTC) for Adverse Events version 3.0. Side effects ≥ grade 3 were scored as high-grade toxicity. High-grade acute organ toxicity CTC ≥ 3 (P < 0.05), especially proctitis (P = 0.03), was significantly reduced in VMAT patients. The 2-year locoregional control (LRC) and disease-free survival (DFS) were both 100 % for VMAT patients compared with 80 and 73 % for 3DCRT patients. VMAT was shown to be a feasible technique, achieving significantly lower rates of acute organ toxicity and promising results for LRC and DFS. Future investigations will aim at assessing the advantages of VMAT with respect to late toxicity and survival after a prolonged follow-up time. (orig.) [German] Die primaere Radiochemotherapie (RCT) gilt als Standardtherapie fuer lokal fortgeschrittene Analkarzinome. In dieser Studie wurde die volumetrisch modulierte Rotationstherapie (''volumetric intensity-modulated arc therapy'', VMAT) mit der klassischen dreidimensionalen konformalen Radiotherapie (3DCRT) hinsichtlich therapieassoziierter Nebenwirkungen und Ueberleben verglichen. Von 1992-2014 wurden 103 aufeinanderfolgende Patienten mit einem Analkarzinom im UICC-Stadium I-III behandelt. Die kombinierte RCT bestand aus der Bestrahlung des gesamten Beckens inklusive der iliakalen und der inguinalen

  17. Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis.

    Science.gov (United States)

    Kim, Yoonseok; Jae, Eunae; Yoon, Myunghee

    2015-06-01

    Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer. We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression. There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73). Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.

  18. Conditional Survival and the Choice of Conditioning Set for Patients With Colon Cancer: An Analysis of NSABP Trials C-03 Through C-07

    Science.gov (United States)

    Zamboni, Beth A.; Yothers, Greg; Choi, Mehee; Fuller, Clifton D.; Dignam, James J.; Raich, Peter C.; Thomas, Charles R.; O'Connell, Michael J.; Wolmark, Norman; Wang, Samuel J.

    2010-01-01

    Purpose Colon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates over time. Conditional survival (probability of surviving y additional years given they have survived x years [CS or OS|OS]) is an alternative measure that accounts for elapsed time since diagnosis, providing more relevant prognostic information. We extend the concept of CS to condition on the set of patients alive, recurrence-free, and second primary cancer-free (disease-free survival [OS|DFS]). Patients and Methods Using data from National Surgical Adjuvant Breast and Bowel Project trials C-03 through C-07, 5-year OS|DFS was calculated on patients who were disease free up to 5 years after diagnosis, stratified by age, stage, nodal status, and performance status (PS). Results For stage II, OS|DFS improved from 87% to 92% at 5 years. For stage III, OS|DFS improved from 69% to 88%. Patients younger than 50 years showed OS|DFS improvement from 79% to 95%; those older than 70 years showed no sustained increase in OS|DFS. Node-negative patients with ≥ 12 nodes resected showed little change (89% to 94%); those with more than four positive nodes showed an improvement (57% to 86%). Patients with a PS of 0 or 1 demonstrated a small improvement; those with a PS of 2 did not (64% to 58%). Conclusion Prognosis improves over time for almost all groups of patients with colon cancer, especially those with positive nodes. OS|DFS is a more relevant measure of prognosis for those who have already survived disease free a period of time after diagnosis. PMID:20406942

  19. Effect of intrauterine infusion of an organic-certified product on uterine health, survival, and fertility of dairy cows with toxic puerperal metritis.

    Science.gov (United States)

    Pinedo, P J; Velez, J S; Bothe, H; Merchan, D; Piñeiro, J M; Risco, C A

    2015-05-01

    The objective was to evaluate the effect of intrauterine infusion of an organic certified product (Optimum UterFlush, Van Beek Natural Science, Orange City, IA) on uterine health, survival, and fertility of cows affected with toxic puerperal metritis (TPM) in an organic dairy farm. Cows with TPM were defined as having an abnormally enlarged uterus and a fetid watery red-brown vaginal discharge, associated with systemic illness and fever (rectal temperature ≥39.5°C), within 12 d postpartum. Cows diagnosed with TPM (n=220; study d 0) were blocked by parity (1 and ≥2) and randomly assigned into 1 of 2 intrauterine treatments applied every other day for a total of 3 applications: (1) control (CON)=200mL of povidone iodine diluted in 2L of distilled water (n=113); (2) Optimum UterFlush (UF)=3.75mL diluted in 117mL of distilled water (n=107). All enrolled cows received hypertonic saline solution (500mL 7.2% i.v.), dextrose (500mL 50% i.v.), and oral aspirin (5 boluses/d). Outcome variables for treatment efficacy included fever and presence of fetid vaginal discharge at study d 6 and 14, survival at study d 6 and 14 and at 30 and 100 DIM, and reproductive performance. Control variables were parity, BCS at enrollment, calving season, and milk yield. Occurrence of fever at d 6 and 14 was not different between the 2 treatment groups. Presence of fetid vaginal discharge at d 6 and 14 was lower in cows treated with UF compared with cows in the CON group (10.7 vs. 28% and 1.1 vs. 9.1%). The odds (95% confidence interval) for survival and remaining in the farm at study d 6 and 14 and at 30 and 100 DIM for cows in the UF treatment were 4.67 (1.38-15.8), 2.77 (1.25-6.10), 3.13 (1.22-8.02), and 2.82 (1.38-5.71) times the odds of cows in the CON group, respectively. The odds of AI until 150 DIM and the interval from calving to first AI were not different between the 2 treatments. However, pregnancy was affected by treatment; the odds (95% confidence interval) of pregnancy at

  20. Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  1. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    Directory of Open Access Journals (Sweden)

    Concetta Laliscia

    2016-12-01

    Full Text Available Purpose : The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR vaginal brachytherapy (BT. Material and methods : Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week. Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results : According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9% and in stage IB (57.9%. Thirty-three patients (26.2% received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS and five-year overall survival (OS were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3% and dyspareunia (7 patients, 5.5%. Two patients (1.6% had more than one toxicity. Late toxicity occurred in 20 patients (15.9%. Grade 1-2 late toxicities were fibrosis (14 patients, 11.1% and telangiectasias (7 patients, 5.5%. Six patients (4.8% had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions : These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.

  2. Never smokers with resected lung cancer: different demographics, similar survival.

    Science.gov (United States)

    Stiles, Brendon M; Rahouma, Mohamed; Hussein, Mohamed Kamel; Nasar, Abu; Nguyen, Andrew B; Harrison, Sebron; Lee, Benjamin; Port, Jeffrey L; Altorki, Nasser K

    2017-11-22

    We sought to examine changes over time in the proportion of never smokers among surgical lung cancer patients and to determine whether smoking history affected survival. We performed a retrospective review of a prospective database. Among never smokers and smokers, demographic and pathological data were compared. Disease-free survival (DFS) and cancer-specific survival (CSS) were analysed. Propensity matching was performed for further comparison of survival in a matched cohort. Among 3232 patients, we identified 718 never smokers (22%), 993 smokers with never smokers increased over time, comprising 26.6% of the cohort after 2007 compared with 16.1% prior thereto (P ≤ 0.001). Never smokers were younger, more likely to be women and Asian, more frequently had adenocarcinoma and lower lobe tumours and were more likely to have pStage I disease. In pStage-matched cohorts, there were no differences in DFS or CSS. Similarly, in propensity-matched groups (498 patients each), there was no difference in 5-year DFS (66% vs 67%, P = 0.661) or in CSS (84% vs 81%, P = 0.350). On univariate analysis of the matched cohort, never smoking status had no effect on DFS (hazard ratio 1.05, P = 0.661) or CSS (hazard ratio 1.16, P = 0.350). The proportion of never smokers undergoing resections for lung cancer is increasing. Never smokers have distinct demographic patterns and tend to be younger women with adenocarcinoma. Despite these differences, stage and propensity-matched never smokers have the same survival as smokers and remain at equal risk for recurrence and death.

  3. S-100B Concentrations Predict Disease-Free Survival in Stage III Melanoma Patients

    NARCIS (Netherlands)

    Kruijff, S.; Bastiaannet, E.; Kobold, A. C. Muller; van Ginkel, R. J.; Suurmeijer, A. J. H.; Hoekstra, H. J.

    2009-01-01

    Elevation of the tumor marker S-100B in melanoma patients is a highly specific indicator of recurrence. The role of S-100B in disease-free survival (DFS) was evaluated in stage III melanoma patients (staged with fluorodeoxyglucose positron emission tomography [FDG-PET] and computed tomography [CT])

  4. Bisphosphonates in the adjuvant setting of breast cancer therapy--effect on survival: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Irit Ben-Aharon

    Full Text Available The role of bisphosphonates (BP in early breast cancer (BC has been considered controversial. We performed a meta-analysis of all randomized controlled trials (RCTs that appraised the effects of BP on survival in early BC.RCTs were identified by searching the Cochrane Library, MEDLINE databases and conference proceedings. Hazard ratios (HRs of overall survival (OS, disease-free survival (DFS and relative risks of adverse events were estimated and pooled.Thirteen trials met the inclusion criteria, evaluating a total of 15,762 patients. Meta-analysis of ten trials which reported OS revealed no statistically significant benefit in OS for BP (HR 0.89, 95% CI = 0.79 to 1.01. Meta-analysis of nine trials which reported the DFS revealed no benefit in DFS (HR 0.95 (0.81-1.12. Meta-analysis upon menopausal status showed a statistically significant better DFS in the BP-treated patients (HR 0.81(0.69-0.95. In meta-regression, chemotherapy was negatively associated with HR of survival.Our meta-analysis indicates a positive effect for adjuvant BP on survival only in postmenopausal patients. Meta-regression demonstrated a negative association between chemotherapy use BP effect on survival. Further large scale RCTs are warranted to unravel the specific subgroups that would benefit from the addition of BP in the adjuvant setting.

  5. Complying with the European Clinical Trials directive while surviving the administrative pressure - an alternative approach to toxicity registration in a cancer trial.

    Science.gov (United States)

    Frandsen, Thomas Leth; Heyman, Mats; Abrahamsson, Jonas; Vettenranta, Kim; Åsberg, Ann; Vaitkeviciene, Goda; Pruunsild, Kaie; Toft, Nina; Birgens, Henrik; Hallböök, Helena; Quist-Paulsen, Petter; Griškevičius, Laimonas; Helt, Louise; Hansen, Birgitte Vilsbøll; Schmiegelow, Kjeld

    2014-01-01

    The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity registration for patients treated according to the Nordic/Baltic acute lymphoblastic leukaemia protocol, NOPHO ALL 2008, for children and young adults, including three randomisations. We used a risk-assessment based approach, avoiding reporting of expected adverse events and instead concentrating on 20 well-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration was excellent with 98.9% of all patients being registered within 5weeks from the requested quarterly registration. Currently, four toxicities (thrombosis, fungal infections, pancreatitis and allergic reactions) have been chosen for further detailed exploration due to the cumulative fraction of patients with positive registrations exceeding 5%. This toxicity registration offers real-time toxicity profiles of the total study cohort and provides early warnings of specific toxicities that require further investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

    2014-11-15

    Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

  7. Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia; Skliarenko, Julia; Craig, Tim [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brierley, James; Wong, Rebecca; Dinniwell, Robert; Bayley, Andrew J.; Dawson, Laura A.; Ringash, Jolie [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Krzyzanowska, Monika K.; Moore, Malcolm J.; Chen, Eric X. [Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Easson, Alexandra M. [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra; Cho, Charles [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John, E-mail: John.Kim@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-11-01

    Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were

  8. Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: results from the OMEGA study of the Dutch breast cancer trialists' group.

    Science.gov (United States)

    Hamaker, M E; Seynaeve, C; Wymenga, A N M; van Tinteren, H; Nortier, J W R; Maartense, E; de Graaf, H; de Jongh, F E; Braun, J J; Los, M; Schrama, J G; van Leeuwen-Stok, A E; de Groot, S M; Smorenburg, C H

    2014-02-01

    To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy. MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index. Frailty on CGA was defined as one or more of the following: IADL ≤ 13, MMSE ≤ 23, GDS ≥ 5, BMI ≤ 20, ≥5 medications or Charlson ≥2. The cut-off for frailty on the GFI was ≥4. Of the randomized 78 patients (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52 (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related toxicity was experienced by 19% of patients without geriatric conditions compared to 56% of patients with two geriatric conditions and 80% of those with three or more (p = 0.002). Polypharmacy was the only individual factor significantly associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a specificity of 76% for frailty on CGA, and was not significantly associated with survival or toxicity. In this study of elderly patients with MBC, the number of geriatric conditions correlated with grade 3-4 chemotherapy-related toxicity. Therefore, in elderly patients for whom chemotherapy is being considered, a CGA could be a useful addition to the decision-making process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor-positive breast cancers.

    Science.gov (United States)

    Krishnamurti, Uma; Wetherilt, Ceyda Sonmez; Yang, Jing; Peng, Limin; Li, Xiaoxian

    2017-06-01

    Correlation between tumor-infiltrating lymphocytes (TILs) and complete pathological response (pCR) in breast cancers in neoadjuvant settings have been reported. In this study, we analyzed the association between TILs and diagnostic and prognostic parameters in estrogen receptor-positive (ER+) and triple-negative breast cancer (TNBC) without neoadjuvant treatments. Three hundred forty-four (344) patients who underwent mastectomy for breast cancer (187 ER+ and 157 TNBC) without neoadjuvant treatments were evaluated. Percentage of overall and peripheral TILs were correlated with lymphovascular invasion (LVI), Nottingham histologic grade (NHG, 1/2 versus 3), stage, lymph node status (LN), overall survival (OS), and disease-free survival (DFS). In TNBC, both peripheral and overall TILs were significantly associated with NHG 3 (PP=.0354) and DFS (HR: 0.95; 95% CI: 0.91-1.00; P=.0314) in univariate and multivariate analysis. In ER+ breast cancer, only peripheral TILs were associated with NHG 3 (P=.018) but not with OS or DFS (both P>.05). In ER+ breast cancer, there was a negative association between Oncotype DX recurrence score and both overall (P=.0007) and peripheral TILs (P=.0119). In conclusion, peripheral but not overall TILs correlate with better OS and DFS in TNBC, indicating the location of TILs may be important in TNBC. The negative association between TILs and Oncotype DX score in ER+ may indicate the possible prognostic value of TILs in ER+ breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Survival Analysis in Patients with Non- metastatic Squamous Cell Carcinoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Ahmed M. Abdel-Rahim

    2011-04-01

    Full Text Available Background: We conducted a retrospective analysis to evaluate overall survival(OAS and disease free survival (DFS rates in patients with squamous cell carcinoma of the urinary bladder according to different prognostic factors. Methods: This retrospective study analyzed the medical records of patients with non-metastatic squamous cell carcinoma of the urinary bladder. All men underwent radical cystectomy and women underwent anterior pelvic exentration. Most patients had postoperative radiation therapy. The log-rank test examined differences in OASand DFS rates. Results: The medical records of 106 patients were analyzed. The median follow-up from the date of enrollment was 30 months and ranged from 2 to 73 months. For the entire group, three-year OAS rates were 46.9% and DFS rates were 44%. For patients with P2 (tumor invasion into the muscularis propria the three-year OAS rate was 53%, for P3 (tumor invasion into perivesical fat it was 45% and 9% for P4 (tumor invasion into adjacent organs, pelvic wall or abdominal wall The OAS rate was statistically significant in favor of P2 disease (P=0.0041. The three-year DFS rate was 50% for P2, 45% for P3 and 9% for P4 disease (P=0.0125. Administration of post-operative radiotherapy did not result in statistically significant improvement in three-year OASand DFS rates. Conclusion: Survival rates were statistically significant and higher in patients with P2 and P3 disease compared to P4 disease. Adjuvant radiotherapy did not result in statistically significant survival improvement.

  11. Duration of adjuvant trastuzumab in HER2 positive breast cancer: Overall and disease free survival results from meta-analyses of randomized controlled trials.

    Science.gov (United States)

    Gyawali, Bishal; Niraula, Saroj

    2017-11-01

    One year of trastuzumab, chosen empirically, improves survival of women with early-stage, HER2-positive breast cancer but also adds substantially to cost, toxicity, and inconvenience. Longer treatment does not improve outcomes, but potentiates toxicities. Medline, Embase, and major conference proceedings were searched systematically in June 2017 to identify Randomized Controlled Trials (RCTs) comparing one year versus shorter durations of trastuzumab in adjuvant treatment of breast cancer. Reported Hazard-Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds-Ratio for cardiac events, with respective 95% Confidence Intervals (CI) from each study was weighted using generic inverse-variance, and pooled in a meta-analysis. Inter-study heterogeneity and sub-group difference (based on hormone-receptors and node-positivity) were assessed using I 2 , and chi 2 statistics, respectively. Four studies (n=7614) satisfied inclusion criteria. Individual RCTs had diverse pre-specified upper-limits of 95% CI for declaring non-inferiority (range: <1.15 to <1.53). Pooled results demonstrated significant improvements in OS (HR 1.28, p=0.04), and DFS (HR 1.24, p=0.005) with 1year of trastuzumab compared to shorter durations. Absence of multiplicity argument allowed for declaring superiority of 1year of trastuzumab based on our results despite non-inferiority designs of individual trials. No influence on overall effect by duration of trastuzumab in experimental arm (9weeks versus 6months) was noted. No statistical interaction by hormone-receptor status and node-positivity on overall results was noticed [p(sub-group difference) 0.73, and 0.52, respectively]. Odds-Ratio for cardiac events was 2.65 (p<0.001) favoring shorter duration. One year of trastuzumab prolongs overall, and disease-free survivals in women with early-stage HER2 positive breast cancer compared to shorter durations and this should remain as the standard of care. Cardiotoxicity increased

  12. Suitability of Invertebrate and Vertebrate Cells in a Portable Impedance-Based Toxicity Sensor: Temperature Mediated Impacts on Long-Term Survival

    Science.gov (United States)

    2013-07-25

    sug- gests that a reptilian cell line stored at 20 C or 25 C, and a cold water fish cell line stored at 6 C are able to survive in the enclosed...115. Stokes, D., Meek, R., 2003. Diurnal body temperatures in semi-captive Tokay Geckos (Gekko gecko); evidence for thermoregulation ? Herpetological

  13. Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure

    Science.gov (United States)

    Freyer, G; Rougier, P; Bugat, R; Droz, J-P; Marty, M; Bleiberg, H; Mignard, D; Awad, L; Herait, P; Culine, S; Trillet-Lenoir, V

    2000-01-01

    Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P< 0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P≤ 0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P≤ 0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent

  14. How do plants manage to survive on toxic spoil-mining sites? Physiological and structural properties of plants on substrates with high As and Hg contents

    OpenAIRE

    Kovářová, Monika

    2010-01-01

    The heavy metals contamination of environment represents a worldwide problem lately. Heavy metals cause harmful effects not only to plants, but also to other organisms. Throught their acumulation in plant biomass, heavy metals enter a food chain and could negatively influence the human health. The impact of heavy metals on plants and their defence mechanisms against toxicity of heavy metals have been in focus of plant physiology and ecology research for decades. Importance of this topic arise...

  15. Conditional disease-free survival after surgical resection of gastrointestinal stromal tumors: a multi-institutional analysis of 502 patients.

    Science.gov (United States)

    Bischof, Danielle A; Kim, Yuhree; Dodson, Rebecca; Jimenez, M Carolina; Behman, Ramy; Cocieru, Andrei; Fisher, Sarah B; Groeschl, Ryan T; Squires, Malcolm H; Maithel, Shishir K; Blazer, Dan G; Kooby, David A; Gamblin, T Clark; Bauer, Todd W; Quereshy, Fayez A; Karanicolas, Paul J; Law, Calvin H L; Pawlik, Timothy M

    2015-04-01

    Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery. To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs. A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada. Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated. Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C = 0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time elapsed. Conditional DFS improves over time following resection of GISTs. This is valuable

  16. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

    DEFF Research Database (Denmark)

    Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques

    2018-01-01

    the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subgroup DFS analyses...... by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio...

  17. Men and women show similar survival rates after breast cancer.

    Science.gov (United States)

    Bender, Paulo Franscisco Mascarenhas; de Oliveira, Letícia Lima; Costa, Célia Regina; de Aguiar, Suzana Sales; Bergmann, Anke; Thuler, Luiz Claudio Santos

    2017-04-01

    To compare the disease-free survival (DFS) and overall survival (OS) rates of men and women undergoing treatment for breast cancer. A retrospective cohort study of patients with breast cancer diagnosed and treated at the Cancer Hospital III of the National Cancer Institute of Brazil, Rio de Janeiro, Brazil, between 1999 and 2013. Male breast cancer cases were matched for age, year of diagnosis, and clinical staging to three female cases (1:3). Patient characteristics were abstracted from hospital records and medical charts. Cases were analyzed using descriptive statistics, and comparisons between the genders were performed using Kaplan-Meier curves and Cox regression analysis with 95% confidence intervals. The study population comprised 98 men and 294 women. There were significant differences (p breast surgery, neoadjuvant chemotherapy, adjuvant radiotherapy, and use of palliative bisphosphonate therapy. Five- and 10-year DFS rates were, respectively, 80.0 and 51.4% for men and 71.4 and 63.5% for women (p = 0.245), and 5- and 10-year OS rates were, respectively, 65.0 and 47.5% for men and 56.5 and 41.4% for women (p = 0.221). There was no significant difference in prognosis (DFS and OS rates) between the genders, but significant differences in sociodemographic and clinical characteristics were detected between male and female breast cancer cases.

  18. Studies of the toxicity of an intravenous fat emulsion. i. Hematologic changes and survival after administration of a soybean oil (FE-S15) in beagles.

    Science.gov (United States)

    Reimold, E W

    1979-01-01

    The potential toxicity of FE-S15 (B. Braun-Melsungen), a soybean-oil fat emulsion used in parenteral nutrition, was studied in dogs. Forty pure-bred beagles, in two experimental groups (FE-S15 at 9 and 4 g/kg/day) and two corresponding control groups (receiving Dextrose-Ringer's solution), were given daily infusions for 28 days via a central venous catheter. Vital signs and hematologic, biochemical, and bacteriologic changes were monitored closely. When compared with control groups, no significant weight loss was observed in either group; the food intake decreased only in animals receiving fat in high doses. Hemoglobin and hematocrit decreased in all groups during infusion, the greatest fall observed in the group receiving high-dose fat infusion where the hematocrit declined from 45.5% to 31.7%. This decrease was significantly different from the controls only during one observation period. Clinical signs, such as lethargy, vomiting, diarrhea, loss of appetite and fever were observed infrequently in both experimental and control animals, more often in those treated with high-dose fat infusion. It appears that the fat emulsion FE-S15 causes only minor side effects but otherwise is well tolerated in dogs at a potentially toxic level.

  19. Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

    Energy Technology Data Exchange (ETDEWEB)

    Pouliliou, Stamatia E. [Department of Radiotherapy/Oncology, Radiobiology and Radiopathology Unit, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Lialiaris, Theodoros S. [Department of Medical Genetics, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Dimitriou, Thespis [Department of Anatomy, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Giatromanolaki, Alexandra [Department of Pathology, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Papazoglou, Dimitrios [Department of Internal Medicine, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Pappa, Aglaia [Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Pistevou, Kyriaki [Department of Radiotherapy/Oncology, Aristotle University of Thessalonica, Thessalonica (Greece); Kalamida, Dimitra [Department of Radiotherapy/Oncology, Radiobiology and Radiopathology Unit, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy/Oncology, Radiobiology and Radiopathology Unit, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece)

    2015-07-01

    Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2{sub [4h]}) and 24 hours (SF2{sub [24h]}) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2{sub (4h)} was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio{sub (30min)} (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio{sub (4h)}/γH2AX-ratio{sub (30min)}) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with

  20. The fish embryo toxicity test as a replacement for the larval growth and survival test: A comparison of test sensitivity and identification of alternative endpoints in zebrafish and fathead minnows.

    Science.gov (United States)

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

    2015-06-01

    The fish embryo toxicity (FET) test has been proposed as an alternative to the larval growth and survival (LGS) test. The objectives of the present study were to evaluate the sensitivity of the FET and LGS tests in fathead minnows (Pimephales promelas) and zebrafish (Danio rerio) and to determine if the inclusion of sublethal metrics as test endpoints could enhance test utility. In both species, LGS and FET tests were conducted using 2 simulated effluents. A comparison of median lethal concentrations determined via each test revealed significant differences between test types; however, it could not be determined which test was the least and/or most sensitive. At the conclusion of each test, developmental abnormalities and the expression of genes related to growth and toxicity were evaluated. Fathead minnows and zebrafish exposed to mock municipal wastewater-treatment plant effluent in a FET test experienced an increased incidence of pericardial edema and significant alterations in the expression of genes including insulin-like growth factors 1 and 2, heat shock protein 70, and cytochrome P4501A, suggesting that the inclusion of these endpoints could enhance test utility. The results not only show the utility of the fathead minnow FET test as a replacement for the LGS test but also provide evidence that inclusion of additional endpoints could improve the predictive power of the FET test. © 2015 SETAC.

  1. Validation of Nomograms for Survival and Metastases after Hysterectomy and Adjuvant Therapy in Uterine Cervical Cancer with Risk Factors

    Directory of Open Access Journals (Sweden)

    Won Sup Yoon

    2017-01-01

    Full Text Available Background. Three nomogram models for early stage uterine cervical cancer have been developed (KROG 13-03 for overall survival [OS], SNUH/AMC for disease-free survival [DFS], and KROG 12-08 for distant metastases-free survival [DMFS] after radical hysterectomy (RH and pelvic lymph node dissection (PLND. This study aimed to validate these models using our cohort with adjuvant radiotherapy. Methods. According to the eligibility criteria of nomogram studies, patients were enrolled in Group A (N=109 for the two KROG models (RH with PLND and whole pelvic irradiation and Group B (N=101 for the SNUH/AMC model (RH with PLND and squamous histology. Using Cox-regression hazard models, the prognostic factors of our cohorts were evaluated. The risk probabilities induced from published nomogram scores were calculated and the concordance indices were evaluated. Results. Group A had 88.1% 5-year OS and 86.0% 5-year DMFS. Group B had 83.0% 5-year DFS. In multivariate analyses, large tumor size for OS (HR 8.62, P<0.001 and DMFS (HR 5.13, P=0.003, young age (≤40 versus 41–64 years for OS (HR 4.63, P=0.097 and DFS (HR 3.44, P=0.051, and multiple lymph node metastases (0 versus ≥3 for DMFS (HR 4.03, P=0.031 and DFS (HR 3.90, P=0.038 were significantly correlated. The concordance indices for OS, DMFS, and DFS were 0.612 (P=0.002, 0.597 (P=0.014, and 0.587 (P=0.020, respectively. Conclusion. The developed nomogram models after RH and PLND are clinically useful in predicting various types of survival with significance.

  2. Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Nan Song

    Full Text Available It is inconclusive whether reproductive factors, which are known as risk factors of breast cancer, also influence survival. We investigated overall and subtype-specific associations between reproductive factors and breast cancer survival.Among 3,430 incident breast cancer patients who enrolled in the Seoul Breast Cancer Study, 269 patients (7.8% died and 528 patients (15.4% recurred. The overall and subtype-specific associations of reproductive factors including age at menarche and menopause, duration of estrogen exposure, menstrual cycle, parity, age at first full-term pregnancy, number of children, age at last birth, time since the last birth, and duration of breastfeeding, on overall and disease-free survival (OS and DFS were estimated by hazard ratios (HRs and 95% confidence intervals (95% CIs using a multivariate Cox proportional hazard model.An older age at menarche (HR for OS=1.10, 95% CI=1.03-1.19, a greater number of children (≥ 4 vs. 2, HR for DFS=1.58, 95% CI=1.11-2.26, and a shorter time since last birth (<5 vs. ≥ 20 years, HR for DFS=1.67, 95% CI=1.07-2.62 were associated with worse survival while longer duration of estrogen exposure with better survival (HR for DFS=0.97, 95% CI=0.96-0.99. In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ HER2+ tumors.It is suggested that reproductive factors, specifically age at menarche, number of children, time since last birth, and duration of estrogen exposure, could influence breast tumor progression, especially in the HR+ HER2+ subtype.

  3. Does HPV status influence survival after vulvar cancer?

    DEFF Research Database (Denmark)

    Rasmussen, Christina Louise; Sand, Freja Laerke; Hoffmann Frederiksen, Marie

    2018-01-01

    High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV...... status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic...... search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I2...

  4. [Disease-free survival related factors in breast cancer].

    Science.gov (United States)

    Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

    2014-10-07

    To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  5. Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer

    Directory of Open Access Journals (Sweden)

    Wiseman Janice

    2011-05-01

    Full Text Available Abstract Background Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS, Disease Free Survival (DFS and Overall Survival (OS. Methods Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2 or four cycles of 3-weekly docetaxel (100 mg/m2. The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. Results At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%, pathological complete response (20% vs. 27%, and breast-conserving surgery (BCS rates (49% vs. 42%. Disease-free survival and overall survival were similar between treatment groups. Conclusions Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS or survival outcomes in the neoadjuvant setting. Trial registration ISRCTN: ISRCTN09184069

  6. Prediction of neoadjuvant radiation chemotherapy response and survival using pretreatment [{sup 18}F]FDG PET/CT scans in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ji-In; Ha, Seunggyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kang, Sung-Bum; Oh, Heung-Kwon [Seoul National University Bundang Hospital, Department of Surgery, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Lee, Keun-Wook [Seoul National University Bundang Hospital, Department of Internal Medicine, Seongnam (Korea, Republic of); Lee, Hye-Seung [Seoul National University Bundang Hospital, Department of Pathology, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kim, Jae-Sung [Seoul National University Bundang Hospital, Department of Radiation Oncology, Seongnam (Korea, Republic of); Lee, Ho-Young [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of)

    2016-03-15

    The aim of this study was to investigate metabolic and textural parameters from pretreatment [{sup 18}F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC). We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [{sup 18}F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses. MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS. Metabolic and textural parameters from initial [{sup 18}F]FDG PET/CT scans could be indexes to assess

  7. 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 human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  8. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy.

    Science.gov (United States)

    Wang, H M; Liao, Z X; Komaki, R; Welsh, J W; O'Reilly, M S; Chang, J Y; Zhuang, Y; Levy, L B; Lu, C; Gomez, D R

    2013-05-01

    Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.

  9. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  10. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence.

    Science.gov (United States)

    Kim, Mi Young; Kim, Jin Hee; Kim, Yonghoon; Byun, Sang Jun

    2016-12-01

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  11. Long-term Survival Outcomes Following Internal Mammary Node Irradiation in Stage II-III Breast Cancer: Results of a Large Retrospective Study With 12-Year Follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Won [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Yong Bae; Lee, Ik Jae; Keum, Ki Chang; Lee, Chang Geol [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Doo Ho [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Suh, Chang-Ok, E-mail: cosuh317@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Huh, Seung Jae, E-mail: sjhuh@smc.samsung.co.kr [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-08-01

    Purpose: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. Methods and Materials: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. Results: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. Conclusions: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

  12. Acute Toxicity of Vildagliptin.

    Science.gov (United States)

    Hoffmann, Peter; Martin, Lori; Keselica, Michael; Gunson, Diane; Skuba, Elizabeth; Lapadula, Dan; Hayes, Michael; Bentley, Phil; Busch, Steve

    2017-01-01

    This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances. In surviving animals, symptoms were reversible even if treatment was continued. Cynomolgus monkeys from Mauritius appear more sensitive than monkeys of Asian origin. The underlying mechanism(s) of these symptoms in cynomolgus monkeys is currently not well understood, although a vascular mechanism including initial vasoconstriction and subsequent vascular leakage in distal extremities may play a role. The monkey data are reviewed and discussed in the context of other preclinical and clinical data, and it is concluded that acute toxicity following vildagliptin treatment is a monkey-specific phenomenon without relevance for humans.

  13. Locally advanced esophageal adenocarcinoma: Response to neoadjuvant chemotherapy and survival predicted by {sup [18F]}FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kauppi, Juha T.; Salo, Jarmo A.; Sihvo, Eero I.; Raesaenen, Jari V. [Helsinki Univ. Central Hospital, Div. of General Thoracic and Esophageal Surgery, Dept. of Cardiothoracic Surgery, Helsinki Univ. Central Hospital, Helsinki (Finland)], Email: jarmo.salo@hus.fi; Oksala, Niku [Dept. of Vascular Surgery, Tampere Univ. Central Hospital, Tampere (Finland); Helin, Heikki [HUSLAB/Dept. of Pathology, Helsinki Univ. Central Hospital, Helsinki (Finland); Karhumaeki, Lauri [HUSLAB/Dept. of Clinical Physiology and Nuclear Medicine, Helsinki Univ. Central Hospital, Helsinki (Finland); Kemppainen, Jukka [PET-Center, Turku Univ., Turku (Finland)

    2012-05-15

    Background. {sup [18F]}fluorodeoxyglucose-Positron Emission Tomography/Computer Tomography ({sup [18F]}FDG-PET/CT) is commonly used in staging of locally advanced esophageal cancer. Its predictive value for response to neoadjuvant therapy and survival after multimodality therapy is controversial. Methods. Sixty-six consecutive patients with locally advanced adenocarcinoma of the esophagus or esophagogastric junction underwent surgery after neoadjuvant chemotherapy. Staging was done prospectively with {sup [18F]}FDG-PET/CT, before and after completion of neoadjuvant therapy. Pre- and post-therapy maximal standardized uptake values for the primary tumor (SUV1 and SUV2) were determined, and their relative change (SUV{Delta}%) calculated. Percentage change in SUV1 was compared with histopathologic response (HPR, complete or subtotal histologic remission), disease-free- (DFS) and overall survival (OS). Results. Resection with negative margins was achieved in 60 patients. HPR rate was 14 of 66 (21.2%). Median follow-up was 16 months (range 4-72). For all patients, OS probability at three years was 59% and DFS 50%. In receiver operating characteristics (ROC) analysis, HPR was optimally predicted by a > 67% change in baseline maximal SUV (sensitivity 79% and specificity 75%). In univariate survival analysis (Cox regression proportional hazards), HPR associated with improved DFS (HR 0.208, p = 0.033) but not OS (HR 0.030, p = 0.101), SUV % > 67% associated with improved OS (HR 0.249, p = 0.027) and DFS (HR 0.383, p 0.040). In a multivariate model (adjusted by age, sex, and ASA score), neither HPR nor SUV{Delta}% > 67% was predictive of improved OS and DFS. However, SUV{Delta}% as a continuous variable was an independent predictor of OS (HR 0.966, p < 0.0001) or DFS (HR 0.973, p < 0.0001). Conclusion. Our results support previous results showing that {sup [18F]}FDG-PET/CT can distinguish a group of patients with worse prognosis after neoadjuvant chemotherapy in

  14. Antimony toxicity

    National Research Council Canada - National Science Library

    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...

  15. Determination of the Toxicity to Aquatic Organisms of HMX and Related Wastewater Constituents. Part 1. The Effects of Food Concentration, Animal Interactions and Water Volume on Survival Growth and Reproduction of Daphnia magna under Flow-through Conditions.

    Science.gov (United States)

    1983-01-01

    Effects of polychlorinated biphenyl’s (PCB’s) on survival and reproduction of Daphnia, Gammarus , and Tanytarsus. Trans. Amer. Fish. Soc. 103(4) : 722-728...WASTEWATER CONSTITUENTS Ruff 1: * THE EFFECTS OF FOOD CONCENTRATION, ANIMAL INTERACTIONS AND WATER VOLUME ON SURVIVAL, GROWTH AND REPRODUCTION OF Daphnia...OF FOOD CONCENTRATION, ANIMAL INTERACTIONS AND WATER VOLUME ON SURVIVAL, GROWTH AND REPRODUCTION OF Daphnia magna UNDER FLOW-THROUGH CONDITIONS

  16. Neoadjuvant chemotherapy induces expression levels of breast cancer resistance protein that predict disease-free survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Baek Kim

    Full Text Available Three main xenobiotic efflux pumps have been implicated in modulating breast cancer chemotherapy responses. These are P-glycoprotein (Pgp, Multidrug Resistance-associated Protein 1 (MRP1, and Breast Cancer Resistance Protein (BCRP. We investigated expression of these proteins in breast cancers before and after neoadjuvant chemotherapy (NAC to determine whether their levels define response to NAC or subsequent survival. Formalin-fixed paraffin-embedded tissues were collected representing matched pairs of core biopsy (pre-NAC and surgical specimen (post-NAC from 45 patients with invasive ductal carcinomas. NAC regimes were anthracyclines +/- taxanes. Immunohistochemistry was performed for Pgp, MRP1 and BCRP and expression was quantified objectively using computer-aided scoring. Pgp and MRP1 were significantly up-regulated after exposure to NAC (Wilcoxon signed-rank p = 0.0024 and p<0.0001, while BCRP showed more variation in response to NAC, with frequent up- (59% of cases and down-regulation (41% contributing to a lack of significant difference overall. Pre-NAC expression of all markers, and post-NAC expression of Pgp and MRP1 did not correlate with NAC response or with disease-free survival (DFS. Post-NAC expression of BCRP did not correlate with NAC response, but correlated significantly with DFS (Log rank p = 0.007, with longer DFS in patients with low post-NAC BCRP expression. In multivariate Cox regression analyses, post-NAC BCRP expression levels proved to predict DFS independently of standard prognostic factors, with high expression associated with a hazard ratio of 4.04 (95% confidence interval 1.3-12.2; p = 0.013. We conclude that NAC-induced expression levels of BCRP predict survival after NAC for breast cancer, while Pgp and MRP1 expression have little predictive value.

  17. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab

    Science.gov (United States)

    GÜNDÜZ, SEYDA; GÖKSU, SEMA SEZGIN; ARSLAN, DENIZ; TATLI, ALI MURAT; UYSAL, MÜKREMIN; GÜNDÜZ, UMUT RIZA; SEVINÇ, MERT MAHSUNI; COŞKUN, HASAN SENOL; BOZCUK, HAKAN; MUTLU, HASAN; SAVAS, BURHAN

    2015-01-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer. PMID:26623060

  18. Perfusion Parameters on Breast Dynamic Contrast-Enhanced MRI Are Associated With Disease-Specific Survival in Patients With Triple-Negative Breast Cancer.

    Science.gov (United States)

    Park, Vivian Youngjean; Kim, Eun-Kyung; Kim, Min Jung; Yoon, Jung Hyun; Moon, Hee Jung

    2017-03-01

    The aim of this study was to investigate the association between perfusion parameters on MRI performed before treatment and survival outcome (disease-free survival [DFS], disease-specific survival [DSS]) in patients with triple-negative breast cancer (TNBC). Sixty-one patients (median age, 50 years; age range, 27-77 years) with TNBC (tumor size on MRI: median, 25.5 mm; range, 11.0-142.0 mm) were included. We analyzed clinical and pathologic variables and MRI parameters. Cox proportional hazards models were used to determine associations with survival outcome. The median follow-up time was 46.1 months (range, 13.9-58.4 months). Eleven of 61 (18.0%) patients had events (i.e., local, regional, or distant recurrence or contralateral breast cancer) and seven (11.5%) died of breast cancer. Among the pretreatment variables, a larger tumor size on MR images (hazard ratio [HR] = 1.024, p = 0.003) was associated with worse DFS at univariate analysis. In multivariate pretreatment models for DSS, a higher fractional volume of extravascular extracellular space per unit volume of tissue (ve) value (HR = 1.658, p = 0.038), higher peak enhancement (HR = 1.843, p = 0.018), and a larger tumor size on MR images (HR = 1.060, p = 0.001) were associated with worse DSS. In multivariate posttreatment models, a larger pathologic tumor size (HR for DFS, 1.074 [p = 0.005]; HR for DSS, 1.050 [p = 0.042]) and metastasis in surgically resected axillary lymph nodes (HR for DFS, 5.789 [p = 0.017]; HR for DSS, 23.717 [p = 0.005]) were associated with worse survival outcome. A higher ve value, higher peak enhancement, and larger tumor size of the primary tumor on pretreatment MRI were independent predictors of worse DSS in patients with TNBC.

  19. Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

    Directory of Open Access Journals (Sweden)

    Sung Hyuna

    2012-05-01

    Full Text Available Abstract Background Although the role of microRNA’s (miRNA’s biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. Methods We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs and both disease free survival (DFS and overall survival (OS among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Results Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779 and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845 and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI, 1.41-4.88 and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69. We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93 and 4.47 (95% CI, 2.45- 8.14, respectively (P for trend, 6.11E-07. Conclusions Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.

  20. Thymidylate Synthase Gene Polymorphism and Survival of Colorectal Cancer Patients Receiving Adjuvant 5-Fluorouracil

    Science.gov (United States)

    Sulzyc-Bielicka, Violetta; Bielicki, Dariusz; Binczak-Kuleta, Agnieszka; Kaczmarczyk, Mariusz; Pioch, Wiesława; Machoy-Mokrzynska, Anna; Ciechanowicz, Andrzej; Gołębiewska, Magdalena

    2013-01-01

    Limited studies indicate a possible association of 5′-UTR thymidylate synthase enhancer region polymorphism and treatment outcome in patients medicated with 5-fluorouracil (5-FU). The study was designed to verify the relationship in patients with colorectal cancer (CRC), a Polish population that received 5-FU-based adjuvant chemotherapy. The study analyzed 145 Astler-Coller B2 and C CRC patients. Genotyping for a variable number of tandem repeats and G to C single-nucleotide polymorphism in the 5′-UTR of the thymidylate synthase (TS) gene was carried out. TS genotypes were classified into high expression (high TS) and low expression types (low TS). High TS was found in 22.8% of patients. The right-side tumors were more frequently associated with high TS than the left-side tumors (p=0.024). High TS was only found in 9.3% of rectal tumors, but in 29.7% of colon cancers (p=0.0042). Disease-free survival after 20 months (DFS 20) was longer in subjects with low TS than in high TS (p=0.043). Patients who underwent chemotherapy had longer DFS 20 in the low TS than in the high TS subgroup (p=0.051). The low TS was found to be an independent good prognostic factor for DFS 20 in the whole group as well as in the subgroup treated with chemotherapy (p=0.024 and p=0.034, respectively). Patients with low TS did not show any differences in DFS 20 whether they were treated with adjuvant chemotherapy or not. Proximal CRC tumors are characterized by higher TS expression genotypes than distal tumors, and are at significantly greater risk of early recurrence during the first 20 months after surgery. PMID:23968134

  1. Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

    Science.gov (United States)

    Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

    2013-01-01

    Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

  2. Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-05-01

    Full Text Available Li Chen,1 Yanjiao Zuo,1 Lihua Zhu,2 Yuxin Zhang,3 Sen Li,1 Fei Ma,4 Yu Han,5 Hongjiang Song,1 Yingwei Xue11Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, 3Department of General Surgery, Mudanjiang First People’s Hospital, Mudanjiang, 4Department of Breast Surgery, 5Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaBackground: Accurate and useful predictors of gastric carcinoma treated with neoadjuvant chemotherapy are lacking at present. We aim to explore the potential prognostic significance of the neutrophil-to-lymphocyte ratio (NLR in advanced gastric cancer receiving S-1 plus oxaliplatin (SOX or oxaliplatin and capecitabine (XELOX regimen.Methods: We enrolled 91 patients with advanced gastric cancer treated with neoadjuvant chemotherapy from August 2008 to September 2015. The peripheral venous blood samples were collected before neoadjuvant chemotherapy. The NLR was divided into two groups: low NLR <2.17 group and high NLR ≥2.17 group. Univariate analysis on disease-free survival (DFS and overall survival (OS were generated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were assessed by univariate analyses, and the independent prognostic factors were evaluated using multivariate analysis (Cox’s proportional-hazards regression model.Results: The univariate analysis showed that median DFS and median OS were worse for high NLR values than low NLR values before neoadjuvant chemotherapy (median DFS: 19.97 and 26.87 months, respectively, P=0.299; median OS: 25.83 and 29.73 months, respectively, P=0.405. Multivariate analysis showed that the NLR before neoadjuvant

  3. Differential toxicity and influence of salinity on acute toxicity of ...

    African Journals Online (AJOL)

    This study investigated the salinity-tolerance of Oreochromis niloticus and the influence of salinity changes on the acute toxicities of copper sulphate (CuSO4) and lead nitrate (Pb[NO3]2) against the fish species. On the basis of daily mortality assessment, O. niloticus was found to be unable to survive in media with salinity ...

  4. Antimony Toxicity

    Science.gov (United States)

    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 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. PMID:21318007

  5. Trends in incidence and survival analysis in non-melanoma skin cancer from 1994 to 2012 in Girona, Spain: A population-based study.

    Science.gov (United States)

    Rubió-Casadevall, J; Hernandez-Pujol, A M; Ferreira-Santos, M C; Morey-Esteve, G; Vilardell, L; Osca-Gelis, G; Vilar-Coromina, N; Marcos-Gragera, R

    2016-12-01

    We present an epidemiological study focused on Non-melanoma skin cancers (NMSC), including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFS) and adnexal and skin appendages neoplasm (ASAN), a neoplasm understudied in cancer registries. We analyze trends of incidence and survival of NMSC registered with the Cancer Registry of Girona, Spain. We found 14389 cases of NMSC, accounting 3,474 SCC, 10729 BCC, 33 MCC, 61 DFSP and 71 ASAN. Incidence increased significantly in SCC and BCC with annual percentage of change of 1.6 and 1.5, respectively, but not in MCC, DFS or ASAN. Five-year relative survival for both sexes was 90.1% in SCC, 99.8% in BCC, 44.2% in MCC, 93.7% in DFS and 84% in ASAN. Our study confirms the increasing incidence and good survival of SCC and BCC and enhances knowledge on the epidemiology of the less incidental NMSC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia.

    Science.gov (United States)

    Hu, Xiaoxia; Fu, Weijun; Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-19

    Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients.

  7. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Gouel, Pierrick [Centre Henri Becquerel and Rouen University Hospital, Department of Nuclear Medicine, Rouen (France); Di Fiore, Frederic [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Centre Henri Becquerel, Department of Medical oncology, Rouen (France); Marre, Charline; Michel, Pierre [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Hapdey, Sebastien; Modzelewski, Romain; Vera, Pierre [Centre Henri Becquerel and Rouen University Hospital, Department of Nuclear Medicine, Rouen (France); University of Rouen, QuantIF (Litis EA 4108 - FR CNRS 3638), Rouen (France); Dubray, Bernard [University of Rouen, QuantIF (Litis EA 4108 - FR CNRS 3638), Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France)

    2014-11-15

    It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes. Included in the study were 67 patients with a histological diagnosis of oesophageal squamous cell carcinoma. Each patient underwent {sup 18}F-FDG PET (4.5 MBq/kg) before chemoradiotherapy. Quantitative analysis was performed using the following parameters: age, weight loss, location, N stage, OMS performance status, MTV{sub p} and MTV{sub p'} (metabolic tumour volume determined by two different physicians), MTV{sub 40%} (volume for a threshold of 40 % of SUVmax), MTV{sub a} (volume automatically determined with a contrast-based adaptive threshold method), SUVmax, SUVmean and TLG (total lesion glycolysis). MTV{sub p} and MTV{sub 40%} were highly correlated (Pearson's index 0.92). SUVmean{sub p} and SUVmean{sub 40%} were also correlated (Pearson's index 0.86), as were TLG{sub p} and TLG{sub 40%} (Pearson's index 0.98). Similarly, the parameters obtained with the adaptive threshold method (MTV{sub a}, SUVmean{sub a} and TLG{sub a}) were correlated with those obtained manually (MTV{sub p}, SUVmean{sub p} and TLG{sub p}). The manual metabolic tumour volume determination (MTV{sub p} and MTV{sub p'}) was reproducible. Multivariate analysis for disease-free survival (DFS) showed that a larger MTV{sub p} was associated with a shorter DFS (p = 0.004) and that a higher SUVmax was associated with a longer DFS (p = 0.02). Multivariate analysis for overall survival (OS) showed that a larger MTV{sub p} was associated with a shorter OS (p = 0.01) and that a tumour in the distal oesophagus was associated with a longer OS (p = 0.005). The associations among the other parameters were not statistically significant. Metabolic tumour volume is a major

  8. Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy.

    Science.gov (United States)

    Li, Sheng; Zhu, Liangjun; Yao, Li; Xia, Lei; Pan, Liangxi

    2014-08-29

    Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan-Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.

  9. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  10. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  11. [Toxic megacolon].

    Science.gov (United States)

    Leppkes, M; Ganslmayer, M; Strauß, R; Neurath, M F

    2015-10-01

    Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care. Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success. This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care. Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step-wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety. Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge.

  12. Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy

    Science.gov (United States)

    Gómez, Rodolfo; Ossa, Carlos Andrés; Montoya, María Elvira; Echeverri, Carolina; Ángel, Gonzalo; Ascuntar, Johana; Borrero, Mauricio; Gil, Mónica; Herrera, Sabrina; Gutiérrez, Eduardo; Herazo, Fernando; Jiménez, Alejo; Madrid, Jorge; Reyes, Pedro Alejandro; Zuluaga, Lina; García, Héctor

    2015-01-01

    Background Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, showing improvement in disease-free survival (DFS) and overall survival (OS) rates in patients achieving pathological complete response (pCR). The relationship between immunohistochemistry-based molecular subtyping (IMS), chemo sensitivity and survival is currently a matter of interest. We explore this relationship in a Hispanic cohort of breast cancer patients treated with NAC. Methods A retrospective survival analysis was performed on Colombian females with breast cancer treated at Instituto de Cancerología-Clinica Las Américas between January 2009 and December 2011. Patients were classified according to immunohistochemistry-based subtyping into the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched, and triple-negative breast cancer. Demographic characteristics, recurrence pattern, and survival rate were reviewed by bivariate and multivariate analysis. Results A total of 328 patients fulfilled the study’s inclusion parameters and the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal B/HER2−: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile range: 31–52). Pathological response to NAC was as follows: complete pathological response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47 (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p = 0.01) and triple negative (p = 0.01). Conclusions pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours and non-pCR showed lower DFS

  13. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates; Adenocarcinoma gastrico avancado. Analise da toxicidade e da influencia da radioterapia pre-operatoria nos indices de sobrevivencia a longo prazo

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1996-12-31

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author) 112 refs., 34 tabs.

  14. Association between clinicopathological features and survival in patients with primary and paired metastatic colorectal cancer and KRAS mutation

    Directory of Open Access Journals (Sweden)

    Pang X

    2017-05-01

    Full Text Available Xue-Lian Pang,* Qiao-Xin Li,* Zhi-Ping Ma, Yi Shi, Yu-Qing Ma, Xin-Xia Li, Wen-Li Cui, Wei Zhang Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS and disease-free survival (DFS in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230, which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001. Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4 and in lymph node (LN metastases (N1/N2 (P=0.029 and P=0.010, respectively. The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001 and in metastatic CRC that had infiltrated more deeply (T3, T4 (P=0.034. In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035. Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively. In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029. The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and

  15. E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

    Science.gov (United States)

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

    2016-07-01

    The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

  16. Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure. CPT-11 F205, F220, F221 and V222 study groups.

    Science.gov (United States)

    Freyer, G; Rougier, P; Bugat, R; Droz, J P; Marty, M; Bleiberg, H; Mignard, D; Awad, L; Herait, P; Culine, S; Trillet-Lenoir, V

    2000-08-01

    Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P<0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P < or =0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P< or =0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single

  17. Toxic metals and autophagy.

    Science.gov (United States)

    Chatterjee, Sarmishtha; Sarkar, Shuvasree; Bhattacharya, Shelley

    2014-11-17

    The earth's resources are finite, and it can no longer be considered a source of inexhaustible bounty for the human population. However, this realization has not been able to contain the human desire for rapid industrialization. The collateral to overusing environmental resources is the high-level contamination of undesirable toxic metals, leading to bioaccumulation and cellular damage. Cytopathological features of biological systems represent a key variable in several diseases. A review of the literature revealed that autophagy (PCDII), a high-capacity process, may consist of selective elimination of vital organelles and/or proteins that intiate mechanisms of cytoprotection and homeostasis in different biological systems under normal physiological and stress conditions. However, the biological system does survive under various environmental stressors. Currently, there is no consensus that specifies a particular response as being a dependable biomarker of toxicology. Autophagy has been recorded as the initial response of a cell to a toxic metal in a concentration- and time-dependent manner. Various signaling pathways are triggered through cellular proteins and/or protein kinases that can lead to autophagy, apoptosis (or necroptosis), and necrosis. Although the role of autophagy in tumorigenesis is associated with promoting tumor cell survival and/or acting as a tumor suppressive mechanism, PCDII in metal-induced toxicity has not been extensively studied. The aim of this review is to analyze the comparative cytotoxicity of metals/metalloids and nanoparticles (As, Cd, Cr, Hg, Fe, and metal-NP) in cells enduring autophagy. It is noted that metals/metalloids and nanoparticles prefer ATG8/LC3 as a potent inducer of autophagy in several cell lines or animal cells. MAP kinases, death protein kinases, PI3K, AKT, mTOR, and AMP kinase have been found to be the major components of autophagy induction or inhibition in the context of cellular responses to metals/metalloids and

  18. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  19. Studying toxicity

    Science.gov (United States)

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  20. Innovations’ Survival

    Directory of Open Access Journals (Sweden)

    Jakub Tabas

    2016-01-01

    Full Text Available Innovations currently represent a tool of maintaining the going concern of a business entity and its competitiveness. However, effects of innovations are not infinite and if an innovation should constantly preserve a life of business entity, it has to be a continual chain of innovations, i.e. continual process. Effective live of a single innovation is limited while the limitation is derived especially from industry. The paper provides the results of research on innovations effects in the financial performance of small and medium-sized enterprises in the Czech Republic. Objective of this paper is to determine the length and intensity of the effects of technical innovations in company’s financial performance. The economic effect of innovations has been measured at application of company’s gross production power while the Deviation Analysis has been applied for three years’ time series. Subsequently the Survival Analysis has been applied. The analyses are elaborated for three statistical samples of SMEs constructed in accordance to the industry. The results obtained show significant differences in innovations’ survival within these three samples of enterprises then. The results are quite specific for the industries, and are confronted and discussed with the results of authors’ former research on the issue.

  1. 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- ...

  2. Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer: results from NCCTG Trial N0147 (Alliance).

    Science.gov (United States)

    Jansson-Knodell, Claire L; Foster, Nathan R; Sargent, Daniel J; Limburg, Paul J; Thibodeau, Stephen N; Smyrk, Thomas C; Sinicrope, Frank A; Jahagirdar, Balkrishna; Goldberg, Richard M; Alberts, Steven R

    2017-02-01

    Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95% confidence interval (CI), 0.78-1.16] for DFS, 0.94 (95% CI, 0.76-1.16) for TTR, and 0.92 (95% CI, 0.74-1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95% CI, 0.45-1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95% CI, 0.81-1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS, TTR, or OS outcomes, with the exception of

  3. Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer: results from NCCTG Trial N0147 (Alliance)

    Science.gov (United States)

    Jansson-Knodell, Claire L.; Foster, Nathan R.; Sargent, Daniel J.; Limburg, Paul J.; Thibodeau, Stephen N.; Smyrk, Thomas C.; Sinicrope, Frank A.; Jahagirdar, Balkrishna; Goldberg, Richard M.

    2017-01-01

    Background Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. Methods To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. Results We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95% confidence interval (CI), 0.78–1.16] for DFS, 0.94 (95% CI, 0.76–1.16) for TTR, and 0.92 (95% CI, 0.74–1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95% CI, 0.45–1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95% CI, 0.81–1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Conclusions Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS

  4. Aspirin/antiplatelet agent use improves disease-free survival and reduces the risk of distant metastases in Stage II and III triple-negative breast cancer patients.

    Science.gov (United States)

    Shiao, J; Thomas, K M; Rahimi, A S; Rao, R; Yan, Jingsheng; Xie, Xian-Jin; DaSilva, M; Spangler, A; Leitch, M; Wooldridge, R; Rivers, A; Farr, D; Haley, B; Kim, D W Nathan

    2017-02-01

    The objective is to define the therapeutic role of antiplatelet agents in a triple-negative breast cancer (TNBC) population. We performed retrospective analysis using the UTSW TNBC registry containing data from 222 Stage II-III TNBC patients treated between 1998 and 2016. Univariate analysis and multivariable logistic regression models were constructed to identify factors associated with disease-free survival (DFS), distant metastases rate (DMR), and overall survival outcomes. Antiplatelet drug use was determined by review of electronic medical records. A total of 65 patients used antiplatelet (AP) agents, and 157 patients did not use AP agents. Median follow-up for AP and non-AP groups was 41.3 and 40.9 months, respectively. There was an improvement in the AP group compared with the control group in 5-year DFS (80.4% at 5 years compared with 62.3% in the control group, p = 0.04) and 5-year DMR (8.8 vs. 31.9%, p = 0.007). In multivariate analysis, AP use was found to be significantly associated with improvements in DFS and DMR. We illustrate that antiplatelet agent use improves DMR and DFS among a stage II and III TNBC population despite our short follow-up evaluation. Longer follow-up evaluation will be required to determine additional outcome advantage for antiplatelet agent use. Our findings support consideration of investigation of antiplatelet therapy as an adjunctive therapy for TNBC at high risk for disease recurrence.

  5. Comparison of 627 patients with right- and left-sided colon cancer in China: Differences in clinicopathology, recurrence, and survival.

    Science.gov (United States)

    Qin, Qiong; Yang, Lin; Sun, Yong-Kun; Ying, Jian-Ming; Song, Yan; Zhang, Wen; Wang, Jin-Wan; Zhou, Ai-Ping

    2017-03-25

    Recent studies have reported increased mortality for right-sided colon cancers; however, the results are conflicting for different stage tumors. We examined the differences in clinicopathology between right- and left-sided colon cancers and the relationships between colon cancer location (right- and left-side) and 5-year disease-free survival (DFS) and overall survival (OS). We identified patients from 2005 to 2008 with stage II/III colon cancer who underwent surgery for curative intent. We explored the impact of the tumor location on the postoperative DFS and OS using univariate and multivariate analyses. Of 627 patients, 50.6% (317/627) had right-sided colon cancer. These patients were more likely to have weight loss, second primary tumor, elevated preoperative carbohydrate antigen 19-9 (CA19-9), increased incidence of non-adenocarcinoma, more poorly differentiated tumors, vascular invasion, defective mismatch repair, and a lighter smoking history (P colon cancer had a higher recurrence incidence compared with left-sided cancer (30.6% vs. 23.2%, P = 0.037), particularly with multiple metastatic sites in the first recurrence (17.5% vs. 5.6%, P = 0.020). Kaplan-Meier survival curves demonstrated a significant difference in the 5-year DFS rate between right- and left-sided cancers across all stages (68.1% vs. 75.2%, P = 0.043). However, there was no significant difference in the 5-year OS rate between the two groups (73.8% vs. 79.0%, P = 0.103). Subgroup analysis demonstrated that patients with left-sided colon cancer had a significantly better 5-year DFS and OS rates compared with those with right-sided disease at stage III (64.3% vs. 46.8%, P = 0.002; 69.5% vs. 53.5%, P = 0.006, respectively); there were no significant differences in the 5-year DFS and OS rates at stage II (85.2% vs. 85.9%, P = 0.819; 89.8% vs. 88.5%, P = 0.803, respectively). Adjusted Cox regression analysis showed no significant differences in the 5-year OS and DFS rates for

  6. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

    Science.gov (United States)

    Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

    2017-03-14

    BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly

  7. E-Cadherin complex protein expression and survival in ovarian carcinoma.

    Science.gov (United States)

    Davidson, B; Gotlieb, W H; Ben-Baruch, G; Nesland, J M; Bryne, M; Goldberg, I; Kopolovic, J; Berner, A

    2000-12-01

    The aim of this study was to analyze the correlation between expression of E-cadherin complex proteins, epidermal growth factor receptor (EGFR), and c-erbB-2 and disease outcome in advanced-stage ovarian carcinomas. Sections from 75 primary ovarian carcinomas (=37) and metastatic lesions (=38) from 45 patients diagnosed with advanced-stage ovarian carcinoma (FIGO stage III-IV) were immunostained and evaluated for staining pattern, extent, and intensity. Patients were divided in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cutoff of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Comparison of all primary and metastatic lesions showed upregulation of gamma-catenin protein expression in the latter (P = 0.05). When segregated according to disease outcome, the expression of all studied proteins, with the exception of EGFR, was more diffuse in tumors of short-term survivors. The presence of cytoplasmic staining for c-erbB-2 was associated with poor survival in the entire cohort (P = 0.007), as well as in primary tumors alone (P = 0.003), in survival analysis. Similar results were seen in the evaluation of primary tumors for gamma-catenin (P = 0.002). gamma-Catenin, and possibly c-erbB-2, are valid markers of poor survival in advanced-stage ovarian carcinoma. Copyright 2000 Academic Press.

  8. [Toxic methemoglobinemia].

    Science.gov (United States)

    Bender, P; Neuhaus, H

    2011-04-01

    A 19 year-old female patient suffered from severe hypoxemia after an ambulant surgery for splayfeet. Local anesthesia had been performed with prilocain and bupivacain. Methemoglobinemia was suspected and treated with ascorbine acid and methylene blue. The patient was then admitted to hospital. The patient was well orientated and awake. She complained of a mild headache and general illness. There was marked central cyanosis. A blood sample was dark-red to brownish. The periphere oxygen saturation was 85%. A cardiac ultrasound and a chest X ray were without pathological findings. Initial arterial blood gas analysis showed a concentration of methemoglobin of 24%. On intensive care clinical and laboratory findings quickly resolved and methemoglobin concentration normalized after one day. The patient had no symptoms anymore and was discharged the next day. In treatment-resistent hypoxemia after local anesthesia toxic methemoglobinaemia should be suspected. Therapy of choice is immediate administration of methylene blue. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Survival after definitive (chemo)radiotherapy in esophageal cancer patients: a population-based study in the north-East Netherlands.

    Science.gov (United States)

    Smit, Justin K; Muijs, Christina T; Burgerhof, Johannes G M; Paardekooper, Gabriel; Timmer, Paul R; Muller, Karin; Woutersen, Dankert; Mul, Véronique E; Beukema, Jannet C; Hospers, Geke A P; van Dijk, Boukje A C; Langendijk, Johannes A; Plukker, John Th M

    2013-06-01

    Definitive (chemo)radiotherapy is employed in esophageal cancer patients as an alternative for patients considered medically unfit for surgery or having unresectable tumors. We evaluated a population-based cohort to improve the selection for intensified nonsurgical strategies and to identify prognostic factors. Patients who had squamous cell carcinoma (SCC) or adenocarcinoma (AC) were treated in four referral centers in the north-east Netherlands with definitive chemoradiotherapy (dCRT) or radiotherapy (dRT) between 1996 and 2008. Of the 287 included patients, 110 were treated with dCRT and 177 with dRT. Median overall survival (OS) was 11 months (95 % confidence interval: 10-12 months), with OS of 22 and 8 % and disease-free survival (DFS) of 16 and 5 % at 2 and 5 years, respectively. DFS at 2 and 5 years was 24 and 9 % for SCC versus 10 and 2 % for AC patients (P = 0.006). OS after 2 and 5 years was 29 and 14 % for SCC patients versus 17 and 3 % for AC patients (P = 0.044). On multivariate Cox regression, SCC was an independent prognostic factor for DFS [P = 0.020, hazard ratio (HR) = 0.71] and OS (P = 0.047, HR = 0.76). On matched cohort analysis, DFS was higher in the dCRT group compared with dRT patients (P = 0.016). The locoregional failure rate was lower in the dCRT group and in SCC patients (P = 0.001 and 0.046). Long-term results and the local control rate in SCC patients were better after definitive (chemo)radiotherapy compared with in AC patients. SCC was an independent prognostic factor for survival. Definitive chemoradiotherapy leads to improved local control rate and DFS.

  10. [Completion of the dog toxicity project at the University of Utah: statistical comparison

    Energy Technology Data Exchange (ETDEWEB)

    Bruenger, F.W.; Lloyd, R.D.

    1999-12-15

    Radium (Ra) toxicity in dogs is a cornerstone for the evaluation of plutonium (Pu) toxicity, as it provides a possible link to Pu toxicity in humans. Survival regression models with covariates were used to estimate the risk to survival and the frequency and latency of bone tumor development. It appears for Ra that dose-rate is a more significant contributor to non-survival and bone tumors than is skeletal dose.

  11. Pretreatment depression as a prognostic indicator of survival and nutritional status in patients with head and neck cancer.

    Science.gov (United States)

    Kim, Shin-Ae; Roh, Jong-Lyel; Lee, Sang-Ah; Lee, Sang-Wook; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2016-01-01

    The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC). For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and nutritional status and laboratory data. Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P nutritional status, and survival outcomes in patients with HNSCC. © 2015 American Cancer Society.

  12. Toxicity assessment of sediment cores from Santa Monica Bay, California.

    Science.gov (United States)

    Greenstein, Darrin; Bay, Steven; Jirik, Andrew; Brown, Jeffrey; Alexander, Clark

    2003-01-01

    During the summer of 1997, sediment core samples were taken at 25 stations in Santa Monica Bay. Toxicity testing was performed on 4-cm sections of the entire length of each core using purple sea urchin fertilization and amphipod survival tests. The sea urchin test identified sections as being toxic at six stations, all located near current or former Hyperion Treatment Plant (HTP) wastewater outfall locations. The amphipod test identified sections from 17 stations as having toxic sediments. The stations having toxic sediments were scattered throughout the bay and toxicity was identified at numerous core depths. Spatial and temporal patterns indicated that toxicity was most strongly associated with the historical disposal of municipal wastewater sludge. Many of the sections toxic to the amphipods did not have chemical levels expected to cause toxicity and were in locations where a source of toxicity was not apparent.

  13. Prognostic nutritional index as a prognostic biomarker for survival in digestive system carcinomas.

    Science.gov (United States)

    Zhao, Yang; Xu, Peng; Kang, Huafeng; Lin, Shuai; Wang, Meng; Yang, Pengtao; Dai, Cong; Liu, Xinghan; Liu, Kang; Zheng, Yi; Dai, Zhijun

    2016-12-27

    The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas.

  14. MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

    Directory of Open Access Journals (Sweden)

    Thomas Pavelitz

    Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

  15. Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

  16. Influence of family history on survival in patients with colon and rectal cancer.

    Science.gov (United States)

    Lee, Seong Dae; Kim, Byung Chang; Han, Kyung Su; Hong, Chang Won; Sohn, Dae Kyung; Park, Ji Won; Park, Sung Chan; Kim, Sun Young; Baek, Ji-Yeon; Chang, Hee Jin; Kim, Dae Yong; Oh, Jae Hwan

    2014-03-01

    We aimed to investigate the association between a family history (FH) of colorectal cancer (CRC) and cancer recurrence and survival in patients with stage III CRC. From April 2001 to December 2007, 1102 patients with stage III CRC were enrolled and their data including FH, clinicopathological characteristics of the tumor were retrospectively analyzed. Of 971 patients that were finally enrolled, 63 (6.5%) reported CRC in at least one first-degree relative. Death occurred in 12.7% of the CRC patients with an FH and 21.8% in those without an FH. A multivariate analysis showed that patients with an FH of CRC, compared with those without FH, had an adjusted hazard ratios (HR) of 0.674 (P = 0.281) for overall survival (OS) and 0.672 (P = 0.220) for disease-free survival (DFS). However, the location of tumor, preoperative carcinoembryonic antigen (CEA) level, tumor invasion (T) stage and lymph node (N) metastasis significantly affected OS and DFS. Furthermore, whereas the FH of CRC patients was associated with a favorable prognosis in stage III colon cancer (HR 0.224, P = 0.040) but not in rectal cancer (HR 1.225, P = 0.640). In patients with stage III CRC, tumor location (especially in the rectum), a high preoperative CEA level and advanced T and N stages indicate a poor prognosis. However, in stage III colon cancer FH is associated with improved survival. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  17. Meta-analysis of the effects of beta blocker on survival time in cancer patients.

    Science.gov (United States)

    Choi, Chel Hun; Song, Taejong; Kim, Tae Hyun; Choi, Jun Kuk; Park, Jin-Young; Yoon, Aera; Lee, Yoo-Young; Kim, Tae-Joong; Bae, Duk-Soo; Lee, Jeong-Won; Kim, Byoung-Gie

    2014-07-01

    This study was to elucidate the potential benefit of beta blockers on cancer survival. We comprehensively searched PubMed, Embase, and the Cochrane Library from their inception to April 2013. Two authors independently screened and reviewed the eligibility of each study and coded the participants, treatment, and outcome characteristics. The primary outcomes were overall survival (OS) and disease-free survival (DFS). Twelve studies published between 1993 and 2013 were included in the final analysis. Four papers reported results from 10 independent groups, resulting in a total of 18 comparisons based on data obtained from 20,898 subjects. Effect sizes (hazard ratios, HR) were heterogeneous, and random-effects models were used in the analyses. The meta-analysis demonstrated that beta blocker use is associated with improved OS (HR 0.79; 95 % CI 0.67-0.93; p = 0.004) and DFS (HR 0.69; 95 % CI 0.53-0.91; p = 0.009). Although statistically not significant, the effect size was greater in patients with low-stage cancer or cancer treated primarily with surgery than in patients with high-stage cancer or cancer treated primarily without surgery (HR 0.60 vs. 0.78, and 0.60 vs. 0.80, respectively). Although only two study codes were analyzed, the studies using nonselective beta blockers showed that there was no overall effect on OS (HR 0.52, 95 % CI 0.09-3.04). This meta-analysis provides evidence that beta blocker use can be associated with the prolonged survival of cancer patients, especially patients with early-stage cancer treated primarily with surgery.

  18. Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status.

    Science.gov (United States)

    Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia; Derchain, Sophie

    2013-04-01

    To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression.

  19. Expression of CUB domain containing protein (CDCP1) is correlated with prognosis and survival of patients with adenocarcinoma of lung.

    Science.gov (United States)

    Ikeda, Jun-ichiro; Oda, Tomofumi; Inoue, Masayoshi; Uekita, Takamasa; Sakai, Ryuichi; Okumura, Meinoshin; Aozasa, Katsuyuki; Morii, Eiichi

    2009-03-01

    CUB domain containing protein (CDCP1), a transmembrane protein with intracellular tyrosine residues which are phosphorylated upon activation, is supposed to be engaged in proliferative activities and resistance to apoptosis of cancer cells. Expression level of CDCP1 was examined in lung adenocarcinoma, and its clinical implications were evaluated. CDCP1 expression was immunohistochemically examined in lung adenocarcinoma from 200 patients. Staining intensity of cancer cells was categorized as low and high in cases with tumor cells showing no or weak and strong membrane staining, respectively. MIB-1 labeling index was also examined. There were 113 males and 87 females with median age of 63 years. Stage of disease was stage I in 144 cases (72.0%), II in 19 (9.5%), and III in 37 (18.5%). Sixty of 200 cases (30.0%) were categorized as CDCP1-high, and the remaining as CDCP1-low. Significant positive correlation was observed between CDCP1-high expression and relapse rate (P < 0.0001), poor prognosis (P < 0.0001), MIB-1 labeling index (P < 0.0001), and occurrence of lymph node metastasis (P = 0.0086). There was a statistically significant difference in disease-free survival (DFS) (P < 0.0001) and overall survival (OS) rates (P < 0.0001) between patients with CDCP1-high and CDCP1-low tumors. Univariate analysis showed that lymph node status, tumor stage, and CDCP1 expression were significant factors for both OS and DFS. Multivariate analysis revealed that only CDCP1 expression was an independent prognostic factor for both OS and DFS. CDCP1 expression level is a useful marker for prediction of patients with lung adenocarcinoma

  20. Ten-year Biochemical Disease-free Survival After High-intensity Focused Ultrasound (HIFU) for Localized Prostate Cancer: Comparison with Four Different Generation Devices

    Science.gov (United States)

    Uchida, T.; Nakano, M.; Shoji, S.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.

    2010-03-01

    HIFU has been recognized as a minimally invasive treatment option for localized prostate cancer. The purpose of the study was to assess with a long-term outcome of HIFU for prostate cancer. From January 1999, a total of 657 patients who had HIFU with at least 2 year follow-up were treated with four different types of Sonablate® (Focus Surgery, Indianapolis, USA) devices. Thirty-three patients were treated with Sonablate® 200 (S200) from 1999 to 2001, 406 patients with Sonablate® 500 (S500) from 2001 to 2005, 200 patients with Sonablate® 500 version 4 (V4) from 2005-2008 and 19 patients with Sonablate® 500 TCM (TCM) from 2007. Biochemical disease-free survival rate (bDFS) in all patients was 59% in 8 years. bDFS in 8 years in patients with S200 and S500 groups were 55% and 56%, and bDFS in 4 and 2 years in patients with V4 and TCM group were 72% and 84%, respectively. bDFS in low, intermediate, and high risk groups were 75%, 54%, and 43% in S200/S500 and 93%, 72%, and 58% in V4/TCM group. Negative prostate biopsy rate after HIFU was 97% in S200, 79% in S500, 94% in V4 and 100% in TCM group. HIFU as primary therapy for prostate cancer is indicated in patients with low- and intermediate-risk (T1-T2b N0M0 disease, a Gleason score of ⩽7, a PSA level of <20 ng/mL) and a prostate volume of less than 40 mL. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

  1. Pulmonary toxicity following bleomycin use: A single-center experience

    Directory of Open Access Journals (Sweden)

    Irappa Madabhavi

    2017-01-01

    Conclusion: BIP is noteworthy lung toxicity as subsequent mortality ranges from 10% to 20% and shrinks survival rate in patients with highly curable malignant conditions. Physicians should be vigilant concerning this impending side effect.

  2. 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....

  3. Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion.

    Science.gov (United States)

    Dang, Tam; Nguyen, Cham; Tran, Phu N

    2017-01-01

    Despite the risk of cyanide toxicity and lack of efficacy, amygdalin is still used as alternative cancer treatment. Due to the highly lethal nature of cyanide toxicity, many patients die before getting medical care. Herein, we describe the case of a 73-year-old female with metastatic pancreatic cancer who developed cyanide toxicity from taking amygdalin. Detailed history and physical examination prompted rapid clinical recognition and treatment with hydroxocobalamin, leading to resolution of her cyanide toxicity. Rapid clinical diagnosis and treatment of cyanide toxicity can rapidly improve patients' clinical outcome and survival. Inquiries for any forms of ingestion should be attempted in patients with clinical signs and symptoms suggestive of poisoning.

  4. Acute toxicity of selected hydrazines to the common guppy

    Energy Technology Data Exchange (ETDEWEB)

    Slonim, A.R.

    1977-01-01

    Hydrazine, unsymmetrical dimethylhydrazine (UDMH), Aerozine-50 and monomethylhydrazine were evaluated, respectively, in three or four static bioassays each using hard and soft water. Hydrazine was the most toxic compound and UDMH the least toxic to common guppies. Hydrazine was significantly more toxic in soft water than hard water, whereas UDMH was the opposite. The results of bioassays in which survival times of fish pre-exposed to these compounds were compared to those previously unexposed, along with other observations, indicate that the toxic effects of the hydrazines are cumulative. The effects of chemical differences in these compounds, of water quality characteristics and of other factors on acute toxicity are discussed.

  5. Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Agarwal, Rajni [Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California (United States); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gray, Christine C. [Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California (United States); Harris, Jeremy P.; Million, Lynn [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Kiamanesh, Eileen F. [Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

    2014-05-01

    Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

  6. Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

    Science.gov (United States)

    Santini, Daniele; Santoni, Matteo; Conti, Alessandro; Procopio, Giuseppe; Verzoni, Elena; Galli, Luca; di Lorenzo, Giuseppe; De Giorgi, Ugo; De Lisi, Delia; Nicodemo, Maurizio; Maruzzo, Marco; Massari, Francesco; Buti, Sebastiano; Altobelli, Emanuela; Biasco, Elisa; Ricotta, Riccardo; Porta, Camillo; Vincenzi, Bruno; Papalia, Rocco; Marchetti, Paolo; Burattini, Luciano; Berardi, Rossana; Muto, Giovanni; Montironi, Rodolfo; Cascinu, Stefano; Tonini, Giuseppe

    2016-01-01

    PURPOSE We retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma. RESULTS 37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms. CONCLUSIONS The prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients. PMID:27027342

  7. Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma.

    Science.gov (United States)

    Santini, Daniele; Santoni, Matteo; Conti, Alessandro; Procopio, Giuseppe; Verzoni, Elena; Galli, Luca; di Lorenzo, Giuseppe; De Giorgi, Ugo; De Lisi, Delia; Nicodemo, Maurizio; Maruzzo, Marco; Massari, Francesco; Buti, Sebastiano; Altobelli, Emanuela; Biasco, Elisa; Ricotta, Riccardo; Porta, Camillo; Vincenzi, Bruno; Papalia, Rocco; Marchetti, Paolo; Burattini, Luciano; Berardi, Rossana; Muto, Giovanni; Montironi, Rodolfo; Cascinu, Stefano; Tonini, Giuseppe

    2016-05-31

    We retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma. 37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms. The prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients.

  8. Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pickles, Martin D. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.pickles@hull.ac.uk; Manton, David J. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: d.j.manton@hull.ac.uk; Lowry, Martin [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.lowry@hull.ac.uk; Turnbull, Lindsay W. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: l.w.turnbull@hull.ac.uk

    2009-09-15

    The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

  9. Does a mandibular access osteotomy improve survival in pT2 oral tongue cancers? Retrospective study at a single institution.

    Science.gov (United States)

    Ong, H S; Gokavarapu, S; Tian, Z; Li, J; Cao, W; Zhang, C P

    2018-03-01

    The surgical approach to the resection of oral tongue cancers can involve transoral resection (TOR) or a temporary mandibulotomy access (TMA). There are no relevant guidelines, and the oncological safety of TOR needs consideration. The objective of this study was to investigate TMA and TOR in pT2 oral tongue cancer surgery with regard to cancer outcomes. Demographic, surgical, and histology data from primary pT2 tongue cancers were recorded and evaluated through multivariate Cox regression for local recurrence (LR), disease-free survival (DFS), and overall survival (OS). A total of 166 patients with pT2 primary oral tongue cancer fulfilled the inclusion criteria; TOR was used in 95 patients and TMA in 71 patients. The minimum follow-up was 29 months. Group comparisons showed a significantly higher frequency of perineural spread (P=0.013) in the TMA group; a higher frequency of involved margins on initial resection was seen in TOR patients (P=0.010). Adjuvant postoperative radiotherapy was preferred in the TMA group, in line with the high pN positive status. Multivariate Cox regression showed significantly higher LR and lower DFS in the TOR group despite stratification of the major prognostic factors. The 5-year survival rate was reduced to 82.2% in the TOR group, while it remained constant at 93.0% in the TMA group. TMA provided superior local control and DFS compared to TOR in pT2 tongue cancers. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Can metastatic lymph node ratio (LNR) predict survival in oral cavity cancer patients?

    Science.gov (United States)

    Sayed, Suhail I; Sharma, Shilpi; Rane, Pawan; Vaishampayan, Sagar; Talole, Sanjay; Chaturvedi, Pankaj; Chaukar, Devendra; Deshmukh, Anuja; Agarwal, Jai Prakash; D'cruz, Anil K

    2013-09-01

    To evaluate the prognostic role of the lymph node ratio (LNR; ratio of total positive nodes to total dissected nodes) in oral squamous cell carcinoma (OSCC) as compared to pN staging with an aim to provide an optimal cut-off value. 1,408 OSCC previously untreated patients who underwent treatment (surgery + neck dissection + adjuvant treatment). LNR sensitivity with respect to survival was calculated using receiver operating characteristic (ROC) curves and Cox regression method. LNR and TNM staging variables were subjected to multivariate analysis. LNR (0.088) showed significant association with survival outcomes. For patients with LNR ≤0.088, the OS, DFS, local control, regional control and distant metastasis rates were 64%, 70%, and 89%; for LNR >0.088 it was 22%, 19%, and 52%, respectively (P analysis LNR of 0.088 was seen to be an independent prognostic factor for 5-year regional control (p, hazard ratio [95% confidence interval]; 0.044, 2.016 (1.019-3.990), DFS, 0.032, 1.858 (1.054-3.276), and OS, 0.040, 1.195 (1.033-1.144). On multivariate analysis LNR categorization showed a statistically significant [0.032, 1.858, (1.054-3.276)] advantage over pN staging [0.527, 1.208 (1.054-3.276)] in predicting survival. LNR is a better prognostic marker than the current N staging of TNM classification. Copyright © 2013 Wiley Periodicals, Inc.

  11. The Carcinoma–Stromal Ratio of Colon Carcinoma Is an Independent Factor for Survival Compared to Lymph Node Status and Tumor Stage

    Directory of Open Access Journals (Sweden)

    Wilma E. Mesker

    2007-01-01

    Full Text Available Background: Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP, as a derivative from the carcinoma-stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. Methods: In a retrospective study of 63 patients with colon cancer (stage I–III, 1990–2001 the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I–III, 1980–1992. (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy. Results: Of 122 analyzed patients 33 (27.0% had a low CP and 89 (73.0% a high CP. The analysis of mean survival revealed: overall-survival (OS 2.13 years, disease-free- survival (DFS 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p < 0.0001, DFS p < 0.0001 with hazard ratio’s of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OSp < 0.001, OSp < 0.001. Conclusions: The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups.

  12. Toxic Response of Nitrobacter to Orange II and Direct Blue 71 ...

    African Journals Online (AJOL)

    Tolerance of Nitrobacter to Orange II (C.L. 15510) and Direct Blue 71 (C.I. 34140) dyes was determined by total viable count. There was decrease in percentage log survival with increase in concentration of the toxicants and increase in exposure time. Percentage survival at 20h was 84.50% and 75.50% at toxicants ...

  13. Sediment toxicity in Boston Harbor: Magnitude, extent, and relationships with chemical toxicants. Technical memo

    Energy Technology Data Exchange (ETDEWEB)

    Long, E.R.; Sloane, G.M.; Carr, R.S.; Scott, K.J.; Thursby, G.B.

    1996-06-01

    A survey of the toxicity of sediments throughout Boston Harbor and vicinity was conducted by NOAA`s National Status and Trends (NS&T) Program. The objectives of the survey were to determine the magnitude and spatial extent of toxicity and the relationship between measures of toxicity and the concentrations of chemical toxicants in the sediments. Multiple toxicity tests were performed including: an amphipod survival test performed with whole sediments, a microbial bioluminescence test performed with organic solvent extracts of the sediments, and sea urchin fertilization and embryological development tests performed with the pore waters extracted from the sediments. Chemical analyses were performed on selected samples for trace metals, polynuclear aromatic hydrcarbons, chlorinated pesticides, PCBs, and butyltins.

  14. A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

    Science.gov (United States)

    Xu, Ling; Li, Jiang-Hong; Ye, Jing-Ming; Duan, Xue-Ning; Cheng, Yuan-Jia; Xin, Ling; Liu, Qian; Zhou, Bin; Liu, Yin-Hua

    2017-08-20

    Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant

  15. Effects of natural phenolic compounds from a desert dominant shrub Larrea divaricata Cav. on toxicity and survival in mice Efectos de los compuestos fenólicos naturales de un arbusto dominante del desierto, Larrea divaricata Cav. sobre la toxicidad y sobrevida en ratones

    Directory of Open Access Journals (Sweden)

    J.M. RÍOS

    2008-06-01

    Full Text Available It is known that generalist herbivores may circumvent intoxication by ingesting small quantities from a mixture of plant secondary metabolites. However a single chemical, a highly toxic one or the most abundant in the mixture could cause toxicity. Survivorship and toxicity in Rockland male mice were measured to determine if the toxic effects of the phenolic resin of creosote bush (Larrea divaricata Cav. is due to its major constituent, the nordihydroguaiaretic acid (NDGA or to the total concentration of phenolic compounds in this resin. This objective was accomplished by exposing mice to voluntary feeding on resin-treated rat chow and by oral gavaging of mice with the following doses and compounds: Resin-100 mg (n = 7, NDGA-15 mg (n = 8, and NDGA-100 mg (n = 10 and Control (n = 6. Our hypothesis was that NDGA is responsible for the toxicity of Larrea divaricata's phenolic resin. Voluntary resin intake by mice had a pronounced toxic effect, producing body mass loss and significant reduction of food intake. Mice gavaged with Resin-100 mg, NDGA-100 mg, and NDGA-15 mg showed a significant reduction in survival probability compared to mice under Control conditions. Animáis exposed to NDGA-15 mg had a higher survivorship compared to the NDGA-100 mg animáis, and equivalent survivorship to the Resin-100 mg (containing 15 mg of NDGA animáis. No significant differences in detoxification, measured as glucuronic acid conjugates in urine, were detected among gavage treatments. Therefore, given that just 15 mg of NDGA were enough to produce the same effect as the whole resin, we suggest that NDGA is the main constituent of Larrea divaricata's resin responsible for the toxic effect of the phenolic resin of this plant.Los herbívoros generalistas pueden evitar la intoxicación ingiriendo pequeñas cantidades de una mezcla de metabolitos secundarios de plantas. Sin embargo, un solo compuesto, uno altamente tóxico o el más abundante en la mezcla es el que

  16. Identification of causes of oil sands coke leachate toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Puttaswamy, N.; Liber, K. [Saskatchewan Univ., Regina, SK (Canada)

    2010-07-01

    The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

  17. Using single-species toxicity tests, community-level responses, and toxicity identification evaluations to investigate effluent impacts

    Energy Technology Data Exchange (ETDEWEB)

    Maltby, L.; Clayton, S.A.; Yu, H.; McLoughlin, N.; Wood, R.M.; Yin, D.

    2000-01-01

    Whole effluent toxicity (WET) tests are increasingly used to monitor compliance of consented discharges, but few studies have related toxicity measured using WET tests to receiving water impacts. Here the authors adopt a four-stage procedure to investigate the toxicity and biological impact of a point source discharge and to identify the major toxicants. In stage 1, standard WET tests were employed to determine the toxicity of the effluent. This was then followed by an assessment of receiving water toxicity using in situ deployment of indigenous (Gammarus pulex) and standard (Daphnia magna) test species. The third stage involved the use of biological survey techniques to assess the impact of the discharge on the structure and functioning of the benthic macroinvertebrate community. In stage 4, toxicity identification evaluations (TIE) were used to identify toxic components in the effluent. Receiving-water toxicity and ecological impact detected downstream of the discharge were consistent with the results of WET tests performed on the effluent. Downstream of the discharge, there was a reduction in D. magna survival, in G. pulex survival and feeding rate, in detritus processing, and in biotic indices based on macroinvertebrate community structure. The TIE studies suggested that chlorine was the principal toxicant in the effluent.

  18. Profile of vemurafenib-induced severe skin toxicities.

    Science.gov (United States)

    Peuvrel, L; Quéreux, G; Saint-Jean, M; Brocard, A; Nguyen, J M; Khammari, A; Knol, A C; Varey, E; Dréno, B

    2016-02-01

    Vemurafenib, a BRAF inhibitor, is commonly associated with skin toxicity. The impact of severe forms is unknown. To determine the rate of permanent vemurafenib discontinuation due to grade 3-4 skin toxicity, features of these toxicities, their recurrence rate after a switch to dabrafenib and their impact on overall survival. Retrospective cohort study of 131 patients treated with vemurafenib for melanoma between November 2010 and December 2014. Data on skin toxicities, the need for vemurafenib adjustment and the impact of switching to dabrafenib were collected. Regarding survival analysis, a conditional landmark analysis was performed to correct lead-time bias. Among the 131 vemurafenib-treated patients, 26% developed grade 3-4 skin toxicity. Forty-four percent of them permanently discontinued their treatment, mainly due to rash and classic skin adverse reactions (Steven-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms). Conversely, photosensitivity and carcinomas rarely required treatment adjustment. Grade 3-4 rashes were associated with clinical or biological abnormalities in 94% of patients. Among the 10 patients who subsequently switched to dabrafenib, skin toxicity recurred only in one patient. Overall survival was significantly prolonged in case of severe skin toxicity emerging within the first 4 (P = 0.014) and 8 weeks (P = 0.038) on vemurafenib, with only a trend at 12 weeks (P = 0.052). Median overall survival was also prolonged in case of severe rash. In this study, vemurafenib was continued in 56% of patients with grade 3-4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and

  19. Toxic hemolytic anemias.

    OpenAIRE

    ZEMANOVÁ, Vendula

    2014-01-01

    This thesis deals with toxic hemolytic anemias which are often unheeded. There are described laboratory signs of hemolytic anemias, their dividing into the various groups and it focuses mainly to toxic and drug-related hemolytic anemias and their causations.

  20. The role of LINE-1 methylation in predicting survival among colorectal cancer patients: a meta-analysis.

    Science.gov (United States)

    Ye, Ding; Jiang, Danjie; Li, Yingjun; Jin, Mingjuan; Chen, Kun

    2017-08-01

    The prognostic value of long interspersed nucleotide element-1 (LINE-1) methylation in patients with colorectal cancer (CRC) remains uncertain. We have therefore performed a meta-analysis to elucidate this issue. The PubMed and Web of Science databases were searched for studies published up to 30 June 2016 which reported on an association between LINE-1 methylation and overall survival (OS), disease-free survival (DFS), or cancer-specific survival (CSS) among CRC patients. The reference lists of the identified studies were also analyzed to identify additional eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects or the random-effects model. Stratification analysis and meta-regression analysis were performed to detect the source of heterogeneity. Analyses of sensitivity and publication bias were also carried out. Thirteen independent studies involving 3620 CRC patients were recruited to the meta-analysis. LINE-1 hypomethylation was found to be significantly associated with shorter OS (HR 2.92, 95% CI 2.20-3.88, p LINE-1 hypomethylation and OS or DFS, with the exception being CSS. Moreover, meta-regression analysis suggested that one of the contributors to between-study heterogeneity on the association between LINE-1 methylation and CSS was statistical methodology. The subgroup analysis suggested that the association in studies using the Cox model statistical method (HR 2.76, 95% CI 1.90-4.01, p LINE-1 methylation is significantly associated with the survival of CRC patients and that it could be a predictive factor for CRC prognosis.

  1. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study.

    Science.gov (United States)

    Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M; Thürlimann, Beat; Mouridsen, Henning; Mauriac, Louis; Forbes, John F; Paridaens, Robert; Láng, István; Smith, Ian; Chirgwin, Jacquie; Pienkowski, Tadeusz; Wardley, Andrew; Price, Karen N; Gelber, Richard D; Coates, Alan S; Goldhirsch, Aron

    2011-03-20

    Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months. Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer.

  2. Antibiotics Reduce Retinal Cell Survival In Vitro.

    Science.gov (United States)

    Lindsey, Amy E; Townes-Anderson, Ellen

    2017-11-02

    Antibiotics such as gentamicin (an aminoglycoside) and penicillin (a beta-lactam antibiotic) are routinely used in retinal cell and explant cultures. In many cases, these in vitro systems are testing parameters regarding photoreceptor transplantation or preparing cells for transplantation. In vivo, milligram doses of gentamicin are neurotoxic to the retina. However, little is known about the effects of antibiotics to retina in vitro and whether smaller doses of gentamicin are toxic to retinal cells. To test toxicity, retinal cells were dissociated from tiger salamander, placed in culture, and treated with either 20 μg/ml gentamicin, 100 μg/ml streptomycin, 100 U/ml antibiotic/antimycotic, 0.25 μg/ml amphotericin B, or 100 U/ml penicillin G. All dosages were within manufacturer's recommended levels. Control cultures had defined medium only. Cells were fixed at 2 h or 7 days. Three criteria were used to assess toxicity: (1) survival of retinal neurons, (2) neuritic growth of photoreceptors assessed by the development of presynaptic varicosities, and (3) survival and morphology of Mueller cells. Rod cells were immunolabeled for rod opsin, Mueller cells for glial fibrillary acidic protein, and varicosities for synaptophysin. Neuronal cell density was reduced with all pharmacological treatments. The number of presynaptic varicosities was also significantly lower in both rod and cone photoreceptors in treated compared to control cultures; further, rods were more sensitive to gentamicin than cones. Penicillin G (100 U/ml) was overall the least inhibitory and amphotericin B the most toxic of all the agents to photoreceptors. Mueller cell survival was reduced with all treatments; reduced survival was accompanied by the appearance of proportionally fewer stellate and more rounded glial morphologies. These findings suggest that even microgram doses of antibiotic and antimycotic drugs can be neurotoxic to retinal cells and reduce neuritic regeneration in cell

  3. Design for Sustainability (DfS) and Dematerialization by design

    Energy Technology Data Exchange (ETDEWEB)

    Marttila, T.; Kohtala, C. [Aalto Univ. School of Art and Design, Helsinki (Finland). Dept. of Design

    2011-07-01

    This workshop explored the possibilities to promote dematerialization by design. During the workshop track the participants gained insight into several design- for-sustainability approaches and methods, in order to exploit the strengths of the design process itself. The student participants were invited to challenge the 'traditional' design approach, which often focuses only on getting a product onto the market on time, and instead looked into new ways to expand stakeholder participation, to increase the basis for decision-making into a collaboratively mediated setting of goals and aims, and to pursue the more widespread participation necessary for sustainable outcomes. The students were then able to use these approaches to work on their predefined interest areas, to find new and meaningful ways to implement design in the pursuit of more sustainable solutions. (orig.)

  4. Impact of "Killer Immunoglobulin-Like Receptor /Ligand" Genotypes on Outcome following Surgery among Patients with Colorectal Cancer: Activating KIRs Are Associated with Long-Term Disease Free Survival.

    Directory of Open Access Journals (Sweden)

    Kemal Beksac

    Full Text Available Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS. Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4 genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR and A-Bw4 (ligand for inhibitory KIR3DL1 were observed more frequently (p=0.017 and p=0.024; and KIR2DS2 and KIR2DS3 (both activating KIRs were observed less frequently (p=0.005 and p=0.043. Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07. The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023. KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028. The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004. In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs

  5. Survival Outcome after Stereotactic Body Radiation Therapy and Surgery for Early Stage Non-Small Cell Lung Cancer: A Meta-Analysis.

    Science.gov (United States)

    Yu, Xiao-Jun; Dai, Wan-Rong; Xu, Yong

    2017-08-22

    Treatment modalities in medically compromised patients with early-stage non-small cell lung cancer (NSCLC) are controversial. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has been increasingly recognized as a favorable alternative to surgical resection for early-stage NSCLC. Many retrospective analyses compared the efficacy of stereotactic body radiotherapy (SBRT) with surgery for early-stage non-small cell lung cancer (NSCLC). However, the efficacy between SBRT and surgery regimens for patients with early-stage NSCLC remains unclear. This study aimed to investigate the efficacy between SBRT and surgery. Publications on comparison SBRT with Surgery in treatment of early stage non-small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Retrospective trials analyzed the summary hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. A systematic literature search was conducted including14 studies. In this meta-analysis, patients with SBRT achieved inferior OS, DFS, LC, RC, LRC and DC, compared with surgery. In this study we found more favorable outcomes with stage I NSCLC treated with SBRT. The surgery had no obvious advantages in this meta-analysis. Although surgery has become the recommended treatment at present, SBRT has potential to be an alternative treatment as a novel non-invasive radiation therapy modality in patients with stage I-II NSCLC.

  6. Concurrent chemoradiotherapy improves survival outcome in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2015-12-15

    To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer.

  7. Survival of experimentally induced Toxoplasma gondii tissue cysts in vacuum packed goat meat and dry fermented goat meat sausages.

    Science.gov (United States)

    Neumayerová, Helena; Juránková, Jana; Saláková, Alena; Gallas, Leo; Kovařčík, Kamil; Koudela, Břetislav

    2014-05-01

    Ingestion of raw or undercooked meat is a potential source of human toxoplasmosis. The aim of this study was to determine the viability of Toxoplasma gondii cysts in vacuum packed (VP) goat meat and in dry fermented sausages (DFS), and evaluate certain physical and chemical parameters, like water activity (aw), pH value, content of salt, dry matter and fat. A portion of muscle tissue from experimentally infected animals was used for production of VP meat with or without addition of 2.5% curing salt, and stored at 4 °C or at -20 °C. Results of bioassay showed that, samples of vacuum packed Toxoplasma positive meat without salt addition were alive after six weeks at 4 °C. Incubation at -20 °C supported the viability after 3 h, but not after 4 h. After 7 days in 2.5% of curing salt, samples of T. gondii VP goat meat were still viable, but not after 14 days at 4 °C. All the DFS samples were not positive for infective cysts which mean that, they do not pose a risk of T. gondii transmission. These data suggest that vacuum packaging increases the survival of T. gondii cysts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Development of marine toxicity data for ordnance compounds.

    Science.gov (United States)

    Nipper, M; Carr, R S; Biedenbach, J M; Hooten, R L; Miller, K; Saepoff, S

    2001-10-01

    A toxicity database for ordnance compounds was generated using eight compounds of concern and marine toxicity tests with five species from different phyla. Toxicity tests and endpoints included fertilization success and embryological development with the sea urchin Arbacia punctulata; zoospore germination, germling length, and cell number with the green macroalga Ulva fasciata; survival and reproductive success of the polychaete Dinophilus gyrociliatus; larvae hatching and survival with the redfish Sciaenops ocellatus; and survival of juveniles of the opossum shrimp Americamysis bahia (formerly Mysidopsis bahia). The studied ordnance compounds were 2,4- and 2,6-dinitrotoluene, 2,4,6-trinitrotoluene, 1,3-dinitrobenzene, 1,3,5-trinitrobenzene, 2,4,6-trinitrophenylmethylnitramine (tetryl), 2,4,6-trinitrophenol (picric acid), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The most sensitive toxicity test endpoints overall were the macroalga zoospore germination and the polychaete reproduction tests. The most toxic ordnance compounds overall were tetryl and 1,3,5-trinitrobenzene. These were also the most degradable compounds, often being reduced to very low or below-detection levels at the end of the test exposure. Among the dinitro- and trinitrotoluenes and benzenes, toxicity tended to increase with the level of nitrogenation. Picric acid and RDX were the least toxic chemicals tested overall.

  9. [Study on the regulation of autophagy against anticancer drugs' toxicity].

    Science.gov (United States)

    Lou, Xiao-e; Zhu, Yi; He, Qiao-jun

    2016-01-01

    Autophagy is a crucial biological process in eukaryotes, which is involved in cell growth, survival and energy metabolism. It has been confirmed that autophagy mediates toxicity of anticancer drugs, especially in heart, liver and neuron. It is important to understand the function and mechanism of autophagy in anticancer drugs-induced toxicity. Given that autophagy is a double-edged sword in the maintenance of the function of heart, liver and neuron, the autophagy-mediated toxicity are very complicated in the body. We provide a review on the concept of autophagy and current status about autophagy-mediated toxicity of anticancer drugs. The knowledge is crucial in the basic study of anticancer drugs-induced toxicity, and provides some strategies for the development of alleviating the toxicity of anticancer drugs.

  10. Association of rs2282679 A>C polymorphism in vitamin D binding protein gene with colorectal cancer risk and survival: effect modification by dietary vitamin D intake.

    Science.gov (United States)

    Zhu, Yun; Wang, Peizhong Peter; Zhai, Guangju; Bapat, Bharati; Savas, Sevtap; Woodrow, Jennifer R; Campbell, Peter T; Li, Yuming; Yang, Ning; Zhou, Xin; Dicks, Elizabeth; Mclaughlin, John R; Parfrey, Patrick S

    2018-02-06

    The rs2282679 A>C polymorphism in the vitamin D binding protein gene is associated with lower circulating levels of vitamin D. We investigated associations of this SNP with colorectal cancer (CRC) risk and survival and whether the associations vary by dietary vitamin D intake and tumor molecular phenotype. A population-based case-control study identified 637 incident CRC cases (including 489 participants with follow-up data on mortality end-points) and 489 matched controls. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip in cases and the Affymetrix Axiom® myDesign™ Array in controls. Logistic regression examined the association between the rs2282679 polymorphism and CRC risk with inclusion of potential confounders. Kaplan-Meier curves and multivariable Cox models assessed the polymorphism relative to overall survival (OS) and disease-free survival (DFS). The rs2282679 polymorphism was not associated with overall CRC risk; there was evidence, however, of effect modification by total vitamin D intake (P interaction  = 0.019). Survival analyses showed that the C allele was correlated with poor DFS (per-allele HR, 1.36; 95%CI, 1.05-1.77). The association of rs2282679 on DFS was limited to BRAF wild-type tumors (HR, 1.58; 95%CI, 1.12-2.23). For OS, the C allele was associated with higher all-cause mortality among patients with higher levels of dietary vitamin D (HR, 2.11; 95%CI, 1.29-3.74), calcium (HR, 1.93; 95%CI, 1.08-3.46), milk (HR, 2.36; 95%CI, 1.26-4.44), and total dairy product intakes (HR, 2.03; 95%CI, 1.11-3.72). The rs2282679 SNP was not associated with overall CRC risk, but may be associated with survival after cancer diagnosis. The association of this SNP on survival among CRC patients may differ according to dietary vitamin D and calcium intakes and according to tumor BRAF mutation status.

  11. Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

    Science.gov (United States)

    Myers, Todd M; Langston, Jeffrey L

    2011-06-01

    To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity. Published by Elsevier B.V.

  12. Multinationals and plant survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2010-01-01

    The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

  13. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    than uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt...uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt.”5...FEMALES AND TOXIC LEADERSHIP A thesis presented to the Faculty of the U.S. Army Command and General Staff College in

  14. CHEMICAL TOXICITY OF URANIUM

    Directory of Open Access Journals (Sweden)

    Sermin Cam

    2007-06-01

    Full Text Available Uranium, occurs naturally in the earth’s crust, is an alpha emitter radioactive element from the actinide group. For this reason, U-235 and U-238, are uranium isotopes with long half lives, have got radiological toxicity. But, for natural-isotopic-composition uranium (NatU, there is greater risk from chemical toxicity than radiological toxicity. When uranium is get into the body with anyway, also its chemical toxicity must be thought. [TAF Prev Med Bull 2007; 6(3.000: 215-220

  15. Evaluation of soil toxicity at Joliet Army Ammunition Plant

    Energy Technology Data Exchange (ETDEWEB)

    Simini, M.; Amos, J.C. [Geo-Centers, Inc., Aberdeen Proving Ground, MD (United States). Gunpowder Branch; Wentsel, R.S.; Checkai, R.T.; Phillips, C.T.; Chester, N.A. [Army ERDEC, Aberdeen Proving Ground, MD (United States); Major, M.A. [Army CHPPM, Frederick, MD (United States)

    1995-04-01

    Environmental toxicity testing and chemical analyses of soil were performed as part of an ecological risk assessment at the Joliet Army Ammunition Plant (JAAP), Joliet, Illinois. Soils were collected from an area where munitions were loaded, assembled, and packed (area L7, group 1), and from an area where waste explosives were burned on unprotected soil (area L2). Control samples were collected from an adjacent field. Soil toxicity was determined using early seedling growth and vigor tests, earthworm survival and growth tests, and Microtox{reg_sign} assays. Relative toxicity of soils was determined within each area based on statistical significant (p = 0.05) of plant and earthworm growth and survival, and the effective concentration at which luminescence of the bacterium Photobacterium phosphoreum was reduced by 50% (EC50) in the Microtox assay. Samples were designated as having high, moderate, or no significant toxicity. Soil that had significant toxicity according to at least one test, and representative samples showing no toxicity, were analyzed for munitions via HPLC. Chemical residues found in soils were 2,4,6-trinitrotoluene (TNT); 1,3,5-trinitrobenzene (TNB); 2,4-dinitrotoluene (2,4-DNT); 2,6-dinitrotoluene; 2-amino-4,6-DNT; 4-amino-2,6-DNT; 1,3,5-trinitro-1,3,5-triazine (RDX); and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). All soils with no significant toxicity were void of these chemicals. However, some soils void of munitions still showed toxicity that may have been caused by elevated levels of heavy metals. Linear regressions of toxicity test results vs. chemical concentrations showed that TNT and TNB accounted for most off the soil toxicity. Lowest-observable-effect concentrations (LOEC) of TNT were determined from these data. This study presents a simple, relatively inexpensive methodology for assessing toxicity of soils containing TNT, RDX, and other contaminants related to munitions production.

  16. Toxic proteins in plants.

    Science.gov (United States)

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  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. Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion

    Directory of Open Access Journals (Sweden)

    Tam Dang

    2017-01-01

    Full Text Available Despite the risk of cyanide toxicity and lack of efficacy, amygdalin is still used as alternative cancer treatment. Due to the highly lethal nature of cyanide toxicity, many patients die before getting medical care. Herein, we describe the case of a 73-year-old female with metastatic pancreatic cancer who developed cyanide toxicity from taking amygdalin. Detailed history and physical examination prompted rapid clinical recognition and treatment with hydroxocobalamin, leading to resolution of her cyanide toxicity. Rapid clinical diagnosis and treatment of cyanide toxicity can rapidly improve patients’ clinical outcome and survival. Inquiries for any forms of ingestion should be attempted in patients with clinical signs and symptoms suggestive of poisoning.

  19. 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.

  20. 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.

  1. Assessing Nanoparticle Toxicity

    Science.gov (United States)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  2. Liquid Nicotine Toxicity.

    Science.gov (United States)

    Kim, Ji Won; Baum, Carl R

    2015-07-01

    E-cigarettes, also known as electronic nicotine delivery systems and electronic cigarettes, are advertised as a healthier alternative product to tobacco cigarettes despite limited data on the consequences of e-cigarette use. Currently, there are no US Food and Drug Administration or other federal regulations of e-cigarettes, and calls to poison control centers regarding liquid nicotine toxicity, especially in children, are on the rise. This article presents the background and mechanism of action of e-cigarettes as well as up-to-date details of the toxicity of liquid nicotine. We also present management strategies in the setting of liquid nicotine toxicity.

  3. Effect of neem azal and neemol on survival, longevity, and ...

    African Journals Online (AJOL)

    The study assessed the biological activity of neem azal and neemol against nymphs and adults of the shield bug, Bathycoelia thalassina, in the laboratory at the Cocoa Research Institute of Ghana. Toxicity of the neem products and their effect on moulting, nymphal survival, development time, adult longevity, and oviposition ...

  4. Effects of acetochlor (herbicide) on the survival and avoidance ...

    African Journals Online (AJOL)

    Jane

    2011-07-06

    Jul 6, 2011 ... This study was designed to evaluate the potential effects of acetochlor (herbicide) on the survival and avoidance behaviour of lycosid spiders example Lycosa terrestris. During the topical toxicity experiment, P. birmanica was found to be more susceptible to acetochlor than L. terrestris. Although, there was ...

  5. Toxicity of chlorpyrifos, carbofuran, mancozeb and their formulations to the tropical earthworm Perionyx excavatus.

    NARCIS (Netherlands)

    De Silva, P.M.C.S.; Pathiratne, A.; van Gestel, C.A.M.

    2010-01-01

    Effects of chlorpyrifos, carbofuran, mancozeb and their formulated products on survival, growth and reproduction of the tropical earthworm Perionyx excavatus were investigated in standard artificial soil. The toxicity of the three chemicals decreased in the order carbofuran > chlorpyrifos >

  6. Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels.

    Science.gov (United States)

    Wang, Wei-Hu; Wang, Zhi; Wu, Jian-Xiong; Zhang, Tao; Rong, Wei-Qi; Wang, Li-Ming; Jin, Jing; Wang, Shu-Lian; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Wang, Wen-Qing; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong

    2015-12-01

    To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels. This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease. Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Network ties and survival

    DEFF Research Database (Denmark)

    Acheampong, George; Narteh, Bedman; Rand, John

    2017-01-01

    Poultry farming has been touted as one of the major ways by which poverty can be reduced in low-income economies like Ghana. Yet, anecdotally there is a high failure rate among these poultry farms. This current study seeks to understand the relationship between network ties and survival chances...... of small commercial poultry farms (SCPFs). We utilize data from a 2-year network survey of SCPFs in rural Ghana. The survival of these poultry farms are modelled using a lagged probit model of farms that persisted from 2014 into 2015. We find that network ties are important to the survival chances...... but this probability reduces as the number of industry ties increases but moderation with dynamic capability of the firm reverses this trend. Our findings show that not all network ties aid survival and therefore small commercial poultry farmers need to be circumspect in the network ties they cultivate and develop....

  8. Aircraft Survivability: Rotorcraft Survivability. Summer 2010

    Science.gov (United States)

    2010-01-01

    protect those who serve to protect us?” The answer is a mixed bag. I am fortunate to have joined a group of dedicated men and women who represent this...and Service subject matter experts on rotorcraft safety and survivability to complete the study and report the results to the Joint Chiefs of...Operations and Support CDD TEMP DT DT/OT LUT IOT &E BLRIP TEMP TEMP LRIP Acquisition & LFT Strategies B C LFT&E Review Requirements Approve TEMPs

  9. 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...

  10. 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...

  11. Local anaesthetic toxicity

    African Journals Online (AJOL)

    treatment strategies. Introduction ... depression and central nervous system and cardiovascular toxicity increased .... requiring analgesic therapy beyond that of surgery. ..... Progress in Biophysics and Molecular Biology 2006;91:1 –82. 32.

  12. [Toxicity of hydroxyquinoline derivatives].

    Science.gov (United States)

    Pashov, D; Simeonov, S P; Drumev, D; Peĭnikova, Ts; Dzhurov, A

    1980-01-01

    We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.

  13. Nitrite therapy improves survival postexposure to chlorine gas

    Science.gov (United States)

    Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis

    2014-01-01

    Exposure to relatively high levels of chlorine (Cl2) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl2 exposure, could prevent Cl2 gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl2 gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl2 exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl2-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl2 gas exposure that is amenable to administration in mass-casualty scenarios. PMID:25326579

  14. Nitrite therapy improves survival postexposure to chlorine gas.

    Science.gov (United States)

    Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis; Patel, Rakesh P

    2014-12-01

    Exposure to relatively high levels of chlorine (Cl₂) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl₂ exposure, could prevent Cl₂ gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl₂ gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl₂ exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl₂-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl₂ gas exposure that is amenable to administration in mass-casualty scenarios. Copyright © 2014 the American Physiological Society.

  15. Recurrent amiodarone pulmonary toxicity.

    Science.gov (United States)

    Chendrasekhar, A; Barke, R A; Druck, P

    1996-01-01

    Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary toxicity, with an estimated mortality of 1% to 33%. Standard treatment for amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and steroid therapy. We report a case of APT that recurred after withdrawal of steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT is a rare clinical entity that has been reported only twice in recent literature.

  16. [Toxic alcohol poisonings].

    Science.gov (United States)

    Kulicki, Paweł; Głogowski, Tomasz

    Accidental or intentional poisonings with ethylene glycol or methanol constitute a serious toxicological problem in many countries. Both alcohols are quickly metabolized by alcohol dehydrogenase to toxic metabolites responsible for high anion gap severe metabolic acidosis and profound neurological, cardiopulmonary, renal disturbances and death. In the early period, the competing inhibition the alcohol dehydrogenase with ethanol or fomepizol may successfully prevent the formation of the toxic metabolites. Once severe acidosis develops an emergency hemodialysis is required.

  17. Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

    Science.gov (United States)

    Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-04-20

    The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

  18. Downregulation of serine protease HTRA1 is associated with poor survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Anna Lehner

    Full Text Available HTRA1 is a highly conserved serine protease which has been implicated in suppression of epithelial-to-mesenchymal-transition (EMT and cell motility in breast cancer. Its prognostic relevance for breast cancer is unclear so far. Therefore, we evaluated the impact of HTRA1 mRNA expression on patient outcome using a cohort of 131 breast cancer patients as well as a validation cohort including 2809 publically available data sets. Additionally, we aimed at investigating for the presence of promoter hypermethylation as a mechanism for silencing the HTRA1 gene in breast tumors. HTRA1 downregulation was detected in more than 50% of the breast cancer specimens and was associated with higher tumor stage (p = 0.025. By applying Cox proportional hazard models, we observed favorable overall (OS and disease-free survival (DFS related to high HTRA1 expression (HR = 0.45 [CI 0.23-0.90], p = 0.023; HR = 0.55 [CI 0.32-0.94], p = 0.028, respectively, with even more pronounced impact in node-positive patients (HR = 0.21 [CI 0.07-0.63], p = 0.006; HR = 0.29 [CI 0.13-0.65], p = 0.002, respectively. Moreover, HTRA1 remained a statistically significant factor predicting DFS among established clinical parameters in the multivariable analysis. Its impact on patient outcome was independently confirmed in the validation set (for relapse-free survival (n = 2809: HR = 0.79 [CI 0.7-0.9], log-rank p = 0.0003; for OS (n = 971: HR = 0.63 [CI 0.48-0.83], log-rank p = 0.0009. In promoter analyses, we in fact detected methylation of HTRA1 in a small subset of breast cancer specimens (two out of a series of 12, and in MCF-7 breast cancer cells which exhibited 22-fold lower HTRA1 mRNA expression levels compared to unmethylated MDA-MB-231 cells. In conclusion, we show that downregulation of HTRA1 is associated with shorter patient survival, particularly in node-positive breast cancer. Since HTRA1 loss was demonstrated to

  19. Responses of Earthworm to Aluminum Toxicity in Latosol

    Science.gov (United States)

    Jia-En Zhang; Jiayu Yu; Ying Ouyang; Huaqin. Xu

    2012-01-01

    Excess aluminum (Al) in soils due to acid rain leaching is toxic to water resources and harmful to soil organisms and plants. This study investigated adverse impacts of Al levels upon earthworms (Eisenia fetida) from the latosol (acidic red soil). Laboratory experiments were performed to examine the survival and avoidance of earthworms from high Al...

  20. Similar long-term overall and disease-free survival after conventional and extralevator abdominoperineal excision

    DEFF Research Database (Denmark)

    Klein, Mads; Colov, Emilie Palmgren; Gögenur, Ismail

    2016-01-01

    , respectively, (log-rank p = 0.59)). In Cox regression, the type of procedure did not affect DFS or OS. Factors of importance for DFS included increasing age, ypN-positive disease and neoadjuvant chemoradiation therapy. Factors of importance for OS included increasing age, circumferential resection margin (CRM...

  1. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

  2. Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

    Science.gov (United States)

    Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

    2017-11-01

    Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;36:3008-3018. © 2017 SETAC. © 2017 SETAC.

  3. Chronic toxicity of arsenic to the Great Salt Lake brine shrimp, Artemia franciscana.

    Science.gov (United States)

    Brix, Kevin V; Cardwell, Rick D; Adams, William J

    2003-02-01

    We determined the chronic toxicity of arsenic (sodium arsenate) to the Great Salt Lake brine shrimp, Artemia franciscana. Chronic toxicity was determined by measuring the adverse effects of arsenic on brine shrimp growth, survival, and reproduction under intermittent flow-through conditions. The study commenced with shrimp growth rather than an arsenic effect. This study represents one of the few full life cycle toxicity tests conducted with brine shrimp.

  4. Evaluation of toxicity: Whole-sediment versus overlying-water exposures with amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Hardesty, D.K.; Kemble, N.E.

    2000-01-01

    A laboratory study was conducted to evaluate the toxicity of whole-sediment versus overlying-water exposures to the amphipod Hyalella azteca using field-collected sediments. Severe toxic effects (5-63% survival) were observed with amphipods exposed for 10 d in direct contact with sediment. In contrast, amphipods exposed only to overlying water in these sediment exposures did not exhibit any toxic effects.

  5. The identification and treatment of toxic megacolon secondary to pseudomembranous colitis.

    Science.gov (United States)

    Earhart, Megan M

    2008-01-01

    Toxic megacolon is an infrequently occurring, potentially life-threatening complication of pseudomembranous colitis. Although toxic megacolon may be considered rare, incidence is expected to increase because of the rapidly increased prevalence of pseudomembranous colitis. This article discusses the pathophysiology, clinical manifestation, diagnosis, treatment, and prognosis for toxic megacolon secondary to pseudomembranous colitis. Critical care nurses should be aware of the disease to intervene early and increase the chance of the patient's survival.

  6. Toxicity of carbon nanotubes to freshwater aquatic invertebrates

    Science.gov (United States)

    Mwangi, Joseph N.; Wang, Ning; Ingersoll, Christopher G.; Hardesty, Doug K.; Brunson, Eric L.; Li, Hao; Deng, Baolin

    2012-01-01

    Carbon nanotubes (CNTs) are hydrophobic in nature and thus tend to accumulate in sediments if released into aquatic environments. As part of our overall effort to examine the toxicity of carbon-based nanomaterials to sediment-dwelling invertebrates, we have evaluated the toxicity of different types of CNTs in 14-d water-only exposures to an amphipod (Hyalella azteca), a midge (Chironomus dilutus), an oligochaete (Lumbriculus variegatus), and a mussel (Villosa iris) in advance of conducting whole-sediment toxicity tests with CNTs. The results of these toxicity tests conducted with CNTs added to water showed that 1.00g/L (dry wt) of commercial sources of CNTs significantly reduced the survival or growth of the invertebrates. Toxicity was influenced by the type and source of the CNTs, by whether the materials were precleaned by acid, by whether sonication was used to disperse the materials, and by species of the test organisms. Light and electron microscope imaging of the surviving test organisms showed the presence of CNTs in the gut as well as on the outer surface of the test organisms, although no evidence was observed to show penetration of CNTs through cell membranes. The present study demonstrated that both the metals solubilized from CNTs such as nickel and the "metal-free" CNTs contributed to the toxicity.

  7. [Toxicity of puffer fish fins].

    Science.gov (United States)

    Honda, Shunichi; Ichimaru, Shunichi; Arakawa, Osamu; Takatani, Tomohiro; Noguchi, Tamao; Ishizaki, Shoichiro; Nagashima, Yuji

    2007-10-01

    Puffer fish is prized as a Japanese traditional food and its fin is also used in the cuisine. However, whether the fin is edible or not is determined for convenience from the toxicity of skin, since little information is available about the toxicity of puffer fish fins. In the present study, we examined the toxicity of fins and skin of three toxic species, Takifugu vermicularis, T. snyderi, and T. porphyreus. The toxicity of T. vermicularis fins (puffer fish with toxic skin also have toxic fins.

  8. Proof-Carrying Survivability

    Science.gov (United States)

    2013-01-15

    pp.289-302 ( Impact factor : 2.09). 2. Julic, J. and Zuo, Y. (2012). “An RFID Survivability Impact Model in the Military Domain”, Proc. of 18 th...Availability, Reliability and Security, 40(4), pp. 406-418 ( Impact factor : 2.016). 10. Zuo, Y. (2010). “A Holistic Approach for Specification of Security... Impact factor : 1.596). 20. Zuo, Y., Pimple, M. and Lande, S. (2009). “A Framework for RFID Survivability Requirement Analysis and Specification”, Proc

  9. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

    Science.gov (United States)

    Genin, A S; De Rycke, Y; Stevens, D; Donnadieu, A; Langer, A; Rouzier, R; Lerebours, F

    2016-12-01

    Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix?--a pilot study.

    Science.gov (United States)

    Datta, Niloy R; Kumar, Piyush; Singh, Shalini; Gupta, Dinesh; Srivastava, Anurita; Dhole, Tapankumar N

    2006-10-01

    To evaluate if pretreatment HPV titers in cancer cervix could predict radiation response and survival outcomes. Twenty-one patients of cancer cervix were treated by radiotherapy (RT) alone. HPV titers were estimated using DNA Hybrid Capture II test. Loco-regional response at 1 month of RT--complete or partial response (CR and PR respectively) and survival outcomes--local disease-free (LDFS), disease-free (DFS) and overall (OS) survivals were evaluated against pre- and posttreatment HPV titers. Pretreatment HPV titers ranged from 0.81 to 3966.10 RLU/cut off (mean +/- SD: 1264.39 +/- 1148.22, median: 1129.98). Of the demographic features evaluated, mean HPV titers were significantly different only for patients achieving CR or PR at completion of RT (mean +/- SD for CR vs. PR: 1616.31 +/- 1146.86 vs. 384.57 +/- 538.80, P = 0.022). HPV titers at end of RT ranged from 0.12 to 487.42 RLU/cut off (mean +/- SD: 37.31 +/- 108.60, median: 2.33). Patients with higher pretreatment HPV titers (>1000 RLU/cutoff) had a higher CR (P = 0.022) and better survival compared to those with or =99.5% fall in HPV had superior survival outcomes than those with 1000 RLU/cutoff) could be considered as a predictor of radiotherapy response and survival in cancer cervix. A reduction in these titers to 99.5% of their baseline values at end of radiotherapy is also associated with better survival outcomes.

  11. Survival in an extreme habitat: the roles of behaviour and energy limitation

    Science.gov (United States)

    Plath, Martin; Tobler, Michael; Riesch, Rüdiger; García de León, Francisco J.; Giere, Olav; Schlupp, Ingo

    2007-12-01

    Extreme habitats challenge animals with highly adverse conditions, like extreme temperatures or toxic substances. In this paper, we report of a fish ( Poecilia mexicana) inhabiting a limestone cave in Mexico. Several springs inside the cave are rich in toxic H2S. We demonstrate that a behavioural adaptation, aquatic surface respiration (ASR), allows for the survival of P. mexicana in this extreme, sulphidic habitat. Without the possibility to perform ASR, the survival rate of P. mexicana was low even at comparatively low H2S concentrations. Furthermore, we show that food limitation affects the survival of P. mexicana pointing to energetically costly physiological adaptations to detoxify H2S.

  12. The toxicity of refrigerants

    Energy Technology Data Exchange (ETDEWEB)

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  13. Survivability via Control Objectives

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  14. Artists’ Survival Rate

    DEFF Research Database (Denmark)

    Bille, Trine; Jensen, Søren

    2017-01-01

    The literature of cultural economics generally finds that an artistic education has no significant impact on artists’ income and careers in the arts. In our research, we have readdressed this question by looking at the artists’ survival in the arts occupations. The results show that an artistic...... education has a significant impact on artists’ careers in the arts and we find important industry differences....

  15. Education for Survival

    Science.gov (United States)

    Aldrich, Richard

    2010-01-01

    This article provides a brief overview of current approaches to education and concludes that none of these is sufficient to meet the challenges that now face the human race. It argues instead for a new concept of education for survival. (Contains 1 note.)

  16. Flexible survival regression modelling

    DEFF Research Database (Denmark)

    Cortese, Giuliana; Scheike, Thomas H; Martinussen, Torben

    2009-01-01

    Regression analysis of survival data, and more generally event history data, is typically based on Cox's regression model. We here review some recent methodology, focusing on the limitations of Cox's regression model. The key limitation is that the model is not well suited to represent time-varyi...

  17. Seeds to survive

    NARCIS (Netherlands)

    Groot, S.P.C.

    2002-01-01

    Seeds are important for man, either as propagation material of crops or directly for the production of foods, fodder and drinks. The natural function of seeds is dispersal of its genes to successive generations. Survival mechanisms seed have evolved sometimes interfere with those preferred by

  18. Survival After Retirement.

    Science.gov (United States)

    Holloway, Clark; Youngblood, Stuart A.

    1986-01-01

    Examined survival rates after retirement in a large corporation. A regression analysis was performed to control for age, sex, job status, and type of work differences that may influence longevity. Short-term suvivors seemed to undergo a different adjustment process than long-term survivors. (Author/ABL)

  19. Relationship Between Metformin Use and Recurrence and Survival in Patients With Resected Stage III Colon Cancer Receiving Adjuvant Chemotherapy: Results From North Central Cancer Treatment Group N0147 (Alliance).

    Science.gov (United States)

    Singh, Preet Paul; Shi, Qian; Foster, Nathan R; Grothey, Axel; Nair, Suresh G; Chan, Emily; Shields, Anthony F; Goldberg, Richard M; Gill, Sharlene; Kahlenberg, Morton S; Sinicrope, Frank A; Sargent, Daniel J; Alberts, Steven R

    2016-12-01

    Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (colon cancer receiving adjuvant FOLFOX (folinic acid, fluorouracil, oxaliplatin)-based chemotherapy. This relationship was not modified by KRAS or BRAF mutation or DNA mismatch repair status. Metformin use did not increase or decrease the likelihood of chemotherapy-related grade 3 or higher adverse events. ©AlphaMed Press.

  20. Toxicity test of xanthone from mangosteen on zebrafish embryos

    Science.gov (United States)

    Noordin, Muhammad Akram Mohd; Noor, Mahanem Mat; Kamaruddin, Wan Mohd Aizat Wan; Lazim, Azwan Mat; Fazry, Shazrul

    2016-11-01

    Xanthone is a chemical compound identified in mangosteen pericarp. A previous study showed that xanthone has anti-proliferating effect on cancer cells. In this study we investigate the toxicity level of xanthone in zebrafish embryo to for future reference on other animal model. We employed Fish Embryo Toxicity (FET) assay to determine the toxicity level of different concentrations of xanthone. Embryos were observed at 24, 48 and 72 hours post fertilization (hpf) under microscope at 4× magnification. The extract showed toxicity effect on embryo at concentrations of 250, 125 and 62.5 µg/mL. Concentrations at 15.63, 7.81 and 3.91 µg / mL of xanthone did not harm the embryos and showed 100% of survival.

  1. Survival After Severe Rhabdomyolysis Following Monensin Ingestion.

    Science.gov (United States)

    Blain, Michela; Garrard, Alexander; Poppenga, Robert; Chen, Betty; Valento, Matthew; Halliday Gittinger, Melissa

    2017-09-01

    Monensin is a veterinary antibiotic with a narrow therapeutic window that has led to lethal intoxication in many animal species. Only two prior cases of human toxicity have been reported, both fatal. We present the first case of survival from severe toxicity following monensin ingestion. A 58-year-old man presented with 8 days of vomiting and abdominal pain. Due to delusions of central nervous system toxoplasmosis, he ingested 300 mg of monensin. His laboratory studies revealed severe rhabdomyolysis without renal dysfunction. Total creatine kinase (CK) peaked above 100,000 U/L. His CK decreased to 5192 U/L after 15 days of aggressive hydration and sodium bicarbonate therapy. His ejection fraction on echocardiogram decreased from 69 to 56%. Reports on acute clinical effects after human exposure to monensin are limited. Ingestion is known to cause skeletal and cardiac muscle rhabdomyolysis and necrosis. Animal studies demonstrate that monensin's toxicity is due to increases in intracellular sodium concentrations and Ca2+ release. To date, no effective antidotal treatment has been described. Monensin is a veterinary medication not approved for human use by the US Food and Drug Administration. Though poorly studied in humans, this case demonstrates the severe harm that may occur following ingestion.

  2. Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy.

    Science.gov (United States)

    Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heunglae; Lee, Ji Young

    2017-03-01

    This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m(2) (range, 17.7 to 35.9 kg/m(2)). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m(2)) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

  3. Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heung Lae; Lee, Ji Young [Inje University Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2017-03-15

    This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

  4. 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...

  5. Respiratory Toxicity Biomarkers

    Science.gov (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  6. ANTIRETROVIRAl TOXICITY IN CHILDREN

    African Journals Online (AJOL)

    vertical transmission prophylaxis (VrP), and the other is treatment for symptomatic HIV infection. Fig. 7. Disease profile ofHN-positivechildren in the Italian. Collaborative Multicentric Study. Antiretroviral (ARV) toxicity is an important issue that must be fully appreciated by prescribing doctors. While the benefits of therapy are ...

  7. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    on the brain, it is used as a major taste enhancer in most eateries and cafeteria in Nigeria. However, information is scanty on the potential of Sida acuta leaf ethanolic extract. (SALEE) to mitigate MSG-induced effect on the brain. This study aimed to investigate the possible toxic effect of MSG, a natural constituent of many ...

  8. Toxicity of a cadmium-contaminated diet to Hyalella azteca.

    Science.gov (United States)

    Ball, Angela L; Borgmann, Uwe; Dixon, D George

    2006-09-01

    Four- and 10-week chronic toxicity tests were conducted using the freshwater amphipod Hyalella azteca and Cd-contaminated Chlorella sp. as a food source. Chlorella sp. was cultured in various Cd concentrations, filtered from solution, rinsed, dried, and ground into food flakes for the H. azteca. Unlike Cd toxicity from water sources, growth was found to be a more sensitive toxicological endpoint than survival, with calculated 50 and 25% effect concentrations (EC50s and EC25s, respectively) of 5.43 and 2.82 nmol/g, respectively, for Cd measured in food. Based on the regression of Cd in Chlorella sp. against Cd in filtered culture medium, the EC50 and EC25 corresponded to dissolved Cd concentrations of 11.30 and 5.09 nmol/L, respectively. Little or no bioaccumulation of Cd was found in the tissues of H. azteca that were fed contaminated food. These results demonstrate an apparent toxicological effect (either direct or indirect) of Cd-contaminated Chlorella sp. to H. azteca that is not associated with Cd accumulation. Toxicity of Cd-contaminated Chlorella sp. differs from waterborne Cd toxicity both in terms of the most sensitive endpoint (growth vs survival) and the relationship between toxicity and bioaccumulation. Unlike Cd toxicity through water exposure, Cd bioaccumulation by H. azteca cannot, therefore, be used to infer toxicity of Cd in a diet of Chlorella sp. Although the concentration of Cd in the algal culture medium that ultimately reduced growth of H. azteca in the present study was higher than Cd in water, which caused mortality to H. azteca in water-only tests during previous studies, further research regarding the contribution of dietary Cd to overall Cd toxicity is needed to verify that water-quality guidelines and risk assessments based on water-only exposures are fully protective.

  9. [Toxicity study of realgar].

    Science.gov (United States)

    Liang, Aihua; Li, Chunying; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bing; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg

    2011-07-01

    To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic. Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated. With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.

  10. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings......, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations...... of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality....

  11. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings......, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations...... of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality....

  12. Metastasis-associated in colon cancer 1 is an independent prognostic biomarker for survival in Klatskin tumor patients.

    Science.gov (United States)

    Lederer, Andri; Herrmann, Pia; Seehofer, Daniel; Dietel, Manfred; Pratschke, Johann; Schlag, Peter; Stein, Ulrike

    2015-09-01

    Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis-associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n = 76) and ICC (n = 80) using real-time quantitative reverse-transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (P history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (P = 0.005). Uni- und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease-free survival (DFS; P = 0.001 and P < 0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389-5.555; P = 0.004). Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an

  13. Cracking the survival code

    Science.gov (United States)

    Füllgrabe, Jens; Heldring, Nina; Hermanson, Ola; Joseph, Bertrand

    2014-01-01

    Modifications of histones, the chief protein components of the chromatin, have emerged as critical regulators of life and death. While the “apoptotic histone code” came to light a few years ago, accumulating evidence indicates that autophagy, a cell survival pathway, is also heavily regulated by histone-modifying proteins. In this review we describe the emerging “autophagic histone code” and the role of histone modifications in the cellular life vs. death decision. PMID:24429873

  14. Artillery Survivability Model

    Science.gov (United States)

    2016-06-01

    experiment mode also enables users to set their own design of experiment by manipulating an editable CSV file. The second one is a real-time mode that...renders a 3D virtual environment of a restricted battlefield where the survivability movements of an artillery company are visualized . This mode...provides detailed visualization of the simulation and enables future experimental uses of the simulation as a training tool. 14. SUBJECT TERMS

  15. Survival analysis models and applications

    CERN Document Server

    Liu, Xian

    2012-01-01

    Survival analysis concerns sequential occurrences of events governed by probabilistic laws.  Recent decades have witnessed many applications of survival analysis in various disciplines. This book introduces both classic survival models and theories along with newly developed techniques. Readers will learn how to perform analysis of survival data by following numerous empirical illustrations in SAS. Survival Analysis: Models and Applications: Presents basic techniques before leading onto some of the most advanced topics in survival analysis.Assumes only a minimal knowledge of SAS whilst enablin

  16. Animal Toxicity of Phytopathogenic Fungi

    Science.gov (United States)

    Main, C. E.; Hamilton, P. B.

    1972-01-01

    Twelve genera of phytopathogenic fungi comprising 27 species previously reported to produce phytotoxins were tested concurrently for animal and plant toxicity. There appeared to be no direct relationship between plant and animal toxicity. PMID:5059620

  17. 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...

  18. Toxic Hazards in Aviation.

    Science.gov (United States)

    1981-04-01

    Specificity in Drosophila Melanogaster . Mutation Res. 16, 1972, 363. 10. Zimmerman, F.K. and R. Schwaren. A Genetic Effect of Symmetric Dimethyl...showed signs of anorexia and general fatigue. Changing diets and forced feedings resulted in the survival of the remaining two dogs. A six-month chronic

  19. Biological Mechanism of Silver Nanoparticle Toxicity

    Science.gov (United States)

    Armstrong, Najealicka Nicole

    Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further

  20. 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.

  1. Toxicity of Depleted Uranium

    Science.gov (United States)

    1997-02-01

    cancer in dogs and humans1 and mice and humans.2 The information for inert metal toxicity in humans is foreign-body carcinogenesis data related to...high dose of Thorotrast® (> 0.4 Bq/g) developed fibrosarcomas from perivascular leakage of some injections.19 Plutonium fragments have been injected...into the footpads of dogs to simulate the plutonium-contaminated wounds of plutonium machinists.2" The plutonium was translocated to the local lymph

  2. 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).

  3. Toxicity and utilization of chemical weapons: does toxicity and venom utilization contribute to the formation of species communities?

    Science.gov (United States)

    Westermann, Fabian L; McPherson, Iain S; Jones, Tappey H; Milicich, Lesley; Lester, Philip J

    2015-08-01

    Toxicity and the utilization of venom are essential features in the ecology of many animal species and have been hypothesized to be important factors contributing to the assembly of communities through competitive interactions. Ants of the genus Monomorium utilize a variety of venom compositions, which have been reported to give them a competitive advantage. Here, we investigate two pairs of Monomorium species, which differ in the structural compositions of their venom and their co-occurrence patterns with the invasive Argentine ant. We looked at the effects of Monomorium venom toxicity, venom utilization, and aggressive physical interactions on Monomorium and Argentine ant survival rates during arena trials. The venom toxicity of the two species co-occurring with the invasive Argentine ants was found to be significantly higher than the toxicity of the two species which do not. There was no correlation between venom toxicity and Monomorium survival; however, three of the four Monomorium species displayed significant variability in their venom usage which was associated with the number of Argentine ant workers encountered during trials. Average Monomorium mortality varied significantly between species, and in Monomorium smithii and Monomorium antipodum, aggressive interactions with Argentine ants had a significant negative effect on their mortality. Our study demonstrates that different factors and strategies can contribute to the ability of a species to withstand the pressure of a dominant invader at high abundance, and venom chemistry appears to be only one of several strategies utilized.

  4. Toxicity of nanomaterials.

    Science.gov (United States)

    Sharifi, Shahriar; Behzadi, Shahed; Laurent, Sophie; Forrest, M Laird; Stroeve, Pieter; Mahmoudi, Morteza

    2012-03-21

    Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity (286 references).

  5. Amiodarone Pulmonary Toxicity

    Directory of Open Access Journals (Sweden)

    Norman Wolkove

    2009-01-01

    Full Text Available Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects.

  6. Amiodarone pulmonary toxicity

    Science.gov (United States)

    Wolkove, Norman; Baltzan, Marc

    2009-01-01

    Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects. PMID:19399307

  7. Applied survival analysis using R

    CERN Document Server

    Moore, Dirk F

    2016-01-01

    Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

  8. 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

  9. Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery.

    Science.gov (United States)

    Kirienko, Margarita; Cozzi, Luca; Antunovic, Lidija; Lozza, Lisa; Fogliata, Antonella; Voulaz, Emanuele; Rossi, Alexia; Chiti, Arturo; Sollini, Martina

    2018-02-01

    Radiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery. A cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built. The Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65-0.85), 0.68 (95%CI: 0.57-0.80), and 0.68 (95%CI: 0.58-0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51-0.69), 0.64 (95%CI: 0.53-0.75), and 0.65 (95%CI: 0.50-0.72) for the CT, the PET, and the PET+CT images, respectively. A radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery.

  10. Diverse microbial species survive high ammonia concentrations

    Science.gov (United States)

    Kelly, Laura C.; Cockell, Charles S.; Summers, Stephen

    2012-04-01

    Planetary protection regulations are in place to control the contamination of planets and moons with terrestrial micro-organisms in order to avoid jeopardizing future scientific investigations relating to the search for life. One environmental chemical factor of relevance in extraterrestrial environments, specifically in the moons of the outer solar system, is ammonia (NH3). Ammonia is known to be highly toxic to micro-organisms and may disrupt proton motive force, interfere with cellular redox reactions or cause an increase of cell pH. To test the survival potential of terrestrial micro-organisms exposed to such cold, ammonia-rich environments, and to judge whether current planetary protection regulations are sufficient, soil samples were exposed to concentrations of NH3 from 5 to 35% (v/v) at -80°C and room temperature for periods up to 11 months. Following exposure to 35% NH3, diverse spore-forming taxa survived, including representatives of the Firmicutes (Bacillus, Sporosarcina, Viridibacillus, Paenibacillus, Staphylococcus and Brevibacillus) and Actinobacteria (Streptomyces). Non-spore forming organisms also survived, including Proteobacteria (Pseudomonas) and Actinobacteria (Arthrobacter) that are known to have environmentally resistant resting states. Clostridium spp. were isolated from the exposed soil under anaerobic culture. High NH3 was shown to cause a reduction in viability of spores over time, but spore morphology was not visibly altered. In addition to its implications for planetary protection, these data show that a large number of bacteria, potentially including spore-forming pathogens, but also environmentally resistant non-spore-formers, can survive high ammonia concentrations.

  11. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... as well as for cost-benefit estimation of new blood safety interventions....

  12. Nuclear War Survival Skills

    Energy Technology Data Exchange (ETDEWEB)

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  13. Design of survivable networks

    CERN Document Server

    Stoer, Mechthild

    1992-01-01

    The problem of designing a cost-efficient network that survives the failure of one or more nodes or edges of the network is critical to modern telecommunications engineering. The method developed in this book is designed to solve such problems to optimality. In particular, a cutting plane approach is described, based on polyhedral combinatorics, that is ableto solve real-world problems of this type in short computation time. These results are of interest for practitioners in the area of communication network design. The book is addressed especially to the combinatorial optimization community, but also to those who want to learn polyhedral methods. In addition, interesting new research problemsare formulated.

  14. Presence survival spores of Bacillus thuringiensis varieties in grain warehouse

    Directory of Open Access Journals (Sweden)

    Sánchez-Yáñez Juan Manuel

    2016-08-01

    Full Text Available Genus Bacillus thuringiensis (Bt synthesized spores and crystals toxic to pest-insects in agriculture. Bt is comospolitan then possible to isolate some subspecies or varieties from warehouse. The aims of study were: i to isolate Bt varieties from grain at werehouse ii to evaluate Bt toxicity on Spodoptera frugiperda and Shit-ophilus zeamaisese iii to analyze Bt spores persistence in Zea mays grains at werehouse compared to same Bt on grains exposed to sun radiation. Results showed that at werehouse were recovered more than one variety of Bt spores. According to each isolate Bt1 o Bt2 were toxic to S. frugiperda or S. zeamaisese. One those Bt belong to var morrisoni. At werehouse these spores on Z. mays grains surviving more time, while the same spores exposed to boicide sun radiation they died.

  15. Number of negative lymph nodes can predict survival of breast cancer patients with four or more positive lymph nodes after postmastectomy radiotherapy.

    Science.gov (United States)

    Wu, San-Gang; Sun, Jia-Yuan; Zhou, Juan; Li, Feng-Yan; Zhou, Hao; Lin, Qin; Lin, Huan-Xin; Bao, Yong; He, Zhen-Yu

    2014-12-16

    This study was conducted to assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with four or more positive lymph nodes after postmastectomy radiotherapy (PMRT). This retrospective study examined 605 breast cancer patients with four or more positive lymph nodes who underwent mastectomy. A total of 371 patients underwent PMRT. The prognostic value of the NLN count in patients with and without PMRT was analyzed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up was 54 months, and the overall 8-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 79.8%, 50.0%, 46.8%, and 57.9%, respectively. The optimal cut-off points for NLN count was 12. Univariate analysis showed that the number of NLNs, lymph node ratio (LNR) and pN stage predicted the LRFS of non-PMRT patients (pnumber of NLNs was an independent prognostic factor affecting the LRFS, patients with a higher number of NLNs had a better LRFS (hazard ratio = 0.132, 95% confidence interval=0.032-0.547, p =0.005). LNR and pN stage had no effect on LRFS. PMRT improved the LRFS (ppatients with 12 or fewer NLNs, but it did not any effect on survival of patients with more than 12 NLNs. PMRT improved the regional lymph node recurrence-free survival (ppatients with 12 or fewer NLNs. The number of NLNs can predict the survival of breast cancer patients with four or more positive lymph nodes after PMRT.

  16. Toxicity of stormwater treatment pond sediments to Hyallela azteca (Amphipoda)

    Science.gov (United States)

    Karouna-Renier, N.K.; Sparling, D.W.

    1997-01-01

    Stormwater wetlands are created to contain runoff from human developments and are designed to retain contaminants such as heavy metals, petroleum hydrocarbons, silt, pesticides, and nutrients before the runoff enter natural waterways. Because of this design, stormwater wetlands have a potential of becoming toxic sinks to organisms utilizing the wetlands for habitat. We conducted a 10-day sediment bioassay on Hyallela azteca as part of a larger study on the possible hazards of stormwater wetlands to aquatic invertebrates. Water and sediments from 10 wetlands separated into reference, residential, commercial, and highway land uses were used. No differences in survival were observed among land use categories, possibly because the ratio of acid volatile sulfides/simultaneously extractable metals (AVS/SEM) was > 1.0 for all of the ponds tested; values > 1 in this ratio are indications that toxic metals may not be bioavailable. Survival and growth rates correlated positively with AVS.

  17. Is LSD toxic?

    Science.gov (United States)

    Nichols, David E; Grob, Charles S

    2018-02-01

    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.

  18. Toxicity of phenanthrene and lindane mixtures to marine invertebrates.

    Science.gov (United States)

    Evans, A D; Nipper, M

    2007-10-01

    Surface waters near industrialized and agricultural areas are contaminated with hundreds of different pollutants from a variety of sources. Methods for measurement of sediment, surface water, and porewater toxicity in marine environments include the sea urchin (Arbacia punctulata) fertilization and embryological development tests and copepod (Schizopera knabeni) survival and hatching success assessment. The concentration addition model was applied to determine whether toxicity of two compounds, phenanthrene (polycyclic aromatic hydrocarbon) and lindane (organochlorine pesticide), when combined can be accurately assessed because of similar modes of action. Mixture analysis determined the sea urchin fertilization test to exhibit additivity (TU(mix) = 1.13), while the copepod test exhibited a synergistic effect (TU(mix) = 0.22). Mixture toxicity data for the sea urchin embryological test were not conclusive because of the lack of toxicity of the individual chemicals. The synergistic effect to copepods is a concern as it indicates that greater toxic effects may occur when the compounds are present in mixtures. Results from this research suggest that increased toxicity to some categories of organisms should be expected near agricultural and industrial areas where pesticides and other types of compounds may occur simultaneously. 2007 Wiley Periodicals, Inc.

  19. Toxic epidermal necrolysis: a paradigm of critical illness

    Science.gov (United States)

    Estrella-Alonso, Alfonso; Aramburu, José Antonio; González-Ruiz, Mercedes Yolanda; Cachafeiro, Lucía; Sánchez, Manuel Sánchez; Lorente, José A.

    2017-01-01

    Toxic epidermal necrolysis is an adverse immunological skin reaction secondary in most cases to the administration of a drug. Toxic epidermal necrolysis, Stevens-Johnson syndrome, and multiform exudative erythema are part of the same disease spectrum. The mortality rate from toxic epidermal necrolysis is approximately 30%. The pathophysiology of toxic epidermal necrolysis is similar in many respects to that of superficial skin burns. Mucosal involvement of the ocular and genital epithelium is associated with serious sequelae if the condition is not treated early. It is generally accepted that patients with toxic epidermal necrolysis are better treated in burn units, which are experienced in the management of patients with extensive skin loss. Treatment includes support, elimination, and coverage with biosynthetic derivatives of the skin in affected areas, treatment of mucosal involvement, and specific immunosuppressive treatment. Of the treatments tested, only immunoglobulin G and cyclosporin A are currently used in most centers, even though there is no solid evidence to recommend any specific treatment. The particular aspects of the treatment of this disease include the prevention of sequelae related to the formation of synechiae, eye care to prevent serious sequelae that can lead to blindness, and specific immunosuppressive treatment. Better knowledge of the management principles of toxic epidermal necrolysis will lead to better disease management, higher survival rates, and lower prevalence of sequelae. PMID:29340540

  20. Nanoparticle toxicity and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Prevenslik, T, E-mail: nanoqed@gmail.com [QED Radiations, Discovery Bay, Hong Kong (Hong Kong)

    2011-07-06

    Nanoparticles (NPs) have provided significant advancements in cancer treatment. But as in any technology, there is a darkside. Experiments have shown NPs in body fluids pose a health risk by causing DNA damage that in of itself may lead to cancer. To avoid the dilemma that NPs are toxic to both cancer cells and DNA alike, the mechanism of NP toxicity must be understood so that the safe use of NPs may go forward. Reactive oxidative species (ROS) of peroxide and hydroxyl radicals damage the DNA by chemical reaction, but require NPs provide energies of about 5 eV not possible by surface effects. Only electromagnetic (EM) radiations beyond ultraviolet (UV) levels may explain the toxicity of NPs. Indeed, experiments show DNA damage from <100 nm NPs mimic the same reaction pathways of conventional sources of ionizing radiation, Hence, it is reasonable to hypothesize that NPs produce their own source of UV radiation, albeit at low intensity. Ionizing radiation from NPs at UV levels is consistent with the theory of QED induced EM radiation. QED stands for quantum electrodynamics. By this theory, fine < 100 nm NPs absorb low frequency thermal energy in the far infrared (FIR) from collisions with the water molecules in body fluids. Since quantum mechanics (QM) precludes NPs from having specific heat, absorbed EM collision energy cannot be conserved by an increase in temperature. But total internal reflection (TIR) momentarily confines the absorbed EM energy within the NP. Conservation proceeds by the creation of QED photons by frequency up-conversion of the absorbed EM energy to the TIR confinement frequency, typically beyond the UV. Subsequently, the QED photons upon scattering from atoms within the NP avoid TIR confinement and leak UV to the surroundings, thereby explaining the remarkable toxicity of NPs. But QED radiation need not be limited to natural or man-made NPs. Extensions suggest UV radiation is produced from biological NPs within the body, e.g., enzyme induced

  1. Neurological oxygen toxicity.

    Science.gov (United States)

    Farmery, Scott; Sykes, Oliver

    2012-10-01

    SCUBA diving has several risks associated with it from breathing air under pressure--nitrogen narcosis, barotrauma and decompression sickness (the bends). Trimix SCUBA diving involves regulating mixtures of nitrogen, oxygen and helium in an attempt to overcome the risks of narcosis and decompression sickness during deep dives, but introduces other potential hazards such as hypoxia and oxygen toxicity convulsions. This study reports on a seizure during the ascent phase, its potential causes and management and discusses the hazards posed to the diver and his rescuer by an emergency ascent to the surface.

  2. Does hypernatremia impact mortality in Toxic Epidermal Necrolysis?

    OpenAIRE

    Mailänder, Peter; Stang, Felix H.; Stollwerck, Peter L.; Siemers, Frank; von Wild, Tobias; Namdar, Thomas; Lange, Thomas

    2010-01-01

    Introduction: In-hospital hypernatremia is associated with increased mortality rates. We want to elucidate the impact of in-hospital acquired hypernatremia in mortality of Toxic Epidermal Necrolysis (TEN).Purpose: Is there an association between hypernatremia and mortality in patients with TEN?Method: Retrospective study of 25 patients with TEN. Laboratory electrolyte results, diuresis and survival were analyzed. Patients were separated in two groups without (Group A) or with (Group B) hyp...

  3. Population growth rate determinants for Arbacia: Evaluating ecological relevance of toxicity test endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Nacci, D.; Gleason, T.; Munns, W.R. Jr. [Environmental Protection Agency, Narragansett, RI (United States). Environmental Research Lab.

    1995-12-31

    A population dynamics model for the sea urchin, Arbacia punctulata, was recently developed incorporating life stage endpoints frequently measured in acute and chronic toxicity studies. Model elasticity analysis was used to demonstrate that population growth rate was influenced most by adult survival and least by early life stage success, calling into question the ecological relevance of results from standardized Arbacia fertilization and larval development toxicity tests. Two approaches were used to continue this evaluation. Actual and hypothetical dose-response curves for toxicant exposures over multiple life stages were used to evaluate contributions to population growth rate of stage-specific toxicant effects. Additionally, relationships between critical life stages were developed from laboratory data for Arbacia. The results of this analysis underscore the importance of understanding both endpoint sensitivity to toxicants and sensitivity of population growth rate to test endpoints in determining the ecological relevance of toxicity tests results.

  4. OBESITY IN CANCER SURVIVAL

    Science.gov (United States)

    Parekh, Niyati; Chandran, Urmila; Bandera, Elisa V.

    2013-01-01

    Although obesity is a well known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colorectal cancer. We note that the evidence over-represents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors. PMID:22540252

  5. Surviving relatives after suicide

    DEFF Research Database (Denmark)

    Nørrelykke, Helle; Cohrt, Pernille

    suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...... and conflicting feelings may result in pathological expansion of grief characterized by extremely reduced quality of life involving severe psychical and social consequences. Suicide a subject of taboo In the 1980s WHO drafted a health policy document (‘Health for all year 2000’) with 38 targets for attaining......We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...

  6. Obesity in cancer survival.

    Science.gov (United States)

    Parekh, Niyati; Chandran, Urmila; Bandera, Elisa V

    2012-08-21

    Although obesity is a well-known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colo-rectal cancer. We note that the evidence overrepresents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors.

  7. Candida survival strategies.

    Science.gov (United States)

    Polke, Melanie; Hube, Bernhard; Jacobsen, Ilse D

    2015-01-01

    Only few Candida species, e.g., Candida albicans, Candida glabrata, Candida dubliniensis, and Candida parapsilosis, are successful colonizers of a human host. Under certain circumstances these species can cause infections ranging from superficial to life-threatening disseminated candidiasis. The success of C. albicans, the most prevalent and best studied Candida species, as both commensal and human pathogen depends on its genetic, biochemical, and morphological flexibility which facilitates adaptation to a wide range of host niches. In addition, formation of biofilms provides additional protection from adverse environmental conditions. Furthermore, in many host niches Candida cells coexist with members of the human microbiome. The resulting fungal-bacterial interactions have a major influence on the success of C. albicans as commensal and also influence disease development and outcome. In this chapter, we review the current knowledge of important survival strategies of Candida spp., focusing on fundamental fitness and virulence traits of C. albicans. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Psychology and survival.

    Science.gov (United States)

    Phillips, D P; Ruth, T E; Wagner, L M

    1993-11-06

    We examined the deaths of 28,169 adult Chinese-Americans, and 412,632 randomly selected, matched controls coded "white" on the death certificate. Chinese-Americans, but not whites, die significantly earlier than normal (1.3-4.9 yr) if they have a combination of disease and birthyear which Chinese astrology and medicine consider ill-fated. The more strongly a group is attached to Chinese traditions, the more years of life are lost. Our results hold for nearly all major causes of death studied. The reduction in survival cannot be completely explained by a change in the behaviour of the Chinese patient, doctor, or death-registrar, but seems to result at least partly from psychosomatic processes.

  9. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer

    OpenAIRE

    Palmela, Carolina; Velho, S?nia; Agostinho, Lisa; Branco, Francisco; Santos, Marta; Santos, Maria Pia Costa; Oliveira, Maria Helena de; Strecht, Jo?o; Maio, Rui; Cravo, Mar?lia; Baracos, Vickie E.

    2017-01-01

    Purpose Neoadjuvant chemotherapy has been shown to improve survival in locally advanced gastric cancer, but it is associated with significant toxicity. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher chemotherapy toxicity and morbi-mortality. The aim of this study was to assess the prevalence of sarcopenia/sarcopenic obesity in patients with gastric cancer, as well as its association with chemotherapy toxicity...

  10. 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.

  11. Low-value practices in oncology contributing to financial toxicity.

    Science.gov (United States)

    Gyawali, Bishal

    2017-01-01

    Financial toxicity of cancer treatment is now a well-recognised problem in cancer medicine leading to patient bankruptcy and even poor survival, including in high-income countries and countries with public health care systems. Many oncologists, despite acknowledging the severity of financial toxicity as a problem, resign the responsibility of reducing the costs of cancer treatment to the government, industry, and oncology societies. However, an oncologist can play an important role in reducing the costs of cancer treatment because all cancer treatment decisions are made between the oncologist and the patient. In this article, I point out a few examples of low value practices from various oncology disciplines that we oncologists can easily replace or abandon in our practice and contribute to lessening the financial toxicities to patients and society. As these examples suggest, reducing cost does not necessarily mean compromising efficacy. We should continuously keep looking for other similar cost-saving strategies in our practice.

  12. Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

    Directory of Open Access Journals (Sweden)

    Seyed Jalal Hosseinimehr

    2014-01-01

    Full Text Available Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2 were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy.

  13. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial.

    Science.gov (United States)

    Solomon, Scott R; Sizemore, Connie A; Sanacore, Melissa; Zhang, Xu; Brown, Stacey; Holland, H Kent; Morris, Lawrence E; Bashey, Asad

    2012-12-01

    Haploidentical hematopoietic stem cell transplant (HSCT) provides an opportunity for nearly all patients to benefit from HSCT. We conducted a trial of haploidentical T cell replete allografting using a busulfan-based myeloablative preparative regimen, peripheral blood stem cells (PBSCs) as the graft source, and posttransplantation cyclophosphamide (Cy). Eligibility was limited to patients at high risk of relapse after nonmyeloablative haploidentical bone marrow transplant (BMT). Twenty patients were enrolled in the study (11 with relapsed/refractory disease and 9 who underwent transplantation while in remission and considered standard risk). Donor engraftment occurred in all 20 patients with full donor T cell and myeloid chimerism by day +30. The cumulative incidence of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) was 30% and 10%, respectively. The cumulative incidence of chronic GVHD (cGVHD) was 35%. Nonrelapse mortality (NRM) at 100 days and 1 year was 10% for all patients and 0% for standard-risk patients. With a median follow-up of 20 months, the estimated 1-year overall survival (OS) and disease-free survival (DFS) was 69% and 50%, respectively, for all patients, and 88% and 67% for standard-risk patients. Myeloablative haploidentical HSCT is associated with excellent rates of engraftment, GVHD, NRM, and DFS, and is a valid option in patients with high-risk malignancies who lack timely access to a conventional donor. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Experiência brasileira utilizando terapia sequencial de alta dose seguido de transplante autólogo de célula-tronco hematopoética para linfomas malignos

    OpenAIRE

    Souza,Cármino A.; Pagnano, Kátia B. B.; Irene Lorand-Metze; Eliana C.M. Miranda; Renata Baldissera; Aranha, Francisco J. P.; Afonso C. Vigorito; Duarte, Bruno K. L.

    2009-01-01

    Using the overall survival (OS), disease free survival (DFS) and progression free survival (PFS), as well as associated toxicity, the purpose of this work was to evaluate the effectiveness of HDS followed by ASCT as salvage therapy. A retrospective analysis was performed of 106 patients with high grade non-Hodgkin lymphoma receiving HDS followed by ASCT, between 1998 and 2006. Median age was 45 years (Range: 8-65), with 66 (62%) men. Histopathological classification was: 78% DLBCL patients, 1...

  15. Experiência Brasileira Utilizando Terapia Sequencial De Alta Dose Seguido De Transplante Autólogo De Célula-tronco Hematopoética Para Linfomas Malignos [brazilian Experience Using High-dose Sequential Therapy (hds) Followed By Autologous Hematopoietic Stem Cell Transplantation (asct) For Malignant Lymphomas

    OpenAIRE

    de Souza C.A.; Pagnano K.B.B.; Lorand-Metze I.; Miranda E.C.M.; Baldissera R.; Aranha F.J.P.; Vigorito A.C.; Duarte B.K.L.

    2009-01-01

    Using the overall survival (OS), disease free survival (DFS) and progression free survival (PFS), as well as associated toxicity, the purpose of this work was to evaluate the effectiveness of HDS followed by ASCT as salvage therapy. A retrospective analysis was performed of 106 patients with high grade non-Hodgkin lymphoma receiving HDS followed by ASCT, between 1998 and 2006. Median age was 45 years (Range: 8-65), with 66 (62%) men. Histopathological classification was: 78% DLBCL patients, 1...

  16. Brazilian experience using high-dose sequential therapy (HDS) followed by autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphomas

    OpenAIRE

    Souza,Cármino A.; Pagnano, Kátia B. B.; Lorand-Metze,Irene; Eliana C.M. Miranda; Baldissera, Renata; Aranha, Francisco J. P.; Afonso C. Vigorito; Duarte, Bruno K. L.

    2009-01-01

    Using the overall survival (OS), disease free survival (DFS) and progression free survival (PFS), as well as associated toxicity, the purpose of this work was to evaluate the effectiveness of HDS followed by ASCT as salvage therapy. A retrospective analysis was performed of 106 patients with high grade non-Hodgkin lymphoma receiving HDS followed by ASCT, between 1998 and 2006. Median age was 45 years (Range: 8-65), with 66 (62%) men. Histopathological classification was: 78% DLBCL patients, 1...

  17. Biological control of toxic cyanobacteria

    CSIR Research Space (South Africa)

    Ndlela, L

    2016-04-01

    Full Text Available • If successful, the biocontrol agent may produce conformational changes to the cyanobacterial toxins or reduced eco-toxicity effects • The laboratory study may give insight into the factors inhibiting the natural balance of predatory bacteria... studies have been done on the eco-toxicity resulting from biocontrol as well as the changes to cyanotoxins, if any. Research Plan The study will be conducted at whole cell level and with specific metabolites and toxins, with eco-toxicity studied...

  18. Sarcopenia and chemotherapy-mediated toxicity.

    Science.gov (United States)

    Vega, Maria Cecília Monteiro Dela; Laviano, Alessandro; Pimentel, Gustavo Duarte

    2016-01-01

    This narrative review focuses on the role of sarcopenia and chemotherapy-induced toxicity in cancer patients. Consistent evidence shows that sarcopenia in cancer patients leads to decreased overall survival by influencing treatment discontinuation and dose reduction. Therefore, sarcopenia should be considered a robust prognostic factor of negative outcome as well as a determinant of increased healthcare costs. RESUMO Esta revisão narrativa descreve o papel da sarcopenia e a toxicidade mediada pela quimioterapia em pacientes com câncer. Diversas evidências consistentes mostram que a sarcopenia em pacientes com câncer induz à menor sobrevida global, por influenciar na interrupção do tratamento e na redução da dose. Portanto, a sarcopenia pode ser considerada um importante fator de prognóstico de desfecho negativo, além de um determinante de maiores custos em saúde.

  19. Role of vegetation in a constructed wetland on nutrient-pesticide mixture toxicity to Hyalella azteca.

    Science.gov (United States)

    Lizotte, Richard E; Moore, Matthew T; Locke, Martin A; Kröger, Robert

    2011-02-01

    The toxicity of a nutrient-pesticide mixture in nonvegetated and vegetated sections of a constructed wetland (882 m² each) was assessed using Hyalella azteca 48-h aqueous whole-effluent toxicity bioassays. Both sections were amended with a mixture of sodium nitrate, triple superphosphate, diazinon, and permethrin simulating storm-event agricultural runoff. Aqueous samples were collected at inflow, middle, and outflow points within each section 5 h, 24 h, 72 h, 7 days, 14 days, and 21 days postamendment. Nutrients and pesticides were detected throughout both wetland sections with concentrations longitudinally decreasing more in vegetated than nonvegetated section within 24 h. Survival effluent dilution point estimates-NOECs, LOECs, and LC₅₀s-indicated greatest differences in toxicity between nonvegetated and vegetated sections at 5 h. Associations of nutrient and pesticide concentrations with NOECs indicated that earlier toxicity (5-72 h) was from permethrin and diazinon, whereas later toxicity (7-21 days) was primarily from diazinon. Nutrient-pesticide mixture concentration-response assessment using toxic unit models indicated that H. azteca toxicity was due primarily to the pesticides diazinon and permethrin. Results show that the effects of vegetation versus no vegetation on nutrient-pesticide mixture toxicity are not evident after 5 h and a 21-day retention time is necessary to improve H. azteca survival to ≥90% in constructed wetlands of this size.

  20. Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Ordonez, R.; Federico, M. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Valenciano, A. [Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Bordon, E. [Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Rodriguez-Gallego, C. [Hospital Universitario de Gran Canaria Dr. Negrin, Immunology Department, Las Palmas de Gran Canaria (Spain)

    2014-02-15

    A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

  1. Assessing the potential toxicity of resuspended sediment

    Energy Technology Data Exchange (ETDEWEB)

    Bonnet, C.; Babut, M.; Ferard, J.F.; Martel, L.; Garric, J.

    2000-05-01

    Two moderately contaminated freshwater sediments (Sorel Harbour, St. Lawrence River, Canada) were subjected to a suspension event. The objective was to assess the environmental impact of the disposal of dredged material in water, in particular, the short-term effects of dumping on the water column and the long-term effects of dredged sediment deposits. In a series of microcosms, the sediments were left to stand for 25 d under flow-through conditions. In a second series of microcosms, sediments were vigorously suspended for 15 min before being left to settle and were submitted to the same treatment as reference sediments during the following 25 d. Physicochemical and biological parameters (Daphnia magna and Hydra attenuata survival) were measured in overlying water throughout the experiment. Sediment toxicity was assessed with Chironomus tentans and Hyalella azteca exposed to sediments collected at both the beginning and end of the 25-d period. Pore-water toxicity was evaluated with D. magna. During the suspension process, in the Sorel Harbour mixed sediment overlying water, the authors observed effects on H. attenuata survival and ammonia and metals (chromium, copper, and zinc) releases. Meanwhile, in reference (nonmixed) and mixed sediments as well as in associated pore waters, there were no significant chemical modifications no biological effects after the 25-d experiments. The developed approach, which attempts to simulate a dumping process, aims at allowing the assessment of the short- and long-term hazards resulting from a resuspension process in overlying water and in resettled sediments using both chemical and biological measurements.

  2. Tapentadol toxicity in children.

    Science.gov (United States)

    Borys, Douglas; Stanton, Matthew; Gummin, David; Drott, Tracy

    2015-02-01

    Tapentadol (Nucynta) is indicated for the treatment of moderate to severe pain in adults. Tapentadol's mechanism of action consists of acting as an agonist on the μ-opioid receptor and by inhibiting the reuptake of norepinephrine. There are no published reports on the toxicity of tapentadol in pediatric patients. The goals of this study are to describe the incidence, medical outcomes, clinical effects, and treatment secondary to tapentadol exposure. This retrospective observational study used data from the National Poison Data System. Inclusion criteria were exposure to tapentadol from November 1, 2008 to December 31, 2013; age 0 to 17 years; single ingestion; and followed to a known outcome. There were 104 patients who met the inclusion criteria. Eighty patients were aged ≤ 6, 2-year-olds the most common age group (60.6%). There were 52 male and 52 female patients. Of the 104 patients, 93 had unintentional exposures. No deaths were reported. Sixty-two of the patients had no effect, 34 had minor effects, 6 had moderate and 2 had major effects. Thirty patients reported drowsiness and lethargy. Other effects reported included nausea, vomiting, miosis, tachycardia, respiratory depression, dizziness/vertigo, coma, dyspnea, pallor, vomiting, edema, hives/welts, slurred speech, pruritus, and hallucinations/delusions. Fifty-three patients were reported to have no medical intervention. This is the first study examining the toxic effects of tapentadol in a pediatric population. Although a majority of the patients in this review developed no effect from their exposure, two had life-threatening events. The most common effects reported were opioidlike. Copyright © 2015 by the American Academy of Pediatrics.

  3. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    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 been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  4. Survival assays using Caenorhabditis elegans.

    Science.gov (United States)

    Park, Hae-Eun H; Jung, Yoonji; Lee, Seung-Jae V

    2017-02-01

    Caenorhabditis elegans is an important model organism with many useful features, including rapid development and aging, easy cultivation, and genetic tractability. Survival assays using C. elegans are powerful methods for studying physiological processes. In this review, we describe diverse types of C. elegans survival assays and discuss the aims, uses, and advantages of specific assays. C. elegans survival assays have played key roles in identifying novel genetic factors that regulate many aspects of animal physiology, such as aging and lifespan, stress response, and immunity against pathogens. Because many genetic factors discovered using C. elegans are evolutionarily conserved, survival assays can provide insights into mechanisms underlying physiological processes in mammals, including humans.

  5. 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…

  6. Surviving a Suicide Attempt

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Harrasi

    2016-09-01

    Full Text Available Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors and protective factors (like religious affiliation and family support. All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor.

  7. Surviving a Suicide Attempt.

    Science.gov (United States)

    Al-Harrasi, Ahmed; Al Maqbali, Mandhar; Al-Sinawi, Hamed

    2016-09-01

    Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors) and protective factors (like religious affiliation and family support). All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor.

  8. Will the olympics survive?.

    Science.gov (United States)

    Khosla, T.

    1977-01-01

    The United States of America dominated 58 events in athletics, field and swimming, which between them accounted for 35 per cent of all events in the Munich Olympiad. 1972; these events favour taller individuals. But, in 25 per cent of other events (1) cycling, (2) fencing, (3) gymnastics, (4) judo, (5) weightlifting and (6) Graeco Roman wrestling the U.S.A. did not win a single medal. The failure of the U.S.A. to maintain her lead in Munich was largely due to weaknesses in these other events in many of which the potential medallists can be derived from the lower half of the height distribution (events 3 to 6). These weaknesses are Russia's strength and they continued to remain unstrengthened at Montreal. Also, the domination held by the U.S.A. in swimming was seriously challenged by East Germany. The present trends indicate that the U.S.A.'s ranking is likely to slip further to the third position in Moscow 1980. Factors inhibiting the survival of the Olympics are pointed. PMID:861436

  9. Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Andrea C. [Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Morris, W. James, E-mail: JMorris@bccancer.bc.ca [Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Lapointe, Vincent [Department of Medical Physics, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Hamm, Jeremy [Department of Population Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Keyes, Mira; Pickles, Tom; McKenzie, Michael [Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Spadinger, Ingrid [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Medical Physics, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada)

    2014-01-01

    Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.

  10. Effects of cell-bound microcystins on survival and feeding of Daphnia spp

    DEFF Research Database (Denmark)

    Rohrlack, T; Dittmann, E; Börner, T

    2001-01-01

    microcystin synthesis, were compared. Additionally, the relationship between microcystin ingestion rate by the Daphnia clones and Daphnia survival time was analyzed. Microcystins ingested with Microcystis cells were poisonous to all Daphnia clones tested. The median survival time of the animals was closely......-producing and -lacking cells, and (iv) the strength of the toxic effect can be predicted from the microcystin ingestion rate of the animals....

  11. Toxicity Determinations for Five Energetic Materials, Weathered and Aged in Soil, to the Collembolan Folsomia Candida

    Science.gov (United States)

    2015-03-01

    invertebrate F. candida to validate the condition of the test species and the reliability and precision of the results. We conducted toxicity tests to...SUPPLEMENTARY NOTES 14. ABSTRACT-LIMIT 200 WORDS We investigated the toxicity of the following chemicals to the soil invertebrate Collembola Folsomia...Protection Agency (USEPA) method 8330A. The data sets for adult survival and juvenile production were analyzed using nonlinear regression models to determine

  12. Lactobacillus plantarum CCFM639 alleviates aluminium toxicity.

    Science.gov (United States)

    Yu, Leilei; Zhai, Qixiao; Liu, Xiaoming; Wang, Gang; Zhang, Qiuxiang; Zhao, Jianxin; Narbad, Arjan; Zhang, Hao; Tian, Fengwei; Chen, Wei

    2016-02-01

    Aluminium (Al) is the most abundant metal in the earth's crust. Al exposure can cause a variety of adverse physiological effects in humans and animals. Our aim was to demonstrate that specific probiotic bacteria can play a special physiologically functional role in protection against Al toxicity in mice. Thirty strains of lactic acid bacteria (LAB) were tested for their aluminium-binding ability, aluminium tolerance, their antioxidative capacity, and their ability to survive the exposure to artificial gastrointestinal (GI) juices. Lactobacillus plantarum CCFM639 was selected for animal experiments because of its excellent performance in vitro. Forty mice were divided into four groups: control, Al only, Al plus CCFM639, and Al plus deferiprone (DFP). CCFM639 was administered at 10(9) CFU once daily for 10 days, followed by a single oral dose of aluminium chloride hexahydrate at 5.14 mg aluminium (LD50) for each mouse. The results showed that CCFM639 treatment led to a significant reduction in the mortality rates with corresponding decrease in intestinal aluminium absorption and in accumulation of aluminium in the tissues and amelioration of hepatic histopathological damage. This probiotic treatment also resulted in alleviation of hepatic, renal, and cerebral oxidative stress. The treatment of L. plantarum CCFM639 has potential as a therapeutic dietary strategy against acute aluminium toxicity.

  13. Identifying the cause of toxicity in an algal whole effluent toxicity study - an unanticipated toxicant.

    Science.gov (United States)

    Naddy, Rami B; Tapp, Kelly; Rehner, Anita B; Pillard, David A; Schrage, Laura

    2011-10-01

    Toxicity was observed in whole effluent toxicity (WET) studies with the freshwater alga, Pseudokirchneriella subcapitata, in three consecutive monthly studies, (NOEC=50-75%). Toxicity was not observed to Ceriodaphnia dubia or the fathead minnow, Pimephales promelas in concurrent studies. Selected toxicity identification evaluation (TIE) tests were conducted in a tiered approach to eliminate possible toxicants and progressively identify the causative agent. Filtration following alkaline adjustment (pH 10 or 11) was effective in eliminating significant growth effects and also reduced phosphate concentration. The TIE studies confirmed that the observed effluent toxicity was caused by excess ortho-phosphate in the effluent not by overstimulation or related to unfavorable N:P ratios; but due to direct toxicity. The 96-h 25% inhibition concentration (IC25) of ortho-phosphate to P. subcapitata was 3.4 mg L⁻¹ while the maximum acceptable toxicant concentration was 4.8 mg L⁻¹. This study illustrates the value of multi-species testing and also provides an example of an effective TIE using algae identifying an unanticipated toxicant. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Mechanisms of chemotherapy-induced behavioral toxicities

    Directory of Open Access Journals (Sweden)

    Elisabeth G Vichaya

    2015-04-01

    Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  15. Externalization of the Toxic Introject

    Science.gov (United States)

    Beck, Michael

    1975-01-01

    The therapist encounters patients who have incorporated toxic introjects. Therapy helps them to provide room for incorporation of a healthy object by externalizing the toxic introject. This technique is illustrated with several cases and comparison is made between the use of this technique in the treatment of adults and children. (Author)

  16. 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…

  17. 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...

  18. The toxicity of X material

    Energy Technology Data Exchange (ETDEWEB)

    Ferry, J.L.

    1943-12-31

    This report addresses toxicity (largely chemical) of Manhattan Project materials from the point of worker protection. Known chemical toxicities of X material (uranium), nitrous fumes, fluorine, vanadium, magnesium, and lime are described followed by safe exposure levels, symptoms of exposure, and treatment recommendations. The report closes with an overview of general policy in a question and answer format.

  19. Polish Toxic Currency Options

    Directory of Open Access Journals (Sweden)

    Waldemar Gontarski

    2009-04-01

    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 banks 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 companys 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 companys 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 managers 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 other hand issuing

  20. Glutamic acid modification of vincristine toxicity.

    Science.gov (United States)

    Jackson, D V; Rosenbaum, D L; Carlisle, L J; Long, T R; Wells, H B; Spurr, C L

    1984-09-01

    The principal limiting feature of the antitumor agent, vincristine, in the clinic has been neurotoxicity; there are no known agents which can routinely prevent or decrease this side effect. Glutamic acid in laboratory and clinical investigations in the early 1960s was found to antagonize vinblastine, another clinically useful vinca alkaloid. Glutamic acid 250 mg/kg/d i.p. was given to normal mice treated with repetitive doses of vincristine 1.5 mg/kg every other day. When glutamic acid was given both before and during vincristine administration, it produced a 49-79% increase in survival compared to control mice receiving vincristine only (p less than 0.01). Other schedules of glutamic acid administration were ineffective. Also, there appeared to be a delay in development of neurotoxic manifestations (toe-walking gait) but the results were not as consistent as the improvement in survival. Glutamic acid given to tumor-bearing mice (P-388 and P-1534 murine leukemia) did not inhibit the antitumor effect of vincristine-induced host toxicity in a schedule-dependent fashion without inhibition of the antitumor effect of vincristine.

  1. Joint acute toxicity of diazinon and copper to Ceriodaphnia dubia.

    Science.gov (United States)

    Banks, Kenneth E; Wood, Sylvia H; Matthews, Cathy; Thuesen, Kevin A

    2003-07-01

    Diazinon and copper are two contaminants that are widely found in urban streams and in municipal wastewater effluents. Because these contaminants may be found concurrently, the potential for their joint toxicity is of interest, particularly with regard to toxicity testing of wastewater effluents and the ecological implications of simultaneous exposures in urban streams. Although interactions between metals are well studied, relatively little is known about interactions between metals and organophosphate compounds such as diazinon. In this study, the interaction between copper and diazinon was evaluated using cladoceran (Ceriodaphnia dubia) in 48-h static tests within laboratory water. Using toxic units derived from concurrently established 48-h median lethal concentration values (LC50) of test organisms of each individual toxicant, the effects of the mixture of copper and diazinon on the survival of C. dubia were shown to be generally nonconcentration additive (LC50 significantly greater than one toxic unit). However, evaluation of the dose-response relationship across the entire range of effect levels revealed that the mortality induced by the mixture of copper and diazinon supported concentration additivity at higher effect levels.

  2. Studies on the toxicity of industrial waste to Macrobrachium dayanum

    Energy Technology Data Exchange (ETDEWEB)

    Verma, S.R.; Mathur, R.P.

    1974-01-01

    The toxic substances in industrial wastes, if discharged untreated into the stream can rapidly harm the aquatic life. It is, therefore, necessary to know the permissible concentration of various wastes. This paper presents data obtained from a series of static bioassay experiments conducted to establish the median tolerance limits (TL/sub m/). The distillery waste and the mixed pulp and paper waste were taken and the range of their toxicity was evaluated. Macrobrachium dayanum, a crustacean, was chosen as the test animal because of experimental convenience and suitability. The results on toxicity indicate that distillery waste is more toxic than the mixed pulp and paper factory waste. The toxicity of distillery waste is due to sulphides and H/sub 2/S. The mixed pulp and paper waste contain colloidal particles of cellulose and lignin which are lethal. The statistical analysis shows that both of the wastes are lethal to the animals separately in their natural form. The difference in survival rates is highly significant.

  3. Survival After Relapse of Medulloblastoma.

    Science.gov (United States)

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.

  4. 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.

  5. Hydrocarbon toxicity: A review.

    Science.gov (United States)

    Tormoehlen, L M; Tekulve, K J; Nañagas, K A

    2014-06-01

    Clinical effects of hydrocarbon exposure have been reported since 1897. These substances are ubiquitous, and their exposures are common. The specific hydrocarbon and route of exposure will determine the clinical effect, and an understanding of this is helpful in the care of the hydrocarbon-exposed patient. To complete a comprehensive review of the literature on hydrocarbon toxicity and summarize the findings. Relevant literature was identified through searches of Medline (PubMed/OVID) and Cochrane Library databases (inclusive of years 1975-2013), as well as from multiple toxicology textbooks. Bibliographies of the identified articles were also reviewed. Search terms included combinations of the following: hydrocarbons, inhalants, encephalopathy, coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death, toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and aspiration pneumonitis. All pertinent clinical trials, observational studies, and case reports relevant to hydrocarbon exposure and published in English were reviewed. Chronic, occupational hydrocarbon toxicity was not included. Exposure to hydrocarbons occurs through one of the following routes: inhalation, ingestion with or without aspiration, or dermal exposure. Inhalational abuse is associated with central nervous system depression, metabolic acidosis, and arrhythmia. The exact mechanism of the CNS depression is unknown, but experimental evidence suggests effects on NMDA, dopamine, and GABA receptors. Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse hydrocarbons are more likely to be polysubstance users, exhibit criminal or violent behavior, and develop memory and other cognitive deficits. Heavy, long-term use results in cerebellar dysfunction, encephalopathy, weakness, and dementia

  6. Toxicity of energy drinks.

    Science.gov (United States)

    Wolk, Brian J; Ganetsky, Michael; Babu, Kavita M

    2012-04-01

    'Energy drinks', 'energy shots' and other energy products have exploded in popularity in the past several years; however, their use is not without risk. Caffeine is the main active ingredient in energy drinks, and excessive consumption may acutely cause caffeine intoxication, resulting in tachycardia, vomiting, cardiac arrhythmias, seizures, and death. The effects of chronic high-dose caffeine intake in children and adolescents are unknown. Caffeine may raise blood pressure, disrupt adolescent sleep patterns, exacerbate psychiatric disease, cause physiologic dependence, and increase the risk of subsequent addiction. Coingestion of caffeine and ethanol has been associated with increased risk-taking behaviors, harm to adolescent users, impaired driving, and increased use of other illicit substances. The toxicity of ingredients often present in energy drinks, such as taurine, niacin, and pyridoxine, is less well defined. Recent and significant literature describing adverse events associated with energy drink use are reviewed. Although prior studies have examined the effects of caffeine in adolescents, energy drinks should be considered a novel exposure. The high doses of caffeine, often in combination with ingredients with unknown safety profiles, mandates urgent research on the safety of energy drink use in children and adolescents. Regulation of pediatric energy drink use may be a necessary step once the health effects are further characterized.

  7. Overcoming ammonium toxicity.

    Science.gov (United States)

    Bittsánszky, András; Pilinszky, Katalin; Gyulai, Gábor; Komives, Tamas

    2015-02-01

    Ammonia (ammonium ion under physiological conditions) is one of the key nitrogen sources in cellular amino acid biosynthesis. It is continuously produced in living organisms by a number of biochemical processes, but its accumulation in cells leads to tissue damage. Current knowledge suggests that a few enzymes and transporters are responsible for maintaining the delicate balance of ammonium fluxes in plant tissues. In this study we analyze the data in the scientific literature and the publicly available information on the dozens of biochemical reactions in which endogenous ammonium is produced or consumed, the enzymes that catalyze them, and the enzyme and transporter mutants listed in plant metabolic and genetic databases (Plant Metabolic Network, TAIR, and Genevestigator). Our compiled data show a surprisingly high number of little-studied reactions that might influence cellular ammonium concentrations. The role of ammonium in apoptosis, its relation to oxidative stress, and alterations in ammonium metabolism induced by environmental stress need to be explored in order to develop methods to manage ammonium toxicity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. High levels of MMP-2, MMP-9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma.

    Science.gov (United States)

    Davidson, B; Goldberg, I; Gotlieb, W H; Kopolovic, J; Ben-Baruch, G; Nesland, J M; Berner, A; Bryne, M; Reich, R

    1999-01-01

    The object of this study was to analyze the potential association between the expression of MMP-2, MMP-9, MT1-MMP and TIMP-2, and disease outcome in advanced-stage ovarian carcinomas. Sections from 70 paraffin-embedded blocks (36 primary ovarian carcinomas and 34 metastatic lesions) from 45 patients diagnosed with advanced stage ovarian carcinomas (FIGO stages III-IV) were studied using mRNA in situ hybridization (ISH) technique. Patients were divided retrospectively in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period for patients that were diagnosed with advanced-stage carcinoma was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Intense mRNA signals were detected more frequently in tumor cells of short-term survivors with use of all four probes. Comparable findings were observed in peritumoral stromal cells with ISH for MMP-2, MMP-9 and TIMP-2 mRNA. Notably, primary tumors with intense mRNA signal for TIMP-2 (No = 14) were uniformly associated with a fatal outcome. In univariate analysis of primary tumors, mRNA levels of TIMP-2 in stromal cells (P = 0.0002), as well as for MMP-9 (P = 0.012) and TIMP-2 (P = 0.02) in tumor cells, correlated with poor outcome. In univariate analysis of metastatic lesions, mRNA levels of TIMP-2 in stromal cells (P = 0.031), as well as for MMP-2 (P = 0.027) and MT1-MMP (P = 0.008) in tumor cells, correlated with poor outcome. Interestingly, the presence of MT1-MMP in stromal cells correlated with longer survival (P = 0.025). In a multivariate analysis of ISH results for primary tumors, TIMP-2 levels in stromal cells (P = 0.006) and MMP-9 levels in tumor cells (P = 0.011) retained their predictive value. We conclude that

  9. Marketing child survival.

    Science.gov (United States)

    Grant, J P

    1984-01-01

    Growth monitoring charts, packets of oral rehydration salts (ORS), and vaccines, are inexpensive, life-saving, growth-protecting technologies which can enable parents to protect their children against the worst effects of poverty. Similarly, a matrix of current and easily understandable information about pregnancy, breast feeding, weaning, feeding during and immediately after illness, child spacing, and preparing and using home-made oral rehydration solutions, also could empower parents to protect the lives and the health of their children. The question arises as to how can these technologies and this information be put at the disposal of millions of families in the low-income world. The initial task of the Child Survival and Development Revolution is the communication of what is now possible, yet little is known about how to communicate information whose principal value is to the poor. There are 2 large-scale precedents: the Green Revolution, which in many instances succeeded in putting into the hands of thousands of small and large farmers the techniques and the knowledge which enabled them to double and treble the yields from their lands; and the campaign to put the knowledge and the means of family planning at the disposal of many millions of people. There are 2 lessons to be learned from these precedents: they have shown that the way to promote a people's technology and to put information at the disposal of the majority is by mobilizing all possible resources and working through all possible channels both to create the demand and to meet it; and neither the Green Revolution nor the family planning movement rally took off until they were viewed as political and economic priorities and given the full support of the nation's political leadership. Nowhere are these 2 lessons more clearly illustrated than in present-day Indonesia. Because the campaign for family planning was given high personal and political priority by the President, and because 85% of all family

  10. Detection of microcystins in Pamvotis lake water and assessment of cyanobacterial bloom toxicity.

    Science.gov (United States)

    Papadimitriou, Theodoti; Armeni, Euthimia; Stalikas, Constantine D; Kagalou, Ifigeneia; Leonardos, Ioannis D

    2012-05-01

    Lake Pamvotis is a shallow, eutrophic Mediterranean lake with ecological significance. This paper deals with the evaluation of cyanobacterial toxicity in Lake Pamvotis. ELISA and HPLC revealed the presence of significant amounts of MCYST-LR. Danio rerio bioassay confirmed the toxic nature of the bloom. Cyanobacterial extracts had adverse toxic effects on development of D. rerio. Also, it was shown that cyanobacterial extracts containing environmentally detected concentrations of MCYST can cause reduced survival rate of fish species. The results clearly indicate that cyanobacterial blooms in Lake Pamvotis may be regarded as human and fish health hazard. Continuous monitoring of the lake is suggested, in order to prevent future possible intoxications.

  11. Comparison and avoidance of toxicity of penetrating cryoprotectants.

    Directory of Open Access Journals (Sweden)

    Edyta A Szurek

    Full Text Available The objective of this study was to elucidate the toxicity of widely used penetrating cryoprotective agents (CPAs to mammalian oocytes. To this end, mouse metaphase II (M II oocytes were exposed to 1.5 M solutions of dimethylsulfoxide (DMSO, ethylene glycol (EG, or propanediol (PROH prepared in phosphate buffered saline (PBS containing 10% fetal bovine serum. To address the time- and temperature-dependence of the CPA toxicity, M II oocytes were exposed to the aforementioned CPAs at room temperature (RT, ∼23°C and 37°C for 15 or 30 minutes. Subsequently, the toxicity of each CPA was evaluated by examining post-exposure survival, fertilization, embryonic development, chromosomal abnormalities, and parthenogenetic activation of treated oocytes. Untreated oocytes served as controls. Exposure of MII oocytes to 1.5 M DMSO or 1.5 M EG at RT for 15 min did not adversely affect any of the evaluated criteria. In contrast, 1.5 M PROH induced a significant increase in oocyte degeneration (54.2% and parthenogenetic activation (16% under same conditions. When the CPA exposure was performed at 37°C, the toxic effect of PROH further increased, resulting in lower survival (15% and no fertilization while the toxicity of DMSO and EG was still insignificant. Nevertheless, it was possible to completely avoid the toxicity of PROH by decreasing its concentration to 0.75 M and combining it with 0.75 M DMSO to bring the total CPA concentration to a cryoprotective level. Moreover, combining lower concentrations (i.e., 0.75 M of PROH and DMSO significantly improved the cryosurvival of MII oocytes compared to the equivalent concentration of DMSO alone. Taken together, our results suggest that from the perspective of CPA toxicity, DMSO and EG are safer to use in slow cooling protocols while a lower concentration of PROH can be combined with another CPA to avoid its toxicity and to improve the cryosurvival as well.

  12. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  13. Foraging response and acclimation of ambush feeding and feeding-current feeding copepods to toxic dinoflagellates

    DEFF Research Database (Denmark)

    Xu, Jiayi; Nielsen, Lasse Tor; Kiørboe, Thomas

    2018-01-01

    Copepods exposed to toxic algae in “black box” incubation experiments show highly varied responses, but the mechanisms cannot be revealed from such experiments and the implications to copepod and phytoplankton population dynamics consequently not evaluated. Here, we use direct video observations...... reticulatum. We hypothesize (1) that ambush feeders are less affected by toxic algae than feeding-current feeders, (2) that copepods acclimate to the toxic algae, and (3) that phytoplankton cells previously exposed to copepod cues elicit stronger responses. Both copepod species consumed the toxic algae...... the copepods to survive harmful algal blooms. However, the implications to algal population dynamics are species/strains specific, with only prey selection providing the toxic algae with a competitive advantage...

  14. The future of toxicity testing.

    Science.gov (United States)

    Andersen, Melvin E; Al-Zoughool, Mustafa; Croteau, Maxine; Westphal, Margit; Krewski, Daniel

    2010-02-01

    In 2007, the U.S. National Research Council (NRC) released a report, "Toxicity Testing in the 21st Century: A Vision and a Strategy," that proposes a paradigm shift for toxicity testing of environmental agents. The vision is based on the notion that exposure to environmental agents leads to adverse health outcomes through the perturbation of toxicity pathways that are operative in humans. Implementation of the NRC vision will involve a fundamental change in the assessment of toxicity of environmental agents, moving away from adverse health outcomes observed in experimental animals to the identification of critical perturbations of toxicity pathways. Pathway perturbations will be identified using in vitro assays and quantified for dose response using methods in computational toxicology and other recent scientific advances in basic biology. Implementation of the NRC vision will require a major research effort, not unlike that required to successfully map the human genome, extending over 10 to 20 years, involving the broad scientific community to map important toxicity pathways operative in humans. This article provides an overview of the scientific tools and technologies that will form the core of the NRC vision for toxicity testing. Of particular importance will be the development of rapidly performed in vitro screening assays using human cells and cell lines or human tissue surrogates to efficiently identify environmental agents producing critical pathway perturbations. In addition to the overview of the NRC vision, this study documents the reaction by a number of stakeholder groups since 2007, including the scientific, risk assessment, regulatory, and animal welfare communities.

  15. The distribution of fruit and seed toxicity during development for eleven neotropical trees and vines in Central Panama.

    Directory of Open Access Journals (Sweden)

    Noelle G Beckman

    Full Text Available Secondary compounds in fruit mediate interactions with natural enemies and seed dispersers, influencing plant survival and species distributions. The functions of secondary metabolites in plant defenses have been well-studied in green tissues, but not in reproductive structures of plants. In this study, the distribution of toxicity within plants was quantified and its influence on seed survival was determined in Central Panama. To investigate patterns of allocation to chemical defenses and shifts in allocation with fruit development, I quantified variation in toxicity between immature and mature fruit and between the seed and pericarp for eleven species. Toxicity of seed and pericarp was compared to leaf toxicity for five species. Toxicity was measured as reduced hyphal growth of two fungal pathogens, Phoma sp. and Fusarium sp., and reduced survivorship of brine shrimp, Artemia franciscana, across a range of concentrations of crude extract. I used these measures of potential toxicity against generalist natural enemies to examine the effect of fruit toxicity on reductions of fruit development and seed survival by vertebrates, invertebrates, and pathogens measured for seven species in a natural enemy removal experiment. The seed or pericarp of all vertebrate- and wind-dispersed species reduced Artemia survivorship and hyphal growth of Fusarium during the immature and mature stages. Only mature fruit of two vertebrate-dispersed species reduced hyphal growth of Phoma. Predispersal seed survival increased with toxicity of immature fruit to Artemia during germination and decreased with toxicity to fungi during fruit development. This study suggests that fruit toxicity against generalist natural enemies may be common in Central Panama. These results support the hypothesis that secondary metabolites in fruit have adaptive value and are important in the evolution of fruit-frugivore interactions.

  16. The distribution of fruit and seed toxicity during development for eleven neotropical trees and vines in Central Panama.

    Science.gov (United States)

    Beckman, Noelle G

    2013-01-01

    Secondary compounds in fruit mediate interactions with natural enemies and seed dispersers, influencing plant survival and species distributions. The functions of secondary metabolites in plant defenses have been well-studied in green tissues, but not in reproductive structures of plants. In this study, the distribution of toxicity within plants was quantified and its influence on seed survival was determined in Central Panama. To investigate patterns of allocation to chemical defenses and shifts in allocation with fruit development, I quantified variation in toxicity between immature and mature fruit and between the seed and pericarp for eleven species. Toxicity of seed and pericarp was compared to leaf toxicity for five species. Toxicity was measured as reduced hyphal growth of two fungal pathogens, Phoma sp. and Fusarium sp., and reduced survivorship of brine shrimp, Artemia franciscana, across a range of concentrations of crude extract. I used these measures of potential toxicity against generalist natural enemies to examine the effect of fruit toxicity on reductions of fruit development and seed survival by vertebrates, invertebrates, and pathogens measured for seven species in a natural enemy removal experiment. The seed or pericarp of all vertebrate- and wind-dispersed species reduced Artemia survivorship and hyphal growth of Fusarium during the immature and mature stages. Only mature fruit of two vertebrate-dispersed species reduced hyphal growth of Phoma. Predispersal seed survival increased with toxicity of immature fruit to Artemia during germination and decreased with toxicity to fungi during fruit development. This study suggests that fruit toxicity against generalist natural enemies may be common in Central Panama. These results support the hypothesis that secondary metabolites in fruit have adaptive value and are important in the evolution of fruit-frugivore interactions.

  17.   Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E.

    the untreated patient group as a reference group, we analyzed the benefit of adjuvant CMF and anthracyclines in TIMP-1 high and low patients, respectively. The median TIMP-1 concentration was used to dichotomize patients into high and low TIMP-1 groups. End points were disease-free and overall survival (DFS, OS...... and high patients benefited differentially from adjuvant CMF and anthracyclines when compared to untreated patients. In particular, patients with high tumor levels of TIMP-1 had little benefit from adjuvant anthracyclines. Hazard ratios (HR) and 95% confidence intervals (CI) are given in the table below...... tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however...

  18. A COMPREHENSIVE REVIEW OF TOXIC LEADERSHIP

    Science.gov (United States)

    2016-02-05

    Definitions of Toxic Leadership ...3 Table 1: Definitions of Toxic Leadership ... leadership . However, there are differing explanations as to the cause, solution, and even the definition of toxic leadership . This research contains

  19. 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...

  20. Global Activities and Plant Survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2014-01-01

    This chapter provides an extensive review of the empirical evidence found for Sweden concerning plant survival. The result reveals that foreign MNE plants and exporting non-MNE plants have the lowest exit rates, followed by purely domestic-oriented plants, and that domestic MNE plants have...... the highest exit rates. Moreover, the exit rates of globally engaged plants seem to be unaffected by increased foreign presence, whereas there appears to be a negative impact on the survival rates of non-exporting non-MNE plants. Finally, the result reveals that the survival ratio of plants of acquired...... exporters, but not other types of plants, improves post acquisition....

  1. Cardiovascular disease incidence and survival

    DEFF Research Database (Denmark)

    Byberg, Stine; Agyemang, Charles; Zwisler, Ann Dorthe

    2016-01-01

    Studies on cardiovascular disease (CVD) incidence and survival show varying results between different ethnic groups. Our aim was to add a new dimension by exploring the role of migrant status in combination with ethnic background on incidence of-and survival from-CVD and more specifically acute...... of some types of cardiovascular disease compared to Danish-born. Family-reunified migrants on the other hand had lower rates of CVD. All migrants had better survival than Danish-born indicating that migrants may not always be disadvantaged in health....

  2. Biological control of toxic cyanobacteri

    CSIR Research Space (South Africa)

    Ndlela, Luyanda L

    2017-05-01

    Full Text Available and applications • If successful, the biocontrol agents may produce conformational changes to the cyanobacterial toxins or reduced eco-toxicity effects • The laboratory study may give insight into the factors inhibiting the natural balance of predatory... on the eco-toxicity resulting from biocontrol as well as the changes to cyanotoxins, if any. Research Plan The study will be conducted at whole cell level and with specific metabolites and toxins, with eco-toxicity studied at three trophic levels...

  3. Developmental Exposure to Environmental Toxicants.

    Science.gov (United States)

    Falck, Alison J; Mooney, Sandra; Kapoor, Shiv S; White, Kimberly M R; Bearer, Cynthia; El Metwally, Dina

    2015-10-01

    Children interact with the physical environment differently than adults, and are uniquely susceptible to environmental toxicants. Routes of absorption, distribution, metabolism, and target organ toxicities vary as children grow and develop. This article summarizes the sources of exposure and known adverse effects of toxicants that are ubiquitous in our environment, including tobacco smoke, ethanol, solvents, heavy metals, volatile organic compounds, persistent organic pollutants, and pesticides. Preventive strategies that may be used in counseling children and their families are highlighted. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. [Imatinib-induced pulmonary toxicity].

    Science.gov (United States)

    Carrillo-Esper, Raúd; Morales-Victorino, Neisser

    2009-01-01

    Antineoplasic agent-induced pulmonary toxicity is an important cause of respiratory failure. These novel antineoplastic agents include imatinib mesylate, a protein tyrosine kinase inhibitor that is encoded by the Bcr-Abl gen created by the Philadelphia chromosome abnormality in chronic myeloid leukemia. Pulmonary toxicity of imatinib is directly related to the dose used. The more severe pulmonary manifestations include pleural effusion by water retention and interstitial pneumonitis. We report the first case published in Mexico ofimatinib-induced pulmonary toxicity and its management in the intensive care unit of the Medica Sur Clinic Foundation.

  5. Toxicity of staphylococcal toxic shock syndrome toxin 1 in rabbits.

    OpenAIRE

    de Azavedo, J C; Arbuthnott, J P

    1984-01-01

    Strains of Staphylococcus aureus associated with toxic shock syndrome produce toxic shock syndrome toxin 1 (TSST 1), which is lethal to conventional rabbits and acts synergistically with gram-negative lipopolysaccharide. The lethal effect of TSST 1 was examined in specific-pathogen-free rabbits on the basis that these rabbits, being less colonized by gram-negative bacteria, would be less susceptible than conventional animals. Although there was no significant difference in mortality between s...

  6. 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.

  7. Variable toxicity of silver nanoparticles to Daphnia magna: effects of algal particles and animal nutrition.

    Science.gov (United States)

    Conine, Andrea L; Frost, Paul C

    2017-01-01

    Aquatic environments vary widely in aspects other than their physicochemical properties that could alter the toxicity of novel contaminants. One factor that could affect chemical toxicity to aquatic consumers is their nutritional environment as it can strongly affect their physiology and life history. Nutrition has the potential to alter an organism's response to the toxin or how the toxin interacts with the consumer through its food. Here we determined how growth and survival responses of Daphnia to an emerging contaminant, silver nanoparticles (AgNPs), are affected by the presence of food and its stoichiometric food quality. We used a series of survival tests, each slightly modified, to determine whether variable toxicity in different nutritional environments resulted from algal sequestration of AgNPs in a nontoxic form or from changes to the nutritional status of the test animals. We found that the presence of algae, of good or poor quality, reduced the toxicity of AgNPs on animal growth and survival. However, the decrease in AgNP toxicity was greater for animals consuming P-rich compared to P-poor food. We found evidence that this effect of food quality was due to greater algal uptake of AgNPs by P-rich than by P-stressed algae. However, we also found animal nutrition, in the absence of algal AgNP binding, could affect toxicity with P-nourished animals surviving slightly better when exposed to AgNPs compared to their P-stressed counterparts. Our results show an important role for algal particles and their P content in determining the toxicity of AgNPs in natural waters primarily due to their binding and uptake abilities and, less so, to their effects on animal nutrition.

  8. Predictors of Chemotherapy-Induced Toxicity and Treatment Outcomes in Elderly Versus Younger Patients With Metastatic Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

    used to evaluate treatment-related toxicity and efficacy. Logistic and Cox regression models were used to predict toxicity and survival. RESULTS: Age ≥ 75 years (odds ratio [OR], 2.33), baseline levels of hemoglobin (OR, 0.89), and previous metastatic epidural spinal cord compression (MESCC; OR, 1......BACKGROUND: In the present study, we examined possible predictors of chemotherapy-induced toxicity, treatment outcomes, and the consequences of dose reductions in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving standard docetaxel. PATIENTS AND METHODS: Medical.......70) were predictive of grade 3 and 4 nonhematologic toxicity. Previous MESCC was associated with a greater risk of febrile neutropenia (OR, 2.74). The median progression-free survival (PFS) and overall survival (OS) were 6.4 and 15.4 months, respectively. Survival was similar in the older (age ≥ 75 years...

  9. An evaluation of the toxicity of contaminated sediments from Waukegan Harbor, Illinois, following remediation

    Science.gov (United States)

    Kemble, N.E.; Hardesty, D.G.; Ingersoll, C.G.; Johnson, B. Thomas; Dwyer, F.J.; MacDonald, D.D.

    2000-01-01

    Waukegan Harbor in Illinois was designated as a Great Lakes Area of Concern due to high concentrations of sediment-associated polychlorinated biphenyls (PCBs). The objective of this study was to evaluate the toxicity of 20 sediment samples collected after remediation (primarily dredging) of Waukegan Harbor for PCBs. A 42-day whole sediment toxicity test with the amphipod Hyalella azteca (28-day sediment exposure followed by a 14-day reproductive phase) and sediment toxicity tests with Microtox® were conducted to evaluate sediments from Waukegan Harbor. Endpoints measured were survival, growth, and reproduction (amphipods) and luminescent light emission (bacteria). Survival of amphipods was significantly reduced in 6 of the 20 sediment samples relative to the control. Growth of amphipods (either length or weight) was significantly reduced relative to the control in all samples. However, reproduction of amphipods identified only two samples as toxic relative to the control. The Microtox basic test, conducted with organic extracts of sediments identified only one site as toxic. In contrast, the Microtox solid-phase test identified about 50% of the samples as toxic. A significant negative correlation was observed between reproduction and the concentration of three polynuclear aromatic hydrocarbons (PAHs) normalized to total organic carbon. Sediment chemistry and toxicity data were evaluated using sediment quality guidelines (consensus-based probable effect concentrations, PECs). Results of these analyses indicate that sediment samples from Waukegan Harbor were toxic to H. azteca contaminated at similar contaminant concentrations as sediment samples that were toxic to H. azteca from other areas of the United States. The relationship between PECs and the observed toxicity was not as strong for the Microtox test. The results of this study indicate that the first phase of sediment remediation in Waukegan Harbor successfully lowered concentrations of PCBs at the site

  10. Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

    Science.gov (United States)

    Nowell, Lisa H.; Norman, Julia E.; Ingersoll, Christopher G.; Moran, Patrick W.

    2016-01-01

    Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical

  11. Effect of Polychlorinated Biphenyls (PCBˈs) on Survival and Reproduction of Daphnia, Gammarus, and Tanytarsus

    National Research Council Canada - National Science Library

    Nebeker, Alan V; Puglisi, Frank A

    1974-01-01

    Continuous‐flow and static bioassays were conducted at 18 C, with survival and reproduction as measures of relative toxicity of eight PCBˈs, Aroclor 1221 (A‐1221), A‐1232, A‐1242, A‐1248, A‐1254, A‐1260, A‐1262, and A‐1268. Three PCB...

  12. Modeling receptor kinetics in the analysis of survival data for organophosphorus pesticides.

    NARCIS (Netherlands)

    Jager, D.T.; Kooijman, S.A.L.M.

    2005-01-01

    Acute ecotoxicological tests usually focus on survival at a standardized exposure time. However, LC50's decrease in time in a manner that depends both on the chemical and on the organism. DEBtox is an existing approach to analyze toxicity data in time, based on hazard modeling (the internal

  13. Stereotactic radiotherapy of meningiomas. Symptomatology, acute and late toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Henzel, M.; Gross, M.W.; Failing, T.; Strassmann, G.; Engenhart-Cabillic, R. [Dept. of Radiation Oncology, Univ. of Gisssen (Germany); Dept. of Radiation Oncology, Marburg Univ. (Germany); Hamm, K.; Surber, G.; Kleinert, G. [Dept. of Stereotactic Neurosurgery and Radiosurgery, Helios Klinikum Erfurt (Germany)

    2006-07-15

    Background and purpose: stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. Patients and methods: between 1997-2003, 224 patients were treated with SRT (n= 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. Results: the median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III ) was rarely seen (2.5%). Clinically significant late morbidity (III -IV ) or new cranial nerve palsies did not occur. Conclusion: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended. (orig.)

  14. Determination of leachate toxicity through acute toxicity using Daphnia pulex and anaerobic toxicity assays

    Directory of Open Access Journals (Sweden)

    Patricia Torres Lozada

    2017-01-01

    Full Text Available The municipal solid waste (MSW of large cities, in particular in developing countries, is mainly disposed of in landfills (LFs, whose inadequate management generates the emission of greenhouse gases and the production of leachates with high concentrations of organic and inorganic matter and occasionally heavy metals. In this study, the toxicity of the leachates from an intermediate-age municipal landfill was evaluated by ecotoxicity and anaerobic digestion tests. The acute toxicity assays with Daphnia pulex presented a toxic unit (TU value of 49.5%, which indicates that these leachates should not be directly discharged into water sources or percolate into the soil because they would affect the ecosystems served by these waters. According to statistical analyses, the leachate toxicity is mainly associated with the inorganic fraction, with chlorides, calcium hardness and calcium having the greatest influence on the toxicity. The anaerobic toxicity assays showed that in the exposure stage, the methanogenic activity exceeded that of the control, which suggests that the anaerobic bacteria easily adapted to the leachate. Therefore, this treatment could be an alternative to mitigate the toxicity of the studied leachates. The inhibition presented in the recovery stage, represented by a reduction of the methanogenic activity, could arise because the amount of supplied substrate was not enough to fulfill the carbon and nutrient requirements of the bacterial population present.

  15. Determination of leachate toxicity through acute toxicity using Daphnia pulex and Anaerobic Toxicity Assays

    Directory of Open Access Journals (Sweden)

    Patricia Torres Lozada

    2017-01-01

    Full Text Available The municipal solid waste (MSW of large cities, in particular in developing countries, is mainly disposed of in landfills (LFs, whose inadequate management generates the emission of greenhouse gases and the production of leachates with high concentrations of organic and inorganic matter and occasionally heavy metals. In this study, the toxicity of the leachates from an intermediate-age municipal landfill was evaluated by ecotoxicity and anaerobic digestion tests. The acute toxicity assays with Daphnia pulex presented a toxic unit (TU value of 49.5%, which indicates that these leachates should not be directly discharged into water sources or percolate into the soil because they would affect the ecosystems served by these waters. According to statistical analyses, the leachate toxicity is mainly associated with the inorganic fraction, with chlorides, calcium hardness and calcium having the greatest influence on the toxicity. The anaerobic toxicity assays showed that in the exposure stage, the methanogenic activity exceeded that of the control, which suggests that the anaerobic bacteria easily adapted to the leachate. Therefore, this treatment could be an alternative to mitigate the toxicity of the studied leachates. The inhibition presented in the recovery stage, represented by a reduction of the methanogenic activity, could arise because the amount of supplied substrate was not enough to fulfill the carbon and nutrient requirements of the bacterial population present.

  16. Non-Toxic HAN Monopropellant Propulsion Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Non-toxic monopropellants have been developed that provide better performance than toxic hydrazine. Formulations based on hydroxylammonium nitrate (HAN) have...

  17. Campylobacter colitis: Rare cause of toxic megacolon

    Directory of Open Access Journals (Sweden)

    Michael Kwok, MBBS

    2016-01-01

    Conclusion: Toxic megacolon should be considered in a patient with Campylobacter colitis who becomes critically unwell. Despite treatment, toxic megacolon is associated with a significant risk of mortality.

  18. [Physical activity and cancer survival].

    Science.gov (United States)

    Romieu, Isabelle; Touillaud, Marina; Ferrari, Pietro; Bignon, Yves-Jean; Antoun, Sami; Berthouze-Aranda, Sophie; Bachmann, Patrick; Duclos, Martine; Ninot, Grégory; Romieu, Gilles; Sénesse, Pierre; Behrendt, Jan; Balosso, Jacques; Pavic, Michel; Kerbrat, Pierre; Serin, Daniel; Trédan, Olivier; Fervers, Béatrice

    2012-10-01

    Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

  19. 2011 NATA - Air Toxics Monitors

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset includes annual (2005 - 2013) statistics of measured ambient air toxics concentrations (in micrograms per cubic meter) and associated risk estimates for...

  20. Methylmercury toxicity and functional programming

    DEFF Research Database (Denmark)

    Grandjean, Philippe

    2007-01-01

    PURPOSE: Adverse health effects of developmental toxicants may induce abnormal functional programming that leads to lasting functional deficits. This notion is considered from epidemiological evidence using developmental methylmercury neurotoxicity as an example. MOST IMPORTANT FINDINGS: Accumula...

  1. Operational slack and venture survival

    OpenAIRE

    Azadegan, Arash; Patel, Pankaj; Parida, Vinit

    2013-01-01

    Slack can act as a double-edged sword. While it can buffer against environmental threats to help ensure business continuity, slack canalso be costly and reduce profitability. In this study, we focus on operational slack, the form related to the firm’s production processes. We investigate the role of operational slack on firm survival during its venture stage, when its survival is significantly challenged by environmental threats. Specifically, we explore how change in three types of environme...

  2. A zebrafish model for uremic toxicity: role of the complement pathway.

    Science.gov (United States)

    Berman, Nathaniel; Lectura, Melisa; Thurman, Josh; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Reinecke, James; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. Copyright © 2013 S. Karger AG, Basel.

  3. TOXIC AND DRUG INDUCED MYOPATHIES

    OpenAIRE

    2009-01-01

    Abstract Although the ?do no harm? dogma of Hippocrates is faithfully followed by all practitioners, drugs used for therapeutic interventions either alone or in combination, may sometimes cause unexpected toxicity to the muscles, resulting in a varying degree of symptomatology, from mild discomfort and inconvenience to permanent damage and disability. The clinician should suspect a toxic myopathy when a patient without a pre-existing muscle disease develops myalgia, fatigue, weakn...

  4. FOLFOX and FLOX regimens for the adjuvant treatment of resected stage II and III colon cancer.

    Science.gov (United States)

    Sharif, Saima; O'Connell, Michael J; Yothers, Greg; Lopa, Samia; Wolmark, Norman

    2008-11-01

    The MOSAIC trial showed that the use of adjuvant oxaliplatin and an infusional regimen of 5-FU/LV in the treatment of stage II/III colon cancer improved disease-free survival (DFS). The NSABP's C-07 trial evaluated the addition of oxaliplatin to a weekly Roswell Park regimen of bolus 5-FU/LV and found a similar improvement in DFS. The benefit of oxaliplatin appears to be independent of the 5-FU/LV regimen used. This paper reviews the efficacy and toxicities of these two regimens and is meant to serve as a guide for clinical practice.

  5. Acute toxicity of chlorpyrifos to embryo and larvae of banded gourami Trichogaster fasciata

    NARCIS (Netherlands)

    Sumon, Kizar Ahmed; Saha, Sampa; Brink, van den Paul J.; Peeters, Edwin T.H.M.; Bosma, Roel H.; Rashid, Harunur

    2017-01-01

    This study elucidated the acute toxicity of chlorpyrifos on the early life stages of banded gourami (Trichogaster fasciata). To determine the acute effects of chlorpyrifos on their survival and development, we exposedthe embryos and two-day-old larvae to six concentrations (0, 0.01, 0.10, 1.0, 10

  6. Acute and chronic toxicity of lead in water and diet to the amphipod Hyalella azteca

    Science.gov (United States)

    Besser, J.M.; Brumbaugh, W.G.; Brunson, E.L.; Ingersoll, C.G.

    2005-01-01

    We evaluated the influence of waterborne and dietary lead (Pb) exposure on the acute and chronic toxicity of Pb to the amphipod Hyalella azteca. Test solutions were generated by a modified diluter with an extended (24-h) equilibration period. Acute (96-h) toxicity of Pb varied with water hardness in the range of 71 to 275 mg/L as CaCO3, despite similar dissolved Pb concentrations. Acute toxicity was greatest in soft test water, with less than 50% survival at the lowest dissolved Pb concentration (151 ??g/L). Survival also was significantly reduced in medium-hardness water but not in hard test water. In chronic (42-d) studies, amphipods were exposed to waterborne Pb and fed either a control diet or a diet equilibrated with waterborne Pb levels. For animals fed the control diet, the median lethal concentration (LC50) for Pb was 24 ??g/L (as dissolved Pb), and significant reductions in survival occurred at 16 ??g/L. Exposure to Pb-treated diets significantly increased toxicity across a wide range of dissolved Pb concentrations, with a LC50 of 16 ??g/L and significant reductions in growth and reproduction at 3.5 ??g/L. Significant effects on growth and reproduction occurred at dissolved Pb concentrations close to the current U.S. chronic water-quality criterion. Our results suggest that both aqueous- and dietary-exposure pathways contribute significantly to chronic Pb exposure and toxic effects in aquatic biota. ?? 2005 SETAC.

  7. The predictive value of {sup 18}F-FDG PET/CT for assessing pathological response and survival in locally advanced rectal cancer after neoadjuvant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Leccisotti, Lucia; Stefanelli, Antonella; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Institute of Nuclear Medicine, Rome (Italy); Gambacorta, Maria Antonietta; Valentini, Vincenzo [Universita Cattolica del Sacro Cuore, Institute of Radiation Oncology, Rome (Italy); De Waure, Chiara [Universita Cattolica del Sacro Cuore, Institute of Public Health, Roma (Italy); Barbaro, Brunella [Universita Cattolica del Sacro Cuore, Institute of Radiology, Rome (Italy); Vecchio, Fabio Maria [Universita Cattolica del Sacro Cuore, Institute of Pathology, Rome (Italy); Coco, Claudio; Persiani, Roberto; Crucitti, Antonio; Tortorelli, Antonino Pio [Universita Cattolica del Sacro Cuore, Department of Surgical Sciences, Rome (Italy)

    2015-04-01

    To evaluate whether metabolic changes in the primary tumour during and after preoperative radiochemotherapy (RCT) can predict the histopathological response in patients with locally advanced rectal cancer as well as disease-free survival (DFS) and overall survival (OS). Consecutive patients with cT2-4 N0-2 rectal adenocarcinoma were included. {sup 18}F-FDG PET/CT was performed at baseline, at the end of the second week of RCT (early PET/CT) and before surgery (late PET/CT). The PET/CT results were compared with histopathological data (ypT0 N0 vs. ypT1-4 N0-2 as well as TRG1 vs.TRG2-5) and survival. The study included 126 patients. Among 124 patients in whom TNM classification was available, 28 (22.6 %) were ypT0 N0, and among all 126 patients, 31 (24.6 %) were TRG1. The areas under the curve of the early response index (RI) for identifying non-complete pathological response (non-cPR) were 0.74 (95 % CI 0.61 - 0.87) for ypT1-4 N0-2 patients and 0.75 (95 % CI 0.62 - 0.88) for TRG2-5 patients. The optimal cut-off for differentiating patients with non-cPR and cPR was found to be a reduction of 61.2 % (83.1 % sensitivity and 65 % specificity in ypT1-4 N0-2 patients; 85.4 % sensitivity and 65.2 % specificity in TRG2-5 patients). The optimal cut-off for late RI could not be found. The qualitative analysis of images obtained after RCT demonstrated 81.5 % sensitivity and 61.3 % specificity in predicting TRG2-5. After a median follow-up of 68 months, the low number of patients with local/distant recurrence or who had died did not allow the value of PET/CT for predicting DFS and OS to be calculated. The early assessment of response to RCT by {sup 18}F-FDG PET/CT can predict non-cPR allowing practical modification of preoperative treatment. Conversely, late RI is not sufficiently accurate for guiding the decision as to whether local excision or even observation is appropriate in an individual patient. Qualitative analysis of late PET/CT images is also not sensitive enough

  8. Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer Patients

    Science.gov (United States)

    Mesker, Wilma E.; Liefers, Gerrit-Jan; Junggeburt, Jan M. C.; van Pelt, Gabi W.; Alberici, Paola; Kuppen, Peter J. K.; Miranda, Noel F.; van Leeuwen, Karin A. M.; Morreau, Hans; Szuhai, Karoly; Tollenaar, Rob A. E. M.; Tanke, Hans J.

    2009-01-01

    Background: For stage I–II colon cancer a significant number (5–25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment. Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: β-catenin, TGF-β-R2 and SMAD4. Methods: In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β-catenin, TGF-β-R2 and SMAD4. Results: Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p < 0.001, HZ 2.73, CI 1.73–4.30; DFS p < 0.001, HZ 2.43, CI 1.55–3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13–13.82, p < 0.001). Conclusion: Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome. PMID:19478385

  9. Toxicity assessment in marine sediment for the Terra Nova environmental effects monitoring program (1997-2010)

    Science.gov (United States)

    Whiteway, Sandra A.; Paine, Michael D.; Wells, Trudy A.; DeBlois, Elisabeth M.; Kilgour, Bruce W.; Tracy, Ellen; Crowley, Roger D.; Williams, Urban P.; Janes, G. Gregory

    2014-12-01

    This paper discusses toxicity test results on sediments from the Terra Nova offshore oil development. The Terra Nova Field is located on the Grand Banks approximately 350 km southeast of Newfoundland (Canada). The amphipod (Rhepoxynius abronius) survival and solid phase luminescent bacteria (Vibrio fischeri, or Microtox) assays were conducted on sediment samples collected from approximately 50 stations per program year around Terra Nova during baseline (1997), prior to drilling, and in 2000, 2001, 2002, 2004, 2006, 2008 and 2010 after drilling began. The frequency of toxic responses in the amphipod toxicity test was low. Of the ten stations that were toxic in environmental effects monitoring (EEM) years, only one (station 30(FE)) was toxic in more than one year and could be directly attributed to Terra Nova project activities. In contrast, 65 (18%) of 364 EEM samples were toxic to Microtox. Microtox toxicity in EEM years was not related to distance from Terra Nova drill centres or concentrations of >C10-C21 hydrocarbons or barium, the primary constituents of the synthetic-based drill muds used at Terra Nova. Of the variables tested, fines and strontium levels showed the strongest (positive) correlations with toxicity. Neither fines nor strontium levels were affected by drill cuttings discharge at Terra Nova, except at station 30(FE) (and that station was not toxic to Microtox). Benthic macro-invertebrate abundance, richness and diversity were greater in toxic than in non-toxic sediments. Therefore, Microtox responses indicating toxicity were associated with positive biological responses in the field. This result may have been an indirect function of the increased abundance of most invertebrate taxa in less sandy sediments with higher gravel content, where fines and strontium levels and, consequently, toxicity to Microtox were high; or chemical substances released by biodegradation of organic matter, where invertebrates are abundant, may be toxic to Microtox. Given

  10. Characterizing toxicity of metal-contaminated sediments from mining areas

    Science.gov (United States)

    Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.

    2015-01-01

    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 communities can help document causal relationships between metal contamination and biological effects. Total or total-recoverable metal concentrations in sediments are the most common measure of metal contamination in sediments, but metal concentrations in labile sediment fractions (e.g., determined as part of selective sediment extraction protocols) may better represent metal bioavailability. Metals released by the weak-acid extraction

  11. Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Stephen K Roberts

    Full Text Available Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

  12. Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Roberts, Stephen K; McAinsh, Martin; Cantopher, Hanna; Sandison, Sean

    2014-01-01

    Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA) revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

  13. Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Fang, Fang; Peters, Tracy L; Beard, John D; Umbach, David M; Keller, Jean; Mariosa, Daniela; Allen, Kelli D; Ye, Weimin; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

    2017-11-01

    Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Management of cyanide toxicity in patients with burns.

    Science.gov (United States)

    MacLennan, Louise; Moiemen, Naiem

    2015-02-01

    The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  15. Toxic stress and child refugees.

    Science.gov (United States)

    Murray, John S

    2018-01-01

    The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life

  16. Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation

    Directory of Open Access Journals (Sweden)

    Niewald Marcus

    2011-10-01

    Full Text Available Abstract Purpose Retrospective evaluation of toxicity and results after radiochemotherapy for glioblastoma. Methods 46 patients with histopathologically proven glioblastoma received simultaneous radiochemotherapy (RCT. The mean age at the beginning of therapy was 59 years, the mean Karnofsky performance index 80%. 44 patients had been operated on before radiotherapy, two had not. A total dose of 60 Gy was applied in daily single fractions of 2.0 Gy within six weeks, 75 mg/m2/day Temozolomide were given orally during the whole radiotherapy period. Results A local progression could be diagnosed in 34/46 patients (70%. The median survival time amounted to 13.6 months resulting in one-year and two-year survival probabilities of 48% and 8%, respectively. Radiotherapy could be applied completely in 89% of the patients. Chemotherapy could be completed according to schedule only in 56.5%, the main reason being blood toxicity (50% of the interruptions. Most of those patients suffered from leucopenia and/or thrombopenia grade III and IV CTC (Common toxicity criteria. Further reasons were an unfavourable general health status or a rise of liver enzymes. The mean duration of thrombopenia and leucopenia amounted to 64 and 20 days. In two patients, blood cell counts remained abnormal until death. In two patients we noticed a rise of liver enzymes. In one of these in the healing phase of hepatitis a rise of ASAT and ALAT CTC grade IV was diagnosed. These values normalized after termination of temozolomide medication. One patient died of pneumonia during therapy. Conclusion Our survival data were well within the range taken from the literature. However, we noticed a considerable frequency and intensity of side effects to bone marrow and liver. These lead to the recommendations that regular examinations of blood cell count and liver enzymes should be performed during therapy and temozolomide should not be applied or application should be terminated according to

  17. Surviving With Smog and Smoke: Precision Interventions?

    Science.gov (United States)

    Cai, Hua; Wang, Chen

    2017-11-01

    Despite continuous efforts of regional governmental agencies, air pollution remains a major threat to public health worldwide. In January 2017, a severe episode of smog similar to the Great Smog of 1952 occurred in London. The longest episode of Chinese haze also developed in Beijing, during which levels of particulate matter smoke. For countries with large populations of smokers, such as China, India, the United States, and Russia, surviving both smog and smoke is a serious problem. With novel genomic and epigenomic studies revealing air pollution- and smoking-induced mutational signatures and epigenetic editing in diseases such as lung cancer, it has become feasible to develop precision strategies for early intervention in the disease-causing pathways driven by the specific mutations or epigenetic regulations, or both. New therapies guided by gene-drug interactions and genomic biomarkers may also be developed. We discuss both perspectives regarding the urgent need to manage the toxic effects of smog and smoke for the benefit of global health and the novel concept of precision intervention to protect the exposed individuals when exposure to smog and secondhand smoke cannot be voluntarily avoided or easily modified. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. Toxicity of ammonia to surf clam (Spisula solidissima) larvae in saltwater and sediment elutriates.

    Science.gov (United States)

    Ferretti, James A; Calesso, Diane F

    2011-04-01

    Ammonia is a natural component of sediments and has been identified as a common contributor to toxicity in marine sediment, elutriate and porewater testing. In our study, the role of ammonia as a possible toxicant in sediment toxicity tests was evaluated using larvae of the surf clam, Spisula solidissima. Elutriates were prepared and tested using six baseline sediment samples. Ammonia was then purged from aliquots of the baseline sediment samples prior to elutriate preparation. Finally, ammonia was spiked into aliquots of the purged elutriates to mimic ammonia concentrations measured in the baseline elutriates. Toxicity was present in all of the baseline samples and was removed in the ammonia purged samples. In most cases, toxicity was comparable in the ammonia spiked samples to levels measured in the baseline samples. Water only toxicity tests revealed that larvae of the surf clam are one of the more ammonia sensitive marine species. The LC50 for survival was 10.6 mg/L total ammonia (.53 mg/L unionized ammonia) and the EC50 for shell development was 2.35 mg/L total ammonia (.12 mg/L unionized ammonia). Toxicity endpoints calculated from the water only ammonia toxicity test were good predictors of effects observed in the sediment elutriate tests. Published by Elsevier Ltd.

  19. Baclofen Toxicity in Kidney Disease.

    Science.gov (United States)

    Wolf, Erin; Kothari, Niraj R; Roberts, John K; Sparks, Matthew A

    2018-02-01

    Baclofen, a commonly prescribed muscle relaxant, is primarily excreted via the kidneys; toxicity is a potentially serious adverse outcome in patients with decreased kidney function. We describe a patient with end-stage kidney disease receiving hemodialysis who developed neurotoxicity and hemodynamic instability after receiving baclofen for muscle spasms. In this case, prompt recognition of baclofen toxicity and urgent hemodialysis were effective in reversing this toxicity. This case is used to examine the pharmacokinetics and pathophysiology of baclofen toxicity and discuss appropriate diagnosis and management of baclofen toxicity. We recommend reducing the baclofen dose in patients who have moderately reduced kidney function (estimated glomerular filtration rate, 30-60mL/min/1.73m 2 ) and avoiding use in patients with severely reduced kidney function (estimated glomerular filtration rate < 30mL/min/1.73m 2 ) or on renal replacement therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  20. Jatropha toxicity--a review.

    Science.gov (United States)

    Devappa, Rakshit K; Makkar, Harinder P S; Becker, Klaus

    2010-08-01

    Jatropha is a nonedible oil seed plant belonging to Euphorbiaceae family. Global awareness of sustainable and alternative energy resources has propelled research on Jatropha oil as a feedstock for biodiesel production. During the past two decades, several cultivation projects were undertaken to produce Jatropha oil. In future, the increased cultivation of toxic Jatropha plants and utilization of its agro-industrial by-products may raise the frequency of contact with humans, animals, and other organisms. An attempt was thus made to present known information on toxicity of Jatropha plants. The toxicity of Jatropha plant extracts from fruit, seed, oil, roots, latex, bark, and leaf to a number of species, from microorganisms to higher animals, is well established. Broadly, these extracts possess moluscicidal, piscicidal, insecticidal, rodenticidal, antimicrobial, and cytotoxic properties, and exert adverse effects on animals including rats, poultry, and ruminants. The toxicity attributed to these seeds due to their accidental consumption by children is also well documented. An attempt was also made to identify areas that need further study. The information provided in this review may aid in enhancing awareness in agroindustries involved in the cultivation, harvesting, and utilization of Jatropha plants and its products with respect to the potential toxicity of Jatropha, and consequently in application and enforcement of occupational safety measures. Data on the wide range of bioactivities of Jatropha and its products were collated and it is hoped will create new avenues for exploiting these chemicals by the phamaceutical industry to develop chemotherapeutic agents.

  1. Emerging exposures of developmental toxicants.

    Science.gov (United States)

    Wolff, Mary S; Buckley, Jessie P; Engel, Stephanie M; McConnell, Rob S; Barr, Dana B

    2017-04-01

    The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to improve utility, to reduce toxicity, or to replace undesirable chemicals. Exposures to less-toxic chemicals may also be significant if they are very commonly used, thereby generating widespread exposure. Sources of exposure include the workplace, personal, home, and office products; food, water, and air. We describe eight exposure categories that contain numerous potential developmental toxicants. References are discussed if reported in PubMed during the past decade at least 10 times more frequently than in 1990-2000. Examples included phthalates, phenols, sunscreens, pesticides, halogenated flame retardants, perfluoroalkyl coatings, nanoparticles, e-cigarettes, and dietary polyphenols. Replacements are often close structural homologs of their precursors. We suggest biomonitoring as preferred means of exposure assessment to emerging chemicals. Some existing analytic methods would require minimal modification to measure these exposures, but others require toxicokinetic and analytic investigation. A deliberate strategy for biomonitoring of emerging replacement chemicals is warranted, especially in view of concerns regarding developmental toxicity. To prevent adverse health effects, it is important to characterize such exposures before they become widely disseminated.

  2. The Study on Acute and Subacute Toxicity and Anti-Cancer Effects of cultivated wild ginseng Herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Ki-Rok, Kwon

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled in mice and rats. Methods : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute LD50 toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture

  3. Survival Processing Eliminates Collaborative Inhibition.

    Science.gov (United States)

    Reysen, Matthew B; Bliss, Heather; Baker, Melissa A

    2017-04-11

    The present experiments examined the effect of processing words for their survival value, relevance to moving, and pleasantness on participants' free recall scores in both nominal groups (non-redundant pooled individual scores) and collaborative dyads. Overall, participants recalled more words in the survival processing conditions than in the moving and pleasantness processing conditions. Furthermore, nominal groups in both the pleasantness condition (Experiment 1) and the moving and pleasantness conditions (Experiment 2) recalled more words than collaborative groups, thereby replicating the oft-observed effect of collaborative inhibition. However, processing words for their survival value appeared to eliminate the deleterious effects of collaborative remembering in both Experiments 1 and 2. These results are discussed in the context of the retrieval strategy disruption hypothesis and the effects of both expertise and collaborative skill on group remembering.

  4. Predicting the toxicity of neat and weathered crude oil: toxic potential and the toxicity of saturated mixtures.

    Science.gov (United States)

    Di Toro, Dominic M; McGrath, Joy A; Stubblefield, William A

    2007-01-01

    The toxicity of oils can be understood using the concept of toxic potential, or the toxicity of each individual component of the oil at the water solubility of that component. Using the target lipid model to describe the toxicity and the observed relationship of the solubility of oil components to log (Kow), it is demonstrated that components with lower log (Kow) have greater toxic potential than those with higher log (Kow). Weathering removes the lower-log (Kow) chemicals with greater toxic potential, leaving the higher-log (Kow) chemicals with lower toxic potential. The replacement of more toxically potent compounds with less toxically potent compounds lowers the toxicity of the aqueous phase in equilibrium with the oil. Observations confirm that weathering lowers the toxicity of oil. The idea that weathering increases toxicity is based on the erroneous use of the total petroleum hydrocarbons or the total polycyclic aromatic hydrocarbons (PAHs) concentration as if either were a single chemical that can be used to gauge the toxicity of a mixture, regardless of its makeup. The toxicity of the individual PAHs that comprise the mixture varies. Converting the concentrations to toxic units (TUs) normalizes the differences in toxicity. A concentration of one TU resulting from the PAHs in the mixture implies toxicity regardless of the specific PAHs that are present. However, it is impossible to judge whether 1 microg/L of total PAHs is toxic without knowing the PAHs in the mixture. The use of toxic potential and TUs eliminates this confusion, puts the chemicals on the same footing, and allows an intuitive understanding of the effects of weathering.

  5. Survival in Women with NSCLC

    Science.gov (United States)

    Katcoff, Hannah; Wenzlaff, Angela S.; Schwartz, Ann G.

    2014-01-01

    Introduction Although lung cancer is the leading cause of cancer death in women, few studies have investigated the hormonal influence on survival after a lung cancer diagnosis and results have been inconsistent. We evaluated the role of reproductive and hormonal factors in predicting overall survival in women with non–small-cell lung cancer (NSCLC). Methods Population-based lung cancer cases diagnosed between November 1, 2001 and October 31, 2005 were identified through the Metropolitan Detroit Surveillance, Epidemiology, and End Results Registry. Interview and follow-up data were collected for 485 women. Cox proportional hazard regression models were used to determine hazard ratios (HRs) for death after an NSCLC diagnosis associated with reproductive and hormonal variables. Results Use of hormone therapy (HT) was associated with improved survival (HR, 0.69; 95% confidence interval, 0.54–0.89), adjusting for stage, surgery, radiation, education level, pack-years of smoking, age at diagnosis, race, and a multiplicative interaction between stage and radiation. No other reproductive or hormonal factor was associated with survival after an NSCLC diagnosis. Increased duration of HT use before the lung cancer diagnosis (132 months or longer) was associated with improved survival (HR, 0.54; 95% confidence interval, 0.37–0.78), and this finding remained significant in women taking either estrogen alone or progesterone plus estrogen, never smokers, and smokers. Conclusion These findings suggest that HT use, in particular use of estrogen plus progesterone, and long-term HT use are associated with improved survival of NSCLC. PMID:24496005

  6. Survival of Sami cancer patients

    Directory of Open Access Journals (Sweden)

    Leena Soininen

    2012-07-01

    Full Text Available Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30 and for non-Sami 1.02 (0.86–1.20, indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

  7. Survival following spinal cord infarction.

    Science.gov (United States)

    New, P W; McFarlane, C L

    2013-06-01

    Retrospective open cohort. To calculate the survival of patients with spinal cord infarction and to compare the cause of death in patients with different mechanisms of ischaemic injury. Spinal Rehabilitation Unit, Melbourne, Victoria, Australia. Consecutive admissions between 1 January 1995 and 31 December 2008 with recent onset of spinal cord infarction. Linkage to the Registry of Births, Deaths and Marriages (Victoria) was used to determine survival following discharge from in-patient rehabilitation and cause of death. A total of 44 patients were admitted (males=26, 59%), with a median age of 72 years (interquartile range (IQR) 62-79). One patient died during their in-patient rehabilitation programme. In all, 14 patients (n=14/44; 33%) died during the follow-up period. The median survival after diagnosis was 56 months (IQR 28-85) and after discharge from in-patient rehabilitation was 46 months (IQR 25-74). The 1- and 5-year mortality rates were 7.0% (n=3/43; 95% confidence interval (CI)=2.4-18.6%) and 20.9% (n=9/43; 95% CI=11.4-35.2%). There was no statistically significant difference in survival between patients with the different aetiologies of spinal cord infarction (other vs idiopathic: χ(2)=0.6, P=0.7; other vs vascular: χ(2)=1.9, P=0.3). There was no relationship between survival and gender (χ(2)=0.2, P=0.6), age (χ(2)=3.0, P=0.08), level of injury (χ(2)=0.0, P=1) or American Spinal Cord Society Impairment Scale grade of spinal cord injury (χ(2)=0.02, P=0.9). Patients with spinal cord infarction appear to have a fair survival after discharge from in-patient rehabilitation, not withstanding the occurrence of risk factors of vascular disease in many patients.

  8. Identifying the causes of oil sands coke leachate toxicity to aquatic invertebrates.

    Science.gov (United States)

    Puttaswamy, Naveen; Liber, Karsten

    2011-11-01

    A previous study found that coke leachates (CL) collected from oil sands field sites were acutely toxic to Ceriodaphnia dubia; however, the cause of toxicity was not known. Therefore, the purpose of this study was to generate CL in the laboratory to evaluate the toxicity response of C. dubia and perform chronic toxicity identification evaluation (TIE) tests to identify the causes of CL toxicity. Coke was subjected to a 15-d batch leaching process at pH 5.5 and 9.5. Leachates were filtered on day 15 and used for chemical and toxicological characterization. The 7-d median lethal concentration (LC50) was 6.3 and 28.7% (v/v) for pH 5.5 and 9.5 CLs, respectively. Trace element characterization of the CLs showed Ni and V levels to be well above their respective 7-d LC50s for C. dubia. Addition of ethylenediaminetetraacetic acid significantly (p ≤ 0.05) improved survival and reproduction in pH 5.5 CL, but not in pH 9.5 CL. Cationic and anionic resins removed toxicity of pH 5.5 CL only. Conversely, the toxicity of pH 9.5 CL was completely removed with an anion resin alone, suggesting that the pH 9.5 CL contained metals that formed oxyanions. Toxicity reappeared when Ni and V were added back to anion resin-treated CLs. The TIE results combined with the trace element chemistry suggest that both Ni and V are the cause of toxicity in pH 5.5 CL, whereas V appears to be the primary cause of toxicity in pH 9.5 CL. Environmental monitoring and risk assessments should therefore focus on the fate and toxicity of metals, especially Ni and V, in coke-amended oil sands reclamation landscapes. Copyright © 2011 SETAC.

  9. Gulf of Mexico mud toxicity limitations

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, H.E.; Beardmore, D.H. (Phillips Petroleum Co., Bartlesville, OK (USA)); Stewart, W.S. (Drilling Specialties Co. (US))

    1989-10-01

    Because of the Environmental Protection Agency's recent toxicity limits on drilling mud discharges for offshore Gulf of Mexico, Phillips Petroleum conducted a mud toxicity study based on both field and lab tests. The study, discussed in this article, found the polyanionic cellulose-sulfomethylated quebracho-chrome lignosulfonate mud Phillips had been using would comfortably pass the toxicity limitations. The study also found barite and thinners were of low toxicity, and hydrocarbons and surfactants were highly toxic.

  10. Survival and Growth of Corophium volutator in Organically Enriched Sediment: A Comparison of Laboratory and Field Experiments

    OpenAIRE

    Bat, Levent; Raffaelli, Dave

    1998-01-01

    In this study, the amphipod Corophium volutator (Pallas) was evaluated as test organisms for use in sediment toxicity tests by adapting standard protocols for conducting 10-day and 28-day sediment toxicity tests. Combine laboratory and field bioas-says showed that Corophium can survive in organically enriched sediment if they have no alternative, suggesting that Corophium is relatively tolerant of organically enriched sediment. Neither were there effects on emergence or reburying behaviour...

  11. Genetic aspects of piglet survival

    OpenAIRE

    Knol, E.F.

    2001-01-01

    Piglet mortality is high. In the USA nearly 20% of the piglets do not survive between late gestation and weaning; 7% of the piglets die during farrowing and some 13% are lost during lactation. These statistics from the USA are no exception to the norm. Selection for increased piglet survival, if possible, could have an important economic impact.

    Litters and sows

    Data on some 33.000 litters and some 400.000 piglets from a commercial breeding progr...

  12. Frailty Models in Survival Analysis

    CERN Document Server

    Wienke, Andreas

    2010-01-01

    The concept of frailty offers a convenient way to introduce unobserved heterogeneity and associations into models for survival data. In its simplest form, frailty is an unobserved random proportionality factor that modifies the hazard function of an individual or a group of related individuals. "Frailty Models in Survival Analysis" presents a comprehensive overview of the fundamental approaches in the area of frailty models. The book extensively explores how univariate frailty models can represent unobserved heterogeneity. It also emphasizes correlated frailty models as extensions of

  13. The Danger of Toxic Substances

    Directory of Open Access Journals (Sweden)

    M. V. Jokl

    2002-01-01

    Full Text Available Toxic (harmful gases enter building interiors partly from outdoors (sulfur oxides, nitrogen oxides, carbon monoxide, ozone, smog and acid rains, partly originate indoors - as a result of human activity (carbon monoxide, tobacco smoke, nitrogen oxides, ozone, hydrocarbons and also emanate from building materials (formaldehyde, volatile organic compounds. The human organism is most often exposed to cigarette smoke (especially nonsmokers are endangered, as cigarette smoke devastes the pulmonary and cardiovasculary system and to smog entering from outdoors, paradoxically during sunny weather. Preventing toxic production is the most effective measure, e.g., by coaxing to coax smokers out of "civilized" areas, by using energy rationally (i.e., conserving energy, to turn to pure fuels and to increase energy production by non-combustion technologies. Besides ventilation and air filtration, the toxic gases can be removed to a remarkable extent by plants (by which decay the substances into nontoxic gases, and by air ionization. Review article.

  14. Aluminium Toxicity Targets in Plants

    Directory of Open Access Journals (Sweden)

    Sónia Silva

    2012-01-01

    Full Text Available Aluminium (Al is the third most abundant metallic element in soil but becomes available to plants only when the soil pH drops below 5.5. At those conditions, plants present several signals of Al toxicity. As reported by literature, major consequences of Al exposure are the decrease of plant production and the inhibition of root growth. The root growth inhibition may be directly/indirectly responsible for the loss of plant production. In this paper the most remarkable symptoms of Al toxicity in plants and the latest findings in this area are addressed. Root growth inhibition, ROS production, alterations on root cell wall and plasma membrane, nutrient unbalances, callose accumulation, and disturbance of cytoplasmic Ca2+ homeostasis, among other signals of Al toxicity are discussed, and, when possible, the behavior of Al-tolerant versus Al-sensitive genotypes under Al is compared.

  15. Long Term Survival Results of Surgery Alone versus Surgery plus 5-Fluorouracil and Leucovorin for Stage II and Stage III Colon Cancer: Pooled Analysis of NSABP C-01 through C-05 Baseline from Which to Compare Modern Adjuvant Trials

    Science.gov (United States)

    Wilkinson, Neal W.; Yothers, Greg; Lopa, Samia; Costantino, Joseph P.; Petrelli, Nicholas J.; Wolmark, Norman

    2010-01-01

    Background The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies. Methods All patients enrolled in NSABP adjuvant trials C-01 through C-05 with stage II and III disease who were treated with surgery or with surgery plus 5-FU/LV were examined for overall survival (OS), disease free survival (DFS), and recurrence free interval (RFI). Time-to-event by treatment group was examined using adjusted Kaplan-Meier estimates and multivariable Cox regression analysis. Results There were 2,966 eligible patients: 693 (23%) surgery and 2,273 (77%) surgery plus 5-FU/LV; 1,255 (42%) stage II and 1,711 (58%) stage III. Age ≥ 60 years {hazard ratio (HR)=1.36, P<0.000], male gender (HR=1.20, P=0.0012), and more nodes positive or fewer nodes examined (P< 0.0001) were associated with worse survival. At 5 years, the adjusted OS was 0.62 [confidence interval (CI)= 0.60-0.63] in the surgery group and 0.76 (CI= 0.74- 0.78) in the surgery plus 5-FU/LV group. Treatment with 5-FU/LV was associated with improved outcome compared with surgery: OS (HR=0.62, P<0.0001), DFS (HR=0.66, P<0.0001) and RFI (HR=0.64, P<0.0001). Improved OS with adjuvant treatment was seen in both stage II (HR=0.58, 95% CI=0.48-0.71) and stage III disease (HR=0.65, 95% CI=0.55-0.75). Conclusions This analysis demonstrates that treatment of colon cancer patients with 5-FU/LV following surgery provides benefit over surgery alone and can provide anticipated survival outcomes from which to compare modern adjuvant trials. PMID:20082144

  16. Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival.

    Science.gov (United States)

    Sato, Kent T; Lewandowski, Robert J; Mulcahy, Mary F; Atassi, Bassel; Ryu, Robert K; Gates, Vanessa L; Nemcek, Albert A; Barakat, Omar; Benson, Al; Mandal, Robert; Talamonti, Mark; Wong, Ching-Yee O; Miller, Frank H; Newman, Steven B; Shaw, John M; Thurston, Kenneth G; Omary, Reed A; Salem, Riad

    2008-05-01

    To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 ((90)Y) glass microspheres. Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of (90)Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients. There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors. (90)Y hepatic

  17. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  18. Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Nowell, Lisa H., E-mail: lhnowell@usgs.gov [U.S. Geological Survey, California Water Science Center, Placer Hall, 6000 J Street, Sacramento, CA 95819 (United States); Norman, Julia E., E-mail: jnorman@usgs.gov [U.S. Geological Survey, Oregon Water Science Center, 2130 SW 5" t" h Avenue, Portland, OR 97201 (United States); Ingersoll, Christopher G., E-mail: cingersoll@usgs.gov [U.S. Geological Survey, Columbia Environmental Research Center, 4200 New Haven Road, Columbia, MO 65021 (United States); Moran, Patrick W., E-mail: pwmoran@usgs.gov [U.S. Geological Survey, Washington Water Science Center, 934 Broadway, Suite 300, Tacoma, WA 98402 (United States)

    2016-04-15

    Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical/chemical characteristics

  19. Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

    Science.gov (United States)

    Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-01-01

    Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

  20. [Amiodarone-induced pulmonary toxicity].

    Science.gov (United States)

    Heisel, A; Berg, M; Stopp, M; Ukena, D; Schieffer, H

    1997-12-01

    Amiodarone is highly effective in suppressing ventricular and supraventricular tachyarrhythmias. The most serious adverse reaction is pulmonary toxicity. The mechanisms involved in amiodarone-induced pulmonary injury are incompletely understood. Several forms of pulmonary disease occur including interstitial pneumonitis, fibrosis or organizing pneumonia. The incidence is generally lower with lower maintenance doses (amiodarone. The diagnosis of amiodarone-induced pulmonary toxicity is one of exclusion. Treatment consists primarily of stopping amiodarone application. Corticosteroid therapy can be life-saving for severe cases and for patients in whom withdrawl of amiodarone is not possible.

  1. The reproductive and developmental toxicity of High Flash Aromatic Naphtha.

    Science.gov (United States)

    McKee, R H; Wong, Z A; Schmitt, S; Beatty, P; Swanson, M; Schreiner, C A; Schardein, J L

    1990-01-01

    Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--High Flash Aromatic Naphtha. A program was initiated to assess the toxicological properties of High Flash Aromatic Naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted to assess the potential for developmental toxicity in the mouse and for reproductive toxicity in the rat. In the developmental toxicity study in CD-1 mice, exposure of dams by inhalation to near lethal levels (1500 ppm) resulted in fetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm, a level at which maternal weight gain was slightly reduced, fetal weight gain was also reduced, but there was no other evidence of developmental effects. The lowest exposure level (100 ppm) did not cause any maternal or developmental toxicity. There was no consistent evidence of reproductive toxicity in rats, even at exposure levels which resulted in significantly reduced parental weight gain. In addition, when parental exposure was stopped on GD (gestation day) 20, birth weights as well as postnatal survival were generally similar to control values, even in the 1500 ppm exposure group. Postnatal weight gain was also similar to controls early in weaning, but, if maternal exposure was reinitiated, weight gain was reduced in the high exposure group. However, when exposure was continued until delivery, pups in the high exposure group exhibited reduced litter size, birth weight and poor survival. Thus it was likely that the reduction in fetal weight

  2. Completion surgery after concomitant chemoradiation in obese women with locally advanced cervical cancer: Evaluation of toxicity and outcome measures.

    Science.gov (United States)

    Legge, Francesco; Margariti, Pasquale A; Lucidi, Alessandro; Macchia, Gabriella; Petrillo, Marco; Iannone, Vito; Carone, Vito; Morganti, Alessio G; Scambia, Giovanni; Ferrandina, Gabriella

    2013-01-01

    This study aims at comparing the morbidity and oncologic outcomes in normal weight, overweight, and obese women with locally advanced cervical cancers (LACC) submitted to radical surgery after chemoradiation. A review of LACC patients with body mass index (BMI) ≥ 18.5 kg/m(2) who underwent neoadjuvant chemoradiation followed by radical surgery between January 1996 and December 2010 was performed. BMI categories were created according to the World Health Organization (WHO) classification. Two hundred sixty-eight women met the inclusion criteria: 118 (44.0%) were normal weight, 100 (37.3%) overweight and 50 (18.7%) obese. The median follow-up was 42 months. Higher BMI was associated with older age (p = 0.0041), while there were no differences among the three groups in Charlson comorbidity score, tumor characteristics, radiotherapy dosing, type of surgery, and pathological response. There were no differences among the three groups in the intraoperative and postoperative complications as well as rate of patients requiring adjuvant treatments: 21 (7.8%) patients experienced grade 3-4 toxicity, including six normal weight, 12 overweight and three obese patients (p = 0.14). Only the rate of grade 1-2 skin toxicity was higher in obese (14%) with respect to overweight (1%) and normal women (0%) (p = 0.00001). There were no differences in the five-year DFS (74%, 77%, and 84% for normal weight, overweight, and obese women, respectively, p = n.s.), and five-year OS (76%, 78%, and 78% for normal weight, overweight, and obese women, respectively, p = n.s.). The role of obesity should not be overestimated when evaluating the chance of enrolment of LACC patients into preoperative chemoradiation protocols.

  3. School Leadership: Handbook for Survival.

    Science.gov (United States)

    Smith, Stuart C., Ed.; And Others

    Based on the assumption that the survival of the nation's schools and their leaders depends on these leaders having real influence over the quality of schooling, this volume draws from the work of many authorities to look at leadership from three perspectives: the person, the structure, and the skills. Chapters focusing on the person who holds the…

  4. Long-term haemodialysis survival

    DEFF Research Database (Denmark)

    Heaf, James; Nielsen, Arne Høj; Hansen, Henrik Post

    2012-01-01

    Haemodialysis (HD) treatment for end-stage renal disease bears a poor prognosis. We present a case of a patient who, apart from two transplant periods lasting 8 months in all, was treated with conventional in-centre HD three times a week and who survived for 41 years. Patients should be aware tha...

  5. Characteristics of Patients Who Survived

    NARCIS (Netherlands)

    Verlaan, Jorrit-Jan; Choi, David; Versteeg, Anne; Albert, Todd; Arts, Mark; Balabaud, Laurent; Bunger, Cody; Buchowski, Jacob Maciej; Chung, Chung Kee; Coppes, Maarten Hubert; Crockard, Hugh Alan; Depreitere, Bart; Fehlings, Michael George; Harrop, James; Kawahara, Norio; Kim, Eun Sang; Lee, Chong-Suh; Leung, Yee; Liu, Zhongjun; Martin-Benlloch, Antonio; Massicotte, Eric Maurice; Mazel, Christian; Meyer, Bernhard; Peul, Wilco; Quraishi, Nasir A.; Tokuhashi, Yasuaki; Tomita, Katsuro; Ulbricht, Christian; Wang, Michael; Oner, F. Cumhur

    2016-01-01

    Purpose Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally

  6. Genetic aspects of piglet survival

    NARCIS (Netherlands)

    Knol, E.F.

    2001-01-01

    Piglet mortality is high. In the USA nearly 20% of the piglets do not survive between late gestation and weaning; 7% of the piglets die during farrowing and some 13% are lost during lactation. These statistics from the USA are no exception to the norm. Selection for increased piglet

  7. Cool echidnas survive the fire

    Science.gov (United States)

    Nowack, Julia; Cooper, Christine Elizabeth; Geiser, Fritz

    2016-01-01

    Fires have occurred throughout history, including those associated with the meteoroid impact at the Cretaceous–Palaeogene (K–Pg) boundary that eliminated many vertebrate species. To evaluate the recent hypothesis that the survival of the K–Pg fires by ancestral mammals was dependent on their ability to use energy-conserving torpor, we studied body temperature fluctuations and activity of an egg-laying mammal, the echidna (Tachyglossus aculeatus), often considered to be a ‘living fossil’, before, during and after a prescribed burn. All but one study animal survived the fire in the prescribed burn area and echidnas remained inactive during the day(s) following the fire and substantially reduced body temperature during bouts of torpor. For weeks after the fire, all individuals remained in their original territories and compensated for changes in their habitat with a decrease in mean body temperature and activity. Our data suggest that heterothermy enables mammals to outlast the conditions during and after a fire by reducing energy expenditure, permitting periods of extended inactivity. Therefore, torpor facilitates survival in a fire-scorched landscape and consequently may have been of functional significance for mammalian survival at the K–Pg boundary. PMID:27075255

  8. Modelling survival and connectivity of

    NARCIS (Netherlands)

    van der Molen, J.; van Beek, J.; Augustine, S.; Vansteenbrugge, L.; van Walraven, L.; van Langenberg, V.; van der Veer, H.W.; Hostens, K.; Pitois, S.; Robbens, J.

    2015-01-01

    Three different models were applied to study the reproduction, survival and dispersal of Mnemiopsis leidyi in the Scheldt estuaries and the southern North Sea: a high-resolution particle tracking model with passive particles, a low-resolution particle tracking model with a reproduction model

  9. Survivability of SCADA Control Loop

    NARCIS (Netherlands)

    Camacho, José; de Boer, Pieter-Tjerk; Remke, Anne Katharina Ingrid

    2009-01-01

    The endorsement of information technologies for critical infrastructures control introduces new threats in their security and surveillance. Along with certain level of protection against attacks, it is desirable for critical processes to survive even if they succeed. A stochastic Petri Nets-based

  10. Toxicity of oiled sediments treated with bioremediation agents: A shoreline experiment in Delaware, USA

    Energy Technology Data Exchange (ETDEWEB)

    Mearna, A. [National Oceanic and Atmospheric Administration, Seattle, WA (United States); Doe, K. [Environment Canada, Dartmouth, Nova Scotia (Canada); Fisher, W. [Environmental Protection Agency, Gulf Breeze, FL (United States); Lee, K. [Department of Fisheries and Oceans, Mont-Joli, Quebec (Canada); Mueller, C. [SAIC, Inc., Narragansett, RI (United States)

    1995-12-31

    Using a randomized complete block design, a battery of five pore water and sediment bioassays were used to monitor and compare toxicity among un-oiled, oiled (light Nigerian crude) and nutrient and bacteria-treated shoreline plots on a sandy beach. Tests included sea urchin fertilization, water and modified-solid phase microtox, 10-day amphipod survival and grass shrimp embryo bioassays. During the 13-week study, bioremediation treatment with nutrients and/or bacteria did not decrease toxicity relative to that in untreated plots. Results from at least one bioassay suggested that, relative to no treatment, treatment may have increased toxicity for several weeks. The least and most sensitive tests were sea urchin fertilization (pore water) and 10-day amphipod test, respectively. Coupled with chemical monitoring, the study produced a large data-base for evaluating toxic concentrations of petroleum hydrocarbons in sandy sediments.

  11. Toxicity of silicon carbide nanowires to sediment-dwelling invertebrates in water or sediment exposures

    Science.gov (United States)

    Mwangi, Joseph N.; Wang, Ning; Ritts, Andrew; Kunz, James L.; Ingersoll, Christopher G.; Li, Hao; Deng, Baolin

    2011-01-01

    Silicon carbide nanowires (SiCNW) are insoluble in water. When released into an aquatic environment, SiCNW would likely accumulate in sediment. The objective of this study was to assess the toxicity of SiCNW to four freshwater sediment-dwelling organisms: amphipods (Hyalella azteca), midges (Chironomus dilutus), oligochaetes (Lumbriculus variegatus), and mussels (Lampsilis siliquoidea). Amphipods were exposed to either sonicated or nonsonicated SiCNW in water (1.0 g/L) for 48 h. Midges, mussels, and oligochaetes were exposed only to sonicated SiCNW in water for 96 h. In addition, amphipods were exposed to sonicated SiCNW in whole sediment for 10 d (44% SiCNW on dry wt basis). Mean 48-h survival of amphipods exposed to nonsonicated SiCNW in water was not significantly different from the control, whereas mean survival of amphipods exposed to sonicated SiCNW in two 48-h exposures (0 or 15% survival) was significantly different from the control (90 or 98% survival). In contrast, no effect of sonicated SiCNW was observed on survival of midges, mussels, or oligochaetes. Survival of amphipods was not significantly reduced in 10-d exposures to sonicated SiCNW either mixed in the sediment or layered on the sediment surface. However, significant reduction in amphipod biomass was observed with the SiCNW either mixed in sediment or layered on the sediment surface, and the reduction was more pronounced for SiCNW layered on the sediment. These results indicated that, under the experimental conditions, nonsonicated SiCNW in water were not acutely toxic to amphipods, sonicated SiCNW in water were acutely toxic to the amphipods, but not to other organisms tested, and sonicated SiCNW in sediment affected the growth but not the survival of amphipods.

  12. Subacute toxicity of propyl gallate

    NARCIS (Netherlands)

    Strik JJTWA; Danse LHJC; Helleman PW; van Leeuwen FXR; Speijers GJA; Vaessen HAMG

    1986-01-01

    The 4 week oral toxicity of propyl gallate in rats, exposed to 0, 1000, 5000 and 25000 mg/kg feed, was investigated. Parameters studied comprised growth, food and water intake, biochemistry, hematology, organ weights and histopathology. In the highest dose group both females and males gained less

  13. Borocaptate sodium (BSH) toxicity issues

    Energy Technology Data Exchange (ETDEWEB)

    LaHann, T.

    1995-11-01

    ISU`s Center for Toxicology Research has been conducting toxicity testing of borocaptate sodium (BSH) to aid in assessing if proposed human studies of BSH are likely to be acceptably safe. This report describes BSH interactions with other biological agents.

  14. Gossypol Toxicity from Cottonseed Products

    Directory of Open Access Journals (Sweden)

    Ivana Cristina N. Gadelha

    2014-01-01

    Full Text Available Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.. Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal’s resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects.

  15. Niagara River Toxics Management Plan

    Science.gov (United States)

    This 2007 Progress Report of the Niagara River Toxics Management Plan (NRTMP) summarizes progress made by the four parties in dealing with the 18 “Priority Toxics” through reductions in point and non-point sources to the Niagara River.

  16. The Biochemistry of Alcohol Toxicity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 10. The Biochemistry of Alochol Toxicity. B Ramachandra Murty. General Article Volume 9 Issue 10 October 2004 pp 41-47. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/009/10/0041-0047 ...

  17. Holiday Plants with Toxic Misconceptions

    Directory of Open Access Journals (Sweden)

    Zabrina N. Evens

    2012-12-01

    Full Text Available Several plants are used for their decorative effect during winter holidays. This review explores the toxic reputation and proposed management for exposures to several of those, namely poinsettia (Euphorbia pulcherrima, English holly (Ilex aquifolium, American holly (Ilex opaca,bittersweet (Solanum dulcamara, Jerusalem cherry (Solanum pseudocapsicum, Americanmistletoe (Phoradendron serotinum, and European mistletoe (Viscum album.

  18. Chronic toxicity of 14 phthalate esters to Daphnia magna and rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Rhodes, J.E.; Adams, W.J. [ABC Labs., Inc., Columbia, MO (United States); Biddinger, G.R. [Exxon Biomedical Sciences Inc., Benecia, CA (United States); Robillard, K.A.; Gorsuch, J.W. [Eastman Kodak Co., Rochester, NY (United States)

    1995-11-01

    Chronic toxicity studies were performed with commercial phthalate esters and Daphnia magna (14 phthalates) and rainbow trout (Oncorhynchus mykiss) (six phthalates). For the lower-molecular-weight phthalate esters--dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and butylbenzyl phthalate (BBP)--the results of the studies indicated a general trend in which toxicity for both species increased as water solubility decreased. The geometric mean maximum acceptable toxicant concentration(GM-MATC) for D. magna ranged from 0.63 to 34.8 mg/L. For the higher-molecular-weight phthalate esters--dihexyl phthalate (DHP), butyl 2-ethylhexyl phthalate (BOP), di-(n-hexyl, n-octyl, n-decyl) phthalate (610P), di-(2-ethylhexyl) phthalate (DEHP), diisooctyl phthalate (DIOP), diisononyl phthalate (DINP), di-(heptyl, nonyl, undecyl) phthalate (711P), diisodecyl phthalate (DIDP), diundecyl phthalate (DUP), and ditridecyl phthalate (DTDP)--the GM-MATC values ranged from 0.042 to 0.15 mg/L. Survival was equally sensitive and sometimes more sensitive than reproduction. The observed toxicity to daphnids with most of the higher-molecular-weight phthalate esters appeared to be due to surface entrapment or a mode of toxicity that is not due to exposure to dissolved aqueous-phase chemical. Early life-stage toxicity studies with rainbow trout indicated that survival (DMP) and growth (DBP) were affected at 24 and 0.19 mg/L, respectively. This pattern of observed toxicity with the lower-molecular-weight phthalate esters and not the higher-molecular-weight phthalate esters is consistent with previously reported acute toxicity studies for several aquatic species.

  19. Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

    2014-11-01

    Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

  20. 10-Day survival of Hyalella azteca as a function of water quality parameters.

    Science.gov (United States)

    Javidmehr, Alireza; Kass, Philip H; Deanovic, Linda A; Connon, Richard E; Werner, Inge

    2015-05-01

    Estuarine systems are among the most impacted ecosystems due to anthropogenic contaminants; however, they present unique challenges to toxicity testing with regard to varying water quality parameters. The euryhaline amphipod species, Hyalella azteca, is widely used in toxicity testing and well suited for testing estuarine water samples. Nevertheless, the influence of relevant water quality parameters on test endpoints must be quantified in order to efficiently use this species for routine monitoring. Here, we studied the influence of five water quality parameters: electrical conductivity, pH, un-ionized ammonia, dissolved oxygen and temperature, on H. azteca survival in a water column toxicity test. A model was developed to quantify and predict the independent and interacting effects of water quality variables on 10-day survival. The model allows simultaneous assessment of multiple potential predictors recorded during the tests. Data used for modeling came from 1089 tests performed on ambient water samples over a period of three years (2006-2008). The final model reflects significant effects of predictors and their two-way interactions. The effect of each level of all predictors on survival probability of H. azteca was examined by comparing levels of each predictor at a time, while holding all others at their lowest (reference) level. This study showed that predictors of survival in water column tests should not be evaluated in isolation in the interpretation of H. azteca water column tests. Our model provides a useful tool to predict expected control survival based on relevant water quality parameters, and thus enables the use of H. azteca tests for toxicity monitoring in estuaries with a wide range of water quality conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A Phase II Trial of Adjuvant Low-dose Total Body Irradiation in non-Hodgkin's Lymphoma Patients following Standard CHOP

    Energy Technology Data Exchange (ETDEWEB)

    Safwat, Akmal; Bayoumi, Yasser; Akkoush, Hany; Mahmoud, Hossam K. [Aarhus Univ. Hospital (Denmark). Medical Oncology Dept.

    2004-07-01

    Because survival results achieved in aggressive NHL with the standard CHOP are not very satisfactory, we investigated adding adjuvant low-dose total body irradiation (LTBI) to standard CHOP in a phase II trial. Thirty-six patients were included between September 1999 and September 2001. All patients were in documented complete remission (CR) after the end of their standard CHOP. LTBI started 4-6 weeks following the last CHOP course and was given in two courses, each with 4 daily fractions of 0.2 Gy, separated by 2 weeks of rest. Patients with bulky disease received involved-field radiotherapy on initial bulky sites starting 4-6 weeks after the last LTBI fraction. Primary end points were disease-free survival (DFS) and overall survival (OS) and the secondary end point was toxicity. The toxicities of LTBI were temporary thrombocytopenia and leucopenia (requiring no transfusions or treatment with growth factors). The 3-year DFS was 61%{+-}9% and the overall survival was 87{+-}6%. Univariate analysis showed time to achieve CR, and whether the patient got LTBI-induced haematological toxicity to be 2 significant prognostic factors affecting DFS. The use of adjuvant LTBI in patients with aggressive NHL in CR after standard chemotherapy is a feasible, non-toxic treatment that is worthy of testing in a future phase III trial.

  2. Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma.

    Science.gov (United States)

    Chen, Fei; Liu, Shangqin; Zhou, Yi; Shen, Hui; Zuo, Xuelan

    2016-08-01

    Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is a rare hematological malignancy with limited results on carcinogenesis and clinical characteristics. The aims of the current study were to examine mitotic arrest deficiency protein 2 (Mad2) expressions in PGI-DLBCL, and assess its association with Ki-67 expression, Helicobacter pylori (H. pylori) infection, BCL-6 gene rearrangement, and clinicopathological variables. Cancer tissues from 38 PGI-DLBCL patients were examined for Mad2, Ki-67, and H. pylori expression by immunohistochemistry, using normal gastrointestinal tissues and nodal DLBCL as controls. BCL-6 gene translocation was analyzed by fluorescence in situ hybridization (FISH), and Mad2 expression status was evaluated along with clinicopathological characteristics. Mad2 expression was increased in PGI-DLBCL patients when compared with controls. The expression of Mad2 was 51.55 ± 22.88% in PGI-DLBCL, which was higher than reactive lymph node (28.77 ± 10.89%) and lymphoid nodule in normal gastrointestinal tissue (26.41 ± 11.30%) (P = 0.002), while it was comparable to nodal DLBCL (57.23 ± 20.79%) (P = 0.358). Mad2 overexpression had a positive correlation with Ki-67 proliferation index (r = 0.55, P = 0.01) in PGI-DLBCL, and patients with BCL-6 gene rearrangement had lower Mad2 expression (P = 0.032) than patients with intact BCL-6, while no relation was found between Mad2 expression and H. pylori infection. PGI-DLBCL patients with higher Mad2 expression had lower estimated disease-free survival (DFS) (17.10% vs. 53.00%) (P = 0.049). However, no correlation was found between Mad2 expression levels and overall survival (OS) (P = 0.443). Aberrant Mad2 expression was associated with cell proliferation and genetic instability, which may contribute to the carcinogenesis of PGI-DLBCL. Mad2 overexpression indicated a poor DFS and may be a potential biomarker for estimating prognosis for PGI

  3. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hentschel, Maria [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Appold, Steffen; Baumann, Michael [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Schreiber, Andreas [Hospital Dresden-Friedrichstadt, Department of Radiotherapy, Dresden (Germany); Abolmaali, Nasreddin [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Institute and Polyclinic of Diagnostic Radiology, Dresden (Germany); Abramyuk, Andrij [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Doerr, Wolfgang [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Kotzerke, Joerg; Zoephel, Klaus [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany)

    2011-07-15

    Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV{sub max}), the average SUV (SUV{sub mean}) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV{sub max} of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT ({delta}SUV{sub max10/20} {>=} 50%) than for patients with {delta}SUV{sub max20} < 50% (2-year OS = 38%; p = 0.02; 2-year LRC 40%; p = 0.06). A pretreatment GTV PET below the median of 10.2 ml predicted a better 2-year OS (34% for GTV PET {>=} 10.2 ml vs 83% for GTV PET < 10.2 ml; p = 0.02). The decrease of SUV{sub max} from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV{sub max}, especially {delta}SUV{sub max10/20}, for an early estimation of therapy outcome. Confirmatory studies are warranted. (orig.)

  4. Application of rotifer Brachionus plicatilis in detecting the toxicity of harmful algae

    Science.gov (United States)

    Yan, Tian; Wang, Yunfeng; Wang, Liping; Chen, Yang; Han, Gang; Zhou, Mingjiang

    2009-05-01

    The toxicity of seven major HAB (harmful algal bloom) species/strains, Prorocentrum donghaiense, Phaeocystis globosa, Prorocentrum micans, Alexandrium tamarense (AT-6, non-PSP producer), Alexandrium lusitanicum, Alexandrum tamarense (ATHK) and Heterosigma akashiwo were studied against rotifer Brachionus plicatilis under laboratory conditions. The results show that P. donghaiense, P. globosa, P. micans, A. tamarense (AT-6), or A. lusitanicum could maintain the individual survival and reproduction, as well as the population increase of the rotifer, but the individual reproduction would decrease when exposed to these five algae at higher densities for nine days; H. akashiwo could decrease the individual survival and reproduction, as well as population increase of the rotifer, which is similar to that of the starvation group, indicating that starvation might be its one lethal factor except for the algal toxins; A. tamarense (ATHK) has strong lethal effect on the rotifer with 48h LC50 at 800 cells/mL. The experiment on ingestion ability indicated by gut pigment change shows that P. donghaiense, P. globosa, P. micans, A. tamarense (AT-6) and A. lusitanicum can be taken by the rotifers as food, but A. tamarense (ATHK) or H. akashiwo can be ingested by the rotifers. The results indicate that all the indexes of individual survival and reproduction, population increase, gut pigment change of the rotifers are good and convenient to be used to reflect the toxicities of HAB species. Therefore, rotifer is suggested as one of the toxicity testing organisms in detecting the toxicity of harmful algae.

  5. Nitrite therapy prevents chlorine gas toxicity in rabbits.

    Science.gov (United States)

    Honavar, Jaideep; Doran, Stephen; Ricart, Karina; Matalon, Sadis; Patel, Rakesh P

    2017-04-05

    Chlorine (Cl 2 ) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl 2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl 2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl 2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl 2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl 2 exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl 2 gas exposure injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

    Energy Technology Data Exchange (ETDEWEB)

    Gault, N. [CEA Fontenay aux Roses, DSV/IRCM/SCSR/LRTS, 92265 Fontenay aux Rose (France); Sandre, C.; Moulin, B.; Bresson, C. [CEA, DEN, SECR, Laboratoire de Speciation des Radionucleides et des Molecules, F-91191 Gif-sur-Yvette (France); Poncy, J.L. [CEA Bruyeres Le Chatel, DSV/IRCM/SREIT/LRT, 91680 Bruyeres Le Chatel (France); Lefaix, J.L. [CEA Caen, DSV/IRCM/SRO/LARIA, 14070 Caen (France)

    2010-07-01

    Cobalt (Co) is an essential trace element well known as a constituent of vitamin B12, but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, {sup 58}Co and {sup 60}Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl{sub 2}) with or without {gamma}-ray doses to mimic contamination by {sup 60}Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate {gamma}-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

  7. Selenium Toxicity to Honey Bee (Apis mellifera L.) Pollinators: Effects on Behaviors and Survival

    OpenAIRE

    Hladun, Kristen R.; Smith, Brian H.; Mustard, Julie A.; Morton, Ray R.; Trumble, John T.

    2012-01-01

    We know very little about how soil-borne pollutants such as selenium (Se) can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER) ...

  8. Determination of Selenium Toxicity for Survival and Reproduction of Enchytraeid Worms in a Sandy Loam Soil

    Science.gov (United States)

    2016-07-01

    Jefferson Davis Highway , Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no...ecotoxicological benchmarks for developing the ecological soil screening levels (Eco-SSLs) for risk assessments of contaminated soils. For the present study, we...invertebrate-based Eco-SSL for Se. 15. SUBJECT TERMS Ecological soil screening level (Eco-SSL) Selenium Natural soil Enchytraeus crypticus Selenate

  9. Deterioration of Intellect among Children Surviving Leukemia: IQ Test Changes Modify Estimates of Treatment Toxicity.

    Science.gov (United States)

    Mulhern, Raymond, K; And Others

    1992-01-01

    Assessed association of young age at treatment, cranial irradiation, and time since treatment with intellectual deterioration among 49 long-term survivors of childhood leukemia. Found no significant effects of treatment group (low-dose cranial irradiation versus high-dose chemotherapy) or age at treatment. Small but statistically significant…

  10. Does ifosfamide therapy improve survival of patients with dedifferentiated chondrosarcoma?

    Science.gov (United States)

    Kawaguchi, Satoshi; Sun, Tao; Lin, Patrick P; Deavers, Michael; Harun, Nusrat; Lewis, Valerae O

    2014-03-01

    Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient- and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. In this small retrospective study, it appeared that ifosfamide

  11. Oleander toxicity: an examination of human and animal toxic exposures.

    Science.gov (United States)

    Langford, S D; Boor, P J

    1996-05-03

    The oleander is an attractive and hardy shrub that thrives in tropical and subtropical regions. The common pink oleander, Nerium oleander, and the yellow oleander, Thevetia peruviana, are the principle oleander representatives of the family Apocynaceae. Oleanders contain within their tissues cardenolides that are capable of exerting positive inotropic effects on the hearts of animals and humans. The cardiotonic properties of oleanders have been exploited therapeutically and as an instrument of suicide since antiquity. The basis for the physiological action of the oleander cardenolides is similar to that of the classic digitalis glycosides, i.e. inhibition of plasmalemma Na+,K+ ATPase. Differences in toxicity and extracardiac effects exist between the oleander and digitalis cardenolides, however. Toxic exposures of humans and wildlife to oleander cardenolides occur with regularity throughout geographic regions where these plants grow. The human mortality associated with oleander ingestion is generally very low, even in cases of intentional consumption (suicide attempts). Experimental animal models have been successfully utilized to evaluate various treatment protocols designed to manage toxic oleander exposures. The data reviewed here indicate that small children and domestic livestock are at increased risk of oleander poisoning. Both experimental and established therapeutic measures involved in detoxification are discussed.

  12. Individual social capital and survival

    DEFF Research Database (Denmark)

    Ejlskov, Linda; Mortensen, Rikke N; Overgaard, Charlotte

    2014-01-01

    BACKGROUND: The concept of social capital has received increasing attention as a determinant of population survival, but its significance is uncertain. We examined the importance of social capital on survival in a population study while focusing on gender differences. METHODS: We used data from...... a Danish regional health survey with a five-year follow-up period, 2007-2012 (n = 9288, 53.5% men, 46.5% women). We investigated the association between social capital and all-cause mortality, performing separate analyses on a composite measure as well as four specific dimensions of social capital while...... controlling for covariates. Analyses were performed with Cox proportional hazard models by which hazard ratios and 95% confidence intervals were calculated. RESULTS: For women, higher levels of social capital were associated with lower all-cause mortality regardless of age, socioeconomic status, health...

  13. Campylobacter virulence and survival factors.

    Science.gov (United States)

    Bolton, Declan J

    2015-06-01

    Despite over 30 years of research, campylobacteriosis is the most prevalent foodborne bacterial infection in many countries including in the European Union and the United States of America. However, relatively little is known about the virulence factors in Campylobacter or how an apparently fragile organism can survive in the food chain, often with enhanced pathogenicity. This review collates information on the virulence and survival determinants including motility, chemotaxis, adhesion, invasion, multidrug resistance, bile resistance and stress response factors. It discusses their function in transition through the food processing environment and human infection. In doing so it provides a fundamental understanding of Campylobacter, critical for improved diagnosis, surveillance and control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Coniferyl Aldehyde Ameliorates Radiation Intestine Injury via Endothelial Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ye Ji; Jung, Myung Gu; Lee, Yoonjin; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yunsil [Ewha Woman' s Univ., Seoul (Korea, Republic of); Ko, Younggyu [Korea Univ., Seoul (Korea, Republic of)

    2014-05-15

    Cancer treatments related gastrointestinal toxicity has also been recognized as a significant economic burden. Especially, extensive apoptosis of microvascular endothelial cell of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Coniferyl aldehyde (CA) is phenolic compounds isolated from cork stoppers, and one of the major pyrolysis products of lignin. Shi H. was support for the empirical use of CA as a medicinal food for cardiovascular diseases. CA has positive effect in broad way but there is no consequence in radiation induced intestine damage. Here, we investigate effect of CA on small intestine after abdominal IR to mice in this study. In this study, CA increased the survival rate in C3H mice against 13.5 Gy abdominal IR. We found CA protects small intestine via preventing endothelial cell apoptosis and enhancing their angiogenic activity. CA also showed protective effect on crypt cell survival. Endothelial cell survival may affect crypt cell protection against IR. From this data, we concluded that CA is effective for protection against abdominal radiation injury. CA could ameliorate side-effect of radiation therapy.

  15. Hypothyroidism improves random-pattern skin flap survival in rats.

    Science.gov (United States)

    Rahimpour, Sina; Nezami, Behtash Ghazi; Karimian, Negin; Sotoudeh-Anvari, Maryam; Ebrahimi, Farzad; Taleb, Shayandokht; Mirazi, Naser; Dehpour, Ahmad Reza

    2012-11-01

    The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps. Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 μg/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent. Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% ± 10.49% and 75.48% ± 12.93% versus 52.26% ± 5.75%, respectively, P hypothyroidism improves survival of random-pattern skin flaps in rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Survival of taylorellae in the environmental amoeba Acanthamoeba castellanii.

    Science.gov (United States)

    Allombert, Julie; Vianney, Anne; Laugier, Claire; Petry, Sandrine; Hébert, Laurent

    2014-03-19

    Taylorella equigenitalis is the causative agent of contagious equine metritis, a sexually-transmitted infection of Equidae characterised in infected mares by abundant mucopurulent vaginal discharge and a variable degree of vaginitis, cervicitis or endometritis, usually resulting in temporary infertility. The second species of the Taylorella genus, Taylorella asinigenitalis, is considered non-pathogenic, although mares experimentally infected with this bacterium can develop clinical signs of endometritis. To date, little is understood about the basic molecular virulence and persistence mechanisms employed by the Taylorella species. To clarify these points, we investigated whether the host-pathogen interaction model Acanthamoeba castellanii was a suitable model for studying taylorellae. We herein demonstrate that both species of the Taylorella genus are internalised by a mechanism involving the phagocytic capacity of the amoeba and are able to survive for at least one week inside the amoeba. During this one-week incubation period, taylorellae concentrations remain strikingly constant and no overt toxicity to amoeba cells was observed. This study provides the first evidence of the capacity of taylorellae to survive in a natural environment other than the mammalian genital tract, and shows that the alternative infection model, A. castellanii, constitutes a relevant alternative system to assess host-pathogen interactions of taylorellae. The survival of taylorellae inside the potential environmental reservoir A. castellanii brings new insight, fostering a broader understanding of taylorellae biology and its potential natural ecological niche.

  17. Does Intelligence Provide Survival Value?

    OpenAIRE

    Cairns, John

    2009-01-01

    Intelligence is defined as a general mental capacity to reason, plan, solve problems, think abstractly, comprehend ideas, and learn. Intelligence can also be defined as the ability to acquire and apply information gathered from the environment to modify its behavior. It is this intelligence that has allowed the genus Homo to survive for 2 million years. However, recently the global financial meltdown and the deleterious effects of climate change raise the question of whether intelligence has ...

  18. Survival on Land and Sea

    Science.gov (United States)

    1943-01-01

    flower, leaf steams, and young leaves may be eaten cooked as greens provided you cook them in several changes of water to remove the bitter taste and...and become a weed almost throughout the tropics. Its bladdery pods contain a single retl tomato-like fruit that is edible. Raspberries, blackberries ...plant that 108 SURVIVAL OK LAND AND SEA is about one foot In height and has blue flowers and inflated leaf stems. The young leaves, leafy stalks

  19. Columbia Crew Survival Investigation Report

    Science.gov (United States)

    2009-01-01

    NASA commissioned the Columbia Accident Investigation Board (CAIB) to conduct a thorough review of both the technical and the organizational causes of the loss of the Space Shuttle Columbia and her crew on February 1, 2003. The accident investigation that followed determined that a large piece of insulating foam from Columbia s external tank (ET) had come off during ascent and struck the leading edge of the left wing, causing critical damage. The damage was undetected during the mission. The CAIB's findings and recommendations were published in 2003 and are available on the web at http://caib.nasa.gov/. NASA responded to the CAIB findings and recommendations with the Space Shuttle Return to Flight Implementation Plan. Significant enhancements were made to NASA's organizational structure, technical rigor, and understanding of the flight environment. The ET was redesigned to reduce foam shedding and eliminate critical debris. In 2005, NASA succeeded in returning the space shuttle to flight. In 2010, the space shuttle will complete its mission of assembling the International Space Station and will be retired to make way for the next generation of human space flight vehicles: the Constellation Program. The Space Shuttle Program recognized the importance of capturing the lessons learned from the loss of Columbia and her crew to benefit future human exploration, particularly future vehicle design. The program commissioned the Spacecraft Crew Survival Integrated Investigation Team (SCSIIT). The SCSIIT was asked to perform a comprehensive analysis of the accident, focusing on factors and events affecting crew survival, and to develop recommendations for improving crew survival for all future human space flight vehicles. To do this, the SCSIIT investigated all elements of crew survival, including the design features, equipment, training, and procedures intended to protect the crew. This report documents the SCSIIT findings, conclusions, and recommendations.

  20. Statistical analysis of survival data.

    Science.gov (United States)

    Crowley, J; Breslow, N

    1984-01-01

    A general review of the statistical techniques that the authors feel are most important in the analysis of survival data is presented. The emphasis is on the study of the duration of time between any two events as applied to people and on the nonparametric and semiparametric models most often used in these settings. The unifying concept is the hazard function, variously known as the risk, the force of mortality, or the force of transition.

  1. Assessment of metal releases and leachate toxicity of oil sands coke

    Energy Technology Data Exchange (ETDEWEB)

    Puttaswamy, N.; Liber, K. [Saskatchewan Univ., Saskatoon, SK (Canada). Toxicology Centre

    2007-07-01

    Large volumes of coke are produced as a by-product of thermal upgrading of oil sands bitumen in Alberta. This paper examined the feasibility of integrating this stored by-product at wetland reclamation sites. Coke leachate water toxicity was evaluated in this study since coke is known to releases trace amounts of metals when it comes in contact with water. The objective was to determine the cause of toxicity by performing toxicity identification evaluations (TIEs) on the leachate. The leachability of metals from coke was examined over a 45 day period in 2-L glass jars using reconstituted water with a hardness of 300 mg/L as calcium carbonate (CaCO{sub 3}) at pH levels 5.5 and 9.5. Coke porewater samples and overlying water samples collected periodically were analyzed for trace metals using inductively coupled plasma mass spectroscopy (ICP-MS). The toxicity of coke leachate was evaluated at the end of the 45 day period using a Ceriodaphnia dubia standard three-brood chronic test with survival and reproduction as endpoints. Coke leachate water from both pH treatments had a negative effect on survival and reproduction of C. dubia. The coke leachate had high concentrations of vanadium, according to metal analysis of leachate water from both pH treatments. In order to identify the cause of toxicity, the coke leachate water will be subjected to several TIE processes.

  2. The influence of algal densities on the toxicity of chromium for Ceriodaphnia dubia Richard (Cladocera, Crustacea

    Directory of Open Access Journals (Sweden)

    S. Rodgher

    Full Text Available Food availability may affect metal toxicity for aquatic organisms. In the present study, the influence of high, medium and low densities of the algae Pseudokirchneriella subcapitata (10(6, 10(5 and 10(4 cells.mL-1, respectively on the chronic toxicity of chromium to the cladoceran Ceriodaphnia dubia was investigated. C. dubia was exposed to a range of chromium concentration from 2.71 to 34.04 µg.L-1 and fed with algae at various densities. In another experiment, the green alga was exposed to chromium concentrations (94 to 774 µg.L-1 and supplied as food in different densities to zooplankton. The survival and reproduction of the cladoceran were measured in these toxicity tests. The IC50 for Cr to P. subcapitata and metal accumulated by algal cells were determined. The results of a bifactorial analysis (metal versus algal densities showed that metal toxicity to zooplankton was dependent on algal densities. Significant toxic effects on the reproduction and survival of C. dubia were observed at 8.73, 18.22 and 34.04 µg.L-1 Cr when the test organisms were fed with 10(6 cells.mL-1 of P. subcapitata. Although the chlorophyta retain low chromium content, a decrease in the reproduction and survival of C. dubia occurred when they were fed with high algal density contaminated with 774 µg.L-1 Cr. It was concluded that high algal density have an appreciable influence on chromium toxicity to daphnids.

  3. LATERAL SURVIVAL: AN OT ACCOUNT

    Directory of Open Access Journals (Sweden)

    Moira Yip

    2004-12-01

    Full Text Available When laterals are the targets of phonological processes, laterality may or may not survive. In a fixed feature geometry, [lateral] should be lost if its superordinate node is eliminated by either the spreading of a neighbouring node, or by coda neutralization. So if [lateral] is under Coronal (Blevins 1994, it should be lost under Place assimilation, and if [lateral] is under Sonorant Voicing (Rice & Avery 1991 it should be lost by rules that spread voicing. Yet in some languages lateral survives such spreading intact. Facts like these argue against a universal attachment of [lateral] under either Coronal or Sonorant Voicing, and in favour of an account in terms of markedness constraints on feature-co-occurrence (Padgett 2000. The core of an OT account is that IFIDENTLAT is ranked above whatever causes neutralization, such as SHARE-F or *CODAF. laterality will survive. If these rankings are reversed, we derive languages in which laterality is lost. The other significant factor is markedness. High-ranked feature co-occurrence constraints like *LATDORSAL can block spreading from affecting laterals at all.

  4. Toxic chemicals: risk prevention through use reduction

    National Research Council Canada - National Science Library

    Higgins, Thomas E; Sachdev, Jayanti A; Engleman, Stephen A

    2011-01-01

    ... on the actual toxicity of chemicals currently in use, discusses variables that contribute to the relative toxicity of a substance, compares alternate emphases in existing programs for reducing environmental...

  5. Boron toxicity in oil palm (Elaeis guineensis)

    Energy Technology Data Exchange (ETDEWEB)

    Rajaratnam, J.A.

    1973-01-01

    Potted oil palms were treated with fertilizer of borate-46 at several concentrations and the plants were observed for boron toxicity effects. Toxicity symptoms were apparent at high rates but not at rates equivalent to typical Malaysian soils.

  6. Toxicity and Phototoxicity of Chemical Sun Filters

    Energy Technology Data Exchange (ETDEWEB)

    Butt, S.T.; Christensen, T

    2000-07-01

    Two chemical sun filters that are ingredients in sunscreen products have been tested for their dark toxicity and possible toxicity to mouse cells after UV irradiation. Increased toxicity as a result of breakdown of a UVB filter, octyl methoxycinnamate, was observed. UV radiation absorbed by the pure chemical sunscreen may lead to breakdown to more reactive chemical compounds than the unexposed sunscreen filter. The UVA filter included in our tests, butyl methoxydibenzoylmethane, was also toxic in the dark, however, it was the more photostable of the two and no additional significant toxicity was induced by UV irradiation. It can be concluded that the two sun filters are toxic to cells in the dark, but the biological role of this dark toxicity in the skin is not clear. Unstable sun filters may be broken down by UV to form photoproducts that are potentially toxic. (author)

  7. Toxic Release Inventory Chemicals by Groupings

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) makes available information for more than 600 toxic chemicals that are being used, manufactured, treated, transported, or released...

  8. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

  9. A comparison between the toxicity of oil and condensate

    Energy Technology Data Exchange (ETDEWEB)

    Foekema, E.; Schobben, H.P.M.; Marquenie, J.; Scholten, M.C.T. [TNO, Den Helder (Netherlands). Lab. for Applied Marine Research

    1995-12-31

    The toxicity of condensate from the `Ameland` gasfield was compared to the toxicity of the standard North Sea oil `Forties`. The comparison was based on the `topped` (residue after distillation at 200 C) fraction. This fraction is comparable with the fraction of the oil that is hazardous to the marine environment because the topped fraction will almost immediately evaporate. Hundred individuals of Corophium were placed in experimental systems with a surface of 500 CM{sup 2} filled with 10 cm sediment and 15 cm of water from the Wadden Sea. After two days the oil and condensate were added to the water surface in concentrations between 100 {micro}g/m{sup 2} to 100 {micro}g/m{sup 2}. After application a low tide was simulated until the oil or condensate covered the sediment. After five hours the sediment was inundated again. After three days the survival of the individuals and the remaining concentrations of oil and condensate in sediment were measured. From video images taken directly after application of the oil it can be seen that the Corophiums crept out of the polluted sediment. Despite the fact that the topped condensate contained much more lower alkanes, almost no difference was found between the toxicity of the topped oil and condensate. This leads to the conclusion that the effect of oil is mainly based on physical damage and not so much on the composition. The results of a later experiment with sunflower oil confirmed this conclusion.

  10. Multigeneration toxicity of imidacloprid and thiacloprid to Folsomia candida.

    Science.gov (United States)

    van Gestel, Cornelis A M; de Lima E Silva, Claudia; Lam, Thao; Koekkoek, Jacco C; Lamoree, Marja H; Verweij, Rudo A

    2017-04-01

    In a recent study, we showed that the springtail Folsomia candida was quite sensitive the neonicotinoid insecticides imidacloprid and thiacloprid. This study aimed at determining the toxicity of both compounds to F. candida following exposure over three generations, in natural LUFA 2.2 standard soil. In the first generation, imidacloprid was more toxic than thiacloprid, with LC50s of 0.44 and 9.0 mg/kg dry soil, respectively and EC50s of 0.29 and 1.5 mg/kg dry soil, respectively. The higher LC50/EC50 ratio suggests that thiacloprid has more effects on reproduction, while imidacloprid shows lethal toxicity to the springtails. In the multigeneration tests, using soil spiked at the start of the first generation exposures, imidacloprid had a consistent effect on survival and reproduction in all three generations, with LC50s and EC50s of 0.21-0.44 and 0.12-0.29 mg/kg dry soil, respectively, while thiacloprid-exposed animals showed clear recovery in the second and third generations (LC50 and EC50 > 3.33 mg/kg dry soil). The latter finding is in agreement with the persistence of imidacloprid and the fast degradation of thiacloprid in the test soil.

  11. Hydrogen sulfide toxicity in a thermal spring: a fatal outcome.

    Science.gov (United States)

    Daldal, Hale; Beder, Bayram; Serin, Simay; Sungurtekin, Hulya

    2010-08-01

    Hydrogen sulfide (H(2)S) is a toxic gas with the smells of "rotten egg"; its toxic effects are due to the blocking of cellular respiratory enzymes leading to cell anoxia and cell damage. We report two cases with acute H(2)S intoxication caused by inhalation of H(2)S evaporated from the water of a thermal spring. Two victims were found in a hotel room were they could take a thermal bath. A 26-year-old male was found unconscious; he was resuscitated, received supportive treatment and survived. A 25-year-old female was found dead. Autopsy showed diffuse edema and pulmonary congestion. Toxicological blood analysis of the female revealed the following concentrations: 0.68 mg/L sulfide and 0.21 mmol/L thiosulfate. The urine thiosulfate concentration was normal. Forensic investigation established that the thermal water was coming from the hotel's own illegal well. The hotel was closed. This report highlights the danger of H(2)S toxicity not only for reservoir and sewer cleaners, but also for individuals bathing in thermal springs.

  12. The toxicity of oil-contaminated muskeg following biodegradation

    Energy Technology Data Exchange (ETDEWEB)

    Farwell, A.; Kelly-Hooper, F.; McAlear, J.; Sinnesael, K.; Dixon, D. [Waterloo Univ., Waterloo, ON (Canada)

    2009-07-01

    The current environmental criteria for the maximum allowable levels of hydrocarbons resulting from an oil spill assume that all detectable hydrocarbons are petroleum hydrocarbons (PHC) and do not account for naturally-occurring biogenic hydrocarbons (BHC). As such, some soils may be wrongfully assessed as being PHC contaminated. A false identification could lead to unnecessary and costly bioremediation that is potentially disruptive to functioning ecosystems. This study is part of a larger project to differentiate between natural and petroleum F3 hydrocarbons in muskeg material that has been impacted by an oil spill. The toxicity of oil-contaminated muskeg was examined following biodegradation in laboratory microcosms. Preliminary acute toxicity tests using locally purchased Sphagnum peat moss contaminated with Federated Crude oil had no effect on the survival of earthworms (Eisenia andrei), but springtails (Orthonychiurus folsomi) were more sensitive. Earthworm and springtail reproduction bioassays and a Northern wheatgrass (Elymus lanceolatus) growth bioassay was used to test the crude-oil-contaminated peat. All 3 test species will be used to test for reduced toxicity following biodegradation of Federated Crude oil-contaminated muskeg from northern Alberta under simulated conditions.

  13. FOR SELECTED ORGANIC MICROPOLLUTANTS ELIMINATION AND CHANGE OF WATER TOXICITY

    Directory of Open Access Journals (Sweden)

    Mariusz Dudziak

    2016-12-01

    Full Text Available All of the available and applicable chemical oxidants were found to affect the quality of the treated water or wastewater. It has been commonly observed that the oxidation processes generate by-products, which often possess unknown biological activity. Accordingly, the present study assessed the degree of degradation of mixture of selected micropollutants and the change of the solution toxicity in the UV/TiO2/H2O2 hybrid process. Water containing bisphenol A and diclofenac at a concentration of 1 mg/dm3 was treated. For toxicological evaluation of solution sample were used three different tests, ie. enzymatic Microtox® using luminescent strain of marine bacteria Aliivibrio fischeri, survival of the crustaceans Daphnia magna and the growth of duckweed Lemna minor. Decomposition of tested micropollutants depend on the processing time and the type of the oxidizing compound. However, during the process we observed adverse effects of water toxicity. The toxicity was documented in both bacteria and water plant.

  14. Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells

    Science.gov (United States)

    Rocha, Gerson M.; Michea, Luis F.; Peters, Eugenia M.; Kirby, Martha; Xu, Yuhui; Ferguson, Douglas R.; Burg, Maurice B.

    2001-01-01

    Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of phenacetin), caffeine, and other related drugs individually and in combination on mouse inner medullary collecting duct cells (mIMCD3). The number of rapidly proliferating cells was reduced by ≈50% by 0.5 mM ASA, salicylic acid, or APAF. The drugs had less effect on confluent cells, which proliferate slowly. Thus, the slow in vivo turnover of IMCD cells could explain why clinical toxicity requires very high doses of these drugs over a very long period. Caffeine greatly potentiated the effect of acetaminophen, pointing to a potential danger of the mixture. Cyclooxygenase (COX) inhibitors, indomethacin and NS-398, did not reduce cell number except at concentrations greatly in excess of those that inhibit COX. Therefore, COX inhibition alone is not toxic. APAF arrests most cells in late G1 and S and produces a mixed form of cell death with both oncosis (swollen cells and nuclei) and apoptosis. APAF is known to inhibit the synthesis of DNA and cause chromosomal aberrations due to inhibition of ribonucleotide reductase. Such effects of APAF might account for renal medullary cell death in vivo and development of uroepithelial tumors from surviving cells that have chromosomal aberrations. PMID:11320259

  15. The Surgical Treatment of Toxic Megacolon in Hirschsprung Disease.

    Science.gov (United States)

    Khasanov, Rasul; Schaible, Thomas; Wessel, Lucas M; Hagl, Cornelia Irene

    2016-11-01

    Enterocolitis remains the most significant cause of morbidity and mortality in Hirschsprung disease (HD). It could progress into toxic megacolon (TM)-acute dilatation of the colon as accompanying toxic complication of Hirschsprung enterocolitis. It is a devastating complication, especially in infants with so far undiagnosed HD. A retrospective analysis of medical records of 4 infants with TM was performed. The diagnosis TM was determined on the basis of clinical information (abdominal pain or tenderness, abdominal distension, diarrhea, bloody diarrhea, and constipation), plain x-rays of the abdomen (segmental or total colonic dilation), and the presence of such criteria (fever, high heart rate, increased white blood cell count, C reactive protein, anemia, dehydration, electrolyte disturbances, hypotension). Surgical management and outcome was evaluated by retrospective chart review. The median duration of symptoms characteristic for TM was 3 days. Toxic megacolon was seen as the first manifestation of previously unknown HD in 3 patients; in 1 newborn, the contrast radiograph was suggestive of HD. In all patients, conservative treatment was failed. Three patients were treated with surgical decompression and ileostomy only. In all these cases, severe complications occurred, consequently 2 of them died. In 1 patient, a resection of the transverse dilated colon additionally was performed. This patient had no complications in postoperative period and survived. Because of the high mortality in patients with TM that were treated medically or with colonic decompression, a resection of massively distended part of the colon should be performed.

  16. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kjeld Schmiegelow

    2017-04-01

    Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

  17. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control.

    Science.gov (United States)

    Glynne-Jones, R; Counsell, N; Quirke, P; Mortensen, N; Maraveyas, A; Meadows, H M; Ledermann, J; Sebag-Montefiore, D

    2014-07-01

    In stage III colon cancer, oxaliplatin/5-fluorouracil (5-FU)-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy. Eligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or six cycles of XELOX. The primary end point was DFS; secondary end points were acute toxicity and OS. 390 patients were required in each arm, to detect an improvement in 3-year DFS from 40% to 50.5%, with 85% power and two-sided 5% significance level. The study closed prematurely in 2008 because of poor accrual. Only 113 patients were randomly assigned to either observation (n = 59) or XELOX (n = 54). Compliance was poor, 93% allocated chemotherapy started and 48% completed six cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 toxicity 40%. After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm had relapsed or died compared with 12 patients (22%) in XELOX. The 3-year DFS rate was 78% with XELOX and 71% with observation [hazard ratio (HR) for DFS = 0.80; 95% confidence interval (CI) 0.38-1.69; P = 0.56]. The 3-year OS for XELOX and observation were 89% and 88%, respectively (HR for OS = 1.18; 95% CI 0.43-3.26; P = 0.75). The observed improvement in DFS for adjuvant XELOX and similar OS were not statistically significant, as expected given the small number of patients and consequent low power. Our findings support the need for trials that test the role of neoadjuvant chemotherapy. NCT00427713. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Toxicity evaluation and hazard review Cold Smoke

    Energy Technology Data Exchange (ETDEWEB)

    Archuleta, M.M.; Stocum, W.E.

    1993-12-01

    Cold Smoke is a dense white smoke produced by the reaction of titanium tetrachloride and aqueous ammonia aerosols. Early studies on the toxicity of this nonpyrotechnically generated smoke indicated that the smoke itself is essentially non-toxic (i.e. exhibits to systemic toxicity or organ damage due to exposure) under normal deployment conditions. The purpose of this evaluation was to review and summarize the recent literature data available on the toxicity of Cold Smoke, its chemical constituents, and its starting materials.

  19. Cetuximab-associated pulmonary toxicity.

    Science.gov (United States)

    Chua, Wei; Peters, Matthew; Loneragan, Robert; Clarke, Stephen

    2009-04-01

    There is increasing evidence for the use of epidermal growth factor receptor (EGFR) inhibitors in head and neck, non-small-cell lung, and colorectal cancers. We report the case of a 78-year-old man with metastatic colorectal cancer (CRC) involving liver and lung who received cetuximab plus irinotecan as third-line treatment. Two months later, he presented with signs and symptoms consistent with bronchiolotis obliterans organizing pneumonia secondary to cetuximab. Reports of cetuximab-associated pulmonary toxicity are rare, although there have been extensive reports of interstitial fibrosis with the use of other EGFR inhibitors such as gefitinib and erlotinib. There are many causes of pulmonary infiltrates in patients treated for advanced CRC, and this case highlights the importance of considering drug toxicity.

  20. A Miniscale Algal Toxicity Test

    DEFF Research Database (Denmark)

    Arensberg, Pia; Hemmingsen, Vicky H.; Nyholm, Niels

    1995-01-01

    A simple miniscale (approx. 1 - 2.5 ml) toxicity test procedure with the freshwater green algaSelenastrum capricornutum is described. The procedure fulfils the validity criteria of the ISO (International Association for Standardization) standard test protocol. Practically identical concentration...... and test volumes (down to 1 ml) could also be used. Tissue culture treated polystyrene microplates were found toxic to algae and thus unusable. pH control is achieved more easily in the minitest than in larger size shake flasks due to greater turbulence and a larger surface/volume ratio which both...... facilitates CO2 mass transfer. Uniform illumination of the individual units of a minitest setup is obtained readily due to the small area that has to be illuminated. Using the rapidly growing green alga S. capricornutum as test organism, it is proposed generally to reduce the standard test duration from 3...

  1. Salicylate toxicity model of tinnitus

    Directory of Open Access Journals (Sweden)

    Daniel eStolzberg

    2012-04-01

    Full Text Available Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs or aging which affects ~14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed.

  2. Engineered Nanoparticle (Eco)Toxicity

    DEFF Research Database (Denmark)

    Cupi, Denisa

    dispersion protocol development. This may serve as a basis for the development of a harmonized dispersion protocol for ENPs. Natural organic matter (NOM) and aging of suspensions prior to testing were employed in an attempt to stabilize aqueous suspensions of three different ENPs. While NOM helped...... in stabilizing ZnO ENPs suspensions, it caused agglomeration in TiO2 ENP stock suspensions and an underestimation of toxicity for Ag ENPs. Likewise, aging only aided in the stability of ZnO ENPs. It was concluded that NOM can mitigate or eliminate toxicity of Ag ENPs and is not recommended for use. The ratio...... of NOM to ENP proved to be important in stabilizing non-capped ENPs. Another attempt towards stable suspensions involved adjusting different standard testing parameters, such as the pH and ionic strength of the test media. It was found that point of zero charge measurements should be conducted prior...

  3. Toxicity of ethion in goats.

    Science.gov (United States)

    Mosha, R D; Gyrd-Hansen, N

    1990-02-01

    Cholinesterase activities were measured in plasma and in red blood cells from 6 goats after iv injection of the organophosphorus insecticide ethion at 3 different dose levels--2 mg/kg, 5 mg/kg and 10 mg/kg. Plasma levels of ethion after injection were established. At 2 mg/kg no signs of toxicity were observed and the blood cholinesterase activity remained above 65% of the control value. After administration of the higher doses the goats showed signs of severe toxicity corresponding to increased parasympathetic stimulation. Cholinesterase activities in blood were reduced to approximately 10% of the control value for the 5 mg/kg group and to approximately 5% for the 10 mg/kg group. Reactivation of cholinesterase activity in blood cells and plasma by means of pralidoxime was very efficient during the first 24 hr after administration of ethion, but was insignificant after 72 hours.

  4. Toxicity of weight loss agents.

    Science.gov (United States)

    Yen, May; Ewald, Michele Burns

    2012-06-01

    With the rise of the obesity epidemic in the United States over the last several decades and the medical complications seen with it, weight loss and dieting have become a national public health concern. Because of their increased use and availability through internet sales, several different dieting agents were reviewed for potential toxicity. These included: syrup of ipecac, cathartics, human chorionic gonadotropin hormone, 2,4 Dinitrophenol, guar gum, phenylpropanolamine, ma huang/ ephedra, caffeine, clenbuterol, fenfluramine, sibutramine, thyroid hormone, orlistat and cannabinoid antagonists. With the internet making even banned products readily accessible, healthcare providers need to be aware of the potential toxicities of a wide range of weight loss agents. Our review covered topics we thought to be most historically significant as well as pertinent to the practice of medical toxicology today.

  5. The Effect of Toxic Leadership

    Science.gov (United States)

    2012-03-15

    leaders are a product of their environment, unlike corporations that hire mid-level and senior level managers to guide their organizations; the...01674544. 5 Tomas Giberson and others, "Leadership and Organizational Culture: Linking Ceo Characteristics to Cultural Values," Journal of Business...Craig; Lim. 23 David Lease, "From Great to Ghastly: How Toxic Organizational Cultures Poison Companies the Rise and Fall of Enron , Worldcom, Healthsouth

  6. Dietary zinc and its toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lantzsch, H.J.

    1973-01-01

    First signs of Zn-toxicity in rats appeared at 1000 to 2000 ppm Zn in food. They were characterized by growth inhibition by the appearance of a microcytic hypochromic anemia by a reversible impairment of the ability to reproduce by disturbances in fat metabolism and by Zn-accumulation especially in the liver and the skeleton. Available results in the literature concerning alimentary Zn-toxicity in horses are few. At a daily doses of 8000 mg Zn during gestation there were no noticeable adverse effects either in the mare or the foal. While with young lambs addition of Zn of up to 1000 ppm enhanced growth, food intake and feed efficiency, with older lambs it gave rise to depressions. Available results of experiments with milk cows are equally insufficient. At Zn-concentration of 40 to 80 ppm, which may be reached in normal foodstuff, there appears to be a disturbance in the metabolism of cellulose in the rumen. In spite of this fact and notwithstanding the insufficiently examined influence of high Zn-concentrations in food on the Cu-metabolism, the limit of Zn-tolerance can be given at 1000 mg per kg of food. If dissolved, Zn is far more toxic. With calves there wre no signs of clinical toxicity up to Zn-concentrations in the food of 3000 ppm. Above 900 ppm there appeared depression in growth and deterioration in the feed efficiency. Ae 1700 ppm there was a decrease infood intake. Increased Zn-intake lead to a growing Zn-accumulation in several organs and tissues, with the accumulation in the liver, bones, kidneys, pancreas and the gastrointestinal tract being of special significance. With cessation of Zn-intake in food, Zn-accumulation slowly disappeared. As a result of high Zn-intake there appears to be synergistic and antagonistic interdependent effects with the metabolism of other trace elements (Cu, Fe) and minerals (Ca, Na, P).

  7. Allergy and "toxic mold syndrome".

    Science.gov (United States)

    Edmondson, David A; Nordness, Mark E; Zacharisen, Michael C; Kurup, Viswanath P; Fink, Jordan N

    2005-02-01

    "Toxic mold syndrome" is a controversial diagnosis associated with exposure to mold-contaminated environments. Molds are known to induce asthma and allergic rhinitis through IgE-mediated mechanisms, to cause hypersensitivity pneumonitis through other immune mechanisms, and to cause life-threatening primary and secondary infections in immunocompromised patients. Mold metabolites may be irritants and may be involved in "sick building syndrome." Patients with environmental mold exposure have presented with atypical constitutional and systemic symptoms, associating those symptoms with the contaminated environment. To characterize the clinical features and possible etiology of symptoms in patients with chief complaints related to mold exposure. Review of patients presenting to an allergy and asthma center with the chief complaint of toxic mold exposure. Symptoms were recorded, and physical examinations, skin prick/puncture tests, and intracutaneous tests were performed. A total of 65 individuals aged 1 1/2 to 52 years were studied. Symptoms included rhinitis (62%), cough (52%), headache (34%), respiratory symptoms (34%), central nervous system symptoms (25%), and fatigue (23%). Physical examination revealed pale nasal mucosa, pharyngeal "cobblestoning," and rhinorrhea. Fifty-three percent (33/62) of the patients had skin reactions to molds. Mold-exposed patients can present with a variety of IgE- and non-IgE-mediated symptoms. Mycotoxins, irritation by spores, or metabolites may be culprits in non-IgE presentations; environmental assays have not been perfected. Symptoms attributable to the toxic effects of molds and not attributable to IgE or other immune mechanisms need further evaluation as to pathogenesis. Allergic, rather than toxic, responses seemed to be the major cause of symptoms in the studied group.

  8. Toxicity of parasporal crystals of Bacillus thuringiensis to the Indian meal moth, Plodia interpunctella.

    Science.gov (United States)

    Schesser, J H; Bulla, L A

    1979-01-01

    Toxicity of Bacillus thuringiensis parasporal crystals to the Indian meal moth, Plodia interpunctella, is described. The numbers of insects killed were in relation to crystal dry weight. Mortality was determined by comparing adult emergence in diets treated with crystals to emergence in untreated diets. There was only a 30% survival at an application of 0.414 microgram/cm2, and the mean 50% lethal concentration value was found to be 0.299 microgram/cm2. The use of emergence data has provided a reliable and reproducible bioassay for comparing relative toxicities of crystals, spores, and other cellular components to this economically important insect. Images PMID:485134

  9. Copper toxicity on juveniles of Hyalella pseudoazteca González and Watling, 2003.

    Science.gov (United States)

    Giusto, Anabella; Ferrari, Lucrecia

    2008-08-01

    The aim of this work is to evaluate the toxic effect of water and sediment contaminated with Cu(2+) on the survival and growth of juveniles of Hyalella pseudoazteca. The LC(50) 96 h for Cu(2+) in moderately hard water was 0.17 mg/L. The concentration of 100 mg Cu(2+)/kg in sediment was found to have an inhibitory growth effect. This study provides information on the toxic effects of Cu(2+) on a native benthic species occurring in the Pampean region, Argentina and contributes to validate, in this region, the interim use of Cu(2+) values recommended by the sediment quality guidelines for the Northern hemisphere.

  10. Toxicity of 56 substances to trees

    DEFF Research Database (Denmark)

    Clausen, Lauge Peter Westergaard; Trapp, Stefan

    2017-01-01

    Toxicity data of substances to higher plants is needed for the purpose of risk assessment, site evaluation, phytoremediation, and plant protection. However, the results from the most common phytotoxicity tests, like the OECD algae and Lemna test, are not necessarily valid for higher terrestrial...... toxicity test is a robust method for relating uptake, accumulation, and metabolism of substances to the toxicity to trees....

  11. Joint toxic effects on Caenorhabditis elegans

    NARCIS (Netherlands)

    Jonker, M.J.

    2003-01-01

    In polluted areas organisms are generally exposed to mixtures of toxic chemicals rather than a single toxicant only. Since the number of mixture toxicity studies with regard to soil systems is limited, the research in this thesis was focused on investigating ecotoxicological consequences of combined

  12. Evaluation of the toxicity of sediments from the Anniston PCB Site to the mussel Lampsilis siliquoidea

    Science.gov (United States)

    Schein, Allison; Sinclair, Jesse A.; MacDonald, Donald D.; Ingersoll, Christopher G.; Kemble, Nile E.; Kunz, James L.

    2015-01-01

    concentrations of PCBs were associated with the highest concentrations of PAHs, PCDDs/PCDFs, and organochlorine pesticides. Specifically, sediments 08, 18, and 19 exceeded probable effect concentration quotients (PEC-Qs) of 1.0 for all organic classes of contaminants. These three sediment samples also had high concentrations of mercury and lead, which were the only metals found at elevated concentrations (i.e., above the probable effect concentration [PEC]) in the samples collected. Many sediment samples were highly contaminated with mercury, based on comparisons to samples collected from reference locations. The whole-sediment laboratory toxicity tests conducted with L. siliquoidea met the test acceptability criteria (e.g., control survival was greater than or equal to 80%). Survival of mussels was high in most samples, with 4 of 23 samples (17%) classified as toxic based on the survival endpoint. Biomass and weight were more sensitive endpoints for the L. siliquoidea toxicity tests, with both endpoints classifying 52% of the samples as toxic. Samples 19 and 30 were most toxic to L. siliquoidea, as they were classified as toxic according to all four endpoints (survival, biomass, weight, and length). Mussels were less sensitive in toxicity tests conducted with sediments from the Anniston PCB Site than Hyalella azteca and Chironomus dilutus. Biomass of L. siliquoidea was less sensitive compared to biomass of H. azteca or biomass of larval C. dilutus. Based on the most sensitive endpoint for each species, 52% of the samples were toxic to L. siliquoidea, whereas 67% of sediments were toxic to H. azteca (based on reproduction) and 65% were toxic to C. dilutus (based on adult biomass). The low-risk toxicity threshold (TTLR) was higher for L. siliquoidea biomass (e.g., 20,400 µg/kg dry weight [DW]) compared to that for H. azteca reproduction (e.g., 499 µg/kg DW) or C. dilutus adult biomass (e.g., 1,140 µg/kg DW; MacDonald et al. 2014). While mussels such as L. sili

  13. CAESAR models for developmental toxicity

    Directory of Open Access Journals (Sweden)

    Piclin Nadège

    2010-07-01

    Full Text Available Abstract Background The new REACH legislation requires assessment of a large number of chemicals in the European market for several endpoints. Developmental toxicity is one of the most difficult endpoints to assess, on account of the complexity, length and costs of experiments. Following the encouragement of QSAR (in silico methods provided in the REACH itself, the CAESAR project has developed several models. Results Two QSAR models for developmental toxicity have been developed, using different statistical/mathematical methods. Both models performed well. The first makes a classification based on a random forest algorithm, while the second is based on an adaptive fuzzy partition algorithm. The first model has been implemented and inserted into the CAESAR on-line application, which is java-based software that allows everyone to freely use the models. Conclusions The CAESAR QSAR models have been developed with the aim to minimize false negatives in order to make them more usable for REACH. The CAESAR on-line application ensures that both industry and regulators can easily access and use the developmental toxicity model (as well as the models for the other four endpoints.

  14. Determinants of carbon nanotube toxicity.

    Science.gov (United States)

    Lanone, Sophie; Andujar, Pascal; Kermanizadeh, Ali; Boczkowski, Jorge

    2013-12-01

    In the last few years questions have been raised regarding the potential toxicity of carbon nanotubes (CNTs) to humans and environment. It is believed that the physico-chemical characteristics of these materials are key determinants of CNT interaction with living organisms, and hence determine their toxicity. As for other nanomaterials, the most important of these characteristics are the length, diameter, surface area, tendency to agglomerate, bio-durability, presence and nature of catalyst residues as well as chemical functionalization of the CNT. This review highlights the recent advancements in the understanding of the CNT properties which are essential in determining CNT toxicity. Hence the focus is on CNT dimensions, surface properties, bio-durability and corona formation as these fields have evolved greatly in recent years. A deeper understanding of these events and their underlying mechanisms could provide a molecular explanation of the biological and physiological responses following CNT administration and therefore help in the development of safe by design materials. © 2013 Elsevier B.V. All rights reserved.

  15. Survival in pulmonary hypertension in Spain: insights from the Spanish registry.

    Science.gov (United States)

    Escribano-Subias, Pilar; Blanco, Isabel; López-Meseguer, Manuel; Lopez-Guarch, Carmen Jimenez; Roman, Antonio; Morales, Pilar; Castillo-Palma, María Jesús; Segovia, Javier; Gómez-Sanchez, Miguel A; Barberà, Joan Albert

    2012-09-01

    A pulmonary hypertension (PH) registry (Spanish Registry of Pulmonary Arterial Hypertension) was undertaken to analyse prevalence, incidence and survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Spain, and to assess the applicability of recent survival prediction equations. Voluntary reporting of previously diagnosed and incident PAH or CTEPH cases (July 2007-June 2008) was performed. Demographic, functional and haemodynamic variables were evaluated. 866 patients with PAH and 162 with CTEPH were included. PAH associated with toxic oil syndrome and pulmonary veno-occlusive disease were reported for the first time in a PAH registry. Estimated prevalences were as follows: PAH, 16 and CTEPH, 3.2 cases per million adult inhabitants (MAI). Estimated incidences were as follows: PAH, 3.7 and CTEPH, 0.9 cases per MAI per yr. 1-, 3- and 5-yr survival was 87%, 75% and 65%, respectively, with no differences between PAH and CTEPH. Male sex, right atrial pressure and cardiac index were independent predictors of death. Matching between observed survival and that predicted by different equations was closer when the characteristics of the cohorts were similar. Epidemiology and survival of PAH patients in the Spanish registry are similar to recent registries. Characteristics of the population from which survival prediction equations are derived influence their applicability to a different cohort. CTEPH is much less prevalent than PAH, although has a similar survival rate.

  16. Every DFS tree of a 3-connected graph contains a contractible edge

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Mehlhorn, Kurt; Schmidt, Jens M.

    2013-01-01

    Tutte proved that every 3-connected graph G on more than 4 vertices contains a contractible edge. We strengthen this result by showing that every depth-first-search tree of G contains a contractible edge. Moreover, we show that every spanning tree of G contains a contractible edge if G is 3-regular...

  17. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model.

    Science.gov (United States)

    Zhou, Kejin; Nguyen, Liem H; Miller, Jason B; Yan, Yunfeng; Kos, Petra; Xiong, Hu; Li, Lin; Hao, Jing; Minnig, Jonathan T; Zhu, Hao; Siegwart, Daniel J

    2016-01-19

    RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC50 75 mg/kg dendrimer repeated dosing). Delivery of let-7 g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer's own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs.

  18. Stage at diagnosis and ovarian cancer survival

    DEFF Research Database (Denmark)

    Maringe, Camille; Walters, Sarah; Butler, John

    2012-01-01

    We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival.......We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival....

  19. Survival of Bacillus thuringiensis strains in gypsy moth (Lymantria dispar) larvae is correlated with production of urease

    Science.gov (United States)

    Phyllis A.W. Martin; Robert R. Jr. Farrar; Michael B. Blackburn

    2011-01-01

    We tested 50 lepidopteran-toxic Bacillus thuringiensis Berliner (Bt) strains with diverse phenotypes for the ability to survive repeated passages through larvae of the gypsy moth, Lymantria dispar (L.), without intervening growth on artificial media. These experiments have revealed a remarkable correlation...

  20. Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series.

    Science.gov (United States)

    Wilcox, Shea William; Aherne, Noel J; McLachlan, Craig Steven; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

    2015-02-01

    We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option. © 2015 The Royal Australian and New Zealand College of Radiologists.

  1. 5-fluorouracil Toxicity Mechanism Determination in Human Keratinocytes: in vitro Study on HaCaT

    Directory of Open Access Journals (Sweden)

    Jan Hartinger

    2018-01-01

    Full Text Available 5-fluorouracil (5-FU and capecitabine therapy is often accompanied by palmar-plantar erythrodysesthesia (PPE which is manifestation of 5-FU toxicity in keratinocytes. The main mechanisms of 5-FU action are thymidylate synthase (TS inhibition which can be abrogated by thymidine and strengthened by calciumfolinate (CF and incorporation of fluorouridinetriphosphate into RNA which can be abrogated by uridine. For proper PPE treatment 5-FU mechanism of action in keratinocytes needs to be elucidated. We used the 5-FU toxicity modulators uridine, thymidine and CF to discover the mechanism of 5-FU action in human keratinocyte cell line HaCaT. To measure the cellular viability, we used MTT test and RTCA test. CF did not augment 5-FU toxicity and 5-FU toxicity was weakened by uridine. Therefore, the primary mechanism of 5-FU toxicity in keratinocytes is 5-FU incorporation into RNA. The uridine protective effect cannot fully develop in the presence of CF. Thymidine addition to 5-FU and uridine treated cells not only prevents the toxicity-augmenting CF effect but it also prolongs the 5-FU treated cells survival in comparison to uridine only. Therefore, it can be assumed that in the presence of uridine the 5-FU toxicity mechanism is switched from RNA incorporation to TS inhibition. Although particular 5-FU toxicity mechanisms were previously described in various cell types, this is the first time when various combinations of pyrimidine nucleosides and CF were used for 5-FU toxicity mechanism elucidation in human keratinocytes. We suggest that for PPE treatment ointment containing uridine and thymidine should be further clinically tested.

  2. Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution.

    Science.gov (United States)

    Bece, Andrej; Tin, Mo Mo; Martin, Darren; Lin, Robert; McLean, Jocelyn; McCaughan, Brian

    2015-06-01

    We aim to report the outcome of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiotherapy with or without chemotherapy at a single Australian institution. Between July 2004 and March 2013, 53 patients were referred for radiation treatment following EPP, of whom 49 were suitable for adjuvant treatment. Radiation treatment initially involved a 3D conformal, mixed electron/photon technique, delivering 45-50.4 Gy in 25-28 fractions (31 patients) and subsequently a nine-field intensity-modulated radiotherapy technique, delivering 50.4-54 Gy in 28-30 fractions (18 patients). Fifty-five per cent of patients also received pre-operative chemotherapy. We assessed toxicity, disease-specific and overall survival in patients who commenced radiation treatment. Forty-one patients (84%) completed treatment as prescribed. Six patients stopped prematurely due to toxicity, and two with disease progression. Most patients discontinuing due to toxicity received over 90% of the prescribed dose. Common acute toxicities included nausea, fatigue, anorexia and dermatitis. Severe early toxicities were rare. Late toxicities were uncommon, with the exception of a persistent elevation in liver enzymes in those with right-sided disease. Neither clinical hepatitis nor radiation pneumonitis was documented. With a median follow up of 18.7 months, median disease-free and overall survival were 21.6 and 30.5 months, respectively, and 2-year overall survival was 57.3%. Hemithoracic radiotherapy following EPP, although associated with significant early toxicity, is well tolerated. Most patients complete the prescribed treatment, and clinically significant late toxicities are rare. © 2015 The Royal Australian and New Zealand College of Radiologists.

  3. Starvation-Survival in Haloarchaea

    Science.gov (United States)

    Winters, Yaicha D.; Lowenstein, Tim K.; Timofeeff, Michael N.

    2015-01-01

    Recent studies claiming to revive ancient microorganisms trapped in fluid inclusions in halite have warranted an investigation of long-term microbial persistence. While starvation-survival is widely reported for bacteria, it is less well known for halophilic archaea—microorganisms likely to be trapped in ancient salt crystals. To better understand microbial survival in fluid inclusions in ancient evaporites, laboratory experiments were designed to simulate growth of halophilic archaea under media-rich conditions, complete nutrient deprivation, and a controlled substrate condition (glycerol-rich) and record their responses. Haloarchaea used for this work included Hbt. salinarum and isolate DV582A-1 (genus Haloterrigena) sub-cultured from 34 kyear Death Valley salt. Hbt. salinarum and DV582A-1 reacted to nutrient limitation with morphological and population changes. Starved populations increased and most cells converted from rods to small cocci within 56 days of nutrient deprivation. The exact timing of starvation adaptations and the physical transformations differed between species, populations of the same species, and cells of the same population. This is the first study to report the timing of starvation strategies for Hbt. salinarum and DV582A-1. The morphological states in these experiments may allow differentiation between cells trapped with adequate nutrients (represented here by early stages in nutrient-rich media) from cells trapped without nutrients (represented here by experimental starvation) in ancient salt. The hypothesis that glycerol, leaked from Dunaliella, provides nutrients for the survival of haloarchaea trapped in fluid inclusions in ancient halite, is also tested. Hbt. salinarum and DV582A-1 were exposed to a mixture of lysed and intact Dunaliella for 56 days. The ability of these organisms to utilize glycerol from Dunaliella cells was assessed by documenting population growth, cell length, and cell morphology. Hbt. salinarum and DV582A-1

  4. Starvation-Survival in Haloarchaea

    Directory of Open Access Journals (Sweden)

    Yaicha D. Winters

    2015-11-01

    Full Text Available Recent studies claiming to revive ancient microorganisms trapped in fluid inclusions in halite have warranted an investigation of long-term microbial persistence. While starvation-survival is widely reported for bacteria, it is less well known for halophilic archaea—microorganisms likely to be trapped in ancient salt crystals. To better understand microbial survival in fluid inclusions in ancient evaporites, laboratory experiments were designed to simulate growth of halophilic archaea under media-rich conditions, complete nutrient deprivation, and a controlled substrate condition (glycerol-rich and record their responses. Haloarchaea used for this work included Hbt. salinarum and isolate DV582A-1 (genus Haloterrigena sub-cultured from 34 kyear Death Valley salt. Hbt. salinarum and DV582A-1 reacted to nutrient limitation with morphological and population changes. Starved populations increased and most cells converted from rods to small cocci within 56 days of nutrient deprivation. The exact timing of starvation adaptations and the physical transformations differed between species, populations of the same species, and cells of the same population. This is the first study to report the timing of starvation strategies for Hbt. salinarum and DV582A-1. The morphological states in these experiments may allow differentiation between cells trapped with adequate nutrients (represented here by early stages in nutrient-rich media from cells trapped without nutrients (represented here by experimental starvation in ancient salt. The hypothesis that glycerol, leaked from Dunaliella, provides nutrients for the survival of haloarchaea trapped in fluid inclusions in ancient halite, is also tested. Hbt. salinarum and DV582A-1 were exposed to a mixture of lysed and intact Dunaliella for 56 days. The ability of these organisms to utilize glycerol from Dunaliella cells was assessed by documenting population growth, cell length, and cell morphology. Hbt. salinarum

  5. Survival of adult martens in Northern Wisconsin

    Science.gov (United States)

    Nicholas P. McCann; Patrick A. Zollner; Jonathan H. Gilbert

    2010-01-01

    Low adult marten (Martes americana) survival may be one factor limiting their population growth >30 yr after their reintroduction in Wisconsin, USA. We estimated annual adult marten survival at 0.81 in northern Wisconsin, with lower survival during winter (0.87) than summer-fall (1.00). Fisher (Martes pennanti) and raptor kills...

  6. Long-term survival after perforated diverticulitis

    NARCIS (Netherlands)

    J. Vermeulen (Jan); M.P. Gosselink (Martijn Pieter); W.C.J. Hop (Wim); E. van der Harst (Erwin); B.E. Hansen (Bettina); G.H.H. Mannaerts (Guido); P-P. Coene (Peter Paul); W.F. Weidema (Wibo); J.F. Lange (Johan)

    2011-01-01

    textabstractAim: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. Method: All patients

  7. Clustered survival data with left-truncation

    DEFF Research Database (Denmark)

    Eriksson, Frank; Martinussen, Torben; Scheike, Thomas H.

    2015-01-01

    Left-truncation occurs frequently in survival studies, and it is well known how to deal with this for univariate survival times. However, there are few results on how to estimate dependence parameters and regression effects in semiparametric models for clustered survival data with delayed entry...

  8. 46 CFR 133.105 - Survival craft.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Survival craft. 133.105 Section 133.105 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS LIFESAVING SYSTEMS Requirements for All OSVs § 133.105 Survival craft. (a) Each survival craft must be approved and equipped as...

  9. 46 CFR 199.201 - Survival craft.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft. 199.201 Section 199.201 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.201 Survival craft. (a) Each survival craft must be approved and equipped as follows: (1) Each lifeboat must be...