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Sample records for compound improves survival

  1. Lithium Improves Survival of PC12 Pheochromocytoma Cells in High-Density Cultures and after Exposure to Toxic Compounds

    Directory of Open Access Journals (Sweden)

    Cinzia Fabrizi

    2014-01-01

    Full Text Available Autophagy is an evolutionary conserved mechanism that allows for the degradation of long-lived proteins and entire organelles which are driven to lysosomes for digestion. Different kinds of stressful conditions such as starvation are able to induce autophagy. Lithium and rapamycin are potent autophagy inducers with different molecular targets. Lithium stimulates autophagy by decreasing the intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts through the inhibition of the mammalian target of rapamycin (mTOR. The correlation between autophagy and cell death is still a matter of debate especially in transformed cells. In fact, the execution of autophagy can protect cells from death by promptly removing damaged organelles such as mitochondria. Nevertheless, an excessive use of the autophagic machinery can drive cells to death via a sort of self-cannibalism. Our data show that lithium (used within its therapeutic window stimulates the overgrowth of the rat Pheochromocytoma cell line PC12. Besides, lithium and rapamycin protect PC12 cells from toxic compounds such as thapsigargin and trimethyltin. Taken together these data indicate that pharmacological activation of autophagy allows for the survival of Pheochromocytoma cells in stressful conditions such as high-density cultures and exposure to toxins.

  2. Improving fish survival through turbines

    International Nuclear Information System (INIS)

    Ferguson, J.W.

    1993-01-01

    Much of what is known about fish passage through hydroturbines has been developed by studying migratory species of fish passing through large Kaplan turbine units. A review of the literature on previous fish passage research presented in the accompanying story illustrates that studies have focused on determining mortality levels, rather than identifying the causal mechanism involved. There is a need for understanding how turbine designs could be altered to improve fish passage conditions, how to retrofit existing units, and how proposed hydro plant operational changes may affect fish survival. The US Army Corps of Engineers has developed a research program to define biologically based engineering criteria for improving fish passage conditions. Turbine designs incorporating these criteria can be evaluated for their effects on fish survival, engineering issues, costs, and power production. The research program has the following objectives: To gain a thorough knowledge of the mechanisms of fish mortality; To define the biological sensitivities of key fish species to these mechanisms of mortality; To develop new turbine design criteria to reduce fish mortality; To construct prototype turbine designs, and to test these designs for fish passage, hydro-mechanical operation, and power production; and To identify construction and power costs associated with new turbine designs

  3. Improving Survival in Decompensated Cirrhosis

    Directory of Open Access Journals (Sweden)

    Amar Nath Mukerji

    2012-01-01

    Full Text Available Mortality in cirrhosis is consequent of decompensation, only treatment being timely liver transplantation. Organ allocation is prioritized for the sickest patients based on Model for End Stage Liver Disease (MELD score. In order to improve survival in patients with high MELD score it is imperative to preserve them in suitable condition till transplantation. Here we examine means to prolong life in high MELD score patients till a suitable liver is available. We specially emphasize protection of airways by avoidance of sedatives, avoidance of Bilevel Positive Airway Pressure, elective intubation in grade III or higher encephalopathy, maintaining a low threshold for intubation with lesser grades of encephalopathy when undergoing upper endoscopy or colonoscopy as pre transplant evaluation or transferring patient to a transplant center. Consider post-pyloric tube feeding in encephalopathy to maintain muscle mass and minimize risk of aspiration. In non intubated and well controlled encephalopathy, frequent physical mobility by active and passive exercises are recommended. When renal replacement therapy is needed, night-time Continuous Veno-Venous Hemodialysis may be useful in keeping the daytime free for mobility. Sparing and judicious use of steroids needs to be borne in mind in treatment of ARDS and acute hepatitis from alcohol or autoimmune process.

  4. Improved survival after rectal cancer in Denmark

    DEFF Research Database (Denmark)

    Bülow, S; Harling, H; Iversen, L H

    2010-01-01

    Objective In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients...... treated from 1994 to 2006. Method The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. Results A total of 10 632 patients were...

  5. Survival of added bacterial species and metabolism of toxic compounds in natural environments

    International Nuclear Information System (INIS)

    King, V.M.

    1987-01-01

    Bacteria able to degrade either 2,4-dichlorophenol (DCP) or phenanthrene (PHEN) were isolated from polluted freshwater environments. Two isolates able to degrade each compound were tested for mineralization with a sensitive 14 C assay and for survival in lake water and sewage using a selective medium. One DCP isolate was identified as Alcaligenes paradoxus and the other as Alcaligenes sp. One PHEN isolate was identified as Pseudomonas fluorescens and the other as Pseudomonas sp. All four isolates survived and grew in sterile environments which indicated that starvation would not be a factor in survival of these strains. The number of organisms declined immediately in number in nonsterile lake water. However, they did survive or even grow in nonsterile sewage for a short period before declining in number. Biotic factors appeared to be influential for survival and mineralization of target compounds in many environments. The removal of protozoa, which prey on bacteria, improved survival of the added cells, but had no influence on the mineralization of 10 μg DCP/L. In comparison, degradation of 10 and 25 mg DCP/L stopped after a few days. Yeast nitrogen base appeared to overcome the lack of nutrient regeneration, a function attributed to protozoa. The additional nutrients increased toxicant mineralization, especially when seeded with appropriate species. Thus, protozoa may limit growth of added cells but appear to be needed for mineralization of higher concentrations of DCP

  6. How can survival processing improve memory encoding?

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    Luo, Meng; Geng, Haiyan

    2013-11-01

    We investigated the psychological mechanism of survival processing advantage from the perspective of false memory in two experiments. Using a DRM paradigm in combination with analysis based on signal detection theory, we were able to separately examine participants' utilization of verbatim representation and gist representation. Specifically, in Experiment 1, participants rated semantically related words in a survival scenario for a survival condition but rated pleasantness of words in the same DRM lists for a non-survival control condition. The results showed that participants demonstrated more gist processing in the survival condition than in the pleasantness condition; however, the degree of item-specific processing in the two encoding conditions did not significantly differ. In Experiment 2, the control task was changed to a category rating task, in which participants were asked to make category ratings of words in the category lists. We found that the survival condition involved more item-specific processing than did the category condition, but we found no significant difference between the two encoding conditions at the level of gist processing. Overall, our study demonstrates that survival processing can simultaneously promote gist and item-specific representations. When the control tasks only promoted either item-specific representation or gist representation, memory advantages of survival processing occurred.

  7. Improvements in or relating to compounds

    International Nuclear Information System (INIS)

    Woodhead, J.L.

    1983-01-01

    The invention provides a process for the preparation of a dispersible product containing a cerium compound which comprises heating a cerium (IV) oxide hydrate in the presence of a salt to cause deaggregation of aggregated crystallites in the cerium (IV) oxide hydrate and produce a dispersible product containing a cerium compound. (author)

  8. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Paximadis, Peter, E-mail: ppaximad@med.wayne.edu [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States); Yoo, George; Lin, Ho-Sheng; Jacobs, John [Department of Otolaryngology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Sukari, Ammar [Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Dyson, Greg [Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Christensen, Michael; Kim, Harold [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  9. Dying scenarios improve recall as much as survival scenarios.

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    Burns, Daniel J; Hart, Joshua; Kramer, Melanie E

    2014-01-01

    Merely contemplating one's death improves retention for entirely unrelated material learned subsequently. This "dying to remember" effect seems conceptually related to the survival processing effect, whereby processing items for their relevance to being stranded in the grasslands leads to recall superior to that of other deep processing control conditions. The present experiments directly compared survival processing scenarios with "death processing" scenarios. Results showed that when the survival and dying scenarios are closely matched on key dimensions, and possible congruency effects are controlled, the dying and survival scenarios produced equivalently high recall levels. We conclude that the available evidence (cf. Bell, Roer, & Buchner, 2013; Klein, 2012), while not definitive, is consistent with the possibility of overlapping mechanisms.

  10. Chemical predictive modelling to improve compound quality.

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    Cumming, John G; Davis, Andrew M; Muresan, Sorel; Haeberlein, Markus; Chen, Hongming

    2013-12-01

    The 'quality' of small-molecule drug candidates, encompassing aspects including their potency, selectivity and ADMET (absorption, distribution, metabolism, excretion and toxicity) characteristics, is a key factor influencing the chances of success in clinical trials. Importantly, such characteristics are under the control of chemists during the identification and optimization of lead compounds. Here, we discuss the application of computational methods, particularly quantitative structure-activity relationships (QSARs), in guiding the selection of higher-quality drug candidates, as well as cultural factors that may have affected their use and impact.

  11. Parental care improves offspring survival and growth in burying beetles

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    Eggert; Reinking; MULLER

    1998-01-01

    Burying beetles (genus Nicrophorus) provide elaborate parental care to their offspring. Parental beetles defend a small vertebrate carcass, which constitutes the sole food source for the larvae. They also manipulate the carcass in various ways and directly regurgitate pre-digested carrion to the young. The benefits of carcass manipulation and regurgitation have been the subject of a few small-scale studies that have yielded conflicting results. In this study, we investigated the benefits of these behaviours and tested for possible beneficial effects on larval survival rates and final body mass in N. vespilloides. In this species: (1) larval survival and mass were significantly higher in broods receiving parental care throughout larval development on the carcass than in broods developing in the absence of adults; (2) parental presence immediately subsequent to larval hatching greatly improved larval survival rates; (3) continued parental presence for several days further improved larval growth, leading to a greater final mass of individual larvae; (4) larval survival and growth were improved by parental preparation of carcasses and by an excision made in the integument of the carcass surface by the parents that allows the larvae ready access to their food; (5) positive effects of parental feeding on larval survival and growth were not mediated by the transfer of symbionts. Copyright 1998 The Association for the Study of Animal Behaviour.

  12. Improved survival in HIV treatment programs in Asia

    Science.gov (United States)

    De La Mata, Nicole L; Kumarasamy, Nagalingeswaran; Khol, Vohith; Ng, Oon Tek; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Durier, Nicolas; Law, Matthew

    2016-01-01

    Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (pAsia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time. PMID:26961354

  13. Adjuvant Medications That Improve Survival after Locoregional Therapy.

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    Boas, F Edward; Ziv, Etay; Yarmohammadi, Hooman; Brown, Karen T; Erinjeri, Joseph P; Sofocleous, Constantinos T; Harding, James J; Solomon, Stephen B

    2017-07-01

    To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  14. Cyber Foraging for Improving Survivability of Mobile Systems

    Science.gov (United States)

    2016-02-10

    Cyber-Foraging for Improving Survivability of Mobile Systems Sebastián Echeverría ( Universidad de los Andes) Grace A. Lewis James Root Ben...NUMBERS FA8721-05-C-0003 6. AUTHOR(S) Sebastián Echeverría ( Universidad de los Andes), Grace A. Lewis, James Root, & Ben Bradshaw 7. PERFORMING

  15. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    International Nuclear Information System (INIS)

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-01-01

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16 INK , p21 and p19 ARF . VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI

  16. Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?

    Science.gov (United States)

    Davenport, Andrew

    2015-01-01

    The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over-hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area. PMID:25385441

  17. Resveratrol: A Multifunctional Compound Improving Endothelial Function

    OpenAIRE

    Li, Huige; F?rstermann, Ulrich

    2009-01-01

    The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

  18. Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

    Science.gov (United States)

    Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

    2017-01-06

    Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor -alpha (TNF-α), prostaglandin E₂ (PGE₂) , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

  19. Combining Gene Signatures Improves Prediction of Breast Cancer Survival

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    Zhao, Xi; Naume, Bjørn; Langerød, Anita; Frigessi, Arnoldo; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Lingjærde, Ole Christian

    2011-01-01

    Background Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123) and test set (n = 81), respectively. Gene sets from eleven previously published gene signatures are included in the study. Principal Findings To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014). Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001). The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. Conclusion Combining the predictive strength of multiple gene signatures improves prediction of breast

  20. Combining gene signatures improves prediction of breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  1. [Medulloblastoma: improved survival in recent decades. Unicentric experience].

    Science.gov (United States)

    Igual Estellés, Lucía; Berlanga Charriel, Pablo; Cañete Nieto, Adela

    2017-01-01

    The aim of the study is to analyse variations in the treatment of medulloblastoma, the most common childhood brain tumour, and its impact on survival over the past two decades, as well as its clinical and pathological features. Survival analysis of all patients under 14 years old diagnosed with medulloblastoma between January 1990 and December 2013 in a Paediatric Oncology Unit. Sixty-three patients were diagnosed and treated for medulloblastoma, with a median follow-up of 5.1 years (range 0.65-21.7 years). The overall survival (OS) at 3 and 5 years was 66±13% and 55±14%, respectively. The OS at 5 years was 44%±25% in patients diagnosed in the 1990's, showing an increase to 70%±23% (p=0.032) since 2000. Clinical prognosis factors were included in the logistic regression model: age (p=0.008), presence of metastases and/or residual tumour (p=0.007), and receiving chemotherapy with radiotherapy after surgery (p=0.008). Statistically significant differences were observed for all of them. In our institution there has been a significant increase in medulloblastoma survival in the last decades. Multivariate analysis showed that this improvement was not related to the date of diagnosis, but with the introduction of chemotherapy in adjuvant treatment. This study confirmed that clinical factors significantly associated with worse outcome were age and presence of metastases at diagnosis. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Home visit program improves technique survival in peritoneal dialysis.

    Science.gov (United States)

    Martino, Francesca; Adıbelli, Z; Mason, G; Nayak, A; Ariyanon, W; Rettore, E; Crepaldi, Carlo; Rodighiero, Mariapia; Ronco, Claudio

    2014-01-01

    Peritoneal dialysis (PD) is a home therapy, and technique survival is related to the adherence to PD prescription at home. The presence of a home visit program could improve PD outcomes. We evaluated its effects on clinical outcome during 1 year of follow-up. This was a case-control study. The case group included all 96 patients who performed PD in our center on January 1, 2013, and who attended a home visit program; the control group included all 92 patients who performed PD on January 1, 2008. The home visit program consisted of several additional visits to reinforce patients' confidence in PD management in their own environment. Outcomes were defined as technique failure, peritonitis episode, and hospitalization. Clinical and dialysis features were evaluated for each patient. The case group was significantly older (p = 0.048), with a lower grade of autonomy (p = 0.033), but a better hemoglobin level (p = 0.02) than the control group. During the observational period, we had 11 episodes of technique failure. We found a significant reduction in the rate of technique failure in the case group (p = 0.004). Furthermore, survival analysis showed a significant extension of PD treatment in the patients supported by the home visit program (52 vs. 48.8 weeks, p = 0.018). We did not find any difference between the two groups in terms of peritonitis and hospitalization rate; however, trends toward a reduction of Gram-positive peritonitis rates as well as prevalence and duration of hospitalization related to PD problems were identified in the case group. The retrospective nature of the analysis was a limitation of this study. The home visit program improves the survival of PD patients and could reduce the rate of Gram-positive peritonitis and hospitalization. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=365168.

  3. In vitro Spatial Compound Scanning for Improved Visualization of Atherosclerosis

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh; Wilhjelm, Jens E.; Sillesen, Henrik

    2000-01-01

    A new off-line multiangle ultrasound (US) compound scanner has been built with the purpose of investigating possible improvements in visualization of vascular structure. Images of two formalin-fixed human atherosclerotic plaques removed by carotid endarterectomy were recorded from seven insonific...

  4. Improving rubber concrete by waste organic sulfur compounds.

    Science.gov (United States)

    Chou, Liang-Hisng; Lin, Chun-Nan; Lu, Chun-Ku; Lee, Cheng-Haw; Lee, Maw-Tien

    2010-01-01

    In this study, the use of crumb tyres as additives to concrete was investigated. For some time, researchers have been studying the physical properties of concrete to determine why the inclusion of rubber particles causes the concrete to degrade. Several methods have been developed to improve the bonding between rubber particles and cement hydration products (C-S-H) with the hope of creating a product with an improvement in mechanical strength. In this study, the crumb tyres were treated with waste organic sulfur compounds from a petroleum refining factory in order to modify their surface properties. Organic sulfur compounds with amphiphilic properties can enhance the hydrophilic properties of the rubber and increase the intermolecular interaction forces between rubber and C-S-H. In the present study, a colloid probe of C-S-H was prepared to measure these intermolecular interaction forces by utilizing an atomic force microscope. Experimental results showed that rubber particles treated with waste organic sulfur compounds became more hydrophilic. In addition, the intermolecular interaction forces increased with the adsorption of waste organic sulfur compounds on the surface of the rubber particles. The compressive, tensile and flexural strengths of concrete samples that included rubber particles treated with organic sulfur compound also increased significantly.

  5. Improved quality control of carbon-14 labelled compounds

    International Nuclear Information System (INIS)

    Leonhardt, J.W.; Fuchs, P.; Standtke, K.

    1997-01-01

    IUT Ltd is a producer of carbon-14 labelled organic compounds like benzene, methanol, phenol, formaldehyde, Na-acetates and also special ordered compounds. The quality control of these compounds is carried out by means of HPLC and GC-MS due to chemical purity. Molar activity was determined by Liquid Scintillation Counting and HPLC being equipped by a radioactivity detector. Unfortunately the accuracy of the activity determination was arrived only ±4% relatively. This error is too high because of the large dilution factors. In respect of the IUT accreditation as an analytical laboratory in Germany the accuracy had to be improved remarkably. Therefore the GC-MS-determination of molar activities of labelled compounds is used as the 14 C-labelled compound. A special evaluation code is used to determine the enrichment values relative to the unlabelled molecules. Taking into account the results of GC-MS the accuracy of molar activity determination is improved to ±2%. The spectra evaluation is demonstrated and some examples are discussed

  6. Formation of heavy compound nuclei, their survival and correlation with longtime-scale fission

    International Nuclear Information System (INIS)

    Karamyan, S.A.; Yakushev, A.B.

    2006-01-01

    Fusion of two massive nuclei with formation of super-heavy compound nucleus (CN) is driven by the potential energy gradient, as follows from the analysis of nuclear reaction cross-sections. The conservative energy of the system is deduced in simple approximation using regularized nuclear mass and interaction barrier values. Different reactions for the synthesis of Z c 110-118 nuclei are compared and the favourable conditions are found for fusion of the stable (W-Pt) isotopes with radioactive fission fragment projectiles, like 94 Kr or 100 Sr. Thus, the cold fusion method can be extended for a synthesis of elements with Z > 113. Survival of the evaporation residue is defined by the neutron-to-fission probability ratio and by the successful emission of gammas at the final step of the reaction. Numerical estimates are presented. Fixation of evaporation residue products must correlate with longtime-scale fission and available experimental results are discussed

  7. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    International Nuclear Information System (INIS)

    Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

    2013-01-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults

  8. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit Kurshan [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wexler, Leonard H. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Singer, Samuel [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Keohan, Mary Louise [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne, E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-05-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

  9. Survival and compound nucleus probability of super heavy element Z = 117

    Energy Technology Data Exchange (ETDEWEB)

    Manjunatha, H.C. [Government College for Women, Department of Physics, Kolar, Karnataka (India); Sridhar, K.N. [Government First grade College, Department of Physics, Kolar, Karnataka (India)

    2017-05-15

    As a part of a systematic study for predicting the most suitable projectile-target combinations for heavy-ion fusion experiments in the synthesis of {sup 289-297}Ts, we have calculated the transmission probability (T{sub l}), compound nucleus formation probabilities (P{sub CN}) and survival probability (P{sub sur}) of possible projectile-target combinations. We have also studied the fusion cross section, survival cross section and fission cross sections for different projectile-target combination of {sup 289-297}Ts. These theoretical parameters are required before the synthesis of the super heavy element. The calculated probabilities and cross sections show that the production of isotopes of the super heavy element with Z = 117 is strongly dependent on the reaction systems. The most probable reactions to synthetize the super heavy nuclei {sup 289-297}Ts are worked out and listed explicitly. We have also studied the variation of P{sub CN} and P{sub sur} with the mass number of projectile and target nuclei. This work is useful in the synthesis of the super heavy element Z = 117. (orig.)

  10. Survival and compound nucleus probability of super heavy element Z = 117

    International Nuclear Information System (INIS)

    Manjunatha, H.C.; Sridhar, K.N.

    2017-01-01

    As a part of a systematic study for predicting the most suitable projectile-target combinations for heavy-ion fusion experiments in the synthesis of "2"8"9"-"2"9"7Ts, we have calculated the transmission probability (T_l), compound nucleus formation probabilities (P_C_N) and survival probability (P_s_u_r) of possible projectile-target combinations. We have also studied the fusion cross section, survival cross section and fission cross sections for different projectile-target combination of "2"8"9"-"2"9"7Ts. These theoretical parameters are required before the synthesis of the super heavy element. The calculated probabilities and cross sections show that the production of isotopes of the super heavy element with Z = 117 is strongly dependent on the reaction systems. The most probable reactions to synthetize the super heavy nuclei "2"8"9"-"2"9"7Ts are worked out and listed explicitly. We have also studied the variation of P_C_N and P_s_u_r with the mass number of projectile and target nuclei. This work is useful in the synthesis of the super heavy element Z = 117. (orig.)

  11. Chronic effects of nitrogenous compounds on survival and growth of juvenile pink shrimp

    Directory of Open Access Journals (Sweden)

    W. J. Wasielesky

    Full Text Available Abstract In response to growing worldwide market demand, intensive shrimp farming, based on high feed, has developed over the past decade. The nitrogenous compounds mainly generated by animal excretion can cause deterioration of water quality and produce chronic or even acute toxicity to aquatic animals. As prevention, theoretical safety levels have been estimated from acute toxicity tests and they are traditionally used to prevent toxic effects on biota. However, are those concentrations of nitrogenous compounds really safe to Farfantepenaeus paulensis? The current study aimed to investigate the lethal and sublethal effects of ammonia, nitrite and nitrate to juvenile F. paulensis based on safety levels. Each experiment was performed independently in 100 L tanks for 30 days. The survival rates and wet weight of all shrimps were recorded every 10 days. The concentrations tested for ammonia, nitrite and nitrate were respectively: treatment “T1/4”, a quarter of the safety level (0.91 mg/L TA-N, 2.55 mg/L NO2--N and 80.7 mg/L NO3--N; treatment “TSL”, the safety level (3.65 mg/L TA-N, 10.2 mg/L NO2--N and 323 mg/L NO3--N; and treatment “T2X”, twice the safety level (7.30 mg/L TA-N, 20.4 mg/L NO2--N and 646 mg/L NO3--N. For F. paulensis cultivation, the real safety level for nitrite was estimated to be 2.55 mg/L NO2--N. For ammonia and nitrate, the recommended concentrations were <0.91 mg/L TA-N corresponding to 0.045 mg/L NH3-N and <80.7 mg/L NO3--N, respectively.

  12. Chronic effects of nitrogenous compounds on survival and growth of juvenile pink shrimp.

    Science.gov (United States)

    Wasielesky, W J; Poersch, L H; Martins, T G; Miranda-Filho, K C

    2017-01-01

    In response to growing worldwide market demand, intensive shrimp farming, based on high feed, has developed over the past decade. The nitrogenous compounds mainly generated by animal excretion can cause deterioration of water quality and produce chronic or even acute toxicity to aquatic animals. As prevention, theoretical safety levels have been estimated from acute toxicity tests and they are traditionally used to prevent toxic effects on biota. However, are those concentrations of nitrogenous compounds really safe to Farfantepenaeus paulensis? The current study aimed to investigate the lethal and sublethal effects of ammonia, nitrite and nitrate to juvenile F. paulensis based on safety levels. Each experiment was performed independently in 100 L tanks for 30 days. The survival rates and wet weight of all shrimps were recorded every 10 days. The concentrations tested for ammonia, nitrite and nitrate were respectively: treatment "T1/4", a quarter of the safety level (0.91 mg/L TA-N, 2.55 mg/L NO2--N and 80.7 mg/L NO3--N); treatment "TSL", the safety level (3.65 mg/L TA-N, 10.2 mg/L NO2--N and 323 mg/L NO3--N); and treatment "T2X", twice the safety level (7.30 mg/L TA-N, 20.4 mg/L NO2--N and 646 mg/L NO3--N). For F. paulensis cultivation, the real safety level for nitrite was estimated to be 2.55 mg/L NO2--N. For ammonia and nitrate, the recommended concentrations were <0.91 mg/L TA-N corresponding to 0.045 mg/L NH3-N and <80.7 mg/L NO3--N, respectively.

  13. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K

    2012-01-01

    PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved...

  14. Improving survival of culture bacteria in frozen desserts by microentrapment.

    Science.gov (United States)

    Sheu, T Y; Marshall, R T; Heymann, H

    1993-07-01

    Lactobacillus bulgaricus cells were entrapped in beads of calcium alginate and evaluated for their ability to survive freezing processes. Cells survived freezing (without agitation) in ice milk mix much better than in distilled water, and more entrapped cells survived than did cells that were not entrapped. Glycerol and mannitol were cryoprotective, but glucose was not, when each was added (6%) separately to the beads. Entrapment protected the lactobacilli in batch frozen and continuously frozen ice milk mixes. The percentage of survival for entrapped and unentrapped cells in continuously frozen ice milk approximated 90 and 40%, respectively. Lactobacilli survived better in beads with mean diameters > 30 microns than in those averaging 15 microns. Addition of entrapped lactobacilli had no measurable effect on the sensory characteristics of the ice milk.

  15. Temozolomide during radiotherapy of glioblastoma multiforme. Daily administration improves survival

    Energy Technology Data Exchange (ETDEWEB)

    Nachbichler, Silke Birgit; Schupp, Gabi; Ballhausen, Hendrik; Niyazi, Maximilian; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany)

    2017-11-15

    Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m{sup 2}) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy. Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1-year survival rates were 33, 52, and 64%, respectively. Kaplan-Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept. Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration. (orig.) [German] Eine Temozolomid-(TMZ-)basierte Radiochemotherapie ist der gegenwaertige Goldstandard in der Behandlung von neu diagnostizierten Glioblastomen. Daten bezueglich des Einflusses der TMZ-Dosisdichte waehrend der Radiochemotherapie sind derzeit nicht vorhanden. Wir haben retrospektiv die Ergebnisse von Patienten verglichen, die entweder kein TMZ, TMZ zur Strahlentherapie nur an Bestrahlungstagen oder TMZ konstant 7 Tage/Woche erhalten hatten. Von 2002-2012 bekamen insgesamt 432 Patienten mit

  16. Improved survival using specialized multidisciplinary board in sarcoma patients.

    Science.gov (United States)

    Blay, J-Y; Soibinet, P; Penel, N; Bompas, E; Duffaud, F; Stoeckle, E; Mir, O; Adam, J; Chevreau, C; Bonvalot, S; Rios, M; Kerbrat, P; Cupissol, D; Anract, P; Gouin, F; Kurtz, J-E; Lebbe, C; Isambert, N; Bertucci, F; Toumonde, M; Thyss, A; Piperno-Neumann, S; Dubray-Longeras, P; Meeus, P; Ducimetière, F; Giraud, A; Coindre, J-M; Ray-Coquard, I; Italiano, A; Le Cesne, A

    2017-11-01

    Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB. © The Author 2017. 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.

  17. Radium-223 Improves Survival in Patients with Advanced Prostate Cancer

    Science.gov (United States)

    ... This well-executed study shows a clear survival benefit in patients who had received the treatments that were available when the study was conducted, including standard chemotherapy,” said Bhupinder Mann, MBBS, of NCI’s Division of ...

  18. The Impact and Oxidation Survival of Selected Meteoritic Compounds: Signatures of Asteroid Organic Material on Planetary Surfaces

    Science.gov (United States)

    Cooper, George; Horz, Fred; Oleary, Alanna; Chang, Sherwood

    2013-01-01

    Polar, non-volatile organic compounds may be present on the surfaces (or near surfaces) of multiple Solar System bodies. If found, by current or future missions, it would be desirable to determine the origin(s) of such compounds, e.g., asteroidal or in situ. To test the possible survival of meteoritic compounds both during impacts with planetary surfaces and under subsequent (possibly) harsh ambient conditions, we subjected known meteoritic compounds to relatively high impact-shock pressures and/or to varying oxidizing/corrosive conditions. Tested compounds include sulfonic and phosphonic acids (S&P), polyaromatic hydrocarbons (PAHs) amino acids, keto acids, dicarboxylic acids, deoxy sugar acids, and hydroxy tricarboxylic acids (Table 1). Meteoritic sulfonic acids were found to be relatively abundant in the Murchison meteorite and to possess unusual S-33 isotope anomalies (non mass-dependent isotope fractionations). Combined with distinctive C-S and C-P bonds, the S&P are potential signatures of asteroidal organic material.

  19. Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!

    DEFF Research Database (Denmark)

    Hailer, N. P.; Lazarinis, S.; MaKela, K. T.

    2015-01-01

    Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients and m...

  20. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

    NARCIS (Netherlands)

    Lutgens, M. W. M. D.; Oldenburg, B.; Siersema, P. D.; van Bodegraven, A. A.; Dijkstra, G.; Hommes, D. W.; de Jong, D. J.; Stokkers, P. C. F.; van der Woude, C. J.; Vleggaar, F. P.

    2009-01-01

    Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. The aim of this study was to compare tumour stage and survival of IBD

  1. Improved survival of newborns receiving leukocyte transfusions for sepsis

    International Nuclear Information System (INIS)

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-01-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions

  2. Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

    NARCIS (Netherlands)

    Ritfeld, G.J.; Nandoe Tewarie, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

    2010-01-01

    We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

  3. Improvements in or relating to calcining reducible compounds

    International Nuclear Information System (INIS)

    Cole, E.A.; Peterson, R.S.

    1974-01-01

    Apparatus is described for calcining compounds of uranium compounds to temperatures of up to about 1000 0 C to produce UO 2 powders of uniform quality and having an oxygen content of less than 2.2 atoms of oxygen per atom of uranium. The apparatus comprises discharge and cooling means having an inlet end operatively joined with an air tight seal to a rotating Kiln to receive hot UO 2 powder therefrom without contact with air. (author)

  4. Assessment by survival analysis of the radioprotective properties of propolis and its polyphenolic compounds

    International Nuclear Information System (INIS)

    Orsolic, N.; Benkovic, V.; Horvat-Knezevic, A.; Basic, I.; Kopjar, N.; Kosalec, I.; Bakmaz, M.; Mihaljevic, Z.; Bendelja, K.

    2007-01-01

    The radioprotective effects of propolis and polyphenolic compounds from propolis on the radiation-induced mortality of mice exposed to 9 Gy of γ-irradiation were studied. Intraperitoneal (i.p.) treatment of mice at doses of 100 mgkg -1 body weight of propolis (water or ethanolic extract; water-soluble derivative of propolis (WSDP) or ethanolic extract of propolis (EEP)) or its polyphenolic compounds (quercetin, naringin caffeic acid, chrysin) consecutively for 3 d before irradiation, delayed the onset of mortality and reduced the symptoms of radiation sickness. All test compounds provided protection against hematopoietic death (death within 30 d after irradiation). The greatest protection was achieved with quercetin; the number of survivors at the termination of the experiment was 63%. According to statistical analyses by the Kaplan-Meier method and the log-rank test, a significant difference between test components and control was found (p<0.001). Treatment with test components after lethal irradiation was ineffective. These results suggest that propolis and its polyphenolic compounds given to mice before irradiation protect mice from the lethal effects of whole-body irradiation. (author)

  5. Data-Driven Derivation of an "Informer Compound Set" for Improved Selection of Active Compounds in High-Throughput Screening.

    Science.gov (United States)

    Paricharak, Shardul; IJzerman, Adriaan P; Jenkins, Jeremy L; Bender, Andreas; Nigsch, Florian

    2016-09-26

    Despite the usefulness of high-throughput screening (HTS) in drug discovery, for some systems, low assay throughput or high screening cost can prohibit the screening of large numbers of compounds. In such cases, iterative cycles of screening involving active learning (AL) are employed, creating the need for smaller "informer sets" that can be routinely screened to build predictive models for selecting compounds from the screening collection for follow-up screens. Here, we present a data-driven derivation of an informer compound set with improved predictivity of active compounds in HTS, and we validate its benefit over randomly selected training sets on 46 PubChem assays comprising at least 300,000 compounds and covering a wide range of assay biology. The informer compound set showed improvement in BEDROC(α = 100), PRAUC, and ROCAUC values averaged over all assays of 0.024, 0.014, and 0.016, respectively, compared to randomly selected training sets, all with paired t-test p-values agnostic fashion. This approach led to a consistent improvement in hit rates in follow-up screens without compromising scaffold retrieval. The informer set is adjustable in size depending on the number of compounds one intends to screen, as performance gains are realized for sets with more than 3,000 compounds, and this set is therefore applicable to a variety of situations. Finally, our results indicate that random sampling may not adequately cover descriptor space, drawing attention to the importance of the composition of the training set for predicting actives.

  6. Role of TIPS in Improving Survival of Patients with Decompensated Liver Disease

    Directory of Open Access Journals (Sweden)

    Sundeep J. Punamiya

    2011-01-01

    Full Text Available Liver cirrhosis is associated with higher morbidity and reduced survival with appearance of portal hypertension and resultant decompensation. Portal decompression plays a key role in improving survival in these patients. Transjugular intrahepatic portosystemic shunts are known to be efficacious in reducing portal venous pressure and control of complications such as variceal bleeding and ascites. However, they have been associated with significant problems such as poor shunt durability, increased encephalopathy, and unchanged survival when compared with conservative treatment options. The last decade has seen a significant improvement in these complications, with introduction of covered stents, better selection of patients, and clearer understanding of procedural end-points. Use of TIPS early in the period of decompensation also appears promising in further improvement of survival of cirrhotic patients.

  7. Improved survival in HIV-infected persons: consequences and perspectives

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Hansen, Ann-Brit Eg; Gerstoft, Jan

    2007-01-01

    -infected individual to be 39 years. The prospect of a near-normal life expectancy has implications for the HIV-infected persons as well as for the handling of the disease in the healthcare system. The patients can now on a long-term perspective plan their professional career, join a pension plan and start a family....... Further, they may expect to be treated equally with other members of society with respect to access to mortgage, health insurance and life insurance. As the infected population ages, more patients will contract age-related diseases, and the disease burden on some individuals may even come to be dominated......, improved drug adherence, prevention and treatment of HIV-unrelated co-morbidity and collaboration with other medical specialists to treat an ageing co-morbidity-acquiring HIV population....

  8. Improvement of child survival in Mexico: the diagonal approach.

    Science.gov (United States)

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Oláiz, Gustavo; Partida, Virgilio; García-García, Lourdes; Valdespino, José Luis

    2006-12-02

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  9. [Improvement of child survival in Mexico: the diagonal approach].

    Science.gov (United States)

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Olaiz, Gustavo; Partida, Virgilio; García-García, Ma de Lourdes; Valdespino, José Luis

    2007-01-01

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  10. Using Online Compound Interest Tools to Improve Financial Literacy

    Science.gov (United States)

    Hubbard, Edward; Matthews, Percival; Samek, Anya

    2016-01-01

    The widespread use of personal computing presents the opportunity to design educational materials that can be delivered online, potentially addressing low financial literacy. The authors developed and evaluated three different educational tools focusing on interest compounding. In the authors' laboratory experiment, individuals were randomized to…

  11. Pioglitazone Improves Survival In Patients With Cancer: The Hypothesis

    Directory of Open Access Journals (Sweden)

    Banshi Saboo

    2015-12-01

    Full Text Available Pioglitazone is currently the only thiazolidinedione approved by regulatory agencies worldwide for the treatment of type 2 diabetes mellitus (T2DM. The use of pioglitazone in patients with T2DM has been limited because earlier studies showed moderate weight gain and an increased incidence of heart failure, osteoporotic fractures, and bladder cancer. However, new studies have shown that pioglitazone improves both systolic and diastolic left ventricular function and that there is no association between pioglitazone and bladder cancer. Furthermore, pioglitazone is associated with a reduced risk of all-cause mortality in patients with T2DM. Pioglitazone was also found to reduce the incidence of lung, head and neck, breast, colorectal, and hepatocellular cancer. There is tremendous preclinical evidence that links thiazolidinediones with anti-cancer effects. Three possible mechanisms of anti-proliferative effects induced by peroxisome proliferator activated receptor gamma (PPARG agonists emerge: 1 activation of PPARG and epidermal growth factor receptor, which actives several intracellular pathways involved in carcinogenesis; 2 increase in serum adiponectin levels and decrease in serum leptin levels, which are associated with lower cancer risk and more favorable outcomes in patients with cancer; 3 modulate insulin-like growth factor 1 (IGF-1 receptor signaling by decreasing IGF-1 levels and increasing the expression of IGF binding protein 1. To date, there are no prospective, placebo-controlled trials that have analyzed the efficacy of pioglitazone in chemotherapy and chemoprevention. Only one ongoing study has shown that pioglitazone has an excellent capability of eradicating quiescent leukemia stem cells in patients with chronic myeloid leukemia and achieving a complete molecular response. Current evidence supports our theory that future case-control studies examining pioglitazone as chemotherapy, or adjuvant chemotherapy, should be performed in

  12. Increasing Winter Maximal Metabolic Rate Improves Intrawinter Survival in Small Birds.

    Science.gov (United States)

    Petit, Magali; Clavijo-Baquet, Sabrina; Vézina, François

    Small resident bird species living at northern latitudes increase their metabolism in winter, and this is widely assumed to improve their chances of survival. However, the relationship between winter metabolic performance and survival has yet to be demonstrated. Using capture-mark-recapture, we followed a population of free-living black-capped chickadees (Poecile atricapillus) over 3 yr and evaluated their survival probability within and among winters. We also measured the size-independent body mass (M s ), hematocrit (Hct), basal metabolic rate (BMR), and maximal thermogenic capacity (Msum) and investigated how these parameters influenced survival within and among winters. Results showed that survival probability was high and constant both within (0.92) and among (0.96) winters. They also showed that while M s , Hct, and BMR had no significant influence, survival was positively related to Msum-following a sigmoid relationship-within but not among winter. Birds expressing an Msum below 1.26 W (i.e., similar to summer levels) had a winter. Our data therefore suggest that black-capped chickadees that are either too slow or unable to adjust their phenotype from summer to winter have little chances of survival and thus that seasonal upregulation of metabolic performance is highly beneficial. This study is the first to document in an avian system the relationship between thermogenic capacity and winter survival, a proxy of fitness.

  13. Low-alcohol Beers: Flavor Compounds, Defects, and Improvement Strategies.

    Science.gov (United States)

    Blanco, Carlos A; Andrés-Iglesias, Cristina; Montero, Olimpio

    2016-06-10

    Beer consumers are accustomed to a product that offers a pleasant and well-defined taste. However, in alcohol-free and alcohol-reduced beers these characteristics are totally different from those in regular beer. Therefore, it is important to evaluate and determine the different flavor compounds that affect organoleptic characteristics to obtain a product that does not contain off-flavors, or taste of grass or wort. The taste defects in alcohol-free beer are mainly attributed to loss of aromatic esters, insufficient aldehydes, reduction or loss of different alcohols, and an indeterminate change in any of its compounds during the dealcoholization process. The dealcoholization processes that are commonly used to reduce the alcohol content in beer are shown, as well as the negative consequences of these processes to beer flavor. Possible strategies to circumvent such negative consequences are suggested.

  14. Are global and regional improvements in life expectancy and in child, adult and senior survival slowing?

    Directory of Open Access Journals (Sweden)

    Ryan J Hum

    Full Text Available Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health-primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.

  15. Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury PRINCIPAL...TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord...care. However, despite these drastic interventions, the cervical injured patient is still susceptible to death due to respiratory complications

  16. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.24 Improved pension...

  17. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

    International Nuclear Information System (INIS)

    Bingham, Brian; Orton, Andrew; Boothe, Dustin; Stoddard, Greg; Huang, Y. Jessica; Gaffney, David K.; Poppe, Matthew M.

    2017-01-01

    Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

  18. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, Brian [Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee (United States); Orton, Andrew; Boothe, Dustin [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Stoddard, Greg [Division of Epidemiology, University of Utah, Salt Lake City, Utah (United States); Huang, Y. Jessica; Gaffney, David K. [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Poppe, Matthew M., E-mail: Matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States)

    2017-04-01

    Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

  19. Survival of Glycolaldehyde and Production of Sugar Compounds via Comet Impact Delivery

    Science.gov (United States)

    Zellner, N.; McCaffrey, V.; Crake, C.; Butler, J.; Robbins, J.; Fodor, A.

    2017-12-01

    Impact experiments using glycolaldehyde (GLA), a two-carbon sugar precursor that has been detected in regions of the interstellar medium and on comets, have been conducted at the Experimental Impact Laboratory at NASA's Johnson Space Center. Samples of GLA and GLA mixed with montmorillonite clays were subjected to the pressure conditions that are found during impact delivery of biomolecules by comets, asteroids, or meteors; pressures ranged from 4.5 GPa to 25 GPa. Results show that large amounts of GLA survived the impacts and moderate amounts of threose, erythrose, and glycolic acid were produced in these impacts. Total amounts are dependent on impact pressure. Ethylene glycol, a reduced variant of GLA that has also been detected in the interstellar medium and on comets, was also produced. The results of these experimental impacts provide evidence that large amounts of GLA, EG, and other biomolecules were available on habitable moons or planets, especially during the era of late heavy bombardment ( 4.2 to 3.7 billion years ago) when life may have been developing on Earth. The presence and availability of these biomolecules, under appropriate conditions, may be important for understanding the origin of life as we know it. Glycolaldehyde in particular, may be an important molecule in the production of ribose, the five-carbon sugar in RNA.

  20. Improving village poultry’s survival rate through community-based poultry health management

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto D.

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of “poultry interest groups” in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due...... to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry’s survival rate...... than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption...

  1. Improving village poultry's survival rate through community-based poultry health management

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto Delphin

    2012-01-01

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of “poultry interest groups” in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due...... to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry's survival rate...... than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption...

  2. Improved survival for rectal cancer compared to colon cancer: the four cohort study.

    Science.gov (United States)

    Buchwald, Pamela; Hall, Claire; Davidson, Callum; Dixon, Liane; Dobbs, Bruce; Robinson, Bridget; Frizelle, Frank

    2018-03-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. This study was undertaken to evaluate survival outcomes and changes of disease outcomes of CRC patients over the last decades. A retrospective analysis of CRC patients in Christchurch was performed in four patient cohorts at 5 yearly intervals; 1993-94, 1998-99, 2004-05 and 2009. Data on cancer location, stage, surgical and oncological treatment and survival were collected. Univariate, multivariate and Kaplan-Meier survival analysis were performed. There were 1391 patients (355, 317, 419 and 300 per cohort), 1037 colon and 354 rectal cancers, respectively. For colon cancer, right-sided cancers appeared more common in later cohorts (P = 0.01). There was a significant decrease in the number of permanent stomas for colon cancer patients (P = 0.001). There was an analogous trend for rectal cancers (P = 0.075). More CRC patients with stage IV disease were treated surgically (P = 0.001) and colon cancer stages I and II tended to have increased survival if operated by a colorectal surgeon (P = 0.06). Oncology referrals have increased remarkably (P = 0.001). Overall 56% of patients were alive at 5 years however rectal cancer patients had significantly better 5-year survival than those with colon cancer (P rectal cancer patients have a better 5-year survival than colon cancer patients. The improved survival with early stage colon cancers operated on by specialist colorectal surgeons needs further exploration. © 2016 Royal Australasian College of Surgeons.

  3. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  4. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

    Science.gov (United States)

    Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

    2015-08-01

    We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Survival in pediatric medulloblastoma: a population-based observational study to improve prognostication.

    Science.gov (United States)

    Weil, Alexander G; Wang, Anthony C; Westwick, Harrison J; Ibrahim, George M; Ariani, Rojine T; Crevier, Louis; Perreault, Sebastien; Davidson, Tom; Tseng, Chi-Hong; Fallah, Aria

    2017-03-01

    Medulloblastoma is the most common form of brain malignancy of childhood. The mainstay of epidemiological data regarding childhood medulloblastoma is derived from case series, hence population-based studies are warranted to improve the accuracy of survival estimates. To utilize a big-data approach to update survival estimates in a contemporary cohort of children with medulloblastoma. We performed a population-based retrospective observational cohort study utilizing the Surveillance, Epidemiology, and End Results Program database that captures all children, less than 20 years of age, between 1973 and 2012 in 18 geographical regions representing 28% of the US population. We included all participants with a presumed or histologically diagnosis of medulloblastoma. The main outcome of interest is survivors at 1, 5 and 10 years following diagnosis. A cohort of 1735 children with a median (interquartile range) age at diagnosis of 7 (4-11) years, with a diagnosis of medulloblastoma were identified. The incidence and prevalence of pediatric medulloblastoma has remained stable over the past 4 decades. There is a critical time point at 1990 when the overall survival has drastically improved. In the contemporary cohort (1990 onwards), the percentage of participants alive was 86, 70 and 63% at 1, 5 and 10 years, respectively. Multivariate Cox-Regression model demonstrated Radiation (HR 0.37; 95% CI 0.30-0.46, p < 0.001) and Surgery (HR 0.42; 95% CI 0.30-0.58, p < 0.001) independently predict survival. The probability of mortality from a neurological cause is <5% in patients who are alive 8 years following diagnosis. The SEER cohort analysis demonstrates significant improvements in pediatric medulloblastoma survival. In contrast to previous reports, the majority of patients survive in the modern era, and those alive 8 years following initial diagnosis are likely a long-term survivor. The importance of minimizing treatment-related toxicity is increasingly apparent given

  6. Improved survival after an out-of-hospital cardiac arrest using new guidelines

    DEFF Research Database (Denmark)

    Steinmetz, Jacob; Barnung, S.; Nielsen, S.L.

    2008-01-01

    BACKGROUND: An out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis. We hypothesized that the implementations of 2005 European Resuscitation Council resuscitation guidelines were associated with improved 30-day survival after OHCA. METHODS: We prospectively recorded data on all....... Treatment after implementation was confirmed as a significant predictor of better 30-day survival in a logistic regression analysis. CONCLUSION: The implementation of new resuscitation guidelines was associated with improved 30-day survival after OHCA Udgivelsesdato: 2008/8...... patients with OHCA treated by the Mobile Emergency Care Unit of Copenhagen in two periods: 1 June 2004 until 31 August 2005 (before implementation) and 1 January 2006 until 31 March 2007 (after implementation), separated by a 4-month period in which the above-mentioned change took place. RESULTS: We found...

  7. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    had died. Published studies of melanoma therapies were tabled for comparison. Conclusion: The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself. Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches. Keywords: advanced melanoma, clinical responses, immunotherapy, prolonged survival

  8. Witnessed arrest, but not delayed bystander cardiopulmonary resuscitation improves prehospital cardiac arrest survival.

    Science.gov (United States)

    Vukmir, R B

    2004-05-01

    This study correlated the effect of witnessing a cardiac arrest and instituting bystander CPR (ByCPR), as a secondary end point in a study evaluating the effect of bicarbonate on survival. This prospective, randomised, double blinded clinical intervention trial enrolled 874 prehospital cardiopulmonary arrest patients encountered in a prehospital urban, suburban, and rural regional emergency medical service (EMS) area. This group underwent conventional advanced cardiac life support intervention followed by empiric early administration of sodium bicarbonate (1 mEq/l), monitoring conventional resuscitation parameters. Survival was measured as presence of vital signs on emergency department (ED) arrival. Data were analysed using chi(2) with Pearson correlation and odds ratio where appropriate. The overall survival rate was 13.9% (110 of 792) of prehospital cardiac arrest patients. The mean (SD) time until provision of bystander cardiopulmonary resuscitation (ByCPR) by laymen was 2.08 (2.77) minutes, and basic life support (BLS) by emergency medical technicians was 6.62 (5.73) minutes. There was improved survival noted with witnessed cardiac arrest-a 2.2-fold increase in survival, 18.9% (76 of 402) versus 8.6% (27 of 315) compared with unwitnessed arrests (ptwo minutes (p = 0.3752). Survival after prehospital cardiac arrest is more likely when witnessed, but not necessarily when ByCPR was performed by laymen.

  9. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

    NARCIS (Netherlands)

    Lutgens, M. W. M. D.; Oldenburg, B.; Siersema, P. D.; van Bodegraven, A. A.; Dijkstra, G.; Hommes, D. W.; de Jong, D. J.; Stokkers, P. C. F.; van der Woude, C. J.; Vleggaar, F. P.

    2009-01-01

    BACKGROUND: Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. METHOD: The aim of this study was to compare tumour stage and

  10. Improved survival of colorectal cancer in Denmark during 2001-2012

    DEFF Research Database (Denmark)

    Iversen, Lene Hjerrild; Green, Anders; Ingeholm, Peter

    2016-01-01

    cancer and 15 213 patients with rectal cancer were included. The stage distribution was almost stable over time. The mortality rate per 100 patient year within one year decreased from 32 to 26 in colon cancer and from 26 to 19 in rectal cancer with associated improvements in absolute survival from 73......% to 78% in colon cancer and from 78% to 83% in rectal cancer. The five-year relative survival of colon cancer improved from 58% to 63% and in rectal cancer from 59% to 65%. Comorbidity had major negative impact on outcome. Irrespective of tumor location, outcome improved relatively more in patients...... with stage III and IV disease. The proportion of patients who were spared surgery increased from 8% to 15% in colon cancer and from 13% to 19% in rectal cancer, and these changes were associated with improved outcome for rectal cancer patients, whereas outcome worsened for colon cancer patients. Conclusion...

  11. Edaravone improves survival and neurological outcomes after CPR in a ventricular fibrillation model of rats.

    Science.gov (United States)

    Qin, Tao; Lei, Ling-Yan; Li, Nuo; Shi, Fangying Ruan; Chen, Meng-Hua; Xie, Lu

    2016-10-01

    Overproduction of free radicals is a main factor contributing to cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). We sought to evaluate the impact of edaravone on the survival and neurological outcomes after CA/CPR in rats. Rats were subjected to CA following CPR. For survival study, the rats with restoration of spontaneous circulation (ROSC) were randomly allocated to one of the two groups (edaravone and saline group, n=20/each group) to received Edaravone (3 mg/kg) or normal saline. Another 10 rats without experiencing CA and CPR served as the sham group. Survival was observed for 72 hours and the neurological deficit score (NDS) was calculated at 12, 24, 48, and 72 hours after ROSC. For the neurological biochemical analysis study, rats were subjected to the same experimental procedures. Then, edaravone group (n=24), saline group (n=24) and sham group (n=16) were further divided into 4 subgroups according to the different time intervals (12, 24, 48, and 72 hours following ROSC). Brain tissues were harvested at relative time intervals for evaluation of oxidative stress, TUNEL staining and apoptotic gene expression. Edaravone improved postresuscitative survival time and neurological deficit, decreased brain malonylaldehyde level, increased superoxide dismutase activities, decreased proapoptotic gene expression of capase-8, capase-3, and Bax, and increased antiapoptotic Bcl-2 expression at 12, 24, 48, and 72 hours after ROSC. Edaravone improves survival and neurological outcomes following CPR via antioxidative and antiapoptotic effects in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Interact to survive: Phyllobacterium brassicacearum improves Arabidopsis tolerance to severe water deficit and growth recovery.

    Directory of Open Access Journals (Sweden)

    Justine Bresson

    Full Text Available Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm, was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture.

  13. Improving the interoperability of biomedical ontologies with compound alignments.

    Science.gov (United States)

    Oliveira, Daniela; Pesquita, Catia

    2018-01-09

    Ontologies are commonly used to annotate and help process life sciences data. Although their original goal is to facilitate integration and interoperability among heterogeneous data sources, when these sources are annotated with distinct ontologies, bridging this gap can be challenging. In the last decade, ontology matching systems have been evolving and are now capable of producing high-quality mappings for life sciences ontologies, usually limited to the equivalence between two ontologies. However, life sciences research is becoming increasingly transdisciplinary and integrative, fostering the need to develop matching strategies that are able to handle multiple ontologies and more complex relations between their concepts. We have developed ontology matching algorithms that are able to find compound mappings between multiple biomedical ontologies, in the form of ternary mappings, finding for instance that "aortic valve stenosis"(HP:0001650) is equivalent to the intersection between "aortic valve"(FMA:7236) and "constricted" (PATO:0001847). The algorithms take advantage of search space filtering based on partial mappings between ontology pairs, to be able to handle the increased computational demands. The evaluation of the algorithms has shown that they are able to produce meaningful results, with precision in the range of 60-92% for new mappings. The algorithms were also applied to the potential extension of logical definitions of the OBO and the matching of several plant-related ontologies. This work is a first step towards finding more complex relations between multiple ontologies. The evaluation shows that the results produced are significant and that the algorithms could satisfy specific integration needs.

  14. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

    2015-01-01

    . Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches

  15. Real-time spatial compound imaging improves reproducibility in evaluation of atherosclerotic carotid plaque

    DEFF Research Database (Denmark)

    Kofoed, Steen Christian; Grønholdt, Marie-Louise M.; Wilhjelm, Jens E.

    2001-01-01

    . The interobserver variation of the gray scale median value (GSM) for conventional technique ranged from -32 to +20 and from -6 to +6 for compound. Likewise, the coefficient of repeatability for the GSM value was 13 for conventional imaging and three for compound imaging, and interobserver variation for the GSM...... value for the overlapping area was 34% and 9% for conventional and compound technique. In conclusion, compound imaging improves intra- and interobserver agreement and reduces interobserver variation in the GSM value in a clinical setting. (C) 2001 World Federation for Ultrasound in Medicine & Biology....

  16. Pravastatin But Not Simvastatin Improves Survival and Neurofunctional Outcome After Cardiac Arrest and Cardiopulmonary Resuscitation

    Directory of Open Access Journals (Sweden)

    Stefan Bergt, MD

    2017-04-01

    Full Text Available Summary: Cardiac arrest (CA followed by cardiopulmonary resuscitation (CPR is associated with high mortality and poor neurological outcome. We compared the effects of pravastatin and simvastatin on survival and neurofunction in a murine model of CA/CPR. Pravastatin, a hydrophilic statin, increased survival and neurofunction during a 28-day follow-up period. This therapy was associated with improved pulmonary function, reduced pulmonary edema, and increased endothelial cell function in vitro. In contrast, lipophilic simvastatin did not modulate survival but increased pulmonary edema and impaired endothelial cell function. Although pravastatin may display a therapeutic option for post-CA syndrome, the application of simvastatin may require re-evaluation. Key Words: cardiac arrest, endothelial cell function, ischemia and reperfusion injury, pravastatin, resuscitation, simvastatin

  17. Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

    Directory of Open Access Journals (Sweden)

    Steve R. Martinez

    2013-02-01

    Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

  18. Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

    Science.gov (United States)

    Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2008-04-01

    Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.

  19. Patient-centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest

    Science.gov (United States)

    Friess, Stuart H.; Naim, Maryam Y.; Lampe, Joshua W.; Bratinov, George; Weiland, Theodore R.; Garuccio, Mia; Nadkarni, Vinay M.; Becker, Lance B.; Berg, Robert A.

    2014-01-01

    Rationale: Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. Objectives: To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). Methods: After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure–targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. Measurements and Main Results: The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9–13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0–12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0–3] vs. 2 [range, 2–2]; P = 0.003). Conclusions: Blood pressure–targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest. PMID:25321490

  20. Patient-centric blood pressure-targeted cardiopulmonary resuscitation improves survival from cardiac arrest.

    Science.gov (United States)

    Sutton, Robert M; Friess, Stuart H; Naim, Maryam Y; Lampe, Joshua W; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A

    2014-12-01

    Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure-targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9-13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0-12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0-3] vs. 2 [range, 2-2]; P = 0.003). Blood pressure-targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest.

  1. Performance Improvement in 503A Compounding Pharmacies: A PLAN FOR ASSESSMENT, IMPLEMENTATION, AND SUSTAINED SUCCESS.

    Science.gov (United States)

    Pritchett, Jon; Mixon, William; O'Connell, Kevin

    2016-01-01

    Performance improvement is the continual effort to objectively assess current performance and then restructure the practices that support it to more closely achieve desired performance. A plan for performance improvement, unlike other approaches to correcting problems in job fulfillment, is a systematic method used to first find the root causes of areas of concern and then apply corrections to remedy those deficits. Implementing a performance improvement plan that can be easily adapted to ensure compliance with evolving and increasingly complex state and federal regulations is crucial to a successful compounding practice. In this article, we discuss the need for performance improvement in 503A compounding pharmacies, list the steps necessary to develop such a plan, and present three case reports of performance improvement plans in differing compounding settings.

  2. Macrophages improve survival, proliferation and migration of engrafted myogenic precursor cells into MDX skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Pierre-François Lesault

    Full Text Available Transplantation of muscle precursor cells is of therapeutic interest for focal skeletal muscular diseases. However, major limitations of cell transplantation are the poor survival, expansion and migration of the injected cells. The massive and early death of transplanted myoblasts is not fully understood although several mechanisms have been suggested. Various attempts have been made to improve their survival or migration. Taking into account that muscle regeneration is associated with the presence of macrophages, which are helpful in repairing the muscle by both cleansing the debris and deliver trophic cues to myoblasts in a sequential way, we attempted in the present work to improve myoblast transplantation by coinjecting macrophages. The present data showed that in the 5 days following the transplantation, macrophages efficiently improved: i myoblast survival by limiting their massive death, ii myoblast expansion within the tissue and iii myoblast migration in the dystrophic muscle. This was confirmed by in vitro analyses showing that macrophages stimulated myoblast adhesion and migration. As a result, myoblast contribution to regenerating host myofibres was increased by macrophages one month after transplantation. Altogether, these data demonstrate that macrophages are beneficial during the early steps of myoblast transplantation into skeletal muscle, showing that coinjecting these stromal cells may be used as a helper to improve the efficiency of parenchymal cell engraftment.

  3. Survival prediction algorithms miss significant opportunities for improvement if used for case selection in trauma quality improvement programs.

    Science.gov (United States)

    Heim, Catherine; Cole, Elaine; West, Anita; Tai, Nigel; Brohi, Karim

    2016-09-01

    Quality improvement (QI) programs have shown to reduce preventable mortality in trauma care. Detailed review of all trauma deaths is a time and resource consuming process and calculated probability of survival (Ps) has been proposed as audit filter. Review is limited on deaths that were 'expected to survive'. However no Ps-based algorithm has been validated and no study has examined elements of preventability associated with deaths classified as 'expected'. The objective of this study was to examine whether trauma performance review can be streamlined using existing mortality prediction tools without missing important areas for improvement. We conducted a retrospective study of all trauma deaths reviewed by our trauma QI program. Deaths were classified into non-preventable, possibly preventable, probably preventable or preventable. Opportunities for improvement (OPIs) involve failure in the process of care and were classified into clinical and system deviations from standards of care. TRISS and PS were used for calculation of probability of survival. Peer-review charts were reviewed by a single investigator. Over 8 years, 626 patients were included. One third showed elements of preventability and 4% were preventable. Preventability occurred across the entire range of the calculated Ps band. Limiting review to unexpected deaths would have missed over 50% of all preventability issues and a third of preventable deaths. 37% of patients showed opportunities for improvement (OPIs). Neither TRISS nor PS allowed for reliable identification of OPIs and limiting peer-review to patients with unexpected deaths would have missed close to 60% of all issues in care. TRISS and PS fail to identify a significant proportion of avoidable deaths and miss important opportunities for process and system improvement. Based on this, all trauma deaths should be subjected to expert panel review in order to aim at a maximal output of performance improvement programs. Copyright © 2016 Elsevier

  4. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    Science.gov (United States)

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

  5. Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study.

    Science.gov (United States)

    Amit, Moran; Yen, Tzu-Chen; Liao, Chun-Ta; Chaturvedi, Pankaj; Agarwal, Jai Prakash; Kowalski, Luiz P; Ebrahimi, Ardalan; Clark, Jonathan R; Kreppel, Matthias; Zöller, Joachim; Fridman, Eran; Bolzoni, Villaret A; Shah, Jatin P; Binenbaum, Yoav; Patel, Snehal G; Gil, Ziv

    2013-12-15

    An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. This was a retrospective, longitudinal, international, population-based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5-year overall survival, from 59% for group A to 70% for group B (P < .001). There was also a significant improvement in disease-specific survival associated with operations performed before and after 2000 (from 69% to 81%, respectively; P < .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage disease were independent predictors of a better outcome in multivariate analysis. The decade of treatment was an independent prognostic factor for cancer-specific mortality (hazard ratio, 0.42; 95% confidence interval, 0.3-0.6). The survival rate of patients with OCSCC improved significantly during the past 2 decades despite older age, more advanced disease stage, and a higher rate of distant metastases. The current results suggest that the prognosis for patients with OCSCC has improved over time, presumably because of advances in imaging and therapy. © 2013 American Cancer Society.

  6. Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

    Science.gov (United States)

    Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

    2013-01-01

    AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P probiotics treated group compared with septic model group (33.3% vs 100.0%, P probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

  7. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jill P Smith

    2010-03-01

    Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

  8. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    International Nuclear Information System (INIS)

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-01-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51–176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%–94.1%) and 62.1% (95% CI 52.9%–71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%–100%) and 79.8% (95% CI 68.0%–91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p 90%.

  9. Does Surgical Repair of Moderate Ischemic Mitral Regurgitation Improve Survival? A Systematic Review.

    Science.gov (United States)

    Chatterjee, Saurav; Tripathi, Byomesh; Virk, Hafeez Ul Hassan; Ahmed, Mohammed; Bavishi, Chirag; Krishnamoorthy, Parasuram; Sardar, Partha; Giri, Jay; Omidvari, Karan; Chikwe, Joanna

    2016-03-01

    Mitral regurgitation (MR) is one of the common complications in myocardial infarction (MI) patients. Almost half of the post MI patients have MR (ischemic MR)(17) which is moderate to severe (grade II-IV). Whether there is a mortality benefit of performing mitral valve repair (MVR) along with coronary artery bypass grafting (CABG) in patients with post MI moderate MR remains inconclusive. Literature search was done from PubMed, Google scholar, Ovid, and Medline databases. Studies which included post MI patients with moderate ischemic MR and reported mortality outcomes of performing CABG and MVR were chosen for the systematic review. Our preliminary literature search identified 194 studies, of which 11 studies met our inclusion criteria. Nine studies showed no survival benefit of performing simultaneous MVR and CABG. One study demonstrated survival benefit of performing CABG plus MVR only in the New York Heart Association (NYHA) class III-IV, and one study suggested survival benefit of performing CABG plus MVR as compared to CABG alone in patient with ischemic MR irrespective of preoperative NYHA functional class. Review of current literature showed mixed results in terms of improvement in functional status but failed to show any survival benefit of performing MVR along with CABG. Limitations of studies include small sample size, difference in baseline demographic variables, and short follow-up period which might influence the outcome of the study. Prospective randomized studies are required to establish clear benefit of performing MVR simultaneously with CABG.

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

    International Nuclear Information System (INIS)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon

    2015-01-01

    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

  11. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    Science.gov (United States)

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

  12. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  13. Improved survival of macroencapsulated islets of Langerhans by preimplantation of the immunoisolating device: a morphometric study.

    Science.gov (United States)

    Rafael, E; Wu, G S; Hultenby, K; Tibell, A; Wernerson, A

    2003-01-01

    Encapsulation of cells in a semipermeable membrane may in the future provide an opportunity to treat a variety of endocrine and neurological disorders, without the need for lifelong immunosuppression. The physiological conditions in the device are crucial factors for graft survival. Previously, we have shown that the exchange across the immunoisolating membrane and the microcirculation around the TheraCyte device increase around 3 months after implantation. The aim of this study was to determine whether preimplantation of the TheraCyte device would improve the survival of a later transplanted islet graft. A TheraCyte device was implanted SC on one side of the back of a nondiabetic SD rat. After 3 months, 1500 islets isolated from SD rats were transplanted via the device port. At the same time, another device, loaded with the same number of islets, was implanted on the other side of the back. Both devices were explanted 2 weeks after islet transplantation (i.e., 3.5 months and 0.5 month after device implantation, respectively). Six pairs of devices were evaluated by morphometery. The volume densities of viable islets were 0.22 +/- 0.04 in the preimplanted device vs. 0.06 +/- 0.03 in the nonpreimplanted one (p TheraCyte device seems to improve the survival of an encapsulated islet graft and reduce fibroblast outgrowth in the device.

  14. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Directory of Open Access Journals (Sweden)

    Saher Hamed

    Full Text Available BACKGROUND: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF-treated and phosphate-buffered saline (PBS-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  15. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Science.gov (United States)

    Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

    2010-11-15

    Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  16. Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs

    Science.gov (United States)

    Haslem, Derrick S.; Chakravarty, Ingo; Fulde, Gail; Gilbert, Heather; Tudor, Brian P.; Lin, Karen; Ford, James M.; Nadauld, Lincoln D.

    2018-01-01

    The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient. We analyzed the outcomes of 22 patients who received genomic testing and targeted therapy (precision oncology) between July 1, 2013 and January 31, 2015, and compared to 22 historically controlled patients (control) who received standard chemotherapy (N = 17) or best supportive care (N = 5). The median overall survival was 51.7 weeks for the targeted treatment group and 25.8 weeks for the control group (P = 0.008) when matching on age, gender, histological diagnosis and previous treatment lines. Average costs over the entire period were $2,720 per week for the targeted treatment group and $3,453 per week for the control group, (P = 0.036). A separate analysis of 1,814 patients with late-stage cancer diagnoses found that those who received a targeted cancer treatment (N = 93) had 6.9% lower costs in the last 3 months of life compared with those who did not. These findings suggest that precision oncology may improve overall survival for refractory cancer patients while lowering average per-week healthcare costs, resource utilization and end-of-life costs. PMID:29552312

  17.  Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

    Science.gov (United States)

    Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

    2016-01-01

     Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

  18. Community-Based Multidisciplinary Computed Tomography Screening Program Improves Lung Cancer Survival.

    Science.gov (United States)

    Miller, Daniel L; Mayfield, William R; Luu, Theresa D; Helms, Gerald A; Muster, Alan R; Beckler, Vickie J; Cann, Aaron

    2016-05-01

    cancer specific survival was 71% in the screened patients, whereas nonscreened lung cancer patients during that time in WHS had an overall survival of only 19% (p < 0.001). A community-based multidisciplinary lung cancer screening program can improve survival of patients with lung cancer outside of a large multicenter study. This survival advantage was caused by a significant stage shift to earlier disease. Lung cancer CT screening may also benefit patients not meeting the National Lung Screening Trial criteria who are at moderate or high risk for lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  1. ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry.

    Science.gov (United States)

    De Blois, Jonathan; Fagerland, Morten Wang; Grundtvig, Morten; Semb, Anne Grete; Gullestad, Lars; Westheim, Arne; Hole, Torstein; Atar, Dan; Agewall, Stefan

    2015-01-01

    To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry. The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival (P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2015. For permissions please email: journals.permissions@oup.com.

  2. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

    Science.gov (United States)

    Brenner, Hermann; Jansen, Lina

    2016-02-01

    Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Phosphodiesterase type 4 inhibitor rolipram improves survival of spiral ganglion neurons in vitro.

    Directory of Open Access Journals (Sweden)

    Katharina Kranz

    Full Text Available Sensorineural deafness is caused by damage of hair cells followed by degeneration of the spiral ganglion neurons and can be moderated by cochlear implants. However, the benefit of the cochlear implant depends on the excitability of the spiral ganglion neurons. Therefore, current research focuses on the identification of agents that will preserve their degeneration. In this project we investigated the neuroprotective effect of Rolipram as a promising agent to improve the viability of the auditory neurons. It is a pharmaceutical agent that acts by selective inhibition of the phosphodiesterase 4 leading to an increase in cyclic AMP. Different studies reported a neuroprotective effect of Rolipram. However, its significance for the survival of SGN has not been reported so far. Thus, we isolated spiral ganglion cells of neonatal rats for cultivation with different Rolipram concentrations and determined the neuronal survival rate. Furthermore, we examined immunocytologically distinct proteins that might be involved in the neuroprotective signalling pathway of Rolipram and determined endogenous BDNF by ELISA. When applied at a concentration of 0.1 nM, Rolipram improved the survival of SGN in vitro. According to previous studies, our immunocytological data showed that Rolipram application induces the phosphorylation and thereby activation of the transcription factor CREB. This activation can be mediated by the cAMP-PKA-signalling pathway as well as via ERK as a part of the MAP-kinase pathway. However, only in cultures pre-treated with BDNF, an endogenous increase of BDNF was detected. We conclude that Rolipram has the potential to improve the vitality of neonatal auditory nerve cells in vitro. Further investigations are necessary to prove the effect of Rolipram in vivo in the adult organism after lesion of the hair cells and insertion of cochlear implants.

  5. Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden.

    Science.gov (United States)

    Strömsöe, A; Afzelius, S; Axelsson, C; Södersved Källestedt, M L; Enlund, M; Svensson, L; Herlitz, J

    2013-06-01

    In a review based on estimations and assumptions, to report the estimated number of survivors after out-of-hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden. An observational study. All ambulance organisations in Sweden. Patients included in the Swedish Cardiac Arrest Registry who suffered an OHCA between January 1, 2008 and December 31, 2010. Approximately 80% of OHCA cases in Sweden in which CPR was started are included. None In 11 005 patients, the 1-month survival rate was 9.4%. There are approximately 5000 OHCA cases annually in which CPR is started and 30-day survival is achieved in up to 500 patients yearly (6 per 100 000 inhabitants). Based on findings on survival in relation to the time to calling for the Emergency Medical Service (EMS) and the start of CPR and defibrillation, it was estimated that, if the delay from collapse to (i) calling EMS, (ii) the start of CPR, and (iii) the time to defibrillation were reduced to <2 min, <2 min, and <8 min, respectively, 300-400 additional lives could be saved. Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300-400 additional OHCA patients yearly (4 per 100 000 inhabitants) could be saved in Sweden. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  6. The Green Roof Microbiome: Improving Plant Survival for Ecosystem Service Delivery

    Directory of Open Access Journals (Sweden)

    Roberta Fulthorpe

    2018-02-01

    Full Text Available Plants are key contributors to ecosystem services delivered by green roofs in cities including stormwater capture, temperature regulation, and wildlife habitat. As a result, current research has primarily focused on their growth in relationship to extensive green roof (e.g., substrates <15 cm depth ecosystem services. Green roofs are exposed to a variety of harsh abiotic factors such as intense solar radiation, wind, and isolation from ground-level habitats, making survival exceedingly difficult. Plants in natural habitats benefit from a variety of interactions with fungi and bacteria. These plant-microbial interactions improve mechanisms of survival and productivity; however, many green roof substrates are sterilized prior to installation and lack microbial communities with unstudied consequences for green roof plant health and subsequent survival and performance. In this paper, we present six hypotheses on the positive role of microbes in green roof applications. In natural and experimental systems, microbial interactions have been linked to plant (1 drought tolerance, (2 pathogen protection, (3 nutrient availability, (4 salt tolerance, (5 phytohormone production, and (6 substrate stabilization, all of which are desirable properties of green roof ecosystems. As few studies exist that directly examine these relationships on green roofs, we explore the existing ecological literature on these topics to unravel the mechanisms that could support more complex green roof ecosystem and lead to new insight into the design, performance, and broader applications in green infrastructure.

  7. Hepatocyte transplantation improves early survival after partial hepatic resection and irradiation

    International Nuclear Information System (INIS)

    Guha, C.; Sharma, A.; Alfieri, A.; Guha, U.; Sokhi, R.; Gagandeep, S.; Gupta, S.; Vikram, B.; RoyChowdhury, J.

    1997-01-01

    Purpose: Radiation therapy (RT) is limited in its role as an adjuvant therapy of intrahepatic malignancies because of lower tolerance of human liver to irradiation (TD (5(5)) -TD (50(5)) ∼ 30-40 Gy). Although, surgical resection of primary or metastatic hepatic tumors has been shown to prolong survival, it is often limited by the presence of residual disease. RT could potentially improve survival of patients with positive surgical margins. However, radiation damage to the liver may be enhanced by hepatocellular proliferation induced by partial hepatic (PH) resection. We hypothesize that hepatocyte transplantation would be able to provide metabolic support and modulate the development of radiation-induced liver disease post-resection. The present study was designed to test the potential of hepatocyte transplantation in modifying the outcome of hepatocellular damage induced by PH and RT. Methods: Adult male Fischer 344 rats (Charles River) received hepatic irradiation of 50 Gy in a single fraction, after surgical exposure and shielding of the stomach and intestine, using a 320 MGC Philips orthovoltage unit. Immediately following irradiation, a two-third partial hepatectomy was performed. Four days post-radiation, the treatment group was injected with 5 x 10 6 syngeneic hepatocytes into the splenic pulp after a left subcostal incision, which allows homogeneous liver engraftment of the transplanted hepatocytes. Hematoxylin and eosin stains of liver biopsies, performed at various time points (3 days, 1, 2, 3 weeks or, anytime when animals died) were used for histologic evaluation. Time-adjusted survival was calculated from the date of irradiation by the product-limit Kaplan-Meier method, adjusting the denominator at every time point for the number of rats at risk. Results: Eight weeks after RT, 30% (n = 11) of the control animals (PH + 50 Gy) were alive compared to 100% (n = 9) of the transplant recipients (p <0.05). The median survival of the control group was 15

  8. Stereotactic radiosurgery improves the survival in patients with solitary brain metastasis: a reasonable alternative to surgery

    International Nuclear Information System (INIS)

    Kwan, H. Cho; Hall, Walter A.; Lee, Andrew K.; Gerbi, Bruce J.; Higgins, Patrick D.; Nussbaum, Eric S.; Chung, K.K. Lee; Bohen, Marva; Clark, H. Brent

    1996-01-01

    (Group 3) (p=0.69 by log-rank test). Conclusion: Although it is difficult to draw a definite conclusion from a retrospective analysis of an unbalanced number of patients among the Groups, our data suggest that SRS improves survival when compared to WBI only and is a reasonable alternative to surgery in the management of solitary brain metastases

  9. Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

    Science.gov (United States)

    Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

    2014-04-01

    Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    Science.gov (United States)

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  11. STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

    International Nuclear Information System (INIS)

    Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E.

    2006-01-01

    Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 μmol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) α and β. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR β antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival

  12. Invited review: Improving neonatal survival in small ruminants: science into practice.

    Science.gov (United States)

    Dwyer, C M; Conington, J; Corbiere, F; Holmøy, I H; Muri, K; Nowak, R; Rooke, J; Vipond, J; Gautier, J-M

    2016-03-01

    Neonatal mortality in small ruminant livestock has remained stubbornly unchanging over the past 40 years, and represents a significant loss of farm income, contributes to wastage and affects animal welfare. Scientific knowledge about the biology of neonatal adaptation after birth has been accumulating but does not appear to have had an impact in improving survival. In this paper, we ask what might be the reasons for the lack of impact of the scientific studies of lamb and kid mortality, and suggest strategies to move forward. Biologically, it is clear that achieving a good intake of colostrum, as soon as possible after birth, is crucial for neonatal survival. This provides fuel for thermoregulation, passive immunological protection and is involved in the development of attachment between the ewe and lamb. The behaviour of the lamb in finding the udder and sucking rapidly after birth is a key component in ensuring sufficient colostrum is ingested. In experimental studies, the main risk factors for lamb mortality are low birthweight, particularly owing to poor maternal nutrition during gestation, birth difficulty, litter size and genetics, which can all be partly attributed to their effect on the speed with which the lamb reaches the udder and sucks. Similarly, on commercial farms, low birthweight and issues with sucking were identified as important contributors to mortality. In epidemiological studies, management factors such as providing assistance with difficult births, were found to be more important than risk factors associated with housing. Social science studies suggest that farmers generally have a positive attitude to improving neonatal mortality but may differ in beliefs about how this can be achieved, with some farmers believing they had no control over early lamb mortality. Facilitative approaches, where farmers and advisors work together to develop neonatal survival strategies, have been shown to be effective in achieving management goals, such as

  13. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

    Science.gov (United States)

    Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

    2017-12-01

    Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

  14. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    Science.gov (United States)

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  15. Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

    Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

  16. Value-based contracting innovated Medicare advantage healthcare delivery and improved survival.

    Science.gov (United States)

    Mandal, Aloke K; Tagomori, Gene K; Felix, Randell V; Howell, Scott C

    2017-02-01

    In Medicare Advantage (MA) with its CMS Hierarchical Condition Categories (CMS-HCC) payment model, CMS reimburses private plans (Medicare Advantage Organizations [MAOs]) with prospective, monthly, health-based or risk-adjusted, capitated payments. The effect of this payment methodology on healthcare delivery remains debatable. How value-based contracting generates cost efficiencies and improves clinical outcomes in MA is studied. A difference in contracting arrangements between an MAO and 2 provider groups facilitated an intervention-control, preintervention-postintervention, difference-in-differences approach among statistically similar, elderly, community-dwelling MA enrollees within one metropolitan statistical area. Starting in 2009, for intervention-group MA enrollees, the MAO and a provider group agreed to full-risk capitation combined with a revenue gainshare. The gainshare was based on increases in the Risk Adjustment Factor (RAF), which modified the CMS-HCC payments. For the control group, the MAO continued to reimburse another provider group through fee-for-service. RAF, utilization, and survival were followed until December 31, 2012. The intervention group's mean RAF increased significantly (P based visits (P based care for these MA enrollees with multiple comorbidities, a 6% survival benefit with a 32.8% lower hazard of death (P Value-based contracting can drive utilization patterns and improve clinical outcomes among chronically ill, elderly MA members.

  17. Improvement of organic compounds labelling method with the use of thermally activated tritium gas

    International Nuclear Information System (INIS)

    Nejman, L.A.; Smolyakov, V.S.; Antropova, L.P.

    1982-01-01

    Use of a support (various types of papers) is recommended for organic compounds labelling by tritium gas activated at a hot tungsten filament. This improvement increases chemical and radiochemical yields and makes the experiment simpler and faster. Generally labelled triethyloxonium tetra-fluoroborate, ethyl-p-aminobenzoate, p-aminobenzoic acid (Na-salt), A-factor (a natural regulator of streptomycin biosynthesis), decapeptide angiotensin I, phospholipid 1, 2 - dimyristoyl-sn-glycero-3--phosphocholine and E. coli tRNAs have been prepared by this method. Molar radioactivity of the labelled compounds is in the range of 1-200 GBg/mmole [ru

  18. Application of bacterial lipopolysaccharide to improve survival of the black tiger shrimp after Vibrio harveyi exposure.

    Science.gov (United States)

    Rungrassamee, Wanilada; Maibunkaew, Sawarot; Karoonuthaisiri, Nitsara; Jiravanichpaisal, Pikul

    2013-10-01

    This study investigates an effect of bacterial lipopolysaccharide (LPS) as feed supplement to improve immunity of the black tiger shrimp (Penaeus monodon). LPS was coated to commercial feed pellets and given to the shrimp once or twice a day for 10 days before an exposure with shrimp pathogenic bacterium Vibrio harveyi. The growth rates, percent weight gains, total hemocyte and granulocyte counts and survival rates of shrimp between the LPS-coated pellet fed groups and a control group where shrimp fed with commercial feed pellets were compared. After 10 days of the feeding trials, growth rates were not significantly different in all groups, suggesting no toxicity from LPS supplement. To determine beneficial effect of LPS diets, each group was subsequently exposed to V. harveyi by immersion method and the survival rates were recorded for seven days after the immersion. Regardless of the dosages of LPS, the shrimp groups fed with LPS-coated pellets showed higher survival rates than the control group. There was no significant difference in survival rates between the two LPS dosages groups. In addition to survival under pathogen challenge, we also determine effect of LPS on immune-related genes after 10-day feeding trial. Gene expression analysis in the P. monodon intestines revealed that antilipopolysaccharide factor isoform 3 (ALF3), C-type lectin, and mucine-like peritrophin (mucin-like PM) were expressed significantly higher in a group fed with LPS supplemental diet once or twice a day than in a control group. The transcript levels of C-type lectin and mucin-like PM had increased significantly when LPS was given once a day, while significant induction of ALF3 transcripts was observed when shrimp were fed with LPS twice a day. The up-regulation of the immune gene levels in intestines and higher resistance to V. harveyi of the shrimp fed with LPS provide the evidence for potential application of LPS as an immunostimulant in P. monodon farming. Copyright © 2013

  19. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    Science.gov (United States)

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

  20. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    Directory of Open Access Journals (Sweden)

    Enjae Jung

    Full Text Available World conditions place large populations at risk from ionizing radiation (IR from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA. While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01. Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01. These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

  1. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    Science.gov (United States)

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

  2. Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.

    Science.gov (United States)

    Kitson, Sarah; Ryan, Neil; MacKintosh, Michelle L; Edmondson, Richard; Duffy, James Mn; Crosbie, Emma J

    2018-02-01

    Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival as well as a reduction in the risk of cardiovascular disease, a frequent cause of death in endometrial cancer survivors. To determine the impact of weight-loss interventions, in addition to standard management of endometrial cancer, on overall survival and the frequency of adverse events.Secondary objectives include an assessment of weight-loss interventions on endometrial cancer-specific survival, weight loss achieved, cardiovascular event frequency and quality of life both overall and stratified according to patient body mass index (BMI), where possible. This review searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase and reference lists of articles, trial registries, and international gynaecological oncology conference abstracts from inception to January 2018. Randomised controlled trials (RCTs) of interventions to facilitate weight loss in overweight or obese women undergoing treatment for, or previously treated for, endometrial cancer were selected. Two review authors independently selected studies, assessed trial quality, and extracted data with disagreements resolved by a third review author. Study authors were contacted to obtain missing data, including details of any adverse events. We included three RCTs in the review, randomising a total of 161 overweight and obese women with endometrial cancer. All studies compared combined behavioural and lifestyle interventions to facilitate weight loss

  3. Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

    Science.gov (United States)

    Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-02-01

    Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

  4. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

    Science.gov (United States)

    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

  5. Improved survival and neurodevelopmental outcomes among extremely premature infants born near the limit of viability.

    Science.gov (United States)

    Younge, Noelle; Smith, P Brian; Gustafson, Kathryn E; Malcolm, William; Ashley, Patricia; Cotten, C Michael; Goldberg, Ronald N; Goldstein, Ricki F

    2016-04-01

    Infants born near the limit of viability are at high risk for death or adverse neurodevelopmental outcomes. It is unclear whether these outcomes have improved over the past 15 years. To determine if death and neurodevelopmental impairment have declined over the past 15 years in infants born at 22 to 24 weeks' gestation. Retrospective cohort study. We identified infants born at 22 to 24 weeks' gestation in our center in two epochs: 1998-2004 (Epoch 1) and 2005-2011 (Epoch 2). The primary outcome, death or neurodevelopmental impairment, was evaluated at 17-25 months' corrected gestational age with neurologic exams and Bayley Scales of Infant Development. Perinatal characteristics, major morbidities, and outcomes were compared between epochs. Birth weight and gestational age were similar between 170 infants in Epoch 1 and 187 infants in Epoch 2. Mortality was significantly lower in Epoch 2, 55% vs. 42% (p=0.02). Among surviving infants, late-onset sepsis (pNeurodevelopmental impairment among surviving infants declined from 68% in Epoch 1 to 47% in Epoch 2, p=0.02. Odds of death or NDI were significantly lower in Epoch 2 vs. Epoch 1, OR=0.31 (95% confidence interval; 0.16, 0.58). Risk of death or neurodevelopmental impairment decreased over time in infants born at 22 to 24 weeks' gestation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Single Agent Polysaccharopeptide Delays Metastases and Improves Survival in Naturally Occurring Hemangiosarcoma

    Directory of Open Access Journals (Sweden)

    Dorothy Cimino Brown

    2012-01-01

    Full Text Available The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.

  7. Going the Extra Mile: Improved Survival for Pancreatic Cancer Patients Traveling to High-volume Centers.

    Science.gov (United States)

    Lidsky, Michael E; Sun, Zhifei; Nussbaum, Daniel P; Adam, Mohamed A; Speicher, Paul J; Blazer, Dan G

    2017-08-01

    This study compares outcomes following pancreaticoduodenectomy (PD) for patients treated at local, low-volume centers and those traveling to high-volume centers. Although outcomes for PD are superior at high-volume institutions, not all patients live in proximity to major medical centers. Theoretical advantages for undergoing surgery locally exist. The 1998 to 2012 National Cancer Data Base was queried for T1-3N0-1M0 pancreatic adenocarcinoma patients who underwent PD. Travel distances to treatment centers were calculated. Overlaying the upper and lower quartiles of travel distance with institutional volume established short travel/low-volume (ST/LV) and long travel/high-volume (LT/HV) cohorts. Overall survival was evaluated. Of 7086 patients, 773 ST/LV patients traveled ≤6.3 (median 3.2) miles to centers performing ≤3.3 PDs yearly, and 758 LT/HV patients traveled ≥45 (median 97.3) miles to centers performing ≥16 PDs yearly. LT/HV patients had higher stage disease (P travel to a high-volume center remained associated with reduced long-term mortality (hazard ratio 0.75, P travel burden, patients treated at high-volume centers had improved perioperative outcomes, short-term mortality, and overall survival. These data support ongoing efforts to centralize care for patients undergoing PD.

  8. Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation

    International Nuclear Information System (INIS)

    Dembo, A.J.; Bush, R.S.; Beale, F.A.; Bean, H.A.; Pringle, J.F.; Sturgeon, J.; Reid, J.G.

    1979-01-01

    A prospective, stratified, randomized study of 190 postoperative ovarian carcinoma patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapies tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significantly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures

  9. Improvements in breast cancer survival between 1995 and 2012 in Denmark

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Ejlertsen, Bent; Mouridsen, Henning T

    2016-01-01

    Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late...... was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were...... in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment...

  10. Nutrition management for head and neck cancer patients improves clinical outcome and survival.

    Science.gov (United States)

    Müller-Richter, Urs; Betz, C; Hartmann, S; Brands, R C

    2017-12-01

    Up to 80% of patients with head and neck cancers are malnourished because of their lifestyle and the risk factors associated with this disease. Unfortunately, nutrition management systems are not implemented in most head and neck cancer clinics. Even worse, many head and neck surgeons as well as hospital management authorities disregard the importance of nutrition management in head and neck cancer patients. In addition, the often extensive resection and reconstruction required for tumors in the upper aerodigestive tract pose special challenges for swallowing and sufficient food intake, placing special demands on nutrition management. This article presents the basics of perioperative metabolism and nutrition management of head and neck cancer patients and makes recommendations for clinical practice. Implementing a nutrition management system in head and neck cancer clinics will improve the clinical outcome and the survival of the patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

    Science.gov (United States)

    Foley, T Raymond; Singh, Gagan D; Kokkinidis, Damianos G; Choy, Ho-Hin K; Pham, Thai; Amsterdam, Ezra A; Rutledge, John C; Waldo, Stephen W; Armstrong, Ehrin J; Laird, John R

    2017-07-15

    The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P =0.14). Demographics including age (68±12 versus 67±10 years, P =0.25), smoking history (76% versus 80%, P =0.42), diabetes mellitus (54% versus 48%, P =0.17), and hypertension (88% versus 89%, P =0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P =0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P =0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P =0.02). In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  12. Survival improvement in patients with disseminated medullary thyroid carcinoma treated with 131I-MIBG therapy

    International Nuclear Information System (INIS)

    Mihaljevic, I.; Topuzovi, N.; Snajder, D.

    2015-01-01

    Full text of publication follows. Introduction and aim: The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of medullary thyroid carcinoma (MTC) with local and distant metastases. MTC is an uncommon thyroid tumor, accounting from 3-5% of all thyroid malignancies, and arises from para-follicular C cells which produce calcitonin (CT). Prognosis of MTC is related to tumor extension at disease detection, but long-term survival in patients with disseminated MTC is still unsatisfactory. Methods: 4 female patients with metastatic MTC (63, 69 and 2 patients aged 73 years), which already underwent total thyroidectomy and selective neck dissection, received therapy with 100 mCi 131 I-MIBG in our Institute. Patients had widespread disease with neck recurrences (all 4 cases), liver and bone metastases (2 cases) and lung metastases (1 case). All those patients received the therapy twice, second one 3 months up to 1 year after the first cycle. After therapy, whole body scintigraphy was performed; tumor marker levels (CT, carcinoembryonic antigen - CEA, neuron specific enolase - NSE, chromogranin A - CgA and pro-gastrin releasing peptide - pro-GRP) were measured before and after therapy. Results: in one patient we observed a slight decrease in CT level after first MIBG therapy, in another one a slight decrease in CEA serum level, and no lung metastases were visible on whole body scan after second 131 I-MIBG therapy. In one of the two remaining cases there was a significant decrease in CT serum level only after neck dissection. In all cases the patients reported an improvement in subjective symptom reduction. Conclusion: 131 I-MIBG therapy could provide additional benefit to patients with MTC and could improve overall survival, but more patient should be treated in order to define the true potential of the therapy. The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of

  13. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  14. Removal of cyanide compounds from coking wastewater by ferrous sulfate: Improvement of biodegradability.

    Science.gov (United States)

    Yu, Xubiao; Xu, Ronghua; Wei, Chaohai; Wu, Haizhen

    2016-01-25

    The effect of ferrous sulfate (FeSO4) treatment on the removal of cyanide compounds and the improvement of biodegradability of coking wastewater were investigated by varying Fe:TCN molar ratios. Results suggested that the reaction between FeSO4 and coking wastewater was a two-step process. At the first step, i.e., 0≤Fe:TCN≤1.0, the reaction mechanisms were dominated by the precipitation of FeS, the complexation of CN(-), and the coagulation of organic compounds. The COD of coking wastewater decreased from 3748.1 mg/L to 3450.2 mg/L, but BOD5:COD (B/C) was improved from 0.30 to 0.51. At the second step, i.e., 1.0cyanide compounds by ferrous ions was the dominating mechanism. The COD showed a continuous increase to 3542.2 mg/L (Fe:TCN=3.2) due to the accumulated ferrous ions in coking wastewater. Moreover, B/C decreased progressively to 0.35, which was attributed to the negative effects of excess ferrous ions on biodegradability. To improve coking wastewater's biodegradability, a minimum ferrous dosage is required to complete the first step reaction. However, the optimum ferrous dosage should be determined to control a safe residual TCN in coking wastewater for the further biological treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Science.gov (United States)

    2010-07-01

    ... elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and... spouses of Spanish-American War veterans. (a) General. A surviving spouse of a Spanish-American War... and attendance. A surviving spouse of a Spanish-American War veteran who is receiving or entitled to...

  16. Low concentrations of Rhodamine-6G selectively destroy tumor cells and improve survival of melanoma transplanted mice.

    Science.gov (United States)

    Kutushov, M; Gorelik, O

    2013-01-01

    Rhodamine-6G is a fluorescent dye binding to mitochondria, thus reducing the intact mitochondria number and inhibiting mitochondrial metabolic activity. Resultantly, the respiratory chain functioning becomes blocked, the cell "suffocated" and eventually destroyed. Unlike normal cells, malignant cells demonstrate a priori reduced mitochondrial numbers and aberrant metabolism. Therefore, a turning point might exist, when Rhodamine-induced loss of active mitochondria would selectively destroy malignant, but spare normal cells. Various malignant vs. non-malignant cell lines were cultured with Rhodamine-6G at different concentrations. In addition, C57Bl mice were implanted with B16-F10 melanoma and treated with Rhodamine-6G at different dosage/time regimens. Viability and proliferation of cultured tumor cells were time and dose-dependently inhibited, up to 90%, by Rhodamine-6G, with profound histological signs of cell death. By contrast, inhibition of normal control cell proliferation hardly exceeded 15-17%. Melanoma-transplanted mice receiving Rhodamine-6G demonstrated prolonged survival, improved clinical parameters, inhibited tumor growth and metastases count, compared to their untreated counterparts. Twice-a-week 10-6M Rhodamine-6G regimen yielded the most prominent results. We conclude that malignant, but not normal, cells are selectively destroyed by low doses of Rhodamine-6G. In vivo, such treatment selectively suppresses tumor progression and dissemination, thus improving prognosis. We suggest that selective anti-tumor properties of Rhodamine-6G are based on unique physiologic differences in energy metabolism between malignant and normal cells. If found clinically relevant, low concentrations of Rhodamine-6G might be useful for replacing, or backing up, more aggressive nonselective chemotherapeutic compounds.

  17. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN...

  18. Nanoliposomal carriers for improvement the bioavailability of high - valued phenolic compounds of pistachio green hull extract.

    Science.gov (United States)

    Rafiee, Zahra; Barzegar, Mohsen; Sahari, Mohammad Ali; Maherani, Behnoush

    2017-04-01

    In present study, nanoliposomes were prepared by thin hydration method with different concentrations of phenolic compounds (500, 750 and 1000ppm) of pure extract and lecithin (1, 2 and 3%w/w) and characterized by considering the particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE) and morphology. The results showed that nanoliposome (90.39-103.78nm) had negative surface charge varied from -51.5±0.9 to -40.2±0.2mV with a narrow size distribution (PDI≈0.069-0.123). Nanoliposomes composed of 1% lecithin with 1000ppm of phenolic compounds had the highest EE (52.93%). The FTIR analysis indicated the formation of hydrogen bonds between the polar zone of phospholipid and the OH groups of phenolic compounds. Phenolic compounds also increased phase transition temperature (Tc) of nanoliposomes (2.01-7.24°C). Moreover, nanoliposomes had considerable stability during storage. Consequently, liposome is an efficient carrier for protection and improving PGHE biofunctional actives in foodstuffs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas.

    Science.gov (United States)

    Venigalla, Sriram; Nead, Kevin T; Sebro, Ronnie; Guttmann, David M; Sharma, Sonam; Simone, Charles B; Levin, William P; Wilson, Robert J; Weber, Kristy L; Shabason, Jacob E

    2018-03-15

    Soft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS). Patients aged ≥18 years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis. Of 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS. In this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to

  20. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    International Nuclear Information System (INIS)

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  1. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E

    2012-07-01

    nausea (n = 1 and headaches (n = 2 that resolved with a short-course of dexamethasone. Conclusion SRT/SRS for brainstem metastases is safe and achieves a high rate of local control. We found higher GPA as well as greater number of treatment fractions and higher prescription dose to be correlated with improved overall survival. Despite this approach, prognosis remains poor and distant intracranial control remains an issue, even in patients previously treated with WBRT.

  2. Renal transplant immunology in the last 20 years: A revolution towards graft and patient survival improvement.

    Science.gov (United States)

    Sá, Helena; Leal, Rita; Rosa, Manuel Santos

    2017-05-04

    To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969 * Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T. The mystique of organ transplantation. J Am Coll Surg 2005 Aug;201(2):160-170]. In fact, the first successful identical-twin kidney transplantation performed by Murray's team in December 1954 (Murray J et al. Renal homotransplantations in identical twins. Surg Forum 1955;6:432-436) was the example of an upside down translation medicine: Human clinical transplantation began and researchers tried to understand the underlying immune response and how to control the powerful rejection pathways through experimental models. In the last 20 years, we have witnessed an amazing progress in the knowledge of immunological mechanisms regarding alloimmune response and an outstanding evolution on the identification and characterization of major and minor histocompatibility antigens. This review presents an historical and clinical perspective of those important advances in kidney transplantation immunology in the last 20 years, which contributed to the improvement in patients' quality of life and the survival of end-stage renal patients. In spite of these significant progresses, some areas still need substantial progress, such as the definition of non-invasive biomarkers for acute rejection; the continuous reduction of immunosuppression; the extension of graft survival, and finally the achievement of real graft tolerance extended to HLA mismatch donor: recipient pairs.

  3. Abandoning Peracetic Acid-Based Dialyzer Reuse Is Associated with Improved Survival

    Science.gov (United States)

    Wang, Weiling; Mooney, Ann; Ofsthun, Norma; Lazarus, J. Michael; Hakim, Raymond M.

    2011-01-01

    Summary Background and objectives Higher mortality risk reported with reuse versus single use of dialyzers is potentially related to reuse reagents that modify membrane surface characteristics and the blood-membrane interface. A key mechanism may involve stimulation of an inflammatory response. Design, setting, participants, & measurements In a prospective crossover design, laboratory markers and mortality from 23 hemodialysis facilities abandoning reuse with peracetic acid mixture were tracked. C-reactive protein (CRP), white blood cell (WBC) count, albumin, and prealbumin were measured for 2 consecutive months before abandoning reuse and subsequently within 3 and 6 months on single use. Survival models were utilized to compare the 6-month period before abandoning reuse (baseline) and the 6-month period on single use of dialyzers after a 3-month “washout period.” Results Patients from baseline and single-use periods had a mean age of approximately 63 years; 44% were female, 54% were diabetic, 60% were white, and the mean vintage was approximately 3.2 years. The unadjusted hazard ratio for death was 0.70 and after case-mix adjustment was 0.74 for single use compared with reuse. Patients with CRP ≥ 5 mg/L during reuse (mean CRP = 26.6 mg/ml in April) declined on single use to 20.2 mg/L by August and 20.4 mg/L by November. WBC count declined slightly during single use, but nutritional markers were unchanged. Conclusions Abandonment of peracetic-acid-based reuse was associated with improved survival and lower levels of inflammatory but not nutritional markers. Further study is needed to evaluate a potential link between dialyzer reuse, inflammation, and mortality. PMID:20947788

  4. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    Science.gov (United States)

    Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

    2014-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

  5. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    Science.gov (United States)

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Postoperative radiotherapy improves local control and survival in patients with uterine leiomyosarcoma

    International Nuclear Information System (INIS)

    Wong, Philip; Han, Kathy; Sykes, Jenna; Catton, Charles; Laframboise, Stephane; Fyles, Anthony; Manchul, Lee; Levin, Wilfred; Milosevic, Michael

    2013-01-01

    To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT. From 1998–2008, 69 patients with primary uterine LMS underwent hysterectomy with or without pelvic radiotherapy to a median dose of 45 Gy. Univariate analysis was performed using the Kaplan-Meier method and cumulative-incidence function, and multivariate analyses using Fine and Gray or Cox proportional hazard models. Following surgery, 32 out of 69 patients received RT. There was no evidence of any correlation between patient, disease and treatment characteristics and the use of RT. Median follow-up was 57 months. RT was associated with reduced local recurrence (3y LR 19% vs. 39%; Gray’s p = 0.019) and improved overall survival (3y OS 69% vs. 35%; log-rank p = 0.025) on univariate analysis. Multivariate analysis demonstrated that RT reduced LR (HR: 0.28, CI: 0.11-0.69, p = 0.006) and increased OS (HR: 0.44, CI: 0.23-0.85, p = 0.014) independent of other clinical and pathologic factors. Positive surgical margins increased the odds of LR (HR: 5.6, CI: 2.3-13.4, p = 0.00012). Large tumor size and advanced stage (II-IV) were associated with the development of distant metastases and inferior OS. Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS

  7. High hospital research participation and improved colorectal cancer survival outcomes: a population-based study.

    Science.gov (United States)

    Downing, Amy; Morris, Eva Ja; Corrigan, Neil; Sebag-Montefiore, David; Finan, Paul J; Thomas, James D; Chapman, Michael; Hamilton, Russell; Campbell, Helen; Cameron, David; Kaplan, Richard; Parmar, Mahesh; Stephens, Richard; Seymour, Matt; Gregory, Walter; Selby, Peter

    2017-01-01

    In 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals. Data for patients diagnosed with CRC in England in 2001-2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation. Most of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer 'centres of excellence', although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (presearch participation, with a reduction in postoperative mortality of 1.5% (6.5%-5%, pstudies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Improving breast cancer survival analysis through competition-based multidimensional modeling.

    Directory of Open Access Journals (Sweden)

    Erhan Bilal

    Full Text Available Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually. As with most cancers, it is a heterogeneous disease and different breast cancer subtypes are treated differently. Understanding the difference in prognosis for breast cancer based on its molecular and phenotypic features is one avenue for improving treatment by matching the proper treatment with molecular subtypes of the disease. In this work, we employed a competition-based approach to modeling breast cancer prognosis using large datasets containing genomic and clinical information and an online real-time leaderboard program used to speed feedback to the modeling team and to encourage each modeler to work towards achieving a higher ranked submission. We find that machine learning methods combined with molecular features selected based on expert prior knowledge can improve survival predictions compared to current best-in-class methodologies and that ensemble models trained across multiple user submissions systematically outperform individual models within the ensemble. We also find that model scores are highly consistent across multiple independent evaluations. This study serves as the pilot phase of a much larger competition open to the whole research community, with the goal of understanding general strategies for model optimization using clinical and molecular profiling data and providing an objective, transparent system for assessing prognostic models.

  9. Assessing Community Based Improved Maternal Neonatal Child Survival (IMNCS Program in Rural Bangladesh.

    Directory of Open Access Journals (Sweden)

    Mahfuzar Rahman

    Full Text Available A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the "Improved Maternal Newborn and Child Survival" (IMNCS project, which was implemented by BRAC in rural communities of Bangladesh.The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12-59 months. A follow-up survey was administered in 2012-13 among 4, 800 women of similar characteristics in the same villages.We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001. Proportion of deliveries with skilled attendant was higher in intervention districts (28% compared to comparison districts (27.4%. The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001. Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts.This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources.

  10. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    International Nuclear Information System (INIS)

    Lee, Ching-Chih; Hung, Shih-Kai; Huang, Tze-Ta; Lee, Moon-Sing; Su, Yu-Chieh; Chou, Pesus; Hsiao, Shih-Hsuan; Chiou, Wen-Yen; Lin, Hon-Yi; Chien, Sou-Hsin

    2011-01-01

    Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001). Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate

  11. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    Directory of Open Access Journals (Sweden)

    Michal Lotem

    2016-01-01

    Full Text Available Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2, MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007. Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.

  12. Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

    Directory of Open Access Journals (Sweden)

    Pasque Michael K

    2007-01-01

    Full Text Available Abstract Objective Patients with severe left ventricular (LV dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+ in the post -operative period was compared to those without ICD (ICD-. Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5% patients received an ICD with a median of 2 (+/-2 years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT. There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

  13. The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages.

    Directory of Open Access Journals (Sweden)

    Wouter B Aan de Stegge

    Full Text Available Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer.In a population-based cohort study, all patients (N = 41,074 diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival.Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%. After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with 75: HR: 0.734 (95% CI, 0.700-0.771 and relative survival ( 75: RER: 0.621 (95% CI, 0.567-0.681 in all three age groups.The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification.

  14. Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.

    Directory of Open Access Journals (Sweden)

    Ikechukwu Okoli

    2009-09-01

    Full Text Available Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans-C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay.

  15. Toxicological Risk Assessment of a Nickel Compound Found on the Surfaces of Replacement Hyperstretch Neoprene (CWU-83P) Neck and Wrist Seals for a Cold water Submersion Survival Suit

    National Research Council Canada - National Science Library

    Arfsten, Darryl

    2001-01-01

    .... The conservative approach for estimating the toxicological risk of nickeldialkyldithiocarbamate exposure to humans is to assume that these compounds have the same toxic properties as soluble nickel compounds. Lifetime average daily dose (LADD) estimates for persons wearing cold water survival suits were calculated using conservative exposure assumptions.

  16. Incorporating movement patterns to improve survival estimates for juvenile bull trout

    Science.gov (United States)

    Bowerman, Tracy; Budy, Phaedra

    2012-01-01

    Populations of many fish species are sensitive to changes in vital rates during early life stages, but our understanding of the factors affecting growth, survival, and movement patterns is often extremely limited for juvenile fish. These critical information gaps are particularly evident for bull trout Salvelinus confluentus, a threatened Pacific Northwest char. We combined several active and passive mark–recapture and resight techniques to assess migration rates and estimate survival for juvenile bull trout (70–170 mm total length). We evaluated the relative performance of multiple survival estimation techniques by comparing results from a common Cormack–Jolly–Seber (CJS) model, the less widely used Barker model, and a simple return rate (an index of survival). Juvenile bull trout of all sizes emigrated from their natal habitat throughout the year, and thereafter migrated up to 50 km downstream. With the CJS model, high emigration rates led to an extreme underestimate of apparent survival, a combined estimate of site fidelity and survival. In contrast, the Barker model, which allows survival and emigration to be modeled as separate parameters, produced estimates of survival that were much less biased than the return rate. Estimates of age-class-specific annual survival from the Barker model based on all available data were 0.218±0.028 (estimate±SE) for age-1 bull trout and 0.231±0.065 for age-2 bull trout. This research demonstrates the importance of incorporating movement patterns into survival analyses, and we provide one of the first field-based estimates of juvenile bull trout annual survival in relatively pristine rearing conditions. These estimates can provide a baseline for comparison with future studies in more impacted systems and will help managers develop reliable stage-structured population models to evaluate future recovery strategies.

  17. Improving the review of standard operating procedures: a novel electronic system for compounding pharmacies.

    Science.gov (United States)

    Brensel, Robert; Brensel, Scott; Ng, Amy

    2013-01-01

    Since the New England Compounding Center disaster in 2012, the importance of following correct procedures during every phase of customized pharmacy has been a focus of governmental interest and action as well as public scrutiny. Many pharmacies rely on the rote review of standard operating procedures to ensure that staff members understand and follow protocols that ensure the safety and potency of all compounds prepared, but that approach to continuing education can be cumbersome and needlessly time-consuming. In addition, documenting and retrieving evidence of employee competence can be difficult. In this article, we describe our use of online technology to improve our methods of educating staff about the full range of standard operating procedures that must be followed in our pharmacy. The system we devised and implemented has proven to be effective, easy to update and maintain, very inexpensive, and user friendly. Its use has reduced the time previously required for a read-over review of standard operating procedures from 30 or 40 minutes to 5 or 10 minutes in weekly staff meetings, and we can now easily document and access proof of employees' comprehension of that content. It is our hope that other small compounding pharmacies will also find this system of online standard operating procedure review helpful.

  18. Improved Gas Chromatographic Determination of Guanidino Compounds Using Isovaleroylacetone and Ethyl Chloroformate as Derivatizing Reagents.

    Science.gov (United States)

    Zounr, Rizwan Ali; Khuhawar, Mumammad Yar; Jahangir, Taj Muhammad; Alamgir, Malik

    2016-01-01

    An improved GC method in terms of sensitivity and decrease in the analysis time has been developed for the analysis of eight guanidino compounds: guanidine (G), methylguanidine (MG), creatinine (CTN), guanidinoacetic acid (GAA), guanidinobutyric acid (GBA), guanidinopropionic acid (GPA), argenine (Arg), and guanidinosuccinic acid (GSA), using isovaleroylacetone (IVA) and ethyl chloroformate (ECF) as derivatizing reagents. The separation was obtained from column HP-5 (30 m × 0.32 mm i.d.) with film thickness of 0.25 μm within 11 min. The linear calibrations were obtained with 0.5 to 50 μg/mL with coefficient of determination (R(2)) within 0.9969 - 0.9998. Limits of detections (LODs) were within 5 - 140 ng/mL. The derivatization, separation and determination was repeatable (n = 6) with relative standard deviation (RSD) within 1.2 - 3.1%. The guanidino compounds were determined in deproteinized serum of healthy volunteers and uremic patients within below LOD to 8.8 μg/mL and below LOD to 43.99 μg/mL with RSD within 1.4 - 3.6%. The recovery of guanidino compounds calculated by standard addition from serum was within 96.1 - 98.9%, with RSD 1.4 - 3.6%.

  19. Improving the Carprofen Solubility: Synthesis of the Zn2Al-LDH Hybrid Compound.

    Science.gov (United States)

    Capsoni, Doretta; Quinzeni, Irene; Bruni, Giovanna; Friuli, Valeria; Maggi, Lauretta; Bini, Marcella

    2018-01-01

    The development of efficient strategies for drug delivery is considerably desired. Indeed, often several issues such as the drug solubility, the control of the drug release rate, the targeted delivery of drugs, the drug bioavailability, and the minimization of secondary effects still present great obstacles. Different methodologies have been proposed, but the use of nano-hybrids compounds that combine organic and inorganic substances seems particularly promising. An interesting inorganic host is the layered double hydroxide (LDH) with a sheets structure and formula [M 2+ 1-x M 3+ x (OH) 2 ](A n- ) x/n yH 2 O (M 2+  = Zn, Mg; M 3+  = Al; A n-  = nitrates, carbonates, chlorides). The possibility to exchange these counterions with drug molecules makes these systems ideal candidates for the drug delivery. In this article, we synthesize by co-precipitation method the hybrid compound Carprofen-Zn 2 Al-LDH. Carprofen, a poorly soluble anti-inflammatory drug, could also benefit of the association with a natural antacid such as LDH, to reduce the gastric irritation after its administration. Through X-ray diffraction and Fourier-transformed infrared spectroscopy (FT-IR), we could verify the effective drug intercalation into LDH. The dissolution tests clearly demonstrate a significant improvement of the drug release rate when carprofen is in the form of hybrid compound. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  1. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Bayanzay K

    2016-08-01

    Full Text Available Karim Bayanzay, Lama Alzoebie Department of Hematology, Gulf Medical University, Ajman, United Arab Emirates Abstract: Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. Keywords: hematology, chelators, deferoxamine, deferiserox, deferiprone, liver iron concentration, iron overload, serum ferritin concentration, hepatic iron storage, iron chelation therapy

  2. Survival Mediterranean Style: Lifestyle Changes to Improve the Health of the US Fire Service.

    Science.gov (United States)

    Korre, Maria; Sotos-Prieto, Mercedes; Kales, Stefanos N

    2017-01-01

    Cardiovascular disease (CVD) causes almost half of all on-duty deaths in US firefighters and is an important and costly cause of morbidity. In addition, cancer is a growing health concern in this population. Obesity and obesity-associated, cardiometabolic risk clustering are major, modifiable risk factors for fire service CVD and cancer risk. The Mediterranean diet (MedDiet) is proven effective in primary and secondary CVD prevention. It is also associated with a decreased risk of cancer and other chronic diseases. Moreover, it can be adapted into successful workplace interventions. Emerging data from our group regarding the US Fire Service show that greater compliance with the MedDiet is associated with improved CVD risk profiles and less weight gain among career firefighters. Moreover, the fact that career firefighters take a considerable number of meals communally on the job also represents an excellent opportunity for a workplace Mediterranean Diet Nutritional Intervention (MDNI). The devastating effects of obesity, CVD, and cancer on the US fire service are recognized, but currently few effective preventive programs exist. The consistently positive health benefits from following a MedDiet and promising preliminary data in the fire service justify translational research to determine the most effective means of delivering MDNIs to US firefighters. Therefore, a high priority should be assigned to efforts, which can help further disseminate and implement our program of novel behavior change strategies, "Survival Mediterranean Style," throughout the US fire service and eventually to other occupations.

  3. Survival Mediterranean Style: Lifestyle Changes to Improve the Health of the US Fire Service

    Directory of Open Access Journals (Sweden)

    Maria Korre

    2017-12-01

    Full Text Available Cardiovascular disease (CVD causes almost half of all on-duty deaths in US firefighters and is an important and costly cause of morbidity. In addition, cancer is a growing health concern in this population. Obesity and obesity-associated, cardiometabolic risk clustering are major, modifiable risk factors for fire service CVD and cancer risk. The Mediterranean diet (MedDiet is proven effective in primary and secondary CVD prevention. It is also associated with a decreased risk of cancer and other chronic diseases. Moreover, it can be adapted into successful workplace interventions. Emerging data from our group regarding the US Fire Service show that greater compliance with the MedDiet is associated with improved CVD risk profiles and less weight gain among career firefighters. Moreover, the fact that career firefighters take a considerable number of meals communally on the job also represents an excellent opportunity for a workplace Mediterranean Diet Nutritional Intervention (MDNI. The devastating effects of obesity, CVD, and cancer on the US fire service are recognized, but currently few effective preventive programs exist. The consistently positive health benefits from following a MedDiet and promising preliminary data in the fire service justify translational research to determine the most effective means of delivering MDNIs to US firefighters. Therefore, a high priority should be assigned to efforts, which can help further disseminate and implement our program of novel behavior change strategies, “Survival Mediterranean Style,” throughout the US fire service and eventually to other occupations.

  4. Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

    Science.gov (United States)

    Pini, Maria; Rhodes, Davina H.; Castellanos, Karla J.; Cabay, Robert J.; Grady, Eileen F.; Fantuzzi, Giamila

    2012-01-01

    Obesity increases severity of acute pancreatitis (AP) by unclear mechanisms. We investigated the effect of the PPAR-gamma agonist rosiglitazone (RGZ, 0.01% in the diet) on severity of AP induced by administration of IL-12+ IL-18 in male C57BL6 mice fed a low fat (LFD) or high fat diet (HFD), under the hypothesis that RGZ would reduce disease severity in HFD-fed obese animals. In both LFD and HFD mice without AP, RGZ significantly increased body weight and % fat mass, with significant upregulation of adiponectin and suppression of erythropoiesis. In HFD mice with AP, RGZ significantly increased survival and hastened recovery from pancreatic inflammation, as evaluated by significantly improved pancreatic histology, reduced saponification of visceral adipose tissue and less severe suppression of erythropoiesis at Day 7 post-AP. This was associated with significantly lower circulating and pancreas-associated levels of IL-6, Galectin-3, osteopontin and TIMP-1 in HFD + RGZ mice, particularly at Day 7 post-AP. In LFD mice with AP, RGZ significantly worsened the degree of intrapancreatic acinar and fat necrosis as well as visceral fat saponification, without affecting other parameters of disease severity or inflammation. Induction of AP lead to major suppression of adiponectin levels at Day 7 in both HFD and HFD + RGZ mice. In conclusion, RGZ prevents development of severe AP in obese mice even though it significantly increases adiposity, indicating that obesity can be dissociated from AP severity by improving the metabolic and inflammatory milieu. However, RGZ worsens selective parameters of AP severity in LFD mice. PMID:22815875

  5. ZTI-01 Treatment Improves Survival of Animals Infected with Multidrug Resistant Pseudomonas aeruginosa

    Science.gov (United States)

    Lawrenz, Matthew B; denDekker, Ashley Eb; Cramer, Daniel E; Gabbard, Jon D; Lafoe, Kathryn M; Pfeffer, Tia L; Sotsky, Julie B; Vanover, Carol D; Ellis-Grosse, Evelyn J; Warawa, Jonathan M

    2017-01-01

    Abstract Background ZTI-01 (fosfomycin, FOS, for injection) is currently under US development to treat complicated urinary tract infections. ZTI-01 is unique compared with other antimicrobials in that it inhibits an early step in cell wall synthesis via covalent binding to MurA. ZTI-01 demonstrates broad in vitro activity against Gram-negative (GN) and -positive (GP) bacteria, including multidrug-resistant (MDR) organisms. Our study goals were to determine the efficacy of ZTI-01 as a monotherapy or in combination with meropenem against MDR Pseudomonas aeruginosa in a preclinical model of pulmonary infection. Methods 8 week old neutropenic mice were infected with a MDR strain of P. aeruginosa via intubation-mediated intratracheal (IMIT) instillation. 3 hours after instillation, mice received treatment with ZTI-01, meropenem, or ZTI-01 plus meropenem (combination therapy) q8h for 5 days. Mice were monitored every 8 hours for 7 days for development of disease and moribund animals were humanely euthanized. Lungs and spleens were harvested at euthanasia, or at 7 days for survivors, and processed for bacterial enumeration and development of pathology. Results Mice were challenged with a lethal dose of P. aeruginosa UNC-D. Mock treated animals succumbed to infection within 36 hours post-infection. Animals that received 6 g/kg/day ZTI-01 showed an increase in the MTD (52 hours) and 25% of the cohort were protected from lethal disease. Combining ZTI-01 with meropenem resulted in a significant increase in survival (≥75% of cohorts survived infection). Combination therapy also significantly decreased bacterial numbers in the lungs and inhibited dissemination to the spleens. Furthermore, animals receiving combination therapy were protected from significant inflammation in the lungs and the development of pneumonia. Conclusion Here we report that combination therapy with ZTI-01 and meropenem provides significant improvements in all disease manifestations over treatment with

  6. A Novel Phenolic Compound, Chloroxynil, Improves Agrobacterium-Mediated Transient Transformation in Lotus japonicus.

    Science.gov (United States)

    Kimura, Mitsuhiro; Cutler, Sean; Isobe, Sachiko

    2015-01-01

    Agrobacterium-mediated transformation is a commonly used method for plant genetic engineering. However, the limitations of Agrobacterium host-plant interactions and the complexity of plant tissue culture often make the production of transgenic plants difficult. Transformation efficiency in many legume species, including soybean and the common bean, has been reported to be quite low. To improve the transformation procedure in legumes, we screened for chemicals that increase the transformation efficiency of Lotus japonicus, a model legume species. A Chemical library was screened and chemicals that increase in transient transformation efficiency of L. japonicus accession, Miyakojima MG-20 were identified. The transient transformation efficiency was quantified by reporter activity in which an intron-containing reporter gene produces the GUS protein only when the T-DNA is expressed in the plant nuclei. We identified a phenolic compound, chloroxynil, which increased the genetic transformation of L. japonicus by Agrobacterium tumefaciens strain EHA105. Characterization of the mode of chloroxynil action indicated that it enhanced Agrobacterium-mediated transformation through the activation of the Agrobacterium vir gene expression, similar to acetosyringone, a phenolic compound known to improve Agrobacterium-mediated transformation efficiency. Transient transformation efficiency of L. japonicus with 5 μM chloroxynil was 60- and 6- fold higher than that of the control and acetosyringone treatment, respectively. In addition, transgenic L. japonicus lines were successfully generated by 5 μM chloroxynil treatment.Furthermore, we show that chloroxynil improves L. japonicus transformation by Agrobacterium strain GV3101 and rice transformation. Our results demonstrate that chloroxynil significantly improves Agrobacterium tumefaciens-mediated transformation efficiency of various agriculturally important crops.

  7. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    Directory of Open Access Journals (Sweden)

    Chou Pesus

    2011-08-01

    Full Text Available Abstract Background Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Methods Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. Results As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p p = 0.001 after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p Conclusions Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

  8. Positive end-expiratory pressure improves survival in a rodent model of cardiopulmonary resuscitation using high-dose epinephrine.

    LENUS (Irish Health Repository)

    McCaul, Conán

    2009-10-01

    Multiple interventions have been tested in models of cardiopulmonary resuscitation (CPR) to optimize drug use, chest compressions, and ventilation. None has studied the effects of positive end-expiratory pressure (PEEP) on outcome. We hypothesized that because PEEP can reverse pulmonary atelectasis, lower pulmonary vascular resistance, and potentially improve cardiac output, its use during CPR would increase survival.

  9. Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

    Science.gov (United States)

    Parmar, S; Kongtim, P; Champlin, R; Dinh, Y; Elgharably, Y; Wang, M; Bashir, Q; Shah, J J; Shah, N; Popat, U; Giralt, S A; Orlowski, R Z; Qazilbash, M H

    2014-08-01

    Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

  10. Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

    Science.gov (United States)

    Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-06-07

    Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

  11. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  12. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A.

    2013-01-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted

  13. Did professional attendance at home births improve early neonatal survival in Indonesia?

    Science.gov (United States)

    Hatt, Laurel; Stanton, Cynthia; Ronsmans, Carine; Makowiecka, Krystyna; Adisasmita, Asri

    2009-07-01

    BACKGROUND Early neonatal mortality has been persistently high in developing countries. Indonesia, with its national policy of home-based, midwife-assisted birth, is an apt context for assessing the effect of home-based professional birth attendance on early neonatal survival. METHODS We pooled four Indonesian Demographic and Health Surveys and used multivariate logistic regression to analyse trends in first-day and early neonatal mortality. We measured the effect of the context of delivery, including place and type of provider, and tested for changes in trend when the 'Midwife in the Village' programme was initiated. RESULTS Reported first-day mortality did not decrease significantly between 1986 and 2002, whereas early neonatal mortality decreased by an average of 3.2% annually. The rate of the decline did not change over the time period, either in 1989 when the Midwife in the Village programme was initiated, or in any year following when uptake of professional care increased. In simple and multivariate analyses, there were no significant differences in first-day or early neonatal death rates comparing home-based births with or without a professional midwife. Early neonatal mortality was higher in public facilities, likely due to selection. Biological determinants (twin births, male sex, short birth interval, previous early neonatal loss) were important for both outcomes. CONCLUSIONS Decreasing newborn death rates in Indonesia are encouraging, but it is not clear that these decreases are associated with greater uptake of professional delivery care at home or in health facilities. This may suggest a need for improved training in immediate newborn care, strengthened emergency referral, and continued support for family planning policies.

  14. Improving the survivability of Nb-encapsulated Ga targets for the production of 68Ge

    Science.gov (United States)

    Bach, H. T.; Claytor, T. N.; Hunter, J. F.; Olivas, E. R.; Kelsey, C. T., IV; Engle, J. W.; Connors, M. A.; Nortier, F. M.; Runde, W. H.; Moddrell, C.; Lenz, J. W.; John, K. D.

    2013-03-01

    At the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility (IPF), radioisotopes are produced for medical, scientific, and industrial applications by irradiating various targets with a 100 MeV, 230 μA proton beam. The medical isotope germanium-68 is produced by irradiating Nb capsules containing molten Ga target material. During irradiation, the Nb is subjected to intense radiation damage, corrosive attack by Ga, and mechanical and thermally-induced stresses for an extended period. Maintaining the structural integrity of the Nb target capsules during irradiation is crucial to contain the molten Ga target and the radioisotope product. In the present work, we focus on potential material related factors and assess the effect of the Nb stock material on target durability. We do so by comparing post-irradiation target mortality information to data collected during pre-irradiation ultrasound testing and X-ray imaging. We also explore possible failure mechanisms by using MCNP6 simulations and ANSYS codes to predict the induced atom displacement levels, hydrogen gas built-up, temperature distribution, and mechanical stresses. Our analysis, performed entirely in the context of an aggressive production program that allows for only limited diagnostic interference, suggests that using Nb stock with reasonably large and uniform grains is the most important factor in reducing early target failure at integrated beam current values <18 mAh and random failure at the face of the rear window at <60 mAh. We discuss possible failure mechanisms of failed targets that were fabricated using the same stock material and grain structure and then irradiated to integrated beam current values of up to 60 mAh and more. Based on these observations, we have enacted new specifications for Nb stock material quality, target design, and limits on integrated beam current. These changes have resulted in improved Nb capsule survivability.

  15. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

    2014-01-01

    in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

  16. High procedure volume is strongly associated with improved survival after lung cancer surgery

    DEFF Research Database (Denmark)

    Lüchtenborg, Margreet; Riaz, Sharma P; Coupland, Victoria H

    2013-01-01

    Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect....

  17. Yeast as a model for the identification of novel survival-promoting compounds applicable to treat degenerative diseases.

    Science.gov (United States)

    Verbandt, Sara; Cammue, Bruno P A; Thevissen, Karin

    2017-01-01

    Programmed cell death (PCD) plays an important role in development and normal metabolic functioning of organisms. Excessive cell death is the cause of many degenerative diseases, like neurodegenerative disorders and Wilson's disease, for which current therapies remain insufficient. Current therapies are mainly focused on decreasing the disease symptoms following cell death, rather than blocking the cell death process itself. The latter can be obtained by either decreasing the presence of the toxic trigger (like protein aggregation in case of many commonly known neurodegenerative diseases) or by blocking death-inducing signaling cascade(s). Given the high conservation in PCD processes between yeast and mammalian cells, in this review, we will focus on yeast as a model organism to study PCD-related diseases as well as on its use for drug discovery purposes. More specifically, we will provide a comprehensive overview of new compounds, which were identified in yeast-based drug screens, that either decrease the amount of toxic trigger or inhibit PCD signaling cascades under PCD-inducing conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken; Carstensen, Bendix

    2014-01-01

    OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors ha...

  19. Quantitative analysis of different volatile organic compounds using an improved electronic nose

    International Nuclear Information System (INIS)

    Gao, Daqi; Ji, Jiuming; Gong, Jiayu; Cai, Chaoqian

    2012-01-01

    This paper sets up an improved electronic nose with an automatic sampling mode, large volumetric vapors and constant temperature for headspace vapors and gas sensor array. In order to facilitate the fast recovery and good repeatability of gas sensors, the steps taken include (A) short-time contact with odors measured; (B) long-time purification using environmental air; (C) exact calibration using clean air before sampling. We employ multiple single-output perceptrons to discriminate and quantify multiple kinds of odors. This task is first regarded as multiple two-class discrimination problems and then multiple quantification problems, and accomplished by multiple single-output perceptrons followed by multiple single-output perceptrons. The experimental results for measuring and quantifying 12 kinds of volatile organic compounds with changing concentrations show that the type of electronic nose with a hierarchical perceptron model has a simple structure, easy operation, good repeatability and good discrimination and quantification performance. (paper)

  20. Activity Prediction of Schiff Base Compounds using Improved QSAR Models of Cinnamaldehyde Analogues and Derivatives

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2015-10-01

    Full Text Available In past work, QSAR (quantitative structure-activity relationship models of cinnamaldehyde analogues and derivatives (CADs have been used to predict the activities of new chemicals based on their mass concentrations, but these approaches are not without shortcomings. Therefore, molar concentrations were used instead of mass concentrations to determine antifungal activity. New QSAR models of CADs against Aspergillus niger and Penicillium citrinum were established, and the molecular design of new CADs was performed. The antifungal properties of the designed CADs were tested, and the experimental Log AR values were in agreement with the predicted Log AR values. The results indicate that the improved QSAR models are more reliable and can be effectively used for CADs molecular design and prediction of the activity of CADs. These findings provide new insight into the development and utilization of cinnamaldehyde compounds.

  1. Quantitative analysis of different volatile organic compounds using an improved electronic nose

    Science.gov (United States)

    Gao, Daqi; Ji, Jiuming; Gong, Jiayu; Cai, Chaoqian

    2012-10-01

    This paper sets up an improved electronic nose with an automatic sampling mode, large volumetric vapors and constant temperature for headspace vapors and gas sensor array. In order to facilitate the fast recovery and good repeatability of gas sensors, the steps taken include (A) short-time contact with odors measured; (B) long-time purification using environmental air; (C) exact calibration using clean air before sampling. We employ multiple single-output perceptrons to discriminate and quantify multiple kinds of odors. This task is first regarded as multiple two-class discrimination problems and then multiple quantification problems, and accomplished by multiple single-output perceptrons followed by multiple single-output perceptrons. The experimental results for measuring and quantifying 12 kinds of volatile organic compounds with changing concentrations show that the type of electronic nose with a hierarchical perceptron model has a simple structure, easy operation, good repeatability and good discrimination and quantification performance.

  2. Improved Survival With Radiation Therapy in High-Grade Soft Tissue Sarcomas of the Extremities: A SEER Analysis

    International Nuclear Information System (INIS)

    Koshy, Matthew; Rich, Shayna E.; Mohiuddin, Majid M.

    2010-01-01

    Purpose: The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. Methods and Materials: A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. Results: Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. Conclusions: To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

  3. Improving the Sustainability of Office Partition Manufacturing: Balancing Options for Reducing Emissions of Volatile Organic Compounds

    Directory of Open Access Journals (Sweden)

    Marc A. Rosen

    2009-06-01

    Full Text Available Options are examined to improve the sustainability of office partition manufacturing by reducing volatile organic compounds (VOC emissions. Base VOC emissions for a typical plant are estimated using a mass balance approach. Pollution prevention and sustainability measures are assessed using realistic criteria and weightings. Sustainability has been considered from an industry perspective, considering factors like economics, environmental impact, quality, health and safety. Through a case study, it is demonstrated that several advantageous options are available for reducing VOC emissions in manufacturing office furniture partitions, and thereby enhancing the sustainability of that industrial operation. The measures deemed most viable include implementing several best management practices, not painting of non-visible parts, switching gluing processes, recycling solvent and modifying attachments. The results are intended to be balanced so as to improve their acceptability and adoptability by industry. It appears that it would be advantageous for manufacturers of office panels to evaluate the feasibility of these measures and to implement the most appropriate. The results are likely extendable to other operations in the wood furniture industry, and would improve their sustainability.

  4. Augmented therapy of extensive Hodgkin's disease: radiation to bulk disease or prolongation of induction chemotherapy did not improve survival

    International Nuclear Information System (INIS)

    Rafla, S.; Coleman, M.; Propert, K.; Glicksman, A.; Peterson, B.; Nissen, N.; Brunner, K.; Kaufmann, T.; Holland, J.; Anderson, J.; Gottlieb, A.

    1996-01-01

    Purpose: This prospective, randomized trial in extensive, untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to 'bulk' disease) compared to standard, six months chemotherapy. Materials and Methods: Two-hundred fifty-eight patients, mostly stage IV, were randomized to four treatment regimens consisting of 6 cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; 6 cycles of CVPP followed by 25 Gray (Gy) radiotherapy; or 3 cycles CVPP, 25 Gy radiotherapy, and 3 cycles CVPP. Results: Complete remissions were achieved in 65% of all patients. A 58% overall 5 year survival was obtained. Relapses in irradiated areas of bulk disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease free survival or overall survival amongst the four regimens. Elderly patients responded less frequently. Conclusion: While radiotherapy provided control of local (bulk) disease, no impact on overall survival was apparent. Likewise doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit when compared to the standard six months of treatment

  5. The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression.

    Directory of Open Access Journals (Sweden)

    Li Bie

    Full Text Available Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001, and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67 labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time.

  6. Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.

    Science.gov (United States)

    Elshaikh, Mohamed A; Ruterbusch, Julie; Cote, Michele L; Cattaneo, Richard; Munkarah, Adnan R

    2013-11-01

    To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (pgeneration compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African-American race, and increased number of dissected LN. Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted.

  7. Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

    Science.gov (United States)

    Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

    2017-11-01

    Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

  8. Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function.

    Science.gov (United States)

    Song, Lili; Sun, Zhen; Kim, Do-Sung; Gou, Wenyu; Strange, Charlie; Dong, Huansheng; Cui, Wanxing; Gilkeson, Gary; Morgan, Katherine A; Adams, David B; Wang, Hongjun

    2017-08-30

    from the adipose of chronic pancreatitis patients improved islet survival and islet function after transplantation. The effects are in part mediated by paracrine secretion of IGF-1, suppression of inflammation, and promotion of angiogenesis. ASCs from chronic pancreatitis patients have the potential to be used as a synergistic therapy to enhance the efficacy of islet transplantation following pancreatectomy.

  9. Improving the quality of survival for infants of birthweight Victorian Infant Collaborative Study Group.

    Science.gov (United States)

    1993-01-04

    To compare between eras the early care of extremely low birthweight (birthweight eras, 1979-1980 and 1985-1987. PATIENTS AND OUTCOMES: Mortality data to two years of age were available for all infants liveborn in non-level-III centres in the two eras (1979-1980, n = 106; 1985-1987, n = 129). In 1979-1980, 47 of 52 infants transferred to a level-III centre were transported by the Newborn Emergency Transport Service (NETS); in 1985-1987, all 49 infants transferred were transported by NETS. Data concerning the immediate care after birth and during transport to a level-III centre were available for all infants transferred by NETS. All survivors were assessed for sensorineural impairments and disabilities at two years of age, corrected for prematurity. In both eras, 18 children born outside and transferred to a level-III centre survived to two years of age. Survivors in both eras had almost identical mean birthweights and gestational ages. There were trends for more survivors to be referred by paediatricians--1979-1980, 61%; 1985-1987, 83%; odds ratio (OR), 2.94; 95% confidence interval (CI), 0.7-12.4--and for quicker referral times to NETS in 1985-1987 (1979-1980, median 34.5 minutes after birth; 1985-1987, median 21.5 minutes after birth; z = 1.91, P = 0.056). It was possible only during 1985-1987 to monitor transcutaneous PO2 during transport. Durations of transport were similar in both eras. However, only in 1985-1987 was it possible in survivors to reduce significantly the inspired oxygen concentration during transport (median reductions in inspired oxygen, 1979-1980 3.5%; 1985-1987 20%; P = 0.028). Neurological impairment rates were substantially lower in survivors transported in the latter era (1979-1980 72% impaired; 1985-1987 22% impaired; OR 0.14, 95% CI 0.04-0.52). Of the neurological impairments, fewer had severe developmental delay alone (1979-1980 22%; 1985-1987 0%; OR 0.09, 95% CI 0.018-0.46), and the rate of blindness was lower, but the latter difference

  10. A macroporous heparin-releasing silk fibroin scaffold improves islet transplantation outcome by promoting islet revascularisation and survival.

    Science.gov (United States)

    Mao, Duo; Zhu, Meifeng; Zhang, Xiuyuan; Ma, Rong; Yang, Xiaoqing; Ke, Tingyu; Wang, Lianyong; Li, Zongjin; Kong, Deling; Li, Chen

    2017-09-01

    Islet transplantation is considered the most promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical islet transplantation is limited by long-term graft dysfunction and attrition. We have investigated the therapeutic potential of a silk fibroin macroporous (SF) scaffold for syngeneic islet transplantation in diabetic mice. The SF scaffold was prepared via lyophilisation, which enables incorporation of active compounds including cytokines, peptide and growth factors without compromising their biological activity. For the present study, a heparin-releasing SF scaffold (H-SF) in order to evaluate the versatility of the SF scaffold for biological functionalisation. Islets were then co-transplanted with H-SF or SF scaffolds in the epididymal fat pad of diabetic mice. Mice from both H-SF and SF groups achieved 100% euglycaemia, which was maintained for 1year. More importantly, the H-SF-islets co-transplantation led to more rapid reversal of hyperglycaemia, complete normalisation of glucose responsiveness and lower long-term blood glucose levels. This superior transplantation outcome is attributable to H-SF-facilitated islet revascularisation and cell proliferation since significant increase of islet endocrine and endothelial cells proliferation was shown in grafts retrieved from H-SF-islets co-transplanted mice. Better intra-islet vascular reformation was also evident, accompanied by VEGF upregulation. In addition, when H-SF was co-transplanted with islets extracted from vegfr2-luc transgenic mice in vivo, sustained elevation of bioluminescent signal that corresponds to vegfr2 expression was collected, implicating a role of heparin-dependent activation of endogenous VEGF/VEGFR2 pathway in promoting islet revascularisation and proliferation. In summary, the SF scaffolds provide an open platform as scaffold development for islet transplantation. Furthermore, given the pro-angiogenic, pro-survival and minimal post

  11. Increased Lymph Node Yield Is Associated with Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Jess, Per; Roikjaer, Ole

    2015-01-01

    patients in Denmark who were diagnosed with International Union Against Cancer stage I to III adenocarcinoma of the rectum and so treated in the period from 2003 to 2011 were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: The observed percentages...

  12. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    . Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival...

  13. Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau.

    Directory of Open Access Journals (Sweden)

    Mette Lundsby Jensen

    Full Text Available BACKGROUND: In urban Guinea-Bissau, adults with a vaccinia scar had better survival but also a higher prevalence of HIV-2 infection. We therefore investigated the association between vaccinia scar and survival and HIV infection in a rural area of Guinea-Bissau. METHODOLOGY/PRINCIPAL FINDINGS: In connection with a study of HIV in rural Guinea-Bissau, we assessed vaccinia and BCG scars in 193 HIV-1 or HIV-2 infected and 174 uninfected participants. Mortality was assessed after 2(1/2-3 years of follow-up. The analyses were adjusted for age, sex, village, and HIV status. The prevalence of vaccinia scar was associated with age, village, and HIV-2 status but not with sex and schooling. Compared with individuals without any scar, individuals with a vaccinia scar had better survival (mortality rate ratio (MR = 0.22 (95% CI 0.08-0.61, the MR being 0.19 (95% CI 0.06-0.57 for women and 0.40 (95% CI 0.04-3.74 for men. Estimates were similar for HIV-2 infected and HIV-1 and HIV-2 uninfected individuals. The HIV-2 prevalence was higher among individuals with a vaccinia scar compared to individuals without a vaccinia scar (RR = 1.57 (95% CI 1.02-2.36. CONCLUSION: The present study supports the hypothesis that vaccinia vaccination may have a non-specific beneficial effect on adult survival.

  14. Special LOFT features for improved monitoring and survival of LOCA transients

    International Nuclear Information System (INIS)

    Goodrich, L.D.; Leach, L.P.; Klingler, T.B.; Morrow, J.C.; Phoenix, W.C.; Satterwhite, D.G.; Sumpter, K.C.; Rouhani, S.Z.; Welland, H.J.

    1980-01-01

    LOFT is designed to monitor and survive Loss-Of-Coolant-Accidents (LOCAs). This report presents the primary design difference from LPWRs that were required to accomplish this. These design differences may be of interest to the nuclear power generator industry. This report should be revised semi-annually or as developments in the LOFT Program require

  15. Factors associated with improved survival among older colorectal cancer patients in the US: a population-based analysis

    Directory of Open Access Journals (Sweden)

    Earle Craig C

    2009-07-01

    Full Text Available Abstract Background The purpose of this study was to estimate the relative impact of changes in demographics, stage at detection, treatment mix, and medical technology on 5-year survival among older colorectal cancer (CRC patients. Methods We selected older patients diagnosed with CRC between 1992 and 2000 from the SEER-Medicare database and followed them through 2005. Trends in demographic characteristics, stage at detection and initial treatment mix were evaluated descriptively. Separate multivariate logistic regression models for colon (CC and rectal cancer (RC patients were estimated to isolate the independent effects of these factors along with technological change (proxied by cohort year on 5-year survival. Results Our sample included 37,808 CC and 13,619 RC patients (combined mean ± SD age: 77.2 ± 7.0 years; 55% female; 87% white. In recent years, more CC patients were diagnosed at Stage I and fewer at Stages II and IV, and more RC patients were diagnosed at Stage I and fewer at Stages II and III. CC and RC patients diagnosed in later years were slightly older with somewhat better Charlson scores and were more likely to be female, from the Northeast, and from areas with higher average education levels. Surgery alone was more common in later years for CC patients while combined surgery, chemotherapy, and radiotherapy was more common for RC patients. Between 1992 and 2000, 5-year observed survival improved from 43.0% to 46.3% for CC patients and from 39.4% to 42.2% for RC patients. Multivariate logistic regressions indicate that patients diagnosed in 2000 had significantly greater odds of 5-year survival than those diagnosed in 1992 (OR: 1.35 for CC, 1.38 for RC. Our decomposition suggests that early detection had little impact on survival; rather, technological improvements (e.g., new medical technologies or more effective use of existing technologies and changing demographics were responsible for the largest share of the change in 5

  16. Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?

    International Nuclear Information System (INIS)

    Poulsen, Michael G.; Rischin, Danny; Porter, Ian; Walpole, Euan; Harvey, Jennifer; Hamilton, Chris; Keller, Jacqui; Tripcony, Lee

    2006-01-01

    Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m 2 i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For

  17. Poly-β-hydroxybutyrate (PHB) accumulating Bacillus spp. improve the survival, growth and robustness of Penaeus monodon (Fabricius, 1798) postlarvae.

    Science.gov (United States)

    Laranja, Joseph Leopoldo Q; Ludevese-Pascual, Gladys L; Amar, Edgar C; Sorgeloos, Patrick; Bossier, Peter; De Schryver, Peter

    2014-10-10

    Low larval survival resulting from suboptimal culture conditions and luminous vibriosis poses a major problem for the larviculture of penaeid shrimp. In this study, a poly-β-hydroxybutyrate (PHB) accumulating mixed bacterial culture (mBC; 48.5% PHB on cell dry weight) and two PHB accumulating bacterial isolates, Bacillus sp. JL47 (54.7% PHB on cell dry weight) and Bacillus sp. JL1 (45.5% PHB on cell dry weight), were obtained from a Philippine shrimp culture pond and investigated for their capacity to improve growth, survival and robustness of Penaeus monodon postlarvae (PL). Shrimp PL1 and shrimp PL30 were provided with the PHB containing bacterial cultures in the feed for 30 days followed by, respectively, a challenge with pathogenic Vibrio campbellii and exposure to a lethal dose of ammonia. Prior to the pathogenic challenge or ammonia stress, growth and survival were higher for shrimp receiving the PHB accumulating bacteria as compared to shrimp receiving diets without bacterial additions. After exposure to the pathogenic challenge the shrimp fed PHB accumulating bacteria showed a higher survival as compared to non-treated shrimp, suggesting an increase in robustness for the shrimp. Similar effects were observed when shrimp PL30 were provided with the PHB accumulating bacterial cultures during a challenge with pathogenic V. campbellii through the water. The survival of shrimp exposed to lethal ammonia stress showed no significant difference between PHB accumulating bacteria-fed shrimp and non-PHB treated shrimp. The data illustrate that bacilli capable of accumulating PHB can provide beneficial effects to P. monodon post-larvae during culture in terms of growth performance, survival and resistance against pathogenic infection and ammonia stress. Further investigations are required to verify the PHB effect of the bacterial cultures on the shrimp. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Improve the biodegradability of post-hydrothermal liquefaction wastewater with ozone: conversion of phenols and N-heterocyclic compounds.

    Science.gov (United States)

    Yang, Libin; Si, Buchun; Martins, Marcio Arêdes; Watson, Jamison; Chu, Huaqiang; Zhang, Yuanhui; Tan, Xiaobo; Zhou, Xuefei; Zhang, Yalei

    2017-04-01

    Hydrothermal liquefaction is a promising technology to convert wet biomass into bio-oil. However, post-hydrothermal liquefaction wastewater (PHWW) is also produced during the process. This wastewater contains a high concentration of organic compounds, including phenols and N-heterocyclic compounds which are two main inhibitors for biological treatment. Thus, proper treatment is required. In this work, ozone was used to convert phenols and N-heterocyclic compounds with a dosage range of 0-4.64 mg O 3 /mL PHWW. After ozone treatment, the phenols were fully converted, and acids were produced. However, N-heterocyclic compounds were found to have a low conversion rate (21.7%). The kinetic analysis for the degradation of phenols and N-heterocyclic compounds showed that the substitute played an important role in determining the priority of ozone reactions. The OH moiety in the ring compounds (phenols and pyridinol) may form hydroxyl radical, which lead to an efficient reaction. A substantial improved biodegradability of PHWW was observed after ozone treatment. The ratio of BOD 5 /COD was increased by about 32.36%, and reached a maximum of 0.41. The improved biodegradability of PHWW was justified by the conversion of phenols and N-heterocyclic compounds.

  19. Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation.

    Science.gov (United States)

    Yannopoulos, Demetris; Bartos, Jason A; George, Stephen A; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P

    2017-01-01

    Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Radiotherapy Is Associated With Improved Survival in Adjuvant and Palliative Treatment of Extrahepatic Cholangiocarcinomas

    International Nuclear Information System (INIS)

    Shinohara, Eric T.; Mitra, Nandita; Guo Mengye; Metz, James M.

    2009-01-01

    Purpose: Extrahepatic cholangiocarcinomas (EHC) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (RT) for EHC have not been performed. The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population. Methods and Materials: This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was overall survival. Results: Patients underwent surgery (28.8%), RT (10.0%), surgery and RT (14.7%), or no RT or surgery (46.4%). The median age of the patient population was 73 years (range, 23-104), 52.5% were men, and 80.7% were white. The median overall survival time was 16 months (95% confidence interval [CI] 15-17), 9 months (95% CI 9-11), 9 months (95% CI 9-10), and 4 months (95% CI 3-4) for surgery and RT, surgery, RT, and no RT or surgery, respectively. The overall survival was significantly different between the surgery and surgery and RT groups (p < .0001) and RT and no RT or surgery groups (p < .0001) on the log-rank test. The propensity score-adjusted analyses of surgery and RT vs. surgery (hazard ratio, 0.94; 95% CI, 0.84-1.05) were not significantly different, but that for RT vs. no RT or surgery (hazard ratio, 0.61; 95% CI, 0.54-0.70) was significantly different. Conclusion: These results suggest that palliative RT prolongs survival in patients with EHC. The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score. Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC.

  1. Virally delivered, constitutively active NFκB improves survival of injured retinal ganglion cells.

    Science.gov (United States)

    Dvoriantchikova, Galina; Pappas, Steve; Luo, Xueting; Ribeiro, Marcio; Danek, Dagmara; Pelaez, Daniel; Park, Kevin K; Ivanov, Dmitry

    2016-12-01

    As axon damage and retinal ganglion cell (RGC) loss lead to blindness, therapies that increase RGC survival and axon regrowth have direct clinical relevance. Given that NFκB signaling is critical for neuronal survival and may regulate neurite growth, we investigated the therapeutic potential of NFκB signaling in RGC survival and axon regeneration. Although both NFκB subunits (p65 and p50) are present in RGCs, p65 exists in an inactive (unphosphorylated) state when RGCs are subjected to neurotoxic conditions. In this study, we used a phosphomimetic approach to generate DNA coding for an activated (phosphorylated) p65 (p65mut), then employed an adeno-associated virus serotype 2 (AAV2) to deliver the DNA into RGCs. We tested whether constitutive p65mut expression prevents death and facilitates neurite outgrowth in RGCs subjected to transient retinal ischemia or optic nerve crush (ONC), two models of neurotoxicity. Our data indicate that RGCs treated with AAV2-p65mut displayed a significant increase in survival compared to controls in ONC model (77 ± 7% vs. 25 ± 3%, P-value = 0.0001). We also found protective effect of modified p65 in RGCs of ischemic retinas (55 ± 12% vs. 35 ± 6%), but not to a statistically significant degree (P-value = 0.14). We did not detect a difference in axon regeneration between experimental and control animals after ONC. These findings suggest that increased NFκB signaling in RGCs attenuates retinal damage in animal models of neurodegeneration, but insignificantly impacts axon regeneration. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Differential improvement in survival among patients with AIDS after the introduction of HAART

    OpenAIRE

    2007-01-01

    Abstract We explored changes in the survival of patients with AIDS (PWA) according to the availability of antiretroviral drugs (1994-2002). We tested whether changes in the hazard ratio of progression to death (HR) have been homogeneous among various groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French National Surveillance Institute by 2002. Four calendar periods were defined: monotherapy (1994-1995), bitherapy-HAART transition (1996), early HAART (19...

  3. Improved survival of mesenchymal stem cells by macrophage migration inhibitory factor

    OpenAIRE

    Xia, Wenzheng; Xie, Congying; Jiang, Miaomiao; Hou, Meng

    2015-01-01

    Macrophage migration inhibitory factor (MIF) is a critical inflammatory cytokine that was recently associated with progenitor cell survival and potently inhibits apoptosis. We examined the protective effect of MIF on hypoxia/serum deprivation (SD)-induced apoptosis of mesenchymal stem cells (MSCs), as well as the possible mechanisms. MSCs were obtained from rat bone marrow and cultured in vitro. Apoptosis was induced by culturing MSCs under hypoxia/SD conditions for up to 24?h and assessed by...

  4. A high ratio of apoptosis to proliferation correlates with improved survival after radiotherapy for cervical adenocarcinoma

    International Nuclear Information System (INIS)

    Sheridan, Mary T.; Cooper, Rachel A.; West, Catharine M.L.

    1999-01-01

    Purpose: A retrospective study was made of the role of apoptosis in determining radiotherapy outcome in 39 adenocarcinoma of the cervix. A comparison was also made of the detection of apoptosis by morphology and the TdT dUtp nick end-labeling (TUNEL) assay. Methods and Materials: The level of apoptosis was assessed in paraffin-embedded sections by cell morphology, the TUNEL assay, and a combination of the two. A total of 2,000 cells were counted per section, to obtain apoptotic (AI) and mitotic (MI) indices. Results: Patients with a high AI had a higher survival rate than those with a low AI, however, the difference was not significant. Using a ratio of apoptosis to proliferation indices, patients with an AI:MI > median had significantly better survival than those with AI:MI < median. This was true where the AI was quantified by morphology alone (p = 0.030) or in combination with the TUNEL assay (p = 0.008). Where the AI was quantified by a combination of morphology and TUNEL, the 5-year survival rates for women with AI:MI greater or less than the median were 81% and 25%, respectively. Conclusion: A high ratio of AI:MI in adenocarcinoma of the cervix indicates a good prognosis. A combination of the TUNEL assay and morphology provided the best discrimination between outcome groups

  5. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2015-01-01

    Full Text Available Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1 or fibroblasts (FB, group 2 under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001 without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  6. Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual.

    Science.gov (United States)

    Morisada, S; Nosaka, N; Tsukahara, K; Ugawa, T; Sato, K; Ujike, Y

    2015-09-30

    The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive burns (SEB) treated before and after implementation of these new guidelines at this institution. The patients included in this study had a burn index (BI) ≥30 or a prognostic burn index (PBI = BI + patient's age) ≥100. The survival rate of the patients with BI ≥30 was 65.2% with the traditional treatment and 100% with the new guidelines. Likewise, the survival rate of the patients with PBI ≥100 was 61.1% with the traditional treatment compared to 100% with the new guidelines. Together, these data demonstrate that the new treatment guidelines dramatically improved the treatment outcome and survival of SEB patients.

  7. Identifying an Inciting Antigen Is Associated With Improved Survival in Patients With Chronic Hypersensitivity Pneumonitis

    Science.gov (United States)

    Swigris, Jeffrey J.; Forssén, Anna V.; Tourin, Olga; Solomon, Joshua J.; Huie, Tristan J.; Olson, Amy L.; Brown, Kevin K.

    2013-01-01

    Background: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. Methods: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis. Results: Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047). Conclusions: Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival. PMID:23828161

  8. Survival following ruptured abdominal aortic aneurysm before and during the IMPROVE Trial: a single-centre series.

    Science.gov (United States)

    Ambler, G K; Twine, C P; Shak, J; Rollins, K E; Varty, K; Coughlin, P A; Hayes, P D; Boyle, J R

    2014-04-01

    The first large-scale randomised trial (Immediate Management of the Patient with Rupture: Open Versus Endovascular repair [IMPROVE]) for endovascular repair of ruptured abdominal aortic aneurysm (rEVAR) has recently finished recruiting patients. The aim of this study was to examine the impact on survival after rEVAR when the IMPROVE protocol was initiated in a high volume abdominal aortic aneurysm (AAA) centre previously performing rEVAR. One hundred and sixty-nine patients requiring emergency infrarenal AAA repair from January 2006 to April 2013 were included. Eighty-four patients were treated before (38 rEVAR, 46 open) and 85 (31 rEVAR, 54 open) were treated during the trial period. A retrospective analysis was performed. Before the trial, there was a significant survival benefit for rEVAR over open repair (90-day mortality 13% vs. 30%, p = .04, difference remained significant up to 2 years postoperatively). This survival benefit was lost after starting randomisation (90-day mortality 35% vs. 33%, p = .93). There was an increase in overall 30-day mortality from 15% to 31% (p = .02), while there was no change for open repair (p = .438). There was a significant decrease in general anaesthetic use (p = .002) for patients treated during the trial. Randomised patients had shorter hospital and intensive treatment unit stays (p = .006 and p = .03 respectively). The change in survival seen during the IMROVE trial highlights the need for randomised rather than cohort data to eliminate selection bias. These results from a single centre reinforce those recently reported in IMPROVE. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  9. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

    Science.gov (United States)

    Brune, Mats; Castaigne, Sylvie; Catalano, John; Gehlsen, Kurt; Ho, Anthony D; Hofmann, Wolf-Karsten; Hogge, Donna E; Nilsson, Bo; Or, Reuven; Romero, Ana I; Rowe, Jacob M; Simonsson, Bengt; Spearing, Ruth; Stadtmauer, Edward A; Szer, Jeff; Wallhult, Elisabeth; Hellstrand, Kristoffer

    2006-07-01

    The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.

  10. Use of natural compounds to improve the microbial stability of Amaranth-based homemade fresh pasta.

    Science.gov (United States)

    Del Nobile, M A; Di Benedetto, N; Suriano, N; Conte, A; Lamacchia, C; Corbo, M R; Sinigaglia, M

    2009-04-01

    A study on the use of natural antimicrobial compounds to improve the microbiological stability of refrigerated amaranth-based homemade fresh pasta is presented in this work. In particular, the antimicrobial activity of thymol, lemon extract, chitosan and grapefruit seed extract (GFSE) has been tested against mesophilic and psychrotrophic bacteria, total coliforms, Staphylococcus spp., yeasts and moulds. A sensory analysis on both fresh and cooked pasta was also run. Results suggest that chitosan and GFSE strongly increase the microbial acceptability limit of the investigated spoilage microorganisms, being the former the most effective. Thymol efficiently reduces the growth of mesophilic bacteria, psychrotrophic bacteria and Staphylococcus spp., whereas it does not affect, substantially, the growth cycle of total coliforms. Lemon extract is the less effective in preventing microbial growth. In fact, it is able to delay only total mesophilic and psychrotrophic bacterial evolution. From a sensorial point of view no significant differences were recorded between the control samples and all the types of loaded amaranth-based pasta.

  11. Improvement of Bioactive Compound Classification through Integration of Orthogonal Cell-Based Biosensing Methods

    Directory of Open Access Journals (Sweden)

    Goran N. Jovanovic

    2007-01-01

    Full Text Available Lack of specificity for different classes of chemical and biological agents, and false positives and negatives, can limit the range of applications for cell-based biosensors. This study suggests that the integration of results from algal cells (Mesotaenium caldariorum and fish chromatophores (Betta splendens improves classification efficiency and detection reliability. Cells were challenged with paraquat, mercuric chloride, sodium arsenite and clonidine. The two detection systems were independently investigated for classification of the toxin set by performing discriminant analysis. The algal system correctly classified 72% of the bioactive compounds, whereas the fish chromatophore system correctly classified 68%. The combined classification efficiency was 95%. The algal sensor readout is based on fluorescence measurements of changes in the energy producing pathways of photosynthetic cells, whereas the response from fish chromatophores was quantified using optical density. Change in optical density reflects interference with the functioning of cellular signal transduction networks. Thus, algal cells and fish chromatophores respond to the challenge agents through sufficiently different mechanisms of action to be considered orthogonal.

  12. Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early–intermediate stage hepatocellular carcinoma

    Science.gov (United States)

    Lee, Teng-Yu; Lin, Chen-Chun; Chen, Chiung-Yu; Wang, Tsang-En; Lo, Gin-Ho; Chang, Chi-Sen; Chao, Yee

    2017-01-01

    Abstract Background/Objective: The survival benefit of treatment for unresectable hepatocellular carcinoma (HCC) with transcatheter arterial chemoembolization (TACE) combined with sorafenib remains uncertain. We compared the survival of patients treated with TACE and sorafenib with that of patients treated with TACE alone. Methods: This was a post hoc analysis of the Study in Asia of the Combination of TACE with Sorafenib in Patients with HCC (START) trial. All patients who received TACE and interrupted dosing of sorafenib for early or intermediate-stage HCC in Taiwan from 2009 to 2010 were recruited into the TACE and sorafenib group. They were randomly matched 1:1 by age, sex, Child–Pugh score, tumor size, tumor number, and tumor stage with patients from Taichung Veterans General Hospital in Taiwan who received TACE alone and who fulfilled the selection criteria of the START trial during the same time period (control group). Patient survival [cumulative incidence and hazard ratio (HR)] of the 2 groups were analyzed and compared. Results: The baseline characteristics of the 36 patients in each group were similar. Tumor response rates were significantly better in the TACE and sorafenib group (P < .04). Overall survival of the TACE and sorafenib group was also significantly better than that of the control (TACE alone) group over the 2 years [78%, 95% confidence interval (95% CI) 64–91 vs 49, 95% CI 32–66; P = .012]. In the multivariate regression analysis, TACE and sorafenib was found to be independently associated with a decreased risk of mortality (HR 0.33, 95% CI 0.12–0.89; P = .015). Multivariate stratified analyses verified this association in each patient subgroup (all HR < 1.0). Conclusion: With a high patient tolerance to an interrupted sorafenib dosing schedule, the combination of TACE with sorafenib was associated with improved overall survival in early–intermediate stage HCC when compared with treatment with TACE alone. PMID

  13. Do intramedullary implants improve survival in elderly patients with trochanteric fractures? A retrospective study.

    Science.gov (United States)

    Vermesan, D; Prejbeanu, R; Poenaru, D V; Petrescu, H; Apostol, E; Inchingolo, F; Dipalma, G; Abbinante, A; Caprio, M; Potenza, M A; Cagiano, R; Malcangi, G; Inchingolo, A D; Haragus, H

    2015-01-01

    There is currently no consensus regarding superiority of the intramedullary fixation over the sliding hip screw. Regional variation remains high and not backed up by solid evidence. Given these premises we aimed to analyze weather implant preference can influence the postoperative survival. Secondary objectives were determining the trend for implant choice and confounding factors associated with intramedullary nails compared to sliding hip screws. Retrospective data was obtained from patient charts with the main diagnosis of extracapsular/ trochanteric fractures, corresponding to ICD S72.1 codes. Between 2008-2012, 441 patients underwent osteosynthesis with a dynamic hip screw and 155 with intramedullary nail respectively. The living status was determined by comparing the patient identification number against the national population evidence records. The lifetable shows similar survival for both implants over the 5 year period. The yearly mortality was 19.4% for the dynamic hip screw and 21.8% for the intramedullary implant respectively, even though the later were used predominantly in older patients. This age difference is significant according to both parametric and non-parametric tests whereas duration of hospital stay are similar. We found a clear increase in the proportion of intramedullary implants, for a total of 11.2% over the 5 year period. There is no difference for the one year mortality and overall survival between sliding screw plates and intramedullary constructs. A clear increase in the use of intramedullary implants for trochanteric fractures was observed. This is even more apparent for older ages, presumably due to an higher surgeon confidence with the biomechanical stability of the intramedullary constructs.

  14. Improved survival with combined modality treatment for Stage IV breast cancer

    International Nuclear Information System (INIS)

    Nervi, C.; Arcangeli, G.; Concolino, F.; Cortese, M.

    1979-01-01

    Between 1974 and 1977, 85 patients with breast cancer at first postmastectomy relapse were irradiated (Radiation 3500 to 6000 rad--3/5 weeks) to all clinically evident lesions. Radiation fields were properly shaped to include a maximum 40% active bone marrow. After 3 to 4 weeks rest, chemotherapy was started as adjuvant therapy for residual or subclinical disease (ADR 30 mg/M 2 Day 1 and 8, 5-FU 400 mg/M 2 Day 1 and 8, CY 100 mg/M 2 Day 1 through 14: repeated after 14 days). ADR was discontinued at 500/M 2 and substituted by MTX 30 mg/M 2 Day 1 and 8 for a total of 2 years. Irradiated sites were chest wall in 35, supraclavicular and internal mammary nodes in 22, bone in 56, single lung lesions in 12, brain in 24. Controls were 52 comparable but non-randomized patients treated with chemotherapy only. Forty days after x-irradiation 68 patients (80%) were free of disease (NED) while in 17 cases (20%) some residual was still present (RED). In 28 of 68 cases (41%) NED after x-irradiation and 13 of 17 (76%) in RED group developed second relapse after a median interval of 26 and 20 mos., respectively. Four of 52 patients (8%) in the control group had complete regression with a median interval to second relapse of 7 mos. Median survival was 30 mos., 24 mos., and 13 mos., respectively, for NED, RED and chemotherapy only. Eighteen patients (26%) are free of disease after 36 to 48 mos. in the combined modality group; none in the chemotherapy group. Combined treatment cases did not show untolerable myelodepression. In 10 long-surviving patients a marked subcutaneous and skin fibrosis developed because of drug additive effect. Stage IV breast cancers rendered clinically free of disease with x-irradiation and subsequently treated with chemotherapy survive significantly longer than with chemotherapy alone

  15. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2016-06-01

    Euthanasia 24 hours Euthanasia 72 hours Normal Saline 2 2 20% DMSO 2 2 BHB/M 1:10 2 2 BHB/M 1:5 2 2 BHB/M 1:2 2 2 BHB/M 1:1...and processed using H&E staining. 4 Table 2. Completed Randomization Groups Randomization Euthanasia 24 hours Euthanasia 72 hours Normal Saline 2...contribution o the individual components of BHB/M to the toxicity profile of the product at MTD. Observation of the preservation of survival benefit

  16. A Decade of Never-smokers Among Lung Cancer Patients-Increasing Trend and Improved Survival.

    Science.gov (United States)

    Toh, Chee-Keong; Ong, Whee-Sze; Lim, Wan-Teck; Tan, Daniel Shao-Weng; Ng, Quan-Sing; Kanesvaran, Ravindran; Seow, Wei-Jie; Ang, Mei-Kim; Tan, Eng-Huat

    2018-03-17

    It is not known whether clinicopathologic characteristics, treatment, and survival of never-smokers among lung cancer incident cases have changed over time. We assessed the trend and overall survival (OS) of these patients within our institution during a 10-year period. We reviewed 2 cohorts of non-small-cell lung cancer patients with a diagnosis from 1999 to 2002 and from 2008 to 2011. The patient characteristics and OS were compared by smoking status within each cohort and between the 2 cohorts over time. Of the 992 patients in the 1999-2002 cohort and the 1318 patients in the 2008-2011 cohort, 902 and 1272 had a known smoking status, respectively. The proportion of never-smokers increased from 31% in 1999-2002 to 48% in 2008-2011 (P never-, former-, and current-smokers have remained largely constant over time. A greater proportion of never-smokers had Eastern Cooperative Oncology Group performance status 0 to 1 and adenocarcinoma. The median OS increased from 15.5 months in 1999-2002 to 24.9 months in 2008-2011 (P = .001) for never-smokers, 12.3 to 15.9 months (P = .150) for former-smokers, and 10.5 to 13.9 months (P = .011) for current-smokers. The larger survival improvement among never-smokers was likely accounted for by the larger increase in never-smokers who were treated with tyrosine kinase inhibitors and pemetrexed over time. We found an increasing trend of never-smokers among incident lung cancer cases and improved survival for these patients during a 10-year period. The documentation of smoking status in any national cancer registry is vital to estimate the true incidence of lung cancer among never-smokers over time. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  18. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

    Science.gov (United States)

    Meanwell, Nicholas A

    2011-09-19

    The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

  19. Vaccination of free-living juvenile wild rabbits (Oryctolagus cuniculus) against myxomatosis improved their survival.

    Science.gov (United States)

    Guitton, Jean-Sébastien; Devillard, Sébastien; Guénézan, Michel; Fouchet, David; Pontier, Dominique; Marchandeau, Stéphane

    2008-04-17

    For several decades, the populations of the European wild rabbit (Oryctolagus cuniculus) have declined, which is partly due to myxomatosis. Vaccination against this disease is expected to contribute to restoration of rabbit populations but the actual impact of myxomatosis is not well known and vaccination might have some negative effects. We analyzed the capture-mark-recapture data obtained in a 4-year field experiment (1991-1994) in a park near Paris, France wherein 300 out of 565 seronegative juvenile rabbits were vaccinated at first capture against myxomatosis with the nontransmissible Dervaximyxo SG33 vaccine. After accounting for weight at first capture, age-class (juvenile/adult), "trap-happiness" and season (spring/autumn) of the capture event, vaccinated rabbits had 1.8-fold greater odds of surviving than the unvaccinated rabbits. The average summer survival risk for vaccinated juveniles was 0.63 (+/-0.08 S.E.) whereas it was 0.48 (+/-0.08 S.E.) for unvaccinated juvenile rabbits.

  20. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

    2016-06-15

    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  1. Improved survival for non-Hodgkin lymphoma patients in New South Wales, Australia

    Directory of Open Access Journals (Sweden)

    O'Connell Dianne L

    2010-05-01

    Full Text Available Abstract Background We evaluated if the survival benefit of adding rituximab to standard chemotherapy for non-Hodgkin lymphoma (NHL observed in clinical trials has been experienced by an Australian NHL patient population. Methods NHL cases diagnosed in 1985-2004 in New South Wales (NSW were followed-up to the end of 2004. Rituximab prescription data were obtained from Medicare Australia. Using a Poisson regression model adjusted for age group, sex, NHL subtype and time period (1990-1994, 1995-1999 and 2000-2004, we estimated excess risk of death after a diagnosis of NHL. To give context to the survival trend, trends in incidence and mortality were also estimated. Results Compared with 1990-1994, after adjusting for age, sex and NHL subtype the relative excess risk of death was significantly lower (p Conclusion It is likely that some benefit of adding rituximab to the standard chemotherapy for NHL has been experienced at the population level.

  2. Improved survival prediction from lung function data in a large population sample

    DEFF Research Database (Denmark)

    Miller, M.R.; Pedersen, O.F.; Lange, P.

    2008-01-01

    Studies relating tung function to survival commonly express lung function impairment as a percent of predicted but this retains age, height and sex bias. We have studied alternative methods of expressing forced expiratory volume in 1 s (FEV1) for predicting all cause and airway related lung disease.......1 respectively. Cut levels of lung function were used to categorise impairment and the HR for multivariate prediction of all cause and airway related lung disease mortality were 10 and 2044 respectively for the worst category of FEV1/ht(2) compared to 5 and 194 respectively for the worst category of FEV1PP....... In univariate predictions of all cause mortality the HR for FEV1/ht(2) categories was 2-4 times higher than those for FEV1PP and 3-10 times higher for airway related tung disease mortality. We conclude that FEV1/ht(2) is superior to FEV1PP for predicting survival. in a general population and this method...

  3. Novel implant design improves implant survival in multirooted extraction sites: a preclinical pilot study.

    Science.gov (United States)

    Sivan-Gildor, Adi; Machtei, Eli E; Gabay, Eran; Frankenthal, Shai; Levin, Liran; Suzuki, Marcelo; Coelho, Paulo G; Zigdon-Giladi, Hadar

    2014-10-01

    The primary aim is to evaluate clinical, radiographic, and histologic parameters of novel implants with "three roots" design that were inserted into fresh multirooted extraction sockets. A secondary aim is to compare this new implant to standard root-form dental implants. Immediate implantation of novel or standard design 6 × 6-mm implants was performed bilaterally into multirooted sockets in mandibles of mini-pigs. Twelve weeks later, clinical, radiographic, stability, histomorphometric, and microcomputed tomography (micro-CT) analyses were performed. Survival rates were significantly higher in the test implants compared with control (92.8% versus 33.3%, respectively; P micro-CT analyses demonstrated bone fill in the inner part of the test implants. Moreover, bone-to-implant contact was higher in the test implants (55.50% ± 3.68% versus 42.47% ± 9.89%). Contrary to the clinical, radiographic, and histomorphometric results, resonance frequency analysis measurements were greater in the control group (77.74 ± 3.21 implant stability quotient [ISQ]) compared with the test group (31.09 ± 0.28 ISQ), P = 0.008. The novel design implants resulted in significantly greater survival rate in multirooted extraction sites. Further studies will be required to validate these findings.

  4. Significant survival improvement of patients with recurrent breast cancer in the periods 2001-2008 vs. 1992-2000

    Directory of Open Access Journals (Sweden)

    Nishimura Sumiko

    2011-03-01

    Full Text Available Abstract Background It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs and trastuzumab. Methods A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared. Results Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P Conclusions The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors.

  5. Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock

    Directory of Open Access Journals (Sweden)

    Charchaflieh J

    2012-07-01

    Full Text Available Jean Charchaflieh,1,2 Georges I Labaze,1 Pulsar Li,1 Holly Van Remmen,3 Haekyung Lee,1 Helen Stutz,1 Arlan Richardson,3 Asher Emanuel,1 Ming Zhang1,41Department of Anesthesiology, State University of New York (SUNY Downstate Medical Center, New York, NY, USA; 2Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 3Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 4Department of Cell Biology, State University of New York (SUNY Downstate Medical Center, New York, NY, USABackground: Protective effects of the antioxidant enzyme Cu-Zn superoxide dismutase (SOD1 against endotoxic shock have not been demonstrated in animal models. We used a murine model to investigate whether overexpression of SOD1 protects against endotoxic shock, and whether the genetic background of SOD1 affects its effective protective effects and susceptibility to endotoxic shock.Methods: Transgenic (tg mice overexpressing human SOD1 and control mice were divided into four groups based on their genetic background: (1 tg mice with mixed genetic background (tg-JAX; (2 wild-type (WT littermates of tg-JAX strain (WT-JAX; (3 tg mice with C57BL/6J background (tg-TX; (4 WT littermates of tg-TX strain (WT-TX. Activity of SOD1 in the intestine, heart, and liver of tg and control mice was confirmed using a polyacrylamide activity gel. Endotoxic shock was induced by intraperitoneal injection of lipopolysaccharide. Survival rates over 120 hours (mean, 95% confidence interval were analyzed using Kaplan–Meier survival curves.Results: Human SOD1 enzymatic activities were significantly higher in the intestine, heart, and liver of both tg strains (tg-JAX and tg-TX compared with their WT littermates (WT-JAX and WT-TX, respectively. Interestingly, the endogenous SOD1 activities in tg-JAX mice were decreased compared with their WT littermates (WT-JAX, but such aberrant changes were not

  6. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

  7. Cold stress improves the ability of Lactobacillus plantarum L67 to survive freezing.

    Science.gov (United States)

    Song, Sooyeon; Bae, Dong-Won; Lim, Kwangsei; Griffiths, Mansel W; Oh, Sejong

    2014-11-17

    The stress resistance of bacteria is affected by the physiological status of the bacterial cell and environmental factors such as pH, salts and temperature. In this study, we report on the stress response of Lactobacillus plantarum L67 after four consecutive freeze-thaw cycles. The cold stress response of the cold-shock protein genes (cspC, cspL and cspP) and ATPase activities were then evaluated. The cold stress was adjusted to 5 °C when the bacteria were growing at the mid-exponential phase. A comparative proteomic analysis was performed with two-dimensional gel electrophoresis (2D SDS-PAGE) and a matrix assisted laser desorption/ionization-mass spectrometer. Only 56% of the L. plantarum L67 cells without prior exposure to cold stress survived after four consecutive freeze-thaw cycles. However, 78% of the L. plantarum L67 cells that were treated with cold stress at 5 °C for 6 h survived after freeze-thaw conditions. After applying cold stress to the culture for 6h, the cells were then stored for 60 days at 5 °C, 25 °C and 35 °C separately. The cold-stressed culture of L. plantarum L67 showed an 8% higher viability than the control culture. After applying cold stress for 6h, the transcript levels of two genes (cspP and cspL) were up-regulated 1.4 (cspP) and 1.2 (cspL) times compared to the control. However, cspC was not up-regulated. A proteomic analysis showed that the proteins increased after a reduction of the incubation temperature to 5 °C. The importance of the expression of 13 other relevant proteins was also determined through the study. The exposure of L. plantarum cells to low temperatures aids their ability to survive through subsequent freeze-thaw processes and lyophilization. Copyright © 2014. Published by Elsevier B.V.

  8. Improving the determination of irradiation efficacy by the identification of surviving bacteria from irradiated spices

    International Nuclear Information System (INIS)

    Koshikawa, Tomihiko; Matsushima, Masako; Hironiwa, Takayuki; Takekawa, Tetsuya; Miyahara, Makoto

    2009-01-01

    The identification of the surviving bacteria isolated from 5 kinds of irradiated spices (all-spice, oregano, sage, paprika and black pepper) was carried out to know whether these bacteria were marker organisms to determine the efficacy of the irradiation treatment. Except in paprika, B.megaterium was detected. In allspice, paprika and black pepper B.pumilus was detected. B.cereus was detected in allspice, oregano and black pepper. Gram negative bacteria such as Methylobacterium and Enterobacter genus were also detected in oregano, sage and paprika. These bacteria were strongly resistant to radiation, and can be used as marker organisms for the determination of the efficacy of the irradiation treatment of spices. (author)

  9. IMP3 expression in human ovarian cancer is associated with improved survival

    DEFF Research Database (Denmark)

    Noske, Aurelia; Faggad, Areeg; Wirtz, Ralph

    2009-01-01

    The insulin-like growth factor-II mRNA-binding protein IMP3 plays an important role in embryogenesis and recent reports suggest an involvement in tumorigenesis. Although IMP3 expression has been well studied in mouse and human fetal and adult gonads, its role in ovarian cancer is unknown. We...... investigated the expression of IMP3 at protein and mRNA levels in a cohort of primary ovarian carcinomas and in 11 ovarian cancer cell lines. Western blot analysis revealed an expression of IMP3 in all ovarian cancer cell lines and immunohistochemistry demonstrated a positive cytoplasmic staining in 32 of 68...... carcinomas (47%). In contrast, epithelium of borderline tumors, as well as, benign ovarian lesions and normal ovaries exhibited only weak or no IMP3 expression. In univariate Kaplan-Meier analysis, IMP3 protein expression was significantly associated with better overall survival (P=0.048). To confirm...

  10. PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse

    International Nuclear Information System (INIS)

    Konishi, Hiroaki; Takagi, Akimitsu; Kurita, Akinobu; Kaneda, Norimasa; Matsuzaki, Takeshi

    2012-01-01

    Advanced ovarian cancer is characterized by peritoneal metastasis and the accumulation of ascites. Peritoneal metastasis of ovarian cancer is a major cause of the negative treatment outcome, as these metastases are resistant to most chemotherapy regimens. The aim of this study was to clarify aggressive pathology of peritoneal metastasis and examine the therapeutic efficacy of a liposomal agent in the model. A human cancer cell line ES-2 of ovarian clear cell carcinoma, known as a chemotherapy-resistant cancer, was cultured in nonadherent plate to form spheroid and single cell suspension was transplanted into mouse peritoneal cavity. The epidermal growth factor receptor (EGFR) pathways in the cellular aggregates were analyzed both spheroid and ascites. The pharmacokinetics and therapeutic efficacy of CPT-11 (45 mg/kg) and IHL-305 (45 mg/kg), an irinotecan-encapsulated liposome, were examined by intravenous administration. Established peritoneal metastasis model showed an accumulation of ascites. The activation of EGFR and Akt was demonstrated in cellular aggregates both in the spheroid and ascites. In ascites samples, the area under the curve of SN-38, the activated form of CPT-11, was 3.8 times higher from IHL-305-treated mice than from CPT-11-treated mice. IHL-305 prolonged the survival time and decreased the accumulation of ascites and tumor metastasis. The median survival time were 22, 37 and 54 days in the control, CPT-11-treated, and IHL-305-treated mice, respectively. EGFR/Akt pathway contributes to the aggressive progression in ES-2 peritoneal metastasis model and effective delivery into ascites of IHL-305 was thought to useful treatment for ovarian cancer with peritoneal metastasis

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

    International Nuclear Information System (INIS)

    Putz, Florian; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer; Putz, Tobias; Eyuepoglu, Ilker; Roessler, Karl

    2016-01-01

    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"2 vs. 33.1 mg/m"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.) [de

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

    Science.gov (United States)

    Putz, Florian; Putz, Tobias; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Eyüpoglu, Ilker; Rössler, Karl; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer

    2016-11-01

    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/m² vs. 33.1 mg/m²; 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.

  13. Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

    Directory of Open Access Journals (Sweden)

    Kentaro Takakura

    2017-11-01

    Full Text Available The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM, which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS, heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life

  14. Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions.

    Science.gov (United States)

    Takakura, Kentaro; Ito, Shogo; Sonoda, Junya; Tabata, Koji; Shiozaki, Motoko; Nagai, Kaoru; Shibata, Masahiro; Koike, Masato; Uchiyama, Yasuo; Gotow, Takahiro

    2017-11-01

    The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS), heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life extension of these

  15. PPARγ agonists improve survival and neurocognitive outcomes in experimental cerebral malaria and induce neuroprotective pathways in human malaria.

    Directory of Open Access Journals (Sweden)

    Lena Serghides

    2014-03-01

    Full Text Available Cerebral malaria (CM is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors. Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone. PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models. Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM. Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF and nerve growth factor (NGF in the brains of infected mice. Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy. In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF. These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM.

  16. Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

    Science.gov (United States)

    Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

    2013-01-01

    Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

  17. Lung Cancer in a Rural Area of China: Rapid Rise in Incidence and Poor Improvement in Survival.

    Science.gov (United States)

    Yang, Juan; Zhu, Jian; Zhang, Yong-Hui; Chen, Yong-Sheng; Ding, Lu-Lu; Kensler, Thomas W; Chen, Jian-Guo

    2015-01-01

    Lung cancer has been a major health problem in developed countries for several decades, and has emerged recently as the leading cause of cancer death in many developing countries. The incidence of lung cancer appears to be increasing more rapidly in rural than in urban areas of China. This paper presents the trends of lung cancer incidence and survival derived from a 40-year population-based cancer monitoring program in a rural area, Qidong, China. The Qidong cancer registration data of 1972- 2011 were used to calculate the crude rate, age-standardized rate by Chinese population (CASR) and by world population (WASR), birth cohort rates, and other descriptive features. Active and passive methods were used to construct the data set, with a deadline of the latest follow-up of April 30, 2012. The total number of lung cancer cases was 15,340, accounting for 16.5% of all sites combined. The crude incidence rate, CASR and WASR of this cancer were 34.1, 15.7 and 25.4 per 100,000, respectively. Males had higher crude rates than females (49.7 vs 19.0). Rapidly increasing trends were found in annual percent change resulting in lung cancer being a number one cancer site after year 2010 in Qidong. Birth cohort analysis showed incidence rates have increased for all age groups over 24 years old. The 5 year observed survival rates were 3.55% in 1973-1977, 3.92 in 1983-1987, 3.69% in 1993-1997, and 6.32% in 2003-2007. Males experienced poorer survival than did females. Lung cancer has become a major cancer-related health problem in this rural area. The rapid increases in incidence likely result from an increased cigarette smoking rate and evolving environmental risk factors. Lung cancer survival, while showing some improvement in prognosis, still remains well below that observed in the developed areas of the world.

  18. Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

    Science.gov (United States)

    Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

    2014-02-01

    Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

  19. Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

    Science.gov (United States)

    Klingensmith, Nathan J; Chen, Ching-Wen; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Arbiser, Jack L; Ford, Mandy L; Coopersmith, Craig M

    2017-10-11

    Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.

  20. Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

    LENUS (Irish Health Repository)

    Hannon, Niamh

    2011-09-01

    Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic).

  1. Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

    Directory of Open Access Journals (Sweden)

    Ballardini Michela

    2006-08-01

    Full Text Available Abstract Background We present our experience of therapeutic vaccination using dendritic cells (DC pulsed with autologous tumor antigens in patients with advanced melanoma. Methods Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL or – homogenate (ATH and 50 μg/ml of keyhole limpet hemocyanin (KLH. The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC (range 4.5 – 82 × 106 and the remaining 13 intradermally with in vitro matured DC (mDC (range 1.2–26 × 106. Subcutaneous interleukin-2 (3 × 106 IU was administered from days 3 to 7 of each treatment cycle. Results Three of the 8 iDC patients obtained stabilizations (SD, each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months, 1 partial response (3 months, 2 mixed responses (6 and 12 months and 3 SD (9, 7+, and 3+ months. Overall responses (OR were observed in 4/21 (19% patients, or 4/13 (30.7% considering mDC treatment only. 10/21 (47.6% patients showed non progressive disease (NPD, with 7/13 (53.8% cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH test to ATL/ATH and/or KLH correlated with increased overall survival (OS. Median OS was 24 months (range 3 – 45 for the 10 DTH-positive (1 iDC and 9 mDC and 5 months (range 3–14 for the 11 DTH-negative patients (P in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75% and clinical outcome (70%. Conclusion Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

  2. Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients.

    Science.gov (United States)

    Ridolfi, Ruggero; Petrini, Massimiliano; Fiammenghi, Laura; Stefanelli, Monica; Ridolfi, Laura; Ballardini, Michela; Migliori, Giuseppe; Riccobon, Angela

    2006-08-16

    We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 microg/ml of autologous-tumor-lysate (ATL) or -homogenate (ATH) and 50 microg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC) (range 4.5-82 x 10(6)) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 x 10(6)). Subcutaneous interleukin-2 (3 x 10(6) IU) was administered from days 3 to 7 of each treatment cycle. Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SD (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3-45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P < 0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

  3. Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

    Science.gov (United States)

    Pineton de Chambrun, Marc; Gousseff, Marie; Mauhin, Wladimir; Lega, Jean-Christophe; Lambert, Marc; Rivière, Sophie; Dossier, Antoine; Ruivard, Marc; Lhote, François; Blaison, Gilles; Alric, Laurent; Agard, Christian; Saadoun, David; Graveleau, Julie; Soubrier, Martin; Lucchini-Lecomte, Marie-Josée; Christides, Christine; Bosseray, Annick; Levesque, Hervé; Viallard, Jean-François; Tieulie, Nathalie; Lovey, Pierre-Yves; Le Moal, Sylvie; Bibes, Béatrice; Malizia, Giuseppe; Abgueguen, Pierre; Lifermann, François; Ninet, Jacques; Hatron, Pierre-Yves; Amoura, Zahir

    2017-10-01

    Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first

  4. Rotavirus Vaccine will Improve Child Survival by More than Just Preventing Diarrhea: Evidence from Bangladesh.

    Science.gov (United States)

    Saha, Senjuti; Santosham, Mathuram; Hussain, Manzoor; Black, Robert E; Saha, Samir K

    2018-02-01

    Despite the high burden of rotavirus diarrhea, uptake of rotavirus vaccines in Asia remains low. This primarily stems from a perception of rotavirus as a non-life-threatening pathogen amidst a background of competing health priorities and limited resources. In the largest pediatric hospital of Bangladesh, where there is a fierce competition for beds, we found that between November 2015 and October 2016, 12% of 23,064 admissions were due to gastrointestinal infections, 54% of which were caused by rotavirus. One in four cases requiring hospitalization, or 5,879 cases, was refused because of unavailability of beds. Most refused cases were of pneumonia (22%), severe perinatal asphyxia (17%), preterm birth complications (7%), and meningitis (2%), all of which bear high risks of death or disability, if not treated timely. When determining vaccine policies and conducting vaccine impact studies, it would be shortsighted to not consider the impact on morbidity and mortality of cases that are refused admission because of the hospitalization of children with a preventable disease as rotavirus diarrhea. In our hospital, routine use of a rotavirus vaccine with 41% efficacy will release 629 beds per year to accommodate previously refused cases. Based on evidence, we make the case that introduction of this vaccine in Bangladesh and the surrounding region will prevent morbidity and mortality, both directly and indirectly, and help us ensure survival and well-being of all children.

  5. Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

    Science.gov (United States)

    Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

    2017-07-01

    Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  6. Does my high blood pressure improve your survival? Overall and subgroup learning curves in health.

    Science.gov (United States)

    Van Gestel, Raf; Müller, Tobias; Bosmans, Johan

    2017-09-01

    Learning curves in health are of interest for a wide range of medical disciplines, healthcare providers, and policy makers. In this paper, we distinguish between three types of learning when identifying overall learning curves: economies of scale, learning from cumulative experience, and human capital depreciation. In addition, we approach the question of how treating more patients with specific characteristics predicts provider performance. To soften collinearity problems, we explore the use of least absolute shrinkage and selection operator regression as a variable selection method and Theil-Goldberger mixed estimation to augment the available information. We use data from the Belgian Transcatheter Aorta Valve Implantation (TAVI) registry, containing information on the first 860 TAVI procedures in Belgium. We find that treating an additional TAVI patient is associated with an increase in the probability of 2-year survival by about 0.16%-points. For adverse events like renal failure and stroke, we find that an extra day between procedures is associated with an increase in the probability for these events by 0.12%-points and 0.07%-points, respectively. Furthermore, we find evidence for positive learning effects from physicians' experience with defibrillation, treating patients with hypertension, and the use of certain types of replacement valves during the TAVI procedure. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Could 3-D conformal radiotherapy improve the overall survival for non-small cell lung cancer?

    International Nuclear Information System (INIS)

    Giraud, P.; Helfre, S.; Lavole, A.; Rosenwald, J.C.; Cosset, J.M.

    2002-01-01

    The conformal radiotherapy approach, three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), is based on modern imaging modalities, efficient 3-D treatment planning systems, sophisticated immobilization devices and demanding quality assurance and treatment verification. The main goal of conformal radiotherapy is to ensure a high dose distribution tailored to the limits of the target volume while reducing exposure of healthy tissues. These techniques would then allow a further dose escalation increasing local control and survival. Non-small cell lung cancer (NSCLC) is one of the most difficult malignant tumors to be treated. It combines geometrical difficulties due to respiratory motion, and number of low tolerance neighboring organs, and dosimetric difficulties because of the presence of huge inhomogeneities. This localization is an attractive and ambitious example for the evaluation of new techniques. However, the published clinical reports in the last years described very heterogeneous techniques and, in the absence of prospective randomized trials, it is somewhat difficult at present to evaluate the real benefits drawn from those conformal radiotherapy techniques. After reviewing the rationale for 3DCRT for NSCLC, this paper will describe the main studies of 3DCRT, in order to evaluate its impact on lung cancer treatment Then the current state-of-the-art of IMRT and the last technical and therapeutic innovations in NSCL will be discussed. (authors)

  8. Exendin-4 improved rat cortical neuron survival under oxygen/glucose deprivation through PKA pathway.

    Science.gov (United States)

    Wang, M-D; Huang, Y; Zhang, G-P; Mao, L; Xia, Y-P; Mei, Y-W; Hu, B

    2012-12-13

    Previous studies demonstrated that exendin-4 (Ex-4) may possess neurotrophic and neuroprotective functions in ischemia insults, but its mechanism remained unknown. Here, by using real-time PCR and ELISA, we identified the distribution of active GLP-1Rs in the rat primary cortical neurons. After establishment of an in vitro ischemia model by oxygen/glucose deprivation (OGD), neurons were treated with various dosages of Ex-4. The MTT assay showed that the relative survival rate increased with the dosage of Ex-4 ranging from 0.2 to 0.8 μg/ml (Pglucose-regulated proteins 78 (GRP78) and reduced C/EBP-homologous protein (CHOP). Western blot analysis demonstrated that, after neurons were treated with Ex-4, GRP78 was up-regulated over time (Pneurons, down-regulated the expression of B-cell lymphoma 2 (Bcl-2) and up-regulated the Bax expression 3h after ODG (Pneurons against OGD by modulating the unfolded protein response (UPR) through the PKA pathway and may serve as a novel therapeutic agent for stroke. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Abrams, Matthew J., E-mail: mabrams@tuftsmedicalcenter.org [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Koffer, Paul P. [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Wazer, David E. [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (United States); Hepel, Jaroslaw T. [Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (United States)

    2017-06-01

    Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods and Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor–positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). Conclusions: There may be a survival benefit with the

  10. Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

    Directory of Open Access Journals (Sweden)

    Sandra Geschka

    Full Text Available A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

  11. Improvement of Nutritional and Bioactive Compound Production by Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), by Spraying Growth Regulators.

    Science.gov (United States)

    Vi, Minhthuan; Yang, Xueqin; Zeng, Xianlu; Chen, Rui'an; Guo, Liqiong; Lin, Junfang; He, Qianyun; Zheng, Qianwang; Wei, Tao

    2018-01-01

    Hericium erinaceus is a popular culinary and medicinal mushroom in China because of its broad beneficial effects. In this study we evaluated the effects of stimulation with 7 growth regulators at 5 different concentrations on improving the production of nutritional and bioactive compounds by H. erinaceus. Results showed that among all the tested regulators, gibberellic acid (GA) increased protein content (165%), free amino acids (100%), polysaccharides (108%), and polyphenols (26%). Spraying nephthyl acetic acid increased polysaccharides and triterpenoids to 4.37 and 17.27 g/100 g, respectively. Spraying chitosan significantly increased polyphenols by 42%. The addition of triacontanol, indole acetic acid, and 2,4-dichlorophenoxyacetic acid improved the production of proteins, free amino acids, polysaccharides, and polyphenols, but not to the extent that GA did. These results indicate that adding certain growth regulators can effectively improve the production of nutritional and bioactive compounds in H. erinaceus.

  12. Minimally invasive surgical approaches offer earlier time to adjuvant chemotherapy but not improved survival in resected pancreatic cancer.

    Science.gov (United States)

    Mirkin, Katelin A; Greenleaf, Erin K; Hollenbeak, Christopher S; Wong, Joyce

    2018-05-01

    Pancreatic surgery encompasses complex operations with significant potential morbidity. Greater experience in minimally invasive surgery (MIS) has allowed resections to be performed laparoscopically and robotically. This study evaluates the impact of surgical approach in resected pancreatic cancer. The National Cancer Data Base (2010-2012) was reviewed for patients with stages 1-3 resected pancreatic carcinoma. Open approaches were compared to MIS. A sub-analysis was then performed comparing robotic and laparoscopic approaches. Of the 9047 patients evaluated, surgical approach was open in 7511 (83%), laparoscopic in 992 (11%), and robotic in 131 (1%). The laparoscopic and robotic conversion rate to open was 28% (n = 387) and 17% (n = 26), respectively. Compared to open, MIS was associated with more distal resections (13.5, 24.3%, respectively, p offered significantly shorter LOS in all types. Multivariate analysis demonstrated no survival benefit for any MIS approach relative to open (all, p > 0.05). When adjusted for patient, disease, and treatment characteristics, TTC was not an independent prognostic factor (HR 1.09, p = 0.084). MIS appears to offer comparable surgical oncologic benefit with improved LOS and shorter TTC. This effect, however, was not associated with improved survival.

  13. 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

  14. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  15. Improvement of a synthetic lure for Anopheles gambiae using compounds produced by human skin microbiota.

    Science.gov (United States)

    Verhulst, Niels O; Mbadi, Phoebe A; Kiss, Gabriella Bukovinszkiné; Mukabana, Wolfgang R; van Loon, Joop J A; Takken, Willem; Smallegange, Renate C

    2011-02-08

    Anopheles gambiae sensu stricto is considered to be highly anthropophilic and volatiles of human origin provide essential cues during its host-seeking behaviour. A synthetic blend of three human-derived volatiles, ammonia, lactic acid and tetradecanoic acid, attracts A. gambiae. In addition, volatiles produced by human skin bacteria are attractive to this mosquito species. The purpose of the current study was to test the effect of ten compounds present in the headspace of human bacteria on the host-seeking process of A. gambiae. The effect of each of the ten compounds on the attractiveness of a basic blend of ammonia, lactic and tetradecanoic acid to A. gambiae was examined. The host-seeking response of A. gambiae was evaluated in a laboratory set-up using a dual-port olfactometer and in a semi-field facility in Kenya using MM-X traps. Odorants were released from LDPE sachets and placed inside the olfactometer as well as in the MM-X traps. Carbon dioxide was added in the semi-field experiments, provided from pressurized cylinders or fermenting yeast. The olfactometer and semi-field set-up allowed for high-throughput testing of the compounds in blends and in multiple concentrations. Compounds with an attractive or inhibitory effect were identified in both bioassays. 3-Methyl-1-butanol was the best attractant in both set-ups and increased the attractiveness of the basic blend up to three times. 2-Phenylethanol reduced the attractiveness of the basic blend in both bioassays by more than 50%. Identification of volatiles released by human skin bacteria led to the discovery of compounds that have an impact on the host-seeking behaviour of A. gambiae. 3-Methyl-1-butanol may be used to increase mosquito trap catches, whereas 2-phenylethanol has potential as a spatial repellent. These two compounds could be applied in push-pull strategies to reduce mosquito numbers in malaria endemic areas.

  16. Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds

    NARCIS (Netherlands)

    Mateo Anson, N.; Selinheimo, E.; Havenaar, R.; Aura, A.-M.; Mattila, I.; Lehtinen, P.; Bast, A.; Poutanen, K.; Haenen, G.R.M.M.

    2009-01-01

    Ferulic acid (FA) is the most abundant phenolic compound in wheat grain, mainly located in the bran. However, its bioaccessibility from the bran matrix is extremely low. Different bioprocessing techniques involving fermentation or enzymatic and fermentation treatments of wheat bran were developed

  17. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

    2016-03-15

    Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

  18. Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

    Science.gov (United States)

    Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

    2014-01-01

    Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

  19. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

    Science.gov (United States)

    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

  20. Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract

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    Hill Colin

    2008-10-01

    Full Text Available Abstract Background The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. However, unlike pathogenic bacteria; they are often inadequately equipped to endure the physicochemical stresses of gastrointestinal (GI delivery in the host. Herein we outline a patho-biotechnology strategy to improve gastric delivery and host adaptation of a probiotic strain Bifidobacterium breve UCC2003 and the generally regarded as safe (GRAS organism Lactococcus lactis NZ9000. Results In vitro bile tolerance of both strains was significantly enhanced (P Listeria monocytogenes bile resistance mechanism BilE. Strains harbouring bilE were also recovered at significantly higher levels (P n = 5, following oral inoculation. Furthermore, a B. breve strain expressing bilE demonstrated increased efficacy relative to the wild-type strain in reducing oral L. monocytogenes infection in mice. Conclusion Collectively the data indicates that bile tolerance can be enhanced in Bifidobacterium and Lactococcus species through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract.

  1. Reperfusion injury protection during Basic Life Support improves circulation and survival outcomes in a porcine model of prolonged cardiac arrest.

    Science.gov (United States)

    Debaty, Guillaume; Lurie, Keith; Metzger, Anja; Lick, Michael; Bartos, Jason A; Rees, Jennifer N; McKnite, Scott; Puertas, Laura; Pepe, Paul; Fowler, Raymond; Yannopoulos, Demetris

    2016-08-01

    Ischemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. Prospective animal investigation. Animal laboratory Female farm pigs (n=46, 39±1kg). Protocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. Protocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p=0.05). There were no significant differences in 24h survival between groups. LVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p=0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone (p=0.027). BLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. 12-11. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Improvement of survival and development of Pacific white shrimp Litopenaeus vannamei larvae by feeding taurine enriched rotifers

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    Dedi Jusadi

    2015-03-01

    Full Text Available ABSTRACTThe objective of the present experiment was to study the most optimum taurine enrichment concentration of rotifers in improving Pacific white shrimp larva Litopenaeus vannamei survival and development. White shrimp larvae at sixth naupliar stage were reared in 12 units of 500 L fibre glass tanks with a stocking density of 125 ind/L. Starting from zoea two stage (Z-2, the larva was provided with rotifers with different taurine enrichment concentration according to the treatments, i.e. 0 mg/L enrichment medium (A, 25 mg/L (B, 50 mg/L(C, and 100 mg/L (D. The results show that different taurine concentration in the enrichment media increased taurine level in rotifers. Furthermore, the administration of taurine enriched rotifers up to 50 mg/L significantly improved larval survival and may accelerate larval development. The experimental results also concluded that a concentration of 50 mg/L is the most optimum taurine enrichment concentration of rotifers for the improvement of white shrimp larval survival and developmental stage.Keywords: taurine, rotifer, white shrimp, enrichmentABSTRAKPenelitian ini bertujuan untuk mengkaji konsentrasi optimum taurin melalui pengayaan pada rotifera terhadap tingkat kelangsungan hidup dan perkembangan stadia larva udang vaname Litopenaeus vannamei. Larva udang vaname stadia naupli-6 dipelihara dalam 12 tangki fiberglass volume 500 L dengan kepadatan 125 ind/L. Dimulai sejak stadia zoea 2 (Z-2 larva diberi rotifera yang diperkaya dengan taurin dengan konsentrasi yang berbeda sesuai dengan perlakuan, yaitu 0 mg/L media pengkaya (A, 25 mg/L (B, 50mg/L (C, dan 100mg/L (D. Hasil penelitian menunjukkan pengayaan taurin pada konsentrasi yang berbeda menyebabkan peningkatan kandungan taurin rotifera. Sementara pemberian rotifera yang diperkaya taurin hingga 50 mg/L meningkatkan kelangsungan hidup dan mempercepat perkembangan stadia larva udang. Berdasarkan hasil penelitian ini dapat disimpulkan bahwa pemberian

  3. The Event Chain of Survival in the Context of Music Festivals: A Framework for Improving Outcomes at Major Planned Events.

    Science.gov (United States)

    Lund, Adam; Turris, Sheila

    2017-08-01

    Despite the best efforts of event producers and on-site medical teams, there are sometimes serious illnesses, life-threatening injuries, and fatalities related to music festival attendance. Producers, clinicians, and researchers are actively seeking ways to reduce the mortality and morbidity associated with these events. After analyzing the available literature on music festival health and safety, several major themes emerged. Principally, stakeholder groups planning in isolation from one another (ie, in silos) create fragmentation, gaps, and overlap in plans for major planned events (MPEs). The authors hypothesized that one approach to minimizing this fragmentation may be to create a framework to "connect the dots," or join together the many silos of professionals responsible for safety, security, health, and emergency planning at MPEs. Adapted from the well-established literature regarding the management of cardiac arrests, both in and out of hospital, the "chain of survival" concept is applied to the disparate groups providing services that support event safety in the context of music festivals. The authors propose this framework for describing, understanding, coordinating and planning around the integration of safety, security, health, and emergency service for events. The adapted Event Chain of Survival contains six interdependent links, including: (1) event producers; (2) police and security; (3) festival health; (4) on-site medical services; (5) ambulance services; and (6) off-site medical services. The authors argue that adapting and applying this framework in the context of MPEs in general, and music festivals specifically, has the potential to break down the current disconnected approach to event safety, security, health, and emergency planning. It offers a means of shifting the focus from a purely reactive stance to a more proactive, collaborative, and integrated approach. Improving health outcomes for music festival attendees, reducing gaps in planning

  4. Technical integrity and continuous improvement: Key to survival beyond the nineties

    International Nuclear Information System (INIS)

    Thorogood, J.L.

    1994-01-01

    Drilling decisions made before a rig reaches location make a significant contribution to an oil company's financial success. Of value to the company is not the ability to drill wells, but the ability to plan with confidence in the knowledge of what is possible. In spite of this, operators have tended to over-work day to day decisions about drilling out of proportion to their significance. Recognition of this fact has resulted in the present wave of contracting initiatives. A major challenge for the industry is to achieve the necessary transfer of responsibility without compromising the operator's license to operate. These changes will compel the service sector to develop a new culture of technical integrity and continuous improvement. To operate safely, measure performance and manage drilling risk, the transformation will oblige the service sector to adopt many technologies presently owned by oil companies

  5. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

    2004-01-01

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131 I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P 131 I-A7 RIT displayed a marked therapeutic effect (n=8) (P 131 I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P 131 I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  6. Long-term survival differences in gastric cancer after D2 lymphadenectomy and an improved assessment of resectability

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    Gabriel Dimofte

    2017-05-01

    Full Text Available Objective. The purpose of this work is to compare the long-term survival between a control group with mostly D1 lymphadenectomy and a study group with mostly D2 lymphadenectomy. Materials and Methods. We analyzed consecutive cases operated by a single surgeon performing mostly D2 lymphadenectomy and a control group of consecutive gastric cancer patients operated by a group of surgeons, performing mostly D1 lymphadenectomy, in a period when D2 lymphadenectomy was not the standard and was introduced as a new technique in our center. Results. We found 30,56% D2 lymphadenectomy in the control groups and 85,1% in the study group. At a five years interval from surgery the control group had no survivors, while the study group had 8 (20% survivors. Conclusions. The spleen and pancreas preserving D2 lymphadenectomy done by experienced surgeons, according to the current guidelines in order to select operable patients improves the overall survival of such gastric cancer patients.

  7. Improved survival and marrow engraftment of mice transplanted with bone marrov of GM-CSF-treated donors

    International Nuclear Information System (INIS)

    Ballin, A.; Sagi, O.; Schiby, G.; Meytes, D.

    1993-01-01

    Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normal donor mice in vivo with GM-CSF. Donor balb/c mice were injected i.p. with GM-CSF (5000 u) or saline. Seventy-two hours later 5 x 105 BM cells from either GM-CSF-treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM-CSF-treated donors, significantly higher CFU-S and significantly higher survival rate (57% [n = 65]; vs. 30% [n = 63]; p < 0.05) were noted. Donor mice of the GM-CSF group did not differ in bone-marrow cellularity and composition from their controls. However, recipients of BM from GM-CSF-treated mice had higher blood counts of haemoglobin, Leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM-CSF may be of benefit in improving survival and marrow engraftment in mice. (au) (13 refs.)

  8. Comprehensive stroke centers may be associated with improved survival in hemorrhagic stroke.

    Science.gov (United States)

    McKinney, James S; Cheng, Jerry Q; Rybinnik, Igor; Kostis, John B

    2015-05-06

    Comprehensive stroke centers (CSCs) provide a full spectrum of neurological and neurosurgical services to treat complex stroke patients. CSCs have been shown to improve clinical outcomes and mitigate disparities in ischemic stroke patients. It is believed that CSCs also improve outcomes in hemorrhagic stroke. We used the Myocardial Infarction Data Acquisition System (MIDAS) database, which includes data on patients discharged with a primary diagnosis of intracerebral hemorrhage (ICH; International Classification of Diseases, Ninth Revision [ICD-9] 431) and subarachnoid hemorrhage (SAH; ICD-9 430) from all nonfederal acute care hospitals in New Jersey (NJ) between 1996 and 2012. Out-of-hospital deaths were assessed by matching MIDAS records with NJ death registration files. The primary outcome variable was 90-day all-cause mortality. The primary independent variable was CSC versus primary stroke center (PSC) and nonstroke center (NSC) admission. Multivariate logistic models were used to measure the effects of available covariates. Overall, 36 981 patients were admitted with a primary diagnosis of ICH or SAH during the study period, of which 40% were admitted to a CSC. Patients admitted to CSCs were more likely to have neurosurgical or endovascular interventions than those admitted to a PSC/NSC (18.9% vs. 4.7%; Pmortality (35.0% vs. 40.3%; odds ratio, 0.93; 95% confidence interval, 0.89 to 0.97) for hemorrhagic stroke. This was particularly true for those admitted with SAH. Hemorrhagic stroke patients admitted to CSCs are more likely to receive neurosurgical and endovascular treatments and be alive at 90 days than patients admitted to other hospitals. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Compounding rifampin suspensions with improved injectability for nasogastric enteral feeding tube administration.

    Science.gov (United States)

    de Villiers, Melgardt M; Vogel, Laura; Bogenschutz, Monica C; Fingerhut, Bonnie J; D'Silva, Joseph B; Moore, Anne

    2010-01-01

    Often medications that have to be administered to patients via a nasogastric enteral feeding tubes are only available as tablets and capsules with no suitable commercial liquid alternatives. In such situations, pharmacists and nurses have to compound the tablets and capsule contents into liquid suspension formulations for dosing. The risk of occlusion of the enteral tubes during administration is reduced by employing liquid suspensions that are composed of small and uniform particles, not subject to rapid rates of settling, resistant to caking, and easily and uniformly re-suspended upon agitation. Present techniques often employ a manual process, such as a mortar and pestle, to accomplish the particle size reduction and subsequent incorporation into a suitable liquid diluent. A new compounding device has been invented that employs an automated wet-milling process in a single-use disposable plastic container to compound the suspensions. The two processes were compared using Rifampin capsules and various liquid diluents. A prototype version of the new device was employed in the experiments. The physical characteristics of the compounded suspensions were evaluated by determining sedimentation rate, sedimentation volume, and particle size and shape using laser light scattering, optical microscopy, and scanning electron microscopy techniques. The use characteristic of the compounded suspensions was evaluated using a nasogastric tube inject ability test. The results indicated that suspensions prepared using the new device were more resistant to sedimentation and caking and were easier to re-disperse into a uniform mixture by gentle shaking. The results were a consequence of the particles generated by the new device which were found to be smaller and more uniform in shape and size. The suspensions prepared using the new device did not cause blockage of the enteral feeding tubes in comparison to those prepared using a mortar and pastle. In conclusion, the results indicate

  10. Cooking techniques improve the levels of bioactive compounds and antioxidant activity in kale and red cabbage.

    Science.gov (United States)

    Murador, Daniella Carisa; Mercadante, Adriana Zerlotti; de Rosso, Veridiana Vera

    2016-04-01

    The aim of this study is to investigate the effects of different home cooking techniques (boiling, steaming, and stir-frying) in kale and red cabbage, on the levels of bioactive compounds (carotenoids, anthocyanins and phenolic compounds) determined by high-performance liquid chromatography coupled with photodiode array and mass spectrometry detectors (HPLC-DAD-MS(n)), and on the antioxidant activity evaluated by ABTS, ORAC and cellular antioxidant activity (CAA) assays. The steaming technique resulted in a significant increase in phenolic content in kale (86.1%; pkale, steaming resulted in significant increases in antioxidant activity levels in all of the evaluation methods. In the red cabbage, boiling resulted in a significant increase in antioxidant activity using the ABTS assay but resulted in a significant decrease using the ORAC assay. According to the CAA assay, the stir-fried sample displayed the highest levels of antioxidant activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Approach to improve the productivity of bioactive compounds of the cyanobacterium Anabaena oryzae using factorial design

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    Ragaa A. Hamouda

    2017-09-01

    Full Text Available Cyanobacteria are one of the richest sources of biomedical relevant compounds with extensive therapeutic pharmaceutical applications and are also known as producer of intracellular and extracellular metabolites with diverse biological activities. The genus Anabaena sp. is known to produce antimicrobial compounds, like phycocyanin and others. The goal of this study was to optimize the production of these bioactive compounds. The Plackett–Burman experimental design was used to screen and evaluate the important medium components that influence the production of bioactive compounds. In this present study, eight independent factors including NaNO3, K2HPO4, MgSO4·7H2O, CaCl2, citric acid, ammonium ferric citrate, ethylene diamine tetraacetic acid disodium magnesium salt (EDTA-Na2Mg and Na2CO3 were surveyed and the effective variables for algal components production of Anabaena oryzae were determined using two-levels Plackett–Burman design. Results analysis showed that the best medium components were NaNO3 (2.25 g l−1; K2HPO4 (0.02 g l−1; MgSO4 (0.0375 g l−1; CaCl2 (0.018 g l−1; citric acid (0.009 g l−1; ammonium ferric citrate (0.009 g l−1 and EDTA-Na2 (0.0015 g l−1 respectively. The total chlorophyll-a, carotenoids, phenol, tannic acid and flavonoid contents in crude extract of Anabaena oryzae were determined. They were 47.7, 4.11, 0.256, 1.046 and 1.83 μg/ml, respectively. The antioxidant capacity was 62.81%.

  12. The application of vacuum redistillation of patchouli oil to improve patchouli alcohol compound

    Science.gov (United States)

    Asnawi, T. M.; Alam, P. N.; Husin, H.; Zaki, M.

    2018-04-01

    Patchouli oil produced by traditional distillation of patchouli leaves and stems by farmers in Aceh still has low patchouli alcohol compound. In order to increase patchouli alcohol concentration, vacuum redistillation process using packed column was introduced. This research was conducted to fractionate terpene (alpha-copinene) from oxygenated hydrocarbon (patchouli alcohol) compound. The operation condition was conducted at two variables that was dependent variable and independent variable. The dependent variable was the 30 cm height distillation packed column, by using raschig ring with 8 mm x 8 mm dimension. And the independent variable was operating temperature 130 °C and 140 °C., vacuum pressure 143,61 mbar, 121,60 mbar and 88,59 mbar and operation time 2 hours, 3 hours and 5 hours. Total of treatments applied in this works were 3 x 3 x 3 or equal to 27 treatments. Patchouli oil used in this research was obtained from Desa Teladan-Lembah Seulawah, Aceh Province. The initial patchouli alcohol compound which analyzed with GC-MS contained 16,02% before treatment applied. After vacuum redistillation process treatment applied patchouli oil concentration increase up to 34,67%. Physico-chemical test of patchouli oil after vacuum redistillation is in accordance with SNI 06-23852006 standard.

  13. Improved Plane-Wave Ultrasound Beamforming by Incorporating Angular Weighting and Coherent Compounding in Fourier Domain.

    Science.gov (United States)

    Chen, Chuan; Hendriks, Gijs A G M; van Sloun, Ruud J G; Hansen, Hendrik H G; de Korte, Chris L

    2018-05-01

    In this paper, a novel processing framework is introduced for Fourier-domain beamforming of plane-wave ultrasound data, which incorporates coherent compounding and angular weighting in the Fourier domain. Angular weighting implies spectral weighting by a 2-D steering-angle-dependent filtering template. The design of this filter is also optimized as part of this paper. Two widely used Fourier-domain plane-wave ultrasound beamforming methods, i.e., Lu's f-k and Stolt's f-k methods, were integrated in the framework. To enable coherent compounding in Fourier domain for the Stolt's f-k method, the original Stolt's f-k method was modified to achieve alignment of the spectra for different steering angles in k-space. The performance of the framework was compared for both methods with and without angular weighting using experimentally obtained data sets (phantom and in vivo), and data sets (phantom) provided by the IEEE IUS 2016 plane-wave beamforming challenge. The addition of angular weighting enhanced the image contrast while preserving image resolution. This resulted in images of equal quality as those obtained by conventionally used delay-and-sum (DAS) beamforming with apodization and coherent compounding. Given the lower computational load of the proposed framework compared to DAS, to our knowledge it can, therefore, be concluded that it outperforms commonly used beamforming methods such as Stolt's f-k, Lu's f-k, and DAS.

  14. Primary Tumour Resection Could Improve the Survival of Unresectable Metastatic Colorectal Cancer Patients Receiving Bevacizumab-Containing Chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhiming Wang

    2016-09-01

    Full Text Available Background: The effect of primary tumour resection (PTR among metastatic colorectal cancer (mCRC patients remains controversial. Combination chemotherapy with bevacizumab could improve the clinical outcomes of these patients, which might change the importance of PTR in the multi-disciplinary treatment pattern. Methods: We performed a non-randomized prospective controlled study of mCRC pts whose performance status (PS scored ≤2 and who received bevacizumab combination chemotherapy (FOLFOX/XELOX/FOLFIRI as a first-line therapy. These patients were classified into the PTR group and the IPT (intact primary tumour group according to whether they underwent PTR before receiving the systemic therapy. The progression free survival (PFS time and overall survival (OS time, which were recorded from the start of the primary diagnosis until disease progression and death or last follow-up, were analysed. We also compared severe clinical events (such as emergency surgery, radiation therapy, and stent plantation between the two groups. Results: One hundred and nighty-one mCRC pts (108 male patients and 93 female patients were entered in this prospective observational study. The median age was 57.5 years old. The clinical characteristics (age, gender, performance status, primary tumour site, RAS status, and the number of metastatic organs did not significantly differ between the two groups. The median PFS and OS times of the PTR group were superior than those of the IPT group (10.0 vs 7.8 months, p Conclusions: The mCRC patients who received PTR and bevacizumab combination chemotherapy had better clinical outcomes than patients who did not receive PTR. PTR also decreased the incidence of severe clinical events and improved quality of life.

  15. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Dominguez, Jessica A; Vithayathil, Paul J; Khailova, Ludmila; Lawrance, Christopher P; Samocha, Alexandr J; Jung, Enjae; Leathersich, Ann M; Dunne, W Michael; Coopersmith, Craig M

    2011-10-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

  16. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    International Nuclear Information System (INIS)

    Boda-Heggemann, J.; Schneider, V.; Weiss, C.

    2013-01-01

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  17. Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.

    Directory of Open Access Journals (Sweden)

    Jiali Zhu

    Full Text Available BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF-alpha, interleukin (IL-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3(+ T cell was inhibited in the thymus. The numbers of CD4(+, CD8(+ T lymphocytes and dendritic cells (DCs were higher, while the number of CD4(+CD25(+ regulatory T cells was lower in the baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin improves survival of mice

  18. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, J.; Schneider, V. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Radiation Oncology; Weiss, C. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Biomathematics and Medical Statistics] [and others

    2013-05-15

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  19. Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology, and Survival in the Mouse Model of Bubonic Plague.

    Science.gov (United States)

    Levy, Yinon; Vagima, Yaron; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Gur, David; Fogel, Itay; Chitlaru, Theodor; Flashner, Yehuda; Mamroud, Emanuelle

    2016-09-15

    Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague. Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-Y. pestis antibodies alone or in combination with the corticosteroid methylprednisolone. The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase 9 in the tissues, and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs. Corticosteroids induce an unexpectedly effective antibacterial response apart from their antiinflammatory properties, thereby improving treatment efficacy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

    Science.gov (United States)

    Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

    2018-02-01

    Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Thermal efficiency improvement in high output diesel engines a comparison of a Rankine cycle with turbo-compounding

    International Nuclear Information System (INIS)

    Weerasinghe, W.M.S.R.; Stobart, R.K.; Hounsham, S.M.

    2010-01-01

    Thermal management, in particular, heat recovery and utilisation in internal combustion engines result in improved fuel economy, reduced emissions, fast warm up and optimized cylinder head temperatures. turbo-compounding is a heat recovery technique that has been successfully used in medium and large scale engines. Heat recovery to a secondary fluid and expansion is used in large scale engines, such as in power plants in the form of heat recovery steam generators (HRSG) . The present paper presents a thermodynamic analysis of turbo-compounding and heat recovery and utilisation through a fluid power cycle, a technique that is also applicable to medium and small scale engines. In a fluid power cycle, the working fluid is stored in a reservoir and expanded subsequently. The reservoir acts as an energy buffer that improves the overall efficiency, significantly. This paper highlights the relative advantage of exhaust heat secondary power cycles over turbo-compounding with the aid of MATLAB based QSS Toolbox simulation results. Steam has been selected as the working fluid in this work for its superior heat capacity over organic fluids and gases.

  2. Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd; Fischer-Valuck, Benjamin W. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Mutch, David G.; Powell, Matthew A. [Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri (United States); Schwarz, Julie K. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Grigsby, Perry W., E-mail: pgrigsby@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2015-11-01

    Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.

  3. Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

    International Nuclear Information System (INIS)

    Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd; Fischer-Valuck, Benjamin W.; Mutch, David G.; Powell, Matthew A.; Schwarz, Julie K.; Grigsby, Perry W.

    2015-01-01

    Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.

  4. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.

    Science.gov (United States)

    Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H

    2014-01-28

    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.

  5. Pattern optimization of compound optical film for uniformity improvement in liquid-crystal displays

    Science.gov (United States)

    Huang, Bing-Le; Lin, Jin-tang; Ye, Yun; Xu, Sheng; Chen, En-guo; Guo, Tai-Liang

    2017-12-01

    The density dynamic adjustment algorithm (DDAA) is designed to efficiently promote the uniformity of the integrated backlight module (IBLM) by adjusting the microstructures' distribution on the compound optical film (COF), in which the COF is constructed in the SolidWorks and simulated in the TracePro. In order to demonstrate the universality of the proposed algorithm, the initial distribution is allocated by the Bezier curve instead of an empirical value. Simulation results maintains that the uniformity of the IBLM reaches over 90% only after four rounds. Moreover, the vertical and horizontal full width at half maximum of angular intensity are collimated to 24 deg and 14 deg, respectively. Compared with the current industry requirement, the IBLM has an 85% higher luminance uniformity of the emerging light, which demonstrate the feasibility and universality of the proposed algorithm.

  6. Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

    Directory of Open Access Journals (Sweden)

    Joerg Berghausen

    2016-03-01

    Full Text Available Solubility can be the absorption limiting factor for drug candidates and is therefore a very important input parameter for oral exposure prediction of compounds with limited solubility. Biorelevant media of the fasted and fed state have been published for humans, as well as for dogs in the fasted state. In a drug discovery environment, rodents are the most common animal model to assess the oral exposure of drug candidates. In this study a rat simulated intestinal fluid (rSIF is proposed as a more physiologically relevant media to describe drug solubility in rats. Equilibrium solubility in this medium was tested as input parameter for physiologically-based pharmacokinetics (PBPK simulations of oral pharmacokinetics in the rat. Simulations were compared to those obtained using other solubility values as input parameters, like buffer at pH 6.8, human simulated intestinal fluid and a comprehensive dissolution assay based on rSIF. Our study on nine different compounds demonstrates that the incorporation of rSIF equilibrium solubility values into PBPK models of oral drug exposure can significantly improve the reliability of simulations in rats for doses up to 300 mg/kg compared to other media. The comprehensive dissolution assay may help to improve further simulation outcome, but the greater experimental effort as compared to equilibrium solubility may limit its use in a drug discovery environment. Overall, PBPK simulations based on solubility in the proposed rSIF medium can improve prioritizing compounds in drug discovery as well as planning dose escalation studies, e.g. during toxicological investigations.

  7. Improvement of chick survival and zootechnical performance of the local hen in a village environment in Senegal

    Directory of Open Access Journals (Sweden)

    G. Nahimana

    2017-09-01

    Full Text Available A one-year longitudinal survey was carried out in 45 poultry farms in Salemata Department (Senegal to assess two management methods of the mother-chick couple, with the aim to improve the productivity of family poultry farming. At hatching, the hens belonging to treatment A (HTA were partially reared in confinement (they were removed from the brooder pen after two weeks, whereas the chicks were kept there for up to four weeks of age. In contrast, hens in treatment B (HTB were kept free range. The results showed that the zootechnical performance of HTAs had improved. The duration of the reproductive cycle was reduced from 113.5 to 62.2 days. As a result, the number of breeding cycles increased from 3.4 to 5.6 per year and the annual egg production from 35.3 to 57.6. The rapid return of HTAs to egg laying did not affect the number of eggs laid per brood (10.3 compared to 10.2 and the hatching rate (82.4% compared to 79.5%. The weight growth of chicks from both hen types has been influenced by the breeding type, genotype and sex. The weight of crossbred chicks was higher than that of the local chick except at hatching. After the first month, the weight of male chicks (crossbred or local was still higher than that of female chicks. The average daily weight gain of HTA chicks has always been higher than that of HTB chicks and has been highest between the 13th and 24th week of age. Chick survival was improved by 41.2%, and the most frequent causes of mortality were predators (raptors, cats. This study showed that the farming type where hens and their chicks are semiconfined optimized poultry productivity.

  8. Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.

    Science.gov (United States)

    Watanabe, Shinichi; Kuwabara, Yui; Suehiro, Satoshi; Yamashita, Daisuke; Tanaka, Mamoru; Tanaka, Akihiro; Ohue, Shiro; Araki, Hiroaki

    2017-03-01

    Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

  9. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    International Nuclear Information System (INIS)

    Adachi, Naoki; Kubota, Yoshitaka; Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe; Kuroda, Masayuki; Mitsukawa, Nobuyuki; Bujo, Hideaki; Satoh, Kaneshige

    2015-01-01

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings

  10. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Naoki [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kubota, Yoshitaka, E-mail: kubota-cbu@umin.ac.jp [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kuroda, Masayuki [Center for Advanced Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Mitsukawa, Nobuyuki [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Bujo, Hideaki [Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University, Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, #285-8741 (Japan); Satoh, Kaneshige [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan)

    2015-08-07

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.

  11. End-Tidal CO2-Guided Chest Compression Delivery Improves Survival in a Neonatal Asphyxial Cardiac Arrest Model.

    Science.gov (United States)

    Hamrick, Justin T; Hamrick, Jennifer L; Bhalala, Utpal; Armstrong, Jillian S; Lee, Jeong-Hoo; Kulikowicz, Ewa; Lee, Jennifer K; Kudchadkar, Sapna R; Koehler, Raymond C; Hunt, Elizabeth A; Shaffner, Donald H

    2017-11-01

    To determine whether end-tidal CO2-guided chest compression delivery improves survival over standard cardiopulmonary resuscitation after prolonged asphyxial arrest. Preclinical randomized controlled study. University animal research laboratory. 1-2-week-old swine. After undergoing a 20-minute asphyxial arrest, animals received either standard or end-tidal CO2-guided cardiopulmonary resuscitation. In the standard group, chest compression delivery was optimized by video and verbal feedback to maintain the rate, depth, and release within published guidelines. In the end-tidal CO2-guided group, chest compression rate and depth were adjusted to obtain a maximal end-tidal CO2 level without other feedback. Cardiopulmonary resuscitation included 10 minutes of basic life support followed by advanced life support for 10 minutes or until return of spontaneous circulation. Mean end-tidal CO2 at 10 minutes of cardiopulmonary resuscitation was 34 ± 8 torr in the end-tidal CO2 group (n = 14) and 19 ± 9 torr in the standard group (n = 14; p = 0.0001). The return of spontaneous circulation rate was 7 of 14 (50%) in the end-tidal CO2 group and 2 of 14 (14%) in the standard group (p = 0.04). The chest compression rate averaged 143 ± 10/min in the end-tidal CO2 group and 102 ± 2/min in the standard group (p tidal CO2-guided chest compression delivery. The response of the relaxation arterial pressure and cerebral perfusion pressure to the initial epinephrine administration was greater in the end-tidal CO2 group than in the standard group (p = 0.01 and p = 0.03, respectively). The prevalence of resuscitation-related injuries was similar between groups. End-tidal CO2-guided chest compression delivery is an effective resuscitation method that improves early survival after prolonged asphyxial arrest in this neonatal piglet model. Optimizing end-tidal CO2 levels during cardiopulmonary resuscitation required that chest compression delivery rate exceed current guidelines

  12. Improving GC-PPC-SAFT equation of state for LLE of hydrocarbons and oxygenated compounds with water

    DEFF Research Database (Denmark)

    Nguyen, Thanh-Binh; Jean-Charles, De Hemptinne; Creton, Benoit

    2014-01-01

    , uαβ, and wαβ are fitted on mutual solubilities of water and organic compounds. The regressed values which are obtained for each chemical family, are subsequently used for predicting infinite dilution activity coefficient in water and n-octanol/water partition coefficient.In general, the results...... obtained are very much improved compared to the predictive approach discussed previously [Nguyen et al. Ind. Eng. Chem. Res. 52 (2013) 7014-7029]. The global deviation values on the decimal log scale for infinite dilution activity coefficient in water, water solubility and n-octanol/water partition...

  13. Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

    OpenAIRE

    Takakura, Kentaro; Ito, Shogo; Sonoda, Junya; Tabata, Koji; Shiozaki, Motoko; Nagai, Kaoru; Shibata, Masahiro; Koike, Masato; Uchiyama, Yasuo; Gotow, Takahiro

    2017-01-01

    The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to â¼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of ...

  14. Improving a variation of the DSC technique for measuring the boiling points of pure compounds at low pressures

    International Nuclear Information System (INIS)

    Troni, Kelly L.; Damaceno, Daniela S.; Ceriani, Roberta

    2016-01-01

    Highlights: • Improvement of a variation of the DSC technique for boiling points at low pressures. • Use of a ballpoint pen ball over the pinhole of the DSC crucible. • Effects of configuration variables of the DSC technique accounted by factorial design. • An optimized region was obtained and tested for selected compounds. - Abstract: This study aims to improve a variation of the differential scanning calorimetry (DSC) technique for measuring boiling points of pure compounds at low pressures. Using a well-known n-paraffin (n-hexadecane), experimental boiling points at a pressure of 3.47 kPa with u(P) = 0.07 kPa were obtained by using a variation of the DSC technique, which consists of placing samples inside hermetically sealed aluminum crucibles, with a pinhole (diameter of 0.8 mm) made on the lid and a tungsten carbide ball with a diameter of 1.0 mm over it. Experiments were configured at nine different combinations of heating rates (K·min"−"1) and sample sizes (mg) following a full factorial design (2"2 trials plus a star configuration and three central points). Individual and combined effects of these two independent variables on the difference between experimental and estimated boiling points (NIST Thermo Data Engine v. 5.0 – Aspen Plus v. 8.4) were investigated. The results obtained in this work reveal that although both factors affect individually the accuracy of this variation of the DSC technique, the effect of heating rate is the most important. An optimized region of combinations of heating rate and sample size for determining boiling points of pure compounds at low pressures was obtained using the response-surface methodology (RSM). Within this optimized region, a selected condition, combining a heating rate of 24.52 K·min"−"1 and a sample size of (4.6 ± 0.5) mg, was tested for six different compounds (92.094–302.37 g mol"−"1) comprising four fatty compounds (tributyrin, monocaprylin, octanoic acid and 1-octadecanol), glycerol and n

  15. Improving of Corrosion Resistance of Aluminum Alloys by Removing Intermetallic Compound

    Energy Technology Data Exchange (ETDEWEB)

    Seri, Osami [Muroran it., Hokkaido (Japan)

    2008-06-15

    It is well known that iron is one of the most common impurity elements sound in aluminum and its alloys. Iron in the aluminum forms an intermetallic compounds such as FeAl{sub 3}. The FeAl{sub 3} particles on the aluminum surface are one of the most detrimental phases to the corrosion process and anodizing procedure for aluminum and its alloys. Trial and error surface treatment will be carried out to find the preferential and effective removal of FeAl{sub 3} particles on the surfaces without dissolution of aluminum matrix around the particles. One of the preferable surface treatments for the aim of getting FeAl{sub 3} free surface was an electrochemical treatment such as cathodic current density of -2 kAm{sup -2} in a 20-30 mass% HNO{sub 3} solution for the period of 300s. The corrosion characteristics of aluminum surface with FeAl{sub 3} free particles are examined in a 0.1 kmol/m{sup 3} NaCl solution. It is found that aluminum with free FeAl{sub 3} particles shows higher corrosion resistance than aluminum with FeAl{sub 3} particles.

  16. Improving of Corrosion Resistance of Aluminum Alloys by Removing Intermetallic Compound

    International Nuclear Information System (INIS)

    Seri, Osami

    2008-01-01

    It is well known that iron is one of the most common impurity elements sound in aluminum and its alloys. Iron in the aluminum forms an intermetallic compounds such as FeAl 3 . The FeAl 3 particles on the aluminum surface are one of the most detrimental phases to the corrosion process and anodizing procedure for aluminum and its alloys. Trial and error surface treatment will be carried out to find the preferential and effective removal of FeAl 3 particles on the surfaces without dissolution of aluminum matrix around the particles. One of the preferable surface treatments for the aim of getting FeAl 3 free surface was an electrochemical treatment such as cathodic current density of -2 kAm -2 in a 20-30 mass% HNO 3 solution for the period of 300s. The corrosion characteristics of aluminum surface with FeAl 3 free particles are examined in a 0.1 kmol/m 3 NaCl solution. It is found that aluminum with free FeAl 3 particles shows higher corrosion resistance than aluminum with FeAl 3 particles

  17. Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.

    Science.gov (United States)

    Chaudhuri, R K; Bojanowski, K

    2017-10-01

    The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin. The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo. IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin. Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  18. An investigation of various wavelength-shifting compounds for improving counting efficiency when 32P-cerenkov radiation is measured in aqueous samples

    NARCIS (Netherlands)

    Ginkel, G. van

    Various water-soluble wavelength-shifting compounds were investigated to assess their suitability for the improvement of counting efficiency when erenkov radiation from phosphorous-32 is measured in a liquid scintillation counter. Of these compounds esculin, β-methyl-umbelliferon and sodium

  19. Unreported births and deaths, a severe obstacle for improved neonatal survival in low-income countries; a population based study

    Directory of Open Access Journals (Sweden)

    Wallin Lars

    2008-03-01

    Full Text Available Abstract Background In order to improve child survival there is a need to target neonatal mortality. In this pursuit, valid local and national statistics on child health are essential. We analyze to what extent births and neonatal deaths are unreported in a low-income country and discuss the consequences at local and international levels for efforts to save newborn lives. Methods Information on all births and neonatal deaths in Quang Ninh province in Northern Vietnam in 2005 was ascertained by systematic inventory through group interviews with key informants, questionnaires and examination of health facility records. Health care staff at 187 Community Health Centers (CHC and 18 hospitals, in addition to 1372 Village Health Workers (VHW, were included in the study. Results were compared with the official reports of the Provincial Health Bureau. Results The neonatal mortality rate (NMR was 16/1000 (284 neonatal deaths/17 519 births, as compared to the official rate of 4.2/1000. The NMR varied between 44/1000 and 10/1000 in the different districts of the province. The under-reporting was mainly attributable to a dysfunctional reporting system and the fact that families, not the health system, were made responsible to register births and deaths. This under-reporting has severe consequences at local, national and international levels. At a local level, it results in a lack of awareness of the magnitude and differentials in NMR, leading to an indifference towards the problem. At a national and international level the perceived low mortality rate is manifested in a lack of investments in perinatal health programs. Conclusion This example of a faulty health information system is reportedly not unique in low and middle income countries where needs for neonatal health reforms are greatest. Improving reporting systems on births and neonatal deaths is a matter of human rights and a prerequisite for reducing neonatal mortality in order to reach the fourth

  20. Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG).

    Science.gov (United States)

    Qin, Lei; Li, Angie; Qu, Jinrong; Reinshagen, Katherine; Li, Xiang; Cheng, Su-Chun; Bryant, Annie; Young, Geoffrey S

    2018-04-01

    Mixed reports leave uncertainty about whether normalization of apparent diffusion coefficient (ADC) to a within-subject white matter reference is necessary for assessment of tumor cellularity. We tested whether normalization improves the previously reported correlation of resection margin ADC with 15-month overall survival (OS) in HGG patients. Spin-echo echo-planar DWI was retrieved from 3 T MRI acquired between maximal resection and radiation in 37 adults with new-onset HGG (25 glioblastoma; 12 anaplastic astrocytoma). ADC maps were produced with the FSL DTIFIT tool (Oxford Centre for Functional MRI). 3 neuroradiologists manually selected regions of interest (ROI) in normal appearing white matter (NAWM) and in non-enhancing tumor (NT) Normalized ADC (nADC) was computed as the ratio of absolute NT ADC to NAWM ADC. Reproducibility of nADC and absolute ADC among the readers' ROI was assessed using intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wCV). Correlations of ADC and nADC with OS were compared using receiver operating characteristics (ROC) analysis. A p value 0.05 was considered statistically significant. Both mean ADC and nADC differed significantly between patients subgrouped by 15-month OS (p = 0.0014 and 0.0073 respectively). wCV and ICC among the readers were similar for absolute and normalized ADC. In ROC analysis of correlation with OS, nADC did not perform significantly better than absolute ADC. Normalization does not significantly improve the correlation of absolute ADC with OS in HGG, suggesting that normalization is not necessary for clinical or research ADC analysis in HGG patients.

  1. Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway.

    Science.gov (United States)

    Katare, Rajesh G; Kakinuma, Yoshihiko; Arikawa, Mikihiko; Yamasaki, Fumiyasu; Sato, Takayuki

    2009-03-01

    Chronic heart failure (CHF) is the major cause of death in the developed countries. Calorie restriction is known to improve the recovery in these patients; however, the exact mechanism behind this protective effect is unknown. Here we demonstrate the activation of cell survival PI3kinase/Akt and VEGF pathway as the mechanism behind the protection induced by intermittent fasting in a rat model of established chronic myocardial ischemia (MI). Chronic MI was induced in rats by occlusion of the left coronary artery. Two weeks later, the rats were randomly assigned to a normal feeding group (MI-NF) and an alternate-day feeding group (MI-IF). After 6 weeks of observation, we evaluated the effect of intermittent fasting on cellular and ventricular remodeling and long-term survival after CHF. Compared with the normally fed group, intermittent fasting markedly improved the survival of rats with CHF (88.5% versus 23% survival, Pfasted hearts. Immunohistochemical studies confirmed increased capillary density (Pfasting also upregulated the expression of other anti-apoptotic factors such as Akt and Bcl-2 and reduced the TUNEL positive apoptotic nuclei in the border zone. Chronic intermittent fasting markedly improves the long-term survival after CHF by activation through its pro-angiogenic, anti-apoptotic and anti-remodeling effects.

  2. Radiation-Induced Differentiated Thyroid Cancer Is Associated with Improved Overall Survival but Not Thyroid Cancer-Specific Mortality or Disease-Free Survival.

    Science.gov (United States)

    White, Michael G; Cipriani, Nicole A; Abdulrasool, Layth; Kaplan, Sharone; Aschebrook-Kilfoy, Briseis; Angelos, Peter; Kaplan, Edwin L; Grogan, Raymon H; Onel, Kenan

    2016-08-01

    Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts (p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05-3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC

  3. Increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with Trypanosoma cruzi and treated with highly diluted Lycopodium clavatum.

    Science.gov (United States)

    Falkowski-Temporini, Gislaine Janaina; Lopes, Carina Ribeiro; Massini, Paula Fernanda; Brustolin, Camila Fernanda; Ferraz, Fabiana Nabarro; Sandri, Patricia Flora; Hernandes, Luzmarina; Aleixo, Denise Lessa; Barion, Terezinha Fátima; Esper, Luiz Gilson; de Araújo, Silvana Marques

    2017-09-01

    Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Prophylactic cranial irradiation could improve overall survival in patients with extensive small cell lung cancer. A retrospective study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [Tsinghua University, Medical Center Tsinghua University, Beijing (China); Li, Jinyu; Hu, Yi; Lin, Zhi; Jiao, Shunchang [Chinese PLA General Hospital, Department of Medical Oncology, Beijing (China); Zhang, Yibao [Peking University Cancer Hospital and Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiotherapy, Beijing (China); Zhao, Zhifei [Chinese PLA General Hospital, Department of Radiation Oncology, Beijing (China)

    2016-12-15

    To evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival (OS) in patients with extensive small cell lung cancer (ESCLC). Between April 2005 and May 2014, 204 patients with ESCLC who had any response (according to RECIST 1.1) to initial chemotherapy were reviewed. All patients had undergone appropriate imaging tests to exclude brain metastases before initial chemotherapy. PCI was performed on 45 patients (22.1 %) and the remaining patients (77.9 %) received no such treatment (control group). Primary endpoint was OS. The incidence of brain metastases, brain metastases-free survival (BMFS), and adverse effects were also evaluated. Survival data of the 204 patients were analyzed statistically. PCI significantly prolonged median OS from 12.6 to 16.5 months as compared to the control group (hazard ratio, HR, 0.63; 95 % confidence interval, CI, 0.41 to 0.96; p = 0.033). PCI significantly lowered the risk of brain metastases (HR 0.48; 95 % CI 0.30 to 0.76; p = 0.001). The 1-year incidence of brain metastases was 17.1 and 55.9 % in the PCI and control group, respectively. PCI significantly correlated with the increased median BMFS (p = 0.002). Additionally, multivariate analyses demonstrated that PCI was a favorable independent predictor of OS, BMFS, and the incidence of brain metastases. Acute and chronic adverse effects were generally low grade and well tolerated in patients receiving PCI. PCI after any response to initial chemotherapy significantly improved OS of ESCLC patients analyzed in this study. (orig.) [German] Beurteilung des Effekts der prophylaktischen kranialen Bestrahlung (PCI) auf das Gesamtueberleben (OS) bei Patienten mit ausgedehntem kleinzelligem Lungenkarzinom (ESCLC). Zwischen April 2005 und Mai 2014 wurden 204 Patienten mit ESCLC nach Ansprechen auf eine initiale Chemotherapie (gemaess RECIST 1.1) untersucht. Vor der Chemotherapie wurden bei allen Patienten Untersuchungen mit entsprechenden Bildgebungsverfahren

  5. Improved mechanical and functional properties of elastomer/graphite nanocomposites prepared by latex compounding

    International Nuclear Information System (INIS)

    Yang Jian; Tian Ming; Jia Qingxiu; Shi Junhong; Zhang Liqun; Lim Szuhui; Yu Zhongzhen; Mai Yiuwing

    2007-01-01

    The facile latex approach has been adopted to finely incorporate graphite nanosheets into elastomeric polymer matrix to obtain high-performance elastomeric nanocomposites with improved mechanical properties and functional properties. Scanning electron microscopy, transmission electron microscopy and X-ray diffraction experiments show that the nanostructures of the final nanocomposites exhibit a high degree of exfoliation and intercalation of graphite in the nitrile-butadiene rubber (NBR) matrix. Mechanical and dynamic-mechanical tests demonstrate that the NBR/graphite nanocomposites possess greatly increased elastic modulus and tensile strength, and desirably strong interfaces. The unexpected self-crosslinking of elastomer/graphite nanocomposites was discovered and then verified by oscillating disc rheometry and equilibrium swelling experiments. After critically examining various polymer types by X-ray photoelectron spectroscopy, electron spin resonance and Fourier transform infrared spectroscopy, a radical initiation mechanism was proposed to explain the self-crosslinking reaction. These NBR/graphite nanocomposites possess significantly improved wear resistance and gas barrier properties, and superior electrical/thermal conductivity. Such versatile functional properties make NBR nanocomposites a promising new class of advanced materials

  6. Improved mechanical and functional properties of elastomer/graphite nanocomposites prepared by latex compounding

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jian [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Key Laboratory on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Tian Ming [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Jia Qingxiu [Key Laboratory on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Shi Junhong [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Zhang Liqun [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Key Laboratory on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China)], E-mail: zhanglq@mail.buct.edu.cn; Lim Szuhui; Yu Zhongzhen [Centre for Advanced Materials Technology (CAMT), School of Aerospace, Mechanical and Mechatronic Engineering (J07), University of Sydney, Sydney, NSW 2006 (Australia); Mai Yiuwing [Centre for Advanced Materials Technology (CAMT), School of Aerospace, Mechanical and Mechatronic Engineering (J07), University of Sydney, Sydney, NSW 2006 (Australia)], E-mail: y.mai@usyd.edu.au

    2007-10-15

    The facile latex approach has been adopted to finely incorporate graphite nanosheets into elastomeric polymer matrix to obtain high-performance elastomeric nanocomposites with improved mechanical properties and functional properties. Scanning electron microscopy, transmission electron microscopy and X-ray diffraction experiments show that the nanostructures of the final nanocomposites exhibit a high degree of exfoliation and intercalation of graphite in the nitrile-butadiene rubber (NBR) matrix. Mechanical and dynamic-mechanical tests demonstrate that the NBR/graphite nanocomposites possess greatly increased elastic modulus and tensile strength, and desirably strong interfaces. The unexpected self-crosslinking of elastomer/graphite nanocomposites was discovered and then verified by oscillating disc rheometry and equilibrium swelling experiments. After critically examining various polymer types by X-ray photoelectron spectroscopy, electron spin resonance and Fourier transform infrared spectroscopy, a radical initiation mechanism was proposed to explain the self-crosslinking reaction. These NBR/graphite nanocomposites possess significantly improved wear resistance and gas barrier properties, and superior electrical/thermal conductivity. Such versatile functional properties make NBR nanocomposites a promising new class of advanced materials.

  7. Apparent survival rates of forest birds in eastern Ecuador revisited: improvement in precision but no change in estimates.

    Directory of Open Access Journals (Sweden)

    John G Blake

    Full Text Available Knowledge of survival rates of Neotropical landbirds remains limited, with estimates of apparent survival available from relatively few sites and species. Previously, capture-mark-recapture models were used to estimate apparent survival of 31 species (30 passerines, 1 Trochilidae from eastern Ecuador based on data collected from 2001 to 2006. Here, estimates are updated with data from 2001-2012 to determine how additional years of data affect estimates; estimates for six additional species are provided. Models assuming constant survival had highest support for 19 of 31 species when based on 12 years of data compared to 27 when based on six; models incorporating effects of transients had the highest support for 12 of 31 species compared to four when based on 12 and six years, respectively. Average apparent survival based on the most highly-supported model (based on model averaging, when appropriate was 0.59 (± 0.02 SE across 30 species of passerines when based on 12 years and 0.57 (± 0.02 when based on six. Standard errors of survival estimates based on 12 years were approximately half those based on six years. Of 31 species in both data sets, estimates of apparent survival were somewhat lower for 13, somewhat higher for 17, and remained unchanged for one; confidence intervals for estimates based on six and 12 years of data overlapped for all species. Results indicate that estimates of apparent survival are comparable but more precise when based on longer-term data sets; standard error of the estimates was negatively correlated with numbers of captures (rs  = -0.72 and recaptures (rs  = -0.93, P<0.001 in both cases. Thus, reasonable estimates of apparent survival may be obtained with relatively few years of data if sample sizes are sufficient.

  8. 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 ov...

  9. Improved survival after an educational project on colon cancer management in the county of Stockholm--a population based cohort study.

    Science.gov (United States)

    Bernhoff, R; Martling, A; Sjövall, A; Granath, F; Hohenberger, W; Holm, T

    2015-11-01

    Outcomes in rectal cancer have improved dramatically after the introduction of total mesorectal excision (TME). Recently, the TME concept has been transformed into that of complete mesocolic excision (CME) in an attempt to improve prognosis for patients with colon cancer. Multidisciplinary team (MDT) workshops including the CME concept were held annually between 2004 and 2008 at the Karolinska University Hospital. The workshops focused on preoperative staging, surgery and histopathology and included lectures and live surgery sessions. To compare survival before and after the "Stockholm Colon Cancer Project" all patients diagnosed with a right sided colon cancer between January 1, 2001 and December 31, 2003 (Group 1) and from January 1, 2006 until December 31, 2008 (Group 2) in Stockholm were identified from the Swedish ColoRectal Cancer Registry (SCRCR). The proportion of patients having a tumour resection and the proportion having emergency surgery was higher in Group 1. There were more early tumours and more R0 resections in Group 2. Overall survival in all diagnosed patients and disease free survival after tumour resection was improved in the second time period. Surgical teaching programmes may have an impact on the management and outcome in colon cancer. The exact impact from the "Stockholm Colon Cancer Project" cannot be established, however it is likely that it contributed to the improved survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Directory of Open Access Journals (Sweden)

    Marcos Perez-Basterrechea

    Full Text Available Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  11. A novel and efficient gene transfer strategy reduces glial reactivity and improves neuronal survival and axonal growth in vitro.

    Directory of Open Access Journals (Sweden)

    Mathieu Desclaux

    Full Text Available BACKGROUND: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi. METHODS AND FINDINGS: In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model -- scratched primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. CONCLUSIONS: Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for

  12. A novel and efficient gene transfer strategy reduces glial reactivity and improves neuronal survival and axonal growth in vitro.

    Science.gov (United States)

    Desclaux, Mathieu; Teigell, Marisa; Amar, Lahouari; Vogel, Roland; Gimenez Y Ribotta, Minerva; Privat, Alain; Mallet, Jacques

    2009-07-14

    The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi). In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model -- scratched primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for increasing glial permissiveness and permitting axonal regeneration

  13. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Science.gov (United States)

    Perez-Basterrechea, Marcos; Esteban, Manuel Martinez; Alvarez-Viejo, Maria; Fontanil, Tania; Cal, Santiago; Sanchez Pitiot, Marta; Otero, Jesus; Obaya, Alvaro Jesus

    2017-01-01

    Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  14. Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure.

    Science.gov (United States)

    Garcia-Martinez, Rita; Andreola, Fausto; Mehta, Gautam; Poulton, Katie; Oria, Marc; Jover, Maria; Soeda, Junpei; Macnaughtan, Jane; De Chiara, Francesco; Habtesion, Abeba; Mookerjee, Rajeshwar P; Davies, Nathan; Jalan, Rajiv

    2015-04-01

    Liver failure is characterized by endothelial dysfunction, which results in hemodynamic disturbances leading to renal failure. Albumin infusion improves hemodynamics and prevents renal dysfunction in advance liver failure. These effects are only partly explained by the oncotic properties of albumin. This study was designed to test the hypothesis that albumin exerts its beneficial effects by stabilising endothelial function. In vivo: systemic hemodynamics, renal function, markers of endothelial dysfunction (ADMA) and inflammation were studied in analbuminaemic and Sprague-Dawley rats, 6-weeks after sham/bile duct ligation surgery. In vitro: human umbilical vein endothelial cells were stimulated with LPS with or without albumin. We studied protein expression and gene expression of adhesion molecules, intracellular reactive oxygen species, and cell stress markers. Compared to controls, analbuminaemic rats had significantly greater hemodynamic deterioration after bile duct ligation, resulting in worse renal function and shorter survival. This was associated with significantly greater plasma renin activity, worse endothelial function, and disturbed inflammatory response. In vitro studies showed that albumin was actively taken up by endothelial cells. Incubation of albumin pre-treated endothelial cells with LPS was associated with significantly less activation compared with untreated cells, decreased intracellular reactive oxygen species, and markers of cell stress. These results show, for the first time, that absence of albumin is characterised by worse systemic hemodynamics, renal function and higher mortality in a rodent model of chronic liver failure and illustrates the important non-oncotic properties of albumin in protecting against endothelial dysfunction. Copyright © 2015. Published by Elsevier B.V.

  15. An investigation of various wavelength-shifting compounds for improving counting efficiency when 32P-Cerenkov radiation is measured in aqueous samples

    International Nuclear Information System (INIS)

    Ginkel, G. van

    1980-01-01

    Various water-soluble wavelength-shifting compounds were investigated to assess their suitability for the improvement of counting efficiency when Cerenkov radiation from phosphorous-32 is measured in a liquid scintillation counter. Of these compounds esculin, β-methyl-umbelliferon and sodium salicylate led to the greatest improvement in counting efficiency. Especially esculin and β-methyl-umbelliferon are fairly stable under a variety of experimental conditions and improve counting efficiencies by a factor of about 1.3 and 1.2 respectively. The use of ethanol as a water-miscible solvent combined with wavelength shifters soluble in both solvents does not improve counting efficiency. (author)

  16. Hypothesis: Co-transfer of genuine embryos and implantation-promoting compounds via artificial containers improve endometrium receptivity.

    Science.gov (United States)

    Celik, Onder; Acet, Mustafa; Celik, Sudenaz; Sahin, Levent; Koc, Onder; Celik, Nilufer

    2017-06-01

    As with other organs endometrial functions are altered with the advancing age. Age related decrease in reproductive functions leads to decline in the number of oocytes retrieved and the synthesis of endometrial receptivity molecules. Despite the significant improvement in assisted reproductive technologies we do not have so many options to enhance endometrial receptivity. Due to lack of drugs having endometrium receptivity enhancement properties, oocyte donation seems to be the only solution for women with implantation failure. The euploid oocytes come from young and healthy donors may overcome age associated endometrial receptivity defect. Nevertheless, many reasons restrict us from using oocyte donation in women with implantation failure. We, therefore, hypothesized that by mimicking a young blastocyst's effect on endometrium, the transfer of genuine embryos and implantation-promoting compounds together might be the new treatment option for infertile women with recurrent implantation failure. Artificial beads, MI or GV oocytes, and empty zona can be used as a container for intrauterine replacement of implantation-promoting compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Improving child survival through a district management strengthening and community empowerment intervention: early implementation experiences from Uganda.

    Science.gov (United States)

    Katahoire, Anne Ruhweza; Henriksson, Dorcus Kiwanuka; Ssegujja, Eric; Waiswa, Peter; Ayebare, Florence; Bagenda, Danstan; Mbonye, Anthony K; Peterson, Stefan Swartling

    2015-08-19

    The Community and District Empowerment for Scale-up (CODES) project pioneered the implementation of a comprehensive district management and community empowerment intervention in five districts in Uganda. In order to improve effective coverage and quality of child survival interventions CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. This paper presents early implementation experiences in five pilot districts and lessons learnt during the first 2 years of implementation. This qualitative study was comprised of 38 in-depth interviews with members of the District Health Teams (DHTs) and two implementing partners. These were supplemented by observations during implementation and documents review. Thematic analysis was used to distill early implementation experiences and lessons learnt from the process. All five districts health teams with support from the implementing partners were able to adopt the UNICEF tools and to develop district health operational work plans that were evidence-based. Members of the DHTs described the approach introduced by the CODES project as a more systematic planning process and very much appreciated it. Districts were also able to implement some of the priority activities included in their work plans but limited financial resources and fiscal decision space constrained the implementation of some activities that were prioritized. Community dialogues based on Citizen Report Cards (CRC) increased community awareness of available health care services, their utilization and led to discussions on service delivery, barriers to service utilization and processes for improvement. Community dialogues were also instrumental in bringing together service users, providers and leaders to discuss problems and

  18. Preoperative radiotherapy for resectable rectal cancer: improved local control is prognostic for distant metastasis occurrence and survival

    International Nuclear Information System (INIS)

    Zlotecki, Robert A.; Mendenhall, William M.; Copeland, Edward M.; Vauthey, Jean-Nicholas; Marsh, Robert D.; McCarley, Dean L.; Million, Rodney R.

    1996-01-01

    Purpose/Objective: To evaluate the effect of preoperative external beam radiotherapy (RT) on local control (LC), distant metastasis (DM), survival, and perioperative complications in a 15-year single-institution experience. Disease and treatment variables potentially prognostic for local-regional control and survival were evaluated, and the importance of LC as a determinant of DM and survival was also examined. Materials and Methods: Two hundred ten patients with potentially resectable cancers of the rectum were treated with preoperative external beam RT at a single institution between 1975 and 1990. Excluded were patients with 'fixed' unresectable tumors and those treated with palliative intent only. All patients were treated with megavoltage RT to minimum tumor doses of 30 Gy using multiple-field techniques. Preoperative chemotherapy was not used. Surgical resection was performed 3-5 weeks after completion of RT. Abdominoperineal resection was performed in 175 cases, low anterior resection in 25 cases, and other surgical procedures in 10 cases. Pathologic tumor staging was by the Astler-Coller modification of the Dukes system. Minimum follow-up was 5 years. Survival analysis was performed using the Kaplan-Meier method, with univariate and multivariate analysis of disease and treatment variables for prognostic significance. Results: No treatment-specific variables were predictive for LC, DM, absolute survival, or cause-specific survival. Disease-specific variables prognostic for LC were deep tumor infiltration or 'tethering' on digital rectal exam and Dukes pathologic stage. Ten-year LC rates were 91% for freely mobile tumors vs. 82% for tethered lesions (p=.009). LC rates for Dukes A, B, and C stage tumors were 100%, 91%, and 73%, respectively (p=.02). Variables prognostic for DM were tumor length, annular involvement, LC, and Dukes pathologic stage. Absolute survival at 5 and 10 years was 57% and 36%, respectively. Variables prognostic for absolute survival were

  19. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; Dipasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-10-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P 14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P 14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

  20. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  1. High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Christina Siesing

    Full Text Available High expression of the RNA-binding motif protein 3 (RBM3 has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS and progression-free survival (PFS.High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively. PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively.High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

  2. Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax

    Science.gov (United States)

    Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S.

    2016-01-01

    The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. PMID:27431219

  3. Improvement of Probiotic Survival in Fruit juice and under Gastrointestinal conditions using Pectin-Nanochitin-Nanolignocellulose as a Novel Prebiotic Gastrointestinal-Resistant Matrix

    Directory of Open Access Journals (Sweden)

    Alireza Chackoshian Khorasani

    2017-08-01

    Full Text Available Background and Objective: Increasing survivability of probiotics in low pH juices and in gastrointestinal conditions is important for probiotic food industry. Nanofibers can reinforce the structure of entrapment matrices protecting probiotics in harsh conditions. This study investigated pectin-based bionanocomposites improved with nanochitin, nanolignocellulose and bacterial nanocellulose to introduce a prebiotic gastrointestinal-resistant matrix for enhancing the survival of Bacillus coagulans as a probiotic.Material and Methods: The bionanocomposites with various compositions were designed using mixture design method. These were fabricated based on cross-linking of calcium ions with pectin for entrapment of Bacillus coagulans. The survivability of probiotic was evaluated at 4°C or 25°C over a 5-week storage in peach juice and under simulated gastrointestinal conditions.Results and Conclusion: The prebiotic score of the pectin-nanochitin-nanolignocellulose (50:25:25% w w-1 was determined as 1.36. The survivability of Bacillus coagulans entrapped within the pectin-nanochitin-nanolignocellulose matrix was ~65% under gastrointestinal treatment. The surface structure of the matrix was relatively smooth coherent, compact and wrinkled due to the three-dimensional arrangement of the nanofibers of chitin and lignocellulose incorporated within pectin. The highest survivability of the entrapped bacteria was ~68% compared to the survivability of the free cell (~53% at the end of 5-week storage period. After 21 day storage in the juice, the survivability of the entrapped bacteria treated under sequential digestion was ~58% as compared to that of the free cell (~43%. The present findings proposed a promising prebiotic matrix to protect probiotics in low pH fruit juice and the gastrointestinal tract.Conflict of interest: The authors declare no conflict of interest.

  4. PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

    Science.gov (United States)

    Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

    2018-03-01

    To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

  5. Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2014-01-01

    Full Text Available Exposure to ionizing radiation alone (RI or combined with traumatic tissue injury (CI is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral followed by 15% total-body-surface-area skin wounds (R-W CI or burns (R-B CI experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.

  6. 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.

  7. Do implantable cardioverter defibrillators improve survival in patients with severe left ventricular systolic dysfunction after coronary artery bypass graft surgery?

    Science.gov (United States)

    Fazal, Iftikhar A; Bates, Matthew G D; Matthews, Iain G; Turley, Andrew J

    2011-06-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether implantable cardioverter defibrillators (ICD) improve survival in patients with severe left ventricular systolic dysfunction (LVSD) after coronary artery bypass graft (CABG) surgery. ICDs are designed to terminate potentially fatal cardiac tachyarrhythmias. A right ventricular lead is mandatory for detection, pacing and defibrillation capabilities. Dual chamber ICDs have an additional right atrial lead and are used for patients with conventional atrioventricular pacing indications. More sophisticated, biventricular devices exist to provide cardiac resynchronisation therapy (CRT) in addition to defibrillation (CRT-D). ICDs have been extensively investigated in patients with LVSD post myocardial infarction and in patients with non-ischaemic cardiomyopathy for both secondary prevention (history of ventricular arrhythmias) and primary prevention (deemed high risk for ventricular arrhythmias). This best evidence topic aims to review the evidence and its applicability to patients post CABG. Nine hundred and sixteen papers were identified using the search method outlined. Eight randomised controlled trials, two meta-analyses, and one non-randomised trial, in addition to international guidelines presented the best evidence to answer the clinical question. The current evidence base and guidelines suggest that ICDs should be considered for all patients with LVSD [ejection fraction (EF) ≤30-40%] receiving optimal pharmacological management, who are ≥40 days post MI [four weeks for National Institute for Health and Clinical Excellence (NICE)] and in New York Heart Association (NYHA) class I-III. UK NICE guidelines require in addition; non-sustained ventricular tachycardia (NSVT) on a Holter monitor and inducible ventricular tachycardia at electrophysiological study for EF between 30 and 35%; or a QRS >120 ms if EF <30%. The North American guidelines

  8. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

    Directory of Open Access Journals (Sweden)

    Wen-Pyng Wu

    Full Text Available Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001. The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001. Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001. Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

  9. Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients.

    Science.gov (United States)

    Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

    2016-02-01

    The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors.Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test.A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P CRM status. Logistic regression analysis revealed that APR (P CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively).This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates.

  10. Strontium-89 for prostate cancer with bone metastases. The potential of cancer control and improvement of overall survival

    International Nuclear Information System (INIS)

    Kuroda, Isao

    2014-01-01

    Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using prostate specific antigen (PSA) as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected. (author)

  11. Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

    Science.gov (United States)

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-04-01

    The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients.

  12. Does accelerometer feedback on high-quality chest compression improve survival rate? An in-hospital cardiac arrest simulation.

    Science.gov (United States)

    Jung, Min Hee; Oh, Je Hyeok; Kim, Chan Woong; Kim, Sung Eun; Lee, Dong Hoon; Chang, Wen Joen

    2015-08-01

    We investigated whether visual feedback from an accelerometer device facilitated high-quality chest compressions during an in-hospital cardiac arrest simulation using a manikin. Thirty health care providers participated in an in-hospital cardiac arrest simulation with 1 minute of continuous chest compressions. Chest compressions were performed on a manikin lying on a bed according to visual feedback from an accelerometer feedback device. The manikin and accelerometer recorded chest compression data simultaneously. The simulated patient was deemed to have survived when the chest compression data satisfied all of the preset high-quality chest compression criteria (depth ≥51 mm, rate >100 per minute, and ≥95% full recoil). Survival rates were calculated from the feedback device and manikin data. The survival rate according to the feedback device data was 80%; however, the manikin data indicated a significantly lower survival rate (46.7%; P = .015). The difference between the accelerometer and manikin survival rates was not significant for participants with a body mass index greater than or equal to 20 kg/m(2) (93.3 vs 73.3%, respectively; P = .330); however, the difference in survival rate was significant in participants with body mass index less than 20 kg/m(2) (66.7 vs 20.0%, respectively; P = .025). The use of accelerometer feedback devices to facilitate high-quality chest compression may not be appropriate for lightweight rescuers because of the potential for compression depth overestimation. Clinical Research Information Service (KCT0001449). Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The use of simple reparameterizations to improve the efficiency of Markov chain Monte Carlo estimation for multilevel models with applications to discrete time survival models.

    Science.gov (United States)

    Browne, William J; Steele, Fiona; Golalizadeh, Mousa; Green, Martin J

    2009-06-01

    We consider the application of Markov chain Monte Carlo (MCMC) estimation methods to random-effects models and in particular the family of discrete time survival models. Survival models can be used in many situations in the medical and social sciences and we illustrate their use through two examples that differ in terms of both substantive area and data structure. A multilevel discrete time survival analysis involves expanding the data set so that the model can be cast as a standard multilevel binary response model. For such models it has been shown that MCMC methods have advantages in terms of reducing estimate bias. However, the data expansion results in very large data sets for which MCMC estimation is often slow and can produce chains that exhibit poor mixing. Any way of improving the mixing will result in both speeding up the methods and more confidence in the estimates that are produced. The MCMC methodological literature is full of alternative algorithms designed to improve mixing of chains and we describe three reparameterization techniques that are easy to implement in available software. We consider two examples of multilevel survival analysis: incidence of mastitis in dairy cattle and contraceptive use dynamics in Indonesia. For each application we show where the reparameterization techniques can be used and assess their performance.

  14. Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse

    Directory of Open Access Journals (Sweden)

    Wu Li-Li

    2011-07-01

    Full Text Available Abstract Background Since transitional cell carcinoma (TCC of the upper urinary tract is a relatively uncommon malignancy, the role of adjuvant radiotherapy is unknown. Methods We treated 133 patients with TCC of the renal pelvis or ureter at our institution between 1998 and 2008. The 67 patients who received external beam radiotherapy (EBRT following surgery were assigned to the radiation group (RT. The clinical target volume included the renal fossa, the course of the ureter to the entire bladder, and the paracaval and para-aortic lymph nodes, which were at risk of harbouring metastatic disease in 53 patients. The tumour bed or residual tumour was targeted in 14 patients. The median radiation dose administered was 50 Gy. The 66 patients who received intravesical chemotherapy were assigned to the non-radiation group (non-RT. Results The overall survival rates for the RT and non-RT groups were not significantly different (p = 0.198. However, there was a significant difference between the survival rates for these groups based on patients with T3/T4 stage cancer. A significant difference was observed in the bladder tumour relapse rate between the irradiated and non-irradiated bladder groups (p = 0.004. Multivariate analysis indicated that improved overall survival was associated with age grade 3 hematologic symptoms also occurred. Conclusion EBRT may improve overall survival for patients with T3/T4 cancer of the renal pelvis or ureter and delay bladder tumour recurrence in all patients.

  15. Microencapsulation of Lactobacillus rhamnosus GG by Transglutaminase Cross-Linked Soy Protein Isolate to Improve Survival in Simulated Gastrointestinal Conditions and Yoghurt.

    Science.gov (United States)

    Li, Chun; Wang, Chun-Ling; Sun, Yu; Li, Ai-Li; Liu, Fei; Meng, Xiang-Chen

    2016-07-01

    Microencapsulation is an effective way to improve the survival of probiotics in simulated gastrointestinal (GI) conditions and yoghurt. In this study, microencapsulation of Lactobacillus rhamnosus GG (LGG) was prepared by first cross-linking of soy protein isolate (SPI) using transglutaminase (TGase), followed by embedding the bacteria in cross-linked SPI, and then freeze-drying. The survival of microencapsulated LGG was evaluated in simulated GI conditions and yoghurt. The results showed that a high microencapsulation yield of 67.4% was obtained. The diameter of the microencapsulated LGG was in the range of 52.83 to 275.16 μm. Water activity did not differ between free and microencapsulated LGG after freeze-drying. The survival of microencapsulated LGG under simulated gastric juice (pH 2.5 and 3.6), intestinal juice (0.3% and 2% bile salt) and storage at 4 °C were significantly higher than that of free cells. The survival of LGG in TGase cross-linked SPI microcapsules was also improved to 14.5 ± 0.5% during storage in yoghurt. The microencapsulation of probiotics by TGase-treated SPI can be a suitable alternative to polysaccharide gelation technologies. © 2016 Institute of Food Technologists®

  16. Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

    Science.gov (United States)

    Ramprasath, Vanu R; Jenkins, David J A; Lamarche, Benoit; Kendall, Cyril W C; Faulkner, Dorothea; Cermakova, Luba; Couture, Patrick; Ireland, Chris; Abdulnour, Shahad; Patel, Darshna; Bashyam, Balachandran; Srichaikul, Korbua; de Souza, Russell J; Vidgen, Edward; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W; Frohlich, Jiri; Jones, Peter J H

    2014-10-18

    Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction

  17. Improvement of hydrogen sorption properties of compounds based on Vanadium “bcc” alloys by mean of intergranular phase development

    International Nuclear Information System (INIS)

    Planté, D.; Raufast, C.; Miraglia, S.; Rango, P. de; Fruchart, D.

    2013-01-01

    Highlights: •Decrease of “bcc” pseudo cell with the increase of amount of additive. •Additive phase improve activation kinetics. •Chromium in the “bcc” matrix decreases the lattice parameter and destabilizes hydride formation/dissociation. •Lower working temperatures could be obtain. -- Abstract: Body centered cubic structure (“bcc”) type alloys based on Vanadium [1] reveal promising characteristics for mobile applications. These disordered solid solutions have particular metal/hydride equilibrium and some regulation aspects have leaded us to pay special attention to this type of material [2]. Compounds based on Vanadium-rich solid solution have been elaborated in order to destabilize γ hydride phase (corresponding to the face centered cubic (“fcc”) structure of VH 2 ). Addition of Ni and Zr-rich Laves phase as a secondary phase results in the development of a particular microstructure composed of a principal “bcc” matrix rounded by intergranular activating phase. This results in a facilitated and faster activation of these compounds. The present study shows that some constituting species of the secondary phase have diffused in the main matrix and therefore have modified the thermodynamic of hydride. In fact, chromium diffusion into the “bcc” matrix destabilizes hydride. It is correlated to the lower stability of chromium hydride compared to Vanadium hydride. The enthalpic terms of each sample have been measured (assuming standard entropy of 130 J mol −1 K −1 ). The equilibrium metal/hydride can be easily switched in order to adapt it to a mobile hydride tank and obtain low working temperature in regard to the potential use

  18. Improved Survival After the Ross Procedure Compared With Mechanical Aortic Valve Replacement.

    Science.gov (United States)

    Buratto, Edward; Shi, William Y; Wynne, Rochelle; Poh, Chin L; Larobina, Marco; O'Keefe, Michael; Goldblatt, John; Tatoulis, James; Skillington, Peter D

    2018-03-27

    It is unclear whether the Ross procedure offers superior survival compared with mechanical aortic valve replacement (AVR). This study evaluated experience and compared long-term survival between the Ross procedure and mechanical AVR. Between 1992 and 2016, a total of 392 Ross procedures were performed. These were compared with 1,928 isolated mechanical AVRs performed during the same time period as identified using the University of Melbourne and Australia and New Zealand Society of Cardiac and Thoracic Surgeons' Cardiac Surgery Databases. Only patients between 18 and 65 years of age were included. Propensity-score matching was performed for risk adjustment. Ross procedure patients were younger, and had fewer cardiovascular risk factors. The Ross procedure was associated with longer cardiopulmonary bypass and aortic cross-clamp times. Thirty-day mortality was similar (Ross, 0.3%; mechanical, 0.8%; p = 0.5). Ross procedure patients experienced superior unadjusted long-term survival at 20 years (Ross, 95%; mechanical, 68%; p mechanical, 84%; p = 0.018). In this Australian, propensity-score matched study, the Ross procedure was associated with better long-term survival compared with mechanical AVR. In younger patients, with a long life expectancy, the Ross procedure should be considered in centers with sufficient expertise. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  19. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

    Science.gov (United States)

    Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

    2014-01-01

    Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, Ppoisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

  20. The rational design of a novel potent analogue of the 5’-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity

    Science.gov (United States)

    Machrouhi, Fouzia; Ouhamou, Nouara; Laderoute, Keith; Calaoagan, Joy; Bukhtiyarova, Marina; Ehrlich, Paula J.; Klon, Anthony E.

    2010-01-01

    We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5’-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK. PMID:20932747

  1. Radiation therapy improves survival in rectal small cell cancer - Analysis of Surveillance Epidemiology and End Results (SEER) data.

    Science.gov (United States)

    Modrek, Aram S; Hsu, Howard C; Leichman, Cynthia G; Du, Kevin L

    2015-04-24

    Small cell carcinoma of the rectum is a rare neoplasm with scant literature to guide treatment. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of radiation therapy in the treatment of this cancer. The SEER database (National Cancer Institute) was queried for locoregional cases of small cell rectal cancer. Years of diagnosis were limited to 1988-2010 (most recent available) to reduce variability in staging criteria or longitudinal changes in surgery and radiation techniques. Two month conditional survival was applied to minimize bias by excluding patients who did not survive long enough to receive cancer-directed therapy. Patient demographics between the RT and No_RT groups were compared using Pearson Chi-Square tests. Overall survival was compared between patients who received radiotherapy (RT, n = 43) and those who did not (No_RT, n = 28) using the Kaplan-Meier method. Multivariate Cox proportional hazards model was used to evaluate important covariates. Median survival was significantly longer for patients who received radiation compared to those who were not treated with radiation; 26 mo vs. 8 mo, respectively (log-rank P = 0.009). We also noted a higher 1-year overall survival rate for those who received radiation (71.1% vs. 37.8%). Unadjusted hazard ratio for death (HR) was 0.495 with the use of radiation (95% CI 0.286-0.858). Among surgery, radiotherapy, sex and age at diagnosis, radiation therapy was the only significant factor for overall survival with a multivariate HR for death of 0.393 (95% CI 0.206-0.750, P = 0.005). Using SEER data, we have identified a significant survival advantage with the use of radiation therapy in the setting of rectal small cell carcinoma. Limitations of the SEER data apply to this study, particularly the lack of information on chemotherapy usage. Our findings strongly support the use of radiation therapy for patients with locoregional small cell rectal cancer.

  2. Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Ponnusamy, Suriyan; Sullivan, Ryan D; You, Dahui; Zafar, Nadeem; He Yang, Chuan; Thiyagarajan, Thirumagal; Johnson, Daniel L; Barrett, Maron L; Koehler, Nikki J; Star, Mayra; Stephenson, Erin J; Bridges, Dave; Cormier, Stephania A; Pfeffer, Lawrence M; Narayanan, Ramesh

    2017-07-01

    Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty. We hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD could be due to diminished anabolic actions of androgens in muscle, and that intervention with an androgen receptor (AR) agonist will reverse musculoskeletal complications and extend survival. While castration of dystrophin and utrophin double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition resulted in premature death, maintenance of androgen levels extended the survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026 significantly increased body weight, lean mass and grip strength by 60-80% over vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx-026 elicits its musculoskeletal effects through pathways that are distinct from dystrophin-regulated pathways, making AR agonists ideal candidates for combination approaches. While castration of mdx-dm mice resulted in weaker muscle and shorter survival, GTx-026 treatment increased the muscle mass, function and survival, indicating that androgens are important for extended survival. These preclinical results support the importance of androgens and the need for intervention with AR agonists to treat DMD-affected boys. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Human platelet lysate improves human cord blood derived ECFC survival and vasculogenesis in three dimensional (3D) collagen matrices.

    Science.gov (United States)

    Kim, Hyojin; Prasain, Nutan; Vemula, Sasidhar; Ferkowicz, Michael J; Yoshimoto, Momoko; Voytik-Harbin, Sherry L; Yoder, Mervin C

    2015-09-01

    Human cord blood (CB) is enriched in circulating endothelial colony forming cells (ECFCs) that display high proliferative potential and in vivo vessel forming ability. Since diminished ECFC survival is known to dampen the vasculogenic response in vivo, we tested how long implanted ECFC survive and generate vessels in three-dimensional (3D) type I collagen matrices in vitro and in vivo. We hypothesized that human platelet lysate (HPL) would promote cell survival and enhance vasculogenesis in the 3D collagen matrices. We report that the percentage of ECFC co-cultured with HPL that were alive was significantly enhanced on days 1 and 3 post-matrix formation, compared to ECFC alone containing matrices. Also, co-culture of ECFC with HPL displayed significantly more vasculogenic activity compared to ECFC alone and expressed significantly more pro-survival molecules (pAkt, p-Bad and Bcl-xL) in the 3D collagen matrices in vitro. Treatment with Akt1 inhibitor (A-674563), Akt2 inhibitor (CCT128930) and Bcl-xL inhibitor (ABT-263/Navitoclax) significantly decreased the cell survival and vasculogenesis of ECFC co-cultured with or without HPL and implicated activation of the Akt1 pathway as the critical mediator of the HPL effect on ECFC in vitro. A significantly greater average vessel number and total vascular area of human CD31(+) vessels were present in implants containing ECFC and HPL, compared to the ECFC alone implants in vivo. We conclude that implantation of ECFC with HPL in vivo promotes vasculogenesis and augments blood vessel formation via diminishing apoptosis of the implanted ECFC. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Role of Intra-operative MRI (iMRI) in Improving Extent of Resection and Survival in Patients with Glioblastoma Multiforme.

    Science.gov (United States)

    Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

    2017-07-01

    Multiple intraoperative aids have been introduced to improve the extent of resection (EOR) in Glioblastoma Multiforme (GBM) patients, avoiding any new neurological deficits. Intraoperative MRI (iMRI) has been debated for its utility and cost for nearly two decades in neurosurgical literature. Review of literature suggests improved EOR in GBM patients who underwent iMRI assisted surgical resections leading to higher overall survival (OS) and progression free survival (PFS). iMRI provides real time intraoperative imaging with reasonable quality. Higher risk for new postoperative deficits with increased EOR is not reported in any study using iMRI. The level of evidence regarding prognostic benefits of iMRI is still of low quality..

  5. Females increase reproductive investment in response to helper-mediated improvements in allo-feeding, nest survival, nestling provisioning and post-fledging survival in the Karoo scrub-robin Cercotrichas coryphaeus

    Science.gov (United States)

    Lloyd, P.; Andrew, Taylor W.; du Plessis, Morné A.; Martin, T.E.

    2009-01-01

    In many cooperatively-breeding species, the presence of one or more helpers improves the reproductive performance of the breeding pair receiving help. Helper contributions can take many different forms, including allo-feeding, offspring provisioning, and offspring guarding or defence. Yet, most studies have focussed on single forms of helper contribution, particularly offspring provisioning, and few have evaluated the relative importance of a broader range of helper contributions to group reproductive performance. We examined helper contributions to multiple components of breeding performance in the Karoo scrub-robin Cercotrichas coryphaeus, a facultative cooperative breeder. We also tested a prediction of increased female investment in reproduction when helpers improve conditions for rearing young. Helpers assisted the breeding male in allo-feeding the incubating female, increasing allo-feeding rates. Greater allo-feeding correlated with greater female nest attentiveness during incubation. Nest predation was substantially lower among pairs breeding with a helper, resulting in a 74% increase in the probability of nest survival. Helper contributions to offspring provisioning increased nestling feeding rates, resulting in a reduced incidence of nestling starvation and increased nestling mass. Nestling mass had a strong, positive effect on post-fledging survival. Controlling for female age and habitat effects, annual production of fledged young was 130% greater among pairs breeding with a helper, and was influenced most strongly by helper correlates with nest survival, despite important helper effects on offspring provisioning. Females breeding with a helper increased clutch size, supporting the prediction of increased female investment in reproduction in response to helper benefits. ?? 2009 J. Avian Biol.

  6. Hypothermic machine perfusion reduces delayed graft function and improves one-year graft survival of kidneys from expanded criteria donors: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Baoping Jiao

    Full Text Available BACKGROUND: Expanded criteria donors (ECDs are currently accepted as potential sources to increase the donor pool and to provide more chances of kidney transplantation for elderly recipients who would not survive long waiting periods. Hypothermic machine perfusion (HMP is designed to mitigate the deleterious effects of simple cold storage (CS on the quality of preserved organs, particularly when the donor is in a marginal status. METHODS: We compared the transplant outcomes in patients receiving ECD kidneys with either HMP or CS graft preservation. Articles from the MEDLINE, EMBASE and Cochrane Library databases were searched and all studies reporting outcomes from HMP versus CS methods of kidney preservation were included in this meta-analysis. The parameters analyzed included the incidence of delayed graft function (DGF, primary non-function (PNF and one-year graft and patient survival. RESULTS: A total of seven studies qualified for the review, involving 2374 and 8716 kidney grafts with HMP or CS preservation respectively, all from ECD donors. The incidence of delayed graft function (DGF was significantly reduced with an odd ratio(OR of 0.59 (95% CI 0.54-0.66, P<0.001 and one-year graft survival was significantly improved with an OR of 1.12 (95% CI 1.03-1.21, P = 0.005 in HMP preservation compared to CS. However, there was no difference in the incidence of PNF (OR 0.54, 95% CI 0.21-1.40, P = 0.20, and one-year patient survival (OR 0.98, 95% CI 0.94-1.02, P = 0.36 between HMP and CS preservation. CONCLUSIONS: HMP was associated with a reduced incidence of DGF and an with increased one-year graft survival, but it was not associated with the incidence of PNF and one-year patient survival.

  7. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    International Nuclear Information System (INIS)

    Breslow, Norman E.; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-01-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes

  8. Exogenous Catalase and Pyruvate Dehydrogenase Improve Survival and Regeneration and Affect Oxidative Stress in Cryopreserved Dendrobium nobile Protocorm-like Bodies.

    Science.gov (United States)

    Di, W; Jia, M X; Xu, J; Li, B L; Liu, Y

    Reactive oxygen species (ROS)-induced oxidative damage is responsible for viability loss in plant tissues following cryopreservation. Antioxidants may improve viability by preventing or repairing the injury. This work aimed at studying the effect of catalase (CAT) and pyruvate dehydrogenase (PDH), which are involved in ROS metabolism and are differentially expressed during pollen cryopreservation, for cryopreservation of Dendrobium nobile Lindl. 'Hamana Lake Dream' protocorm-like bodies (PLBs). Different concentrations of exogenous CAT or PDH were added at the loading, PVS2 treatment, unloading steps during vitrification-cryopreservation of PLBs. Their survival and regeneration were evaluated and correlated with physiological oxidative indexes. PLB survival increased significantly when CAT and PDH were added separately to the unloading solution at a suitable concentration. CAT at 400 U·ml -1 increased PLB survival and regeneration by 33.5 and 14.6 percent respectively. It had no impact on the production of superoxide anion radical (·O2-) and on superoxide dismutase (SOD) activity, but it reduced the hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) contents and enhanced ascorbic acid (AsA) and endogenous CAT levels compared to PLBs cryopreserved using the standard vitrification protocol (CK1). PDH at 0.1 U·ml -1 significantly improved PLB survival (by 2.5 percent), but it had no marked effect on regeneration compared to the CK1 group. It induced the same variations in ·O2-, AsA and endogenous CAT levels that were observed following CAT addition. However, PDH did not affect the H 2 O 2 and MDA content but significantly increased SOD activity. These results indicate that the addition of 400 U·ml -1 CAT and 0.1 U·ml -1 PDH at the unloading step increased survival of cryopreserved PLBs and that this improvement was associated with scavenging of H 2 O 2 and the repair of oxidative damage. Exogenous CAT also significantly improved PLB regeneration after

  9. Reduced Self-Diploidization and Improved Survival of Semi-cloned Mice Produced from Androgenetic Haploid Embryonic Stem Cells through Overexpression of Dnmt3b

    Directory of Open Access Journals (Sweden)

    Wenteng He

    2018-02-01

    Full Text Available Summary: Androgenetic haploid embryonic stem cells (AG-haESCs hold great promise for exploring gene functions and generating gene-edited semi-cloned (SC mice. However, the high incidence of self-diploidization and low efficiency of SC mouse production are major obstacles preventing widespread use of these cells. Moreover, although SC mice generation could be greatly improved by knocking out the differentially methylated regions of two imprinted genes, 50% of the SC mice did not survive into adulthood. Here, we found that the genome-wide DNA methylation level in AG-haESCs is extremely low. Subsequently, downregulation of both de novo methyltransferase Dnmt3b and other methylation-related genes was determined to be responsible for DNA hypomethylation. We further demonstrated that ectopic expression of Dnmt3b in AG-haESCs could effectively improve DNA methylation level, and the high incidence of self-diploidization could be markedly rescued. More importantly, the developmental potential of SC embryos was improved, and most SC mice could survive into adulthood. : Ectopic expression of Dnmt3b could rescue DNA methylation level in repetitive sequences of hypomethylated AG-haESCs, suppress high incidence of self-diploidization, and promote developmental potential of SC embryos, and most SC mice could survive into adulthood. Keywords: androgenetic haploid embryonic stem cells, self-diploidization, semi-cloned mice, DNA methylation, Dnmt3b

  10. Long-Term Survival and Improved Quality of Life following Multiple Repeat Gamma Knife Radiosurgeries for Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Erik W. Larson

    2013-01-01

    Full Text Available The management of glioblastoma multiforme (GBM is in most cases complex and must be specifically tailored to the needs of the patient with the goals of extended survival and improved quality of life. Despite advancements in therapy, treatment outcomes remain almost universally poor. Salvage treatment options for the recurrence of the disease is an area of intense study. The following case highlights the utility of Gamma Knife Radiosurgery (GKRS as a salvage treatment. In this clinical situation, three sequential GKRS treatments led to prolonged survival (beyond four years after diagnosis and improved quality of life in a patient who was unable to receive further chemotherapy regimens and was unwilling to undergo further aggressive resection. To date, there have been few reports of three or more sequential GKRS treatment sessions utilized as salvage therapy for recurrent GBM in patients who can no longer tolerate chemotherapy. This report provides evidence that aggressive local treatment with GKRS at the time of recurrence may be appropriate, depending on a patient’s individual clinical situation, and can lead to prolonged survival and improved quality of life.

  11. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

    2010-01-01

    as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

  12. Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial.

    Science.gov (United States)

    Klek, Stanislaw; Scislo, Lucyna; Walewska, Elzbieta; Choruz, Ryszard; Galas, Aleksander

    2017-04-01

    The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed. Analysis of the overall survival time did not reveal differences between groups (P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together. The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual

    OpenAIRE

    Morisada, S.; Nosaka, N.; Tsukahara, K.; Ugawa, T.; Sato, K.; Ujike, Y.

    2015-01-01

    The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive b...

  14. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer.

    Science.gov (United States)

    He, X; Esteva, F J; Ensor, J; Hortobagyi, G N; Lee, M-H; Yeung, S-C J

    2012-07-01

    Insulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer. We reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed. A Cox regression analysis showed that DM2 [P=0.026, hazard ratio (HR)=1.42, 95 % confidence interval (95 % CI) 1.04-1.94] predicted poor survival of stage≥2 HER2+ breast cancer. In Kaplan-Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P=0.041, HR=0.52, 95 % CI 0.28-0.97) and thiazolidinediones (P=0.036; HR=0.41, 95% CI 0.18-0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P=0.023, HR=0.47, 95% CI 0.24-0.90 and P=0.044, HR=0.42, 95 % CI 0.18-0.98, respectively). Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.

  15. Deferasirox and vitamin D improves overall survival in elderly patients with acute myeloid leukemia after demethylating agents failure.

    Directory of Open Access Journals (Sweden)

    Etienne Paubelle

    Full Text Available The prognosis of acute myeloid leukemia (AML in elderly (≥65 years patients is poor and treatment remains non-consensual especially for those who are not eligible for intensive therapies. Our group has shown that in vitro the iron chelator deferasirox (DFX synergizes with vitamin D (VD to promote monocyte differentiation in primary AML cells. Herein, we present results from a retrospective case-control study in which the association of DFX (1-2 g/d and 25-hydroxycholecalciferol (100,000 IU/week (DFX/VD was proposed to patients following demethylating agents failure. Median survival of patients treated with DFX/VD combination (n = 17 was significantly increased in comparison with matched patients receiving best supportive care (BSC alone (n = 13 (10.4 versus 4 months respectively. In addition, the only factor associated to an increased overall survival in DFX/VD-treated patients was serum VD levels. We conclude that DFX/VD treatment correlated with increased overall survival of AML patients in this retrospective cohort of elderly patients.

  16. Daily home gardening improved survival for older people with mobility limitations: an 11-year follow-up study in Taiwan.

    Science.gov (United States)

    Lêng, Chhian Hūi; Wang, Jung-Der

    2016-01-01

    To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50-64 years) and older (≥65 years) cohort in Taiwan. The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996-2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71-0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48-0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression.

  17. Synbiotic Amazonian palm berry (açai, Euterpe oleracea Mart.) ice cream improved Lactobacillus rhamnosus GG survival to simulated gastrointestinal stress.

    Science.gov (United States)

    Costa, Mayra Garcia Maia; Ooki, Gabriela Namur; Vieira, Antônio Diogo Silva; Bedani, Raquel; Saad, Susana Marta Isay

    2017-02-22

    The effect of açai pulp ice cream and of its supplementation with inulin (I), whey protein concentrate (WC), and/or whey protein isolate (WI) on the viability and resistance to simulated gastrointestinal stress of the probiotic Lactobacillus (Lb.) rhamnosus GG strain throughout storage at -18 °C for up to 112 days was evaluated and morphological changes during stress were monitored. Lb. rhamnosus GG viability was stable in all formulations for up to 112 days of storage, preserving populations around 9 log CFU g -1 . Compared to the fresh culture, Lb. rhamnosus GG showed higher survival under simulated gastrointestinal conditions when incorporated into açai ice cream, indicating that the presence of the food matrix contributed to the microorganism survival. A reduction of at least 5 log cycles of Lb. rhamnosus GG was observed in all formulations after the gastrointestinal simulation in all storage periods assessed. The addition of I, WC, and/or WI did not show any significant effect on the probiotic survival under simulated gastrointestinal stress (p ice cream. Thus, the açai pulp ice cream was shown to be a suitable matrix for Lb. rhamnosus GG, improving its survival under in vitro simulated gastrointestinal conditions.

  18. Bioavailability of Heavy Metals in Soil: Impact on Microbial Biodegradation of Organic Compounds and Possible Improvement Strategies

    Science.gov (United States)

    Olaniran, Ademola O.; Balgobind, Adhika; Pillay, Balakrishna

    2013-01-01

    Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation), treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals. PMID:23676353

  19. Fractionation of yeast extract by nanofiltration process to assess key compounds involved in CHO cell culture improvement.

    Science.gov (United States)

    Mosser, Mathilde; Kapel, Romain; Chevalot, Isabelle; Olmos, Eric; Marc, Ivan; Marc, Annie; Oriol, Eric

    2015-01-01

    Yeast extract (YE) is known to greatly enhance mammalian cell culture performances, but its undefined composition decreases process reliability. Accordingly, in the present study, the nature of YE compounds involved in the improvement of recombinant CHO cell growth and IgG production was investigated. First, the benefits of YE were verified, revealing that it increased maximal concentrations of viable cells and IgG up to 73 and 60%, respectively compared to a reference culture. Then, the analyses of YE composition highlighted the presence of molecules such as amino acids, vitamins, salts, nucleobase, and glucose that were contained in reference medium, while others including peptides, trehalose, polysaccharides, and nucleic acids were not. Consequently, YE was fractionated by a nanofiltration process to deeper evaluate its effects on CHO cell cultures. The YE molecules already contained in reference medium were mainly isolated in the permeate fraction together with trehalose and short peptides, while other molecules were concentrated in the retentate. Permeate, which was free of macromolecules, exhibited a similar positive effect than raw YE on maximal concentrations. Additional studies on cell energetic metabolism underlined that dipeptides and tripeptides in permeate were used as an efficient source of nitrogenous substrates. © 2015 American Institute of Chemical Engineers.

  20. Bioavailability of Heavy Metals in Soil: Impact on Microbial Biodegradation of Organic Compounds and Possible Improvement Strategies

    Directory of Open Access Journals (Sweden)

    Balakrishna Pillay

    2013-05-01

    Full Text Available Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation, treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals.

  1. 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.

  2. Implementation of Extensive Cytoreduction Resulted in Improved Survival Outcomes for Patients with Newly Diagnosed Advanced-Stage Ovarian, Tubal, and Peritoneal Cancers.

    Science.gov (United States)

    Raspagliesi, Francesco; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Chiappa, Valentina; Borghi, Chiara; Scaffa, Cono; Morano, Federica; Maltese, Giuseppa; Lorusso, Domenica

    2017-10-01

    Residual disease (RD) after primary debulking surgery (PDS) is one of the main factors driving ovarian cancer prognosis. The primary end point of this study was assessment of the impact that surgery had on survival outcomes for patients with advanced ovarian cancer. Data on the effect of newly diagnosed advanced-stage ovarian, tubal, and peritoneal cancers were analyzed during two study periods (T1: 2001-2006 and T2: 2007-2012), in which the concepts of optimal and complete cytoreduction were introduced and implemented. In this study, 260 patients (36%) had surgery during T1 and 462 patients (64%) had surgery during T2. The rate of PDS increased, from 55.4% (144/260) during T1 to 85.5% (395/462) during T2 (p < 0.001). At the time of PDS, complete resection (RD0) was achieved for 45.1% of the patients during T1 and 76.7% of the patients during T2 (p < 0.001), whereas optimal resection (RD < 1 cm) was achieved for 60.4% of the patients during T1 and 85.3% of the patients during T2 (p < 0.001). Disease-free survival improved during the study periods (p = 0.006). Overall survival was similar in T1 and T2 (p = 0.18). The preoperative CA125 level, disease stage, and RD remained independently associated with disease-free survival (p ≤ 0.05). The performance of interval debulking surgery (IDS) instead of PDS correlated with worse survival outcomes (hazard ratio [HR] 1.47; 95% confidence interval [CI] 1.24-1.92; p = 0.02), whereas achievement of RD0 and RD < 1 cm independently improved overall survival (HR 0.45; 95% CI 0.22-0.91; p = 0.02 for RD0 and HR 0.47; 95% CI 0.23-0.96; p = 0.03 for RD0). The implementation of extensive cytoreduction allows improvement of patient outcomes. Further studies are needed to assess the risk-to-benefit ratio between PDS and IDS and to identify patients who benefit much more from one treatment method than from another.

  3. Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

    Science.gov (United States)

    Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

    2008-05-01

    Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination

  4. Effects of transgenic sterilization constructs and their repressor compounds on hatch, developmental rate and early survival of electroporated channel catfish embryos and fry.

    Science.gov (United States)

    Su, Baofeng; Shang, Mei; Li, Chao; Perera, Dayan A; Pinkert, Carl A; Irwin, Michael H; Peatman, Eric; Grewe, Peter; Patil, Jawahar G; Dunham, Rex A

    2015-04-01

    Channel catfish (Ictalurus punctatus) embryos were electroporated with sterilization constructs targeting primordial germ cell proteins or with buffer. Some embryos then were treated with repressor compounds, cadmium chloride, copper sulfate, sodium chloride or doxycycline, to prevent expression of the transgene constructs. Promoters included channel catfish nanos and vasa, salmon transferrin (TF), modified yeast Saccharomyces cerevisiae copper transport protein (MCTR) and zebrafish racemase (RM). Knock-down systems were the Tet-off (nanos and vasa constructs), MCTR, RM and TF systems. Knock-down genes included shRNAi targeting 5' nanos (N1), 3' nanos (N2) or dead end (DND), or double-stranded nanos RNA (dsRNA) for overexpression of nanos mRNA. These constructs previously were demonstrated to knock down nanos, vasa and dead end, with the repressors having variable success. Exogenous DNA affected percentage hatch (% hatch), as all 14 constructs, except for the TF dsRNA, TF N1 (T), RM DND (C), vasa DND (C), vasa N1 (C) and vasa N2 (C), had lower % hatch than the control electroporated with buffer. The MCTR and RM DND (T) constructs resulted in delayed hatch, and the vasa and nanos constructs had minimal effects on time of hatch (P nanos constructs, doxycycline greatly delayed hatch (P < 0.05). Adverse effects of the transgenes and repressors continued for several treatments for the first 6 days after hatch, but only in a few treatments during the next 10 days. Repressors and gene expression impacted the yield of putative transgenic channel catfish fry, and need to be considered and accounted for in the hatchery phase of producing transgenically sterilized catfish fry and their fertile counterparts. This fry output should be considered to ensure that sufficient numbers of transgenic fish are produced for future applications and for defining repressor systems that are the most successful.

  5. The HER4 isoform JM-a/CYT2 relates to improved survival in bladder cancer patients but only if the estrogen receptor α is not expressed

    DEFF Research Database (Denmark)

    Munk, Mathias; Memon, Ashfaque Ahmed; Poulsen, Steen Seier

    2013-01-01

    Abstract Bladder cancer tumors expressing human epidermal growth factor receptor 4 (HER4) demonstrate improved patient survival. HER4 isoforms and estrogen receptor alpha (ER-α) can form chaperone complexes causing cell-proliferation. We wanted to explore if HER4 isoforms and ER-α could correlate...... to poor prognosis in bladder cancers. We developed mRNA assays for HER4 isoforms (JM-a, JM-b, CYT1, and CYT2) and for ER-α. Expression was analyzed in tumors from 85 bladder cancer patients and compared to overall survival (median follow-up of 5.1 years). ER-α was expressed in 38% (n = 32) of tumors...... and half of those (18/36) expressed both isoforms. JM-a/CYT2 expression correlated to improved survival (p = 0.004), but not when ER-α was co-expressed (p = 0.897). Immunohistochemistry revealed protein expression of HER4 and ER-α in tumor cells. Growth of RT4 bladder cancer cells, expressing both JM...

  6. Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience.

    Science.gov (United States)

    Katodritou, Eirini; Terpos, Evangelos; Kastritis, Efstathios; Delimpasis, Sossana; Symeonidis, Argiris S; Repousis, Panagiotis; Kyrtsonis, Marie-Christine; Vadikolia, Chrysa; Michalis, Eurydiki; Polychronidou, Genovefa; Michael, Michael; Papadaki, Sofia; Papathanasiou, Maria; Kokoviadou, Kyriaki; Kioumi, Anna; Vlachaki, Eythimia; Hadjiaggelidou, Christina; Kouraklis, Alexandra; Patsias, Ioannis; Gavriatopoulou, Maria; Kotsopoulou, Maria; Verrou, Evgenia; Gastari, Vasiliki; Christoulas, Dimitrios; Giannopoulou, Evlambia; Pouli, Anastasia; Konstantinidou, Pavlina; Anagnostopoulos, Achilles; Dimopoulos, Meletios-Athanasios

    2015-12-01

    Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.

  7. Intracranial AAV-IFN-β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model.

    Science.gov (United States)

    GuhaSarkar, Dwijit; Neiswender, James; Su, Qin; Gao, Guangping; Sena-Esteves, Miguel

    2017-02-01

    The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN-β eliminates invasive human GBM8 tumors and promotes long-term survival. Next, we screened five AAV-IFN-β vectors with different promoters to drive safe expression of mouse IFN-β in the brain in the context of syngeneic GL261 tumors. Two AAV-IFN-β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2-Int-mIFN-β vector. We also assessed the therapeutic effect of combining AAV-IFN-β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second-strand DNA synthesis of single-stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV-IFN-β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV-IFN-β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  8. Vector control improves survival of three species of prairie dogs (Cynomys) in areas considered enzootic for plague

    Science.gov (United States)

    Biggins, Dean E.; Godbey, Jerry L.; Gage, Kenneth L.; Carter, Leon G.; Montenieri, John A.

    2010-01-01

    Plague causes periodic epizootics that decimate populations of prairie dogs (PDs) (Cynomys), but the means by which the causative bacterium (Yersinia pestis) persists between epizootics are poorly understood. Plague epizootics in PDs might arise as the result of introductions of Y. pestis from sources outside PD colonies. However, it remains possible that plague persists in PDs during interepizootic periods and is transmitted at low rates among highly susceptible individuals within and between their colonies. If this is true, application of vector control to reduce flea numbers might reduce mortality among PDs. To test whether vector control enhances PD survival in the absence of obvious plague epizootics, we reduced the numbers of fleas (vectors for Y. pestis) 96–98% (1 month posttreatment) on 15 areas involving three species of PDs (Cynomys leucurus, Cynomys parvidens in Utah, and Cynomys ludovicianus in Montana) during 2000–2004 using deltamethrin dust delivered into burrows as a pulicide. Even during years without epizootic plague, PD survival rates at dusted sites were 31–45% higher for adults and 2–34% higher for juveniles compared to survival rates at nondusted sites. Y. pestis was cultured from 49 of the 851 flea pools tested (6882 total fleas) and antibodies against Y. pestis were identified in serum samples from 40 of 2631 PDs. Although other explanations are possible, including transmission of other potentially fatal pathogens by fleas, ticks, or other ectoparasites, our results suggest that plague might be maintained indefinitely in PD populations in the absence of free epizootics and widespread mortality among these animals. If PDs and their fleas support enzootic cycles of plague transmission, there would be important implications for the conservation of these animals and other species.

  9. The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival

    Directory of Open Access Journals (Sweden)

    Anna G. Antonacopoulou

    2010-01-01

    Full Text Available Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.

  10. 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.

  11. Neuraxial anesthesia improves long-term survival after total joint replacement: a retrospective nationwide population-based study in Taiwan.

    Science.gov (United States)

    Chen, Wei-Hung; Hung, Kuo-Chuan; Tan, Ping-Heng; Shi, Hon-Yi

    2015-04-01

    This study explored the effects of general (GA) and neuraxial (NA) anesthesia on the outcomes of primary total joint replacement (TJR) in terms of postoperative mortality, length of stay (LOS), and hospital treatment costs. From 1997 to 2010, this nationwide population-based study retrospectively evaluated 7,977 patients in Taiwan who underwent primary total hip or knee replacement. We generated two propensity-score-matched subgroups, each containing an equal number of patients who underwent TJR with either GA or NA. Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%) underwent NA. Propensity-score matching was used to create comparable GA and NA groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and surgeon volume. Survival over the first three years following surgery was similar. The proportion of patients alive up to 14 years postoperatively for those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia was associated with lower median [interquartile range; IQR] hospital treatment cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P anesthesia costs are removed. The mechanism underlying the association between NA and long-term survival is unknown.

  12. Pulse seed germination improves antioxidative activity of phenolic compounds in stripped soybean oil-in-water emulsions.

    Science.gov (United States)

    Xu, Minwei; Jin, Zhao; Peckrul, Allen; Chen, Bingcan

    2018-06-01

    The purpose of this study was to investigate antioxidative activity of phenolic compounds extracted from germinated pulse seed including chickpeas, lentils and yellow peas. Phenolic compounds were extracted at different germination time and total phenolic content was examined by Folin Ciocalteu's reaction. Antioxidative activity of extracts was characterized by in vitro assay including 2, 2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH), oxygen radical absorbance capacity (ORAC), iron-binding assay, and in stripped soybean oil-in-water emulsions. The results suggested that germination time is critical for phenolic compounds production. The form variation of phenolic compounds influenced the antioxidative activity of phenolic compounds both in vitro assay and in emulsion systems. Soluble bound phenolic compounds showed higher antioxidative ability in emulsion system with the order of chickpea > yellow pea > lentil. On the basis of these results, soluble bound phenolic compounds may be considered as a promising natural antioxidant to prevent lipid oxidation in foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Wei [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nezolosky, Michelle [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Den, Robert B. [Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States)

    2016-03-15

    Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95-0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test P=.0005; AHR: 0.91, 95% CI: 0.86-0.96, P=.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate

  14. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    International Nuclear Information System (INIS)

    Christofidou-Solomidou, Melpo; Cengel, Keith A; Tyagi, Sonia; Tan, Kay-See; Hagan, Sarah; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Heitjan, Daniel F; Solomides, Charalambos C

    2011-01-01

    Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease

  15. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    Directory of Open Access Journals (Sweden)

    Arguiri Evguenia

    2011-06-01

    Full Text Available Abstract Background Flaxseed (FS is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD. Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT. However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. Methods We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6 in 2 separate experiments (n = 15-25 mice/group on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Results Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not, maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the

  16. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Christofidou-Solomidou, Melpo [Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Cengel, Keith A [Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Tyagi, Sonia [Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Tan, Kay-See [Biostatistics & Epidemiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Hagan, Sarah [Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia [Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Heitjan, Daniel F [Biostatistics & Epidemiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 (United States); Solomides, Charalambos C [Department of Pathology, Jefferson University Hospital, Philadelphia, PA 19140 (United States)

    2011-06-24

    Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of

  17. Estimating cost-effectiveness of mass cardiopulmonary resuscitation training strategies to improve survival from cardiac arrest in private locations.

    Science.gov (United States)

    Swor, Robert; Compton, Scott

    2004-01-01

    Most cardiopulmonary resuscitation (CPR) trainees are young, and most cardiac arrests occur in private residences witnessed by older individuals. To estimate the cost-effectiveness of a CPR training program targeted at citizens over the age of 50 years compared with that of current nontargeted public CPR training. A model was developed using cardiac arrest and known demographic data from a single suburban zip code (population 36,325) including: local data (1997-1999) regarding cardiac arrest locations (public vs. private); incremental survival with CPR (historical survival rate 7.8%, adjusted odds ratio for CPR 2.0); arrest bystander demographics obtained from bystander telephone interviews; zip code demographics regarding population age and distribution; and 12.50 dollars per student for the cost of CPR training. Published rates of CPR training programs by age were used to estimate the numbers typically trained. Several assumptions were made: 1) there would be one bystander per. arrest; 2) the bystander would always perform CPR if trained; 3) cardiac arrest would be evenly distributed in the population; and 4) CPR training for a proportion of the population would proportionally increase CPR provision. Rates of arrest, bystanders by age, number of CPR trainees needed to result in increased arrest survival, and training cost per life saved for a one-year study period were calculated. There were 24.3 cardiac arrests per year, with 21.9 (90%) occurring in homes. In 66.5% of the home arrests, the bystander was more than 50 years old. To yield one additional survivor using the current CPR training strategy, 12,306 people needed to be trained (3,510 bystanders aged 50 years), which resulted in CPR provision to 7.14 additional patients. The training cost per life saved for a bystander aged 50 years was 785,040 dollars. Using a strategy of training only those cost of 53,383 dollars per life saved. Using these assumptions, current CPR training strategy is not a cost

  18. Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

    Science.gov (United States)

    Koller, Kristian M; Mackley, Heath B; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D; Pameijer, Colette; Neves, Rogerio I; Anderson, Bryan; Kokolus, Kathleen M; Mallon, Carol A; Drabick, Joseph J

    2017-01-02

    There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

  19. Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis.

    Science.gov (United States)

    Wang, Li; Yan, Lan; Li, Xing Xing; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2015-01-01

    Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host-fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-α in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis.

  20. Treating fat grafts with human endothelial progenitor cells promotes their vascularization and improves their survival in diabetes mellitus.

    Science.gov (United States)

    Hamed, Saher; Ben-Nun, Ohad; Egozi, Dana; Keren, Aviad; Malyarova, Nastya; Kruchevsky, Danny; Gilhar, Amos; Ullmann, Yehuda

    2012-10-01

    Bone marrow-derived endothelial progenitor cells are required for vascularization of a fat graft to form a functional microvasculature within the graft and to facilitate its integration into the surrounding tissues. Organ transplantation carries a high risk of graft loss and rejection in patients with diabetes mellitus because endothelial progenitor cell function is impaired. The authors investigated the influence of endothelial progenitor cell treatment on the phenotype and survival of human fat grafts in immunocompromised mice with experimentally induced diabetes mellitus. The authors injected 1 ml of human fat tissue into the scalps of 14 nondiabetic and 28 diabetic immunocompromised mice, and then treated some of the grafts with endothelial progenitor cells that was isolated from the blood of a human donor. The phenotype of the endothelial progenitor cell-treated fat grafts from the 14 diabetic mice was compared with that of the untreated fat grafts from 14 nondiabetic and 14 diabetic mice, 18 days and 15 weeks after fat transplantation. Determination of graft phenotype included measurements of weight and volume, vascular endothelial growth factor levels, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and caspase 3 expression levels, and histologic analysis of the extent of vascularization. The untreated grafts from the diabetic mice were fully resorbed 15 weeks after fat transplantation. The phenotype of endothelial progenitor cell-treated fat grafts from the diabetic mice was similar to that of the untreated fat grafts from the nondiabetic mice. Endothelial progenitor cell treatment of transplanted fat can increase the survival of a fat graft by inducing its vascularization and decreasing the extent of apoptosis.

  1. Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

    Science.gov (United States)

    Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

    2015-03-01

    We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Ehteda, Anahid; Galettis, Peter; Pillai, Krishna; Morris, David L

    2013-01-01

    Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated. Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone. The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment

  3. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

  4. International trends in patient selection for elective endovascular aneurysm repair: sicker patients with safer anatomy leading to improved 1-year survival.

    Science.gov (United States)

    Fitridge, Robert A; Boult, Margaret; Mackillop, Clare; De Loryn, Tania; Barnes, Mary; Cowled, Prue; Thompson, Matthew M; Holt, Peter J; Karthikesalingam, Alan; Sayers, Robert D; Choke, Edward; Boyle, Jonathan R; Forbes, Thomas L; Novick, Teresa V

    2015-02-01

    To review the trends in patient selection and early death rate for patients undergoing elective endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) in 3 countries. For this study, audit data from 4,163 patients who had undergone elective infrarenal EVAR were amalgamated. The data originated from Australia, Canada (Ontario), and England (London, Cambridge, and Leicester). Statistical analyses were undertaken to determine whether patient characteristics and early death rate varied between and within study groups and over time. The study design was retrospective analysis of data collected prospectively between 1999 and 2012. One-year survival improved over time (P = 0.0013). Canadian patients were sicker than those in Australia or England (P international comparison, several trends were noted including improved 1-year survival despite declining patient health (as measured by increasing ASA status). This may reflect greater knowledge regarding EVAR that centers from different countries have gained over the last decade and improved medical management of patients with aneurysmal disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

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

  6. Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

    Directory of Open Access Journals (Sweden)

    Golden Daniel W

    2012-09-01

    Full Text Available Abstract Background Unresectable pancreatic cancer (UPC has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS. Methods From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy. All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other and 24 received adjuvant chemotherapy. Results 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy. Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT Conclusions CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9

  7. Survival curves to support quality improvement in hospitals with excess 30-day mortality after acute myocardial infarction, cerebral stroke and hip fracture: a before-after study.

    Science.gov (United States)

    Kristoffersen, Doris Tove; Helgeland, Jon; Waage, Halfrid Persdatter; Thalamus, Jacob; Clemens, Dirk; Lindman, Anja Schou; Rygh, Liv Helen; Tjomsland, Ole

    2015-03-25

    To evaluate survival curves (Kaplan-Meier) as a means of identifying areas in the clinical pathway amenable to quality improvement. Observational before-after study. In Norway, annual public reporting of nationwide 30-day in-and-out-of-hospital mortality (30D) for three medical conditions started in 2011: first time acute myocardial infarction (AMI), stroke and hip fracture; reported for 2009. 12 of 61 hospitals had statistically significant lower/higher mortality compared with the hospital mean. Three hospitals with significantly higher mortality requested detailed analyses for quality improvement purposes: Telemark Hospital Trust Skien (AMI and stroke), Østfold Hospital Trust Fredrikstad (stroke), Innlandet Hospital Trust Gjøvik (hip fracture). Survival curves, crude and risk-adjusted 30D before (2008-2009) and after (2012-2013). Unadjusted survival curves for the outlier hospitals were compared to curves based on pooled data from the other hospitals for the 30-day period 2008-2009. For patients admitted with AMI (Skien), stroke (Fredrikstad) and hip fracture (Gjøvik), the curves suggested increased mortality from the initial part of the clinical pathway. For stroke (Skien), increased mortality appeared after about 8 days. The curve profiles were thought to reflect suboptimal care in various phases in the clinical pathway. This informed improvement efforts. For 2008-2009, hospital-specific curves differed from other hospitals: borderline significant for AMI (p=0.064), highly significant (p≤0.005) for the remainder. After intervention, no difference was found (p>0.188). Before-after comparison of the curves within each hospital revealed a significant change for Fredrikstad (p=0.006). For the three hospitals, crude 30D declined and they were non-outliers for risk-adjusted 30D for 2013. Survival curves as a supplement to 30D may be useful for identifying suboptimal care in the clinical pathway, and thus informing design of quality improvement projects

  8. Tumor-Infiltrating Merkel Cell Polyomavirus-Specific T Cells Are Diverse and Associated with Improved Patient Survival. | Office of Cancer Genomics

    Science.gov (United States)

    Tumor-infiltrating CD8+ T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8+ T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome.

  9. Optimization of a fermented pumpkin-based beverage to improve Lactobacillus mali survival and α-glucosidase inhibitory activity: A response surface methodology approach

    Directory of Open Access Journals (Sweden)

    W.Y. Koh

    2018-03-01

    Full Text Available The aim of this research was to develop an optimum fermentation and composition model for a new fermented pumpkin-based beverage with high probiotic survival and α-glucosidase inhibitory activity. Relationship between fermentation temperature, inoculum and ingredient concentration with response variables (fermentation time at the fermentation endpoint pH 4.5, survival rate of Lactobacillus mali K8 in pumpkin-based beverage treated with simulated gastrointestinal tract enzyme fluids, α-glucosidase inhibitory activity and sensory overall acceptability after 4 weeks of refrigerated storage was investigated using response surface methodology. Optimal formulation was obtained at an approximation of 40% pumpkin puree concentration, 8 Log CFU/mL inoculum and at 35 °C. The product derived from this optimum formula reached the fermentation endpoint after 28.34 ± 0.10 h and the quality change during 4 weeks storage was studied. The product achieved 88.56 ± 0.67% of L. mali survival after treatment with simulated gastric and intestinal juices; demonstrated 95.89 ± 0.30% α-glucosidase inhibitory activity, as well as scored 6.99 ± 0.40 on sensory overall acceptability after 4 weeks of storage. These findings illustrated that the model is effective in improving probiotic survival and α-glucosidase inhibitory activity with excellent sensory acceptability, thus may offer a dietary means for the management of hyperglycaemia. Keywords: Probiotics, Response surface methodology, Box-Behnken, Hyperglycaemia, Functional food

  10. Early or Up-Front Radiotherapy Improved Survival of Localized Extranodal NK/T-Cell Lymphoma, Nasal-Type in the Upper Aerodigestive Tract

    International Nuclear Information System (INIS)

    Huang Meijuan; Jiang Yu; Liu Weiping; Li Zhiping; Li Mei; Zhou Lin; Xu Yong; Yu Chunhua; Li Qiu; Peng Feng; Liu Jiyan; Luo Feng; Lu You

    2008-01-01

    Purpose: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Methods and Materials: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. Results: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving ≥54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Conclusion: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease

  11. Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

    LENUS (Irish Health Repository)

    2011-04-01

    Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study.

  12. Complete resection of the primary lesion improves survival of certain patients with stage IV non-small cell lung cancer.

    Science.gov (United States)

    Chikaishi, Yasuhiro; Shinohara, Shinji; Kuwata, Taiji; Takenaka, Masaru; Oka, Soichi; Hirai, Ayako; Yoneda, Kazue; Kuroda, Kouji; Imanishi, Naoko; Ichiki, Yoshinobu; Tanaka, Fumihiro

    2017-12-01

    The standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) is systemic chemotherapy. However, certain patients, such as those with oligometastasis or M1a disease undergo resection of the primary lesion. We conducted a retrospective review of the records of 1,471 consecutive patients with NSCLC who underwent resection of the primary lesion for between June 2005 and May 2016. The present study included 38 patients with stage IV NSCLC who underwent complete resection of the primary lesion as first-line treatment. The median follow-up duration for the 38 patients (27 men) was 17.7 months (range, 1-82.3 months). The T factors were T1/T2/T3/T4 in 4/16/12/6 patients, respectively. The N factors were N0/N1/N2/N3 in 16/8/12/2 patients, respectively. The M factors were M1a/M1b/M1c in 19/13/6 patients, respectively. Of the 19 M1a patients, 11 were classified as cM0. We introduced the novel classification M-better/M-worse. M-better includes cM0 patients and M1b and M1c patients in whom all lesions have been locally controlled. M-worse includes cM1a patients and M1b and M1c patients in whom lesions cannot be locally controlled. The new M-better/M-worse statuses were 24/14 patients, respectively. The histology of NSCLC was adenocarcinoma/squamous cell carcinoma/others in 30/5/3 patients, respectively. The 5-year overall survival rate was 29%, and the median survival time was 725 days. Squamous cell carcinoma and M-worse were significant factors predicting poor outcomes (P=0.0017, P=0.0007, respectively). Even for stage IV NSCLC patients, resection of the primary lesion may be beneficial, especially for those with M-better status and those not diagnosed with squamous-cell carcinoma (SCC).

  13. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan; Tan, Ren-Xiang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  14. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    International Nuclear Information System (INIS)

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong; Gu, Yan-Hong; Shen, Yan; Tan, Ren-Xiang; Sun, Yang; Xu, Qiang

    2012-01-01

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  15. 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

    Science.gov (United States)

    Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

    2014-01-01

    Purpose 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. Patients and Methods 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. Results 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. Conclusions 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. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

  16. 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.

  17. Transplantation of Gene-Edited Hepatocyte-like Cells Modestly Improves Survival of Arginase-1-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Yuan Yan Sin

    2018-03-01

    Full Text Available Progress in gene editing research has been accelerated by utilizing engineered nucleases in combination with induced pluripotent stem cell (iPSC technology. Here, we report transcription activator-like effector nuclease (TALEN-mediated reincorporation of Arg1 exons 7 and 8 in iPSCs derived from arginase-1-deficient mice possessing Arg1Δ alleles lacking these terminal exons. The edited cells could be induced to differentiate into hepatocyte-like cells (iHLCs in vitro and were subsequently used for transplantation into our previously described (Sin et al., PLoS ONE 2013 tamoxifen-inducible Arg1-Cre arginase-1-deficient mouse model. While successful gene-targeted repair was achieved in iPSCs containing Arg1Δ alleles, only minimal restoration of urea cycle function could be observed in the iHLC-transplanted mice compared to control mice, and survival in this lethal model was extended by up to a week in some mice. The partially rescued phenotype may be due to inadequate regenerative capacity of arginase-1-expressing cells in the correct metabolic zones. Technical hurdles exist and will need to be overcome for gene-edited iPSC to iHLC rescue of arginase-1 deficiency, a rare urea cycle disorder.

  18. Methods to Improve Survival and Growth of Planted Alternative Species Seedlings in Black Ash Ecosystems Threatened by Emerald Ash Borer

    Directory of Open Access Journals (Sweden)

    Nicholas Bolton

    2018-03-01

    Full Text Available Emerald ash borer (EAB continues to spread across North America, infesting native ash trees and changing the forested landscape. Black ash wetland forests are severely affected by EAB. As black ash wetland forests provide integral ecosystem services, alternative approaches to maintain forest cover on the landscape are needed. We implemented simulated EAB infestations in depressional black ash wetlands in the Ottawa National Forest in Michigan to mimic the short-term and long-term effects of EAB. These wetlands were planted with 10 alternative tree species in 2013. Based on initial results in the Michigan sites, a riparian corridor in the Superior Municipal Forest in Wisconsin was planted with three alternative tree species in 2015. Results across both locations indicate that silver maple (Acer saccharinum L., red maple (Acer rubrum L., American elm (Ulmus americana L., and northern white cedar (Thuja occidentalis L. are viable alternative species to plant in black ash-dominated wetlands. Additionally, selectively planting on natural or created hummocks resulted in two times greater survival than in adjacent lowland sites, and this suggests that planting should be implemented with microsite selection or creation as a primary control. Regional landowners and forest managers can use these results to help mitigate the canopy and structure losses from EAB and maintain forest cover and hydrologic function in black ash-dominated wetlands after infestation.

  19. Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis.

    Science.gov (United States)

    He, Guodong; Zhang, Xu; Chen, Yanhua; Chen, Jing; Li, Li; Xie, Yubo

    2017-06-01

    Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of mortality worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Isoalantolactone (IAL), a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless, little is known about the anti-inflammatory effects of IAL, and the role of IAL in sepsis is unclear. In this study, we demonstrated that IAL decreased lipopolysaccharide (LPS)-mediated production of nitric oxide, PEG 2 and cytokines (IL-6, TNF-α) in peritoneal macrophages and RAW 264.7 macrophages. Moreover, molecular mechanism studies indicated that IAL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-κB pathway in peritoneal macrophages. In vivo, IAL reduced the secretion of IL-6 and TNF-α in serum, and increased the survival rate of mice with LPS-induced sepsis. In addition, IAL attenuated the activation of NF-κB pathway in liver. Taken together, our data suggest that IAL may represent a potentially new drug candidate for the treatment of sepsis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

    Science.gov (United States)

    van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

    2016-01-01

    Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

  1. The Fibrin-Derived Peptide Bβ15-42 (FX06) Ameliorates Vascular Leakage and Improves Survival and Neurocognitive Recovery: Implications From Two Animal Models of Cardiopulmonary Resuscitation.

    Science.gov (United States)

    Bergt, Stefan; Gruenewald, Matthias; Beltschany, Claudia; Grub, Andrea; Neumann, Tobias; Albrecht, Martin; Vollmar, Brigitte; Zacharowski, Kai; Roesner, Jan P; Meybohm, Patrick

    2016-10-01

    The fibrin-derived peptide Bβ15-42 (FX06) has been proven to attenuate ischemia/reperfusion injury. We tested the hypothesis that Bβ15-42 improves survival rate and neurocognitive recovery after cardiopulmonary resuscitation. Pig and mouse model of cardiopulmonary resuscitation. Two university hospitals. Pigs and mice. Pigs (n = 16) were subjected to 8-minute cardiac arrest. Successful resuscitated pigs (n = 12) were randomized either to 3 mg/kg Bβ15-42 followed by a continuous infusion of 1 mg/kg/hr for 5 hours (pFX06; n = 6) or the control group (pCONTROL; n = 6). Cardiac damage, function, and hemodynamics were recorded up to 8 hours. Mice (n = 52) were subjected to 4-minute cardiac arrest followed by cardiopulmonary resuscitation, and randomized either to two boli of 2.4 mg/kg Bβ15-42 (mFX06; n = 26) or the control group (mCONTROL; n = 26). Fourteen-day survival rate, neurocognitive function, and endothelial integrity (additional experiment with n = 26 mice) were evaluated. Bβ15-42 reduced cumulative fluid intake (3,500 [2,600-4,200] vs 6,800 [5,700-7,400] mL; p = 0.004) within 8 hours in pigs. In mice, Bβ15-42 improved 14-day survival rate (mFX06 vs mCONTROL; 11/26 vs 6/26; p Water-Maze test (15/26 vs 9/26 mice with competence to perform test; p < 0.05). Bβ15-42-treated mice showed a significant higher length of intact pulmonary endothelium and reduced pulmonary leukocyte infiltration. This study confirms the new concept of an important role of fibrin derivatives in global ischemia/reperfusion injury, which can be attenuated by the fibrin-derived peptide Bβ15-42.

  2. Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response.

    Science.gov (United States)

    Katare, Rajesh; Caporali, Andrea; Emanueli, Costanza; Madeddu, Paolo

    2010-10-01

    Benfotiamine (BFT) is a transketolase activator that directs glucose to the pentose phosphate pathway. The present study investigated whether BFT improves the recovery after myocardial infarction (MI) and explored underlying mechanisms of protection. Non-diabetic and streptozotocin-induced type 1 diabetic mice were supplemented with BFT (70 mg/kg/day in drinking water) for 4 weeks and then subjected to MI or sham operation. Cardiac function was monitored by echocardiography. At two weeks post-MI, intra-ventricular pressure was measured by Millar tip-catheter and hearts were collected for biochemical, immunohistochemical and expressional analyses. No treatment effect was observed in sham-operated mice. Post-MI mortality was higher in diabetic mice and hemodynamic studies confirmed the worsening effect of diabetes on functional recovery. Furthermore, diabetic mice demonstrated increased cardiomyocyte apoptosis, reduced reparative angiogenesis, larger scars, enhanced oxidative stress, and blunted activation of the pro-survival VEGF receptor-2/Akt/Pim-1 signaling pathway. BFT improved post-MI survival, functional recovery and neovascularization and reduced cardiomyocyte apoptosis and neurohormonal activation in diabetic as well as in non-diabetic mice. In addition, BFT stimulated the activity of pentose phosphate pathway enzymes, leading to reduction of oxidative stress, phosphorylation/activation of VEGF receptor-2 and Akt and increased Pim-1, pBad and Bcl-2 levels. These effects were contrasted on silencing glucose-6-phosphate dehydrogenase, the key enzyme in pentose phosphate pathway, or inhibiting Akt. BFT benefits post-MI recovery through stimulation of pro-survival mechanisms and containment of neurohormonal response. These results may have implications for the treatment of myocardial ischemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.

    Science.gov (United States)

    Summers, Brooke L; Rofe, Allan M; Coyle, Peter

    2009-04-01

    We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.

  4. Survival Improvement in Human Retinal Pigment Epithelial Cells via Fas Receptor Targeting by miR-374a.

    Science.gov (United States)

    Tasharrofi, Nooshin; Kouhkan, Fatemeh; Soleimani, Masoud; Soheili, Zahra-Sheila; Kabiri, Mahboubeh; Mahmoudi Saber, Mohaddeseh; Dorkoosh, Farid Abedin

    2017-12-01

    Oxidative conditions of the eye could contribute to retinal cells loss through activating the Fas-L/Fas pathway. This phenomenon is one of the leading causes of some ocular diseases like age-related macular degeneration (AMD). By targeting proteins at their mRNA level, microRNAs (miRNAs) can regulate gene expression and cell function. The aim of the present study is to investigate Fas targeting by miR-374a and find whether it can inhibit Fas-mediated apoptosis in primary human retinal pigment epithelial (RPE) cells under oxidative stress. So, the primary human RPE cells were transfected with pre-miR-374a pLEX construct using polymeric carrier and were exposed to H 2 O 2 (200 μM) as an oxidant agent for induction of Fas expression. Fas expression at mRNA and protein level was evaluated by quantitative real-time PCR and Western blot analysis, respectively. These results revealed that miR-374a could prevent Fas upregulation under oxidative conditions. Moreover, Luciferase activity assay confirmed that Fas could be a direct target of miR-374a. The cell viability studies demonstrated that caspase-3 activity was negligible in miR-374a treated cells compared to the controls. Our data suggest miR-374a is a negative regulator of Fas death receptor which is able to enhance the cell survival and protect RPE cells against oxidative conditions. J. Cell. Biochem. 118: 4854-4861, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Arbuscular mycorrhizal inoculation following biocide treatment improves Calocedrus decurrens survival and growth in nursery and outplanting sites

    Science.gov (United States)

    Michael Amaranthus; David Steinfeld

    2005-01-01

    Commercial production of tree seedlings often includes various biocidal soil treatments for disease control. Such treatments can be effective in eliminating or reducing disease organisms in the soil, but may also eliminate non-targeted beneficial soil organisms, such as mycorrhizal fungi, that improve seedling performance, both in the nursery as well as the outplanted...

  6. Trichoderma harzianum enhances the production of nematicidal compounds in vitro and improves biocontrol of Meloidogyne javanica by Pseudomonas fluorescens in tomato.

    Science.gov (United States)

    Siddiqui, I A; Shaukat, S S

    2004-01-01

    To determine the influence of soil-borne fungus Trichoderma harzianum on the biocontrol performance of Pseudomonas fluorescens strain CHA0 and its 2,4-diacetylphloroglucinol (DAPG) overproducing derivative CHA0/pME3424 against Meloidogyne javanica. Amendment of the culture filtrate (CF) or methanol extract of the CF of a T. harzianum strain Th6 to P. fluorescens growth medium enhanced the production of nematicidal compound(s) by bacterial inoculants in vitro. In addition, bacteria overwhelmingly expressed phl'-'lacZ reporter gene when the medium was amended with CF of T. harzianum. Pseudomonas fluorescens and T. harzianum applied together in unsterilized sandy loam soil caused greater reduction in nematode population densities in tomato roots. Trichoderma harzianum improves root-knot nematode biocontrol by the antagonistic rhizobacterium P. fluorescens both in vitro and under glasshouse conditions. The synergistic effect of T. harzianum on the production of nematicidal compound(s) critical in biocontrol may improve the efficacy of biocontrol bacteria against plant-parasitic nematodes. Considering the inconsistent performance of the biocontrol agents under field conditions, application of a mixture of compatible T. harzianum and P. fluorescens would more closely mimic the natural situation and might broaden the spectrum of biocontrol activity with enhanced efficacy and reliability of control.

  7. Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved long-term survival.

    Science.gov (United States)

    Ali, Ayyaz; Patel, Amit; Ali, Ziad; Abu-Omar, Yasir; Saeed, Amber; Athanasiou, Thanos; Pepper, John

    2011-08-01

    Aortic valve replacement in patients with aortic stenosis is usually followed by regression of left ventricular hypertrophy. More complete resolution of left ventricular hypertrophy is suggested to be associated with superior clinical outcomes; however, its translational impact on long-term survival after aortic valve replacement has not been investigated. Demographic, operative, and clinical data were obtained retrospectively through case note review. Transthoracic echocardiography was used to measure left ventricular mass preoperatively and at annual follow-up visits. Patients were classified according to their reduction in left ventricular mass at 1 year after the operation: group 1, less than 25 g; group 2, 25 to 150 g; and group 3, more than 150 g. Kaplan-Meier and multivariable Cox regression were used. A total of 147 patients were discharged from the hospital after aortic valve replacement for aortic stenosis between 1991 and 2001. Preoperative left ventricular mass was 279 ± 98 g in group 1 (n = 47), 347 ± 104 g in group 2 (n = 62), and 491 ± 183 g in group 3 (n = 38) (P regression such as ischemic heart disease or hypertension, valve type, or valve size used. Ten-year actuarial survival was not statistically different in patients with enhanced left ventricular mass regression when compared with the log-rank test (group 1, 51% ± 9%; group 2, 54% ± 8%; and group 3, 72% ± 10%) (P = .26). After adjustment, left ventricular mass reduction of more than 150 g was demonstrated as an independent predictor of improved long-term survival on multivariate analysis (P = .02). Our study is the first to suggest that enhanced postoperative left ventricular mass regression, specifically in patients undergoing aortic valve replacement for aortic stenosis, may be associated with improved long-term survival. In view of these findings, strategies purported to be associated with superior left ventricular mass regression should be considered when undertaking

  8. Brachytherapy Improves Biochemical Failure–Free Survival in Low- and Intermediate-Risk Prostate Cancer Compared With Conventionally Fractionated External Beam Radiation Therapy: A Propensity Score Matched Analysis

    International Nuclear Information System (INIS)

    Smith, Graham D.; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Vigneault, Eric; Cury, Fabio L.; Morris, Jim; Catton, Charles; Lukka, Himu; Warner, Andrew; Yang, Ying; Rodrigues, George

    2015-01-01

    Purpose: To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone. Methods and Materials: Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups. Results: Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500). Conclusions: Propensity score matched analysis showed that BT options led

  9. An improvement study on the closed chamber distillation system for recovery of renewable salts from salt wastes containing radioactive rare earth compounds

    International Nuclear Information System (INIS)

    Eun, H.C.; Cho, Y.Z.; Lee, T.K.; Kim, I.T.; Park, G.I.; Lee, H.S.

    2013-01-01

    In this paper, an improvement study on the closed chamber distillation system for recovery of renewable salts from salt wastes containing radioactive rare earth compounds was performed to determine optimum operating conditions. It was very important to maintain the pressure in the distillation chamber below 10 Torr for a high efficiency (salt recovery >99 %) of the salt distillation. This required increasing the salt vaporization and condensation rates in the distillation system. It was confirmed that vaporization and condensation rates could be improved controlling the given temperature of top of the condensation chamber. In the distillation tests of the salt wastes containing rare earth compounds, the operation time at a given temperature was greatly reduced changing the given temperature of top of the condensation chamber from 780 to 700 deg C. (author)

  10. Improved overall survival after early recurrence of lung cancer following the introduction of CT-based follow-up for patients initially treated with curative intent by (chemo)radiotherapy (CRT)

    DEFF Research Database (Denmark)

    Hansen, Niels-Chr. G.; Laursen, Christian B.; Jeppesen, Stefan S.

    2017-01-01

    years after the introduction of CT-based follow-up. The difference between the periods is statistically significant (p = 0.009, log rank test).View this table:Conclusion: The CT-based follow-up program has most likely contributed to the improved survival as the survival difference between the periods......Background: After introduction in July 2010 of follow-up by contrast enhanced CT of thorax and upper abdomen every 3 months for two years and then every 6 months for three years we found improved survival after early recurrence in patients initially treated by surgery (Eur Respir J 2015; 46 suppl...

  11. Improving the quality of adult mortality data collected in demographic surveys: validation study of a new siblings' survival questionnaire in Niakhar, Senegal.

    Science.gov (United States)

    Helleringer, Stéphane; Pison, Gilles; Masquelier, Bruno; Kanté, Almamy Malick; Douillot, Laetitia; Duthé, Géraldine; Sokhna, Cheikh; Delaunay, Valérie

    2014-05-01

    In countries with limited vital registration, adult mortality is frequently estimated using siblings' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data. We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15-59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents' tendency to round reports of dates and ages to the nearest multiple of five or ten ("heaping"). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing. The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings. Controlled-Trials.com ISRCTN06849961

  12. Improving the Quality of Adult Mortality Data Collected in Demographic Surveys: Validation Study of a New Siblings' Survival Questionnaire in Niakhar, Senegal

    Science.gov (United States)

    Helleringer, Stéphane; Pison, Gilles; Masquelier, Bruno; Kanté, Almamy Malick; Douillot, Laetitia; Duthé, Géraldine; Sokhna, Cheikh; Delaunay, Valérie

    2014-01-01

    Background In countries with limited vital registration, adult mortality is frequently estimated using siblings' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data. Methods and Findings We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15–59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents' tendency to round reports of dates and ages to the nearest multiple of five or ten (“heaping”). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing. Conclusions The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings. Trial Registration Controlled-Trials.com ISRCTN06849961

  13. Maintained benefits and improved survival of dynamic cardiomyoplasty by activity-rest stimulation: 5-year results of the Italian trial on "demand" dynamic cardiomyoplasty.

    Science.gov (United States)

    Rigatelli, Gianluca; Barbiero, Mario; Rigatelli, Giorgio; Riccardi, Roberto; Cobelli, Franco; Cotogni, Angelo; Bandello, Attilio; Carraro, Ugo

    2003-01-01

    Latissimus dorsi (LD) muscular degeneration caused by continuous electrical stimulation has been the main cause of the poor results of dynamic cardiomyoplasty (DCMP) and its exclusion from the recent international guidelines on heart failure. To avoid full transformation of the LD and to improve results, a new stimulation protocol was developed; fewer impulses per day are delivered, providing the LD wrap with daily periods of rest ("demand" stimulation), based on a heart rate cut-off. The aim of this work is to report the results at 5 years of follow-up of the Italian Trial of Demand Dynamic Cardiomyoplasty and to discuss their impact on the destiny of this type of cardiac assistance. Twelve patients with dilated myocardiopathy (M/F=11/1, mean age 58.2+/-5.8 years, sinus rhythm/atrial fibrillation=11/1) were submitted during the period 1993-1996 to DCMP and at different intervals to demand protocol. Clinical, echocardiographic, mechanographic and cardiac invasive assessments were scheduled before initiating the demand protocol and during the follow-up at 0, 6 and every 12 months. The mean duration of follow-up was 40.2+/-13.8 months (range 18-64). There were no perioperative deaths. The demand stimulation protocol showed a decrease in 5 years in New York Health Association (NYHA) class (3.17+/-0.38-1.67+/-0.77, P=0.0001), an improvement of left ventricular ejection fraction (22.6+/-4.38-32.0+/-7.0, Pactuarial survival of 83.3% (one patient was switched to heart transplantation programme due to clinical worsening and another one died of massive pulmonary embolism). Demand DCMP maintains over time LD muscular properties, enhances clinical benefits and improves survival of DCMP, thus reopening the debate whether this type of treatment should be considered in patients with end-stage heart failure.

  14. A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

    Science.gov (United States)

    Haslem, Derrick S; Van Norman, S Burke; Fulde, Gail; Knighton, Andrew J; Belnap, Tom; Butler, Allison M; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P; Lin, Karen; Stone, Gary R; Loughmiller, David L; Mishra, Pravin J; Srivastava, Rajendu; Ford, James M; Nadauld, Lincoln D

    2017-02-01

    The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

  15. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    International Nuclear Information System (INIS)

    Sernbo, Sandra; Gustavsson, Elin; Brennan, Donal J; Gallagher, William M; Rexhepaj, Elton; Rydnert, Frida; Jirström, Karin; Borrebaeck, Carl AK; Ek, Sara

    2011-01-01

    The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. SOX11 expression and clinicopathological data was compared using χ 2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours

  16. Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro

    International Nuclear Information System (INIS)

    Cordes, N.; Meineke, V.

    2003-01-01

    Background: Cell-extracellular matrix (ECM) contact is thought to have great impact on cellular mechanisms resulting in increased cell survival upon exposure to ionizing radiation. Several human tumor cell lines and normal human fibroblastic cell strains of different origin, all of them expressing the wide-spread and important integrin subunit β1, were irradiated, and clonogenic cell survival, β1-integrin cell surface expression, and adhesive functionality were investigated. Material and Methods: Human tumor cell lines A172 (glioblastoma), PATU8902 (pancreas carcinoma), SKMES1 (lung carcinoma), A549 (lung carcinoma), and IPC298 (melanoma) as well as normal human skin (HSF1) and lung fibroblasts (CCD32) and human keratinocytes (HaCaT) were irradiated with 0-8 Gy. Besides colony formation assays, β1-integrin cell surface expression by flow cytometry and adhesive functionality by adhesion assays were analyzed. Results: All cell lines showed improved clonogenic survival after irradiation in the presence of fibronectin as compared to plastic. Irradiated cells exhibited a significant, dose-dependent increase in β1-integrin cell surface expression following irradiation. As a parameter of the adhesive functionality of the β1-integrin, a radiation-dependent elevation of cell adhesion to fibronectin in comparison with adhesion to plastic was demonstrated. Conclusion: The in vitro cellular radiosensitivity is highly influenced by fibronectin according to the phenomenon of cell adhesion-mediated radioresistance. Additionally, our emerging data question the results of former and current in vitro cytotoxicity studies performed in the absence of an ECM. These findings might also be important for the understanding of malignant transformation, anchorage-independent cell growth, optimization of radiotherapeutic regimes and the prevention of normal tissue side effects on the basis of experimental radiobiological data. (orig.)

  17. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    LENUS (Irish Health Repository)

    Sernbo, Sandra

    2011-09-24

    Abstract Background The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods SOX11 expression and clinicopathological data was compared using χ2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5\\'-Aza-2\\'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.

  18. Stereotactic body radiotherapy and treatment at a high volume facility is associated with improved survival in patients with inoperable stage I non-small cell lung cancer

    International Nuclear Information System (INIS)

    Koshy, Matthew; Malik, Renuka; Mahmood, Usama; Husain, Zain; Sher, David J.

    2015-01-01

    Background: This study examined the comparative effectiveness of no treatment (NoTx), conventional fractionated radiotherapy (ConvRT), and stereotactic body radiotherapy (SBRT) in patients with inoperable stage I non-small cell lung cancer. This population based cohort also allowed us to examine what facility level characteristics contributed to improved outcomes. Methods: We included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n = 13,036). Overall survival (OS) was estimated using Kaplan–Meier methods and Cox proportional hazard regression. Results: The median follow up was 68 months (interquartile range: 35–83 months) in surviving patients. Among the cohort, 52% received NoTx, 41% received ConvRT and 6% received SBRT. The 3-year OS was 28% for NoTx, 36% for ConvRT radiotherapy, and 48% for the SBRT cohort (p < 0.0001). On multivariate analysis, the hazard ratio for SBRT and ConvRT were 0.67 and 0.77, respectively, as compared to NoTx (1.0 ref) (p < 0.0001). Patients treated at a high volume facility vs. low volume facility had a hazard ratio of 0.94 vs. 1.0 (p = 0.01). Conclusions: Patients with early stage inoperable lung cancer treated with SBRT and at a high volume facility had a survival benefit compared to patients treated with ConvRT or NoTx or to those treated at a low volume facility

  19. Surviving floods: leaf gas films improve O₂ and CO₂ exchange, root aeration, and growth of completely submerged rice.

    Science.gov (United States)

    Pedersen, Ole; Rich, Sarah Meghan; Colmer, Timothy David

    2009-04-01

    When completely submerged, the leaves of some species retain a surface gas film. Leaf gas films on submerged plants have recently been termed 'plant plastrons', analogous with the plastrons of aquatic insects. In aquatic insects, surface gas layers (i.e. plastrons) enlarge the gas-water interface to promote O₂ uptake when under water; however, the function of leaf gas films has rarely been considered. The present study demonstrates that gas films on leaves of completely submerged rice facilitate entry of O₂ from floodwaters when in darkness and CO₂ entry when in light. O₂ microprofiles showed that the improved gas exchange was not caused by differences in diffusive boundary layers adjacent to submerged leaves with or without gas films; instead, reduced resistance to gas exchange was probably due to the enlarged water-gas interface (cf. aquatic insects). When gas films were removed artificially, underwater net photosynthesis declined to only 20% of the rate with gas films present, such that, after 7 days of complete submergence, tissue sugar levels declined, and both shoot and root growth were reduced. Internal aeration of roots in anoxic medium, when shoots were in aerobic floodwater in darkness or when in light, was improved considerably when leaf gas films were present. Thus, leaf gas films contribute to the submergence tolerance of rice, in addition to those traits already recognized, such as the shoot-elongation response, aerenchyma and metabolic adjustments to O₂ deficiency and oxidative stress. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd.

  20. Chronic obstructive pulmonary disease: getting it right. Does optimal management of chronic obstructive pulmonary disease alter disease progression and improve survival?

    Science.gov (United States)

    Russell, Richard E

    2014-03-01

    We live in a world where people live longer lives. The standardized mortality rate for many diseases is decreasing. Chronic obstructive pulmonary disease (COPD) is not following this trend. Over the last 10 years, interventions for COPD have been developed, but have any changed the prognosis or trajectory of this modern epidemic? We review the most recent and classical literature in order to answer this question. Recent analyses of data have clarified which interventions are effective in COPD and which are not. New studies have defined what is achievable with the current therapies. Only two interventions have been demonstrated to improve survival: smoking cessation and long-term oxygen therapy. Other treatments do reduce exacerbations, improve lung function and improve the patient's quality of life, but do not affect physiological disease progression or mortality. There is much work to do, not only to improve the treatments we have for this disease, but also to diagnose it early, intervene at the right time, reduce the treatment side-effects and most importantly understand the pathophysiology better. Moreover, we are duty bound to look at each patient and review what we are trying to achieve for each one through appropriate phenotyping as well as sometimes taking a more palliative approach.

  1. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Geferson Fischer

    2010-11-01

    Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

  2. Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Ma, Jinli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Chen, Xingxing; Guo, Xiaomao; Chen, Jiayi

    2013-09-01

    Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P RPA class II/III patients.

  3. Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

    Science.gov (United States)

    Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

    2009-01-01

    renal transplantations, ATG-F induction therapy administered as a part of immunosuppressive therapy significantly improves patient survival and reduces the risk of graft failure and transplant rejections.

  4. Improving Newborn Survival in Southern Tanzania (INSIST) trial; community-based maternal and newborn care economic analysis.

    Science.gov (United States)

    Manzi, Fatuma; Daviaud, Emmanuelle; Schellenberg, Joanna; Lawn, Joy E; John, Theopista; Msemo, Georgina; Owen, Helen; Barger, Diana; Hanson, Claudia; Borghi, Josephine

    2017-10-01

    Despite health systems improvements in Tanzania, gaps in the continuum of care for maternal, newborn and child health persist. Recent improvements have largely benefited those over one month of age, leading to a greater proportion of under-five mortality in newborns. Community health workers providing home-based counselling have been championed as uniquely qualified to reach the poorest. We provide financial and economic costs of a volunteer home-based counselling programme in southern Tanzania. Financial costs of the programme were extracted from project accounts. Ministry of Health and Social Welfare costs associated with programme implementation were collected based on staff and project monthly activity plans. Household costs associated with facility-based delivery were also estimated based on exit interviews with post-natal women. Time spent on the programme by implementers was assessed by interviews conducted with volunteers and health staff. The programme involved substantial design and set-up costs. The main drivers of set-up costs were activities related to volunteer training. Total annualized costs (design, set-up and implementation) amounted to nearly US$300 000 for financial costs and just over US$400 000 for economic costs. Volunteers (n = 842) spent just under 14 hours per month on programme-related activities. When volunteer time was valued under economic costs, this input amounted to just under half of the costs of implementation. The economic consequences of increased service use to households were estimated at US$36 985. The intervention cost per mother-newborn pair visited was between US$12.60 and US$19.50, and the incremental cost per additional facility-based delivery ranged from US$85.50 to US$137.20 for financial and economic costs (with household costs). Three scale-up scenarios were considered, with the financial cost per home visit respectively varying from $1.44 to $3.21 across scenarios. Cost-effectiveness compares well with supply

  5. Surviving "Payment by Results": a simple method of improving clinical coding in burn specialised services in the United Kingdom.

    Science.gov (United States)

    Wallis, Katy L; Malic, Claudia C; Littlewood, Sonia L; Judkins, Keith; Phipps, Alan R

    2009-03-01

    Coding inpatient episodes plays an important role in determining the financial remuneration of a clinical service. Insufficient or incomplete data may have very significant consequences on its viability. We created a document that improves the coding process in our Burns Centre. At Yorkshire Regional Burns Centre an inpatient summary sheet was designed to prospectively record and present essential information on a daily basis, for use in the coding process. The level of care was also recorded. A 3-month audit was conducted to assess the efficacy of the new forms. Forty-nine patients were admitted to the Burns Centre with a mean age of 27.6 years and TBSA ranging from 0.5% to 65%. The total stay in the Burns Centre was 758 days, of which 22% were at level B3-B5 and 39% at level B2. The use of the new discharge document identified potential income of about 500,000 GB pound sterling at our local daily tariffs for high dependency and intensive care. The new form is able to ensure a high quality of coding with a possible direct impact on the financial resources accrued for burn care.

  6. Inclusion of emergency department patients in early stages of sepsis in a quality improvement programme has the potential to improve survival: a prospective dual-centre study.

    Science.gov (United States)

    De Groot, Bas; Struyk, Bastiaan; Najafi, Rashed; Halma, Nieke; Pelser, Loekie; Vorst, Denise; Mertens, Bart; Ansems, Annemieke; Rijpsma, Douwe

    2017-09-01

    Sepsis quality improvement programmes typically focus on severe sepsis (ie, with acute organ failure). However, quality of ED care might be improved if these programmes included patients whose progression to severe sepsis could still be prevented (ie, infection without acute organ failure). We compared the impact on mortality of implementing a quality improvement programme among ED patients with a suspected infection with or without acute organ failure. This prospective observational study among ED patients hospitalised with suspected infection was conducted in two hospitals in the Netherlands. After stratification by sepsis category (with or without organ failure), in-hospital mortality was compared between a full compliance ( all quality performance measures achieved) and an incomplete compliance group. Multivariable logistic regression analysis was used to quantify the impact of full compliance on in-hospital mortality, adjusting for disease severity, disposition and hospital. There were 1732 ED patients and 130 deaths. Full compliance was independently associated with approximately two-thirds reduction in the odds of hospital mortality ( adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar in patients with and without organ failure. Among the 1379 patients with suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%) in the full compliance group and 49 (3.6%) in the incomplete compliance group (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54 (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI 8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and incomplete compliance groups, and 34 (45%) who benefited were those without acute organ failure. Sepsis quality improvement programmes should incorporate ED patients in earlier stages of sepsis given the potential to reduce in

  7. Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

    Energy Technology Data Exchange (ETDEWEB)

    Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

    2016-07-15

    The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

  8. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  9. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  10. Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

    Science.gov (United States)

    Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

    2018-05-02

    Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

    Directory of Open Access Journals (Sweden)

    Kuo YC

    2017-03-01

    Full Text Available Yung-Chih Kuo,1 Che-Yu Lin,1 Jay-Shake Li,2 Yung-I Lou3 1Department of Chemical Engineering, 2Department of Psychology, National Chung Cheng University, Chia-Yi, 3Department of Accounting, Providence University, Taichung, Taiwan, Republic of China Abstract: Curcumin (CRM and nerve growth factor (NGF were entrapped in liposomes (LIP with surface wheat germ agglutinin (WGA to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD therapy. Cardiolipin (CL-conjugated LIP carrying CRM (CRM-CL/LIP and also carrying NGF (NGF-CL/LIP were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ. We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38, phosphorylated c-Jun N-terminal kinase (p-JNK, and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD. Keywords: liposome, Alzheimer’s disease, β-amyloid, neurodegeneration, blood–brain barrier, wheat germ agglutinin

  12. Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Matthew W., E-mail: matthew.jackson@ucdenver.edu [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rusthoven, Chad G.; Jones, Bernard L. [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Kamdar, Manali [Department of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado (Unite