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Sample records for pulp improves survival

  1. Açai palm fruit (Euterpe oleracea Mart.) pulp improves survival of flies on a high fat diet.

    PubMed

    Sun, Xiaoping; Seeberger, Jeanne; Alberico, Thomas; Wang, Chunxu; Wheeler, Charles T; Schauss, Alexander G; Zou, Sige

    2010-03-01

    Reducing oxidative damage is thought to be an effective aging intervention. Açai, a fruit indigenous to the Amazon, is rich in phytochemicals that possesses high anti-oxidant activities, and has anti-inflammatory, anti-cancer and anti-cardiovascular disease properties. However, little is known about its potential anti-aging properties especially at the organismal level. Here we evaluated the effect of açai pulp on modulating lifespan in Drosophila melanogaster. We found that açai supplementation at 2% in the food increased the lifespan of female flies fed a high fat diet compared to the non-supplemented control. We measured transcript changes induced by açai for age-related genes. Although transcript levels of most genes tested were not altered, açai increased the transcript level of l(2)efl, a small heat-shock-related protein, and two detoxification genes, GstD1 and MtnA, while decreasing the transcript level of phosphoenolpyruvate carboxykinase (Pepck), a key gene involved in gluconeogenesis. Furthermore, açai increased the lifespan of oxidative stressed females caused by sod1 RNAi. This suggests that açai improves survival of flies fed a high fat diet through activation of stress response pathways and suppression of Pepck expression. Açai has the potential to antagonize the detrimental effect of fat in the diet and alleviate oxidative stress in aging. Published by Elsevier Inc.

  2. Açai Palm Fruit (Euterpe oleracea Mart.) Pulp Improves Survival of Flies on a High Fat Diet

    PubMed Central

    Sun, Xiaoping; Seeberger, Jeanne; Alberico, Thomas; Wang, Chunxu; Wheeler, Charles T.; Schauss, Alexander G.; Zou, Sige

    2010-01-01

    Reducing oxidative damage is thought to be an effective aging intervention. Açai, a fruit indigenous to the Amazon, is rich in phytochemicals that possesses high anti-oxidant activities, and has anti-inflammatory, anti-cancer and anti-cardiovascular disease properties. However, little is known about its potential anti-aging properties especially at the organismal level. Here we evaluated the effect of açai pulp on modulating lifespan in Drosophila melanogaster. We found that açai supplementation at 2% in the food increased the lifespan of female flies fed a high fat diet compared to the non-supplemented control. We measured transcript changes induced by açai for age-related genes. Although transcript levels of most genes tested were not altered, açai increased the transcript level of l(2)efl, a small heat-shock-related protein, and two detoxification genes, gstD1 and mtnA, while decreasing the transcript level of phosphoenolpyruvate carboxykinase (Pepck), a key gene involved in gluconeogenesis. Furthermore, açai increased the lifespan of oxidative stressed females caused by sod1 RNAi. This suggests that açai improves survival of flies fed a high fat diet through activation of stress response pathways and suppression of Pepck expression. Açai has the potential to antagonize the detrimental effect of fat in the diet and alleviate oxidative stress in aging. PMID:20080168

  3. Survival analysis applied to the sensory shelf-life dating of high hydrostatic pressure processed avocado and mango pulps.

    PubMed

    Jacobo-Velázquez, D A; Ramos-Parra, P A; Hernández-Brenes, C

    2010-08-01

    High hydrostatic pressure (HHP) pasteurized and refrigerated avocado and mango pulps contain lower microbial counts and thus are safer and acceptable for human consumption for a longer period of time, when compared to fresh unprocessed pulps. However, during their commercial shelf life, changes in their sensory characteristics take place and eventually produce the rejection of these products by consumers. Therefore, in the present study, the use of sensory evaluation was proposed for the shelf-life determinations of HHP-processed avocado and mango pulps. The study focused on evaluating the feasibility of applying survival analysis methodology to the data generated by consumers in order to determine the sensory shelf lives of both HHP-treated pulps of avocado and mango. Survival analysis proved to be an effective methodology for the estimation of the sensory shelf life of avocado and mango pulps processed with HHP, with potential application for other pressurized products. Practical Application: At present, HHP processing is one of the most effective alternatives for the commercial nonthermal pasteurization of fresh tropical fruits. HHP processing improves the microbial stability of the fruit pulps significantly; however, the products continue to deteriorate during their refrigerated storage mainly due to the action of residual detrimental enzymes. This article proposes the application of survival analysis methodology for the determination of the sensory shelf life of HHP-treated avocado and mango pulps. Results demonstrated that the procedure appears to be simple and practical for the sensory shelf-life determination of HHP-treated foods when their main mode of failure is not caused by increases in microbiological counts that can affect human health.

  4. Enzymatic treatment of mechanical pulp fibers for improving papermaking properties.

    PubMed

    Wong, K K; Richardson, J D; Mansfield, S D

    2000-01-01

    Three enzyme preparations (crude cellulase, laccase, and proteinase) were evaluated for their potential to improve the papermaking properties of mechanical pulp. After treating a long fibre-rich fraction of the pulp with enzyme, the fibres were recombined with untreated fines for handsheet making and testing. None of the enzymes altered the retention of fines or the consolidation of the furnish mix during handsheet formation. All three enzymes increased tensile stiffness index, which is a measure of the initial resistance of the handsheets to strain. Only the laccase preparation, an enzyme that modifies pulp lignin, consistently increased fibre bonding to enhance other strength properties of the handsheets.

  5. Retrospective Study of the Survival Rates of Indirect Pulp Therapy Versus Different Pulpotomy Medicaments.

    PubMed

    Wunsch, Patrice Barsamian; Kuhnen, Marissa M; Best, Al M; Brickhouse, Tegwyn H

    2016-10-15

    The purposes of this retrospective chart review were to determine: (1) how primary molars in need of vital pulp therapy (VPT) have been treated over a period of four years at a university-based pediatric dental practice (UBP); and which treatments-indirect pulp therapy (IPT), formocresol pulpotomy (FCP), and ferric sulfate pulpotomy (FSP)-have been successful. Electronic patient records (axiUm) that contained the procedure codes D3120 (pulp cap-indirect) or D3220 (therapeutic pulpotomy) were totaled by year. Visit records were queried again to identify treatment failures (i.e., extractions [D7140] or pulpectomy [D3221/D3240]). A total of 2,001 primary molar teeth were included in the study. Success was compared using a Kaplan-Meier analysis. At the three-year follow-up, IPT had a 96.2 percent survival rate, FCP had a 65.8 percent survival rate, and FSP had a 62.9 percent survival rate (P<.0001). Over a four-year period of time, IPT became the more commonly used vital pulp therapy treatment at a university-based pediatric dental practice and had a significantly better survival rate than FCP or FSP.

  6. Effects of size and age on the survival and growth of pulp and paper mills

    Treesearch

    Xiaolei Li; Joseph Buongiorno; Peter J. Ince

    2004-01-01

    The growth of pulp and paper mills in the US from 1970 to 2000 depended mostly on size and age. Mills grew according to Gibrat’s law, and post-1970 mills grew faster than pre-1971 mills. Mills stopped growing at approximately 22 years of age. But most mills survived beyond that, thus growth was not necessary for survival, but characteristic of the early phase of the...

  7. Improving Survival after Cardiac Arrest.

    PubMed

    Bjørshol, Conrad Arnfinn; Søreide, Eldar

    2017-02-01

    Each year, approximately half a million people suffer out-of-hospital cardiac arrest (CA) in Europe: The majority die. Survival after CA varies greatly between regions and countries. The authors give an overview of the important elements necessary to promote improved survival after CA as a function of the chain of survival and formula for survival concepts. The chain of survival incorporates bystanders (who identify warning symptoms, call the emergency dispatch center, initiate cardiopulmonary resuscitation [CPR]), dispatchers (who identify CA, and instruct and reassure the caller), first responders (who provide high-quality CPR, early defibrillation), paramedics and other prehospital care providers (who continue high-quality CPR, and provide timely defibrillation and advanced life support, transport to CA center), and hospitals (targeted temperature management, percutaneous coronary intervention, delayed prognostication). The formula for survival concept consists of (1) medical science (international guidelines), (2) educational efficiency (e.g., low-dose, high-frequency training for lay people, first responders, and professionals; and (3) local implementation of all factors in the chain of survival and formula for survival. Survival rates after CA can be advanced through the improvement of the different factors in both the chain of survival and the formula for survival. Importantly, the neurologic outcome in the majority of CA survivors has continued to improve.

  8. Novel bleaching of thermomechanical pulp for improved paper properties

    Treesearch

    Marguerite S. Sykes; John H. Klungness; Freya. Tan

    2002-01-01

    Production of mechanical pulp is expected to increase significantly to meet the growing global demand for paper. Mechanical pulping uses wood resources more efficiently with less negative impact on the environment than does chemical pulping. However, several problems related to mechanical pulping need to be resolved: high energy consumption, low paper strength...

  9. Improving fish survival through turbines

    SciTech Connect

    Ferguson, J.W. )

    1993-04-01

    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.

  10. Improved paper pulp from plants with suppressed cinnamoyl-CoA reductase or cinnamyl alcohol dehydrogenase.

    PubMed

    O'Connell, Ann; Holt, Karen; Piquemal, Joël; Grima-Pettenati, Jacqueline; Boudet, Alain; Pollet, Brigitte; Lapierre, Catherine; Petit-Conil, Michel; Schuch, Wolfgang; Halpin, Claire

    2002-10-01

    Transgenic plants severely suppressed in the activity of cinnamoyl-CoA reductase were produced by introduction of a partial sense CCR transgene into tobacco. Five transgenic lines with CCR activities ranging from 2 to 48% of wild-type values were selected for further study. Some lines showed a range of aberrant phenotypes including reduced growth, and all had changes to lignin structure making the polymer more susceptible to alkali extraction. The most severely CCR-suppressed line also had significantly decreased lignin content and an increased proportion of free phenolic groups in non-condensed lignin. These changes are likely to make the lignin easier to extract during chemical pulping. Direct Kraft pulping trials confirmed this. More lignin could be removed from the transgenic wood than from wild-type wood at the same alkali charge. A similar improvement in pulping efficiency was recently shown for poplar trees expressing an antisense cinnamyl alcohol dehydrogenase gene. Pulping experiments performed here on CAD-antisense tobacco plants produced near-identical results--the modified lignin was more easily removed during pulping without any adverse effects on the quality of the pulp or paper produced. These results suggest that pulping experiments performed in tobacco can be predictive of the results that will be obtained in trees such as poplar, extending the utility of the tobacco model. On the basis of our results on CCR manipulation in tobacco, we predict that CCR-suppressed trees may show pulping benefits. However, it is likely that CCR-suppression will not be the optimal target for genetic manipulation of pulping character due to the potential associated growth defects.

  11. Salmonella enterica serovar Enteritidis and Listeria monocytogenes in mango (Mangifera indica L.) pulp: growth, survival and cross-contamination.

    PubMed

    Penteado, Ana L; de Castro, M Fernanda P M; Rezende, Ana C B

    2014-10-01

    This study examined the ability of Salmonella enterica serovar Enteritidis and Listeria monocytogenes to grow or survive in mango pulp stored at -20°C, 4°C, 10°C and 25°C, as well as to cross-contaminate mangoes by means of a knife contaminated with different levels of these pathogens. At 25°C lag phase durations of 19 h and 7.2 h and generation times of 0.66 and 1.44 were obtained, respectively, for S. Enteritidis and L. monocytogenes. At 10°C only the growth of L. monocytogenes was observed. At 4°C both bacteria survived for 8 days. At -20°C S. Enteritidis was able to survive for 5 months while L. monocytogenes survived for 8 months. Cross-contamination was observed for knives contaminated with 10⁶, 10⁵ and 10⁴ CFU mL⁻¹ of S. Enteritidis and 10⁶ and 10⁵ CFU mL⁻¹ of L. monocytogenes. Both microorganisms can grow well in mango pulp at 25°C, thus lower temperatures for the maintenance of the pulps are crucial to avoid growth of these microorganisms. A refrigeration temperature of 10°C will avoid only the growth of S. Enteritidis. Thus good handling practices should be rigidly enforced to avoid any contamination as even at refrigeration and freezing temperatures survival of these pathogens may occur. © 2014 Society of Chemical Industry.

  12. A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties.

    PubMed

    Mastrogiacomo, S; Güvener, N; Dou, W; Alghamdi, H S; Camargo, W A; Cremers, J G O; Borm, P J A; Heerschap, A; Oosterwijk, E; Jansen, J A; Walboomers, X F

    2017-08-24

    Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a

  13. Improving the performance of enzymes in hydrolysis of high solids paper pulp derived from MSW

    PubMed Central

    2013-01-01

    Background The research aimed to improve the overall conversion efficiency of the CTec® family of enzymes by identifying factors that lead to inhibition and seeking methods to overcome these through process modification and manipulation. The starting material was pulp derived from municipal solid waste and processed in an industrial-scale washing plant. Results Analysis of the pulp by acid hydrolysis showed a ratio of 55 : 12 : 6 : 24 : 3 of glucan : xylan : araban/galactan/mannan : lignin : ash. At high total solids content (>18.5% TS) single-stage enzyme hydrolysis gave a maximum glucan conversion of 68%. It was found that two-stage hydrolysis could give higher conversion if sugar inhibition was removed by an intermediate fermentation step between hydrolysis stages. This, however, was not as effective as direct removal of the sugar products, including xylose, by washing of the residual pulp at pH 5. This improved the water availability and allowed reactivation of the pulp-bound enzymes. Inhibition of enzyme activity could further be alleviated by replenishment of β-glucosidase which was shown to be removed during the wash step. Conclusions The two-stage hydrolysis process developed could give an overall glucan conversion of 88%, with an average glucose concentration close to 8% in 4 days, thus providing an ideal starting point for ethanol fermentation with a likely yield of 4 wt%. This is a significant improvement over a single-step process. This hydrolysis configuration also provides the potential to recover the sugars associated with residual solids which are diluted when washing hydrolysed pulp. PMID:23885832

  14. [Vital pulp therapy of damaged dental pulp].

    PubMed

    Xuedong, Zhou; Dingming, Huang; Jianguo, Liu; Zhengwei, Huang; Xin, Wei; Deqin, Yang; Jin, Zhao; Liming, Chen; Lin, Zhu; Yanhong, Li; Jiyao, Li

    2017-08-01

    The development of an expert consensus on vital pulp therapy can provide practical guidance for the improvement of pulp damage care in China. Dental pulp disease is a major type of illness that adversely affects human oral health. Pulp capping and pulpotomy are currently the main methods for vital pulp therapy. Along with the development of minimal invasion cosmetic dentistry, using different treatment technologies and materials reasonably, preserving healthy tooth tissue, and extending tooth save time have become urgent problems that call for immediate solution in dental clinics. This paper summarizes the experiences and knowledge of endodontic experts. We develop a clinical path of vital pulp therapy for clinical work by utilizing the nature, approach, and degree of pulp damage as references, defense and self-repairing ability of pulp as guidance, and modern technologies of diagnosis and treatment as means.

  15. Changing incidence and improved survival of gliomas.

    PubMed

    Ho, Vincent K Y; Reijneveld, Jaap C; Enting, Roelien H; Bienfait, Henri P; Robe, Pierre; Baumert, Brigitta G; Visser, Otto

    2014-09-01

    Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma and low-grade gliomas. Data on 21,085 gliomas (excluding grade I tumours) were obtained from the Netherlands Cancer Registry, including tumours of the CNS without pathological confirmation. We calculated the age-standardised incidence rates and the estimated annual percentage change (EAPC) for all glioma subtypes. Crude and relative survival rates were estimated using information on the vital status obtained from the Dutch Municipal Personal Records Database. Incidence of gliomas in adults increased over time, from 4.9 per 100,000 in 1989 to 5.9 in 2010 (EAPC 0.7%, p<0.001). Two thirds were astrocytoma, 10% oligodendroglioma/oligoastrocytoma, 3% ependymoma and 21% were unspecified. Within the group of astrocytic tumours, the proportion of glioblastoma rose, while the proportion of anaplastic and unspecified astrocytoma decreased. Unspecified neoplasms also decreased, but this was significant only after 2005. Over the course of the study period, glioblastoma patients more often received multimodality treatment with chemotherapy concomitant and adjuvant to radiotherapy. The crude two-year survival rate of glioblastoma patients improved significantly, from 5% in the time period 1989-1994 to 15% in 2006-2010, with median survival increasing from 5.5 to 9 months. The incidence of low-grade gliomas did not change over time. Survival rates for low-grade oligodendroglial and mixed tumours show a modest improvement. The incidence rate for the total group of gliomas slightly increased, with a decrease of anaplastic and unspecified tumours and an increase of glioblastoma. Following the introduction of combined chemoradiation, two-year survival rates for glioblastoma significantly improved

  16. Yield Improvement and Energy Savings Uing Phosphonates as Additives in Kraft pulping

    SciTech Connect

    Ulrike W. Tschirner; Timothy Smith

    2007-03-31

    Project Objective: Develop a commercially viable modification to the Kraft process resulting in energy savings, increased yield and improved bleachability. Evaluate the feasibility of this technology across a spectrum of wood species used in North America. Develop detailed fundamental understanding of the mechanism by which phosphonates improve KAPPA number and yield. Evaluate the North American market potential for the use of phosphonates in the Kraft pulping process. Examine determinants of customer perceived value and explore organizational and operational factors influencing attitudes and behaviors. Provide an economic feasibility assessment for the supply chain, both suppliers (chemical supply companies) and buyers (Kraft mills). Provide background to most effectively transfer this new technology to commercial mills.

  17. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells

    PubMed Central

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-01

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:26775677

  18. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells.

    PubMed

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-18

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.

  19. Synthesis and Characteristic of Xylan-grafted-polyacrylamide and Application for Improving Pulp Properties

    PubMed Central

    Xu, Gui-Bin; Kong, Wei-Qing; Sun, Run-Cang; Ren, Jun-Li

    2017-01-01

    Recently, more attentions have been focused on the exploration of hemicelluloses in the paper industry. In this work, xylan-grafted-polyacrylamide (xylan-g-PAM) biopolymers were synthesized by the graft copolymerization of xylan with acrylamide, and their interaction with fibers was also investigated to improve waste newspaper pulp properties with or without cationic fiber fines. The influences of synthesis conditions were studied on the grafting ratio and the grafting efficiency of biopolymers. Prepared biopolymers were characterized by FTIR, 13C NMR, TGA and rheology. It was found that the grafting of PAM on xylan was conductive to improve xylan properties, such as the solubility in water, rheological features, and thermal stability, and the maximum grafting ratio was achieved to 14.7%. Moreover, xylan-g-PAM could obviously enhance the mechanical properties of waste paper pulps. Xylan-g-PAM also played the dominant role in increasing the strength of paper in the combination with prepared cationic fine fibers. When the amounts of xylan-g-PAM and cationic fiber fines were 1.0 wt % and 0.5 wt %, the mechanical properties such as the tensile index was increased by 49.09%, tear index was increased by 36.54%, and the burst index was increased by 20.67%, when compared with the control handsheets. Therefore, xylan-g-PAM as the new biopolymer could be promising in the application of strength agents for the paper industry as well as cationic fiber fines. PMID:28825640

  20. Improved survival time trends in Hodgkin's lymphoma.

    PubMed

    Koshy, Matthew; Fairchild, Andrew; Son, Christina H; Mahmood, Usama

    2016-06-01

    There have been dramatic changes in the staging and treatment of Hodgkin's lymphoma (HL) over the past 30 years. We undertook this study to determine if a stage migration had occurred and also examined if treatment associated with later years has improved survival. Patients with stage I-IV HL between 1983 and 2011 were selected from the Surveillance, Epidemiology, and End Results database. Multivariable analysis (MVA) was performed using Cox proportional hazards modeling. The study cohort included 35,680 patients. The stage breakdown in 1983 according to A and B symptoms was follows: 18%, 21%, 12%, and 5% for stage IA, IIA, IIIA, and IVA disease, respectively, and 6%, 11%, 12%, and 15% for stage IB, IIB, IIIB, and IVB disease. The stage breakdown in 2011 according to A and B symptoms was follows: 9%, 29%, 10%, and 6% for stage IA, IIA, IIIA, and IVA disease, respectively, and 4%, 16%, 12%, and 13% for stage IB, IIB, IIIB, and IVB disease. The median follow-up for the entire cohort is 6.1 years. On MVA, the HR for mortality of patients diagnosed in 2006 was 0.60 (95% Confidence Interval (CI): 0.52-0.70) compared to 1983. For stage I and II patients diagnosed in 2006 the HR was 0.62 (95% CI: 0.44-0.87) and 0.40 (95% CI: 0.30-0.55), respectively, compared to patients diagnosed in 1983. For stage III and IV patients diagnosed in 2006 the HR was 0.72 (95% CI: 0.53-0.98) and 0.74 (95% CI: 0.56-0.99), respectively, compared to patients diagnosed in 1983. This is the first study to demonstrate a significant stage migration in early stage Hodgkin's lymphoma. Furthermore, these results demonstrate an improvement in survival over time for patients with Hodgkin's lymphoma which was particularly notable for those with early stage disease.

  1. Dietary citrus pulp improves protein stability in lamb meat stored under aerobic conditions.

    PubMed

    Gravador, Rufielyn S; Jongberg, Sisse; Andersen, Mogens L; Luciano, Giuseppe; Priolo, Alessandro; Lund, Marianne N

    2014-06-01

    The antioxidant effects of dried citrus pulp on proteins in lamb meat, when used as a replacement of concentrate in the feed, was studied using meat from 26 male Comisana lambs. The lambs of age 90 days had been grouped randomly to receive one of the three dietary treatments: (1) commercial concentrate with 60% barley (Control, n=8), (2) concentrate with 35% barley and 24% citrus pulp (Cp24, n=9), or (3) concentrate with 23% barley and 35% citrus pulp (Cp35, n=9). Slices from the longissimus thoracis et lomborum muscle were packed aerobically and stored for up to 6days at 4°C in the dark. The citrus pulp groups, Cp24 and Cp35, significantly decreased protein radicals and carbonyls, and preserved more thiols within six days of storage compared to the Control group. The citrus pulp groups significantly slowed down the rate of protein oxidation, indicating that dietary citrus pulp reduced oxidative changes in meat proteins.

  2. Understanding the Nature and Reactivity of Residual Lignin for Improved Pulping and Bleaching Efficiency

    SciTech Connect

    Yuan-Zong Lai

    2001-11-30

    One of the most formidable challenges in kraft pulping to produce bleached chemical pulps is how to effectively remove the last 5-10% of lignin while maintaining the fiber quality. To avoid a severe fiber degradation, kraft pulping is usually terminated in the 25-30 kappa number range and then followed by an elementally chlorine free (ECF) or a totally chlorine free (TCF) bleaching sequence to reduce the environmental impacts.

  3. Improving the efficiency of enzyme utilization for sugar beet pulp hydrolysis.

    PubMed

    Zheng, Yi; Cheng, Yu-Shen; Yu, Chaowei; Zhang, Ruihong; Jenkins, Bryan M; VanderGheynst, Jean S

    2012-11-01

    Sugar beet pulp (SBP) is a carbohydrate-rich residue of table sugar processing. It shows promise as a feedstock for fermentable sugar and biofuel production via enzymatic hydrolysis and microbial fermentation. This research focused on the enzymatic hydrolysis of SBP and examined the effects of solid loading (2-10 %, dry basis), enzyme preparation, and enzyme recycle on the production of fermentable sugars. The enzyme partitioning to the solid and liquid phases during SBP enzymatic hydrolysis and loss during recycling were investigated using SDS-PAGE and Zymogram analysis. Without considering product inhibition, the cellulase added initially to the SBP hydrolysis lost only 6 % filter paper activity and negligible carboxymethyl cellulose activity upon multiple cycles of SBP hydrolysis. It was found that enzyme dosage can be reduced by 50 % while maintaining similar, and in some cases higher fermentable sugar yield. The removal of hydrolysis products will further improve enzymatic hydrolysis of SBP for biofuel production.

  4. Survival Continues to Improve for Most Cancers

    MedlinePlus

    ... and breast cancers. However, death rates rose for cancers of the liver, pancreas and brain in men and for the liver ... myeloma and leukemia. The lowest survival rates for cancers diagnosed between 2006 and 2012 were: pancreas (8.5 percent survival five years after diagnosis); ...

  5. Improvement of Pulping Uniformity by Measurement of Single Fiber Kappa Number

    SciTech Connect

    Richard R. Gustafson; James B. Callis

    2001-11-20

    A method to measure the kappa of single fibers by staining with a fluorescent dye, Acridine Orange (AO), has been developed. This method is now applied to develop and automated flow-through instrument that permits routine kappa analysis on thousands of images of AO stained fibers to give the fiber kappa number distribution of a pulp sample in a few minutes. The design and operation of the instrument are similar to that of a flow cytometer but with the addition of extensive fiber imaging capability. Fluorescence measurements in the flow-through instrument are found to be consistent with those made with fluorescence microscope provided the signal processing in the flow-thou instrument is handled propertly. The kappa distributions of pulps that were analyzed by means of a density gradient column are compared to those measured with the flow-through instrument with good results. The kappa distributions of various laboratory pulps and commercial pulps have been measured. It has been found that all pulps are non-uniform but that ommercial pulps generally have broader kappa distributions thatn their laboratory counterparts. The effects of different pulping methods and chip pretreatments on pulp uniformity are discussed in the report. Finally, the application of flow-through fluorescence technology to other single fiber measurements are presented.

  6. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  7. Method for improving separation of carbohydrates from wood pulping and wood or biomass hydrolysis liquors

    DOEpatents

    Griffith, William Louis; Compere, Alicia Lucille; Leitten, Jr., Carl Frederick

    2010-04-20

    A method for separating carbohydrates from pulping liquors includes the steps of providing a wood pulping or wood or biomass hydrolysis pulping liquor having lignin therein, and mixing the liquor with an acid or a gas which forms an acid upon contact with water to initiate precipitation of carbohydrate to begin formation of a precipitate. During precipitation, at least one long chain carboxylated carbohydrate and at least one cationic polymer, such as a polyamine or polyimine are added, wherein the precipitate aggregates into larger precipitate structures. Carbohydrate gel precipitates are then selectively removed from the larger precipitate structures. The method process yields both a carbohydrate precipitate and a high purity lignin.

  8. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    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

    2016-01-01

    Abstract 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. PMID:27082623

  9. Microwaving logs for energy savings and improved paper properties for mechanical pulps

    Treesearch

    C. Tim Scott; John Klungness; Mike Lentz; Eric Horn; Masood Akhtar

    2002-01-01

    High-power microwave cooking of commercial black spruce pulpwood logs was investigated as a pretreatment for mechanical pulping. Several dozen logs were treated at a variety of power levels (10 to 50 kW) and for various times (1 to 10 min). The mechanical pulping trials resulted in significant energy savings-up to 15% for the highest power level. In addition, there was...

  10. New Approaches in Vital Pulp Therapy in Permanent Teeth

    PubMed Central

    Ghoddusi, Jamileh; Forghani, Maryam; Parisay, Iman

    2014-01-01

    Vitality of dental pulp is essential for long-term tooth survival. The aim of vital pulp therapy is to maintain healthy pulp tissue by eliminating bacteria from the dentin-pulp complex. There are several different treatment options for vital pulp therapy in extensively decayed or traumatized teeth. Pulp capping or pulpotomy procedures rely upon an accurate assessment of the pulp status, and careful management of the remaining pulp tissue. The purpose of this review is to provide an overview of new approaches in vital pulp therapy in permanent teeth. PMID:24396371

  11. Platonin improves survival of skin allografts.

    PubMed

    Cheng, Shih-Ping; Lee, Jie-Jen; Chi, Chin-Wen; Chang, Kuo-Ming; Chen, Yu-Jen

    2010-11-01

    Platonin is an immunomodulator with NF-κB inhibitory activity. It not only inhibits interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production in sepsis, but also attenuates heatstroke reactions. In addition, platonin redirects differentiation of dendritic cells toward an intermediate stage of maturation. The study was designed to examine whether platonin can reduce acute graft rejection. A C57BL/6 to BALB/c mice skin transplantation model was used. Platonin was given intraperitoneally to transplant recipients at various doses. Skin grafts were submitted to histologic analysis. NF-κB DNA binding activity and inducible nitric oxide synthase (iNOS) expression were determined in harvested draining lymph nodes. Leukocyte count, hepatic and renal functions were serially assessed. An array of serum cytokines was evaluated on d 1, 3, 5, and 7 after skin transplantation. Platonin resulted in significantly prolonged skin allograft survival in a dose- and time-dependent manner. Histologic changes in the skin allografts paralleled the gross appearance of rejection. Serum cytokine analysis shows that platonin significantly suppressed the production of the proinflammatory cytokines IL-6 and TNF-α. However, no significant changes occurred in the serum levels of Th1-type and Th2-type cytokines. NF-κB activity and iNOS expression were remarkably suppressed in draining lymph nodes. In terms of toxicity, there were no significant differences in body weight, leukocyte count, plasma alanine aminotransferase, or creatinine between the platonin-treated and control groups. Platonin effectively prolongs skin allograft survival without major toxicity. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Effect of storage in juice with or without pulp and/or calcium lactate on the subsequent survival of Escherichia coli O157:H7 in simulated gastric fluid.

    PubMed

    Yuk, Hyun-Gyun; Jo, Seong-Chun; Seo, Hye-Kyung; Park, Sun-Min; Lee, Seung-Cheol

    2008-04-30

    A study was conducted to evaluate the effect of storing Escherichia coli O157:H7 in fruit or vegetable juices with or without pulp and/or calcium lactate, on the bacterial resistance to a simulated gastric fluid (SGF, pH 1.5). Apple, carrot, orange, and tomato juices containing pulp or freed from pulp by filtration were used in this study. Calcium lactate at about 1.4 g/l was added to juices to obtain calcium supplemented juices. Juices with or without pulp and/or calcium lactate were inoculated with E. coli O157:H7 and then were stored at 7 degrees C for 0, 1, 2, or 4 days. The acid resistance of cells stored in juices with or without pulp and/or calcium lactate was determined by incubating in SGF for 90 or 240 min at 37 degrees C. Cells stored in apple juice for 4 days, carrot juice for 2 days, and orange juice for 4 days with pulp only had greater acid resistance, while all cells stored in tomato juice with pulp had greater acid resistance than cells stored in juice without pulp. The D-values of cells stored in supplemented apple and orange juices with calcium lactate declined 1.7-3.5 fold, whereas D-values of cells stored in supplemented tomato juice decreased by about 1.4-fold when compared to cells stored in juice without calcium lactate after exposure in SGF. These results indicate that storing E. coli O157:H7 in juices with pulp had little or no effect on the acid resistance of cells during subsequent exposure in SGF. Calcium lactate supplemented into juices could dramatically decrease the ability of E. coli O157:H7 to survive in SGF, possibly reducing the risk of foodborne illness by juice products.

  13. Method for Improving Separation of Carbohydrates from Wood Pulping Liquors and Wood or Biomass Hydrolysis Liquors

    SciTech Connect

    Compere, A L; Marcoccia, B S; Elliott, J

    2012-08-31

    Work with industrial partners to perform the studies needed to commercialize U.S. patent 7,699,958 for separation of carbohydrates from wood pulping liquors and wood or biomass hydrolysis liquors. These include: 1) selection of the best pulp mill liquor withdrawal sites, 2) additional purification or enzyme hydrolysis required to obtain acceptable sugar feedstocks, 3) and work with partners to optimize the stream and purification methods to provide acceptable feedstocks for algal fuels and industrial chemicals production, and 4) preparation of samples large enough for testing by downstream partners.

  14. Feeding orange pulp improved bone quality in a rat model of male osteoporosis.

    PubMed

    Morrow, Rori; Deyhim, Farzad; Patil, Bhimanagouda S; Stoecker, Barbara J

    2009-04-01

    Oxidative stress and inflammation have been linked to bone loss. We evaluated the effects of feeding orange pulp (OP), a source of vitamin C and flavonoids, on bone quality in a rat model of male osteoporosis. One-year-old retired breeder rats (n = 43) were orchidectomized (ORX) or sham-operated (SHAM). Three days postsurgery, ORX rats were randomly assigned to treatments: ORX or ORX with 2.5% OP, 5% OP, or 10% OP. Diets were isonitrogenous, isocaloric, modified AIN-93M diets with equal fiber content. All ORX rats were fed for 4 months to the mean food intake of the SHAM group. At the end of the study blood, urine and bone samples were collected. Plasma antioxidant capacity and urinary deoxypyridinoline (DPD) were determined. Bone density, structure, and strength were assessed using dual energy X-ray absorptiometry, microcomputed tomography, and finite element analyses. ORX decreased (P < .05) antioxidant status, while OP as low as 2.5% maintained the antioxidant capacity of ORX rats comparable to that of the SHAM group. Cortical thickness at the tibial midshaft was significantly decreased by ORX and increased by OP, and urinary DPD was significantly increased by ORX and decreased by OP. In fourth lumbar trabecular cores, ORX rats had significantly reduced bone volume fraction, connectivity density, and trabecular number and increased trabecular separation. OP significantly increased bone volume fraction and trabecular number and decreased trabecular separation in ORX rats. Improvements due to OP in microarchitectural properties of vertebral bones and in cortical thickness of long bones were subtle but significant. The consistently negative impacts of ORX on bone density, structure, and strength parameters confirm the previously reported importance of testosterone for bone.

  15. Investigation of the Maillard Reaction between Polysaccharides and Proteins from Longan Pulp and the Improvement in Activities.

    PubMed

    Han, Miao-Miao; Yi, Yang; Wang, Hong-Xun; Huang, Fei

    2017-06-05

    The purpose of this study was to investigate the Maillard reaction between polysaccharides and proteins from longan pulp and the effects of reaction on their in vitro activities. The polysaccharide-protein mixtures of fresh longan pulp (LPPMs) were co-prepared by an alkali extraction-acid precipitation method. They were then dry-heated under controlled conditions for monitoring the characterization of the Maillard reaction by the measurement of the free amino group content, ultraviolet-visible spectrum, Fourier transform infrared spectrum and molecular weight distribution. All the physicochemical analyses indicated the development of the Maillard reaction between polysaccharides and proteins. The in vitro activity evaluation indicated that the Maillard reaction could effectively enhance the antioxidant, antitumor and immunostimulating activities of LPPMs. The enhancement of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power displayed both a positive correlation with the reaction time (p < 0.05). LPPMs dry-heated for three days obtained relatively strong inhibitory activity against HepG2 cells and SGC7901 cells, as well as strong immunostimulating effects on the nitric oxide production and tumor necrosis factor α secretion of macrophages. Maillard-type intermacromolecular interaction is suggested to be an effective and controllable method for improving the functional activities of polysaccharides and proteins from longan pulp.

  16. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Cancer.gov

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  17. Vapor-phase diethyl oxalate pretreatment of wood chips. Part 1, Energy savings and improved pulps

    Treesearch

    William Kenealy; Eric Horn; Carl Houtman

    2007-01-01

    Diethyl oxalate (DEO) was injected into a digester containing wood chips (pine, spruce, or aspen) preheated to 130–1408C and held for 30 min at the same temperature. When mechanical pulps were produced from these pretreated chips, savings in electrical refiner energy could be achieved. For southern yellow pine (Pinus taeda), the electrical refiner energy required to...

  18. Solid-State Fermentation: an Alternative to Improve the Nutritive Value of Coffee Pulp

    PubMed Central

    Peñaloza, Walter; Molina, Mario R.; Brenes, Roberto Gomez; Bressani, Ricardo

    1985-01-01

    Coffee pulp was subjected to a solid-state fermentation process, using Aspergillus niger. The initial moisture content of the pulp, as well as the fermentation time and temperature, had a significant effect on the increase in total amino acid content of the material. The increase in total amino acids showed a significant correlation with the dry matter recovered (r = −0.98) and the increase in pH during the process (r = 0.98). With a moisture content of 80%, a pH of 3.5, a temperature of 35°C, and an aeration of 8 liters/min per kg as fermentation conditions, it was found that the maximum concentration of total amino acids was attained after 43 h. The fermented product had a higher total amino acid content and a lower cell wall constituent value (primarily cellulose and hemicellulose) than the original pulp. A growing chicken's ration containing 10% of the fermented product had a feed efficiency (2.14) similar to that of the standard ration (2.19) and was significantly better than that of the diet containing 10% of the original pulp (2.53). The difference observed in feed intake and weight gain between the standard diet and that with 10% of the fermented product is considered to be due to palatability factors which should be studied further. PMID:16346724

  19. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation-Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Greg Beilman...Hibernation-Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...political conflict. The injuries sustained are often accompanied by severe blood loss , and shock from this blood loss is the most common cause of

  20. Survival improvements with adjuvant therapy in patients with glioblastoma.

    PubMed

    Jayamanne, Dasantha; Wheeler, Helen; Cook, Raymond; Teo, Charles; Brazier, David; Schembri, Geoff; Kastelan, Marina; Guo, Linxin; Back, Michael F

    2017-09-18

    Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database. The primary endpoint was the median survival. Univariate predictors of survival were evaluated with respect to tumour resection, age and Eastern Cooperative Oncology Group (ECOG) performance status using log-rank comparisons. Two hundred and thirty-three patients were managed under the protocol and analysed for outcome. The median age was 57 years; the rate of gross total resection, subtotal resection and biopsy were 47.2%, 35.2% and 17.6%, respectively. At progression, 49 patients had re-resection, and in addition to second-line chemotherapy, 86 patients had Bevacizumab including 26 with re-irradiation. Median survival was 17.0 months (95% CI: 15.4-18.6). On univariate evaluation, extent of resection (P = 0.001), age, ECOG performance status and recursive partitioning analysis class III were shown to significantly improve survival (P < 0.0001). The median survival for gross total resection, age <50 years, ECOG 0-1 and recursive partitioning analysis class III were 21, 27, 20 and 47 months, respectively. This study confirms the significant improvement in median survival in GBM that has occurred in recent years since introduction of the EORTC-NCIC protocol. Further improvements have occurred presumably related to subspecialized care, improved resection rates, sophisticated radiotherapy targeting and early systemic salvage therapies. However, the burden of the disease within the community remains high and the median survival improvements over time have plateaued. © 2017 Royal Australasian College of

  1. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    PubMed Central

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  2. Improving the hydrogen peroxide bleaching efficiency of aspen chemithermomechanical pulp by using chitosan.

    PubMed

    Li, Zongquan; Dou, Hongyan; Fu, Yingjuan; Qin, Menghua

    2015-11-05

    The presence of transition metals during the hydrogen peroxide bleaching of pulp results in the decomposition of hydrogen peroxide, which decreases the bleaching efficiency. In this study, chitosans were used as peroxide stabilizer in the alkaline hydrogen peroxide bleaching of aspen chemithermomechanical pulp (CTMP). The results showed that the brightness of the bleached CTMP increased 1.5% ISO by addition of 0.1% chitosan with 95% degree of deacetylation during peroxide bleaching. Transition metals in the form of ions or metal colloid particles, such as iron, copper and manganese, could be adsorbed by chitosans. Chitosans could inhibit the decomposition of hydrogen peroxide catalyzed by different transition metals under alkaline conditions. The ability of chitosans to inhibit peroxide decomposition depended on the type of transition metals, chitosan concentration and degree of deacetylation applied. The addition of chitosan slightly reduced the concentration of the hydroxyl radical formed during the hydrogen peroxide bleaching of aspen CTMP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Challenges to Improving Combat Casualty Survivability on the Battlefield

    DTIC Science & Technology

    2015-01-01

    closing the gap in prehospital survival. Improving pre - hospital combat casualty care, however, may be significantly more challenging than improving...facts must be collected on each case; however, as we discuss shortly, pre - hospital data are often difficult to collect. The potentially preventable

  4. Analysis of reasons for decline of bioleaching efficiency of spent Zn-Mn batteries at high pulp densities and exploration measure for improving performance.

    PubMed

    Xin, Baoping; Jiang, Wenfeng; Li, Xin; Zhang, Kai; Liu, Changhao; Wang, Renqing; Wang, Yutao

    2012-05-01

    The reasons for decline of bioleaching efficiency of Zn and Mn from spent batteries at high pulp densities were analyzed; the measures for improving bioleaching efficiency were investigated. The results showed that extraction efficiency of Zn dropped from 100% at 1% of pulp density to 29.9% at 8% of pulp density, with Mn from 94% to only 2.5%. It was almost the linear reduction of the activity of the sulfur-oxidizing bacteria with increase of pulp density that witnessed declined bioleaching efficiency of Zn; it was the complete inactivation of the iron-oxidizing bacteria at 2% of pulp density or higher that witnessed declined bioleaching dose of Mn. By means of reducing initial pH value of leaching media, increasing concentration of energy matters and exogenous acid adjustment of media during bioleaching, the maximum extraction efficiency of almost 100% for Zn and 89% for Mn at 4% of pulp density was attained, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Process controls for improving bioleaching performance of both Li and Co from spent lithium ion batteries at high pulp density and its thermodynamics and kinetics exploration.

    PubMed

    Niu, Zhirui; Zou, Yikan; Xin, Baoping; Chen, Shi; Liu, Changhao; Li, Yuping

    2014-08-01

    Release of Co and Li from spent lithium ion batteries (LIBs) by bioleaching has attracted growing attentions. However, the pulp density was only 1% or lower, meaning that a huge quantity of media was required for bioleaching. In this work, bioleaching behavior of the spent LIBs at pulp densities ranging from 1% to 4% was investigated and process controls to improve bioleaching performance at pulp density of 2% were explored. The results showed that the pulp density exerted a considerable influence on leaching performance of Co and Li. The bioleaching efficiency decreased respectively from 52% to 10% for Co and from 80% to 37% for Li when pulp density rose from 1% to 4%. However, the maximum extraction efficiency of 89% for Li and 72% for Co was obtained at pulp density of 2% by process controls. Bioleaching of the spent LIBs has much greater potential to occur than traditional chemical leaching based on thermodynamics analysis. The product layer diffusion model described best bioleaching behavior of Co and Li.

  6. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    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.

  7. Breast Cancer in Developing Countries: Opportunities for Improved Survival

    PubMed Central

    Shulman, Lawrence N.; Willett, Walter; Sievers, Amy; Knaul, Felicia M.

    2010-01-01

    Breast cancer survival in the USA has continually improved over the last six decades and has largely been accredited to the use of mammography, advanced surgical procedures, and adjuvant therapies. Data indicate, however, that there were substantial improvements in survival in the USA even prior to these technological and diagnostic advances, suggesting important opportunities for early detection and treatment in low- and middle-income countries where these options are often unavailable and/or unaffordable. Thus, while continuing to strive for increased access to more advanced technology, improving survival in these settings should be more immediately achievable through increased awareness of breast cancer and of the potential for successful treatment, a high-quality primary care system without economic or cultural barriers to access, and a well-functioning referral system for basic surgical and hormonal treatment. PMID:21253541

  8. The remarkable improvements in survival at older ages.

    PubMed

    Vaupel, J W

    1997-12-29

    The belief that old-age mortality is intractable remains deeply held by many people. Remarkable progress, however, has been made since 1950, and especially since 1970, in substantially improving survival at older ages, even the most advanced ages. The pace of mortality improvement at older ages continues to be particularly rapid in Japan, even though mortality levels in Japan are lower than elsewhere. The progress in improving survival has accelerated the growth of the population of older people and has advanced the frontier of human survival substantially beyond the extremes of longevity attained in pre-industrial times. Little, however, is known about why mortality among the oldest-old has been so plastic since 1950. The little that is known has largely been learned within the past few years. New findings, especially concerning genetic factors that influence longevity, are emerging at accelerating rate.

  9. Regenerative potential of dental pulp.

    PubMed

    Trope, Martin

    2008-07-01

    The regenerative potential of dental pulp, particularly in mature teeth, has been considered extremely limited. However, our improved understanding of pulpal inflammation and repair and improved dental materials and technologies make vital pulp therapy a viable alternative to root canal treatment. This article explores our knowledge in this regard and the future potential of saving or even regenerating the pulp as a routine dental procedure.

  10. Regenerative potential of dental pulp.

    PubMed

    Trope, Martin

    2008-01-01

    The regenerative potential of dental pulp, particularly in mature teeth, has been considered extremely limited. However, our improved understanding of pulpal inflammation and repair and improved dental materials and technologies make vital pulp therapy a viable alternative to root canal treatment. This article explores our knowledge in this regard and the future potential of saving or even regenerating the pulp as a routine dental procedure.

  11. Reducing synuclein accumulation improves neuronal survival after spinal cord injury

    PubMed Central

    Fogerson, Stephanie M.; van Brummen, Alexandra J.; Busch, David J.; Allen, Scott R.; Roychaudhuri, Robin; Banks, Susan M. L.; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R.

    2016-01-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson’s and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the “molecular tweezer” inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID:26854933

  12. Surviving Performance Improvement "Solutions": Aligning Performance Improvement Interventions

    ERIC Educational Resources Information Center

    Bernardez, Mariano L.

    2009-01-01

    How can organizations avoid the negative, sometimes chaotic, effects of multiple, poorly coordinated performance improvement interventions? How can we avoid punishing our external clients or staff with the side effects of solutions that might benefit our bottom line or internal efficiency at the expense of the value received or perceived by…

  13. Surviving Performance Improvement "Solutions": Aligning Performance Improvement Interventions

    ERIC Educational Resources Information Center

    Bernardez, Mariano L.

    2009-01-01

    How can organizations avoid the negative, sometimes chaotic, effects of multiple, poorly coordinated performance improvement interventions? How can we avoid punishing our external clients or staff with the side effects of solutions that might benefit our bottom line or internal efficiency at the expense of the value received or perceived by…

  14. Improving survival after endometrial cancer: the big picture.

    PubMed

    Kwon, Janice S

    2015-07-01

    To improve survival in women with endometrial cancer, we need to look at the "big picture" beyond initial treatment. Although the majority of women will be diagnosed with early stage disease and are cured with surgery alone, there is a subgroup of women with advanced and high-risk early stage disease whose life expectancy may be prolonged with the addition of chemotherapy. Immunohistochemistry will help to identify those women with Lynch syndrome who will benefit from more frequent colorectal cancer surveillance and genetic counseling. If they happen to be diagnosed with colorectal cancer, this information has an important therapeutic implication. And finally, because the majority of women will survive their diagnosis of endometrial cancer, they remain at risk for breast and colorectal cancer, so these women should be counselled about screening for these cancers. These three interventions will contribute to improving the overall survival of women with endometrial cancer.

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

    SciTech Connect

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

    2008-11-14

    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{sup INK}, p21 and p19{sup 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. Nitrite therapy improves survival postexposure to chlorine gas

    PubMed Central

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

    2014-01-01

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

  17. Xylan-hydrolyzing enzyme system from Bacillus pumilus CBMAI 0008 and its effects on Eucalyptus grandis kraft pulp for pulp bleaching improvement.

    PubMed

    Duarte, Marta C Teixeira; da Silva, Elizete Cristina; de Bulhões Gomes, Isabel Menezes; Ponezi, Alexandre Nunes; Portugal, Edilberto Princi; Vicente, João Roberto; Davanzo, Ednilson

    2003-05-01

    The extracellular productions of beta-xylanase, beta-xylosidase, beta-glucosidase, beta-mannanase, arabinosidase, alpha-glucuronidase, alpha-galactosidase and Fpase from Bacillus pumilus CBMAI 0008 were investigated with three different xylan sources as substrate. The enzymatic profiles on birchwood, Eucalyptus grandis and oat were studied at alkaline and acidic pH conditions. B. pumilus CBMAI 0008 grown on the three carbon sources produced mainly beta-xylanase. At pH 10, the levels of xylanase were 328, 160 and 136 U/ml, for birch, oat and E. grandis, respectively. beta-Mannanase production was induced on E. grandis (5 U/ml) and arabinofuranosidase on oat (5 U/ml). Although small quantities of alpha-glucuronidase had been produced at pH 10, activity at pH 4.8 was 1.5 U/ml, higher than observed for Aspergillus sp. in literature reports. Preliminary assays carried out on E. grandis kraft pulp from an industrial paper mill (RIPASA S.A. Celulose e Papel, Limeira, SP, Brazil) showed a reduction of 0.3% of chlorine use in the pulp treated with the enzymes, resulting in increased brightness, compared to conventional bleaching. The enzymes were more efficient if applied before the initial bleaching sequence, in a non-pre-oxygenated pulp.

  18. Improved survival of children and adolescents with sickle cell disease.

    PubMed

    Quinn, Charles T; Rogers, Zora R; McCavit, Timothy L; Buchanan, George R

    2010-04-29

    The survival of young children with sickle cell disease (SCD) has improved, but less is known about older children and adolescents. We studied the Dallas Newborn Cohort (DNC) to estimate contemporary 18-year survival for newborns with SCD and document changes in the causes and ages of death over time. We also explored whether improvements in the quality of medical care were temporally associated with survival. The DNC now includes 940 subjects with 8857 patient-years of follow-up. Most children with sickle cell anemia (93.9%) and nearly all children with milder forms of SCD (98.4%) now live to become adults. The incidence of death and the pattern of mortality changed over the duration of the cohort. Sepsis is no longer the leading cause of death. All the recent deaths in the cohort occurred in patients 18 years or older, most shortly after the transition to adult care. Quality of care in the DNC has improved over time, with significantly more timely initial visits and preventive interventions for young children. In summary, most children with SCD now survive the childhood years, but young adults who transition to adult medical care are at high risk for early death.

  19. Sodium hypochlorite with reduced surface tension does not improve in situ pulp tissue dissolution.

    PubMed

    De-Deus, Gustavo; de Berredo Pinho, Marco André; Reis, Claudia; Fidel, Sandra; Souza, Erick; Zehnder, Matthias

    2013-08-01

    Sodium hypochlorite (NaOCl) solutions with added wetting agents are advertised to dissolve necrotic tissue in root canals faster than their counterparts without a lowered surface tension. This was tested in the current study, and the null hypothesis formulated was that there was no difference between a commercially available NaOCl solution with a lowered surface tension (Chlor-XTRA; Vista Dental Products, Racine, WI) and a counterpart containing the same amount of available chlorine without added wetting agents regarding the soft tissue that remains in oval-shaped canals after mechanical preparation and irrigation. Formerly vital extracted teeth (N = 44, 22 pairs) with similar anatomy were radiographically paired and chemomechanically prepared. In 1 tooth from each pair, a 5.25% NaOCl solution with reduced surface tension was used; in the other, a pure, technical-grade NaOCl solution of 5.25% was used. The percentage of remaining pulp tissue (PRPT) was histologically assessed in root cross-sections. The non-Gaussian raw data were subjected to Kruskal-Wallis and Mann-Whitney U tests to verify the respective effect of the cross-section level and solution on the PRPT. The relationship between the cross-section level and the PRPT was estimated by the Spearman correlation test. The alpha-type error was set at 5%. The cross-section level significantly influenced the PRPT (P < .05), whereas the PRPT was not influenced by the solution used (P > .05). A significant inverse correlation was found between the cross-section level and the PRPT (P < .05, r = -0.330). The lower the distance to the apex, the higher the PRPT regardless of the solution used. Contrary to the advertised statement, the dental solution with a reduced surface tension did not dissolve vital pulp tissue in oval root canals any better than a conventional NaOCl solution of similar strength. Closer to the apex, pulp tissue dissolution is less efficient irrespective of the solution. Copyright © 2013 American

  20. Ten case history studies of energy efficiency improvements in pulp and paper mills. Final report

    SciTech Connect

    Not Available

    1981-01-01

    The ten technologies chosen for case history development are: sonic sootblowing in boilers, boiler operation on oil-water emulsified fuel, energy efficient motors, computerized control of excess air for boilers, boiler control and load allocation, driving of waste-activated sludge by multiple effect evaporation, pre-drying of hog fuel, lime kiln computerization, heat wheel for process heat recovery, and organic Rankine bottoming cycle for thermomechanical pulping heat recovery. For each case study, there is given: the company name, employee contact, plant summary, a description of the energy consuming process and of the energy-saving action, an assessment of energy savings, and the decision process leading to the adoption of the measure. A data summary for discounted cash flow analysis is tabulated for each case. (LEW)

  1. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  2. Improving rotorcraft survivability to RPG attack using inverse methods

    NASA Astrophysics Data System (ADS)

    Anderson, D.; Thomson, D. G.

    2009-09-01

    This paper presents the results of a preliminary investigation of optimal threat evasion strategies for improving the survivability of rotorcraft under attack by rocket propelled grenades (RPGs). The basis of this approach is the application of inverse simulation techniques pioneered for simulation of aggressive helicopter manoeuvres to the RPG engagement problem. In this research, improvements in survivability are achieved by computing effective evasive manoeuvres. The first step in this process uses the missile approach warning system camera (MAWS) on the aircraft to provide angular information of the threat. Estimates of the RPG trajectory and impact point are then estimated. For the current flight state an appropriate evasion response is selected then realised via inverse simulation of the platform dynamics. Results are presented for several representative engagements showing the efficacy of the approach.

  3. Peripherally administered orexin improves survival of mice with endotoxin shock

    PubMed Central

    Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi

    2016-01-01

    Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin’s direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock. DOI: http://dx.doi.org/10.7554/eLife.21055.001 PMID:28035899

  4. Improving Oral Cancer Survival: The Role of Dental Providers

    PubMed Central

    MESSADI, DIANA V.; WILDER-SMITH, PETRA; WOLINSKY, LAWRENCE

    2010-01-01

    Oral cancer accounts for 2 percent to 4 percent of all cancers diagnosed each year in the United States. In contrast to other cancers, the overall U.S. survival rate from oral cancer has not improved during the past 50 years, mostly due to late-stage diagnosis. Several noninvasive oral cancer detection techniques that emerged in the past decade will be discussed, with a brief overview of most common oral cancer chemopreventive agents. PMID:19998655

  5. Improving survival rates after civilian gunshot wounds to the brain.

    PubMed

    Joseph, Bellal; Aziz, Hassan; Pandit, Viraj; Kulvatunyou, Narong; O'Keeffe, Terence; Wynne, Julie; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2014-01-01

    Gunshot wounds to the brain are the most lethal of all firearm injuries, with reported survival rates of 10% to 15%. The aim of this study was to determine outcomes in patients with gunshot wounds to the brain, presenting to our institution over time. We hypothesized that aggressive management can increase survival and the rate of organ donation in patients with gunshot wounds to the brain. We analyzed all patients with gunshot wounds to the brain presenting to our level 1 trauma center over a 5-year period. Aggressive management was defined as resuscitation with blood products, hyperosmolar therapy, and/or prothrombin complex concentrate (PCC). The primary outcome was survival and the secondary outcome was organ donation. There were 132 patients with gunshot wounds to the brain, and the survival rates increased incrementally every year, from 10% in 2008 to 46% in 2011, with the adoption of aggressive management. Among survivors, 40% (16 of 40) of the patients had bi-hemispheric injuries. Aggressive management with blood products (p = 0.02) and hyperosmolar therapy (p = 0.01) was independently associated with survival. Of the survivors, 20% had a Glasgow Coma Scale score ≥ 13 at hospital discharge. In patients who died (n = 92), 56% patients were eligible for organ donation, and they donated 60 organs. Aggressive management is associated with significant improvement in survival and organ procurement in patients with gunshot wounds to the brain. The bias of resource use can no longer be used to preclude trauma surgeons from abandoning aggressive attempts to save patients with gunshot wound to the brain. Published by Elsevier Inc.

  6. Does radiotherapy or lymphadenectomy improve survival in endometrial stromal sarcoma?

    PubMed

    Barney, Brandon; Tward, Jonathan D; Skidmore, Thomas; Gaffney, David K

    2009-10-01

    Endometrial stromal sarcoma (ESS) is a rare uterine malignancy characterized by cells resembling proliferative-phase endometrial stroma. Standard treatment is total hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). The roles of radiation therapy (RT) and lymphadenectomy (LAD) remain unclear. Using a large population database, we retrospectively evaluated the addition of RT and LAD to surgery for survival impact. We identified 1010 women with ESS between 1983 and 2002 from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Kaplan-Meier method was used to estimate overall survival (OS) and cause-specific survival (CSS). Outcomes for patients treated by TAH-BSO alone and surgery plus RT were compared using Cox proportional hazards regression model. A multivariate analysis controlling for age, International Federation of Gynecology and Obstetrics (FIGO) stage, LAD, race, year of diagnosis, and tumor grade was performed. Univariate analyses were performed for individual FIGO stages, low- and high-grade tumors, and surgery with and without LAD. A literature review was performed to compile studies showing LAD data for ESS. The median follow-up was 54 months (range, 1-248 months). The 5-year OS and CSS for patients undergoing surgery plus RT were 72.2% and 80.1% and 83.2% and 90.7% for surgery alone, respectively. Worse prognoses were associated with increasing FIGO stage, tumor grade, and age. Neither did adjuvant RT correlate with improved survival within any FIGO stage nor did it alter survival for low- or high-grade tumor groups. Adding lymphadenectomy to TAH-BSO did not change survival.

  7. Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

    PubMed Central

    Ayub, Ahmar; Poulose, Ninu; Raju, Raghavan

    2015-01-01

    Resveratrol has been shown to potentiate mitochondrial function and extend longevity; however, there is no evidence to support whether resveratrol can improve survival or prolong life following hemorrhagic shock. We sought to determine whether (a) resveratrol can improve survival following hemorrhage and resuscitation and (b) prolong life in the absence of resuscitation. Using a hemorrhagic injury (HI) model in the rat, we describe for the first time that the naturally occurring small molecule, resveratrol, may be an effective adjunct to resuscitation fluid. In a series of three sets of experiments we show that resveratrol administration during resuscitation improves survival following HI (p < 0.05), resveratrol and its synthetic mimic SRT1720 can significantly prolong life in the absence of resuscitation fluid (<30 min versus up to 4 h; p < 0.05), and resveratrol as well as SRT1720 restores left ventricular function following HI. We also found significant changes in the expression level of mitochondria-related transcription factors Ppar-α and Tfam, as well as Pgc-1α in the left ventricular tissues of rats subjected to HI and treated with resveratrol. The results indicate that resveratrol is a strong candidate adjunct to resuscitation following severe hemorrhage. PMID:25879628

  8. Exposure to sperm competition risk improves survival of virgin males.

    PubMed

    Moatt, Joshua P; Dytham, Calvin; Thom, Michael D F

    2013-04-23

    Sperm competition between the ejaculates of multiple males for the fertilization of a given set of ova is taxonomically widespread. Males have evolved remarkable adaptations to increase their reproductive success under postcopulatory sexual selection, which in many species includes the ability to modify behaviour and ejaculate characteristics plastically to match the perceived level of sperm competition. Males of the model species Drosophila melanogaster increase mating duration and modify seminal fluid composition in response to short-term changes in sperm competition risk. If these responses increase a male's total investment in reproduction, he must either trade-off this cost against other life-history traits or suffer reduced survival. We tested whether mounting a plastic sperm competition response bears an instantaneous survival cost, and instead found that male D. melanogaster exposed to a high risk of sperm competition survive 12 per cent longer than those at low risk, equating to a 49 per cent reduction in the hourly hazard of death. This striking effect was found only among virgins: the high cost of mating in this species eliminates any such benefit among non-virgin males. Our results suggest that the improvement in survival found among virgins may be a product of males' tactical responses to sperm competition.

  9. Microvascular Fragment Transplantation Improves Rat Dorsal Skin Flap Survival

    PubMed Central

    Rathbone, Christopher R.

    2016-01-01

    Background: The development of flap necrosis distally remains a concern during microsurgical flap transfers because, at least in part, of decreased perfusion. Microvascular fragments (MVFs) are microvessels isolated from adipose tissue that are capable of improving tissue perfusion in a variety of tissue defects. The aim of this study was to determine whether the transplantation of MVFs in a dorsal rat skin flap model can improve flap survival. Methods: A 10 × 3 cm flap was raised in a cranial to caudal fashion on the dorsal side of 16 Lewis rats, with the caudal side remaining intact. The rats were equally divided into a treatment group (MVFs) and a control group (sterile saline). At the time of surgery, sterile saline with or without MVFs was injected directly into the flap. Microvessel density was determined after harvesting flap tissue by counting vessels that positively stained for Griffonia simplicifolia lectin I-isolectin B4. Laser Doppler was used to measure blood flow before and after surgery and 7 and 14 days later. Flap survival was evaluated 7 and 14 days after surgery by evaluating the percentage of viable tissue of the flap with photodigital planimetry. Results: Despite the lack of a significant difference in microvessel density and tissue perfusion, flap survival increased 6.4% (P < 0.05) in MVF-treated animals compared with controls. Conclusions: The use of MVFs may be a means to improve flap survival. Future studies are required to delineate mechanisms whereby this occurs and to further optimize their application. PMID:28293502

  10. Oxalic acid pretreatment for mechanical pulping greatly improves paper strength while maintaining scattering power and reducing shives and triglycerides

    Treesearch

    Ross Swaney; Masood Akhtar; Eric Horn; Michael Lentz; John Klungness; Marc Sabourin

    2003-01-01

    In this paper we introduce a new technology based on a mild chemical pretreatment process prior to mechanical pulping. Chips are treated with a dilute solution of oxalic acid (OA) for only 10 minute at 130°C, in a typical example. The properties of the pulp produced by this OA process are quite different from those obtained via conventional chemical pretreatments,...

  11. Lipopolysaccharide stimulation improves the odontoblastic differentiation of human dental pulp cells.

    PubMed

    Huang, Yihua; Jiang, Hongwei; Gong, Qimei; Li, Xuyan; Ling, Junqi

    2015-05-01

    Lipopolysaccharide (LPS) is one of the causative agents of pulpitis and previous studies have demonstrated that the LPS stimulation of human aortic valve interstitial cells induces inflammatory mediators and the gene expression of osteogenic factors. Therefore, in the present study, it was hypothesized that LPS affects the odontoblastic differentiation of human dental pulp cells (hDPCs). In order to investigate this, an in vitro study using hDPCs was performed. Increased alkaline phosphatase (ALP) activity was observed in the hDPCs treated with LPS, which was more marked when the cells were costimulated with odontogenic induction medium (OM). LPS also appeared to increase the gene expression levels of dentin sialophosphoprotein and dentin matrix protein‑1 and the protein expression level of dental sialoprotein in the hDPCs, particularly in combination with OM. In addition, the size and the number of nodules formed in the hDPCs exposed to OM and LPS were increased compared to those stimulated by OM alone. To determine the role of nuclear factor κB (NF‑κB) during the LPS‑induced odontoblastic differentiation of hDPCs, immunofluorescence was performed. The nuclear translocation of NF‑κB, induced by LPS was confirmed, suggesting its involvement in the LPS‑induced increase in odontoblastic differentiation of hDPCs. In conclusion, there may be an association between LPS stimulation, with or without OM, and odontoblastic differentiation.

  12. Biomechanical pulping : a mill-scale evaluation

    Treesearch

    Masood. Akhtar; Gary M. Scott; Ross E. Swaney; Mike J. Lentz; Eric G. Horn; Marguerite S. Sykes; Gary C. Myers

    1999-01-01

    Mechanical pulping process is electrical energy intensive and results in low paper strength. Biomechanical pulping, defined as the fungal treatment of lignocellulosic materials prior to mechanical pulping, has shown at least 30% savings in electrical energy consumption, and significant improvements in paper strength properties compared to the control at a laboratory...

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

    PubMed

    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

  14. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival

    PubMed Central

    2011-01-01

    Background We hypothesized that, in patients with pulmonary fibrosis combined with emphysema, clinical characteristics and outcomes may differ from patients with pulmonary fibrosis without emphysema. We identified 102 patients who met established criteria for pulmonary fibrosis. The amount of emphysema (numerical score) and type of emphysema (centrilobular, paraseptal, or mixed) were characterized in each patient. Clinical characteristics, pulmonary function tests and patient survival were analysed. Results Based on the numerical emphysema score, patients were classified into those having no emphysema (n = 48), trivial emphysema (n = 26) or advanced emphysema (n = 28). Patients with advanced emphysema had a significantly higher amount of smoking in pack/years than patients with no emphysema or trivial emphysema (P < 0.0001). Median survival [1st, 3rd quartiles] of patients with advanced emphysema was 63 [36, 82] months compared to 29 [18, 49] months in patients without emphysema and 32 [19, 48] months in patients with trivial emphysema (P < 0.001). Median forced vital capacity (FVC) and total lung capacity (TLC) were higher in the advanced emphysema group compared to patients with no emphysema (P < 0.01 and P < 0.001, respectively), whereas median DLCO did not differ among groups and was overall low. Within the advanced emphysema group (n = 28), further characterization of the type of emphysema was performed and, within these subgroups of patients, survival was 75 [58, 85] months for patients with centrilobular emphysema, 75 [48, 85] months for patients with mixed centrilobular/paraseptal emphysema, and 24 [22, 35] months for patients with paraseptal emphysema (P < 0.01). Patients with advanced paraseptal emphysema had similar survival times to patients without emphysema. Conclusions Patients with pulmonary fibrosis combined with advanced centrilobular or mixed emphysema have an improved survival compared with patients with pulmonary fibrosis without emphysema

  15. Combining Gene Signatures Improves Prediction of Breast Cancer Survival

    PubMed Central

    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

  16. Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

    PubMed Central

    Lindsay, Robert M.; Cuerden, Meaghan S.; Garg, Amit X.; Port, Friedrich; Austin, Peter C.; Moist, Louise M.; Pierratos, Andreas; Chan, Christopher T.; Zimmerman, Deborah; Lockridge, Robert S.; Couchoud, Cécile; Chazot, Charles; Ofsthun, Norma; Levin, Adeera; Copland, Michael; Courtney, Mark; Steele, Andrew; McFarlane, Philip A.; Geary, Denis F.; Pauly, Robert P.; Komenda, Paul; Suri, Rita S.

    2012-01-01

    Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5–5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34–0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown. PMID:22362910

  17. Synbiotic Amazonian palm berry (açai, Euterpe oleracea Mart.) ice cream improved Lactobacillus rhamnosus GG survival to simulated gastrointestinal stress.

    PubMed

    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 < 0.05). Compared to the fresh culture, fewer morphological changes were observed when the probiotic was added to 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. Has survival following pancreaticoduodenectomy for pancreas adenocarcinoma improved over time?

    PubMed

    Salem, Ahmed I; Alfi, Mina; Winslow, Emily; Cho, Clifford S; Weber, Sharon M

    2015-11-01

    Survival following resection of pancreas cancer is poor. It is uncertain whether outcome improved overtime. Due to the recent advances in surgical techniques, diagnostic evaluation, and systemic treatment, we sought to evaluate pancreas cancer outcome over time. Prospectively collected data on patients who underwent pancreaticoduodenectomy for pathologically confirmed pancreatic adenocarcinoma from 1999 to 2012 were analyzed. Perioperative and long-term outcomes were analyzed, comparing patients from era 1 (1999-2005) to patients from era 2 (2006-2012). Two-hundred sixteen patients were evaluated, including 76 in era 1 and 140 in era 2. There was no difference in 30-day mortality (1.3%, era 1 vs. 1.4%, era 2; P = 0.95) or rates of overall 30-day morbidity (49%, era 1 vs. 62%, era 2; P = 0.06). On multivariable analysis after adjusting for perineural invasion, lymphovascular invasion, margin status, EBL, and venous resection, there was no difference in survival between eras (HR = 0.81, P = 0.27, CI = 0.57-1.16). After adjusting for clinicopathological features, there was no association of improved outcome over time. However, despite an increasing prevalence of anatomically advanced and histologically aggressive tumors, perioperative outcomes such as blood loss and margin negativity improved over time, with no increase in 30-day mortality. © 2015 Wiley Periodicals, Inc.

  19. Significant improvement of survival by intrasplenic hepatocyte transplantation in totally hepatectomized rats.

    PubMed

    Vogels, B A; Maas, M A; Bosma, A; Chamuleau, R A

    1996-01-01

    The effect of intrasplenic hepatocyte transplantation (HTX) was studied in an experimental model of acute liver failure in rats with chronic liver atrophy. Rats underwent a portacaval shunt operation on Day -14 to induce liver atrophy, and underwent total hepatectomy on Day 0 as a start of acute liver failure. Intrasplenic hepatocyte or sham transplantation was performed on Day -7,-3, or -1 (n = 4 to 6 per group). During the period following hepatectomy, mean arterial blood pressure was maintained above 80 mm Hg and hypoglycaemia was prevented. Severity of hepatic encephalopathy was assessed by clinical grading and EEG spectral analysis, together with determination of blood ammonia and plasma amino acid concentrations, and "survival" time. Histological examination of the spleen and lungs was performed after sacrifice. Intrasplenic hepatocyte transplantation resulted in a significant improvement in clinical grading in all transplanted groups (p < 0.05), whereas a significant improvement in EEG left index was seen only in the group with transplantation on Day -1 (p < 0.05). In contrast to hepatocyte transplantation 1 day before total hepatectomy, rats with hepatocyte transplantation 3 and 7 days before total hepatectomy showed a significant 3- and 2-fold increase in "survival" time compared to sham transplanted controls: HTX at Day -1: 7.5 +/- 0.3 h vs. 5.9 +/- 0.6 h (p > 0.05), HTX at Day -3: 19.7 +/- 3.7 h vs. 6.5 +/- 0.3 h (p < 0.05), and HTX at Day -7: 13.8 +/- 3.2 h vs. 6.3 +/- 0.3 h (p < 0.05). Furthermore, rats with hepatocyte transplantation on Day -3 and -7 showed significantly lower blood ammonia concentrations after total hepatectomy (p < 0.0001). Histological examination of the spleens after sacrifice showed clusters of hepatocytes in the red pulp. Hepatocytes present in the spleen for 3 and 7 days showed bile accumulation and spots of beginning necrosis. The present data show that in a hard model of complete liver failure in portacaval shunted rats

  20. Free toe pulp flap for finger pulp and volar defect reconstruction

    PubMed Central

    Balan, Jyoshid R.

    2016-01-01

    Background: Fingertip injury requiring flap cover is very common in the modern era. The ideal cover should fulfill both functional and aesthetic improvement. Materials and Methods: From June 2015 to April 2016, we performed seven free toe pulp flaps for finger defect reconstruction. All patients were males. Five flaps were done in emergency post-traumatic cases, and two were done in elective set up. The cases included reconstruction of three thumbs, one index and one ring finger in an emergency set up and two ring fingers in the elective. Thumb reconstruction was done with great toe lateral pulp and the other digits reconstructed with second toe pulp flap. Follow-up evaluation included both functional and aesthetic assessment. Results: Five flaps survived completely, one suffered partial loss, and one flap failed completely. The median follow-up period was 9 months. The median duration of surgery was 255 min (range 210 to 300 min). The median two-point discrimination was 6.5 mm (range 4–8 mm). There was the return of temperature sensation in all patients; two had cold intolerance. The Semmes-Weinstein monofilament score varied from 3.61 to 5.07 (median filament index value 4.31/pressure value of 2 g/mm2). Three patients had delayed donor site wound healing. Conclusions: The free toe pulp flap is an efficient choice for fingertip and volar finger defects reconstruction with an excellent tissue match. PMID:27833279

  1. A combined acidification/PEO flocculation process to improve the lignin removal from the pre-hydrolysis liquor of kraft-based dissolving pulp production process.

    PubMed

    Shi, Haiqiang; Fatehi, Pedram; Xiao, Huining; Ni, Yonghao

    2011-04-01

    The presence of lignin impairs the utilization of the hemicelluloses dissolved in the pre-hydrolysis liquor (PHL) of the kraft-based dissolving pulp production process. In this paper, a novel process was developed by combining the acidification and poly ethylene oxide (PEO) flocculation concepts to improve the lignin removal. The results showed that the lignin removal was improved by the addition of PEO to the acidified PHL, particularly at a low pH of 1.5. The main mechanisms involved are the lignin/PEO complex formation and the bridging of the formed complexes. This hypothesis was supported by the turbidity, FTIR and particle size measurements. Interestingly, the hemicelluloses removal from the acidification/PEO flocculation was marginal, which would be beneficial for the down-stream ethanol production from the PHL. Additionally, a process flow diagram was proposed that incorporates this new concept into the existing configuration of kraft-based dissolving pulp production process.

  2. Starvation Improves Survival of Bacteria Introduced into Activated Sludge

    PubMed Central

    Watanabe, Kazuya; Miyashita, Mariko; Harayama, Shigeaki

    2000-01-01

    A phenol-degrading bacterium, Ralstonia eutropha E2, was grown in Luria-Bertani (LB) medium or in an inorganic medium (called MP) supplemented with phenol and harvested at the late-exponential-growth phase. Phenol-acclimated activated sludge was inoculated with the E2 cells immediately after harvest or after starvation in MP for 2 or 7 days. The densities of the E2 populations in the activated sludge were then monitored by quantitative PCR. The E2 cells grown on phenol and starved for 2 days (P-2 cells) survived in the activated sludge better than those treated differently: the population density of the P-2 cells 7 days after their inoculation was 50 to 100 times higher than the population density of E2 cells without starvation or that with 7-day starvation. LB medium-grown cells either starved or nonstarved were rapidly eliminated from the sludge. The P-2 cells showed a high cell surface hydrophobicity and retained metabolic activities. Cells otherwise prepared did not have one of these two features. From these observations, it is assumed that hydrophobic cell surface and metabolic activities higher than certain levels were required for the inoculated bacteria to survive in the activated sludge. Reverse transcriptase PCR analyses showed that the P-2 cells initiated the expression of phenol hydroxylase within 1 day of their inoculation into the sludge. These results suggest the utility of a short starvation treatment for improving the efficacy of bioaugumentation. PMID:10966407

  3. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    SciTech Connect

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

    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.

  4. Improved oil-off survivability of tapered roller bearings

    NASA Technical Reports Server (NTRS)

    Kreider, Gary E.; Lee, Peter W.

    1987-01-01

    The aim of this program is to improve the oil-off survivability of a tapered roller bearing when applied to a helicopter transmission, since the tapered bearing has shown a performance advantage in this application. However, the critical roller end-rib conjunction is vulnerable to damage in an oil-off condition. Three powdered metal materials were selected to use as the rib material for oil-off evaluation. These were: M2 steel to a 65% density, CBS 1000M 65% density, and CBS 1000M 75% density. The bearing styles tested were ribbed cone (inner race) and ribbed cup (outer race). Carburized solid CBS 600 was also used as a ribbed material for comparison of oil-off results. The tests were conducted at six speeds from 4000 rpm (0.26 million DN) through 37000 rpm (2.4 million DN).The ribbed cup style bearing achieved longer lives than the ribbed cone style. A standard bearing lasted only 10 minutes at 4000 rpm; however, the 30-min oil-off goal was achieved through 11000 rpm using the survivable ribbed cup bearing. The oil-off lives at 37000 rpm were less than 10 seconds. The grinding of the powder metal materials and surface preparation to achieve an open porosity is extremely critical to the oil-off performance of the powder metal component.

  5. Improving halva quality with dietary fibres of sesame seed coats and date pulp, enriched with emulsifier.

    PubMed

    Elleuch, Mohamed; Bedigian, Dorothea; Maazoun, Bouthaina; Besbes, Souhail; Blecker, Christophe; Attia, Hamadi

    2014-02-15

    Supplementation of halva with waste products of manufacturing, for example defatted sesame seed coats (testae) and date fibre concentrate, can improve its nutritional and organoleptic qualities. These constituents provide high fibre content and technological potential for retaining water and fat. Standard halva supplemented with date fibre concentrate, defatted sesame testae and emulsifier was evaluated for oil separation, texture and colour changes, sensory qualities and acceptability to a taste panel. Addition of both fibres with an emulsifier, improved emulsion stability and increased the hardness of halva significantly. The functional properties of sesame testae and date fibres promote nutrition and health, supplying polyphenol antioxidants and laxative benefits.

  6. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

    PubMed

    Hankey, Kim G; Farese, Ann M; Blaauw, Erica C; Gibbs, Allison M; Smith, Cassandra P; Katz, Barry P; Tong, Yan; Prado, Karl L; MacVittie, Thomas J

    2015-06-01

    Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data

  7. The relative merit of ruminal undegradable protein from soybean meal or soluble fiber from beet pulp to improve nitrogen utilization in dairy cows.

    PubMed

    Borucki Castro, S I; Phillip, L E; Lapierre, H; Jardon, P W; Berthiaume, R

    2008-10-01

    Early lactating dairy cows were used to determine whether the replacement of solvent-extracted soybean meal [SSBM; a source of rumen-degradable protein (RDP)] with expeller soybean meal (ESBM; a source of rumen-undegradable protein), or the replacement of high-moisture shelled corn (HMSC) with beet pulp (a source of soluble fiber) would be effective in improving efficiency of N usage for milk production. The study was designed as a replicated 4 x 4 Latin square with 21-d periods. Eight multiparous Holstein cows were fed, ad libitum, the following diets, which were based on alfalfa silage and HMSC, and formulated to be isocaloric: 1) basal diet without a protein supplement (negative control diet: NC); 2) NC supplemented with solvent-extracted SBM (diet SSBM); 3) NC supplemented with expeller SBM (diet ESBM); 4) SSBM in which unmolassed dried beet pulp replaced half of the HMSC (diet SSBMBP). Compared with diet NC, protein supplementation increased intake of organic matter and dry matter. Milk and milk protein yields were lower with NC but this diet resulted in the greatest efficiency of N usage for milk production (30% milk N/N intake). Supplementation with ESBM, a proven source of RUP, increased plasma concentrations of histidine and branched-chain amino acids, and reduced milk urea N concentration, but failed to improve the yields of milk or milk protein. Milk fat yield tended to decrease with RUP supplementation. Replacing part of HMSC with soluble fiber from beet pulp (SSBMBP) tended to decrease milk production compared with SSBM; the effect was due to a reduction in dry matter intake. There were no differences among diets SSBM, ESBM, or SSBMBP in urinary excretion of purine derivatives. Neither substitution of ESBM for SSBM nor partial replacement of HMSC with beet pulp altered the efficiency of N usage for milk production or manure N excretion.

  8. Improving wet and dry strength properties of recycled old corrugated carton (OCC) pulp using various polymers.

    PubMed

    Hamzeh, Yahya; Sabbaghi, Sanaz; Ashori, Alireza; Abdulkhani, Ali; Soltani, Farshid

    2013-04-15

    In this study, the application of different dosages of low and high molecular weights (MW) of chitosan (Ch), cationic starch (CS) and poly vinyl alcohol (PVA) were systematically investigated using old corrugated carton (OCC) furnishes. Various sequences of above-mentioned polymeric additives were also examined to find out the optimal combination for improving both wet and dry tensile strength. For each treatment, 4 handsheets, each having basis weight of 100 g/m(2), were made. In general, the tensile strength of handsheets was significantly affected by the addition of polymeric agents. The enhancing effect of additives on dry tensile property was much higher than wet condition. The results also showed that the tensile strength of the samples made from OCC furnishes were improved upon the addition of high molecular weight chitosan (ChI) compared to the untreated ones (control). The low MW chitosan did not change the properties of handsheets dramatically. Application of polymeric agents moderately decreased the stretch to rupture, however with increasing dosage the stretch was improved. Sequential addition of used polymers showed that triple application of polymers was beneficial to both dry and wet tensile strength, although the effect was larger for dry. The best results in wet and dry tensile strengths were achieved using sequential of PVA-ChI-CS. Sequential addition of oppositely charged polymers forms a macromolecular layered structure of polyelectrolytes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Improvement of growth and nitrogen utilization in sheep using sugar beet pulp treated with Trichoderma reesei or urea.

    PubMed

    Okab, Aly B; Ayoub, Mostafa A; Samara, Emad M; Abdoun, Khalid A; Al-Haidary, Ahmed A; Koriem, Ahmed A; Hassan, Ayman A

    2012-10-01

    Twenty-five intact Barki lambs with mean body weight of 24.81 ± 0.16 kg were used to investigate the effect of including in the diet sugar beet pulp (SBP) treated biologically with Trichoderma reesei or chemically with urea 4 % on nutrients digestibility, growth performance, nitrogen (N) utilization, and hematological and biochemical parameters. Two experiments were conducted. In the growth experiment, five lambs were randomly assigned to one of five dietary treatments. Lambs were offered isonitrogenous and isoenergetic concentrate feed mixture containing on dry matter basis 0 % SBP (D0), 50 % SBP (D1), 50 % SBP treated with 4 % urea (D2), 50 % SBP treated with T. reesei (D3), and 25 % SPB treated with 4 % urea plus 25 % SPB treated with T. reesei (D4). In the metabolism experiment, five rams were used in a 5 × 5 Latin square design and housed in metabolism crates for 21 days. The present study showed that inclusion of SBP at the level of 50 % (D1) negatively affected diet digestibility coefficients of crude protein, crude fiber, and ether extract, in addition to average daily gain, feed conversion, and N utilization. However, treatment of SBP with urea (D2), T. reesei (D3), or the combination (D4) of both had improved (P < 0.05) these parameters with superiority of D3. Despite the significant differences in the tested hematological and biochemical parameters of lambs fed on biologically or chemically treated SBP diets, their levels remained within the physiological ranges which could indicate that treated SBP did not have any adverse effect on lambs' health.

  10. Citrus pulp for cattle.

    PubMed

    Arthington, John D; Kunkle, William E; Martin, Amy M

    2002-07-01

    Citrus pulp is classified as an energy concentrate by-product feed. Citrus by-products fed to beef cattle include citrus molasses, citrus meal, wet citrus pulp, dried citrus pulp, and pelleted citrus pulp; however, in current production systems, pulp (wet, dry, and pelleted) is the only by-product commonly used. Citrus pulp production in the United States is limited to specific subtropical regions, of which south central Florida remains the largest with additional production in California and Texas.

  11. Developing a rat model of dilated cardiomyopathy with improved survival* #

    PubMed Central

    Shen, Li-juan; Lu, Shu; Zhou, Yong-hua; Li, Lan; Xing, Qing-min; Xu, Yong-liang

    2016-01-01

    To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and 18F-fluoro-deoxyglucose-positron emission tomography (18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate. PMID:27921402

  12. Pulp Regeneration: Current Approaches and Future Challenges

    PubMed Central

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), stem cell factor (SCF), and Granulocyte Colony-Stimulating Factor (G-CSF) were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration. PMID:27014076

  13. Pulp Regeneration: Current Approaches and Future Challenges.

    PubMed

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), stem cell factor (SCF), and Granulocyte Colony-Stimulating Factor (G-CSF) were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration.

  14. [Pulp treatment of young permanent teeth after traumatic dental injury].

    PubMed

    Qin, Man

    2009-06-01

    Dental trauma could be largely classified into three groups: Hard tissue injuries, pulp injuries and periodontal tissue injuries. Since pulp injuries are reported in tooth fracture, displacement and avulsion, it is commonly thought that pulp injuries were involved in almost every type of dental injuries. The sequelae of pulp tissue after dental injuries include pulp survival, pulp calcification and pulp necrosis. Dental trauma mostly occurs in 7-15 year-old children. The treatment and prognosis of dental trauma in children are more complicated than those in adults because of the developmental nature of the young permanent teeth. The evaluation of pulp damage and treatment after dental injuries in growing young permanent teeth are discussed in this paper.

  15. Private Payer's Status Improves Male Breast Cancer Survival.

    PubMed

    Shi, Runhua; Taylor, Hannah; Liu, Lihong; Mills, Glenn; Burton, Gary

    2016-01-01

    Survival from male breast cancer is influenced by many factors. This study assessed payer's status effect on survival of male breast cancer patients. This study included 8,828 male breast cancer patients diagnosed between 1998-2006 and followed to 2011 in the National Cancer Data Base. Cox regression was used to investigate the effect of payer's status and other factors on overall survival. Patients had 36.2%, 42.7%, 14.7%, and 6.5% of stage I to IV cancer, respectively. Payer status was private 47.7%, Medicare 42.6%, Medicaid 3.24%, unknown 3.59%, and uninsured 2.95%. Median overall survival (MOS) for all patients was 10.6 years. In multivariate analysis, Direct adjusted MOS was 12.46, 11.89, 9.99, 9.02, and 8.29 years for private, "unknown," Medicare, uninsured, and Medicaid payer's status, respectively. Patients with private and "unknown" payer's status showed a significant difference in survival compared to uninsured patients, while Medicaid and Medicare patients did not. Age, race, stage, grade, income, comorbidity, distance travelled, and diagnosing/treating facility were also significant predictors of survival. Treatment delay and cancer program did not have a significant influence on survival. © 2015 Wiley Periodicals, Inc.

  16. Timber Bamboo Pulp

    Treesearch

    Troy Runge; Carl Houtman; Alberto Negri; Jackie Heinricher

    2013-01-01

    Fast-growing biomass, such as bamboo, has the potential to serve an important future role in the pulp and paper industry with potential to both lower resource costs and improve a product’s sustainability. Moso bamboo is particularly interesting due to its fast growth and size, which allows it to be handled and chipped similarly to wood resources. In this study, we will...

  17. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Cancer.gov

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  18. Method of freezing living cells and tissues with improved subsequent survival

    DOEpatents

    Senkan, Selim M.; Hirsch, Gerald P.

    1980-01-01

    This invention relates to an improved method for freezing red blood cells, ther living cells, or tissues with improved subsequent survival, wherein constant-volume freezing is utilized that results in significantly improved survival compared with constant-pressure freezing; optimization is attainable through the use of different vessel geometries, cooling baths and warming baths, and sample concentrations.

  19. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  20. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  1. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  2. Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

    PubMed Central

    Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

    2014-01-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

  3. Caloric restriction improves health and survival of rhesus monkeys.

    PubMed

    Mattison, Julie A; Colman, Ricki J; Beasley, T Mark; Allison, David B; Kemnitz, Joseph W; Roth, George S; Ingram, Donald K; Weindruch, Richard; de Cabo, Rafael; Anderson, Rozalyn M

    2017-01-17

    Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

  4. Caloric restriction improves health and survival of rhesus monkeys

    PubMed Central

    Mattison, Julie A.; Colman, Ricki J.; Beasley, T. Mark; Allison, David B.; Kemnitz, Joseph W.; Roth, George S.; Ingram, Donald K.; Weindruch, Richard; de Cabo, Rafael; Anderson, Rozalyn M.

    2017-01-01

    Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health. PMID:28094793

  5. Opportunities to improve energy efficiency and reduce greenhouse gas emissions in the US pulp and paper industry

    SciTech Connect

    Martin, Nathan; Anglani, N.; Einstein, D.; Khrushch, M.; Worrell, E.; Price, L.K.

    2000-07-01

    The pulp and paper industry accounts for over 12% of total manufacturing energy use in the US (US EIA 1997a), contributing 9% to total manufacturing carbon dioxide emissions. In the last twenty-five years primary energy intensity in the pulp and paper industry has declined by an average of 1% per year. However, opportunities still exist to reduce energy use and greenhouse gas emissions in the manufacture of paper in the US This report analyzes the pulp and paper industry (Standard Industrial Code (SIC) 26) and includes a detailed description of the processes involved in the production of paper, providing typical energy use in each process step. We identify over 45 commercially available state-of-the-art technologies and measures to reduce energy use and calculate potential energy savings and carbon dioxide emissions reductions. Given the importance of paper recycling, our analysis examines two cases. Case A identifies potential primary energy savings without accounting for an increase in recycling, while Case B includes increasing paper recycling. In Case B the production volume of pulp is reduced to account for additional pulp recovered from recycling. We use a discount rate of 30% throughout our analysis to reflect the investment decisions taken in a business context. Our Case A results indicate that a total technical potential primary energy savings of 31% (1013 PJ) exists. For case A we identified a cost-effective savings potential of 16% (533 PJ). Carbon dioxide emission reductions from the energy savings in Case A are 25% (7.6 MtC) and 14% (4.4 MtC) for technical and cost-effective potential, respectively. When recycling is included in Case B, overall technical potential energy savings increase to 37% (1215 PJ) while cost-effective energy savings potential is 16%. Increasing paper recycling to high levels (Case B) is nearly cost-effective assuming a cut-off for cost-effectiveness of a simple payback period of 3 years. If this measure is included, then the

  6. Opportunities to improve energy efficiency and reduce greenhouse gas emissions in the U.S. pulp and paper industry

    SciTech Connect

    Martin, Nathan; Anglani, N.; Einstein, D.; Khrushch, M.; Worrell, E.; Price, L.K.

    2000-07-01

    The pulp and paper industry accounts for over 12% of total manufacturing energy use in the U.S. (U.S. EIA 1997a), contributing 9% to total manufacturing carbon dioxide emissions. In the last twenty-five years primary energy intensity in the pulp and paper industry has declined by an average of 1% per year. However, opportunities still exist to reduce energy use and greenhouse gas emissions in the manufacture of paper in the U.S. This report analyzes the pulp and paper industry (Standard Industrial Code (SIC) 26) and includes a detailed description of the processes involved in the production of paper, providing typical energy use in each process step. We identify over 45 commercially available state-of-the-art technologies and measures to reduce energy use and calculate potential energy savings and carbon dioxide emissions reductions. Given the importance of paper recycling, our analysis examines two cases. Case A identifies potential primary energy savings without accounting for an increase in recycling, while Case B includes increasing paper recycling. In Case B the production volume of pulp is reduced to account for additional pulp recovered from recycling. We use a discount rate of 30% throughout our analysis to reflect the investment decisions taken in a business context. Our Case A results indicate that a total technical potential primary energy savings of 31% (1013 PJ) exists. For case A we identified a cost-effective savings potential of 16% (533 PJ). Carbon dioxide emission reductions from the energy savings in Case A are 25% (7.6 MtC) and 14% (4.4 MtC) for technical and cost-effective potential, respectively. When recycling is included in Case B, overall technical potential energy savings increase to 37% (1215 PJ) while cost-effective energy savings potential is 16%. Increasing paper recycling to high levels (Case B) is nearly cost-effective assuming a cut-off for cost-effectiveness of a simple payback period of 3 years. If this measure is included, then

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

    DTIC Science & Technology

    2011-10-01

    Award Number: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Gregory...SUBTITLE 5a. CONTRACT NUMBER Hibernation -Based Therapy to Improve Survival of Severe Blood Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM...death. The overall strategy is to use strategies learned from study of hibernating mammals to survive a potentially life-threatening blood loss and allow

  8. Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury PRINCIPAL...Aug 2015 - 14 Aug 2016 4. TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After... respiratory complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing

  9. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    PubMed Central

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

  10. Summer Fallowinng Improves Survival and Growth of Cottonwood on Old Fields

    Treesearch

    James B. Baker; B. G. Blackmon

    1973-01-01

    Fallowing an old-field site during the summer prior to planting and applying a herbicide in September improved survival and growth of eastern cottonwood cuttings. Summer fallowing without applying herbicide also improved height growth of cottonwood through age 2. Deep plowing and cover cropping, alone or in combination, did not influence growth or survival during the...

  11. Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

    PubMed Central

    Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

    2015-01-01

    Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

  12. Metallic ions catalysis for improving bioleaching yield of Zn and Mn from spent Zn-Mn batteries at high pulp density of 10.

    PubMed

    Niu, Zhirui; Huang, Qifei; Wang, Jia; Yang, Yiran; Xin, Baoping; Chen, Shi

    2015-11-15

    Bioleaching of spent batteries was often conducted at pulp density of 1.0% or lower. In this work, metallic ions catalytic bioleaching was used for release Zn and Mn from spent ZMBs at 10% of pulp density. The results showed only Cu(2+) improved mobilization of Zn and Mn from the spent batteries among tested four metallic ions. When Cu(2+) content increased from 0 to 0.8 g/L, the maximum release efficiency elevated from 47.7% to 62.5% for Zn and from 30.9% to 62.4% for Mn, respectively. The Cu(2+) catalysis boosted bioleaching of resistant hetaerolite through forming a possible intermediate CuMn2O4 which was subject to be attacked by Fe(3+) based on a cycle of Fe(3+)/Fe(2+). However, poor growth of cells, formation of KFe3(SO4)2(OH)6 and its possible blockage between cells and energy matters destroyed the cycle of Fe(3+)/Fe(2+), stopping bioleaching of hetaerolite. The chemical reaction controlled model fitted best for describing Cu(2+) catalytic bioleaching of spent ZMBs. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Biological bleaching of chemical pulps.

    PubMed

    Bajpai, Pratima

    2004-01-01

    Use of biotechnology in pulp bleaching has attracted considerable attention and achieved interesting results in recent years. Enzymes of the hemicellulolytic type, particularly xylan-attacking enzymes, xylanases are now used commercially in the mills for pulp treatment and subsequent incorporation into bleach sequences. The aims of the enzymatic treatment depend on the actual mill conditions and may be related to environmental demands, reduction of chemical costs or maintenance or even improvement of product quality. The use of oxidative enzymes from white-rot fungi, that can directly attack lignin, is a second-generation approach, which could produce larger chemical savings than xylanase but has not yet been developed to the full scale. It is being studied in several laboratories in Canada, Japan, the U.S.A. and Europe. Certain white-rot fungi can delignify kraft pulps increasing their brightness and their responsiveness to brightening with chemicals. The fungal treatments are too slow but the enzyme manganese peroxidase and laccase can also delignify pulps and enzymatic processes are likely to be easier to optimize and apply than the fungal treatments. Development work on laccase and manganese peroxidase continues. This article presents an overview of developments in the application of hemicellulase enzymes, lignin-oxidizing enzymes and white-rot fungi in bleaching of chemical pulps. The basic enzymology involved and the present knowledge of the mechanisms of the action of enzymes as well as the practical results and advantages obtained on the laboratory and industrial scale are discussed.

  14. Methanol-reinforced kraft pulping

    SciTech Connect

    Norman, E.; Olm, L.; Teder, A. )

    1993-03-01

    The addition of methanol to a high-sulfidity kraft cook on Scandinavian softwood chips was studied under different process conditions. Delignification and the degradation of carbohydrates were accelerated, but the effect on delignification was greater. Thus, methanol addition improved selectivity. The positive effect of methanol could also be observed for modified kraft cooks having a leveled out alkali concentration and lower concentration of sodium ions and dissolved lignin at the end of the cook. Methanol addition had no discernible effect on pulp strength or on pulp bleachability.

  15. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.

  16. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival: a response.

    PubMed

    Cottin, Vincent; Cordier, Jean-François; Wells, Athol U

    2011-07-25

    Better survival in combined pulmonary fibrosis and emphysema than in lone pulmonary fibrosis: bias or reality? A response to Centrilobular emphysema combined with pulmonary fibrosis results in improved survival by Todd et al., Fibrogenesis & Tissue Repair 2011, 4:6.Please see related letter http://fibrogenesis.com/content/4/1/17.

  17. Improving village poultry's survival rate through community-based poultry health management: evidence from Benin.

    PubMed

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

    2013-01-01

    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 of technologies--poultry vaccination, construction of henhouses, and improved feed--disseminated through the CBM also significantly improves the survival rate. The access to markets for inputs and veterinary services is also important in improving the survival rate of poultry. Finally, the study suggests that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry improvement technologies.

  18. Genetic improvement of laying hens viability using survival analysis

    PubMed Central

    Ducrocq, Vincent; Besbes, Badi; Protais, Michel

    2000-01-01

    The survival of about eight generations of a large strain of laying hens was analysed separating the rearing period (RP) from the production period (PP), after hens were housed. For RP (respectively PP), 97.8% (resp., 94.1% ) of the 109 160 (resp., 100 665) female records were censored after 106 days (resp., 313 days) on the average. A Cox proportional hazards model stratified by flock (= season) and including a hatch-within-flock (HWF) fixed effect seemed to reasonably fit the RP data. For PP, this model could be further simplified to a non-stratified Weibull model. The extension of these models to sire-dam frailty (mixed) models permitted the estimation of the sire genetic variances at 0.261 ± 0.026 and 0.088 ± 0.010 for RP and PP, respectively. Heritabilities on the log scale were equal to 0.48 and 0.19. Non-additive genetic effects could not be detected. Selection was simulated by evaluating all sires and dams, after excluding all records from the last generation. Then, actual parents of this last generation were distributed into four groups according to their own pedigree index. Raw survivor curves of the progeny of extreme parental groups substantially differed (e.g., by 1.7% at 300 days for PP), suggesting that selection based on solutions from the frailty models could be efficient, despite the very large proportion of censored records. PMID:14736405

  19. Improved survival of newborns receiving leukocyte transfusions for sepsis

    SciTech Connect

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

    1984-11-01

    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.

  20. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    PubMed Central

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-01-01

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  1. Low protein diets improve survival from peritonitis in guinea pigs.

    PubMed Central

    Peck, M D; Alexander, J W; Gonce, S J; Miskell, P W

    1989-01-01

    Enteral diets with different protein content were tested to determine their effect on outcome in a model of protracted bacterial peritonitis. Hartley guinea pigs were provided with gastrostomies, and 1 week later, osmotic pumps were implanted into the peritoneal cavity to allow for continuous release of live bacteria over the course of 1 week. Three days after pump implantation, the animals began receiving isocaloric enteral diets that contained 5%, 10%, 15%, or 20% of total calories as protein. After 2 weeks of observation, the survivors were killed. All animals lost weight during the 2-weeks period, but there was no difference in weight lost. Nitrogen balance correlated with dietary protein. The mortality rate was significantly higher in the groups that received 15% and 20% of total calories compared with the group that received 5% (p less than 0.05). Although dietary protein in the 5% group was insufficient for meeting the nutritional needs of the animal, survival was best in this group. Possible explanations are that protein restriction in this model may either augment host defence or impair bacterial virulence. PMID:2494959

  2. Thermo-mechanical processing of sugar beet pulp. III. Study of extruded films improvement with various plasticizers and cross-linkers.

    PubMed

    Rouilly, A; Geneau-Sbartaï, C; Rigal, L

    2009-06-01

    Thermoplastic sugar beet pulp (thermo-mechanical processing was discussed in previous studies) was formed into film strips by extrusion. Film tensile properties are discussed according to the molecular structure of external plasticizer. Sorbitol, fructose and adipic acid have a marked antiplasticizing effect, while urea and xylitol gave higher ultimate tensile stress than glycerol for a comparable strain at break. Xylitol can be considered as the best plasticizer with UTS and EL of, respectively, 4.9 MPa and 11.3% and water absorption (85% RH, 25 degrees C) was less than 25%. Glycidyl methacrylate was directly used in the extrusion process as cross-linker. In high humidity atmosphere (97% RH, 25 degrees C), film water absorption was then kept under 40% while tensile strength and strain were improved of 50% and with a 30 min UV post-treatment the mass gain in absorption was even less than 30% after 5 days.

  3. The Impact of Improved Population Life Expectancy in Survival Trend Analyses of Specific Diseases.

    PubMed

    van Walraven, Carl

    2016-08-01

    Survival trend analyses examine mortality outcomes over time. The impact of conducting survival trend analyses without accounting for improved population survival has not been systematically studied. The 1-year risk of death in the 100 most common hospital admissions for Ontario adults in 1994, 1999, 2004, and 2009 was determined. Generalized linear models were used to determine if adjusted death risk changed significantly over time with and without accounting for population survival. The statistical significance of temporal trends in survival changed after accounting for population life expectancy in 16 diagnoses (16 percent) (in 13 of 55 diagnoses, statistically significant decreasing mortality trends became insignificant; in 3 of 15 diagnoses, insignificant trends changed to a significant increase in mortality risk over time). These results highlight the importance of accounting for population life-expectancy changes in survival trend analyses. © Health Research and Educational Trust.

  4. Improving the Survivability of a Stochastic Communication Network

    DTIC Science & Technology

    1988-12-01

    algorithm is called a labelling algorithm, and it has been the basis for other researchers, such as Edmonds and Karp [15], for developing a more...15. Edmonds, J. and R. M. Karp . "Theoretical Improvements in Logorithmic Effi- ciency for Network Flow Problems," Jour. A CM, 19: 248-264 (April, 1972...Conference Proceedings, 41: 49-54 (1972). 19. Hillier, Frederick S. and Gerald J. Lievernan. Introduction to Opt rafio., R(- search (Fourth Edition). Oakland

  5. Application of Artificial Intelligence to Improve Aircraft Survivability.

    DTIC Science & Technology

    1985-12-01

    AD-A164 172 APPLICATION OF ARTIFICIAL INTELLIGENCE TO IMPROVE 1/1 AIRCRAFT SURVASRILITY(U) NAVAL POSTGRADUATE SCHOOL UNCR7SIFEDMONTEREY CA N L DECKER...4 5- * . . . . . . 5~5~ * . . - -- &:~~-::-~&~ S.- ~ ~ S. . ~ ~.’ ~ VV ~ NAVAL POSTGRADUATE SCHOOL Monterey, California DTIC FEB 1406 D4 THESIS... School 6 7 Naval Postgraduate School 6C ADDRESS (City, State. and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Monterey, California 93943-5100

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

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation-Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Greg Beilman...Hibernation-Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...political conflict. The injuries sustained are often accompanied by severe blood loss , and shock from this blood loss is the most common cause of

  7. Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.

    PubMed

    Koskivuo, I; Vihinen, P; Mäki, M; Talve, L; Vahlberg, T; Suominen, E

    2017-03-01

    Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.

  8. Does removal of the original pulp tissue before autotransplantation influence ingrowth of new tissue in the pulp chamber?

    PubMed

    Laureys, Wim G M; Dermaut, Luc R; Cuvelier, Claude A; De Pauw, Guy A M

    2010-10-01

    In an attempt to extend the indication area for autotransplantation of vital teeth, two possibilities can be proposed: (i) The enlargement of the apical foramen, with the aim to facilitate revascularization and ingrowth of new tissue. The ingrowth of tissue will eliminate the need for endodontic treatment when mature teeth are transplanted and (ii) the cryopreservation of teeth in case they cannot be transplanted immediately to the receptor site. Teeth with an ideal stage of root formation can be cryopreserved to perform transplantation later. Although pulpcell cultures survive crypreservation in vitro, the pulp tissue cannot survive the cryopreservation procedures when it is kept inside the pulpchamber. Therefore, the pulp tissue has to be removed before cryopreservation. It has been demonstrated that revascularization and ingrowth of new tissue can occur in an empty pulp chamber (1). The aim of this study was to find out if revascularization and ingrowth of new pulp tissue is influenced by removal of the original pulp tissue before autotransplantation. Twenty nine single-rooted teeth from three adult beagle dogs were transplanted after resection of the root tip. One group of teeth (n = 14) had the pulp tissue removed before transplantation. The other group (n = 15) had the original pulp left in situ. The transplanted teeth were histologically analysed 90 days post-transplantation. In the group with the tissue left in situ, 12 teeth (80%) showed a pulp chamber totally filled or at least 1/3 to 2/3 filled with viable tissue. In the group with the pulp tissue removed, 11 teeth (79%) had no or little vital tissue in the pulp chamber. The necrotic masses that develop in the original pulp tissue immediately after transplantation are a possible stimulating factor in the repair process of the pulp. As a conclusion, it can be stated that in case of autotransplantation of teeth, it is advisable to leave the pulp tissue in situ to stimulate the revascularization and

  9. Pulp and paper program fact sheets

    SciTech Connect

    1995-07-01

    Summaries are presented of Argonne technology transfer research projects in: sustainable forest management, environmental performance, energy performance, improved capital effectiveness, recycling, and sensors and controls. Applications in paper/pulp industry, other industries, etc. are covered.

  10. Improved Survival with the Patients with Variceal Bleed

    PubMed Central

    Sharma, Praveen; Sarin, Shiv K.

    2011-01-01

    Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB) and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin) and endoscopic variceal ligation has become the first line treatment in the management of AVB. Short-term antibiotic prophylaxis, early use of lactulose for prevention of hepatic encephalopathy, application of early transjugular intrahepatic portasystemic shunts (TIPS), fully covered self-expandable metallic stent in patients for AVB may be useful in those cases where balloon tamponade is considered. Early and wide availability of liver transplantation has changed the armamentarium of the clinician for patients with AVB. High hepatic venous pressure gradient (HVPG) >20 mmHg in AVB has become a useful predictor of outcomes and more aggressive therapies with early TIPS based on HVPG measurement may be the treatment of choice to reduce mortality further. PMID:21994853

  11. Improved survival with the patients with variceal bleed.

    PubMed

    Sharma, Praveen; Sarin, Shiv K

    2011-01-01

    Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB) and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin) and endoscopic variceal ligation has become the first line treatment in the management of AVB. Short-term antibiotic prophylaxis, early use of lactulose for prevention of hepatic encephalopathy, application of early transjugular intrahepatic portasystemic shunts (TIPS), fully covered self-expandable metallic stent in patients for AVB may be useful in those cases where balloon tamponade is considered. Early and wide availability of liver transplantation has changed the armamentarium of the clinician for patients with AVB. High hepatic venous pressure gradient (HVPG) >20 mmHg in AVB has become a useful predictor of outcomes and more aggressive therapies with early TIPS based on HVPG measurement may be the treatment of choice to reduce mortality further.

  12. Improved Survival Among Children with Spina Bifida in the United States

    PubMed Central

    Shin, Mikyong; Kucik, James E.; Siffel, Csaba; Lu, Chengxing; Shaw, Gary M.; Canfield, Mark A.; Correa, Adolfo

    2015-01-01

    Objective To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. Study design A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. Results During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. Conclusions The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival. PMID:22727874

  13. Combination of soya pulp and Bacillus coagulans lilac-01 improves intestinal bile acid metabolism without impairing the effects of prebiotics in rats fed a cholic acid-supplemented diet.

    PubMed

    Lee, Yeonmi; Yoshitsugu, Reika; Kikuchi, Keidai; Joe, Ga-Hyun; Tsuji, Misaki; Nose, Takuma; Shimizu, Hidehisa; Hara, Hiroshi; Minamida, Kimiko; Miwa, Kazunori; Ishizuka, Satoshi

    2016-08-01

    Intestinal bacteria are involved in bile acid (BA) deconjugation and/or dehydroxylation and are responsible for the production of secondary BA. However, an increase in the production of secondary BA modulates the intestinal microbiota due to the bactericidal effects and promotes cancer risk in the liver and colon. The ingestion of Bacillus coagulans improves constipation via the activation of bowel movement to promote defaecation in humans, which may alter BA metabolism in the intestinal contents. BA secretion is promoted with high-fat diet consumption, and the ratio of cholic acid (CA):chenodeoxycholic acid in primary BA increases with ageing. The dietary supplementation of CA mimics the BA environment in diet-induced obesity and ageing. We investigated whether B. coagulans lilac-01 and soya pulp influence both BA metabolism and the maintenance of host health in CA-supplemented diet-fed rats. In CA-fed rats, soya pulp significantly increased the production of secondary BA such as deoxycholic acid and ω-muricholic acids, and soya pulp ingestion alleviated problems related to plasma adiponectin and gut permeability in rats fed the CA diet. The combination of B. coagulans and soya pulp successfully suppressed the increased production of secondary BA in CA-fed rats compared with soya pulp itself, without impairing the beneficial effects of soya pulp ingestion. In conclusion, it is possible that a combination of prebiotics and probiotics can be used to avoid an unnecessary increase in the production of secondary BA in the large intestine without impairing the beneficial functions of prebiotics.

  14. Lack of improvement in survival rates for women under 50 with endometrial cancer, 2000-2011.

    PubMed

    Rodriguez, Ana M; Schmeler, Kathleen M; Kuo, Yong-Fang

    2016-04-01

    To assess how first course of treatment affects cancer-specific survival in women diagnosed with endometrial cancer younger than 50 years old. Public-use data from the Surveillance, Epidemiology, and End Results program were used. The study included 82,721 women diagnosed with primary, invasive endometrial cancer between 2000 and 2011. We assessed type of treatment using Cox's proportional hazards models to determine survival disparity by age and stage. Cancer-specific survival significantly improved for those aged ≥50 years with late stage, but did not improve for those <50. First course of treatment significantly affected cancer-specific survival for endometrial cancer patients. Regardless of age, survival was greatly improved for late-stage patients who received a combination of surgery and radiation [hazard ratio (HR) 0.62 [95 % confidence interval (CI) 0.47-0.78] and 0.64 (95 % CI 0.59-0.68)] compared to those who received total hysterectomy with removal of ovaries and tubes. However, the proportion of patients who received combination therapy decreased over time. The magnitude of decrease was larger in patients <50 than in those aged ≥50. Overall, about 24-57 % of the difference in cancer-specific survival over time in patients aged <50 was explained by their initial treatment. Improvement in cancer-specific survival was only seen in older women with late-stage diagnosis. Despite improvements in diagnoses and treatments, the difference in age-specific survival indicates that more should be done to understand why these rates are not improving for those younger than 50 years old.

  15. Probabilistic mortality forecasting with varying age-specific survival improvements.

    PubMed

    Bohk-Ewald, Christina; Rau, Roland

    2017-01-01

    Many mortality forecasting approaches extrapolate past trends. Their predictions of the future development can be quite precise as long as turning points and/or age-shifts of mortality decline are not present. To account even for such mortality dynamics, we propose a model that combines recently developed ideas in a single framework. It (1) uses rates of mortality improvement to model the aging of mortality decline, and it (2) optionally combines the mortality trends of multiple countries to catch anticipated turning points. We use simulation-based Bayesian inference to estimate and run this model that also provides prediction intervals to quantify forecast uncertainty. Validating mortality forecasts for British and Danish women from 1991 to 2011 suggest that our model can forecast regular and irregular mortality developments and that it can perform at least as well as other widely accepted approaches like, for instance, the Lee-Carter model or the UN Bayesian approach. Moreover, prospective mortality forecasts from 2012 to 2050 suggest gradual increases for British and Danish life expectancy at birth.

  16. SRT1720 improves survival and healthspan of obese mice

    PubMed Central

    Minor, Robin K.; Baur, Joseph A.; Gomes, Ana P.; Ward, Theresa M.; Csiszar, Anna; Mercken, Evi M.; Abdelmohsen, Kotb; Shin, Yu-Kyong; Canto, Carles; Scheibye-Knudsen, Morten; Krawczyk, Melissa; Irusta, Pablo M.; Martín-Montalvo, Alejandro; Hubbard, Basil P.; Zhang, Yongqing; Lehrmann, Elin; White, Alexa A.; Price, Nathan L.; Swindell, William R.; Pearson, Kevin J.; Becker, Kevin G.; Bohr, Vilhelm A.; Gorospe, Myriam; Egan, Josephine M.; Talan, Mark I.; Auwerx, Johan; Westphal, Christoph H.; Ellis, James L.; Ungvari, Zoltan; Vlasuk, George P.; Elliott, Peter J.; Sinclair, David A.; de Cabo, Rafael

    2011-01-01

    Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals. PMID:22355589

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

    PubMed

    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.

  18. Improved survival using oxygen free radical scavengers in the presence of ischemic bowel anastomosis.

    PubMed

    Bergren, C T; Bodzin, J H; Cortez, J A

    1988-06-01

    A rat model was developed to determine the efficacy of oxygen free radical scavenger compounds in improving small bowel anastomotic healing in ischemia. 50 Sprague-Dawley rats underwent laparotomy and were divided into groups: I. sham operation; II. ischemia produced by ligation of mesenteric vessels along 3-5 cm of bowel; III. bowel transection and anastomosis; IV. ligation of vessels with bowel transection and anastomosis; V. ligation of vessels, bowel transection and IV administration of superoxide dismutase (SOD) (5000 U/kg) prior to anastomosis. All surviving animals were sacrificed after 2 weeks. Anastomotic tensile strength and histology were evaluated. Percent survival and the average length of survival for all groups is seen in the table below. (table: see text) A significant decrease in survival was present with the anastomotic group and the ischemic anastomotic group when compared with controls. An improved survival similar to ischemia alone was present in SOD group. No significant difference was noted between SOD and control groups. The results of this study indicate an improved survival rate and length of survival similar to controls in animals undergoing ischemic and penetrating injury to the bowel with the use of oxygen free radical scavenger compounds prior to anastomosis.

  19. Halofuginone improves muscle-cell survival in muscular dystrophies.

    PubMed

    Bodanovsky, Anna; Guttman, Noga; Barzilai-Tutsch, Hila; Genin, Ola; Levy, Oshrat; Pines, Mark; Halevy, Orna

    2014-07-01

    Halofuginone has been shown to prevent fibrosis via the transforming growth factor-β/Smad3 pathway in muscular dystrophies. We hypothesized that halofuginone would reduce apoptosis--the presumed cause of satellite-cell depletion during muscle degradation-in the mdx mouse model of Duchenne muscular dystrophy. Six-week-old mdx mouse diaphragm exhibited fourfold higher numbers of apoptotic nuclei compared with wild-type mice as determined by a TUNEL assay. Apoptotic nuclei were found in macrophages and in Pax7-expressing cells; some were located in centrally-nucleated regenerating myofibers. Halofuginone treatment of mdx mice reduced the apoptotic nuclei number in the diaphragm, together with reduction in Bax and induction in Bcl2 levels in myofibers isolated from these mice. A similar effect was observed when halofuginone was added to cultured myofibers. No apparent effect of halofuginone was observed in wild-type mice. Inhibition of apoptosis or staurosporine-induced apoptosis by halofuginone in mdx primary myoblasts and C2 myogenic cell line, respectively, was reflected by less pyknotic/apoptotic cells and reduced Bax expression. This reduction was reversed by a phosphinositide-3-kinase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase inhibitors, suggesting involvement of these pathways in mediating halofuginone's effects on apoptosis. Halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The data suggest an additional mechanism by which halofuginone improves muscle pathology and function in muscular dystrophies.

  20. Biomechanical pulping: A mill-scale evaluation

    SciTech Connect

    Akhtar, M.; Scott, G.M.; Swaney, R.E.; Shipley, D.F.

    1999-07-01

    Mechanical pulping process is electrical energy intensive and results in low paper strength. Biomechanical pulping, defined as the fungal treatment of lignocellulosic materials prior to mechanical pulping, has shown at least 30% savings in electrical energy consumption, and significant improvements in paper strength properties compared to the control at a laboratory scale. In an effort to scale-up biomechanical pulping to an industrial level, fifty tons of spruce wood chips were inoculated with the best biopulping fungus in a continuous operation and stored in the form of an outdoor chip pile for two weeks. The pile was ventilated with conditioned air to maintain the optimum growth temperature and moisture throughout the pile. The control and fungus-treated chips were refined through a thermomechanical pulp mill (TMP) producing lightweight coated paper. The fungal pretreatment saved 33% electrical energy and improved paper strength properties significantly compared to the control. Since biofibers were stronger than the conventional TMP fibers, the authors were able to reduce the amount of bleached softwood kraft pulp by at least 5% in the final product. Fungal pretreatment reduced brightness, but brightness was restored to the level of bleached control with 60% more hydrogen peroxide. The economics of biomechanical pulping look attractive.

  1. Steroidal and nonsteroidal antiinflammatory medications can improve photoreceptor survival after laser retinal photocoagulation.

    PubMed

    Brown, Jeremiah; Hacker, Henry; Schuschereba, Steven T; Zwick, Harry; Lund, David J; Stuck, Bruce E

    2007-10-01

    To determine whether methylprednisolone or indomethacin can enhance photoreceptor survival after laser retinal injury in an animal model. Experimental study. Twenty rhesus monkeys. Twenty rhesus monkeys (Macaca mulatta) received a grid of argon green (514.5 nm, 10 ms) laser lesions in the macula of the right eye and a grid of neodymium:yttrium-aluminum-garnet (Nd:YAG; 1064 nm, 10 ns) lesions in the macula of the left eye, followed by randomization to 2 weeks of treatment in 1 of 4 treatment groups: high-dose methylprednisolone, moderate-dose methylprednisolone, indomethacin, or control. The lesions were assessed at day 1, day 14, 2 months, and 4 months. The authors were masked to the treatment group. This report discusses the histologic results of ocular tissue harvested at 4 months. The number of surviving photoreceptor cell nuclei within each lesion was compared with the number of photoreceptor nuclei in surrounding unaffected retina. The proportion of surviving photoreceptor nuclei was compared between each treatment group. Argon retinal lesions in the high-dose steroid treatment group and the indomethacin treatment group demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Hemorrhagic Nd:YAG lesions demonstrated improved survivability with indomethacin treatment compared with controls (P = 0.003). In nonhemorrhagic Nd:YAG laser retinal lesions, the lesions treated with moderate-dose steroids demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Based on histologic samples of retinal laser lesions 4 months after injury, treatment with indomethacin resulted in improved photoreceptor survival in argon laser lesions and hemorrhagic Nd:YAG laser lesions. Treatment with systemic methylprednisolone demonstrated improved photoreceptor survival in argon retinal lesions and in nonhemorrhagic Nd:YAG lesions.

  2. Basic effects of pulp refining on fiber properties--a review.

    PubMed

    Gharehkhani, Samira; Sadeghinezhad, Emad; Kazi, Salim Newaz; Yarmand, Hooman; Badarudin, Ahmad; Safaei, Mohammad Reza; Zubir, Mohd Nashrul Mohd

    2015-01-22

    The requirement for high quality pulps which are widely used in paper industries has increased the demand for pulp refining (beating) process. Pulp refining is a promising approach to improve the pulp quality by changing the fiber characteristics. The diversity of research on the effect of refining on fiber properties which is due to the different pulp sources, pulp consistency and refining equipment has interested us to provide a review on the studies over the last decade. In this article, the influence of pulp refining on structural properties i.e., fibrillations, fine formation, fiber length, fiber curl, crystallinity and distribution of surface chemical compositions is reviewed. The effect of pulp refining on electrokinetic properties of fiber e.g., surface and total charges of pulps is discussed. In addition, an overview of different refining theories, refiners as well as some tests for assessing the pulp refining is presented.

  3. The fall in mortality from ischemic heart disease in Australia: has survival after myocardial infarction improved?

    PubMed

    Martin, C A; Hobbs, M S; Armstrong, B K

    1984-08-01

    Trends in mortality and survival after myocardial infarction (MI) were studied by use of computerised death and hospital discharge records for 25 to 64 year old residents of the Perth Statistical Division between 1971 and 1979. Highly significant falls in ischemic heart disease (IHD) mortality rates were found for men (18%) and women (29%) but 4, 26 and 52 week survival after hospital admission for MI remained constant at around 88%, 84% and 81% respectively. Further, as 75% of all IHD deaths between 1971 and 1979 occurred before the victim was admitted to hospital, the survival of those receiving treatment would have had to be greatly improved to influence total mortality from IHD appreciably. As the age and sex composition of persons hospitalised for MI and the proportion of MI victims hospitalised did not change during the study period it would seem that improved survival after hospital admission for MI did not contribute to the fall in IHD deaths between 1971 and 1979.

  4. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    PubMed Central

    Del Rivero, Jaydira; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level. Improving access to molecular testing and treatment are key to maximizing the survival benefits at a population level. PMID:28149768

  5. [Improvment of survival in cystic fibrosis patients from 1962 to 1971].

    PubMed

    Högger, G P

    1975-07-01

    The survival rate of 42 patients with cystic fibrosis diagnosed during the five year period before institution of full prophylactic aerosol, mist tent and postural drainage therapy in 1967 was compared with that of 32 cases diagnosed in the five following years. The mean survival rate of the latter group was 81%, 81% and 73% at 1, 2 and 3 years respectivly, compared with 64%, 59% and 57% in the former group. The main difference was due to the significantly improved survival rate of cases diagnosed during the first year of life.

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

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Gregory...PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE 3. DATES COVERED 4. TITLE AND SUBTITLE Hibernation -Based Therapy to... hibernating mammals to aid in salvage of a patient with a potentially life-threatening blood loss, permitting survival to reach effective medical

  7. Fontan Patient Survival After Pediatric Heart Transplantation Has Improved in the Current Era.

    PubMed

    Simpson, Kathleen E; Pruitt, Elizabeth; Kirklin, James K; Naftel, David C; Singh, Rakesh K; Edens, R Erik; Barnes, Aliessa P; Canter, Charles E

    2017-04-01

    Historically, patients with a prior Fontan procedure for complex congenital heart disease (CHD) have been considered at higher risk for death after heart transplant (HT) compared with other HT transplant candidates. With the overall trend of improved survival of pediatric HT recipients, it is unclear of Fontan patient post-HT survival has also improved in the current era. Data from the Pediatric Heart Transplant Study database for Fontan patients who underwent HT was compared between the early era (1993 to 2006, n = 150) and late era (2007 to 2014, n = 252). Post-HT survival and pre-HT characteristics were compared among eras and also with non-Fontan CHD patients. At time of HT, Fontan patients in the late era were more likely to require inotropic support, have protein-losing enteropathy, have failure to thrive, and be further from time of Fontan, although less likely to be on ventilator support. Only ventilator support and earlier year of HT were significant risk factors for death in the multivariate analysis. Post-HT Fontan patient survival significantly improved from the early to late era (p = 0.02), particularly in the early phase, with 1-year survival of 77% in the early era and 89% in the late era. Late era non-Fontan CHD patient 1-year post-HT survival was similar to Fontan patients at 92%. Survival of Fontan patients after HT has significantly improved in the current era. Currently, expected post-HT survival for Fontan patients is on par with other CHD patients. Fontan patients should not be excluded from consideration for HT solely on a history of Fontan. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. An active lifestyle prior to coronary surgery is associated with improved survival in elderly patients.

    PubMed

    Rengo, Giuseppe; Galasso, Gennaro; Vitale, Dino F; Furgi, Giuseppe; Zincarelli, Carmela; Golino, Luca; Femminella, Grazia D; Piscione, Federico; Rengo, Franco; Leosco, Dario

    2010-07-01

    An active lifestyle is associated with a reduced cardiovascular risk in middle-aged as well as in elderly patients. In the present study, we investigated the association between physical activity habits of elderly participants prior to coronary artery bypass grafting (CABG) and survival free from both all-cause and cardiac death. Study population consisted of 587 elderly patients (>or=70 years) CABG patients stratified, according to the Physical Activity Scale for the Elderly (PASE), into less active (low PASE) and exercised (high PASE) groups. At follow-up (mean: 44.3 +/- 21.0 months), 33 (37.1%) of 89 total deaths occurred for cardiac causes. Sixty-month survival rate was 65% and 96% for low-PASE and high-PASE groups, respectively (log rank = 49.460, p < .0001). Cox survival analysis indicated a significant (p < .0001) nonlinear association between PASE score increments and improved survival with the most evident differences in the lowest score categories. A robust association was also found between low PASE score and increased cardiac-related mortality (p < .0001). Our data indicate that a more active lifestyle is significantly associated with improved survival in elderly CABG patients. The nonlinearity of the relation suggests that more sedentary patients could have the most benefit on survival by increasing their exercise lifestyle habits. The improved outcome is explained by both cardiac and overall mortality reduction.

  9. Pulp stones: a review.

    PubMed

    Goga, R; Chandler, N P; Oginni, A O

    2008-06-01

    Pulp stones are a frequent finding on bitewing and periapical radiographs but receive relatively little attention in textbooks. A review of the literature was therefore performed, initially using the PubMed database and beginning the search with 'pulp calcifications' and 'pulp stones'. Each term provided more than 400 references, many of which related to pulp calcification in general rather than pulp stones, and focussed largely on the problems these changes presented to clinicians. A manual search using references from this source was carried out. Contemporary textbooks in endodontology were also consulted, and an historic perspective gained from a number of older books and references. The factors involved in the development of the pulp stones are largely unknown. Further research may determine the reasons for their formation, but with current endodontic instruments and techniques this is unlikely to alter their relevance to clinicians.

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

    PubMed

    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 (Ms), 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 Ms, 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 <50% chance of survival, while birds with an Msum above 1.35 W had at least a 90% chance of surviving through the 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.

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

    PubMed

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

    2017-04-01

    To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. 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. 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). 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis.

    PubMed

    Ganatra, Hammad A; Varisco, Brian M; Harmon, Kelli; Lahni, Patrick; Opoka, Amy; Wong, Hector R

    2017-01-01

    Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified. We found a significant survival benefit and decreased bacterial burden among zinc supplemented mice when compared with the control group. Zinc supplementation also resulted in enhanced phagocytic activity, greater neutrophil recruitment in the peritoneal cavity and NET formation, suggesting a possible mechanism for improved bacterial clearance and survival. We also noted decreased serum cytokine levels and decreased myeloperoxidase activity in lung tissue following zinc supplementation, suggesting attenuation of the systemic inflammatory response. In conclusion, zinc supplementation improves bacterial clearance, and hence survival, in juvenile mice with polymicrobial sepsis.

  13. Metabolic control improves long-term renal allograft and patient survival in type 1 diabetes.

    PubMed

    Morath, Christian; Zeier, Martin; Döhler, Bernd; Schmidt, Jan; Nawroth, Peter P; Opelz, Gerhard

    2008-08-01

    It is a matter of debate whether pancreas allografts independently contribute to renal allograft and patient survival in individuals who have type 1 diabetes and receive a simultaneous pancreas and kidney transplant (SPK). Using data from the Collaborative Transplant Study, we studied patients who had type 1 diabetes and were recipients of deceased-donor kidneys (DDK), living-donor kidneys (LDK), or SPK. We analyzed graft and patient survival rates with a maximum of 18 yr of follow-up. DDK recipients had inferior graft and patient survival compared with LDK and SPK recipients. LDK recipients had superior graft and patient survival rates initially, but SPK recipients demonstrated equal survival rates toward the end of follow-up. Multivariate analysis, adjusting for pretransplantation cardiovascular risk, showed that patient survival of SPK recipients was superior to that of LDK recipients beyond the 10th year after transplantation (hazard ratio 0.55; P = 0.005). In summary, the early survival advantage of LDK over SPK is lost during long-term follow-up, probably as a result of improved glycemic control in SPK recipients.

  14. Parasitic Infection Improves Survival from Septic Peritonitis by Enhancing Mast Cell Responses to Bacteria in Mice

    PubMed Central

    Sutherland, Rachel E.; Xu, Xiang; Kim, Sophia S.; Seeley, Eric J.; Caughey, George H.; Wolters, Paul J.

    2011-01-01

    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 KitW-sh/KitW-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to KitW-sh/KitW-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. PMID:22110673

  15. Improving survival of probiotic bacteria using bacterial poly-γ-glutamic acid.

    PubMed

    Bhat, A R; Irorere, V U; Bartlett, T; Hill, D; Kedia, G; Charalampopoulos, D; Nualkaekul, S; Radecka, I

    2015-03-02

    A major hurdle in producing a useful probiotic food product is bacterial survival during storage and ingestion. The aim of this study was to test the effect of γ-PGA immobilisation on the survival of probiotic bacteria when stored in acidic fruit juice. Fruit juices provide an alternative means of probiotic delivery, especially to lactose intolerant individuals. In addition, the survival of γ-PGA-immobilised cells in simulated gastric juice was also assessed. Bifidobacteria strains (Bifidobacteria longum, Bifidobacteria breve), immobilised on 2.5% γ-PGA, survived significantly better (P<0.05) in orange and pomegranate juice for 39 and 11 days respectively, compared to free cells. However, cells survived significantly better (P<0.05) when stored in orange juice compared to pomegranate juice. Moreover, both strains, when protected with 2.5% γ-PGA, survived in simulated gastric juice (pH2.0) with a marginal reduction (<0.47 log CFU/ml) or no significant reduction in viable cells after 4h, whereas free cells died within 2h. In conclusion, this research indicates that γ-PGA can be used to protect Bifidobacteria cells in fruit juice, and could also help improve the survival of cells as they pass through the harsh conditions of the gastrointestinal tract (GIT). Following our previous report on the use of γ-PGA as a cryoprotectant for probiotic bacteria, this research further suggests that γ-PGA could be used to improve probiotic survival during the various stages of preparation, storage and ingestion of probiotic cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Prefabricated Flaps: Identification of Microcirculation Structure and Supercharging Technique Improving Survival Area.

    PubMed

    Xu, Heng; Feng, Shaoqing; Xia, Yimeng; Steinberger, Zvi; Xi, Wenjing; Fang, Hongwei; Li, Zhiwei; Xie, Yixin; Zhang, Yixin

    2017-02-01

    Background Microcirculation is an important factor frequently overlooked when studying the survival of prefabricated flaps. In the current study, we use different prefabrication techniques for characterizing microcirculation within the flap, with the goal of finding an effective way to improve its survival area. Methods An abdominal prefabricated flap rodent model was created using a two-stage operation. All rats were randomly divided into six groups (n = 10/group): group A, prefabricated femoral vessels; group B, prefabricated femoral artery with a connected superficial inferior epigastric vein (SIEV); group C, connected superficial inferior epigastric artery (SIEA) with a prefabricated femoral vein; group D was similar to group A along with a prefabricated SIEA, and group E was similar to group A along with a prefabricated SIEV; and group F acted as a control group and consisted of an axial flap nourished by superficial inferior epigastric vessels. Flaps were assessed for survival area, blood perfusion area, and capillary density using macroscopic analysis, near-infrared fluorescence imaging (NIFI), and histology. Results The survival area was not significantly different when comparing groups B to C, and D to E. The survival area of groups D and E was larger than that of groups B and C. Groups B through E had a smaller survival area in comparison to group F and a larger survival area than group A. NIFI were consistent with the macroscopic outcomes. The capillary density was not significantly different between groups A to C and groups D to F. Conclusion Both arterial and venous supercharging could potentially improve the survival area of prefabricated flaps. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Oocyte maturation and embryo survival in nulliparous female pigs (gilts) is improved by feeding a lupin-based high-fibre diet.

    PubMed

    Weaver, A C; Kelly, J M; Kind, K L; Gatford, K L; Kennaway, D J; Herde, P J; van Wettere, W H E J

    2013-01-01

    Inclusion of high levels of the high-fibre ingredient sugar-beet pulp in pre-mating diets has been shown to increase gonadotrophin concentrations and improve oocyte quality in nulliparous pigs (gilts). This study evaluated the effects of two alternative fibre sources on reproductive performance in gilts. Gilts received one of three diets from 3 weeks before puberty stimulation until Day 19 of the first oestrous cycle: control (39 g kg⁻¹ fibre), bran (500 g kg⁻¹ wheat bran, 65 g kg⁻¹ fibre) or lupin (350 g kg⁻¹ lupin, 118 g kg⁻¹ crude fibre). Diet did not affect circulating LH concentrations or ovarian follicle size. However, a higher percentage of oocytes collected from lupin-supplemented gilts reached metaphase II in vitro compared with those collected from bran-fed or control gilts (89±5% versus 72±5% and 66±5%, respectively; P<0.05). Furthermore, in a second experiment, gilts fed the same lupin-based diet before mating had improved embryo survival (92±5%) on Day 28 after mating compared with control gilts (76±4%; P<0.05). Therefore, feeding a high-fibre diet before mating can improve oocyte quality in gilts without changes in circulating LH, but this effect is dependent on the fibre source.

  18. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia.

    PubMed

    Singleton, Kristen D; Wischmeyer, Paul E

    2006-03-01

    No pharmacologic agent has shown benefit in treating heatstroke. Previous data indicate that enhanced heat shock protein 70 (HSP-70) expression can improve survival postexperimental heatstroke. Glutamine (GLN) can enhance HSP-70 expression in other injury models. This study assessed if orally administered GLN could enhance tissue HSP expression and could improve survival following whole body hyperthermia. Intestinal permeability and plasma endotoxin were assayed to determine if enhanced HSP expression correlated with improved organ function. GLN (0.65 g/kg) or an iso-nitrogenous control (Travasol; T) was given to rats via gavage twice daily for 5 days pre-heatstroke. Hyperthermia was performed in anesthetized rats by heating animals to 42 degrees C (rectal temperature) for 30 min. HSP-70 analyzed via Western blot. Gut permeability was measured 6 and 24 h post-hyperthermia. Plasma endotoxin was measured 24 h post-hyperthermia. Survival was analyzed for 5 days post-hyperthermia. GLN administration enhanced gut and lung HSP-70 post-hyperthermia. GLN administration led to significantly enhanced gut heat shock factor 1 (HSF-1) activation before heatstroke and at 1 h postheat stress. GLN decreased gut permeability at 6 and 24 h post-hyperthermia versus T. Plasma endotoxin also decreased in GLN-treated rats 24 h post-hyperthermia. Oral GLN therapy significantly improved survival (P < 0.05). Our results indicate that oral GLN can enhance tissue HSP-70 and HSF-1 activation post-hyperthermia. These results also indicate that enhanced HSP-70 may have functional significance as GLN-treated animals had decreased gut permeability, plasma endotoxin, and improve survival following lethal hyperthermia. Enhanced expression of HSP-70 may be an important mechanism leading to enhanced survival via GLN. These data indicate that oral GLN may useful in prevention of mortality from heatstroke in at risk populations.

  19. Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

    PubMed

    Wood, T F; DiFronzo, L A; Rose, D M; Haigh, P I; Stern, S L; Wanek, L; Essner, R; Morton, D L

    2001-09-01

    Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection. A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2000. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure. Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases. In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.

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

    PubMed

    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.

  1. SynCAM 1 improves survival of adult-born neurons by accelerating synapse maturation.

    PubMed

    Doengi, Michael; Krupp, Alexander J; Körber, Nils; Stein, Valentin

    2016-03-01

    The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons.

  2. Evaluation of risk factors associated with clinical improvement and survival of horses with equine protozoal myeloencephalitis.

    PubMed

    Saville, W J; Morley, P S; Reed, S M; Granstrom, D E; Kohn, C W; Hinchcliff, K W; Wittum, T E

    2000-10-15

    To investigate risk factors for use in predicting clinical improvement and survival of horses with equine protozoal myeloencephalitis (EPM). Longitudinal epidemiologic study. 251 horses with EPM. Between 1992 and 1995, 251 horses with EPM were admitted to our facility. A diagnosis of EPM was made on the basis of neurologic abnormalities and detection of antibody to Sarcocystis neurona or S neurona DNA in CSF. Data were obtained from hospital records and through telephone follow-up interviews. Factors associated with clinical improvement and survival were analyzed, using multivariable logistic regression. The likelihood of clinical improvement after diagnosis of EPM was lower in horses used for breeding and pleasure activities. Treatment for EPM increased the probability that a horse would have clinical improvement. The likelihood of survival among horses with EPM was lower among horses with more severe clinical signs and higher among horses that improved after EPM was diagnosed. Treatment of horses with EPM is indicated in most situations; however, severity of clinical signs should be taken into consideration when making treatment decisions. Response to treatment is an important indicator of survival.

  3. Innovative endodontic therapy for anti-inflammatory direct pulp capping of permanent teeth with a mature apex

    PubMed Central

    Komabayashi, Takashi; Zhu, Qiang

    2010-01-01

    Direct pulp capping is a treatment of an exposed vital pulp with a dental material to facilitate the formation of reparative dentin and maintenance of vital pulp. It has been studied as an alternate way to avoid vital pulp extirpation. However, the success rate of pulp capping is much lower than that of vital pulp extirpation. Therefore, direct pulp capping is currently considered controversial by many clinicians. To increase success rate, a critical need exists to develop new biologically-based therapeutics that reduce pulp inflammation, promote the continued formation of new dentin-pulp complex, and restore vitality by stimulating the regrowth of pulpal tissue. Bioengineered anti-inflammatory direct pulp capping materials, together with adhesive materials for leakage prevention, have great potential to improve the condition of the existing pulp from an inflamed to a non-inflamed status and lead to a high rate of long-term success. PMID:20416524

  4. Improved patient survival using a modified resuscitation protocol for out-of-hospital cardiac arrest.

    PubMed

    Garza, Alex G; Gratton, Matthew C; Salomone, Joseph A; Lindholm, Daniel; McElroy, James; Archer, Rex

    2009-05-19

    Cardiac arrest continues to have poor survival in the United States. Recent studies have questioned current practice in resuscitation. Our emergency medical services system made significant changes to the adult cardiac arrest resuscitation protocol, including minimizing chest compression interruptions, increasing the ratio of compressions to ventilation, deemphasizing or delaying intubation, and advocating chest compressions before initial countershock. This retrospective observational cohort study reviewed all adult primary ventricular fibrillation and pulseless ventricular tachycardia cardiac arrests 36 months before and 12 months after the protocol change. Primary outcome was survival to discharge; secondary outcomes were return of spontaneous circulation and cerebral performance category. Survival of out-of-hospital arrest of presumed primary cardiac origin improved from 7.5% (82 of 1097) in the historical cohort to 13.9% (47 of 339) in the revised protocol cohort (odds ratio, 1.80; 95% confidence interval, 1.19 to 2.70). Similar increases in return of spontaneous circulation were achieved for the subset of witnessed cardiac arrest patients with initial rhythm of ventricular fibrillation from 37.8% (54 of 143) to 59.6% (34 of 57) (odds ratio, 2.44; 95% confidence interval, 1.24 to 4.80). Survival to hospital discharge also improved from an unadjusted survival rate of 22.4% (32 of 143) to 43.9% (25 of 57) (odds ratio, 2.71; 95% confidence interval, 1.34 to 1.59) with the protocol. Of the 25 survivors, 88% (n=22) had favorable cerebral performance categories on discharge. The changes to our prehospital protocol for adult cardiac arrest that optimized chest compressions and reduced disruptions increased the return of spontaneous circulation and survival to discharge in our patient population. These changes should be further evaluated for improving survival of out-of-hospital cardiac arrest patients.

  5. Improved renal survival in Japanese children with IgA nephropathy.

    PubMed

    Yata, Nahoko; Nakanishi, Koichi; Shima, Yuko; Togawa, Hiroko; Obana, Mina; Sako, Mayumi; Nozu, Kandai; Tanaka, Ryojiro; Iijima, Kazumoto; Yoshikawa, Norishige

    2008-06-01

    Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976-1989 and 1990-2004. Actuarial survivals were calculated by Kaplan-Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990-2004 period was significantly better than that in 1976-1989 (p=0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p=0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N.

  6. Improved renal survival in Japanese children with IgA nephropathy

    PubMed Central

    Yata, Nahoko; Nakanishi, Koichi; Shima, Yuko; Togawa, Hiroko; Obana, Mina; Sako, Mayumi; Nozu, Kandai; Tanaka, Ryojiro; Iijima, Kazumoto

    2008-01-01

    Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976–1989 and 1990–2004. Actuarial survivals were calculated by Kaplan–Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990–2004 period was significantly better than that in 1976–1989 (p = 0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p = 0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N. PMID:18224344

  7. Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy.

    PubMed

    Calvo, Emiliano; Schmidinger, Manuela; Heng, Daniel Y C; Grünwald, Viktor; Escudier, Bernard

    2016-11-01

    Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab. The identification of predictive and prognostic factors of survival is increasing, and both clinical predictive factors and pathology-related prognostic factors are being evaluated. Serum-based biomarkers and certain histologic subtypes of RCC, as well as clinical factors such as dose intensity and the development of some class effect adverse events, have been identified as predictors of survival. Expression levels of microRNAs, expression of chemokine receptor 4, hypermethylation of certain genes, VEGF polymorphisms, and elevation of plasma fibrinogen or d-dimer have been shown to be prognostic indicators of survival. In the future, prognosis and treatment of patients with mRCC might be based on genomic classification, especially of the 4 most commonly mutated genes in RCC (VHL, PBRM1, BAP1, and SETD2). Median overall survival has improved for patients treated with a first-line targeted agent compared with survival of patients treated with first-line interferon-α, and results of clinical trials have shown a survival benefit of sequential treatment with targeted agents. Prognosis of patients with mRCC will likely improve with optimization and individualization of current sequential treatment with targeted agents.

  8. Use of laccase in pulp and paper industry.

    PubMed

    Virk, Antar Puneet; Sharma, Prince; Capalash, Neena

    2012-01-01

    Laccase, through its versatile mode of action, has the potential to revolutionize the pulping and paper making industry. It not only plays a role in the delignification and brightening of the pulp but has also been described for the removal of the lipophilic extractives responsible for pitch deposition from both wood and nonwood paper pulps. Laccases are capable of improving physical, chemical, as well as mechanical properties of pulp either by forming reactive radicals with lignin or by functionalizing lignocellulosic fibers. Laccases can also target the colored and toxic compounds released as effluents from various industries and render them nontoxic through its polymerization and depolymerization reactions. This article reviews the use of both fungal and bacterial laccases in improving pulp properties and bioremediation of pulp and paper mill effluents.

  9. Improvement of osteogenesis in dental pulp pluripotent-like stem cells by oligopeptide-modified poly(β-amino ester)s.

    PubMed

    Núñez-Toldrà, Raquel; Dosta, Pere; Montori, Sheyla; Ramos, Víctor; Atari, Maher; Borrós, Salvador

    2017-04-15

    Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. Recently, a new family of poly(β-amino ester)s (pBAEs) with oligopeptide-modified termini showing high transfection efficiency of both siRNA and DNA plasmid has been developed. In this study, oligopeptide-modified pBAEs were used to simultaneously deliver anti-OCT3/4 siRNA, anti-NANOG siRNA, and RUNX2 plasmid to cells from the dental pulp with pluripotent-like characteristics (DPPSC) in order to promote their osteogenic differentiation. Results indicate that transient inhibition of the pluripotency marker OCT3/4 and the overexpression of RUNX2 at day 7 of differentiation markedly increased and accelerated the expression of osteogenic markers. Furthermore, terminally-differentiated cells exhibited higher matrix mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicate that this co-delivery system has high chromosomal stability and minimal cytotoxicity. Therefore, we conclude that such co-delivery strategy is a safe and a quick option for the improvement of DPPSC osteogenic differentiation. Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. In this study, we propose the use of a new family of oligopeptide-modified pBAEs developed in our group to control the differentiation of dental pulp pluripotential stem cells (DPPSC). In order to promote their osteogenic differentiation. The strategy proposed markedly increased and accelerated the expression of osteogenic markers, cell mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicated that this co-delivery system has high chromosomal stability and

  10. Improving survival of disassociated human embryonic stem cells by mechanical stimulation using acoustic tweezing cytometry.

    PubMed

    Chen, Di; Sun, Yubing; Deng, Cheri X; Fu, Jianping

    2015-03-24

    Dissociation-induced apoptosis of human embryonic stem cells (hESCs) hampers their large-scale culture. Herein we leveraged the mechanosensitivity of hESCs and employed, to our knowledge, a novel technique, acoustic tweezing cytometry (ATC), for subcellular mechanical stimulation of disassociated single hESCs to improve their survival. By acoustically actuating integrin-bound microbubbles (MBs) to live cells, ATC increased the survival rate and cloning efficiency of hESCs by threefold. A positive correlation was observed between the increased hESC survival rate and total accumulative displacement of integrin-anchored MBs during ATC stimulation. ATC may serve as a promising biocompatible tool to improve hESC culture. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Starch filler and osmoprotectants improve the survival of rhizobacteria in dried alginate beads.

    PubMed

    Schoebitz, Mauricio; Simonin, Hélène; Poncelet, Denis

    2012-01-01

    This work deals with optimising the cell survival of rhizobacteria encapsulated in alginate beads filled with starch. Immobilisation of rhizobacteria was done by dripping alginate-starch solution mixed with rhizobacteria into a calcium solution. Beads were analysed based on matrix formulation, bacteria growth phase, osmoprotectants and nature of calcium solution. Maximum cell recovery was obtained on Raoultella terrigena grown in medium supplemented with trehalose and calcium gluconate as gelling agent. Furthermore, dried beads containing Azospirillum brasilense presented 76% of viable cells after one year of storage. The survival of rhizobacteria during the bioencapsulation process can be improved by incorporating starch on beads composition, varying the growth phase of cells and using trehalose in growth culture medium. This work provides a selection of appropriate methods to improve the surviving rate of encapsulated cells during their production and long-term storage (∼1 year at 4°C).

  12. Paper Pulp Panoply.

    ERIC Educational Resources Information Center

    Marque, Margo E.

    1999-01-01

    Explains that creating paper-pulp bowls is designed to acquaint students with the beginning vocabulary and finger dexterity needed to sculpt clay. Describes the process of making paper-pulp bowls and identifies important vocabulary words. Provides directions for making paper bowl forms and lists the materials. (CMK)

  13. Paper Pulp Panoply.

    ERIC Educational Resources Information Center

    Marque, Margo E.

    1999-01-01

    Explains that creating paper-pulp bowls is designed to acquaint students with the beginning vocabulary and finger dexterity needed to sculpt clay. Describes the process of making paper-pulp bowls and identifies important vocabulary words. Provides directions for making paper bowl forms and lists the materials. (CMK)

  14. Bioceramic Materials and the Changing Concepts in Vital Pulp Therapy.

    PubMed

    Cao, Yangpei; Bogen, George; Lim, Jung; Shon, Won-Jun; Kang, Mo K

    2016-05-01

    Vital pulp therapy (VPT) is devised to preserve and maintain vitality of pulpally involved teeth challenged by a variety of intraoral conditions. Notable progress has been made in this field due to a better understanding of pulp physiology, improved clinical protocols and advanced bioceramic materials paired with adhesive technology. With focused case selection, conservative VPT can provide reliable treatment options for permanent teeth diagnosed with normal pulps or reversible pulpitis.

  15. Vemurafenib Improves Survival for Patients with Metastatic Melanoma | Division of Cancer Prevention

    Cancer.gov

    Patients with metastatic melanoma whose tumors harbor a specific genetic mutation have improved overall survival with the targeted therapy vemurafenib (Zelboraf), according to longer-term follow-up data from a  |

  16. Alpha (1,2)-fucosyltransferase M307A polymorphism improves piglet survival.

    PubMed

    Kim, Kyungtae; Nguyen, Dinh Truong; Choi, Minkyung; Kim, Jin-Hoi; Seo, Han Geuk; Dadi, Hailu; Cha, Se-Yeoun; Seo, Kunho; Lee, Yun-Mi; Kim, Jong-Joo; Park, Chankyu

    2013-01-01

    To confirm the beneficial effects of alpha (1,2)-fucosyltransferase (FUT1) M307 (A) on piglet survival on commercial farms, we performed PCR-RFLP analysis of FUT1 M307 in successfully marketed (n = 245) and disease affected/deceased pigs during weaning (n = 252) at a commercial farm. We also evaluated the FUT1 genotypes of 190 healthy pigs from three different genetic backgrounds. The distribution of genotypes differed between the successfully marketed and disease affected/deceased pig groups. The frequency of the A allele, associated with resistance to edema and post-weaning diarrhea, was higher in the post-weaning survival group (0.21) than in the non-survival group (0.16, P < 0.05). The odds ratio for piglet survival between AA and GG genotypes was 1.98; thus, piglet survival for individuals with the AA genotype was almost two-fold greater than for GG individuals. The FUT1 gene polymorphism can be used as an effective marker for selection programs to improve post-weaning piglet survival.

  17. Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

    PubMed Central

    Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

    2014-01-01

    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. PMID:25226036

  18. MK-801 is neuroprotective but does not improve survival in severe forebrain ischemia.

    PubMed

    Von Lubitz, D K; McKenzie, R J; Lin, R C; Devlin, T M; Skolnick, P

    1993-03-16

    The effects of MK-801 on postischemic recovery, survival and neuronal preservation in the cortex, hippocampus and striatum were studied in Mongolian gerbils. The drug was administered 30 min prior to 20 of min forebrain ischemia induced by bilateral ligation of the carotids. Neurological recovery and survival were monitored for 7 days. At the end of the monitoring period neuronal damage was analyzed in the brains of the survivors in both groups. Treatment with MK-801 did not improve either neurological recovery or end-point survival. However, significant (P < 0.01) neuronal protection was observed in the hippocampi and striata of the drug treated animals while cortical neurons were not significantly protected. These findings demonstrate that protection against ischemic neuronal damage can be observed without concomitant improvement in either postischemic neurological recovery or survival. Protection of selectively vulnerable brain regions, often used as the predictor of the therapeutic potential of an agent, does not appear to correlate well with postischemic survival in this animal model of ischemia.

  19. Prior Infection Does Not Improve Survival against the Amphibian Disease Chytridiomycosis

    PubMed Central

    Cashins, Scott D.; Grogan, Laura F.; McFadden, Michael; Hunter, David; Harlow, Peter S.; Berger, Lee; Skerratt, Lee F.

    2013-01-01

    Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis) to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d) using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery. PMID:23451076

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

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81xwh-10-2-0121 TITLE: Hibernation -Based Therapy to Improve...COVERED 1 October 2012 to 30 September 2013 4. TITLE AND SUBTITLE Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT...risk for bleeding to death. Our overall strategy in this series of studies is to capitalize on the physiologic adaptive responses seen in hibernating

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

    DTIC Science & Technology

    2012-10-01

    AD_________________ Award Number: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve... Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...physiologic adaptive responses in hibernating mammals to aid in slavage of a patient with a potentially life-threatening blood loss, permitting

  2. Familiarity with breeding habitat improves daily survival in colonial cliff swallows

    PubMed Central

    BROWN, CHARLES R.; BROWN, MARY BOMBERGER; BRAZEAL, KATHLEEN R.

    2008-01-01

    One probable cost of dispersing to a new breeding habitat is unfamiliarity with local conditions such as the whereabouts of food or the habits of local predators, and consequently immigrants may have lower probabilities of survival than more experienced residents. Within a breeding season, estimated daily survival probabilities of cliff swallows (Petrochelidon pyrrhonota) at colonies in southwestern Nebraska were highest for birds that had always nested at the same site, followed by those for birds that had nested there in some (but not all) past years. Daily survival probabilities were lowest for birds that were naïve immigrants to a colony site and for yearling birds that were nesting for the first time. Birds with past experience at a colony site had monthly survival 8.6% greater than that of naïve immigrants. All colonies where experienced residents did better than immigrants were smaller than 750 nests in size, and in colonies greater than 750 nests, naïve immigrants paid no survival costs relative to experienced residents. Removal of nest ectoparasites by fumigation resulted in higher survival probabilities for all birds, on average, and diminished the differences between immigrants and past residents, probably by improving bird condition to the extent that effects of past experience were relatively less important and harder to detect. The greater survival of experienced residents could not be explained by condition or territory quality, suggesting that familiarity with a local area confers survival advantages during the breeding season for cliff swallows. Colonial nesting may help to moderate the cost of unfamiliarity with an area, likely through social transfer of information about food sources and enhanced vigilance in large groups. PMID:19802326

  3. Cardiocerebral resuscitation improves survival of patients with out-of-hospital cardiac arrest.

    PubMed

    Kellum, Michael J; Kennedy, Kevin W; Ewy, Gordon A

    2006-04-01

    The guidelines for cardiopulmonary resuscitation (CPR) have been in place for decades; but despite their international scope and periodic updates, there has been little improvement in survival rates in out-of-hospital cardiac arrest for patients who did not receive early defibrillation. The Emergency Medical Service directors in 2 rural Wisconsin counties initiated a new protocol for the pre-hospital management of adult cardiac arrest victims in an attempt to improve survival rates. The results observed after implementation of this protocol are presented and compared with those observed during a three-year period that preceded initiation of the project. The protocol, based upon the principles of cardiocerebral resuscitation, was significantly different from the standard CPR protocol. A major objective was to minimize interruptions of chest compressions. Each defibrillation, including the first, was preceded by 200 uninterrupted chest compressions. Single shocks, rather than stacked shocks, were utilized. Post shock rhythm and pulse checks were eliminated, and chest compressions were resumed immediately after a shock was delivered. Initial airway management was limited to an oral pharyngeal device and supplemental oxygen. If the arrest was witnessed, assisted ventilations and intubation were delayed until either a return of spontaneous circulation or until three series of "compressions + analysis +/- shock" were completed. In the 3 years preceding the change in protocol, where standard CPR was utilized, there were 92 witnessed out-of-hospital adult cardiac arrests with an initially shockable rhythm. Eighteen patients survived, and 14 of 92 (15%) were neurologically intact. After implementing the new protocol in early 2004, there were 33 witnessed out-of-hospital adult cardiac arrests with an initially shockable rhythm. Nineteen survived, and 16 of 33 (48%) were neurologically normal. Differences in both total and neurologically normal survival are significant (chi

  4. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    PubMed Central

    Li, Liangpeng; Chen, Xiongwen; Wang, Wei Eric; Zeng, Chunyu

    2016-01-01

    Mesenchymal stem cell (MSC) is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question. PMID:26681958

  5. Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study.

    PubMed

    Pigneux, Arnaud; Béné, Marie C; Guardiola, Philippe; Recher, Christian; Hamel, Jean-Francois; Sauvezie, Mathieu; Harousseau, Jean-Luc; Tournilhac, Olivier; Witz, Francis; Berthou, Christian; Escoffre-Barbe, Martine; Guyotat, Denis; Fegueux, Nathalie; Himberlin, Chantal; Hunault, Mathilde; Delain, Martine; Lioure, Bruno; Jourdan, Eric; Bauduer, Frederic; Dreyfus, Francois; Cahn, Jean-Yves; Sotto, Jean-Jacques; Ifrah, Norbert

    2017-02-01

    Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m(2) on days 1 to 5, cytarabine 100 mg/m(2) on days 1 to 7, and lomustine 200 mg/m(2) on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m(2) on day 1, cytarabine 100 mg/m(2) on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30

  6. Does Glucagon Improve Survival in a Porcine (Sus Scrofa) of Adult Asphyxial Cardiac Arrest in Addition to Standard Epinephrine Therapy?

    DTIC Science & Technology

    2012-01-17

    UDIIILI: oa. I..UN I ItA!.. I NUMDI:It Does Glucagon improve survival in a porcine (Sus Scrofa ) of adult asphyxial cardiac arrest in addition to...EXPIRATION DATE: 25 Mar 13 PROTOCOL TITLE: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial Cardiac Arrest in Addition...Additions: Deletions: 2 Protocol No: A-2007-03 Protocol Title: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial

  7. Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

    PubMed Central

    Nieder, Carsten; Marienhagen, Kirsten; Dalhaug, Astrid; Norum, Jan

    2008-01-01

    Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer. PMID:19259331

  8. Reporting quality of survival analyses in medical journals still needs improvement. A minimal requirements proposal.

    PubMed

    Abraira, Víctor; Muriel, Alfonso; Emparanza, José I; Pijoan, José I; Royuela, Ana; Plana, María Nieves; Cano, Alejandra; Urreta, Iratxe; Zamora, Javier

    2013-12-01

    We reviewed publications with two main objectives: to describe how survival analyses are reported across medical journal specialties and to evaluate changes in reporting across periods and journal specialties. Systematic review of clinical research articles published in 1991 and 2007, in 13 high-impact medical journals. The number of articles performing survival analysis published in 1991 (104) and 2007 (240) doubled (17% vs. 33.5%; P = 0.000), although not uniformly across specialties. The percentage of studies using regression models and the number of patients included also increased. The presentation of results improved, although only the reporting of precision of effect estimates reached satisfactory levels (53.1% in 1991 vs. 94.2% in 2007; P = 0.000). Quality of reporting also varied across specialties; for example, cardiology articles were less likely than oncology ones to discuss sample size estimation (odds ratio = 0.12; 95% confidence interval: 0.05, 0.30). We also detected an interaction effect between period and specialty regarding the likelihood of reporting precision of curves and precision of effect estimates. The application of survival analysis to medical research data is increasing, whereas improvement in reporting quality is slow. We propose a list of minimum requirements for improved application and description of survival analysis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Changes in pulp web properties by addition of natural filler

    NASA Astrophysics Data System (ADS)

    Kamaludin, Nurul Hasanah; Ghazali, Arniza; Daud, Wan Rosli Wan; Ghazali, Salmi

    2012-09-01

    Development of the desired pulp-based products eco-properties are governed by factors like choice and suitability of raw material, the design and operation of pulping process and choice of additives. Fines recovered during refining discharge of an alkaline peroxide pulping system were collected based on their retention on varying mesh-sizes screens. Analysis shows that 12% of the 400-mesh fines added to the web enhances paper tensile strength by 100%. This defines the usefulness of fibrillar particles whose cell wall collapsibility increases the web density by increasing bonding ability and thus, strength of pulp-based products such as paper. The study acknowledges fines functioning as natural filler in pulp network and collection of fines from the refining discharge was found to reduce 70% turbidity and this improvement will help reduce the costs pertinent to generation of whitewater from the pulping system.

  10. Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats

    PubMed Central

    Xu, Bin; Li, Yang; Deng, Bo; Liu, Xiaojing; Wang, Lin; Zhu, Qing-Lei

    2017-01-01

    Myocardial infarction (MI) remains the leading cause of cardiovascular-associated mortality and morbidity. Improving the retention rate, survival and cardiomyocyte differentiation of mesenchymal stem cells (MSCs) is important in improving the treatment of patients with MI. In the present study, temperature-responsive chitosan hydrogel, an injectable scaffold, was used to deliver MSCs directly into the infarcted myocardium of rats following MI. Histopathology and immunohistochemical staining were used to evaluate cardiac cell survival and regeneration, and cardiac function was assessed using an echocardiograph. It was demonstrated that chitosan hydrogel increased graft size and cell retention in the ischemic heart, promoted MSCs to differentiate into cardiomyocytes and increased the effects of MSCs on neovasculature formation. Furthermore, chitosan hydrogel enhanced the effect of MSCs on the improvement of cardiac function and hemodynamics in the infarcted area of rats following MI. These findings suggest that chitosan hydrogel is an appropriate material to deliver MSCs into infarcted myocardium. PMID:28352335

  11. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial.

  12. Inhibition of Peptidylarginine Deiminase Attenuates Inflammation and Improves Survival in a Rat Model of Hemorrhagic Shock

    PubMed Central

    He, Wei; Zhou, Peter; Chang, Zhigang; Liu, Baoling; Liu, Xuefeng; Wang, Yanming; Li, Yongqing; Alam, Hasan B.

    2015-01-01

    Background We have recently shown that inhibition of peptidylarginine deiminase (PAD) improves survival in a rodent model of lethal cecal ligation and puncture (CLP). The roles of PAD inhibitors in hemorrhagic shock (HS), however, are largely unknown. The goal of this study was to investigate the effects of YW3-56, a novel PAD inhibitor, on survival following severe HS. Methods Mouse macrophages were exposed to hypoxic conditions followed by reoxygenation in the presence or absence of YW3-56. Enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of secreted tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the culture medium. Cell viability was determined by methyl thiazolyl tetrazolium assay. In the survival experiment, anesthetized male Wistar-Kyoto rats (n=10/group) were subjected to 55% blood loss, treated with or without YW3-56 (10 mg/kg, intraperitoneally). Survival was monitored for 12 h. In the non-survival experiment, morphorlogic changes of the lungs were examined. Levels of circulating cytokine-induced neutrophil chemoattractant 1 (CINC-1) and myeloperoxidase (MPO) in the lungs were measured by ELISA. Expression of lung intercellular adhesion molecules-1 (ICAM-1) was also determined by Western blotting. Results Hypoxia/reoxygenation (H/R) insult induced TNF-α and IL-6 secretion from macrophages, which was significantly attenuated by YW3-56 treatment. YW3-56 treatment also increased cell viability when macrophages were exposed to H/R up to 6/15h, and improved survival rate from 20% to 60% in lethal HS rat model. Compared to the sham groups, pulmonary MPO activity and ICAM-1 expression in the HS group were significantly increased, and acute lung injury was associated with a higher degree of CINC-1 levels in serum. Intraperitoneal delivery of YW3-56 significantly reduced pulmonary MPO and ICAM-1 expression and attenuated acute lung injury (ALI). Conclusions Our results demonstrate for the first time that administration of YW3

  13. Survival improvement in hormone-responsive young breast cancer patients with endocrine therapy.

    PubMed

    Yoon, Tae In; Hwang, Ui-Kang; Kim, Eui Tae; Lee, SaeByul; Sohn, Guiyun; Ko, Beom Seok; Lee, Jong Won; Son, Byung Ho; Kim, Seonok; Ahn, Sei Hyun; Kim, Hee Jeong

    2017-09-01

    We investigated the oncologic outcomes by intrinsic subtype and age in young breast cancer patients and whether survival differences were related to treatment changes over time. A retrospective analysis was performed on 9633 invasive breast cancer patients treated at Asan Medical Center from January 1989 to December 2008. We also enrolled a matched cohort adjusting for tumor size, lymph node metastasis, subtypes, and tumor grade. Patients aged <35 years were included in the younger group (n = 602) and those aged ≥35 years were included in the older group (n = 3009). The younger patients showed a significantly higher T stage, a more frequent axillary node presentation, higher histologic grade, and higher incidence of triple-negative subtype tumors than older patients and also received more chemotherapy and were less likely to undergo hormone therapy. The younger patients with hormone receptor (HR)-positive tumors showed significantly poorer disease-free survival (DFS), loco-regional recurrence-free survival, distant metastasis-free survival, and breast cancer-specific survival outcomes than older patients. Younger patients with HR-positive and human epidermal growth factor receptor 2 (HER2)-negative tumor subtypes had a significantly improved DFS over time (p = 0.032). Within the HR-positive/Her2-negative subtype, more women received gonadotropin-releasing hormone agonist and tamoxifen treatment from 2003 to 2008 compared with 1989 to 2002 (p = 0.001 and p = 0.075, respectively). HR-positive young breast cancer patients have a poorer survival compared with older patients, even with more frequent chemotherapy, but more recent use of tamoxifen and ovarian suppression might improve this outcome in these patients.

  14. Systemic sclerosis associated pulmonary hypertension: improved survival in the current era

    PubMed Central

    Williams, M H; Das, C; Handler, C E; Akram, M R; Davar, J; Denton, C P; Smith, C J; Black, C M; Coghlan, J G

    2006-01-01

    Objectives To measure survival, haemodynamic function and functional class in patients with systemic sclerosis associated pulmonary arterial hypertension (SSc‐PAH) in two treatment eras. Methods Six year longitudinal study of 92 consecutive patients with SSc‐PAH diagnosed by cardiac catheterisation. Data were collected both prospectively and retrospectively. Patients were given basic treatment (diuretics, digoxin, oxygen and warfarin). Where clinically indicated, a prostanoid was used as advanced treatment (historical control group). From 2002, the range of treatments available expanded to include bosentan, which was generally the preferred treatment (current treatment era group). Survival was measured from the date of diagnosis of pulmonary hypertension by cardiac catheterisation. Six minute walking distance and haemodynamic function were measured at the time of diagnosis and at least one month after treatment was started. Results The historical control group comprised 47 patients, all of whom received basic treatment; 27 of these were also treated with prostanoids. The current treatment era group comprised 45 patients, all of whom received bosentan as preferred treatment. Kaplan–Meier survival in the historical control group was 68% at one year and 47% at two years. Survival in the current treatment era group was 81% and 71% (p  =  0.016) at one and two years, respectively. Pulmonary vascular resistance increased in the historical control group (by 147 dyn·s·cm−5), whereas in the current treatment era group, it remained stable over an average of nine months (decrease of 16 dyn·s·cm−5, p < 0.006). Conclusion Survival of selected patients with SSc‐PAH has improved in the current treatment era. In contrast to patients treated historically with basic drugs and prostanoids, patients treated in the current treatment era had improved survival associated with a lack of deterioration in cardiac haemodynamic function. PMID:16339813

  15. A Systematic Case Study of the Course, Offshore Survival Systems Training, To Improve the Practice of Marine Survival Training.

    ERIC Educational Resources Information Center

    Zambon, Franco

    A major applied research project evaluated the effectiveness of a novel course, Offshore Survival Systems Training. The major course outcome that was evaluated was the increase in frequency with which offshore personnel correctly launched the covered powered survival craft on offshore drilling rigs. The evaluation methodology included the 628…

  16. Nutrition and Hydration Status of Aircrew Members Consuming The Food Packet, Survival, General Purpose, Improved During A Simulated Survival Scenario

    DTIC Science & Technology

    1992-11-01

    22. Schoeller, D.A., C.A. Leitch, and C. Brown. Doubly labeled water method: in vivo oxygen and hydrogen isotope fractionation. Am. J. Physiol. 251: R1...Got tired of chewing the New Generation Survival Ration d. Gums were too sore to eat the New Genration Survival Ration e. Not enough time to eat

  17. A Systematic Case Study of the Course, Offshore Survival Systems Training, To Improve the Practice of Marine Survival Training.

    ERIC Educational Resources Information Center

    Zambon, Franco

    A major applied research project evaluated the effectiveness of a novel course, Offshore Survival Systems Training. The major course outcome that was evaluated was the increase in frequency with which offshore personnel correctly launched the covered powered survival craft on offshore drilling rigs. The evaluation methodology included the 628…

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

    PubMed

    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

  19. Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival.

    PubMed

    Chen, YiMing; Gokavarapu, Sandhya; Shen, QingCheng; Liu, Feng; Cao, Wei; Ling, YueHua; Ji, Tong

    2017-10-01

    Osteosarcoma is an aggressive bone malignancy presenting uncommonly in head and neck sites. Surgery is mainstay in treatment. However; trials show an improved survival with addition of chemotherapy in the treatment of extremity osteosarcoma. The head and neck osteosarcomas(HNOs) were excluded in these trials because of atypical presentation and disease course. Further; sufficient numbers were not possible for a trial. We present the largest retrospective study from single institute investigating the role of chemotherapy in the management of HNOs. The retrospective cohort of HNOs treated from 2007 to 2015 of a tertiary hospital were charted. The therapeutic and prognostic factors were analyzed for overall survival(OS), disease free survival(DFS), local control(LC) and metastasis(MT) in univariate and multivariate analysis. The minimum and median period of follow up was 12months and 56.04months respectively. There was a total of 157 patients definitively treated with surgery in the time period. 7 patients had positive margins and all were maxillary or skull base tumors. The multivariate cox regression showed significance of tumor site(p=0.034), margin status (p=0.006), chemotherapy(p=0.025), histological subtype(p=0.012) as predictors of overall survival. The margin status(p=0.002), Radiotherapy(p=0.005) were significant predictors for local recurrence. The age and histology subtype(p=0.058) were borderline significant predictors of metastasis(p=0.065). The KM method for OS of different chemotherapy groups(p=0.013), and survival with and without chemotherapy(p=0.007) was significant. The OS was significantly better with adjuvant chemotherapy among various treatment plans(p=0.034). Adjuvant chemotherapy improved OS while adjuvant radiotherapy improved local control of HNOs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Radiotherapy Improves Survival in Unresected Stage I-III Bronchoalveolar Carcinoma

    SciTech Connect

    Urban, Damien; Mishra, Mark; Onn, Amir; Dicker, Adam P.; Symon, Zvi; Pfeffer, M. Raphael; Lawrence, Yaacov Richard

    2012-11-01

    Purpose: To test the hypothesis that radiotherapy (RT) improves the outcome of patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by performing a population-based analysis within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods and Materials: Inclusion criteria were as follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007. Exclusion criteria included unknown stage, unknown primary treatment modality, Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment details, and overall survival were retrieved from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 6933 patients with Stage I-III BAC were included in the analysis. The median age at diagnosis was 70 years (range, 10-101 years). The majority of patients were diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical resection. Unresected patients were more likely to be older (p < 0.0001), male (p = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in Stage I, II, and III, respectively. Factors associated with improved survival included female sex, earlier stage at diagnosis, and use of RT. Median survival in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs. 33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31, nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003). Conclusions: The use of RT is associated with improved prognosis in unresected Stage I-III BAC. Less than a third of patients who could have potentially benefited from RT received it, suggesting that the medical specialists involved in the care of these patients underappreciate the importance of RT.

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

    PubMed Central

    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

  2. Metformin Improves Overall Survival of Colorectal Cancer Patients with Diabetes: A Meta-Analysis

    PubMed Central

    Meng, Fanqiang

    2017-01-01

    Introduction. Diabetic population has a higher risk of colorectal cancer (CRC) incidence and mortality than nondiabetics. The role of metformin in CRC prognosis is still controversial. The meta-analysis aims to investigate whether metformin improves the survival of diabetic CRC patients. Methods. PubMed, EMBASE, and Cochrane Library were searched till July 1, 2016. Cohort studies were included. All articles were evaluated by Newcastle-Ottawa Scale. Hazard Ratios (HRs) with 95% confidence intervals (CIs) for each study were calculated and pooled HRs with corresponding 95% CIs were generated using the random-effects model. Heterogeneity and publication bias were assessed. Results. We included seven cohort studies with a medium heterogeneity (I2 = 56.1% and p = 0.033) in our meta-analysis. An improved overall survival (OS) for metformin users over nonusers among colorectal cancers with diabetes was noted (HR 0.75; 95% CI 0.65 to 0.87). However, metformin reveals no benefits for cancer-specific survival (HR 0.79, 95%, CI 0.58 to 1.08). Conclusions. Metformin prolongs the OS of diabetic CRC patients, but it does not affect the CRC-specific survival. Metformin may be a good choice in treating CRC patients with diabetes mellitus in clinical settings.

  3. Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

    PubMed

    Boeck, L; Eggimann, P; Smyrnios, N; Pargger, H; Thakkar, N; Siegemund, M; Marsch, S; Rakic, J; Tamm, M; Stolz, D

    2011-03-01

    Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

  4. Matrix Metalloproteinase-3 Accelerates Wound Healing following Dental Pulp Injury

    PubMed Central

    Zheng, Li; Amano, Kazuharu; Iohara, Koichiro; Ito, Masataka; Imabayashi, Kiyomi; Into, Takeshi; Matsushita, Kenji; Nakamura, Hiroshi; Nakashima, Misako

    2009-01-01

    Matrix metalloproteinases (MMPs) are implicated in a wide range of physiological and pathological processes, including morphogenesis, wound healing, angiogenesis, inflammation, and cancer. Angiogenesis is essential for reparative dentin formation during pulp wound healing. The mechanism of angiogenesis, however, still remains unclear. We hypothesized that certain MMPs expressed during pulp wound healing may support recovery processes. To address this issue, a rat pulp injury model was established to investigate expression of MMPs during wound healing. Real-time RT-PCR analysis showed that expression MMP-3 and MMP-9 (albeit lower extent) was up-regulated at 24 and 12 hours after pulp injury, respectively, whereas expression of MMP-2 and MMP-14 was not changed. MMP-3 mRNA and protein were localized in endothelial cells and/or endothelial progenitor cells in injured pulp in vivo. In addition, MMP-3 enhanced proliferation, migration, and survival of human umbilical vein endothelial cells in vitro. Furthermore, the topical application of MMP-3 protein on the rat-injured pulp tissue in vivo induced angiogenesis and reparative dentin formation at significantly higher levels compared with controls at 24 and 72 hours after treatment, respectively. Inhibition of endogenous MMP-3 by N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid resulted in untoward wound healing. These results provide suggestive evidence that MMP-3 released from endothelial cells and/or endothelial progenitor cells in injured pulp plays critical roles in angiogenesis and pulp wound healing. PMID:19834065

  5. S-Nitrosoglutathione Reductase Deficiency Confers Improved Survival and Neurological Outcome in Experimental Cerebral Malaria.

    PubMed

    Elphinstone, Robyn E; Besla, Rickvinder; Shikatani, Eric A; Lu, Ziyue; Hausladen, Alfred; Davies, Matthew; Robbins, Clinton S; Husain, Mansoor; Stamler, Jonathan S; Kain, Kevin C

    2017-09-01

    Artesunate remains the mainstay of treatment for cerebral malaria, but it is less effective in later stages of disease when the host inflammatory response and blood-brain barrier integrity dictate clinical outcomes. Nitric oxide (NO) is an important regulator of inflammation and microvascular integrity, and impaired NO bioactivity is associated with fatal outcomes in malaria. Endogenous NO bioactivity in mammals is largely mediated by S-nitrosothiols (SNOs). Based on these observations, we hypothesized that animals deficient in the SNO-metabolizing enzyme, S-nitrosoglutathione reductase (GSNOR), which exhibit enhanced S-nitrosylation, would have improved outcomes in a preclinical model of cerebral malaria. GSNOR knockout (KO) mice infected with Plasmodium berghei ANKA had significantly delayed mortality compared to WT animals (P < 0.0001), despite higher parasite burdens (P < 0.01), and displayed markedly enhanced survival versus the wild type (WT) when treated with the antimalarial drug artesunate (77% versus 38%; P < 0.001). Improved survival was associated with higher levels of protein-bound NO, decreased levels of CD4(+) and CD8(+) T cells in the brain, improved blood-brain barrier integrity, and improved coma scores, as well as higher levels of gamma interferon. GSNOR KO animals receiving WT bone marrow had significantly reduced survival following P. berghei ANKA infection compared to those receiving KO bone barrow (P < 0.001). Reciprocal transplants established that survival benefits of GSNOR deletion were attributable primarily to the T cell compartment. These data indicate a role for GSNOR in the host response to malaria infection and suggest that strategies to disrupt its activity will improve clinical outcomes by enhancing microvascular integrity and modulating T cell tissue tropism. Copyright © 2017 American Society for Microbiology.

  6. Arundo donax L. reed: new perspectives for pulping and bleaching. 5. Ozone-based TCF bleaching of organosolv pulps.

    PubMed

    Shatalov, A A; Pereira, H

    2008-02-01

    Three selected alkali-based organosolv pulps (alkali-sulfite-anthraquinone-methanol (ASAM), alkali-anthraquinone-methanol (organocell) and ethanol-soda) from agrofibre crop giant reed (Arundo donax L.) were bleached by an ozone-based TCF (totally chlorine- free) bleaching sequence AZE(R)QP (where A is an acidic pulp pre-treatment, Z is an ozone stage, (E(R)) is an alkaline extraction in the presence of reducing agent, Q is a pulp chelating, P is a hydrogen peroxide stage) without oxygen pre-bleaching, and compared with a conventional kraft pulp used as a reference. The different response on bleaching conditions within each bleaching stage was noted for all tested pulps. The pulp bleachability, in terms of brightness improvement or lignin removal per unit of applied chemicals, was found higher for the organocell pulp. The ASAM and ethanol-soda pulps showed the highest bleaching selectivity, expressed by viscosity loss per unit of lignin removed or brightness improved. The overall bleaching results of organosolv pulps were superior to kraft.

  7. Improving code team performance and survival outcomes: implementation of pediatric resuscitation team training.

    PubMed

    Knight, Lynda J; Gabhart, Julia M; Earnest, Karla S; Leong, Kit M; Anglemyer, Andrew; Franzon, Deborah

    2014-02-01

    To determine whether implementation of Composite Resuscitation Team Training is associated with improvement in survival to discharge and code team performance after pediatric in-hospital cardiopulmonary arrest. We conducted a prospective observational study with historical controls at a 302-bed, quaternary care, academic children's hospital. Inpatients who experienced cardiopulmonary arrest between January 1, 2006, and December 31, 2009, were included in the control group (123 patients experienced 183 cardiopulmonary arrests) and between July 1, 2010, and June 30, 2011, were included in the intervention group (46 patients experienced 65 cardiopulmonary arrests). Code team members were introduced to Composite Resuscitation Team Training and continued training throughout the intervention period (January 1, 2010-June 30, 2011). Training was integrated via in situ code blue simulations (n = 16). Simulations were videotaped and participants were debriefed for education and process improvement. Primary outcome was survival to discharge after cardiopulmonary arrest. Secondary outcome measures were 1) change in neurologic morbidity from admission to discharge, measured by Pediatric Cerebral Performance Category, and 2) code team adherence to resuscitation Standard Operating Performance variables. The intervention group was more likely to survive than the control group (60.9% vs 40.3%) (unadjusted odds ratio, 2.3 [95% CI, 1.15-4.60]) and had no significant change in neurologic morbidity (mean change in Pediatric Cerebral Performance Category 0.11 vs 0.27; p = 0.37). Code teams exposed to Composite Resuscitation Team Training were more likely than control group to adhere to resuscitation Standard Operating Performance (35.9% vs 20.8%) (unadjusted odds ratio, 2.14 [95% CI, 1.15-3.99]). After adjusting for adherence to Standard Operating Performance, survival remained improved in the intervention period (odds ratio, 2.13 [95% CI, 1.06-4.36]). With implementation of Composite

  8. Three-dimensional simulated microgravity culture improves the proliferation and odontogenic differentiation of dental pulp stem cell in PLGA scaffolds implanted in mice.

    PubMed

    Li, Yanping; He, Lina; Pan, Shuang; Zhang, Lin; Zhang, Weiwei; Yi, Hong; Niu, Yumei

    2017-02-01

    Tooth regeneration through stem cell-based therapy is a promising treatment for tooth decay and loss. Human dental pulp stem cells (hDPSCs) have been widely identified as the stem cells with the most potential for tooth tissue regeneration. However, the culture of hDPSCs in vitro for tissue engineering is challenging, as cells may proliferate slowly or/and differentiate poorly in vivo. Dynamic three‑dimensional (3D) simulated microgravity (SMG) created using the rotary cell culture system is considered to an effective tool, which contributes to several cell functions. Thus, the present study aimed to investigate the effect of dynamic 3D SMG culture on the proliferation and odontogenic differentiation abilities of hDPSCs in poly (lactic‑co‑glycolic acid) (PLGA) scaffolds in nude mice. The hDPSCs on PLGA scaffolds were maintained separately in the 3D SMG culture system and static 3D cultures with osteogenic medium for 7 days in vitro. Subsequently, the cell‑PLGA complexes were implanted subcutaneously on the backs of nude mice for 4 weeks. The results of histological and immunohistochemical examinations of Ki‑67, type I collagen, dentin sialoprotein and DMP‑1 indicated that the proliferation and odontogenic differentiation abilities of the hDPSCs prepared in the 3D SMG culture system were higher, compared with those prepared in the static culture system. These findings suggested that dynamic 3D SMG culture likely contributes to tissue engineering by improving the proliferation and odontogenic differentiation abilities of hDPSCs in vivo.

  9. Transplantation of stem cells obtained from murine dental pulp improves pancreatic damage, renal function, and painful diabetic neuropathy in diabetic type 1 mouse model.

    PubMed

    Guimarães, Elisalva Teixeira; Cruz, Gabriela da Silva; Almeida, Tiago Farias de; Souza, Bruno Solano de Freitas; Kaneto, Carla Martins; Vasconcelos, Juliana Fraga; Santos, Washington Luis Conrado dos; Santos, Ricardo Ribeiro-dos; Villarreal, Cristiane Flora; Soares, Milena Botelho Pereira

    2013-01-01

    Diabetes mellitus (DM) is one of the most common and serious chronic diseases in the world. Here, we investigated the effects of mouse dental pulp stem cell (mDPSC) transplantation in a streptozotocin (STZ)-induced diabetes type 1 model. C57BL/6 mice were treated intraperitoneally with 80 mg/kg of STZ and transplanted with 1 × 10(6) mDPSCs or injected with saline, by an endovenous route, after diabetes onset. Blood and urine glucose levels were reduced in hyperglycemic mice treated with mDPSCs when compared to saline-treated controls. This correlated with an increase in pancreatic islets and insulin production 30 days after mDPSC therapy. Moreover, urea and proteinuria levels normalized after mDPSC transplantation in diabetic mice, indicating an improvement of renal function. This was confirmed by a histopathological analysis of kidney sections. We observed the loss of the epithelial brush border and proximal tubule dilatation only in saline-treated diabetic mice, which is indicative of acute renal lesion. STZ-induced thermal hyperalgesia was also reduced after cell therapy. Three days after transplantation, mDPSC-treated diabetic mice exhibited nociceptive thresholds similar to that of nondiabetic mice, an effect maintained throughout the 90-day evaluation period. Immunofluorescence analyses of the pancreas revealed the presence of GFP(+) cells in, or surrounding, pancreatic islets. Our results demonstrate that mDPSCs may contribute to pancreatic β-cell renewal, prevent renal damage in diabetic animals, and produce a powerful and long-lasting antinociceptive effect on behavioral neuropathic pain. Our results suggest stem cell therapy as an option for the control of diabetes complications such as intractable diabetic neuropathic pain.

  10. Schwann-like cells differentiated from human dental pulp stem cells combined with a pulsed electromagnetic field can improve peripheral nerve regeneration.

    PubMed

    Hei, Wei-Hong; Kim, Soochan; Park, Joo-Cheol; Seo, Young-Kwon; Kim, Soung-Min; Jahng, Jeong Won; Lee, Jong-Ho

    2016-03-15

    The purpose of this study was to investigate the effect of Schwann-like cells combined with pulsed electromagnetic field (PEMF) on peripheral nerve regeneration. Schwann-like cells were derived from human dental pulp stem cells (hDPSCs) and verified with CD104, S100, glial fibrillary acidic protein (GFAP), laminin, and P75(NTR) immunocytochemistry. Gene expression of P75(NTR) and S100 were analyzed. Male Sprague-Dawley rats (200-250g, 6-week-old) were divided into seven groups (n = 10 each): control, sham, PEMF, hDPSCs, hDPSCs + PEMF, Schwann-like cells, Schwann-like cells + PEMF. Cells were transplanted (1 × 10(6) /10µl/rat) at crush-injury site or combined with PEMF (50 Hz, 1 h/day, 1 mT). Nerve regeneration was evaluated with functional test, histomorphometry and retrograde labelled neurons. Schwann-like cells expressed CD104, S100, GFAP, laminin, and p75 neurotrophin receptor (P75(NTR) ). P75(NTR) and S100 mRNA expression was highest in Schwann-like cells + PEMF group, which also showed increased Difference and Gap scores. Axons and retrograde labeled neurons increased in all treatment groups. Schwann-like cells, hDPSCs with or without PEMF, and PEMF only improved peripheral nerve regeneration. Schwann-like cells + PEMF showed highest regeneration ability; PEMF has additive effect on hDPSCs, Schwann-like cell in vitro and nerve regeneration ability after transplantation in vivo. Bioelectromagnetics. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Inhibition of peptidylarginine deiminase attenuates inflammation and improves survival in a rat model of hemorrhagic shock.

    PubMed

    He, Wei; Zhou, Peter; Chang, Zhigang; Liu, Baoling; Liu, Xuefeng; Wang, Yanming; Li, Yongqing; Alam, Hasan B

    2016-02-01

    We have recently shown that inhibition of peptidylarginine deiminase (PAD) improves survival in a rodent model of lethal cecal ligation and puncture. The roles of PAD inhibitors in hemorrhagic shock (HS), however, are largely unknown. The goal of this study was to investigate the effects of YW3-56, a novel PAD inhibitor, on survival after severe HS. Mouse macrophages were exposed to hypoxic conditions followed by reoxygenation in the presence or absence of YW3-56. Enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of secreted tumor necrosis factor α and interleukin-6 in the culture medium. Cell viability was determined by methyl thiazolyl tetrazolium assay. In the survival experiment, anesthetized male Wistar-Kyoto rats (n = 10/group) were subjected to 55% blood loss, and treated with or without YW3-56 (10 mg/kg, intraperitoneally). Survival was monitored for 12 h. In the nonsurvival experiment, morphologic changes of the lungs were examined. Levels of circulating cytokine-induced neutrophil chemoattractant 1 (CINC-1) and myeloperoxidase (MPO) in the lungs were measured by ELISA. Expression of lung intercellular adhesion molecules-1 (ICAM-1) was also determined by Western blotting. Hypoxia/reoxygenation (H/R) insult induced tumor necrosis factor α and interleukin-6 secretion from macrophages, which was significantly attenuated by YW3-56 treatment. YW3-56 treatment also increased cell viability when macrophages were exposed to H/R up to 6/15 h and improved survival rate from 20% to 60% in lethal HS rat model. Compared to the sham groups, pulmonary MPO activity and ICAM-1 expression in the HS group were significantly increased, and acute lung injury was associated with a higher degree of CINC-1 levels in serum. Intraperitoneal delivery of YW3-56 significantly reduced pulmonary MPO and ICAM-1 expression and attenuated acute lung injury. Our results demonstrate for the first time that administration of YW3-56, a novel PAD inhibitor, can improve

  12. Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration.

    PubMed

    Saghiri, Mohammad Ali; Asatourian, Armen; Sorenson, Christine M; Sheibani, Nader

    2015-06-01

    Dental pulp regeneration is a part of regenerative endodontics, which includes isolation, propagation, and re-transplantation of stem cells inside the prepared root canal space. The formation of new blood vessels through angiogenesis is mandatory to increase the survival rate of re-transplanted tissues. Angiogenesis is defined as the formation of new blood vessels from preexisting capillaries, which has great importance in pulp regeneration and homeostasis. Here the contribution of human dental pulp stem cells and proangiogenic and antiangiogenic factors to angiogenesis process and regeneration of dental pulp is reviewed. A search was performed on the role of angiogenesis in dental pulp regeneration from January 2005 through April 2014. The recent aspects of the relationship between angiogenesis, human dental pulp stem cells, and proangiogenic and antiangiogenic factors in regeneration of dental pulp were assessed. Many studies have indicated an intimate relationship between angiogenesis and dental pulp regeneration. The contribution of stem cells and mechanical and chemical factors to dental pulp regeneration has been previously discussed. Angiogenesis is an indispensable process during dental pulp regeneration. The survival of inflamed vital pulp and engineered transplanted pulp tissue are closely linked to the process of angiogenesis at sites of application. However, the detailed regulatory mechanisms involved in initiation and progression of angiogenesis in pulp tissue require investigation. Published by Elsevier Inc.

  13. Role of Angiogenesis in Endodontics: Contributions of Stem Cells and Proangiogenic and Antiangiogenic Factors to Dental Pulp Regeneration

    PubMed Central

    Saghiri, Mohammad Ali; Asatourian, Armen; Sorenson, Christine M.; Sheibani, Nader

    2016-01-01

    Introduction Dental pulp regeneration is a part of regenerative endodontics, which includes isolation, propagation, and re-transplantation of stem cells inside the prepared root canal space. The formation of new blood vessels through angiogenesis is mandatory to increase the survival rate of re-transplanted tissues. Angiogenesis is defined as the formation of new blood vessels from preexisting capillaries, which has great importance in pulp regeneration and homeostasis. Here the contribution of human dental pulp stem cells and proangiogenic and antiangiogenic factors to angiogenesis process and regeneration of dental pulp is reviewed. Methods A search was performed on the role of angiogenesis in dental pulp regeneration from January 2005 through April 2014. The recent aspects of the relationship between angiogenesis, human dental pulp stem cells, and proangiogenic and antiangiogenic factors in regeneration of dental pulp were assessed. Results Many studies have indicated an intimate relationship between angiogenesis and dental pulp regeneration. The contribution of stem cells and mechanical and chemical factors to dental pulp regeneration has been previously discussed. Conclusions Angiogenesis is an indispensable process during dental pulp regeneration. The survival of inflamed vital pulp and engineered transplanted pulp tissue are closely linked to the process of angiogenesis at sites of application. However, the detailed regulatory mechanisms involved in initiation and progression of angiogenesis in pulp tissue require investigation. PMID:25649306

  14. The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap

    PubMed Central

    Swartz, Justin E.; Aarts, Mark C.J.; Swart, Karin M.A.; Disa, Joseph J.; Gerressen, Marcus; Kuo, Yur-Ren; Wax, Mark K.; Grolman, Wilko; Braunius, Weibel W

    2016-01-01

    Background Free radial forearm flap (FRFF) reconstruction is a valuable technique in head and neck surgery, that allows closure of large defects while striving to maintain functionality. Anticoagulative drugs are often administered to improve flap survival, although evidence regarding effectiveness is lacking. Objective of review To investigate the effectiveness of postoperative anticoagulants to improve survival of the FRFF in head and neck reconstruction. Type of review Systematic review and multicenter, individual patient data meta-analysis. Search strategy MEDLINE, EMBASE, Web of Science and CINAHL were searched for synonyms of ‘anticoagulants’ and ‘free flap reconstruction’. Evaluation method Studies were critically appraised for directness of evidence and risk of bias. Authors of the highest quality publications were invited to submit their original data for meta-analysis. Results Five studies were of adequate quality and data from four studies (80%) were available for meta-analysis, describing 759 FRFF procedures. Anticoagulants used were: aspirin (12%), low-molecular weight dextran (18.3%), unfractioned heparin (28.1%), low-molecular weight heparin (49%) and prostaglandin-E1 (2.1%). Thirty-one percent did not receive anticoagulants. Flap failure occurred in 40 of 759 patients (5.3%) On univariate analysis, use of unfractioned heparin was associated with a higher rate of flap failure. However, these regimens were often administered to patients who had revision surgery of the anastomosis. In multivariate logistic regression analysis, anticoagulant use was not associated with improved flap survival or flap-related complications. Conclusions The studied anticoagulative drugs did not improve FRFF survival or lower the rate of flap-related complications. In addition some anticoagulants may cause systemic complications. PMID:25823832

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

    PubMed Central

    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

    Objective 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. Design 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. Results 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 (p<0.001) and improved survival (p<0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in postoperative mortality of 1.5% (6.5%–5%, p<2.2×10−6) and an improvement in survival (p<10−19; 5-year difference: 3.8% (41.0%–44.8%)) comparing high participation for ≥4 years with 0 years. Conclusions There is a strong independent association between survival and participation in interventional clinical studies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation. PMID:27797935

  16. HEMODYNAMIC RESUSCITATION CHARACTERISTICS ASSOCIATED WITH IMPROVED SURVIVAL AND SHOCK RESOLUTION AFTER CARDIAC ARREST

    PubMed Central

    Janiczek, Jonathan A.; Winger, Daniel G.; Coppler, Patrick; Sabedra, Alexa R.; Murray, Holt; Pinsky, Michael R.; Rittenberger, Jon C.; Reynolds, Joshua C.; Dezfulian, Cameron

    2015-01-01

    Purpose To determine which strategy of early post-cardiac arrest hemodynamic resuscitation was associated with best clinical outcomes. We hypothesized that higher mean arterial pressure (MAP) achieved using IV fluids over vasopressors would yield better outcomes. Methods Retrospective cohort study of post-cardiac arrest patients between March 2011 and June 2012. Patients successfully resuscitated from cardiac arrest, admitted to an ICU and surviving at least 24 hours were included. Patients missing data for >2 hours after ROSC were excluded. The institutional standard for post-resuscitation MAP was ≥65 mmHg with no guidelines on how MAP was supported. We examined the association between early (6h) average MAP, vasopressor use summarized as cumulative vasopressor index (CVI) and fluid intake with outcomes including survival to discharge, favorable neurologic outcome based on Cerebral Performance Category (CPC) 1 or 2, and the surrogate outcome measure of lactate clearance using Pearson correlation and multivariable regression. Results Of 118 patients, 55 (46%) survived to hospital discharge, 21 (18%) with favorable neurologic outcome. Higher 6h mean CVI was independently associated with worsened survival (OR 0.67; 95% CI 0.53, 0.85; p = 0.001). Resuscitation subgroups receiving higher than median vasopressors had worsened survival to hospital discharge regardless of fluid intake. In addition, higher MAP-6h correlated with increased lactate clearance (r=0.29; p= 0.011) Conclusions Early post-ROSC hemodynamic resuscitation achieving higher MAP using fluid preferentially over vasopressors is associated with improved survival to hospital discharge as well as better lactate clearance. PMID:26717104

  17. Pancreatectomy Predicts Improved Survival for Pancreatic Adenocarcinoma: Results of an Instrumental Variable Analysis

    PubMed Central

    McDowell, Bradley D.; Chapman, Cole G.; Smith, Brian J.; Button, Anna M.; Chrischilles, Elizabeth A.; Mezhir, James J.

    2014-01-01

    Background and Objective Pancreatic resection is the standard therapy for patients with stage I/II pancreatic ductal adenocarcinoma (PDA), yet many studies demonstrate low rates of resection. The objective of this study is to evaluate whether increasing resection rates would result in an increase in average survival in patients with stage I/II PDA. Methods SEER data were analyzed for patients with stage I/II pancreatic head cancers treated from 2004–2009. Pancreatectomy rates were examined within Health Service Areas (HSA) across 18 SEER regions. An instrumental variables (IV) analysis was performed, using HSA rates as an instrument, to determine the impact of increasing resection rates on survival. Results Pancreatectomy was performed in 4,322 of the 8,323 patients evaluated with stage I/II PDA (overall resection rate=51.9%). The resection rate across HSAs ranged from an average of 38.6% in the lowest quintile to 67.3% in the highest quintile. Median survival was improved in HSAs with higher resection rates. IV analysis revealed that, for patients whose treatment choices were influenced by the rates of resection in their geographic region, pancreatectomy was associated with a statistically significant increase in overall survival. Conclusions When controlling for confounders using IV analysis, pancreatectomy is associated with a statistically significant increase in survival for patients with resectable PDA. Based on these results, if resection rates were to increase in select patients, then average survival would also be expected to increase. It is important that this information be provided to physicians and patients so they can properly weigh the risks and advantages of pancreatectomy as treatment for PDA. PMID:24979599

  18. Improved survival and function of rat cryopreserved islets by coculture with sertoli cells.

    PubMed

    Li, Yang; Xue, Wujun; Tian, Xiaohui; Ding, Xiaoming; Tian, Puxun; Feng, Xinshun; Song, Yong; Luo, Xiaohui; Liu, Hongbao; Wang, Xiaohong; Ding, Chenguang

    2011-06-01

    In order to investigate how to improve the function and survival of cryopreserved islets, we cocultured cryopreserved thawed rat islets with rat Sertoli cells. After thawing, the islets were divided into the Sertoli cell coculture group and the control group. Using light and transmission electron microscopes, we examined the morphology of islets and measured their apoptosis index (AI) and insulin release stimulation index (SI). Moreover, we measured apoptosis protein and mRNA by western-blot and reverse transcription polymerase chain reaction and cytokine concentrations in supernatant by ELISA. We examined islet graft survival time in diabetic mice and detected insulin in grafts by immunohistochemistry. We found that the morphology, AI, and SI of the coculture group were all significantly improved. The relative expression levels of cleaved caspase-3 P20, P11, and caspase-7 in the coculture group were lower than those in the control group. Compared with the control group, the expression level of Bax was decreased, but that of Bcl-2 was increased. After transplantation, islet survival in the coculture group was similar to that of fresh islets but longer than that in the control group. These results suggest that coculture with rat Sertoli cells significantly improves the yield and function of rat cryopreserved thawed islets by effectively reducing islet apoptosis.

  19. Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis.

    PubMed Central

    Sevransky, J E; Shaked, G; Novogrodsky, A; Levitzki, A; Gazit, A; Hoffman, A; Elin, R J; Quezado, Z M; Freeman, B D; Eichacker, P Q; Danner, R L; Banks, S M; Bacher, J; Thomas, M L; Natanson, C

    1997-01-01

    Tyrosine kinase-dependent cell signaling is postulated to be a pivotal control point in inflammatory responses initiated by bacterial products and TNF. Using a canine model of gram-negative septic shock, we investigated the effect of tyrosine kinase inhibitors (tyrphostins) on survival. Animals were infected intraperitoneally with Escherichia coli 0111: B4, and then, in a randomized, blinded fashion, were treated immediately with one of two tyrphostins, AG 556 (n = 40) or AG 126 (n = 10), or with control (n = 50), and followed for 28 d or until death. All animals received supplemental oxygen, fluids, and antibiotics. Tyrphostin AG 556 improved survival times when compared to controls (P = 0.05). During the first 48 h after infection, AG 556 also improved mean arterial pressure, left ventricular ejection fraction, cardiac output, oxygen delivery, and alveolar-arterial oxygen gradient compared to controls (all P < or = 0.05). These improvements in organ injury were significantly predictive of survival. Treatment with AG 556 had no effect on clearance of endotoxin or bacteria from the blood (both P = NS); however, AG 556 did significantly lower serum TNF levels (P = 0.03). These data are consistent with the conclusion that AG 556 prevented cytokine-induced multiorgan failure and death during septic shock by inhibiting cell-signaling pathways without impairing host defenses as determined by clearance of bacteria and endotoxin. PMID:9109441

  20. The development of advanced hydroelectric turbines to improve fish passage survival

    SciTech Connect

    Cada, Glenn F.

    2001-09-01

    Recent efforts to improve the survival of hydroelectric turbine-passed juvenile fish have explored modifications to both operation and design of the turbines. Much of this research is being carried out by power producers in the Columbia River basin (U.S. Army Corps of Engineers and the public utility districts), while the development of low impact turbines is being pursued on a national scale by the U.S. Department of Energy. Fisheries managers are involved in all aspects of these efforts. Advanced versions of conventional Kaplan turbines are being installed and tested in the Columbia River basin, and a pilot scale version of a novel turbine concept is undergoing laboratory testing. Field studies in the last few years have shown that improvements in the design of conventional turbines have increased the survival of juvenile fish. There is still much to be learned about the causes and extent of injuries in the turbine system (including the draft tube and tailrace), as well as the significance of indirect mortality and the effects of turbine passage on adult fish. However, improvements in turbine design and operation, as well as new field, laboratory, and modeling techniques to assess turbine-passage survival, are contributing toward resolution of the downstream fish passage issue at hydroelectric power plants.

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

    PubMed

    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 <65 years, male sex, nonwhite race, use of a community treatment facility, non-Medicare insurance, and diagnosis before 2004. Improved and 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, <12 lymph nodes evaluated, positive resection margins, or T4 histology), age, or chemotherapy regimen, even after adjustment for covariates and propensity score weighting (hazard ratio, 0.76; P<.001). There was no difference in survival noted between single and multiagent adjuvant chemotherapy regimens. In what to the authors' knowledge is the largest group of patients with stage II colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy

  2. Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection.

    PubMed

    Laurence, Graham; Ahuja, Vanita; Bell, Ted; Grim, Rod; Ahuja, Nita

    2017-09-01

    Multivisceral resection (MVR) is considered a radical operation with many surgeons only using it as a last resort. However, when locally advanced colorectal cancers invade adjacent organs, MVR is an important consideration for select patients. The current study addresses the outcomes of MVR in locally advanced recto-sigmoid cancer patients subsequent to these recommendations and hypothesizes that MVR yields improved survival. SEER data (1988-2008) was used to identify all eligible patients with MVR. Patients were limited to single primary locally advanced non-metastatic colorectal cancers originating from the sigmoid and rectum. A total of 4111 locally advanced non-metastatic recto sigmoid cancer patients were included in the study. Cox regression analysis showed variables predictive of MVR were female (OR = 1.95) and late year period (OR = 1.90). Kaplan Meier analysis showed that five-year survival was highest for MVR (52.7%, 48 months), followed by standard surgery (SS; 38.9%, 32 months) and no surgery (NS; 16.6%, 12 months, P < 0.001). With radiation treatment, five year survival improved for all groups, with the highest being MVR (57%, 52 months). With no radiation treatment, five year survival decreased for all groups, with the highest being MVR (45.1%, 44 months), followed by SS (27.3%, 19 months), and NS (8.7%, 6 months, P < 0.001). The present study supports that MVR offers greater survival advantage in patients with locally advanced colorectal cancer. MVR are extensive surgical procedures with significant associated morbidity that usually require specialized training and sometimes the coordination of multiple surgical specialists. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Early administration of isosorbide dinitrate improves survival of cyanide-poisoned rabbits.

    PubMed

    Lavon, Ophir

    2015-01-01

    More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the survival of cyanide-poisoned mice. To evaluate the effectiveness of isosorbide dinitrate compared with that of sodium nitrite in cyanide poisoning. A comparative animal study was performed using 18 rabbits, randomized into 3 study groups. Animals were poisoned intravenously with potassium cyanide (1 mg/kg). The first group was not given any further treatment. The second and third groups were treated intravenously 1 min after poisoning with sodium nitrite (6 mg/kg) and isosorbide dinitrate (50 μg/kg), respectively. The primary outcome was short-term survival of up to 30 min. Secondary outcomes included time to death, a clinical score, mean blood pressure, pulse, blood pH, and lactate and methemoglobin levels. Rabbits treated with isosorbide dinitrate or sodium nitrite survived while only one untreated rabbit survived. Median time to death of the 5 poisoned and untreated animals was 10 min. All the animals collapsed soon after poisoning, exhibiting rapidly disturbed vital signs and developed lactic metabolic acidosis; average peak blood lactate levels were 15.5-19.1 mmol/L at 10 min after poisoning. The treated animals improved gradually with practically full recovery of the clinical scores, vital signs, and blood gas levels. Sodium nitrite administration raised methemoglobin to an average peak of 7.9%, while isosorbide dinitrate did not change methemoglobin levels. Early administration of isosorbide dinitrate improved the short-term survival of cyanide-poisoned rabbits. Isosorbide dinitrate shows potential as an antidote for cyanide poisoning and may exert its effect using a nitric-oxide-dependent mechanism.

  4. Evidence of improving survival of patients with rectal cancer in France: a population based study

    PubMed Central

    Finn-Faivre, C; Maurel, J; Benhamiche, A; Herbert, C; Mitry, E; Launoy, G; Faivre, J

    1999-01-01

    BACKGROUND—Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. 
AIMS—To determine trends in management and prognosis of rectal cancer in two French regions. 
SUBJECTS—1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. 
METHODS—Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. 
RESULTS—Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17.7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). 
CONCLUSIONS—Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival. 

 Keywords: rectal cancer; treatment; stage at diagnosis; survival; time trends; cancer registries PMID:10026324

  5. Icodextrin decreases technique failure and improves patient survival in peritoneal dialysis patients.

    PubMed

    Wang, I-Kuan; Li, Yu-Fen; Chen, Jin-Hua; Liang, Chih-Chia; Liu, Yao-Lung; Lin, Hsin-Hung; Chang, Chiz-Tzung; Tsai, Wen-Chen; Yen, Tzung-Hai; Huang, Chiu-Ching

    2015-03-01

    It remains unclear whether long-term daily icodextrin use can decrease technique failure and improve survival in peritoneal dialysis (PD) patients. The aim of the present study was to investigate whether icodextrin use, once daily, can decrease technique failure and prolong patient survival in incident PD patients. Incident PD patients who survived more than 90 days were recruited from the China Medical University Hospital, Taiwan, between 1 January 2007 and 31 December 2011. All patients were followed until transfer to haemodialysis (HD), renal transplantation, transfer to another centre, death, or 31 December 2011. A total of 306 incident PD patients (89 icodextrin users, 217 icodextrin non-users) were recruited during the study period. Icodextrin users were more likely to have hypertension, diabetes and high or high-average peritoneal transport compared with non-users. During the follow-up period, 43 patients were transferred to HD: seven (7.87%) of the icodextrin group, and 36 (16.59%) of the non-icodextrin group. Thirty-two patients died during the follow-up period: five (5.62%) of the icodextrin group, and 27 (12.44%) of the non-icodextrin group. Icodextrin use was significantly associated with a better prognosis, in terms of technique failure (adjusted HR = 0.32; 95% CI = 0.14-0.72). With regard to patient survival, icodextrin use (adjusted HR = 0.33; 95% CI = 0.12-0.87) was associated with a significantly lower risk of death. The use of icodextrin once daily may decrease technique failure and improve survival in incident PD patients. © 2014 Asian Pacific Society of Nephrology.

  6. Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer.

    PubMed

    Ingersoll, Susan B; Ahmad, Sarfraz; McGann, Hasina C; Banks, Robert K; Stavitzski, Nicole M; Srivastava, Milan; Ali, Ghazanfar; Finkler, Neil J; Edwards, John R; Holloway, Robert W

    2015-09-01

    Studies have shown enhanced survival of ovarian cancer patients in which the tumors are infiltrated with tumor infiltrating lymphocytes and natural killer cells showing the importance of immune surveillance and recognition in ovarian cancer. Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFNα-2b) in a xenograft mouse model of ovarian cancer. SKOV3-AF2 ovarian cancer cells were injected intra-peritoneally (IP) into athymic nude mice. On day 7 post-tumor cell injection, mice were injected IP with peripheral blood mononuclear cells (PBMC; 5 × 10(6) PBMC) and cytokine combinations [IL-2 ± pegylated-IFNα-2b (IFN)]. Cytokine injections were continued weekly for IFN (12,000 U/injection) and thrice weekly for IL-2 (4000 U/injection). Mice were euthanized when they became moribund due to tumor burden at which time tumor and ascitic fluid were measured and collected. Treatment efficacy was measured by improved survival at 8 weeks and overall survival by Kaplan-Meier analysis. We observed that the mice tolerated all treatment combinations without significant weight loss or other apparent illness. Mice receiving PBMC plus IL-2 showed improved median survival (7.3 weeks) compared to mice with no treatment (4.2 weeks), IL-2 (3.5 weeks), PBMC (4.0 weeks), or PBMC plus IL-2 and IFN (4.3 weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5 weeks, p > 0.05). We demonstrate that cytokine-stimulated cellular immune therapy with PBMC and IL-2 was well tolerated and resulted in survival advantage compared to untreated controls and other cytokine combinations in the nude-mouse model.

  7. Cyclosporine withdrawal improves long-term graft survival in renal transplantation.

    PubMed

    Gallagher, Martin; Jardine, Meg; Perkovic, Vlado; Cass, Alan; McDonald, Stephen; Petrie, James; Eris, Josette

    2009-06-27

    The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival. Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear. This randomized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens: azathioprine and prednisolone (AP), long-term cyclosporine alone (Cy), or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL). Between 1983 and 1986, 489 patients were randomized with 98% follow-up to a median of 20.6 years. Mean graft survival (censoring deaths) was superior in the WDL group (14.8 years) when compared with both AP (12.4 years, P=0.01 log-rank test) and Cy (12.5 years, P=0.01 log-rank test) groups by intention-to-treat. Without death censoring, graft survival with WDL was superior to AP (9.5 years vs. 6.7 years, P=0.04) and of borderline superiority to Cy (9.5 years vs. 8.5 years, P=0.06). Patient survival was not different between the three groups. Renal function was superior in AP (at 1, 10, and 15 years posttransplant) and WDL (at 1, 5, 10, 15, and 20 years) groups when compared with Cy. This study illustrates superior long-term renal transplant survival and preservation of renal function with a protocol using cyclosporine withdrawal. If long-term renal transplant outcomes are to improve, we should reconsider guidelines recommending universal maintenance use of cyclosporine.

  8. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer's disease.

    PubMed

    Mita, Tsuneyuki; Furukawa-Hibi, Yoko; Takeuchi, Hideyuki; Hattori, Hisashi; Yamada, Kiyofumi; Hibi, Hideharu; Ueda, Minoru; Yamamoto, Akihito

    2015-10-15

    Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by a decline in cognitive abilities and the appearance of β-amyloid plaques in the brain. Although the pathogenic mechanisms associated with AD are not fully understood, activated microglia releasing various neurotoxic factors, including pro-inflammatory cytokines and oxidative stress mediators, appear to play major roles. Here, we investigated the therapeutic benefits of a serum-free conditioned medium (CM) derived from the stem cells of human exfoliated deciduous teeth (SHEDs) in a mouse model of AD. The intranasal administration of SHEDs in these mice resulted in substantially improved cognitive function. SHED-CM contained factors involved in multiple neuroregenerative mechanisms, such as neuroprotection, axonal elongation, neurotransmission, the suppression of inflammation, and microglial regulation. Notably, SHED-CM attenuated the pro-inflammatory responses induced by β-amyloid plaques, and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like microglia. Our data suggest that SHED-CM may provide significant therapeutic benefits for AD.

  9. DENTAL PULP TISSUE ENGINEERING

    PubMed Central

    Demarco, FF; Conde, MCM; Cavalcanti, B; Casagrande, L; Sakai, V; Nör, JE

    2013-01-01

    Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research. PMID:21519641

  10. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis

    PubMed Central

    Ma, Shu-Juan; Zheng, Yi-Xiang; Zhou, Peng-Cheng; Xiao, Yan-Ni; Tan, Hong-Zhuan

    2016-01-01

    Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable, pooled HR ranged from 0.47 to 0.57. The results indicated that metformin use improved survival of diabetic liver cancer patients. However, the results should be interpreted with caution given the possibility of residual confounding. Further prospective studies are still needed to confirm the prognostic benefit of metformin use. PMID:27494848

  11. PRP&F/P MPs improved survival of dorsal paired pedicle skin flaps in rats.

    PubMed

    Takikawa, Megumi; Sumi, Yuki; Ishihara, Masayuki; Kishimoto, Satoko; Nakamura, Shingo; Yanagibayashi, Satoshi; Hattori, Hidemi; Azuma, Ryuichi; Yamamoto, Naoto; Kiyosawa, Tomoharu

    2011-09-01

    Skin flap necrosis is a problem encountered postoperatively. The purpose of this study was to evaluate the effects of platelet-rich plasma containing fragmin/protamine microparticles (PRP&F/P MPs) on viability in a rat dorsal paired pedicle skin (DPPS) flap. Two symmetrical adjoining rectangular flaps (8 × 2 cm each) were drawn on the rat dorsum. Two days after PRP&F/P MPs-, PRP-, F/P MPs-, and saline (control)-injections (n = 8 each), flaps were elevated as a random pattern flap without the lateral thoracic, posterior intercostal, and deep circumflex iliac vessels. The flaps were immediately sutured back and the flap survival area was measured 7 d after flap elevation. The flap survival rate in PRP&F/P MPs-injected groups (73.1% ± 4.2%) was significantly higher than those in PRP (64.9% ± 4.0%), F/P MPs (59.4 ± 4.5%), and control (61.2% ± 4.2%) groups. Histologic observation of the flaps showed survived thick granulation tissue and neovascularization in PRP&F/P MPs-injected groups. When PRP&F/P MPs are administered 2 d before the flap elevation, the improved flap survivals are observed. The pre-injection of PRP&F/P MPs may thus represent a promising treatment to prevent skin flap necrosis in reconstructive surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. A childhood chemotherapy protocol improves overall survival among adults with T-lymphoblastic lymphoma

    PubMed Central

    Xia, Zhong-jun; Chen, Xiao-qin; Geng, Qi-rong; Wang, Wei-da; Wang, Liang; Lu, Yue

    2016-01-01

    A broadly accepted standard treatment for adult T-lymphoblastic lymphoma (T-LBL) has not yet been defined. To address that issue, we retrospectively compared three chemotherapy regimens used to treat 110 adult patients with newly diagnosed T-LBL. These included two adult regimens (ECOG2993 and hyper-CVAD) and a childhood regimen (BFM-90). These intensive drug regimens are mainly used to treat childhood and adult acute lymphoblastic leukemia. They included induction, consolidation, and maintenance chemotherapy protocols and were administered over the course of 2 years. Seventy-five patients (80%) achieved a complete remission (CR). Within a median follow-up time of 31 months (range: 5–152 months), the 5-year overall survival (OS) and progression-free survival (PFS) rates were 47.7% (95% CI, 35.0–69.8%) and 45.7% (95% CI, 27.6–56.6%), respectively. Shorter survival was associated with age > 40 years, poor ECOG PS and bone marrow involvement. Elevated lactic dehydrogenase (LDH) level, Ann Arbor stage and International Prognostic Index (IPI) score had no prognostic value. The childhood chemotherapy regimen improved CR and the overall survival rate more than the adult regimen in patients aged < 40 years. PMID:27150061

  13. Survival of women with microinvasive adenocarcinoma of the cervix is not improved by radical surgery.

    PubMed

    Bean, Lisa M; Ward, Kristy K; Plaxe, Steven C; McHale, Michael T

    2017-09-01

    (local excision compared with simple hysterectomy [P = .64]; local excision compared with radical hysterectomy [P = .82]; or simple hysterectomy compared with radical hysterectomy [P = .70]). Among patients with adenocarcinoma, 0.97% had positive pelvic lymph nodes, none had positive aortic lymph nodes, and 91.85% had confirmed negative lymph nodes. For squamous cell carcinoma, 0.72% of patients had positive pelvic lymph nodes and 0.10% had positive aortic lymph nodes. There was no significant difference in survival when patients were compared by cell type or procedure, suggesting that survival of patients with microinvasive adenocarcinoma is not improved by utilizing more invasive surgical methods. Regardless of histology, the frequency of nodal involvement was very low among both groups, supporting an overall excellent prognosis for all patients with microinvasive disease. We submit these data as evidence that preoperative planning of more conservative techniques is appropriate, not just for those with squamous histology or who desire future fertility, but for all patients with microinvasive cervical disease. Copyright © 2017. Published by Elsevier Inc.

  14. Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy.

    PubMed

    Heiduschka, Gregor; Grah, Anja; Oberndorfer, Felicitas; Kadletz, Lorenz; Altorjai, Gabriela; Kornek, Gabriela; Wrba, Fritz; Thurnher, Dietmar; Selzer, Edgar

    2015-03-01

    In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear. We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95% stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan-Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Expression of p16 or high-risk HPV-DNA was detected in 60.3% and 39.6% of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91%] as well as HPV infection (OS at 2 years: 95%) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival. p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct "very high-risk patient group" that may benefit from intensified or novel treatment combinations.

  15. Early Enhanced Local Neutrophil Recruitment in Peritonitis-Induced Sepsis Improves Bacterial Clearance and Survival

    PubMed Central

    Craciun, Florin L.; Schuller, Elizabeth R.; Remick, Daniel G.

    2017-01-01

    Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis. PMID:21041722

  16. Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival.

    PubMed

    Craciun, Florin L; Schuller, Elizabeth R; Remick, Daniel G

    2010-12-01

    Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis.

  17. Dry Kraft Pulping at Ambient Pressure for Cost Effective Energy Saving and Pollution Deduction

    SciTech Connect

    Yulin Deng; Art Ragauskas

    2012-08-28

    evaporated first under vacuum condition at low temperature. Then, the dry woodchips were baked at high temperature (120-130 C) at atmospheric pressure. The qualities of the pulp made with this method were improved compared to that made with method one. The pulp shows higher brightness and lower bulk than Kraft pulping. The tensile strength is significantly higher than the pulp made from the first method. Although the pulp is stronger than that of TMP pulp, it is still lower than conventional Kraft fiber. Method Three: The third dry method was done in a Kraft pulping digester at elevated pressure but without free liquid in the digester. With this method, pulp that has almost the same qualities as conventional Kraft pulp could be produced. The screen yield, Kappa number, fiber brightness, pulp strength and pulp bulk are almost identical to the conventional Kraft pulp. The key advantages of this dry pulping method include ca. 55 % of cooking energy saved during the pulping process, as high as 50 wt% of NaOH saving as well as 3 wt% of Na2S saving comparing to Kraft one. By analyzing fiber properties, yields, chemical and energy consumptions, we concluded that the dry pulping method based on Liquid Free Chemical Pulping, LFCP, could be very attractive for the pulp and paper industry. More fundamental studies and scale up trials are needed to fully commercialize the technology. We expect to conduct pilot trials between 12 to 24 months of period if the DOE or industry can provide continual research funding. Based on the technology we demonstrated in this report, several pilot trial facilities in the United States will be available after small modifications. For example, the Herty Foundation in Savannah, Georgia is one of these potential locations. DOE funding for continuous study and final lead to commercialization of the technique is important.

  18. Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups.

    PubMed

    Pulte, Dianne; Redaniel, Maria Theresa; Jansen, Lina; Brenner, Hermann; Jeffreys, Mona

    2013-02-01

    The survival of younger patients with acute leukemia has improved in the early 21(st) century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21(st) century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes.

  19. Melatonin receptors mediate improvements of survival in a model of polymicrobial sepsis.

    PubMed

    Fink, Tobias; Glas, Michael; Wolf, Alexander; Kleber, Astrid; Reus, Erik; Wolff, Martin; Kiefer, Daniel; Wolf, Beate; Rensing, Hauke; Volk, Thomas; Mathes, Alexander M

    2014-01-01

    Melatonin has been demonstrated to improve survival after experimental sepsis via antioxidant effects. Yet, recent evidence suggests that this protective capacity may also rely on melatonin receptor activation. Therefore, the present study was designed to investigate whether selective melatonin receptor-agonist ramelteon may influence survival and immune response in a model of polymicrobial sepsis in rats, wild-type and melatonin receptor MT1/MT2 double knockout mice. Prospective, randomized, controlled study. University research laboratory. Male Sprague-Dawley rats (200-250 g) and male C3H/HeN wild-type and MT1/MT2 receptor knockout mice (20-22 g). Animals underwent cecal ligation and incision and remained anesthetized for evaluation of survival for 12 hours (rats: n = 15 per group) or 15 hours (mice: n = 10 per group). Analysis of immune response by means of enzyme-linked immunosorbent assay was performed before and 5 hours after cecal ligation and incision (rats only; n = 5 per group). After induction of sepsis, animals were treated IV with vehicle, different doses of melatonin (rats: 0.01/0.1/1.0/10 mg/kg; mice: 1.0 mg/kg), ramelteon, melatonin receptor-antagonist luzindole, ramelteon + luzindole, or melatonin + luzindole (each 1.0 mg/kg). Sham controls underwent laparotomy but not cecal ligation and incision. Compared with vehicle, administration of ramelteon or melatonin significantly improved median survival time in rats (sepsis/melatonin [0.1 mg/kg], 554 min, [1.0 mg/kg] 570 min, [10 mg/kg] 579 min; sepsis/ramelteon, 468 min; each p < 0.001 vs sepsis/vehicle, 303 min) and wild-type mice (sepsis/melatonin, 781 min; sepsis/ramelteon, 701 min; both p < 0.001 vs sepsis/vehicle, 435 min). This effect was completely antagonized by coadministration of luzindole in all groups. Melatonin, ramelteon, or luzindole had no significant effect on survival time in knockout mice. Significantly elevated concentrations of tumor necrosis factor

  20. Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

    PubMed Central

    Chamorro-Marín, Virginia; García-Delgado, Manuel; Touma-Fernández, Angel; Aguilar-Alonso, Eduardo; Fernández-Mondejar, Enrique

    2008-01-01

    Intoduction Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. β-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether β-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). Methods This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. Results In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 ± 0.27 versus 4.9 ± 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when

  1. A hemodynamic-directed approach to pediatric cardiopulmonary resuscitation (HD-CPR) improves survival.

    PubMed

    Morgan, Ryan W; Kilbaugh, Todd J; Shoap, Wesley; Bratinov, George; Lin, Yuxi; Hsieh, Ting-Chang; Nadkarni, Vinay M; Berg, Robert A; Sutton, Robert M

    2017-02-01

    Most pediatric in-hospital cardiac arrests (IHCAs) occur in ICUs where invasive hemodynamic monitoring is frequently available. Titrating cardiopulmonary resuscitation (CPR) to the hemodynamic response of the individual improves survival in preclinical models of adult cardiac arrest. The objective of this study was to determine if titrating CPR to systolic blood pressure (SBP) and coronary perfusion pressure (CoPP) in a pediatric porcine model of asphyxia-associated ventricular fibrillation (VF) IHCA would improve survival as compared to traditional CPR. After 7min of asphyxia followed by VF, 4-week-old piglets received either hemodynamic-directed CPR (HD-CPR; compression depth titrated to SBP of 90mmHg and vasopressor administration to maintain CoPP ≥20mmHg); or Standard Care (compression depth 1/3 of the anterior-posterior chest diameter and epinephrine every 4min). All animals received CPR for 10min prior to the first defibrillation attempt. CPR was continued for a maximum of 20min. Protocolized intensive care was provided to all surviving animals for 4h. The primary outcome was 4-h survival. Survival rate was greater with HD-CPR (12/12) than Standard Care (6/10; p=0.03). CoPP during HD-CPR was higher compared to Standard Care (point estimate +8.1mmHg, CI95: 0.5-15.8mmHg; p=0.04). Chest compression depth was lower with HD-CPR than Standard Care (point estimate -14.0mm, CI95: -9.6 to -18.4mm; p<0.01). Prior to the first defibrillation attempt, more vasopressor doses were administered with HD-CPR vs. Standard Care (median 5 vs. 2; p<0.01). Hemodynamic-directed CPR improves short-term survival compared to standard depth-targeted CPR in a porcine model of pediatric asphyxia-associated VF IHCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Activation of AMPK by Metformin Improves Left Ventricular Function and Survival in Heart Failure

    PubMed Central

    Gundewar, Susheel; Calvert, John W.; Jha, Saurabh; Toedt-Pingel, Iris; Ji, Sang Yong; Nunez, Denise; Ramachandran, Arun; Anaya-Cisneros, Mauricio; Tian, Rong; Lefer, David J.

    2009-01-01

    Clinical studies have reported that the widely used anti-hyperglycemic drug metformin significantly reduces cardiac risk factors and improves clinical outcomes in patients with heart failure. The mechanisms by which metformin exerts these cardioprotective effects remain unclear and may be independent of anti-hyperglycemic effects. We tested the hypothesis that chronic activation of AMPK with low-dose metformin exerts beneficial effects on cardiac function and survival in in vivo murine models of heart failure. Mice were subjected to permanent left coronary artery (LCA) occlusion or to 60 min LCA occlusion followed by reperfusion for 4 wks. High-resolution, two-dimensional echocardiography was performed at baseline and 4 wk post myocardial infarction to assess left ventricular (LV) dimensions and function. Metformin (125 μg/kg) administered to mice at ischemia and then daily, improved survival by 47% (p < 0.05 vs. vehicle) at 4 wk following permanent LCA occlusion. Additionally, metformin given at reperfusion and then daily, preserved LV dimensions and LV ejection fraction (p < 0.01 vs. vehicle) at 4 wk. The improvement in cardiac structure and function was associated with increases in AMPK and eNOS phosphorylation as well as increased PGC-1α expression in cardiac myocytes. Furthermore, metformin significantly improved myocardial cell mitochondrial respiration and ATP synthesis compared to vehicle. The cardioprotective effects of metformin were ablated in mice lacking functional AMPK or eNOS. This study demonstrates that metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1α in a murine model of heart failure. PMID:19096023

  3. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

    PubMed Central

    Yeo, C J; Abrams, R A; Grochow, L B; Sohn, T A; Ord, S E; Hruban, R H; Zahurak, M L; Dooley, W C; Coleman, J; Sauter, P K; Pitt, H A; Lillemoe, K D; Cameron, J L

    1997-01-01

    of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis. PMID:9193189

  4. Exogenous administration of recombinant human FSH does not improve germ cell survival in human prepubertal xenografts.

    PubMed

    Van Saen, Dorien; Goossens, Ellen; Haentjens, Patrick; Baert, Yoni; Tournaye, Herman

    2013-03-01

    In a previous study, meiotic activity was observed in human intratesticular xenografts from peripubertal patients. However, full spermatogenesis could not be established. The present study aimed to evaluate whether the administration of recombinant human FSH could improve the spermatogonial survival and the establishment of full spermatogenesis in intratesticular human xenografts. Human testicular tissue was obtained from six boys (aged 2.5-12.5years). The testicular biopsy was fragmented and one fragment of 1.5-3.0mm(3) was transplanted to the testis of immunodeficient nude mice. Transplanted mice were assigned to different experimental groups to enable evaluation of the effects of FSH administration and freezing. The structural integrity of the seminiferous tubules, the spermatogonial survival and the presence of differentiated cells were evaluated by histology and immunohistochemistry. Freezing or administration of FSH did not influence tubule integrity and germ cell survival in human xenografts. Meiotic germ cells were observed in the xenografts. More tubules containing only Sertoli cells were observed in frozen-thawed grafts, and more tubules with meiotic cells were present in fresh grafts. There was no clear influence of FSH treatment on meiotic differentiation. Administration of FSH did not improve the establishment of full spermatogenesis after intratesticular tissue grafting. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis.

    PubMed

    Goldfarb, Roy D; Parker, Thomas S; Levine, Daniel M; Glock, Dana; Akhter, Imran; Alkhudari, Azzam; McCarthy, Robert J; David, Eric M; Gordon, Bruce R; Saal, Stuart D; Rubin, Albert L; Trenholme, Gordon M; Parrillo, Joseph E

    2003-02-01

    Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-alpha, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.

  6. Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons.

    PubMed

    Grumbles, Robert M; Sesodia, Sanjay; Wood, Patrick M; Thomas, Christine K

    2009-07-01

    Motoneuron death can occur over several spinal levels with disease or trauma, resulting in muscle denervation. We tested whether cotransplantation of embryonic neurons with 1 or more neurotrophic factors into peripheral nerve improved axon regeneration, muscle fiber area, reinnervation, and function to a greater degree than cell transplantation alone. Sciatic nerves of adult Fischer rats were cut to denervate muscles; 1 week later, embryonic ventral spinal cord cells (days 14-15) were transplanted into the tibial nerve stump as the only source of neurons for muscle reinnervation. Factors that promote motoneuron survival (cardiotrophin 1; fibroblast growth factor 2; glial cell line-derived neurotrophic factor; insulin-like growth factor 1; leukemia inhibitory factor; and hepatocyte growth factor) were added to the transplant individually or in combinations. Inclusion of a single factor with the cells resulted in comparable myelinated axon counts, muscle fiber areas, and evoked electromyographic activity to cells alone 10 weeks after transplantation. Only cell transplantation with glial cell line-derived neurotrophic factor, hepatocyte growth factor, and insulin-like growth factor 1 significantly increased motoneuron survival, myelinated axon counts, muscle reinnervation, and evoked electromyographic activity compared with cells alone. Thus, immediate application of a specific combination of factors to dissociated embryonic neurons improves survival of motoneurons and the long-term function of reinnervated muscle.

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

    PubMed

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

    2017-09-06

    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.

  8. Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

    PubMed

    Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

    2017-02-01

    Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI. Of 118 patients with hematologic malignancies who had AMI, 58 (49%) had sTP. Twenty-five patients (43%) with sTP received aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p = .0001) and thienopyridine treatment (27% vs. 3%; p = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count < 50,000 cells/µL), guideline-recommended medical therapy is often withheld because of the fear of major bleeding. In this study, aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © Alpha

  9. Nanoshell-mediated photothermal therapy improves survival in a murine glioma model.

    PubMed

    Day, Emily S; Thompson, Patrick A; Zhang, Linna; Lewinski, Nastassja A; Ahmed, Nabil; Drezek, Rebekah A; Blaney, Susan M; West, Jennifer L

    2011-08-01

    We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica-gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-Prkdc(SCID) mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

  10. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy

    PubMed Central

    Wang, Chunyu; Fu, Xiaolong; Cai, Xuwei; Wu, Xianghua; Hu, Xichun; Fan, Min; Xiang, Jiaqing; Zhang, Yawei; Chen, Haiquan; Jiang, Guoliang; Zhao, Kuaile

    2016-01-01

    Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09–0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC. PMID:26766917

  11. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

    PubMed Central

    Chapman, Paul B.; Hauschild, Axel; Robert, Caroline; Haanen, John B.; Ascierto, Paolo; Larkin, James; Dummer, Reinhard; Garbe, Claus; Testori, Alessandro; Maio, Michele; Hogg, David; Lorigan, Paul; Lebbe, Celeste; Jouary, Thomas; Schadendorf, Dirk; Ribas, Antoni; O’Day, Steven J.; Sosman, Jeffrey A.; Kirkwood, John M.; Eggermont, Alexander M.M.; Dreno, Brigitte; Nolop, Keith; Li, Jiang; Nelson, Betty; Hou, Jeannie; Lee, Richard J.; Flaherty, Keith T.; McArthur, Grant A.

    2013-01-01

    Background Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. Methods We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. Results At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Conclusions Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann–La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.) PMID:21639808

  12. Preservation of venous outflow improves transverse rectus abdominis musculocutaneous flap survival following vascular delay.

    PubMed

    Tsoutsos, D; Gravvanis, A; Kakagia, D; Ghali, S; Papalois, A

    2009-01-01

    The rat abdominal island model has proved to be a reliable and reproducible model for the study of surgical delay procedures. It has been customary to simultaneously divide both the artery and the accompanying vein to obtain maximum survival of the rat TRAM flap undergoing delay procedure. This study evaluates the effect of selective arterial interruption compared to standard vascular delay on flap survival in the rat TRAM flap model. Thirty-six Wistar rats were randomly assigned to three groups (n=12), depending on the vascular ligation selected for the initial experimental delay stage. In group A (control group) no vessels were ligated. In group B the right deep inferior epigastric vessels were preserved and the right superior and left inferior and superior deep vessels were ligated. In group C the right inferior epigastric vessels and the left inferior epigastric vein were preserved while superior epigastric vessels and the left inferior epigastric artery were ligated. For the second stage one week later, TRAM flaps were elevated based on the right deep inferior epigastric vessels, re-inset in their original position and digitally photographed. Skin island viability was determined 96 hours later using digital photography and image-analysis software SigmaScan (SPSS, Inc., Chicago, IL). The percentage of flap survival in control group A was 50+/-6%, in group B 60+/-4% and in group C 85+/-4%. The occlusion of the three vascular pairs in group B improved the survival percentage in comparison to the control group A, but this did not achieve statistical significance. In contrast, the percentage of flap survival in control group C was statistically significant compared to groups A and B (p<0.05, ANOVA). Zone IV exhibited no necrosis in any group C animals. This indicates that delay with preservation of the venous outflow of zone IV results in increased blood supply.

  13. Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

    PubMed

    Chapman, Paul B; Hauschild, Axel; Robert, Caroline; Haanen, John B; Ascierto, Paolo; Larkin, James; Dummer, Reinhard; Garbe, Claus; Testori, Alessandro; Maio, Michele; Hogg, David; Lorigan, Paul; Lebbe, Celeste; Jouary, Thomas; Schadendorf, Dirk; Ribas, Antoni; O'Day, Steven J; Sosman, Jeffrey A; Kirkwood, John M; Eggermont, Alexander M M; Dreno, Brigitte; Nolop, Keith; Li, Jiang; Nelson, Betty; Hou, Jeannie; Lee, Richard J; Flaherty, Keith T; McArthur, Grant A

    2011-06-30

    Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).

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

    PubMed

    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.

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

    PubMed

    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.

  16. Bypass system modification at Bonneville Dam on the Columbia River improved the survival of juvenile salmon

    USGS Publications Warehouse

    Ferguson, J.W.; Sandford, B.P.; Reagan, R.E.; Gilbreath, L.G.; Meyer, E.B.; Ledgerwood, R.D.; Adams, N.S.

    2007-01-01

    From 1987 to 1992, we evaluated a fish bypass system at Bonneville Dam Powerhouse 2 on the Columbia River. The survival of subyearling Chinook salmon Oncorhynchus tshawytscha released into the system ranged from 0.774 to 0.911 and was significantly lower than the survival of test fish released into turbines and the area immediately below the powerhouse where bypass system flow reentered the river. Yearling and subyearling Chinook salmon and yearling coho salmon O. kisutch released into the bypass system were injured or descaled. Also, levels of blood plasma cortisol and lactate were significantly higher in yearling and subyearling Chinook salmon that passed through the bypass system than in fish released directly into a net located over the bypass exit. This original system was then extensively modified using updated design criteria, and the site where juvenile fish reentered the river was relocated 2.8 km further downstream to reduce predation on bypassed fish by northern pikeminnow Ptychocheilus oregonensis. Based on studies conducted from 1999 to 2001, the new bypass system resulted in high fish survival, virtually no injuries to fish, fish passage times that were generally similar to water travel times, and mild stress responses from which fish recovered quickly. The mean estimated survival of subyearling Chinook salmon passing through the new bypass system was 0.946 in 2001, which was an usually low-flow year. Survival, physical condition, passage timing, and blood physiological indicators of stress were all useful metrics for assessing the performance of both bypass systems and are discussed. The engineering and hydraulic criteria used to design the new bypass system that resulted in improved fish passage conditions are described.

  17. Improved survival after hemostatic resuscitation: does the emperor have no clothes?

    PubMed

    Magnotti, Louis J; Zarzaur, Ben L; Fischer, Peter E; Williams, Regan F; Myers, Adrianne L; Bradburn, Eric H; Fabian, Timothy C; Croce, Martin A

    2011-01-01

    In light of recent data, controversy surrounds the apparent 30-day survival benefit of patients achieving a fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratio of at least 1:2 in the face of massive transfusions (MT) (≥10 units of PRBC within 24 hours of admission). We hypothesized that initial studies suffer from survival bias because they do not consider early deaths secondary to uncontrolled exsanguinating hemorrhage. To help resolve this controversy, we evaluated the temporal relationship between blood product administration and mortality in civilian trauma patients receiving MT. Patients requiring MT over a 22-month period were identified from the resuscitation registry of a Level I trauma center. Shock severity at admission and timing of shock-trauma admission, blood product administration, and death were determined. Patients were divided into high- and low-ratio groups (≥1:2 and<1:2 FFP:PRBC, respectively) and compared. Kaplan-Meier analysis and log-rank test was used to examine 24-hour survival. One hundred three patients (63% blunt) were identified (66 high-ratio and 37 low-ratio). Those patients who achieved a high-ratio in 24 hours had improved survival. However, severity of shock was less in the high-group (base excess: -8.0 vs. -11.2, p=0.028; lactate: 6.3 vs. 8.4, p=0.03). Seventy-five patients received MT within 6 hours. Of these, 29 received a high-ratio in 6 hours. Again, severity of shock was less in the high-ratio group (base excess: -7.6 vs. -12.7, p=0.008; lactate: 6.7 vs. 9.4, p=0.02). For these patients, 6-hour mortality was less in the high-group (10% vs. 48%, p<0.002). After accounting for early deaths, groups were similar from 6 hours to 24 hours. Improved survival was observed in patients receiving a higher plasma ratio over the first 24 hours. However, temporal analysis of mortality using shorter time periods revealed those who achieve early high-ratio are in less shock and less likely to die early from uncontrolled

  18. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

    PubMed

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G; Muenzer, Jared T; Ferguson, Thomas A; Chang, Katherine; Osborne, Dale F; Clark, Andrew T; Coopersmith, Craig M; McDunn, Jonathan E; Hotchkiss, Richard S

    2010-02-01

    IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder.

  19. Traditional Chinese medicine therapy improves the survival of systemic lupus erythematosus patients.

    PubMed

    Ma, Yi-Chun; Lin, Cheng-Chieh; Li, Chia-Ing; Chiang, Jen-Huai; Li, Tsai-Chung; Lin, Jaung-Geng

    2016-04-01

    No previous studies have evaluated the effect of traditional Chinese medicine (TCM) treatment on the survival of patients with systemic lupus erythematosus (SLE). Hence, in this study, we determined whether TCM treatment affects the survival of SLE patients. This nationwide population-based retrospective cohort study assessed 23,084 patients newly diagnosed with SLE between 1999 and 2009, using the database of the Taiwan National Health Insurance program. Among these patients, 9267 (40.15%) used TCM for SLE treatment and exhibited a significantly decreased risk of death [hazard ratio (HR) = 0.73; 95% confidence interval (CI): 0.68-0.78], with multivariate adjustment, compared with those without TCM use. A similar significant protective effect of TCM use was found across various subgroups of comorbidities. TCM use 1 year before diagnosis also reduced the risk of death. Our study findings indicated that Zhi Bo Di Huang Wan (HR = 0.54; 95% CI: 0.32-0.91), Jia Wei Xiao Yao San (HR = 0.35; 95% CI: 0.16-0.73), Liu Wei Di Huang Wan (HR = 0.51; 95% CI: 0.28-0.93), Gan Lu Yin (HR = 0.40; 95% CI: 0.17-0.96), and Yin Qiao San (HR = 0.22; 95% CI: 0.05-0.86) were the most effective TCM agents that improved survival. This nationwide retrospective cohort study provided information that combined therapy with TCM may improve the survival in SLE patients. This study also suggests that TCM may be used as an integral element of effective therapy for SLE. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT.

    PubMed

    Danby, R D; Zhang, W; Medd, P; Littlewood, T J; Peniket, A; Rocha, V; Roberts, D J

    2016-01-01

    Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3(+)CD4(+)CD25(+)FOXP3(+)CD127(dim/-)) dose transplanted was 4.7 × 10(6)/kg, with Tregs accounting for a median of 2.96% of CD4(+) T cells. Patients transplanted with grafts containing a Treg/CD4(+) T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4(+) T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4(+) T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation.

  1. High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT

    PubMed Central

    Danby, R D; Zhang, W; Medd, P; Littlewood, T J; Peniket, A; Rocha, V; Roberts, D J

    2016-01-01

    Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3+CD4+CD25+FOXP3+CD127dim/−) dose transplanted was 4.7 × 106/kg, with Tregs accounting for a median of 2.96% of CD4+ T cells. Patients transplanted with grafts containing a Treg/CD4+ T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4+ T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4+ T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation. PMID:26389831

  2. Bubble Size Control to Improve Oxygen-Based Bleaching: Characterization of Flow Regimes in Pulp-Water-Gas Three-Phase Flows

    SciTech Connect

    S.M. Ghiaasiaan and Seppo Karrila

    2006-03-20

    Flow characteristics of fibrous paper pulp-water-air slurries were investigated in a vertical circular column 1.8 m long, with 5.08 cm diameter. Flow structures, gas holdup (void fraction), and the geometric and population characteristics of gas bubbles were experimentally investigated, using visual observation, Gamma-ray densitometry, and flash X-ray photography. Five distinct flow regimes could be visually identified: dispersed bubbly, layered bubbly, plug, churn-turbulent, and slug. Flow regime maps were constructed, and the regime transition lines were found to be sensitive to consistency. The feasibility of using artificial neural networks (ANNs) for the identification of the flow regimes, using the statistical characteristics of pressure fluctuations measured by a single pressure sensor, was demonstrated. Local pressure fluctuations at a station were recorded with a minimally-intrusive transducer. Three-layer, feed-forward ANNs were designed that could identify the four major flow patterns (bubbly, plug, churn, and slug) well. The feasibility of a transportable artificial neural network (ANN) - based technique for the classification of flow regimes was also examined. Local pressures were recorded at three different locations using three independent but similar transducers. An ANN was designed, trained and successfully tested for the classification of the flow regimes using one of the normalized pressure signals (from Sensor 1). The ANN trained and tested for Sensor 1 predicted the flow regimes reasonably well when applied directly to the other two sensors, indicating a good deal of transportability. An ANN-based method was also developed, whereby the power spectrum density characteristics of other sensors were adjusted before they were used as input to the ANN that was based on Sensor 1 alone. The method improved the predictions. The gas-liquid interfacial surface area concentration was also measured in the study. The gas absorption technique was applied

  3. Dental pulp stem cells in regenerative dentistry.

    PubMed

    Casagrande, Luciano; Cordeiro, Mabel M; Nör, Silvia A; Nör, Jacques E

    2011-01-01

    Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

  4. Biogas generation apple pulp.

    PubMed

    Llaneza Coalla, H; Blanco Fernández, J M; Morís Morán, M A; López Bobo, M R

    2009-09-01

    In view of the pressing problem that appears in our region (Asturias, north of Spain) with the residues from the cider production, it was decided to test this kind of material as a co-substrate joint with slaughterhouse waste in a laboratory unit. The anaerobic digestion of apple pulp was investigated for biogas production. This paper presents the results where apple pulp was co-digested with slaughterhouse waste (pig intestine and bovine stomach content) in a biogas laboratory unit (10 l CSTR reactor). The production of biogas has reached very satisfactory values during the whole test (0.8m(3)kg(-1)OTS), verifying that the process is kept in stable conditions of pH (near 8.0), and the volatile fatty acids was always underneath 3000 mg/l, when the pulp amount was lower than 100g in mesophilic conditions. The fat concentration into the digester remained always below the value that causes inhibition of the methanogenic bacteria, 500 mg/l. Finally, methane concentration (77-80%) and H(2)S concentration (400 ppm) in the biogas, they were similar to those obtained when the test was run out in the absence of apple pulp. The process efficiency with respect to COD removal was high, near 80% of the total COD. Finally, inhibitory effects of methanogenic bacteria were observed when pulp concentration was around 10% in the input material.

  5. Decellularized Human Dental Pulp as a Scaffold for Regenerative Endodontics.

    PubMed

    Song, J S; Takimoto, K; Jeon, M; Vadakekalam, J; Ruparel, N B; Diogenes, A

    2017-06-01

    Teeth undergo postnatal organogenesis relatively late in life and only complete full maturation a few years after the crown first erupts in the oral cavity. At this stage, development can be arrested if the tooth organ is damaged by either trauma or caries. Regenerative endodontic procedures (REPs) are a treatment alternative to conventional root canal treatment for immature teeth. These procedures rely on the transfer of apically positioned stem cells, including stem cells of the apical papilla (SCAP), into the root canal system. Although clinical success has been reported for these procedures, the predictability of expected outcomes and the organization of the newly formed tissues are affected by the lack of an available suitable scaffold that mimics the complexity of the dental pulp extracellular matrix (ECM). In this study, we evaluated 3 methods of decellularization of human dental pulp to be used as a potential autograft scaffold. Tooth slices of human healthy extracted third molars were decellularized by 3 different methods. One of the methods generated the maximum observed decellularization with minimal impact on the ECM composition and organization. Furthermore, recellularization of the scaffold supported the proliferation of SCAP throughout the scaffold with differentiation into odontoblast-like cells near the dentinal walls. Thus, this study reports that human dental pulp from healthy extracted teeth can be successfully decellularized, and the resulting scaffold supports the proliferation and differentiation of SCAP. The future application of this form of an autograft in REPs can fulfill a yet unmet need for a suitable scaffold, potentially improving clinical outcomes and ultimately promoting the survival and function of teeth with otherwise poor prognosis.

  6. Influence of kraft pulping on carboxylate content of softwood kraft pulps

    Treesearch

    Zheng Dang; Thomas Elder; Arthur J. Ragauskas

    2006-01-01

    This study characterizes changes in fiber charge, which is the carboxylate content of fibers, for two sets of kraft pulps: (1) conventional laboratory cooked loblolly pine kraft pulps and (2) conventional pulping (CK) versus low solids pulping (LS) pulps. Laboratory kraft pulping of loblolly pine was carried out to study the influence of pulping conditions, including...

  7. Dental Pulp Testing: A Review

    PubMed Central

    Chen, Eugene; Abbott, Paul V.

    2009-01-01

    Dental pulp testing is a useful and essential diagnostic aid in endodontics. Pulp sensibility tests include thermal and electric tests, which extrapolate pulp health from sensory response. Whilst pulp sensibility tests are the most commonly used in clinical practice, they are not without limitations and shortcomings. Pulp vitality tests attempt to examine the presence of pulp blood flow, as this is viewed as a better measure of true health than sensibility. Laser Doppler flowmetry and pulse oximetry are examples of vitality tests. Whilst the prospect is promising, there are still many practical issues that need to be addressed before vitality tests can replace sensibility tests as the standard clinical pulp diagnostic test. With all pulp tests, the results need to be carefully interpreted and closely scrutinised as false results can lead to misdiagnosis which can then lead to incorrect, inappropriate, or unnecessary treatment. PMID:20339575

  8. Time on the scene and interventions are associated with improved survival in pediatric out-of-hospital cardiac arrest

    PubMed Central

    Tijssen, Janice A.; Prince, David K.; Morrison, Laurie J.; Atkins, Dianne L.; Austin, Michael A.; Berg, Robert; Brown, Siobhan P.; Christenson, Jim; Egan, Debra; Fedor, Preston J.; Fink, Ericka L.; Meckler, Garth D.; Osmond, Martin H.; Sims, Kathryn A.; Hutchison, James S.

    2015-01-01

    Background Survival is less than 10% for pediatric patients following out-of-hospital cardiac arrest. It is not known if more time on the scene of the cardiac arrest and advanced life support interventions by emergency services personnel are associated with improved survival. Aim This study was performed to determine which times on the scene and which prehospital interventions were associated with improved survival. Methods We studied patients aged 3 days to 19 years old with out-of-hospital cardiac arrest, using the Resuscitation Outcomes Consortium cardiac arrest database from 11 North American regions, from 2005 to 2012. We evaluated survival to hospital discharge according to on-scene times (< 10, 10 to 35 and > 35 minutes). Results Data were available for 2244 patients (1017 infants, 594 children and 633 adolescents). Infants had the lowest rate of survival (3.7%) compared to children (9.8%) and adolescents (16.3%). Survival improved over the 7 year study period especially among adolescents. Survival was highest in the 10 to 35 minute on-scene time group (10.2%) compared to the > 35 minute group (6.9%) and the < 10 minute group (5.3%, p=0.01). Intravenous or intra-osseous access attempts and fluid administration were associated with improved survival, whereas advanced airway attempts were not associated with survival and resuscitation drugs were associated with worse survival. Conclusions In this observational study, a scene time of 10 to 35 minutes was associated with the highest survival, especially among adolescents. Access for fluid resuscitation was associated with increased survival but advanced airway and resuscitation drugs were not. PMID:26095301

  9. Novel Pulping Technology: Directed Green Liquor Utilization (D-GLU) Pulping

    SciTech Connect

    Lucian A. Lucia

    2005-11-15

    The general objectives of this new project are the same as those described in the original proposal. Conventional kraft pulping technologies will be modified for significant improvements in pulp production, such as strength, bleachability, and yield by using green liquor, a naturally high, kraft mill-derived sulfidity source. Although split white liquor sulfidity and other high sulfidity procedures have the promise of addressing several of the latter important economic needs of pulp mills, they require considerable engineering/capital retrofits, redesigned production methods, and thus add to overall mill expenditures. Green liquor use, however, possesses the required high sulfidity to obtain in general the benefits attributable to higher sulfidity cooking, without the required capital constraints for implementation. Before introduction of green liquor in our industrial operations, a stronger understanding of its fundamental chemical interaction with the lignin and carbohydrates in US hardwood and softwoods must be obtained. In addition, its effect on bleachability, enhancement of pulp properties, and influence on the overall energy and recovery of the mill requires further exploration before the process witnesses widespread mill use in North America. Thus, proof of principle will be accomplished in this work and the consequent effect of green liquor and other high sulfide sources on the pulping and bleaching operations will be explored for US kraft mills. The first year of this project will generate the pertinent information to validate its ability for implementation in US pulping operations, whereas year two will continue this work while proceeding to analyze pulp bleachability and final pulp/paper properties and develop a general economic and feasibility analysis for its eventual implementation in North America.

  10. Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro

    PubMed Central

    Kranz, Katharina; Warnecke, Athanasia; Lenarz, Thomas; Durisin, Martin; Scheper, Verena

    2014-01-01

    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. PMID:24642701

  11. Chemokine-Releasing Microparticles Improve Bacterial Clearance and Survival of Anthrax Spore-Challenged Mice

    PubMed Central

    Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

    2016-01-01

    In this study the hydrogel microparticles (MPs) were used to enhance migration of neutrophils in order to improve outcome of anthrax infection in a mouse model. Two MP formulations were tested. In the first one the polyacrylamide gel MPs were chemically coupled with Cibacron Blue (CB) affinity bait. In the second one the bait molecules within the MPs were additionally loaded with neutrophil-attracting chemokines (CKs), human CXCL8 and mouse CCL3. A non-covalent interaction of the bait with the CKs provided their gradual release after administration of the MPs to the host. Mice were challenged into footpads with Bacillus anthracis Sterne spores and given a dose of MPs a few hours before and/or after the spores. Pre-treatment with a single dose of CK-releasing MPs without any additional intervention was able to induce influx of neutrophils to the site of spore inoculation and regional lymph nodes correlating with reduced bacterial burden and decreased inflammatory response in footpads. On average, in two independent experiments, up to 53% of mice survived over 13 days. All control spore-challenged but MP-untreated mice died. The CB-coupled particles were also found to improve survival likely due to the capacity to stimulate release of endogenous CKs, but were less potent at decreasing the inflammatory host response than the CK-releasing MPs. The CK post-treatment did not improve survival compared to the untreated mice which died within 4 to 6 days with a strong inflammation of footpads, indicating quick dissemination of spores though the lymphatics after challenge. This is the first report on the enhanced innate host resistance to anthrax in response to CKs delivered and/or endogenously induced by the MPs. PMID:27632537

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

    PubMed

    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.

  13. Improved survival with an ambulatory model of non-invasive ventilation implementation in motor neuron disease.

    PubMed

    Sheers, Nicole; Berlowitz, David J; Rautela, Linda; Batchelder, Ian; Hopkinson, Kim; Howard, Mark E

    2014-06-01

    Non-invasive ventilation (NIV) increases survival and quality of life in motor neuron disease (MND). NIV implementation historically occurred during a multi-day inpatient admission at this institution; however, increased demand led to prolonged waiting times. The aim of this study was to evaluate the introduction of an ambulatory model of NIV implementation. A prospective cohort study was performed. Inclusion criteria were referral for NIV implementation six months pre- or post-commencement of the Day Admission model. This model involved a 4-h stay to commence ventilation with follow-up in-laboratory polysomnography titration and outpatient attendance. Outcome measures included waiting time, hospital length of stay, adverse events and polysomnography data. Results indicated that after changing to the Day Admission model the median waiting time fell from 30 to 13.5 days (p < 0.04) and adverse events declined (4/17 pre- (three deaths, one acute admission) vs. 0/12 post-). Survival was also prolonged (median (IQR) 278 (51-512) days pre- vs 580 (306-1355) days post-introduction of the Day Admission model; hazard ratio 0.41, p = 0.04). Daytime PaCO2 was no different. In conclusion, reduced waiting time to commence ventilation and improved survival were observed following introduction of an ambulatory model of NIV implementation in people with MND, with no change in the effectiveness of ventilation.

  14. The Hartford Consensus to improve survivability in mass casualty events: Process to policy.

    PubMed

    Jacobs, Lenworth; Burns, Karyl J

    2014-01-01

    The Joint Committee to Create a National Policy to Enhance Survivability from Mass Casualty Shooting Events was formed to make recommendations to improve survival from intentional mass casualty incidents. This article describes the development of the Hartford Consensus and the process used to disseminate and implement its findings. Members of the Committee included individuals from select public safety organizations. The first meeting of the Committee was held on April 2, 2013, and a second meeting was held on July 11, 2013. Attendance at the second meeting was enlarged and included representatives from the Federal Emergency Management Agency and the National Security Staff of the Office of the President. The results of these meetings became known as the Hartford Consensus. The ideas generated at the meetings produced two documents, one from each meeting. These are referred to as Hartford Consensus I and II. Hartford Consensus I is a concept document and Hartford Consensus II is a call to action that no one should die from uncontrolled bleeding. The recommendations are being incorporated into training programs and have been endorsed by many organizations whose members are involved in the response to mass casualty incidents. The Joint Committee to Create a National Policy to Enhance Survivability from Mass Casualty Shooting Events was successful in stimulating policy to bring about change. Training and resources including tourniquets and hemostatic dressing are being directed to help ameliorate the unfortunate reality of intentional mass injury.

  15. Oxygen cycling to improve survival of stem cells for myocardial repair: A review.

    PubMed

    Dall, Christopher; Khan, Mahmood; Chen, Chun-An; Angelos, Mark G

    2016-05-15

    Heart disease represents the leading cause of death among Americans. There is currently no clinical treatment to regenerate viable myocardium following myocardial infarction, and patients may suffer progressive deterioration and decreased myocardial function from the effects of remodeling of the necrotic myocardium. New therapeutic strategies hold promise for patients who suffer from ischemic heart disease by directly addressing the restoration of functional myocardium following death of cardiomyocytes. Therapeutic stem cell transplantation has shown modest benefit in clinical human trials with decreased fibrosis and increased functional myocardium. Moreover, autologous transplantation holds the potential to implement these therapies while avoiding the immunomodulation concerns of heart transplantation. Despite these benefits, stem cell therapy has been characterized by poor survival and low engraftment of injected stem cells. The hypoxic tissue environment of the ischemic/infracting myocardium impedes stem cell survival and engraftment in myocardial tissue. Hypoxic preconditioning has been suggested as a viable strategy to increase hypoxic tolerance of stem cells. A number of in vivo and in vitro studies have demonstrated improved stem cell viability by altering stem cell secretion of protein signals and up-regulation of numerous paracrine signaling pathways that affect inflammatory, survival, and angiogenic signaling pathways. This review will discuss both the mechanisms of hypoxic preconditioning as well as the effects of hypoxic preconditioning in different cell and animal models, examining the pitfalls in current research and the next steps into potentially implementing this methodology in clinical research trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    PubMed

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  17. Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

    PubMed Central

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening −34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  18. Fibrin glue improves the therapeutic effect of MSCs by sustaining survival and paracrine function.

    PubMed

    Kim, Inok; Lee, Sung Koo; Yoon, Jung In; Kim, Da Eun; Kim, Mihyung; Ha, Hunjoo

    2013-11-01

    Fibrin glue has been widely investigated as a cell delivery vehicle for improving the therapeutic effects of mesenchymal stem cells (MSCs). Implanted MSCs produce their therapeutic effects by secreting paracrine factors and by replacing damaged tissues after differentiation. While the influence of fibrin glue on the differentiation potential of MSCs has been well documented, its effect on paracrine function of MSCs is largely unknown. Herein we investigated the influence of fibrin glue on the paracrine effects of MSCs. MSCs were isolated from human adipose tissue. The effects of fibrin glue on survival, migration, secretion of growth factors, and immune suppression of MSCs were investigated in vitro. MSCs in fibrin glue survived and secreted growth factors such as the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) over 14 days. VEGF and immune modulators, including the transforming growth factor (TGF)-β1 and prostaglandin E2, secreted from MSCs in fibrin glue significantly increased under inflammatory conditions. Thus, MSCs in fibrin glue effectively suppressed immune reactions. In addition, fibrin glue protected the MSCs from oxidative stress and prevented human dermal fibroblast death induced by exposure to extreme stress. In contrast, MSCs within fibrin glue hardly migrated. These results suggest that fibrin glue may sustain survival of implanted MSCs and their paracrine function. Our results provide a mechanistic data to allow further development of MSCs with fibrin glue as a clinical treatment.

  19. Paper pulp from sugar mill bagasse

    SciTech Connect

    Krueger, H.; Berndt, W.; Schwartzkopff, U.; Reitter, F.J.; Hoepner, T.; Muehlig, H.J.

    1981-04-07

    This is a continuation-in-part of US Serial No. 884,513, abandoned. Neutral sulfite semichemical (NSSC) cooking of depithed bagasse gave pulp with improved physicomechanical properties for use in the production of newsprint paper. Thus, the NSSC cooking at 170-175/sup 0/ gave pulp in 70-75% yield. The NSSC pulp as above was bleached with alkali H/sub 2/O/sub 2/ at 50-70/sup 0/ to give a product with breaking load 8.7 kg, tensile 3.9%, breaking length 7.13 km, absolute tearing strength 135 cmg/cm, absolute bursting strength 3.8 kg/sq. cm and Elrepho brightness 61.

  20. Significant increases in pulping efficiency in C4H-F5H-transformed poplars: improved chemical savings and reduced environmental toxins.

    PubMed

    Huntley, Shannon K; Ellis, Dave; Gilbert, Margarita; Chapple, Clint; Mansfield, Shawn D

    2003-10-08

    The gene encoding ferulate 5-hydroxylase (F5H) was overexpressed in poplar (Populus tremula x Populus alba) using the cinnamate-4-hydroxylase (C4H) promoter to drive expression specifically in cells involved in the lignin biosynthetic pathway and was shown to significantly alter the mole percentage of syringyl subunits in the lignin, as determined by thioacidolysis. Analysis of poplar transformed with a C4H-F5H construct demonstrated significant increases in chemical (kraft) pulping efficiency from greenhouse-grown trees. Compared to wild-type wood, decreases of 23 kappa units and increases of >20 ISO brightness units were observed in trees exhibiting high syringyl monomer concentrations. These changes were associated with no significant modification in total lignin content and no observed phenotypic differences. C4H-F5H-transformed trees could increase pulp throughputs at mills by >60% while concurrently decreasing chemicals employed during processing (chemical pulping and bleaching) and, consequently, the amount of deleterious byproducts released into the environment.

  1. Use of Sleeve Nets to Improve Survival of the Boisduval Silkworm, Anaphe panda, in the Kakamega Forest of Western Kenya

    PubMed Central

    Mbahin, N.; Raina, S. K.; Kioko, E. N.; Mueke, J. M.

    2010-01-01

    Prospects for development of a wild silk industry in Africa would be improved if silkworm survival during mass production could be improved. A study on the survival of the Boisduval silkworm, Anaphe panda (Boisduval) (Lepidoptera: Thaumetopoeidae) was conducted with and without protection by net sleeves in two different forest habitats (natural and modified) in the Kakamega forest of western Kenya. Overall, cohort survival was significantly higher (P < 0.001) in the natural than in the modified forest, but larval survival was improved over three-fold by protection with net sleeves in both habitat types. In the modified forest, only 16.8% of unprotected larvae survived to the pupal stage and formed cocoons, whereas 62.3% survived in the same environment when they were protected with net sleeves. In the natural forest, 20.4% of unprotected larvae survived, whereas 67.7% survived in net sleeves. There was also a significant effect of season; cohorts of larvae that eclosed in the wet season had significantly lower survival than those eclosing in the dry season (P = 0.02). Sources of mortality appeared to be natural enemies (parasites, predators and diseases) and climatic factors. PMID:20569137

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

    PubMed Central

    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 < 0.05). The total viable counts of bacteria in ascites decreased significantly in probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P < 0.05). The total positive rate of hemoculture decreased significantly in probiotics treated group compared with septic model group (33.3% vs 100.0%, P < 0.05). The population of Escherichia coli and Staphylococcus aureus in ascites of probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P < 0.05; 2.80 ± 1.04 vs 5.39 ± 1.21, P < 0.05). With 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 < 0.01). CONCLUSION: Escherichia coli and Staphylococcus aureus may be primary pathogens in septic rats. Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

  3. Local Therapy Improves Overall Survival in Patients With Newly Diagnosed Metastatic Prostate Cancer.

    PubMed

    Parikh, Rahul R; Byun, John; Goyal, Sharad; Kim, Isaac Yi

    2017-05-01

    The role of local therapy, in the form of radiation therapy (RT) or radical prostatectomy(RP), and its association on outcomes is not well established in patients with metastatic prostate cancer. Using the National Cancer Database (NCDB), we evaluated patterns of care and outcomes among patients diagnosed with metastatic prostate cancer from 2004 to 2013 treated with local therapy (RP, intensity-modulated radiation therapy [IMRT], or 2D/3D-conformal radiation therapy [CRT]). The association between local therapy, co-variates, and outcomes was assessed in a multivariable Cox proportional hazards model and Propensity score (PS) matching was performed to balance confounding factors. Survival was estimated using the Kaplan-Meier method. Among the 1,208,180 patients in the NCDB with prostate cancer, 6,051 patients met the inclusion criteria. No local therapy was used in 5,224 patients, while 622 (10.3%), 52 (0.9%), 153 (2.5%) patients received RP, IMRT, and 2D/3D-CRT, respectively. Use of local therapy was associated with younger age (≤70), lower co-morbidity score, lower T-stage, Gleason score <8, node-negative status, private, and Medicare insurance, higher income quartile, and treatment at comprehensive or academic/research programs (P < 0.05). Five-year overall survival for patients receiving local therapy was 45.7% versus 17.1% for those not receiving local therapy (P < 0.01). In multivariate analysis, RP (HR = 0.51; 95%CI, 0.45-0.59, P < 0.01) and IMRT (HR = 0.47; 95%CI, 0.31-0.72, P < 0.01) were independently associated with superior overall survival. After PS-matching, the use of local therapy (RP or IMRT) remained significantly associated with overall survival (HR = 0.35; 95%CI, 0.30-0.41, P < 0.01). The use of RP and IMRT, to treat the primary disease, was associated with improvements in overall survival for patients with metastatic prostate cancer. We have identified patient-specific variations in the use of local therapy

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

    PubMed

    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.

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

    PubMed

    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.

  6. Resection of pulmonary metastases in pediatric patients with Ewing sarcoma improves survival.

    PubMed

    Letourneau, Phillip A; Shackett, Brett; Xiao, Lianchun; Trent, Jonathan; Tsao, Kuo Jen; Lally, Kevin; Hayes-Jordan, Andrea

    2011-02-01

    Ewing sarcoma (ES) is the second most common bone tumor in children, and survival of those with metastatic ES has not improved. Previous studies have shown a survival benefit to whole lung irradiation in patients with pulmonary metastases and may be given either before, after, or instead of surgical pulmonary metastasectomy (PM). The contribution of surgery compared with irradiation in ES has not previously been studied. A retrospective review of patients younger than 21 years (median age, 16 years) treated at a single institution (1990-2006) was performed. Kaplan-Meier survival curves were compared using log-rank test and a multivariate Cox proportional hazards model. P ≤ .05 was regarded as significant. Eighty patients with ES were identified. Of these, 31 (39%) had pulmonary metastases. Nine patients had incomplete details of their full treatment regimen, but the following groups could be defined from the remainder: resection alone (n = 5), radiation alone (n = 3), radiation and resection (n = 3), or chemotherapy alone (n = 11). There were 24 deaths overall, with a median overall survival (OS) of 2.7 (95% confidence interval [CI], 1.7-5.2) years. Patients who had PM had the best OS (80%), whereas those who underwent radiation to the lung without PM compared with chemotherapy only for pulmonary metastasis both had similar OS of 0% at 5 years (P = .002). Patients who had radiation followed by PM for lung metastasis had a 5-year OS of 65%. Patients with PM had a longer OS compared with those without lung resection (P < .0001). These data suggest a possible benefit for ES patients who undergo surgical resection of lung metastases. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch's Membrane

    PubMed Central

    Sugino, Ilene K.; Gullapalli, Vamsi K.; Sun, Qian; Wang, Jianqiu; Nunes, Celia F.; Cheewatrakoolpong, Noounanong; Johnson, Adam C.; Degner, Benjamin C.; Hua, Jianyuan; Liu, Tong; Chen, Wei; Li, Hong

    2011-01-01

    Purpose. To determine whether resurfacing submacular human Bruch's membrane with a cell-deposited extracellular matrix (ECM) improves retinal pigment epithelial (RPE) survival. Methods. Bovine corneal endothelial (BCE) cells were seeded onto the inner collagenous layer of submacular Bruch's membrane explants of human donor eyes to allow ECM deposition. Control explants from fellow eyes were cultured in medium only. The deposited ECM was exposed by removing BCE. Fetal RPE cells were then cultured on these explants for 1, 14, or 21 days. The explants were analyzed quantitatively by light microscopy and scanning electron microscopy. Surviving RPE cells from explants cultured for 21 days were harvested to compare bestrophin and RPE65 mRNA expression. Mass spectroscopy was performed on BCE-ECM to examine the protein composition. Results. The BCE-treated explants showed significantly higher RPE nuclear density than did the control explants at all time points. RPE expressed more differentiated features on BCE-treated explants than on untreated explants, but expressed very little mRNA for bestrophin or RPE65. The untreated young (<50 years) and African American submacular Bruch's membrane explants supported significantly higher RPE nuclear densities (NDs) than did the Caucasian explants. These differences were reduced or nonexistent in the BCE-ECM-treated explants. Proteins identified in the BCE-ECM included ECM proteins, ECM-associated proteins, cell membrane proteins, and intracellular proteins. Conclusions. Increased RPE survival can be achieved on aged submacular human Bruch's membrane by resurfacing the latter with a cell-deposited ECM. Caucasian eyes seem to benefit the most, as cell survival is the worst on submacular Bruch's membrane in these eyes. PMID:21398292

  8. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I; Serralde-Zúñiga, Aurora E; Cruz-Herrera, Javier; Pérez-Torres, Eduardo; Abdo-Francis, Juan M; Salas-Gordillo, Francisco; Pérez-Hernández, José L

    2015-01-01

    AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the “Hospital General de México, Dr. Eduardo Liceaga”. We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX. PMID:25945012

  9. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis.

    PubMed

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I; Serralde-Zúñiga, Aurora E; Cruz-Herrera, Javier; Pérez-Torres, Eduardo; Abdo-Francis, Juan M; Salas-Gordillo, Francisco; Pérez-Hernández, José L

    2015-04-28

    To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). This study was an open-label clinical trial, performed at the "Hospital General de México, Dr. Eduardo Liceaga". We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.

  10. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas.

    PubMed

    Lasolle, Hélène; Cortet, Christine; Castinetti, Fréderic; Cloix, Lucie; Caron, Philippe; Delemer, Brigitte; Desailloud, Rachel; Jublanc, Christel; Lebrun-Frenay, Christine; Sadoul, Jean-Louis; Taillandier, Luc; Batisse-Lignier, Marie; Bonnet, Fabrice; Bourcigaux, Nathalie; Bresson, Damien; Chabre, Olivier; Chanson, Philippe; Garcia, Cyril; Haissaguerre, Magalie; Reznik, Yves; Borot, Sophie; Villa, Chiara; Vasiljevic, Alexandre; Gaillard, Stephan; Jouanneau, Emmanuel; Assié, Guillaume; Raverot, Gérald

    2017-06-01

    Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. Multicenter retrospective study by members of the French Society of Endocrinology. Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols. © 2017 European Society of Endocrinology.

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

    SciTech Connect

    Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E. . E-mail: Dennis.Hallahan@mcmail.vanderbilt.edu

    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 {mu}mol/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) {alpha} and {beta}. 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 {beta} 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. Crocetin Reduces Activation of Hepatic Apoptotic Pathways and Improves Survival in Experimental Hemorrhagic Shock

    PubMed Central

    Yang, Rongjie; Vernon, Kathy; Thomas, Ann; Morrison, David; Qureshi, Nilofer; Van Way, Charles W

    2014-01-01

    Background Hemorrhagic shock results in cellular damage and cell death. A primary mechanism is cellular apoptosis from mitochondrial damage. This study demonstrated that administration of crocetin to experimental animals during resuscitation from shock significantly improved postshock survival and reduced apoptosis. Crocetin is a component of saffron and has long been used in traditional medicine in Asia. Methods Male Sprague-Dawley rats (350 ± 30g) were randomly assigned to 1 of 4 groups of 8 animals. Hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure was 35–40 mm Hg, and blood pressure was maintained at that level for 60 minutes with further withdrawals as needed. Resuscitation was carried out by administration of 21 mL/kg lactated Ringer’s solution and return of shed blood, with or without concurrent administration of crocetin (2 mg/kg). Control animals were sham-treated with surgical preparation, without shock or resuscitation, and with and without crocetin. Rats were sacrificed 24 hours after completion of resuscitation. The extent of activation of hepatic apoptosis was established by measuring levels of hepatic cytosolic cytochrome c, caspase-3, and bcl-2. A separate group of 53 animals treated identically was used to assess survival. Results Crocetin administration during resuscitation resulted in less extensive activation of hepatic apoptosis and significantly increased survival relative to controls. Conclusions Crocetin administration to experimental animals during resuscitation post hemorrhage increased survival, at least in part by protecting the liver from activation of apoptotic cell death. This agent continues to show promise as a potential treatment strategy for hemorrhagic shock. PMID:21224437

  13. Empirical use of fluoroquinolones improves the survival of critically ill patients with tuberculosis mimicking severe pneumonia

    PubMed Central

    2012-01-01

    Introduction Empirical use of fluoroquinolones may delay the initiation of appropriate therapy for tuberculosis (TB). This study aimed to evaluate the impact of empirical fluoroquinolone use on the survival of patients with pulmonary TB that mimicked severe community-acquired pneumonia (CAP) requiring intensive care. Methods Patients aged >18 years with culture-confirmed pulmonary TB who presented as severe CAP and were admitted to the ICU were divided into fluoroquinolone (FQ) and nonfluoroquinolone (non-FQ) groups based on the type of empirical antibiotics used. Those patients with previous anti-TB treatment or those who died within 3 days of hospitalization were excluded. The primary end point was 100-day survival. Results Of the 77 patients identified, 43 (56%) were in the FQ group and 34 (44%) were in the non-FQ group. The two groups had no statistically significant difference in co-morbidities (95% vs. 97%, P > 0.99) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores (21.2 ± 7.1 vs. 22.5 ± 7.5, P = 0.46) on ICU admission. Overall, 91% and 82% of patients in the FQ and non-FQ groups, respectively, had sputum examinations for TB within 1 week of admission (P = 0.46), and results were positive in 7% and 15% (P = 0.47), respectively. For both groups, 29% received appropriate anti-TB therapy within 2 weeks after ICU admission. The 100-day mortality rate was 40% and 68% for the FQ and non-FQ groups, respectively (P = 0.02). By Cox regression analysis, APACHE score <20, no bacteremia during the ICU stay, and empirical fluoroquinolone use were independently associated with survival. Conclusion Empirical use of fluoroquinolones may improve the survival of ICU patients admitted for pulmonary TB mimicking severe CAP. PMID:23098258

  14. Bryostatin improves survival and reduces ischemic brain injury in aged rats following acute ischemic stroke

    PubMed Central

    Tan, Zhenjun; Turner, Ryan C.; Leon, Rachel L.; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F.; Naser, Zachary J.; Alkon, Daniel L.; Rosen, Charles L.; Huber, Jason D.

    2014-01-01

    Background and Purpose Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer's disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator (tPA) reperfusion in aged rats. Methods Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20 month old female Sprague-Dawley rats using an autologous blood clot with tPA-mediated reperfusion. Bryostatin was administered at 6 h post-MCAO then at 3, 6, 9, 12, 15, and 18 d after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 d after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 d post-MCAO. Histological assessment of PKC isozymes was performed at 24 h post-MCAO. Results Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 d. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 d post-MCAO. Changes in PKC alpha expression and PKC epsilon expression in neurons were noted in bryostatin-treated rats at 24 h post-MCAO. Conclusions Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome following MCAO. PMID:24172582

  15. Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

    PubMed

    Tan, Zhenjun; Turner, Ryan C; Leon, Rachel L; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F; Naser, Zachary J; Alkon, Daniel L; Rosen, Charles L; Huber, Jason D

    2013-12-01

    Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

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

    PubMed

    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

  17. Does Social Feeding Improve Larval Survival of the Two-Spotted Lady Beetle, Adalia bipunctata?

    PubMed Central

    Moore, Michael P.; Burt, Charles R.; Whitney, Thomas D.; Hastings, Steven A.; Chang, Gary C.

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions. PMID:23425121

  18. Does social feeding improve larval survival of the two-spotted lady beetle, Adalia bipunctata?

    PubMed

    Moore, Michael P; Burt, Charles R; Whitney, Thomas D; Hastings, Steven A; Chang, Gary C

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions.

  19. Bone marrow mesenchymal stem cell‑derived extracellular vesicles improve the survival of transplanted fat grafts.

    PubMed

    Huang, He; Feng, Shaoqing; Zhang, Wenjie; Li, Wei; Xu, Peng; Wang, Xiangsheng; Ai, Ai

    2017-09-01

    Autologous fat grafting is a promising surgical technique for soft tissue augmentation, reconstruction and rejuvenation. However, it is limited by the low survival rate of the transplanted fat, due to the slow revascularization of such grafts. Previous studies have demonstrated that bone marrow mesenchymal stem cell‑derived extracellular vesicles (BMSC‑EVs) are proangiogenic. The present study aimed to investigate whether BMSC‑EVs could improve the survival of transplanted fat grafts. Extracellular vesicles were isolated from the supernatant of cultured rat bone marrow mesenchymal stem cells, and characterized by flow cytometry and scanning electron microscopy. Their proangiogenic potential was measured in vitro using tube formation and cell migration assays. Subsequently, human fat tissue grafts, alongside various concentrations of BMSC‑EVs, were subcutaneously injected into nude mice. A total of 12 weeks following transplantation, the mice were sacrificed and the grafts were harvested. The grafts from the experimental group had a higher survival rate and an increased number of vessels compared with grafts from the control group, as demonstrated by tissue volume, weight and histological analyses. Reverse transcription‑quantitative polymerase chain reaction analysis indicated that the expression levels of proangiogenic factors were increased in the experimental group compared with in the control group, thus suggesting that BMSC‑EVs may promote neovascularization by stimulating the secretion of proangiogenic factors. The present study is the first, to the best of our knowledge, to demonstrate that supplementation of fat grafts with BMSC‑EVs improves the long‑term retention and quality of transplanted fat.

  20. Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

    PubMed Central

    White, Nathan J.; Wang, Xu; Liles, W. Conrad; Stern, Susan

    2014-01-01

    The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (N=7 per group) were then randomized to receive either; 1. No fluid resuscitation (Neg Control), 2. Limited resuscitation in the form of two boluses of 10ml/kg of 6% hydroxyethyl starch solution (HEX) given 30 minutes apart, or 3. The same fluid regimen with one dose of 120mg/kg fibrinogen concentrate given with the first HEX bolus (FBG). Animals were then observed for a total of 6 hours with aortic repair and aggressive resuscitation with shed blood taking place at 3 hours. Survival to 6 hours was significantly increased with FBG (7/8, 86%) vs. HEX (2/7, 29%), and Neg Control (0/7, 0%) (FBG vs. HEX, Kaplan Meier LR p=0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4ml/kg/min) when compared to FBG (0.1mg/kg/min, p=0.047) and Neg Control (0.1ml/kg/min, p=0.041). Systemic and cerebral hemodynamics also showed improvement with FBG vs. HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock. PMID:25337778

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

    PubMed

    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.

  2. Amantadine improves cognitive outcome and increases neuronal survival after fluid percussion traumatic brain injury in rats.

    PubMed

    Wang, Tao; Huang, Xian-Jian; Van, Ken C; Went, Gregory T; Nguyen, Jack T; Lyeth, Bruce G

    2014-02-15

    This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day. Terminal blood draws were obtained from TBI rats at the time of euthanasia at varying time points after the last amantadine dose. Pharmacokinetics analysis confirmed that the doses of AMT achieved serum concentrations similar to those observed in humans receiving therapeutic doses (100-400 mg/day). Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 12-16 after TBI. Brain tissues were collected and stained with Cresyl-violet for long-term cell survival analysis. Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI.

  3. Improved survival in patients enrolled promptly into remote monitoring following cardiac implantable electronic device implantation.

    PubMed

    Mittal, Suneet; Piccini, Jonathan P; Snell, Jeff; Prillinger, Julie B; Dalal, Nirav; Varma, Niraj

    2016-08-01

    Guidelines advocate remote monitoring (RM) in patients with a cardiac implantable electronic device (CIED). However, it is not known when RM should be initiated. We hypothesized that prompt initiation of RM (within 91 days of implant) is associated with improved survival compared to delayed initiation. This retrospective, national, observational cohort study evaluated patients receiving new implants of market-released St. Jude Medical™ pacemakers (PM), implantable cardioverter defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices. Patients were assigned to one of two groups: an "RM Prompt" group, in which RM was initiated within 91 days of implant; and an "RM Delayed" group, in which RM was initiated >91 days but ≤365 days of implant. The primary endpoint was all-cause mortality. The cohort included 106,027 patients followed for a mean of 2.6 ± 0.9 years. Overall, 47,014 (44 %) patients had a PM, 31,889 (30 %) patients had an ICD, 24,005 (23 %) patients had a CRT-D, and 3119 (3 %) patients had a CRT-P. Remote monitoring was initiated promptly (median 4 weeks [IQR 2, 8 weeks]) in 66,070 (62 %) patients; in the other 39,957 (38 %) patients, RM initiation was delayed (median 24 weeks [IQR 18, 34 weeks]). In comparison to delayed initiation, prompt initiation of RM was associated with a lower mortality rate (4023 vs. 4679 per 100,000 patient-years, p < 0.001) and greater adjusted survival (HR 1.18 [95 % CI 1.13-1.22], p < 0.001). Our data, for the first time, show improved survival in patients enrolled promptly into RM following CIED implantation. This advantage was observed across all CIED device types.

  4. Fibrinogen concentrate improves survival during limited resuscitation of uncontrolled hemorrhagic shock in a Swine model.

    PubMed

    White, Nathan J; Wang, Xu; Liles, Conrad; Stern, Susan

    2014-11-01

    The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4-mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (n = 7 per group) were then randomized to receive (i) no fluid resuscitation (neg control) or (ii) limited resuscitation in the form of two boluses of 10 mL/kg of 6% hydroxyethyl starch solution given 30 min apart (HEX group), or (iii) the same fluid regimen with one dose of 120-mg/kg fibrinogen concentrate given with the first hydroxyethyl starch bolus (FBG). Animals were then observed for a total of 6 h with aortic repair and aggressive resuscitation with shed blood taking place at 3 h. Survival to 6 h was significantly increased with FBG (7/8, 86%) versus HEX (2/7, 29%) and neg control (0/7, 0%) (FBG vs. HEX, Kaplan-Meier log-rank P = 0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4 mL/kg per minute) when compared with FBG (0.1 mg/kg per minute, P = 0.047) and neg control (0.1 mL/kg per minute, P = 0.041). Systemic and cerebral hemodynamics also showed improvement with FBG versus HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock.

  5. Quantifying and Improving International Space Station Survivability Following Orbital Debris Penetration

    NASA Technical Reports Server (NTRS)

    Williamsen, Joel; Evans, Hilary; Bohl, Bill; Evans, Steven; Parker, Nelson (Technical Monitor)

    2001-01-01

    The increase of the orbital debris environment in low-earth orbit has prompted NASA to develop analytical tools for quantifying and lowering the likelihood of crew loss following orbital debris penetration of the International Space Station (ISS). NASA uses the Manned Spacecraft and Crew Survivability (MSCSurv) computer program to simulate the events that may cause crew loss following orbital debris penetration of ISS manned modules, including: (1) critical cracking (explosive decompression) of the module; (2) critical external equipment penetration (such as hydrazine and high pressure tanks); (3) critical internal system penetration (guidance, control, and other vital components); (4) hazardous payload penetration (furnaces, pressure bottles, and toxic substances); (5) crew injury (from fragments, overpressure, light flash, and temperature rise); (6) hypoxia from loss of cabin pressure; and (7) thrust from module hole causing high angular velocity (occurring only when key Guidance, Navigation, and Control (GN&C) equipment is damaged) and, thus, preventing safe escape vehicle (EV) departure. MSCSurv is also capable of quantifying the 'end effects' of orbital debris penetration, such as the likelihood of crew escape, the probability of each module depressurizing, and late loss of station control. By quantifying these effects (and their associated uncertainties), NASA is able to improve the likelihood of crew survivability following orbital debris penetration due to improved crew operations and internal designs.

  6. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  7. Significant Improvement in Survival after Unrelated Donor Hematopoietic Cell Transplantation in the Recent Era

    PubMed Central

    Majhail, Navneet S; Chitphakdithai, Pintip; Logan, Brent; King, Roberta; Devine, Steven; Rossmann, Susan N; Hale, Gregory; Hartzman, Robert J; Karanes, Chatchada; Laport, Ginna G; Nemecek, Eneida; Snyder, Edward L; Switzer, Galen E; Miller, John; Navarro, Willis; Confer, Dennis L; Levine, John E

    2014-01-01

    Patients and physicians may defer unrelated donor hematopoietic cell transplantation (HCT) as curative therapy due to mortality risk associated with the procedure. Therefore, it is important for physicians to know the current outcomes data when counseling potential candidates. To provide this information, we evaluated 15,059 unrelated donor HCT recipients between 2000-2009. We compared outcomes before and after 2005 for four cohorts: age <18 years with malignant diseases (N=1,920), 18-59 years with malignant diseases (N=9,575), ≥60 years with malignant diseases (N=2,194), and non-malignant diseases (N=1,370). Three-year overall survival in 2005-2009 was significantly better in all four cohorts (<18 years: 55% vs. 45%, 18-59 years: 42% vs. 35%, ≥60 years: 35% vs. 25%, non-malignant diseases: 69% vs. 60%, P<0.001 for all comparisons). Multivariate analyses in leukemia patients receiving HLA 7-8/8 matched transplants showed significant reduction in overall and non-relapse mortality in the first 1-year after HCT among patients transplanted in 2005-2009; however, risks for relapse did not change over time. Significant survival improvements after unrelated donor HCT have occurred over the recent decade and can be partly explained by better patient selection (e.g., HCT earlier in the disease course and lower disease risk), improved donor selection (e.g., more precise allele-level matched unrelated donors) and changes in transplant practices. PMID:25445638

  8. Structural analogs of huperzine A improve survival in guinea pigs exposed to soman.

    PubMed

    Gunosewoyo, Hendra; Tipparaju, Suresh K; Pieroni, Marco; Wang, Ying; Doctor, Bhupendra P; Nambiar, Madhusoodana P; Kozikowski, Alan P

    2013-03-01

    Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures. The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose. It is hypothesized that analogs of both (+)- and (-)-huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents. In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1.2 or 2×LD(50).

  9. Diabetes and cardiovascular disease: changing the focus from glycemic control to improving long-term survival.

    PubMed

    Wang, Cecilia C Low; Reusch, Jane E B

    2012-11-06

    Diabetes mellitus (DM) is the fifth-leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease, including CAD, stroke, peripheral vascular disease, and other vascular disease. While glycemic management remains a cornerstone of DM care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction, and prevention of long-term consequences associated with DM are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, low-density cholesterol-lowering therapy, blood pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of DM in the pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence on the degree of glycemic control and mortality, and available evidence for a multifaceted approach to improve long-term outcomes for patients.

  10. Quality Improvement of Staphylococcus aureus Bacteremia Management and Predictors of Relapse-free Survival.

    PubMed

    Townsend, Jennifer; Pelletier, Jamie; Peterson, Gail; Matulevicius, Susan; Sreeramoju, Pranavi

    2016-02-01

    The purpose of this study is to improve the quality of care and patient outcomes for Staphylococcus aureus bacteremia. A quasi-experimental pre- and postintervention study design was used to compare process and clinical endpoints before and after a quality-improvement initiative. All inpatients >18 years of age with a positive blood culture for S. aureus during the specified pre- and postintervention period with clinical information available in the electronic medical record were included. An institutional protocol for the care of patients with S. aureus bacteremia was developed, formalized, and distributed to providers using a pocket card, an electronic order set, and targeted lectures over a 9-month period. There were 167 episodes of S. aureus bacteremia (160 patients) identified in the preintervention period, and 127 episodes (123 patients) in the postintervention period. Guideline adherence improved in the postintervention period for usage of transesophageal echocardiogram (43.9% vs 20.2%, P <.01) and adequate duration of intravenous therapy (71% vs 60%, P = .05). In a multivariate Cox proportional hazard model, the variables associated with increased relapse-free survival were postintervention period (hazard ratio [HR] 0.48; confidence interval [CI], 0.24-0.95; P .035) and appropriate source control (HR 0.53; CI, 0.24-0.92; P .027). Regardless of intervention, presence of cancer was associated with an increased risk of relapse or mortality at 90 days (HR 2.88; P <.0001; CI, 1.35-5.01). A bundled educational intervention to promote adherence to published guidelines for the treatment of S. aureus bacteremia resulted in a significant improvement in provider adherence to guidelines as well as increased 90-day relapse-free survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine Exposed Rats.

    PubMed

    Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M; Garlick, Rhonda B; Rioux, Jacqueline S; Murphy, Angela L; Roe, Gates B; White, Carl W; Veress, Livia A

    2017-08-28

    Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4h of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures exist for massive chlorine exposure, and supportive care measures lack controlled trials. Adult rats were exposed to chlorine gas (LD58-67) in a whole-body exposure chamber, and given oxygen (0.8 FiO2) or air (0.21 FiO2) for 6h after obtaining baseline measurements. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia, hypotonia) and seizures resulting in early death. Oxygen improved survival to 6h (87% vs. 42%), and prevented observed seizure-related deaths. However, oxygen administration worsened severity of acute respiratory failure compared to control, with increased respiratory acidosis (pH 6.91 ± 0.04 vs. 7.06 ± 0.01 at 2h) and increased hypercapnia (180.0 ± 19.8 vs. 103.2 ± 3.9 mmHg at 2h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multi-organ damage. Oxygen administration can improve short-term survival, but appears to worsen respiratory failure, with no improvements in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and need for early assisted ventilation should be assessed in victims.

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27439911

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

    PubMed

    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.

  14. Improvement in burn wound infection and survival with antimicrobial peptide D2A21 (Demegel).

    PubMed

    Chalekson, Charles P; Neumeister, Michael W; Jaynes, Jesse

    2002-04-01

    load, allowing for a markedly significant improvement in survival in this infected burn-wound model.

  15. Improved survival trend of patients with hepatocellular carcinoma at an Australian tertiary hospital between 1995-2009.

    PubMed

    Wong, N; Haydon, A; Kemp, W; Wijeratne, P; Roberts, S

    2013-02-01

    To evaluate trends in survival of patients with hepatocellular carcinoma (HCC) at The Alfred over a 15-year period from 1995-2009 A retrospective cohort study of patients with HCC comparing epidemiology, clinical presentation, treatment parameters and overall survival of those diagnosed between 1995-2001 and 2002-2009. Overall survival of patients with primary liver cancer. The study population consisted of 215 patients; 110 diagnosed between 1995-2001 (Cohort A) and 105 between 2002-2009 (Cohort B). Overall survival increased significantly between 1995-2010 (P = 0.016); median survival was 365 days in Cohort A compared with 665 in Cohort B. The improvement in survival was associated with an increase in the proportion of cases detected at an asymptomatic stage (P = 0.012), a decline in the severity of liver disease at diagnosis (P = 0.002) and increased utilisation of loco-regional therapy (P = 0.001) over the same period. Survival of patients detected through screening was significantly higher than those detected through non-screening methods (1309 vs 233 days, P < 0.001). The survival of patients with HCC managed at a tertiary referral centre has improved over the period 1995-2009. This improvement may relate to the increased detection of the disease at an asymptomatic stage (e.g. through screening) as well as increased utilisation of effective loco-regional therapies for HCC. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

  16. Can auger planting improve survival of Douglas-fir seedlings? Res

    Treesearch

    Richard E. Miller

    1969-01-01

    Survival and apparent vigor of Douglas-fir seedlings were compared after: (1) hoe planting of root-trimmed seedlings; (2) as above plus manual site preparation; (3) auger planting of untrimmed seedlings. After two growing seasons, surviving with method (3) but not (2) was significantly greater than survival with method (1). After the third season, survival...

  17. Biomechanical pulping of kenaf

    Treesearch

    Aziz Ahmed; Masood Akhtar; Gary C. Myers; Gary M. Scott

    1999-01-01

    The objective of this study was to investigate the effect of fungal pretreatment of whole kenaf prior to refining on refiner electrical energy consumption, paper strength, and optical properties. We also explored the suitability of whole kenaf biomechanical pulp for making newsprint in terms of ISO brightness and strength properties. Kenaf was sterilized by autoclaving...

  18. [Survival elongation of Pseudomonas aeruginosa improves power output of microbial fuel cells].

    PubMed

    You, Ting; Liu, Jihua; Liang, Rubing; Liu, Jianhua

    2017-04-25

    The secondary metabolites, phenazine products, produced by Pseudomonas aeruginosa can mediate the electrons transfer in microbial fuel cells (MFCs). How increase the total electricity production in MFCs by improving the characteristics of Pseudomonas aeruginosa is one of research hot spots and problems. In this study, P. aeruginosa strain SJTD-1 and its knockout mutant strain SJTD-1 (ΔmvaT) were used to construct MFCs, and the discharge processes of the two MFCs were analyzed to determine the key factors to electricity yields. Results indicated that not only phenazine but also the viable cells in the fermentation broth were essential for the discharge of MFCs. The mutant strain SJTD-1 (ΔmvaT) could produce more phenazine products and continue discharging over 160 hours in MFCs, more than that of the wild-type SJTD-1 strain (90 hours discharging time). The total electricity generated by SJTD-1 (ΔmvaT) strain could achieve 2.32 J in the fermentation process, much higher than the total 1.30 J electricity of the wild-type SJTD-1 strain. Further cell growth analysis showed that the mutant strain SJTD-1 (ΔmvaT) could keep a longer stationary period, survive much longer in MFCs and therefore, discharge more electron than those of the wild-type SJTD-1 strain. Therefore, the cell survival elongation of P. aeruginosa in MFCs could enhance its discharging time and improve the overall energy yield. This work could give a clue to improve the characteristics of MFCs using genetic engineering strain, and could promote related application studies on MFCs.

  19. MEDEVAC: survival and physiological parameters improved with higher level of flight medic training.

    PubMed

    Holland, Seth R; Apodaca, Amy; Mabry, Robert L

    2013-05-01

    Determine if a higher level of Army flight medic (AFM) training was associated with improved physiological state on arrival to a combat support hospital (CSH). A retrospective study comparing casualties who were evacuated by two AFM units with only Emergency Medical Technicians-Basic (EMT-Bs) to an Army National Guard unit with Critical Care Flight Paramedics (CCFPs) in Afghanistan with an injury severity score >16 in different time periods looking at their 48-hour mortality, hematocrit (HCT), base deficit (BD), oxygen saturation (SpO2), and physiological parameters on arrival to the CSH. The CCFP group had better HCT [36.5 (8.8)] than the EMT-B group [33.1 (11.4); p ≤ 0.001]. BD and SpO2 were better in the CCFP group [-3.2 (4.7)]/[97.8 (4.8)] than the EMT-B group [-4.4 (5.5)]/[96.3 (10.9)] [p ≤ 0.014]. The CCFP group had a 72% lower estimated risk ratio of mortality with an associated improvement in 48-hour survivability of 4.9% versus 15.8% for the EMT-B-group. There is a statistically significant improvement in the HCT, BD, SpO2, and 48-hour survivability at the CSH in the cohort transported by the CCFP group when compared to the cohort transported by the EMT-B group. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

  20. Sigma-1R agonist improves motor function and motoneuron survival in ALS mice.

    PubMed

    Mancuso, Renzo; Oliván, Sara; Rando, Amaya; Casas, Caty; Osta, Rosario; Navarro, Xavier

    2012-10-01

    Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1(G93A) mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1(G93A) animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca(2+) influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS.

  1. Tissue Engineering Considerations in Dental Pulp Regeneration

    PubMed Central

    Nosrat, Ali; Kim, Jong Ryul; Verma, Prashant; S. Chand, Priya

    2014-01-01

    Regenerative endodontic procedure is introduced as a biologically based treatment for immature teeth with pulp necrosis. Successful clinical and radiographic outcomes following regenerative procedures have been reported in landmark case reports. Retrospective studies have shown that this conservative treatment allows for continued root development and increases success and survival rate of the treated teeth compared to other treatment options. Although the goal of treatment is regeneration of a functional pulp tissue, histological analyses show a different outcome. Developing predictable protocols would require the use of key elements for tissue engineering: stem cells, bioactive scaffolds, and growth factors. In this study we will review the evidence based steps and outcomes of regenerative endodontics. PMID:24396373

  2. Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

    PubMed Central

    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. PMID:24204769

  3. Extracorporeal membrane oxygenation support improves survival of patients with severe Hantavirus cardiopulmonary syndrome.

    PubMed

    Dietl, Charles A; Wernly, Jorge A; Pett, Stuart B; Yassin, Said F; Sterling, José P; Dragan, Robert; Milligan, Karen; Crowley, Mark R

    2008-03-01

    The purposes of this study are to evaluate the outcome of extracorporeal membrane oxygenation support in a subgroup of patients with Hantavirus cardiopulmonary syndrome who had a predicted mortality of 100% and to assess the complications associated with this treatment modality and with different cannulation techniques. Thirty-eight patients with severe Hantavirus cardiopulmonary syndrome were supported with extracorporeal membrane oxygenation between April 1994 and June 2006. Cannulation of the femoral vessels was performed on an emergency basis by a percutaneous approach in 15 (39.5%) and by an open technique in 23 (60.5%) patients. Duration of extracorporeal membrane oxygenation averaged 132 hours (range: 5-276 hours). Complications from percutaneous cannulation occurred in 4 (26.6%) of 15 patients: retroperitoneal hematoma in 2 (13.3%) and lower extremity ischemia in 2 (13.3%) patients, which resolved after insertion of a distal perfusion cannula. Complications from open femoral cannulation occurred in 8 (34.8%) of 23 patients: severe bleeding in 7 (30.4%) patients and lower extremity ischemia in 1 (4.3%) patient who required a leg amputation. The overall survival was 60.5% (23/38 patients). Six (40%) of the 15 patients cannulated percutaneously and 9 (39.1%) of 23 patients who had open cannulation died. All survivors recovered completely and were discharged from the hospital after a mean hospital stay of 20.8 days (range: 10-39 days). Almost two thirds of the patients with severe Hantavirus cardiopulmonary syndrome who were supported with extracorporeal circulation survived and recovered completely. The complications associated with both types of femoral cannulation may be attributed to the fact that all patients were in shock or in full cardiac arrest, and the procedure had to be done expeditiously. Earlier institution of extracorporeal membrane oxygenation may decrease the complication rates and improve the overall survival.

  4. Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy.

    PubMed

    An, J; Kim, K W; Han, S; Lee, J; Lim, Y-S

    2014-06-01

    Spontaneous portosystemic shunt (SPSS) is a frequent cause of recurrent hepatic encephalopathy (HE) in patients with cirrhosis. To assess the effectiveness and optimal candidate selection for embolisation of SPSS, for the treatment of recurrent HE in patients with cirrhosis. This retrospective cohort study compared 17 patients with recurrent HE who achieved complete occlusion of SPSS by angiographic embolisation and 17 control patients. Most baseline characteristics were similar in the two groups. The 2-year HE recurrence rate was significantly lower in the embolisation than in the control group (39.9% vs. 79.9%, P = 0.02), whereas their 2-year overall survival rates were similar (64.7% vs. 53.4%, P = 0.98). Model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) score were significant predictors of 2-year patient mortality in the embolisation group. Analysis of patients with MELD <15 in the absence of hepatocellular carcinoma (HCC) showed that 2-year overall survival rate was significantly higher in the embolisation group than in the control group (100% vs. 60%, P = 0.03). The median changes in MELD (-1.6 vs. 2.5, P < 0.01), CTP score (-3 vs. 0, P < 0.01), and liver volume (61 mL vs. -117 mL; P = 0.046) at 1 year significantly favoured the embolisation group. Serious clinical complications after embolisation occurred only in patients who had MELD ≥15 and/or HCC at baseline, with all six dying within 1 year. Embolisation of a large spontaneous portosystemic shunt may be associated with improved survival and liver function, as well as prevention of hepatic encephalopathy in cirrhotic patients with recurrent hepatic encephalopathy and modestly preserved liver function. © 2014 John Wiley & Sons Ltd.

  5. Resveratrol improves motoneuron function and extends survival in SOD1(G93A) ALS mice.

    PubMed

    Mancuso, Renzo; del Valle, Jaume; Modol, Laura; Martinez, Anna; Granado-Serrano, Ana B; Ramirez-Núñez, Omar; Pallás, Mercé; Portero-Otin, Manel; Osta, Rosario; Navarro, Xavier

    2014-04-01

    Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2-5 years after diagnosis. Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1(G93A) ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests. We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1(G93A) mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1(G93A) spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.

  6. Removal of lipophilic extractives from paper pulp by laccase and lignin-derived phenols as natural mediators.

    PubMed

    Gutiérrez, Ana; Rencoret, Jorge; Ibarra, David; Molina, Setefilla; Camarero, Susana; Romero, Javier; Del Río, José C; Martínez, Angel T

    2007-06-01

    In this paper, we show for the first time that lignin-derived phenols can act as laccase mediators for the removal of lipophilic compounds from paper pulp. These natural mediators represent an alternative to synthetic mediators, such as 1-hydroxybenzotriazole (HBT), that cause some economic and environmental concerns. Unbleached kraft pulp from eucalypt wood, which contained free and conjugated sterols responsible for pitch deposition in the manufacture of totally chlorine free paper, was treated with a fungal laccase in the presence of syringaldehyde, acetosyringone, and p-coumaric acid as mediators. The composition of lipophilic extractives in the pulps after the enzymatic treatment followed by a hydrogen peroxide stage was analyzed by gas chromatography and gas chromatography/mass spectrometry. The enzymatic treatment using syringaldehyde as laccase mediator caused the highest removal (over 90%) of free and conjugated sitosterol, similar to that attained with HBT, followed by acetosyringone (over 60% removal), whereas p-coumaric acid was barely effective. Moreover, recalcitrant oxidized steroids surviving laccase-HBT treatment could be removed when using these natural mediators. Pulp brightness was also improved (from 57% to 66% ISO brightness) by the laccase treatment in the presence of the above phenols followed by the peroxide stage due to the simultaneous removal of lignin.

  7. Working to improve survival and health for babies born very preterm: the WISH project protocol.

    PubMed

    Crowther, Caroline A; Middleton, Philippa F; Bain, Emily; Ashwood, Pat; Bubner, Tanya; Flenady, Vicki; Morris, Jonathan; McIntyre, Sarah

    2013-12-19

    Babies born very preterm (before 30 weeks gestation) are at high risk of dying in their first weeks of life, and those who survive are at risk of developing cerebral palsy in childhood. Recent high-quality evidence has shown that giving women magnesium sulphate immediately prior to very early birth can significantly increase the chances of their babies surviving free of cerebral palsy. In 2010 Australian and New Zealand clinical practice guidelines recommended this therapy. The WISH (Working to Improve Survival and Health for babies born very preterm) Project aims to bi-nationally improve and monitor the use of this therapy to reduce the risk of very preterm babies dying or having cerebral palsy. The WISH Project is a prospective cohort study. The 25 Australian and New Zealand tertiary level maternity hospitals will be provided with a package of active implementation strategies to guide the introduction and local adaptation of guideline recommendations. Surveys will be conducted at individual hospitals to evaluate outcomes related to local implementation progress and the use and value of the WISH implementation strategies. For the hospitals participating in the 'WISH audit of uptake and health outcomes data collection', the primary health outcomes (assessed through case note review, and 24 month corrected age questionnaires) will be: the proportion of eligible women receiving antenatal magnesium sulphate; and rates of death prior to primary hospital discharge and cerebral palsy at two years corrected age in infants born to eligible mothers. For hospitals wishing to assess factors influencing translation locally, barriers and facilitators will be measured through interviews with health care professionals, to further guide implementation strategies. Study outcomes for the early phase of the project (Year 1) will be compared with the later intervention phase (Years 2 and 3). The WISH Project will offer insight into the effectiveness of a multifaceted implementation

  8. Working to improve survival and health for babies born very preterm: the WISH project protocol

    PubMed Central

    2013-01-01

    Background Babies born very preterm (before 30 weeks gestation) are at high risk of dying in their first weeks of life, and those who survive are at risk of developing cerebral palsy in childhood. Recent high-quality evidence has shown that giving women magnesium sulphate immediately prior to very early birth can significantly increase the chances of their babies surviving free of cerebral palsy. In 2010 Australian and New Zealand clinical practice guidelines recommended this therapy. The WISH (Working to Improve Survival and Health for babies born very preterm) Project aims to bi-nationally improve and monitor the use of this therapy to reduce the risk of very preterm babies dying or having cerebral palsy. Methods/Design The WISH Project is a prospective cohort study. The 25 Australian and New Zealand tertiary level maternity hospitals will be provided with a package of active implementation strategies to guide the introduction and local adaptation of guideline recommendations. Surveys will be conducted at individual hospitals to evaluate outcomes related to local implementation progress and the use and value of the WISH implementation strategies. For the hospitals participating in the ‘WISH audit of uptake and health outcomes data collection’, the primary health outcomes (assessed through case note review, and 24 month corrected age questionnaires) will be: the proportion of eligible women receiving antenatal magnesium sulphate; and rates of death prior to primary hospital discharge and cerebral palsy at two years corrected age in infants born to eligible mothers. For hospitals wishing to assess factors influencing translation locally, barriers and facilitators will be measured through interviews with health care professionals, to further guide implementation strategies. Study outcomes for the early phase of the project (Year 1) will be compared with the later intervention phase (Years 2 and 3). Discussion The WISH Project will offer insight into the

  9. Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury.

    PubMed

    Nosrat, I V; Widenfalk, J; Olson, L; Nosrat, C A

    2001-10-01

    Interactions between ingrowing nerve fibers and their target tissues form the basis for functional connectivity with the central nervous system. Studies of the developing dental pulp innervation by nerve fibers from the trigeminal ganglion is an excellent example of nerve-target tissue interactions and will allow specific questions regarding development of the dental pulp nerve system to be addressed. Dental pulp cells (DPC) produce an array of neurotrophic factors during development, suggesting that these proteins might be involved in supporting trigeminal nerve fibers that innervate the dental pulp. We have established an in vitro culture system to study the interactions between the dental pulp cells and trigeminal neurons. We show that dental pulp cells produce several neurotrophic factors in culture. When DPC are cocultured with trigeminal neurons, they promote survival and a specific and elaborate neurite outgrowth pattern from trigeminal neurons, whereas skin fibroblasts do not provide a similar support. In addition, we show that dental pulp tissue becomes innervated when transplanted ectopically into the anterior chamber of the eye in rats, and upregulates the catecholaminergic nerve fiber density of the irises. Interestingly, grafting the dental pulp tissue into hemisected spinal cord increases the number of surviving motoneurons, indicating a functional bioactivity of the dental pulp-derived neurotrophic factors in vivo by rescuing motoneurons. Based on these findings, we propose that dental pulp-derived neurotrophic factors play an important role in orchestrating the dental pulp innervation.

  10. Dycal versus Nd:YAG laser and Vitrebond for direct pulp capping in permanent teeth.

    PubMed

    Santucci, P J

    1999-04-01

    To determine the efficacy of laser-assisted direct pulp capping by comparing the survival rates of permanent teeth treated with Nd:YAG laser and Vitrebond (3M Corporation, St. Paul, MN) direct pulp caps to permanent teeth treated with the traditional calcium hydroxide direct pulp cap over intervals of up to 54 months. While there are case reports and evaluations of various laser techniques in the literature, statistical studies comparing the success of laser-assisted applications to traditional techniques are needed. This is a retrospective investigation of one such laser assisted application. A retrospective chart review of all active and inactive patients resulted in the identification of 83 patients who received direct pulp caps in a total of 93 permanent teeth; 29 with calcium hydroxide and 64 with Nd:YAG laser and Vitrebond. Life table analysis of the data of this retrospective study demonstrated that the teeth treated with the laser and Vitrebond direct pulp cap showed significantly greater survival rates than those treated with Dycal direct pulp cap over intervals of nine to 54 months postoperatively. The cumulative proportion of teeth surviving postoperatively for the Dycal (L.D. Caulk Corporation, Milford, CT) direct pulp cap was 89.7% at 1 month declining to 79.4% at 3 months and 76% at 6 months and then continued to decline in the final two intervals finishing after 54 months at 43.6%. For the laser and Vitrebond direct pulp cap the cumulative proportion surviving stood at 98.4% after 1 month, declining to 93.8% at 3 months and 90.3% after 6 months but then held steady in the final 2 intervals finishing at 90.3% after 54 months. The laser and Vitrebond direct pulp cap produces a significantly more predictable pulpal response after the first 6 months than the Dycal direct pulp cap. The survival rate of teeth treated with the laser and Vitrebond direct pulp cap is significantly greater than those treated with the Dycal direct pulp cap over intervals of 9

  11. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  12. Cardiac trauma: has survival improved? A university hospital experience in Bangkok, Thailand.

    PubMed

    Kritayakirana, Kritaya; Sriussadaporn, Sukanya; Pak-Art, Rattaplee; Prichayudh, Supparerk; Samorn, Pasurachate; Sriussadaporn, Suvit

    2013-02-01

    Cardiac trauma, if not recognized and properly treated, will lead to a fatal outcome. For the past 16 years, the authors' policy for diagnosing and treating cardiac trauma has not changed but the survival rate in our institute has improved when compared between the two cohorts. Study the factors for survival in patients with cardiac trauma. Data was collected from chart review between September 1994 and April 2010. Patients presenting in extremis with suspected cardiac trauma will receive emergency room thoracotomy. Patients with equivocal Focused Assessment with Sonography for Trauma will receive formal transthoracic echocardiography. If still in doubt, the authors' policy will proceed with intra operative subxiphoid window and a set up for median sternotomy. Throughout the study period, 44 patients had cardiac trauma and the overall mortality rate was 13.6%. Four patients had blunt injury resulting in one ventricular septal defect and three ruptured right atrium. Right ventricle was injured the most 44%, right atrium 23%, left ventricle 20%, left atrium 2%, one patient had superior vena cava injury, and another patient had inferior vena cava injury. In this cohort, 30% underwent emergency room thoracotomy. Associated injuries were presented in 38% of cases. High index of suspicion and prompt management for cardiac trauma should be considered in patients presenting with injuries to the chest, which has been the authors' policy for the past 16 years. The mortality rate had dropped from 26% to 4% but is not statistically significant.

  13. Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme.

    PubMed

    Salomón, Débora G; Fermento, María E; Gandini, Norberto A; Ferronato, María J; Arévalo, Julián; Blasco, Jorge; Andrés, Nancy C; Zenklusen, Jean C; Curino, Alejandro C; Facchinetti, María M

    2014-05-01

    Vitamin D and its analogs have been shown to display anti-proliferative effects in a wide variety of cancer types including glioblastoma multiforme (GBM). These anticancer effects are mediated by its active metabolite, 1α, 25-dihydroxyvitamin D3 (calcitriol) acting mainly through vitamin D receptor (VDR) signaling. In addition to its involvement in calcitriol action, VDR has also been demonstrated to be useful as a prognostic factor for some types of cancer. However, to our knowledge, there are no studies evaluating the expression of VDR protein and its association with outcome in gliomas. Therefore, we investigated VDR expression by using immunohistochemical analysis in human glioma tissue microarrays, and analyzed the association between VDR expression and clinico-pathological parameters. We further investigated the effects of genetic and pharmacologic modulation of VDR on survival and migration of glioma cell lines. Our data demonstrate that VDR is increased in tumor tissues when compared with VDR in non-malignant brains, and that VDR expression is associated with an improved outcome in patients with GBM. We also show that both genetic and pharmacologic modulation of VDR modulates GBM cellular migration and survival and that VDR is necessary for calcitriol-mediated effects on migration. Altogether these results provide some limited evidence supporting a role for VDR in glioma progression.

  14. Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer

    PubMed Central

    Mei, Hong; Pu, Jiarui; Xiang, Xuan; Jiao, Wanju; Song, Huajie; Qu, Hongxia; Huang, Kai; Zheng, Liduan; Tong, Qiangsong

    2015-01-01

    Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory lectin, in human cancers. Our previous studies have implicated the potential roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated the functions, downstream targets, and clinical significance of ITLN1 in the progression of gastric cancer. We demonstrated that ITLN1 increased the levels of hepatocyte nuclear factor 4 alpha (HNF4α), resulting in suppression of nuclear translocation and transcriptional activity of β-catenin in gastric cancer cells. Mechanistically, ITLN1 attenuated the activity of nuclear factor-kappa B, a transcription factor repressing the HNF4α expression, in gastric cancer cells through inactivating the phosphoinositide 3-kinase/AKT/Ikappa B kinase signaling. Gain- and loss-of-function studies demonstrated that ITLN1 suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. In addition, restoration of HNF4α expression prevented the gastric cancer cells from ITLN1-mediated changes in these biological features. In clinical gastric cancer tissues, HNF4α expression was positively correlated with that of ITLN1. Patients with high ITLN1 or HNF4α expression had greater survival probability. Taken together, these data indicate that ITLN1 suppresses the progression of gastric cancer through up-regulation of HNF4α, and is associated with improved survival in patients with gastric cancer. PMID:25965823

  15. Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.

    PubMed

    Li, Dan; Zhao, Xiang; Xiao, Yong; Mei, Hong; Pu, Jiarui; Xiang, Xuan; Jiao, Wanju; Song, Huajie; Qu, Hongxia; Huang, Kai; Zheng, Liduan; Tong, Qiangsong

    2015-06-30

    Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory lectin, in human cancers. Our previous studies have implicated the potential roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated the functions, downstream targets, and clinical significance of ITLN1 in the progression of gastric cancer. We demonstrated that ITLN1 increased the levels of hepatocyte nuclear factor 4 alpha (HNF4α), resulting in suppression of nuclear translocation and transcriptional activity of β-catenin in gastric cancer cells. Mechanistically, ITLN1 attenuated the activity of nuclear factor-kappa B, a transcription factor repressing the HNF4α expression, in gastric cancer cells through inactivating the phosphoinositide 3-kinase/AKT/Ikappa B kinase signaling. Gain- and loss-of-function studies demonstrated that ITLN1 suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. In addition, restoration of HNF4α expression prevented the gastric cancer cells from ITLN1-mediated changes in these biological features. In clinical gastric cancer tissues, HNF4α expression was positively correlated with that of ITLN1. Patients with high ITLN1 or HNF4α expression had greater survival probability. Taken together, these data indicate that ITLN1 suppresses the progression of gastric cancer through up-regulation of HNF4α, and is associated with improved survival in patients with gastric cancer.

  16. Prenatal Therapy Improves the Survival of Premature Infants with Congenital Chylothorax.

    PubMed

    Lee, Chia-Jung; Tsao, Po-Nien; Chen, Chien-Yi; Hsieh, Wu-Shiun; Liou, Jyun-You; Chou, Hung-Chieh

    2016-04-01

    Chylothorax is a rare condition among neonates, although it is considered clinically significant, as it is difficult to manage in these patients. In addition, the course of chylothorax varies widely. Therefore, we aimed to elucidate the clinical features and effect of prenatal therapy on the prognosis of congenital chylothorax in neonates. We retrospectively reviewed the medical records of all infants with congenital chylothorax who were admitted to National Taiwan University Hospital, Taipei, Taiwan between January 2000 and December 2012. Their demographic characteristics, as well as their antenatal, perinatal, and postnatal information, were collected for our analysis of the mortality risk. We found 29 infants who were diagnosed with congenital chylothorax during the study period. The median gestational age at birth was 34 weeks (range, 28-41 weeks), and 71% of the infants presented with hydrops fetalis. Most cases of congenital chylothorax were bilateral (bilateral: 86.2%, unilateral: 13.79%), and the overall survival rate was 59.6%. Among the cases with a prenatal diagnosis at ≤ 34 weeks of gestation, infants who received prenatal therapy had a significantly higher survival rate, compared to infants who did not receive prenatal therapy (76.9% vs. 11%, respectively; p = 0.008). We found that infants whose chylothorax was diagnosed ≤ 34 weeks of gestation, and who subsequently received prenatal therapy, experienced a better perinatal condition and exhibited improved postnatal outcomes. Copyright © 2016. Published by Elsevier B.V.

  17. TMA secondary to SLE: rituximab improves overall but not renal survival.

    PubMed

    Sun, Fangfang; Wang, Xiaodong; Wu, Wanlong; Wang, Kaiwen; Chen, Zhiwei; Li, Ting; Ye, Shuang

    2017-08-30

    Thrombotic microangiopathy (TMA) includes a series of life-threatening disorders. Systemic lupus erythematosus (SLE) is one of the most common acquired causes. To identify predictors of prognosis in patients with TMA secondary to SLE, we conducted a single-center historical study. From January 2013 to June 2016, of 2182 SLE hospitalized patients in the Ren Ji Hospital, a total of 21 consecutive patients with TMA secondary to SLE were identified. The 90-day short-term mortality was 33.3%. The kidney involvement (66.7%) was associated with poor prognosis, while the administration of rituximab (n = 13) was an independent protective factor according to logistic regression analysis. Compared to conventional treatment, i.e., plasma exchange, high-dose glucocorticoids, and intravenous immunoglobulin, the overall survival is significantly higher among patients receiving rituximab add-on (92.2 vs 33.3%, p = 0.0173); however, five out of seven patients with renal involvement in the rituximab group were eventually hemodialysis dependent. Our data indicated that add-on rituximab in the background of conventional therapy may improve the overall but not the renal survival in SLE-TMA patients.

  18. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group.

    PubMed

    Meyers, Paul A; Schwartz, Cindy L; Krailo, Mark D; Healey, John H; Bernstein, Mark L; Betcher, Donna; Ferguson, William S; Gebhardt, Mark C; Goorin, Allen M; Harris, Michael; Kleinerman, Eugenie; Link, Michael P; Nadel, Helen; Nieder, Michael; Siegal, Gene P; Weiner, Michael A; Wells, Robert J; Womer, Richard B; Grier, Holcombe E

    2008-02-01

    To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma. Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival. In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96). The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.

  19. Palliative resection of a primary tumor in patients with unresectable colorectal cancer: could resection type improve survival?

    PubMed Central

    Jang, Hyun Seok; Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin

    2016-01-01

    Purpose The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC). Methods A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined. Results Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786). Conclusion Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002). PMID:27757394

  20. Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis.

    PubMed

    Li, Peiwei; Wu, Han; Zhang, Honghe; Shi, Yu; Xu, Jinming; Ye, Yao; Xia, Dajing; Yang, Jun; Cai, Jianting; Wu, Yihua

    2015-09-01

    The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC). Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC. Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05). These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Metallofullerene-Nanoplatform-Delivered Interstitial Brachytherapy Improved Survival in a Murine Model of Glioblastoma Multiforme

    PubMed Central

    Wilson, John D.; Broaddus, William C.; Dorn, Harry C.; Fatouros, Panos P.; Chalfant, Charles E.; Shultz, Michael D.

    2012-01-01

    Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene (177Lu-DOTA-f-Gd3N@C80) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM). A dose-dependent improvement in survival was also shown. The in vivo stability of the agent was verified through dual label measurements of biological elimination from the tumor. Overall, these results provide evidence that nanomaterial platforms can be used to deliver effective interstitial brachytherapy. PMID:22881865

  2. Chemical chaperone TUDCA prevents apoptosis and improves survival during polymicrobial sepsis in mice

    PubMed Central

    Doerflinger, Marcel; Glab, Jason; Nedeva, Christina; Jose, Irvin; Lin, Ann; O’Reilly, Lorraine; Allison, Cody; Pellegrini, Marc; Hotchkiss, Richard S.; Puthalakath, Hamsa

    2016-01-01

    Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice. Furthermore, in a ‘two-hit’ pneumonia model in mice, we have been able to demonstrate that administration of the chemical chaperone TUDCA helped to maintain lymphocyte homeostasis by significantly reducing lymphocyte apoptosis and this correlated with four-fold improvement in survival. Our results demonstrate a novel therapeutic opportunity for treating sepsis-induced lymphopenia in humans. PMID:27694827

  3. Effective Treatment for Improving the Survival Rate of Raccoon Dogs Infected with Sarcoptes scabiei

    PubMed Central

    KIDO, Nobuhide; OMIYA, Tomoko; KAMEGAYA, Chihiro; WADA, Yuko; TAKAHASHI, Maya; YAMAMOTO, Yasuhiko

    2014-01-01

    ABSTRACT Sarcoptes scabiei is one of the important external parasites. Although ivermectin is the recommended treatment, many raccoon dogs (Nyctereutes procyonoides) that were rescued and brought to the Kanazawa Zoological Gardens (Yokohama, Japan) have died because of S. scabiei, even after receiving single ivermectin treatment. Therefore, supportive treatment should be required. The present study revealed the number of animals that survived was greater after the administration of ivermectin along with an antibiotic for all raccoon dogs, as well as following the administration of fluid therapy to the debilitated raccoon dogs infected with S. scabiei, immediately after the rescue. During the initial period, treatment to improve the general clinical condition was required prior to deworming treatment for S. scabiei. PMID:24813465

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

    PubMed Central

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    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. PMID:27540317

  5. Does Computer Assisted Navigation Improve Functional Outcomes and Implant Survivability after Total Knee Arthroplasty?

    PubMed

    Roberts, Timothy D; Clatworthy, Mark G; Frampton, Chris M; Young, Simon W

    2015-09-01

    The objective of this study was to determine whether computer assisted navigation in total knee arthroplasty (TKA) improves functional outcomes and implant survivability using data from a large national database. We analysed 9054 primary TKA procedures performed between 2006 and 2012 from the New Zealand National Joint Registry. Functional outcomes were assessed using Oxford Knee Questionnaires at six months and five years. On multivariate analysis, there was no significant difference in mean Oxford Knee Scores between the navigated and non-navigated groups at six months (39.0 vs 38.1, P=0.54) or five years (42.2 vs 42.0, P=0.76). At current follow-up, there was no difference in revision rates between navigated and non-navigated TKA (0.46 vs 0.43 revisions 100 component years, P=0.8).

  6. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease

    SciTech Connect

    Lindvall, O.; Brundin, P.; Widner, H.; Rehncrona, S.; Gustavii, B.; Frackowiak, R.; Leenders, K.L.; Sawle, G.; Rothwell, J.C.; Marsden, C.D. )

    1990-02-02

    Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-({sup 18}F)fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the on-off phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

  7. [Coffee hulls and pulp. XII. Effect of storage of coffee pulp on its nutritive value for calves].

    PubMed

    Cabezas, M T; Estrada, E; Murillo, B; González, J M; Bressani, R

    1976-06-01

    Coffee pulp, dehydrated and stored for 7, 13 and 17 months or ensiled for 4, 10 and 14 months, was studied in calves with a rapid growing rate. Storage of dehydrated coffee pulp did not affect its chemical composition, but ensiling reduced crude fiber and increased its nitrogen free extract content after 10 and 14 months. Three growth trials were carried out with Holstein calves averaging 95 kg in the first and second trials, and 130 kg in the third. Eighteen calves were used in the first trial and 24 in each of the other two. In each trial the animals were divided into three equal groups and randomly assigned to one of the following treatments: control, which contained 48% cottonseed hulls, and the other two, with 30% dehydrated coffee pulp or 30% ensiled coffee pulp. Basically, the difference between trials consisted in the time of storage or ensiling of coffee pulp. In all trials, weight gains of calves fed coffee pulp (1.00, 0.90 and 0.98 kg/day, and 1.06, 0.94 and 1.08 kg/day, respectively) were significantly lower (P less than 0.05) than the weight gains induced by the control ration (1.21, 1.08 and 1.19 kg/day). Feed intake was also lower, but feed conversion ratio was higher for those rations containing coffee pulp. Calf performance was better with ensiled than with deydrated coffee pulp, particularly in the third trial, where the differences in weight gains were significantly higher (P less than 0.05). It is concluded that storage time does not change nutritive value of coffee pulp; and the ensiling is an adequate process for storing pulp during coffee harvesting, and, possibly also, for improving its nutritive value.

  8. Intravenous hydrogen sulfide does not induce hypothermia or improve survival from hemorrhagic shock in pigs.

    PubMed

    Drabek, Tomas; Kochanek, Patrick M; Stezoski, Jason; Wu, Xianren; Bayir, Hülya; Morhard, Ryan C; Stezoski, S William; Tisherman, Samuel A

    2011-01-01

    Several laboratory studies suggested that induced hypothermia during hemorrhagic shock improves survival. Inhaled hydrogen sulfide (H2S) induced hypothermia and decreased metabolism in mice and rats but not in piglets. We tested the hypothesis that i.v. H2S will induce hypothermia, reduce oxygen consumption (VO2), and improve outcome in prolonged hemorrhagic shock in pigs. We also assessed markers of organ injury (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, creatinine, and troponin) and level of protein thiols to monitor H2S metabolism. In a prospective randomized study, pigs were subjected to volume-controlled hemorrhagic shock with limited fluid resuscitation to maintain MAP 30 mmHg or greater. The study group received infusion of H2S at 5 mg·kg·h; the control group received vehicle (n = 8 per group). Dose was based on the highest tolerated dose in pilot studies. Full resuscitation was initiated after 3 h. There were no differences in survival at 24 h between groups (2/8 in H2S vs. 3/8 in control group). Heart rate increased similarly during hemorrhagic shock in both groups. Cardiac output was better preserved in the delayed phase of hemorrhagic shock in the control group. Temperature and VO2 were similar in both groups during hemorrhagic shock and resuscitation. Markers of organ injury and protein thiols markedly increased in both groups with no differences between groups. In conclusion, we were not able to demonstrate the hypothermia-inducing effect or a reduction in VO2 from H2S infusion in our model of hemorrhagic shock in pigs. Our data mirror those seen in piglets and provide additional evidence of difficulty in translating the hypothermia effect of H2S to large animals in a clinically relevant postinsult paradigm.

  9. Brain metastasis in sarcoma: Does metastasectomy or aggressive multi-disciplinary treatment improve survival outcomes.

    PubMed

    Chua, Clarinda; Raaj, Jeevan; Pan, Summer; Farid, Mohamad; Lee, Jin Fu Marcus; Ho, Zhen Chong; Sairi, Alisa; Sittampalam, Kesavan; Tao, Miriam; Tay, Kevin; Lim, Soon Thye; Chin, Francis; Teo, Melissa; Quek, Richard

    2016-03-01

    Brain metastasis is rare in sarcoma. Prognostic factors, optimal management strategies and therapeutic outcomes of such patients are not well studied. We aimed to evaluate the incidence, clinical characteristics and treatment outcomes of parenchymal brain metastasis in sarcoma patients. This is a single center retrospective analysis. Overall survival (OS) was calculated from the time of diagnosis of brain metastasis to time of death. Sixteen patients (2.1%) with complete electronic medical records treated at our institution from 2002 to 2010 were identified. Median age was 52 years; 88% had additional sites of metastases. Eight different subtypes of soft tissue and bone sarcoma were identified. Eighty-one percent of the patients developed metachronous brain metastasis at a median of 14 months after initial sarcoma diagnosis. Thirty-eight percent of patients had solitary brain metastasis and 44% underwent aggressive therapy for brain metastasis, defined as either surgical resection or multimodality treatment. The remaining 56% received conservative treatment (either whole brain radiation alone, chemotherapy alone or best supportive care). Median OS for the entire cohort was 3.5 months (95% CI 1.1-6.3 months). A trend toward improved OS was observed with an aggressive treatment approach, 3.7 months versus 1.2 months (P = 0.077) and the usage of chemotherapy (P = 0.071). Brain metastasis in sarcoma is rare, usually coexists with significant systemic disease and is associated with a grave prognosis. Use of chemotherapy and an aggressive treatment approach in well-selected patients may be associated with improved survival. Prospective studies are needed to confirm these findings. © 2013 Wiley Publishing Asia Pty Ltd.

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

    PubMed

    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.

  11. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance.

    PubMed

    Modell, Bernadette; Khan, Maren; Darlison, Matthew; Westwood, Mark A; Ingram, David; Pennell, Dudley J

    2008-09-25

    The UK Thalassaemia Register records births, deaths and selected clinical data of patients with thalassaemia who are resident in the UK. A study of survival and causes of death was undertaken which aimed to include the possible impact of T2* cardiovascular magnetic resonance (CMR). The Register was updated to the end of 2003, copies of death certificates were obtained, and causes of death in beta thalassaemia major were extracted. In addition, patients who had T2* CMR assessment of cardiac iron load and/or received the oral iron chelator deferiprone were identified from clinical records. The main causes of death were anaemia (before 1980), infections, complications of bone marrow transplantation and cardiac disease due to iron overload. From 1980 to 1999 there were 12.7 deaths from all causes per 1,000 patient years. Forty per cent of patients born before 1980 had T2* cardiovascular magnetic resonance between 2000 and 2003, and 36% of these patients were prescribed deferiprone before end of 2003. In 2000-2003, the death rate from all causes fell significantly to 4.3 per 1,000 patient years (-62%, p < 0.05). This was mainly driven by the reduction in the rate of deaths from iron overload which fell from 7.9 to 2.3 deaths per 1,000 patient years (-71%, p < 0.05). Since 1999, there has been a marked improvement in survival in thalassaemia major in the UK, which has been mainly driven by a reduction in deaths due to cardiac iron overload. The most likely causes for this include the introduction of T2* CMR to identify myocardial siderosis and appropriate intensification of iron chelation treatment, alongside other improvements in clinical care.

  12. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis

    PubMed Central

    Gerber, Yannick N.; Privat, Alain; Perrin, Florence E.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-methyl-D-aspartate (NMDA)-mediated cell death and impairment of the glutamate-transport has been suggested to play a key role in ALS pathophysiology. Thus, evaluating NMDAR antagonists is of high therapeutic interest. Gacyclidine, also named GK11, is a high affinity non-competitive NMDAR antagonist that may protect against motor neuron death in an ALS context. Moreover, GK11 presents a low intrinsic neurotoxicity and has already been used in two clinical trials for CNS lesions. In the present study, we investigated the influence of chronic administration of two doses of GK11 (0.1 and 1 mg/kg) on the survival and the functional motor activity of hSOD1G93A mice, an animal model of ALS. Treatment started at early symptomatic age (60 days) and was applied bi-weekly until the end stage of the disease. We first confirmed that functional alteration of locomotor activity was evident in the hSOD1G93A transgenic female mice by 60 days of age. A low dose of GK11 improved the survival of the mice by 4.3% and partially preserved body weight. Improved life span was associated with a delay in locomotor function impairment. Conversely, the high dose treatment worsened motor functions. These findings suggest that chronic administration of GK11 beginning at early symptomatic stage may be beneficial for patients with ALS. PMID:24409117

  13. Improved Survival with T Cell Clonotype Stability After Anti–CTLA-4 Treatment in Cancer Patients

    PubMed Central

    Cha, Edward; Klinger, Mark; Hou, Yafei; Cummings, Craig; Ribas, Antoni; Faham, Malek; Fong, Lawrence

    2015-01-01

    Cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) blockade can promote antitumor T cell immunity and clinical responses. The mechanism by which anti–CTLA-4 antibodies induces antitumor responses is controversial. To determine the effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β (TCRβ) genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes. CTLA-4 blockade in patients with metastatic castration-resistant prostate cancer and metastatic melanoma resulted in both expansion and loss of T cell clonotypes, consistent with a global turnover of the T cell repertoire. Overall, this treatment increased TCR diversity as reflected in the number of unique TCR clonotypes. The repertoire of clonotypes continued to evolve over subsequent months of treatment. Whereas the number of clonotypes that increased with treatment was not associated with clinical outcome, improved overall survival was associated with maintenance of high-frequency clones at baseline. In contrast, the highest-frequency clonotypes fell with treatment in patients with short overall survival. Stably maintained clonotypes included T cells having high-avidity TCR such as virus-reactive T cells. Together, these results suggest that CTLA-4 blockade induces T cell repertoire evolution and diversification. Moreover, improved clinical outcomes are associated with less clonotype loss, consistent with the maintenance of high-frequency TCR clonotypes during treatment. These clones may represent the presence of preexisting high-avidity T cells that may be relevant in the antitumor response. PMID:24871131

  14. Morphological and mechanical effects of extended beating on EFB pulp web

    NASA Astrophysics Data System (ADS)

    Zukeri, Mohd Ridzuan Hafiz Mohd; Ghazali, Arniza; Lazin, Mohd Azli Khairil Mat

    2012-09-01

    The pulp extracted from the alkaline peroxide pulping (APP) of EFB was beaten from 500 revolutions to 10000 revolutions using PFI mill to investigate the morphological changes undergone by the pulp and the resultant effect on paper sheet properties. As a result of beating, pulp elements were observed as intensely fibrillated, reducing the amounts of fibre bundles and thus, reducing interruption in the inter-fiber bonding. To a defined extent, beating was also seen as unwinding the structure of vessel element to a single strand of loose spiral body. These fibrillated vessel elements of APP pulp from EFB, plus the fines element germinating from further segmentation of the vessels, were the factors contributing to the overall strength improvement of the produced EFB pulp network. The applied increment in beating revolution had apparently widened the known broad spectrum quality of APP pulp from EFB. This demonstrates EFB potential for application in specialty paper production.

  15. Recognition and management of atlanto-occipital dislocation: improving survival from an often fatal condition

    PubMed Central

    Fisher, Charles G.; Sun, John C.L.; Dvorak, Marcel

    2001-01-01

    Objective To provide an overview of atlanto-occipital dislocation and associated occipital condyle fractures so as to alert physicians to this rare injury and potentially improve patient outcome. The pertinent anatomy, mechanism of injury, clinical and radiologic evaluation and the management of these rare injuries are discussed in an attempt to alert physicians to this type of injury and to improve outcome. Data sources The data were obtained from a MEDLINE search of the English literature from 1966 to 1999 and the experience of 4 spine surgeons at a quaternary care acute spinal cord injury unit. Study selection Detailed anatomic and epidemiologically sound radiology studies were identified and analyzed. Only small retrospective studies or case series were available in the literature. Data extraction Valid anatomic, biomechanical and radiologic evaluation was extracted from studies. Clinical data came from limited studies and expert opinion. Data synthesis Early diagnosis is essential and is facilitated by a detailed clinical examination and strict adherence to an imaging algorithm that includes CT and MRI scanning. When the dislocation is identified, timely gentle reduction and prompt stabilization throuigh nonoperative or operative means is found to optimize patient outcome. Conclusions Atlanto-occipital dislocation should be suspected in any patient involved in a high speed motor vehicle or pedestrian collision. Once suspected, proper imaging and appropriate management of these once fatal injuries can improve survival and neurologic outcome. PMID:11764873

  16. Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews.

    PubMed

    Lassi, Zohra S; Middleton, Philippa F; Crowther, Caroline; Bhutta, Zulfiqar A

    2015-08-01

    Evidence-based interventions and strategies are needed to improve child survival in countries with a high burden of neonatal and child mortality. An overview of systematic reviews can focus implementation on the most effective ways to increase child survival. In this overview we included published Cochrane and other systematic reviews of experimental and observational studies on antenatal, childbirth, postnatal and child health interventions aiming to prevent perinatal/neonatal and child mortality using the WHO list of essential interventions. We assessed the methodological quality of the reviews using the AMSTAR criteria and assessed the quality of the outcomes using the GRADE approach. Based on the findings from GRADE criteria, interventions were summarized as effective, promising or ineffective. The overview identified 148 Cochrane and other systematic reviews on 61 reproductive, maternal, newborn and child health interventions. Of these, only 57 reviews reported mortality outcomes. Using the GRADE approach, antenatal corticosteroids for preventing neonatal respiratory distress syndrome in preterm infants; early initiation of breastfeeding; hygienic cord care; kangaroo care for preterm infants; provision and promotion of use of insecticide treated bed nets (ITNs) for children; and vitamin A supplementation for infants from six months of age, were identified as clearly effective interventions for reducing neonatal, infant or child mortality. Antenatal care, tetanus immunization in pregnancy, prophylactic antimalarials during pregnancy, induction of labour for prolonged pregnancy, case management of neonatal sepsis, meningitis and pneumonia, prophylactic and therapeutic use of surfactant, continuous positive airway pressure for neonatal resuscitation, case management of childhood malaria and pneumonia, vitamin A as part of treatment for measles associated pneumonia for children above 6 months, and home visits across the continuum of care, were identified as

  17. Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews

    PubMed Central

    Lassi, Zohra S.; Middleton, Philippa F.; Crowther, Caroline; Bhutta, Zulfiqar A.

    2015-01-01

    Background Evidence-based interventions and strategies are needed to improve child survival in countries with a high burden of neonatal and child mortality. An overview of systematic reviews can focus implementation on the most effective ways to increase child survival. Methods In this overview we included published Cochrane and other systematic reviews of experimental and observational studies on antenatal, childbirth, postnatal and child health interventions aiming to prevent perinatal/neonatal and child mortality using the WHO list of essential interventions. We assessed the methodological quality of the reviews using the AMSTAR criteria and assessed the quality of the outcomes using the GRADE approach. Based on the findings from GRADE criteria, interventions were summarized as effective, promising or ineffective. Findings The overview identified 148 Cochrane and other systematic reviews on 61 reproductive, maternal, newborn and child health interventions. Of these, only 57 reviews reported mortality outcomes. Using the GRADE approach, antenatal corticosteroids for preventing neonatal respiratory distress syndrome in preterm infants; early initiation of breastfeeding; hygienic cord care; kangaroo care for preterm infants; provision and promotion of use of insecticide treated bed nets (ITNs) for children; and vitamin A supplementation for infants from six months of age, were identified as clearly effective interventions for reducing neonatal, infant or child mortality. Antenatal care, tetanus immunization in pregnancy, prophylactic antimalarials during pregnancy, induction of labour for prolonged pregnancy, case management of neonatal sepsis, meningitis and pneumonia, prophylactic and therapeutic use of surfactant, continuous positive airway pressure for neonatal resuscitation, case management of childhood malaria and pneumonia, vitamin A as part of treatment for measles associated pneumonia for children above 6 months, and home visits across the continuum of

  18. Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review.

    PubMed

    McNeill, G; Bryden, D

    2013-12-01

    For critical care to be effective it must have a system in place to achieve optimal care for the deteriorating ward patient. To systematically review the available literature to assess whether either early warning systems or emergency response teams improve hospital survival. In the event of there being a lack of evidence regarding hospital survival, secondary outcome measures were considered (unplanned ICU admissions, ICU mortality, length of ICU stay, length of hospital stay, cardiac arrest rates). The Ovid Medline, EMBASE, CINAHL, Web of Science, Cochrane library and NHS databases were searched in September 2012 along with non-catalogued resources for papers examining the effect of early warning systems or emergency response teams on hospital survival. Inclusion criteria were original clinical trials and comparative studies in adult inpatients that assessed either an early warning system or emergency response team against any of the predefined outcome measures. Exclusion criteria were previous systematic reviews, non-English abstracts and studies incorporating paediatric data. Studies were arranged in to sections focusing on the following interventions: Early warning systems - Single parameter systems - Aggregate weighted scoring systems (AWSS) Emergency response teams - Medical emergency teams - Multidisciplinary outreach services . In each section an appraisal of the level of evidence and a recommendation has been made using the SIGN grading system. 43 studies meeting the review criteria were identified and included for analysis. 2 studies assessed single parameter scoring systems and 4 addressed aggregate weighted scoring systems. A total of 20 studies examined medical emergency teams and 22 studies examined multidisciplinary outreach teams. The exclusion of non English studies and those including paediatric patients does limit the applicability of this review. Much of the available evidence is of poor quality. It is clear that a 'whole system' approach

  19. Harnessing the natural regenerative potential of the dental pulp.

    PubMed

    Smith, Anthony J; Smith, James G; Shelton, Richard M; Cooper, Paul R

    2012-07-01

    Biological solutions for the repair and regeneration of the dental tissues offer significant potential for improved clinical treatment outcomes. Translation of dental tissue-engineering approaches to the clinic will make considerable contributions to these outcomes in the future, but exploiting the natural regenerative potential of dentin-pulp to enhance wound-healing responses offers solutions for maintaining pulp vitality now. Strategies to harness the natural regenerative potential of the pulp must be based on a sound biological understanding of the cellular and molecular events taking place, and require careful consideration of the interplay of infection, inflammation, and regeneration. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Guidelines are advantageous, though not essential for improved survival among breast cancer patients.

    PubMed

    Wolters, Regine; Wischhusen, Jörg; Stüber, Tanja; Weiss, Claire Rachel; Krockberger, Mathias; Bartmann, Catharina; Blettner, Maria; Janni, Wolfgang; Kreienberg, Rolf; Schwentner, Lukas; Novopashenny, Igor; Wischnewsky, Manfred; Wöckel, Achim; Diessner, Joachim

    2015-07-01

    The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991-2000 (TI1) and 2001-2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100% guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p < 0.001, HR = 0.57, 95% CI (0.49-0.67); OS: p < 0.001, HR = 0.76, 95% (CI 0.66-0.87)]. OS and RFS of guideline non-adherent patients also improved in TI2 compared to TI. Comparing risk profiles, determined by Nottingham Prognostic Score reveals a significant (p = 0.001) enhancement in the time cohort TI2. Furthermore, the percentage of guideline-conforming systemic therapy (endocrine therapy and chemotherapy) significantly increased (p < 0.001) in the time cohort TI2 to TI for the non-adherent group. The general improvement of clinical outcome of patients during the last 20 years is also valid in the subgroup of women who received treatments, which deviated from the guidelines. The shift in risk profiles as well as medical advances are major reasons for this improvement. Nevertheless, patients with 100% guideline-conforming therapy always had a better outcome compared to patients with guideline non-adherent therapy.

  1. Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge

    PubMed Central

    Mahmud, Shawn A.; Lambert, Michele P.; Poncz, Mortimer; Slungaard, Arne

    2007-01-01

    Pharmacologic infusion of activated protein C (APC) improves survival in severe sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate thrombin-infusion model. We now tested whether endogenous platelet PF4 content affects APC generation. Mice completely deficient in PF4 (mPF4−/−) had impaired APC generation and survival after thrombin infusion, similar to the impairment seen in heterozygote protein C–deficient (PC+/−) mice. Transgenic mice overexpressing human PF4 (hPF4+) had increased plasma APC generation. Overexpression of platelet PF4 compensated for the defect seen in PC+/− mice. In both a thrombin and a lipopolysaccharide (LPS) survival model, hPF4+ and PC+/−/hPF4+ mice had improved survival. Further, infusion of hPF4+ platelets improved survival of wild-type mice after an LPS challenge. These studies suggest that endogenous PF4 release may have biologic consequences for APC generation and survival in clinical sepsis. Infusions of PF4-rich platelets may be an effective strategy to improve outcome in this setting. PMID:17540840

  2. Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge.

    PubMed

    Kowalska, M Anna; Mahmud, Shawn A; Lambert, Michele P; Poncz, Mortimer; Slungaard, Arne

    2007-09-15

    Pharmacologic infusion of activated protein C (APC) improves survival in severe sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate thrombin-infusion model. We now tested whether endogenous platelet PF4 content affects APC generation. Mice completely deficient in PF4 (mPF4(-/-)) had impaired APC generation and survival after thrombin infusion, similar to the impairment seen in heterozygote protein C-deficient (PC(+/-)) mice. Transgenic mice overexpressing human PF4 (hPF4(+)) had increased plasma APC generation. Overexpression of platelet PF4 compensated for the defect seen in PC(+/-) mice. In both a thrombin and a lipopolysaccharide (LPS) survival model, hPF4(+) and PC(+/-)/hPF4(+) mice had improved survival. Further, infusion of hPF4(+) platelets improved survival of wild-type mice after an LPS challenge. These studies suggest that endogenous PF4 release may have biologic consequences for APC generation and survival in clinical sepsis. Infusions of PF4-rich platelets may be an effective strategy to improve outcome in this setting.

  3. Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest.

    PubMed

    Bebarta, Vikhyat S; Pitotti, Rebecca L; Dixon, Patricia S; Valtier, Sandra; Esquivel, Luis; Bush, Anneke; Little, Charles M

    2012-10-01

    To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48

  4. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2010 CFR

    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...

  5. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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...

  6. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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...

  7. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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...

  8. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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...

  9. Improved survival of patients with hepatocellular carcinoma and disparities by age, race, and socioeconomic status by decade, 1983-2012.

    PubMed

    Wang, Shuncong; Sun, Huanhuan; Xie, Zhinan; Li, Jie; Hong, Guobin; Li, Dan; Mallampati, Saradhi; Zhou, Xiuling; Zhou, Cuiling; Zhang, Hongyu; Cheng, Zhibin; Shan, Hong; Ma, Haiqing

    2016-09-13

    Hepatocellular carcinoma (HCC), accounting for the majority of liver cancer, is a highly aggressive malignancy with poor prognosis and therefore adds up the financial burden. Incidence data of HCC in three decades during 1983-2012 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with incidence rates of 1.9, 3.1 and 4.9 per 100,000 respectively. In addition, to evaluate the survival changes in the same period, a total of 63,640 HCC cancer cases were accessed from SEER database. The six-month relative survival rates improved each decade from 31.0% to 42.9% to 57.2% and the higher increase can be seen in the last two decades. More importantly, the disparities of survival among different racial groups and socioeconomic status (SES) were confirmed by the inferiority of survival in Black race and high-poverty group respectively. This research analyzed the incidence and survival data of HCC in the past three decades and may help predict the future trends of incidence and survival. Furthermore, this study may help better design healthcare policies and clinical management programs to balance the disparities of survival between SES groups, races, ages and sexes confirmed in this study and thereby improve the clinical management of HCC.

  10. Improved survival of patients with hepatocellular carcinoma and disparities by age, race, and socioeconomic status by decade, 1983–2012

    PubMed Central

    Li, Jie; Hong, Guobin; Li, Dan; Mallampati, Saradhi; Zhou, Xiuling; Zhou, Cuiling; Zhang, Hongyu; Cheng, Zhibin; Shan, Hong; Ma, Haiqing

    2016-01-01

    Hepatocellular carcinoma (HCC), accounting for the majority of liver cancer, is a highly aggressive malignancy with poor prognosis and therefore adds up the financial burden. Incidence data of HCC in three decades during 1983-2012 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with incidence rates of 1.9, 3.1 and 4.9 per 100,000 respectively. In addition, to evaluate the survival changes in the same period, a total of 63,640 HCC cancer cases were accessed from SEER database. The six-month relative survival rates improved each decade from 31.0% to 42.9% to 57.2% and the higher increase can be seen in the last two decades. More importantly, the disparities of survival among different racial groups and socioeconomic status (SES) were confirmed by the inferiority of survival in Black race and high-poverty group respectively. This research analyzed the incidence and survival data of HCC in the past three decades and may help predict the future trends of incidence and survival. Furthermore, this study may help better design healthcare policies and clinical management programs to balance the disparities of survival between SES groups, races, ages and sexes confirmed in this study and thereby improve the clinical management of HCC. PMID:27486977

  11. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  12. Improvement in 2-year survival for ventricular assist device patients after implementation of an intensive surveillance protocol.

    PubMed

    Pamboukian, Salpy V; Tallaj, José A; Brown, Robert N; Holman, William L; Blood, Margaret; George, James F; Costanzo, Maria Rosa; Cadeiras, Martin; Smallfield, Melissa C; McGiffin, David C; Kirklin, James K

    2011-08-01

    This study was conducted to determine the effect of a disease-management model termed an "intensive surveillance protocol" (ISP) on survival in ventricular assist device (VAD) patients. This intervention consisted of a formalized, protocol-driven, multi-disciplinary team approach to VAD patient follow-up initiated August 1, 2006. The goal was to attain an internal program benchmark of 70% survival at 2 years. Historically, 2-year survival after VAD implant has been sub-optimal, and no patient management algorithms have been formally tested to determine their effect on 2-year survival. The study comprised 76 patients, of whom 26 had a VAD as destination therapy (DT) and 50 as a bridge to transplant (BTT), from July 1, 2003, to June 30, 2008. Survival before and after initiation of ISP was compared. A parametric hazard multivariable analysis, with a time-varying covariable for implementation of ISP, was used to evaluate of other factors affecting survival. Survival at 16 months was 100% for DT patients who received a VAD after August 1, 2006 vs 64% for the earlier era (p = 0.06). For BTT, 16- month survival was 71% vs 43% (p = 0.03). Predicted 2-year survival before and after implementation of the ISP improved from 30% to 87% for DT (p = 0.02) and from 20% to 61% for BTT patients (p = 0.01). Predictors of midterm survival by multivariable analysis included ISP (p = 0.004), younger age (p = 0.03), non-emergent implant (p < 0.0001), and isolated left ventricular VAD (p < 0.0001). After adjustment for covariables, the ISP was associated with a 70% reduction in the hazard for death for the entire cohort (p = 0.004). The effect of ISP was also significant in the patients who received the HeartMate XVE (Thoratec, Pleasanton, CA), which spanned both eras of the study. Survival improved for DT and BTT VAD patients after implementation of the ISP, with a dramatic decrease in hazard for death. Although the transition from pulsatile to axial flow technology occurred during the

  13. Improved patient survival with simultaneous pancreas and kidney transplantation in recipients with diabetic end-stage renal disease.

    PubMed

    Lindahl, J P; Hartmann, A; Horneland, R; Holdaas, H; Reisæter, A V; Midtvedt, K; Leivestad, T; Oyen, O; Jenssen, T

    2013-06-01

    We aimed to determine whether simultaneous pancreas and kidney (SPK) transplantation would improve patient and kidney graft survival in diabetic end-stage renal disease (ESRD) compared with kidney transplantation alone (KTA). Follow-up data were retrieved for all 630 patients with diabetic ESRD who had received SPK or KTA at our centre from 1983 to the end of 2010. Recipients younger than 55 years of age received either an SPK (n = 222) or, if available, a single live donor kidney (LDK; n = 171). Older recipients and recipients with greater comorbidity received a single deceased donor kidney (DDK; n = 237). Survival was analysed by the Kaplan-Meier method and in multivariate Cox regression analysis adjusting for recipient and donor characteristics. Patient survival was superior in SPK compared with both LDK and DDK recipients in univariate analysis. Follow-up time (mean ± SD) after transplantation was 7.1 ± 5.7 years. Median actuarial patient survival was 14.0 years for SPK, 11.5 years for LDK and 6.7 years for DDK recipients. In multivariate analyses including recipient age, sex, treatment modality, time on dialysis and era, SPK transplantation was protective for all-cause mortality compared with both LDK (p = 0.02) and DDK (p = 0.029) transplantation. After the year 2000, overall patient survival improved compared with previous years (HR 0.40, 95% CI 0.30, 0.55; p < 0.001). Pancreas graft survival also improved after 2000, with a 5 year graft survival rate of 78% vs 61% in previous years (1988-1999). Recipients of SPK transplants have superior patient survival compared with both LDK and DDK recipients, with improved results seen over the last decade.

  14. Ozone delignification of pine and eucalyptus kraft pulps. 2: Selectivity

    SciTech Connect

    Simoes, R.M.S.; Castro, J.A.A.M.

    1999-12-01

    The selectivity of ozone in the delignification of unbleached pine and eucalyptus kraft pulps is studied at ultralow consistency in a stirred reactor under closely controlled experimental conditions. The effect of several operating variables is analyzed, but special attention is paid to the depolymerization rate of polysaccharides with the particular goal of evaluating the influence of the lignin contents on its kinetics. By using substantially different ozone concentrations in the pulp suspension and different reaction temperatures, it is possible to show that ozone selectivity can only be slightly improved by manipulating these operating variables. Furthermore, for the same type of material, it was observed that the initial rate of delignification plays the most important role on selectivity. In fact, for a given pulp, selectivity decreases with a decrease of the initial lignin contents, and such results can be well justified by the corresponding reduction of the initial rates of delignification. To further investigate the effect of lignin on pulp degradation, experiments were carried out at 4 C between ozone and holocellulose, which represent the polysaccharides of the unbleached pulps. The results suggest that molecular ozone can be responsible for an important part of the polysaccharides depolymerization during the delignification process. Moreover, the comparison of the kinetic behavior of holocellulose and of the corresponding unbleached pulp also reveals that the presence of lignin in the pulp enhances both the depolymerization and the degradation rates of polysaccharides.

  15. Alkaline peroxide mechanical pulping of wheat straw with enzyme treatment.

    PubMed

    Zhao, Jian; Li, Xuezhi; Qu, Yinbo; Gao, Peiji

    2004-01-01

    Alkaline peroxide mechanical pulping (APMP) of wheat straw with enzyme treatment was studied. Instead of direct enzyme pretreatment on wheat straw, an alternative treatment method was used, in which coarse pulps from refiner defibrated wheat straw rather than wheat straw were pretreated with a crude enzyme containing mainly xylanase, then impregnated with alkaline H2O2 solution and further refined. The optimum conditions of enzyme treatment were xylanase dosage of 10-15 IU/g of oven-dried wheat straw, 90 min, 50-60 degrees C, pulp consistency of 5-10%, and initial pH of 5.0, and those for chemical impregnation were 6% NaOH, 70-80 degrees C, 60-90 min, and 4 to 5% H2O2. Enzyme treatment improved pulpability of wheat straw by the APMP process, and final pulp quality such as brightness, breaking length, and burst index of pulp. Pulp from the APMP process with enzyme treatment could be bleached to a brightness of 70.5% ISO by two-stage H2O2 bleaching sequence with only 4% H2O2, and breaking length of the bleach pulp reached 4470 m

  16. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients

    PubMed Central

    Wu, L; Sluiter, A A; Guo, Ho-fu; Balesar, R A; Swaab, D F; Zhou, Jiang-Ning; Verwer, R W H

    2008-01-01

    Abstract Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control participants with rat embryonic day 14 (E14) neural stem cells. Viability staining based on the exclusion of ethidium bromide by intact plasma membranes showed that there were strikingly more viable cells and fewer dead cells in slices co-cultured with neural stem cells than in untreated slices. The presence of Alzheimer pathology in the brain slices did not influence this effect, although the slices from Alzheimer patients, in general, contained fewer viable cells. Co-culturing with rat E14 fibroblasts did not improve the viability of neurons in the human brain slices. Since the human slices and neural stem cells were separated by a membrane during co-culturing our data show for the first time that neural stem cells release diffusible factors that may improve the survival of aged and degenerating neurons in human brains. PMID:18088384

  17. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients.

    PubMed

    Wu, L; Sluiter, A A; Guo, Ho-Fu; Balesar, R A; Swaab, D F; Zhou, Jiang-Ning; Verwer, R W H

    2008-01-01

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control participants with rat embryonic day 14 (E14) neural stem cells. Viability staining based on the exclusion of ethidium bromide by intact plasma membranes showed that there were strikingly more viable cells and fewer dead cells in slices co-cultured with neural stem cells than in untreated slices. The presence of Alzheimer pathology in the brain slices did not influence this effect, although the slices from Alzheimer patients, in general, contained fewer viable cells. Co-culturing with rat E14 fibroblasts did not improve the viability of neurons in the human brain slices. Since the human slices and neural stem cells were separated by a membrane during co-culturing our data show for the first time that neural stem cells release diffusible factors that may improve the survival of aged and degenerating neurons in human brains.

  18. Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model.

    PubMed

    Prabhakar, Shilpa; Zhang, Xuan; Goto, June; Han, Sangyeul; Lai, Charles; Bronson, Roderick; Sena-Esteves, Miguel; Ramesh, Vijaya; Stemmer-Rachamimov, Anat; Kwiatkowski, David J; Breakefield, Xandra O

    2015-10-01

    We examined the potential benefit of gene therapy in a mouse model of tuberous sclerosis complex (TSC) in which there is embryonic loss of Tsc1 (hamartin) in brain neurons. An adeno-associated virus (AAV) vector (serotype rh8) expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1(cc) (homozygous for a conditional floxed Tsc1 allele) SynI-cre(+), in which Tsc1 is lost selectively in neurons starting at embryonic day 12. Vector-treated Tsc1(cc)SynIcre(+) mice showed a marked improvement in survival from a mean of 22 days in non-injected mice to 52 days in AAV hamartin vector-injected mice, with improved weight gain and motor behavior in the latter. Pathologic studies showed normalization of neuron size and a decrease in markers of mTOR activation in treated as compared to untreated mutant littermates. Hence, we show that gene replacement in the brain is an effective therapeutic approach in this mouse model of TSC1. Our strategy for gene therapy has the advantages that therapy can be achieved from a single application, as compared to repeated treatment with drugs, and that AAV vectors have been found to have minimal to no toxicity in clinical trials for other neurologic conditions. Although there are many additional issues to be addressed, our studies support gene therapy as a useful approach in TSC patients. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

    Bilal, Erhan; Dutkowski, Janusz; Guinney, Justin; Jang, In Sock; Logsdon, Benjamin A; Pandey, Gaurav; Sauerwine, Benjamin A; Shimoni, Yishai; Moen Vollan, Hans Kristian; Mecham, Brigham H; Rueda, Oscar M; Tost, Jorg; Curtis, Christina; Alvarez, Mariano J; Kristensen, Vessela N; Aparicio, Samuel; Børresen-Dale, Anne-Lise; Caldas, Carlos; Califano, Andrea; Friend, Stephen H; Ideker, Trey; Schadt, Eric E; Stolovitzky, Gustavo A; Margolin, Adam A

    2013-01-01

    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.

  20. Improving Breast Cancer Survival Analysis through Competition-Based Multidimensional Modeling

    PubMed Central

    Bilal, Erhan; Dutkowski, Janusz; Guinney, Justin; Jang, In Sock; Logsdon, Benjamin A.; Pandey, Gaurav; Sauerwine, Benjamin A.; Shimoni, Yishai; Moen Vollan, Hans Kristian; Mecham, Brigham H.; Rueda, Oscar M.; Tost, Jorg; Curtis, Christina; Alvarez, Mariano J.; Kristensen, Vessela N.; Aparicio, Samuel; Børresen-Dale, Anne-Lise; Caldas, Carlos; Califano, Andrea; Friend, Stephen H.; Ideker, Trey; Schadt, Eric E.; Stolovitzky, Gustavo A.; Margolin, Adam A.

    2013-01-01

    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. PMID:23671412

  1. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

    PubMed Central

    2012-01-01

    High expression of HLA-E occurred in the majority of all histopathological subtypes of cervical cancer; especially in cervical AC. High HLA-E expression in cervical AC was associated with improved patient survival. This study also highlights the importance of careful evaluation of cervical carcinomas to distinguish histopathological subtypes. In the future, insight into the biological behaviour and distinct molecular carcinogenetic processes of the AC, ASC, and SCC subtypes may contribute to the development of more tumour-specific treatment strategies. PMID:22947189

  2. Nuclear Expression of the Deubiquitinase CYLD Is Associated with Improved Survival in Human Hepatocellular Carcinoma

    PubMed Central

    Welte, Stefan; Urbanik, Toni; Elßner, Christin; Kautz, Nicole; Koehler, Bruno Christian; Waldburger, Nina; Bermejo, Justo Lorenzo; Pinna, Federico; Weiss, Karl-Heinz; Schemmer, Peter; Jaeger, Dirk; Longerich, Thomas; Breuhahn, Kai; Schulze-Bergkamen, Henning

    2014-01-01

    Background & Aims The deubiquitinase CYLD removes (K-63)-linked polyubiquitin chains from proteins involved in NF-κB, Wnt/ß-catenin and Bcl-3 signaling. Reduced CYLD expression has been reported in different tumor entities, including hepatocellular carcinoma (HCC). Furthermore, loss of CYLD has been shown to contribute to HCC development in knockout animal models. This study aimed to assess subcellular CYLD expression in tumor tissues and its prognostic significance in HCC patients undergoing liver resection or liver transplantation. Methods Subcellular localization of CYLD was assessed by immunohistochemistry in tumor tissues of 95 HCC patients undergoing liver resection or transplantation. Positive nuclear CYLD staining was defined as an immunhistochemical (IHC) score ≥3. Positive cytoplasmic CYLD staining was defined as an IHC score ≥6. The relationship with clinicopathological parameters was investigated. Cell culture experiments were performed to analyze subcellular CYLD expression in vitro. Results Cytoplasmic CYLD expression was observed in 57 out of 95 (60%) HCC specimens (cyt°CYLD+). Nuclear CYLD staining was positive in 52 out of 95 specimens (55%, nucCYLD+). 13 out of 52 nucCYLD+ patients (25%) showed a lack of cytoplasmic CYLD expression. nucCYLD+ was associated with prolonged overall survival in patients after resection or liver transplantation (P = 0.007). 5-year overall survival rates were 63% in nucCYLD+ vs. 26% in nucCYLD- patients. Nuclear CYLD staining strongly correlated with tumor grading (P<0.001) and Ki67 positivity (P = 0.005). nucCYLD+ did not prove to be an independent prognostic parameter. In vitro, Huh7, Hep3B and HepG2 showed reduced CYLD levels compared to the non-malignant liver cell line THLE-2. Induction of CYLD expression by doxorubicin treatment led to increased cytoplasmic and nuclear expression of CYLD. Conclusions Expression of nuclear CYLD is a novel prognostic factor for improved survival in patients with HCC

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

    SciTech Connect

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

    2012-11-01

    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 {mu}g 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

  4. Improved Survival and Hematopoietic Differentiation of Murine Embryonic Stem Cells on Electrospun Polycaprolactone Nanofiber

    PubMed Central

    Dehdilani, Nima; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Amoughli Tabrizi, Bahram; Parsa, Hamed; Sabagi, Fatemeh

    2016-01-01

    differentiation between the PCL and TCP culture systems. There were more CD34+(Sca1+) and CD133+cells subpopulations in the PCL group compared to the conventional TCP culture system. Conclusion The nanofiber scaffold, as an effective surface, improves survival and differentiation of mESCs into mHSCs compared to gelatin coated TCP. More studies are necessary to understand how the topographical features of electrospun fibers af- fect cell growth and behavior. This can be achieved by designing biomimetic scaffolds for tissue engineering. PMID:26862522

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

    PubMed

    Leeman, Jonathan E; Clump, David A; Wegner, Rodney E; Heron, Dwight E; Burton, Steven A; Mintz, Arlan H

    2012-07-11

    resolved with a short-course of dexamethasone. 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.

  6. Chloroquine improves survival and hematopoietic recovery following lethal low dose- rate radiation

    PubMed Central

    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 anti-malarial 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 total of 12.8 Gy delivered at 9.4 cGy/hr. 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 hrs and 4 hrs before irradiation. Bone marrow cells isolated from tibia, fibula and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retro orbital injection. Chimerism was assessed by flow cytometry. In vitro methyl cellulose colony forming assay of whole bone marrow cells as well as FACS analysis of lineage depleted cells was used to assess the effect of chloroquine on progenitor cells. Results Mice pretreated with chloroquine prior to radiation exhibited a significantly higher survival rate compared to mice treated with radiation alone (80 vs.31 percent, p=0.0026). Chloroquine administration prior to radiation did not impact 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 the transplantation (4.2 percent vs. 0.4 percent, p=0.015). Conclusion Chloroquine administration prior to 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 against the

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

    PubMed

    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.

  8. Low-molecular-weight polyethylene glycol improves survival in experimental sepsis.

    PubMed

    Ackland, Gareth L; Gutierrez Del Arroyo, Ana; Yao, Song T; Stephens, Robert C; Dyson, Alexander; Klein, Nigel J; Singer, Mervyn; Gourine, Alexander V

    2010-02-01

    For several chronic inflammatory disease states, therapy is enhanced by improving the pharmacokinetic properties of anti-inflammatory drugs through conjugation with polyethylene glycol. We hypothesized that part of the beneficial action of PEGylated drugs may be derived from the anti-inflammatory properties of polyethylene glycol (PEG) itself. Randomized, double-blinded, controlled ex vivo and in vivo laboratory studies. University research laboratories. Human neutrophils and mononuclear cells, macrophage cell line, and adult rats and mice. The effect of PEG (either low-molecular-weight [200-400] or high-molecular-weight [>4000]) was assessed on survival after systemic inflammation induced by lipopolysaccharide or zymosan. The effects of PEG on zymosan, lipopolysaccharide, or streptolysin-induced inflammatory and bioenergetic responses of immune cells were also assessed. Low-molecular-weight PEG reduced inflammatory cytokine expression, pyrexia, and mortality by >50% in both lipopolysaccharide and zymosan models of sepsis. Low-molecular-weight PEG reduced cytokine expression both in vivo and in vitro, and attenuated activation of human neutrophils in response to lipopolysaccharide or zymosan. By contrast, high-molecular-weight PEG conferred less significant survival effects after lipopolysaccharide and zymosan, and it did not exhibit such profound anti-inflammatory effects. Low-molecular-weight PEG attenuated lipopolysaccharide-induced activation of pro-apoptotic pathways (lysophosphatidic acid receptor and caspase-domain signaling) in the livers of endotoxemic rats. Streptolysin-induced necrosis of human neutrophils was reduced by low-molecular-weight PEG, indicating a mechanism that involves coating and/or stabilizing the cellular membrane. Low-molecular-weight PEG preserved human neutrophil responses to septic serum and bioenergetic function in macrophages and neutrophils. PEG is a commonly used, safe, nonimmunogenic molecule possessing hitherto unappreciated

  9. Prolonged survival and improved glycemia in BB diabetic rats after early sustained exposure to GLP-1

    PubMed Central

    Yanay, Ofer; Moralejo, Daniel; Kernan, Kelly; Brzezinski, Margaret; Fuller, Jessica M.; Barton, Randall; Lernmark, Ake; Osborne, William R.

    2010-01-01

    Background Type I diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Methods Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte™ encapsulation devices, implanted subcutaneously (SQ) and rats monitored for diabetes. Results In untreated control rats plasma GLP-1 levels were 34.5 to 39.5 pg/ml whereas in treated rats plasma levels were elevated ranging from 90 pg/ml to 250.4 pg/ml. Hypoglycemia was not detected and this was anticipated from the glucose regulated action of GLP-1. Diabetes onset in untreated rats occurred at 56.5±0.6 SEM (n=6) days of age and in GLP-1 treated rats was delayed until 76.4±3.3 SEM (n=5) days of age (p<0.001). After disease onset untreated control rats showed rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset insulin secreting islets were absent in untreated rats. In contrast, treated rats maintained weight for up to 143 days of age and showed insulin secreting beta cells. Conclusions Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed improved clinical outcome suggesting the potential for treating patients using long lasting GLP-1 analogues. PMID:20527046

  10. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    PubMed

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  11. Pharmacologic cholinesterase inhibition improves survival in acetaminophen-induced acute liver failure in the mouse.

    PubMed

    Steinebrunner, Niels; Mogler, Carolin; Vittas, Spiros; Hoyler, Birgit; Sandig, Catharina; Stremmel, Wolfgang; Eisenbach, Christoph

    2014-08-19

    Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic pharmaceutical substances in the world and accounts for most cases of drug induced liver injury resulting in acute liver failure. Acute liver failure initiates a sterile inflammatory response with release of cytokines and innate immune cell infiltration in the liver. This study investigates, whether pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver damage in acute liver failure via the cholinergic anti-inflammatory pathway. Acute liver failure was induced in BALB/c mice by a toxic dose of acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied therapeutically at set time points and the survival was investigated. Liver damage was assessed by serum parameters, histopathology and serum cytokine assays 12 h after initiation of acute liver failure. Serum parameters, histopathology and serum cytokine assays showed pronounced features of acute liver failure 12 h after application of acetaminophen (APAP). Neostigmine treatment led to significant reduction of serum liver enzymes (LDH (47,147 ± 12,726 IU/l vs. 15,822 ± 10,629 IU/l, p = 0.0014) and ALT (18,048 ± 4,287 IU/l vs. 7,585 ± 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP + neostigmine-treated mice), inflammatory cytokine levels (IL-1β (147 ± 19 vs. 110 ± 25, p = 0.0138) and TNF-α (184 ± 23 vs. 130 ± 33, p = 0.0086), APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and histopathological signs of damage.Animals treated with NAC in combination with the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and improved outcome. Neostigmine is an acetylcholinesterase inhibitor that ameliorates the effects of APAP-induced acute liver failure in the mouse and therefore may provide new treatment options for affected patients.

  12. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer

    PubMed Central

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-01-01

    Abstract More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients. A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan–Meier curves. Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44–0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51–0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04–0.94). The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  13. Improvement of graft function and animal survival by fat emulsion in liver transplant rats.

    PubMed

    Ma, Zheng-Wei; Liu, Li-Dong; Li, Kun; Zhang, Yu-Jun; Dong, Jia-Hong

    2007-01-15

    Nutritional supports are required for liver transplant patients. However, no systematical assessment has been made of the optimal composition of energy yielding substrates in these patients. This study is to evaluate whether mixed energy system consisting of carbohydrate and lipid emulsions is more advantageous over single energy source of glucose for nutritional support in liver transplant recipients and whether structured lipid emulsion (STG) is superior to medium-chain triglyceride/long-chain triglycerides (MCT/LCT) and long-chain triglycerides (LCT) using a total parenteral nutrition model. Liver transplant rats were randomly divided to four groups according to the energy source, i.e. glucose (GLU), MCT/LCT, STG and LCT groups. Sham operated rats served as control. Hepatic function and lipid profile were determined to investigate the roles of lipid emulsion in hepatic function and lipid metabolism. Morphological changes of liver were observed, and nitrogen balance was determined. The results showed that infusion of lipid emulsion was well tolerated. The 1-week survival rate in the lipid emulsion groups was significantly higher than in the GLU group (100% versus 50%, P<0.05); compared with the GLU group, hepatic function recovered quickly and returned to normal level, and morphological alterations were less severer in the lipid emulsion groups, especially in the STG group; the lipid emulsions groups had normal serum TG and TC levels, especially STG and MCT/LCT groups; the lipid emulsions groups achieved a positive nitrogen balance on day 7 compared with the GLU group, and the STG group had the highest nitrogen balance. In conclusion, lipid emulsion is beneficial in improving hepatic function and the recipients' survival and does not influence the lipid metabolism. Mixed energy system consisting of carbohydrate and lipid is more advantageous over single energy source of glucose after liver transplantation, and STG is superior to MCT/LCT and LCT.

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

    PubMed Central

    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

  15. Improving male mating competitiveness and survival in the field for medfly, Ceratitis capitata (Diptera: Tephritidae) SIT programs.

    PubMed

    McInnis, D O; Shelly, T E; Komatsu, J

    2002-09-01

    The success of the sterile insect technique (SIT) depends critically upon mating between released sterilized males and wild females. In Hawaii, improvements in the efficiency of sterile males were attempted on two separate fronts--mating enhancement and survival improvement. In the former, two methods have been investigated--selective breeding and aromatherapy. In the latter, flies which survived in field cages for several days were selected and bred to produce progeny with enhanced survival ability compared to control flies. Regarding mating selection, standard laboratory-reared males that successfully mated with wild females in field cages were allowed to breed. F1 offspring were inbred, then the selection procedure was repeated for four additional cycles. In the aromatherapy procedure, laboratory-reared males were exposed to ginger root oil for several hours 1 day prior to testing in field cages. Compared to controls, the selected flies improved the mating competitiveness of male flies ca. 3-fold, irradiation reduced this increase to ca. 2.5-fold. Exposing the selected, hybrid strain raised the fitness of the lab males to ca. 9-fold that of wild males. In the ongoing survival selection study, we have obtained lines in which the selected males survived ca. 2-fold better than laboratory control males over several days in an outdoor field cage, with food and water provided. The goal is to combine the traits of higher survival and mating ability into a single strain for SIT release.

  16. [Application of enzymes in pulp and paper industry].

    PubMed

    Lin, Ying

    2014-01-01

    The application of enzymes has a high potential in the pulp and paper industry to improve the economics of the paper production process and to achieve, at the same time, a reduced environmental burden. Specific enzymes contribute to reduce the amount of chemicals, water and energy in various processes. This review is aimed at presenting the latest progresses of applying enzymes in bio-pulping, bio-bleaching, bio-deinking, enzymatic control of pitch and enzymatic modification of fibers.

  17. Combination of alkaline and enzymatic treatments as a process for upgrading sisal paper-grade pulp to dissolving-grade pulp.

    PubMed

    Ibarra, David; Köpcke, Viviana; Larsson, Per Tomas; Jääskeläinen, Anna-Stiina; Ek, Monica

    2010-10-01

    A sequence of treatments consisting of an initial xylanase treatment followed by cold alkaline extraction and a final endoglucanase treatment was investigated as a process for upgrading non-wood paper-grade pulps to dissolving-grade pulps for viscose production. Five commercial dried bleached non-wood soda/AQ paper pulps, from flax, hemp, sisal, abaca, and jute, were studied for this purpose. Commercial dried bleached eucalyptus dissolving pulp was used as reference sample. Sisal pulp showed the highest improvement in Fock's reactivity, reaching levels nearly as high or even higher than that of eucalyptus dissolving pulp (65%), and a low hemicellulose content (3-4%) when was subjected to this sequence of treatments. The viscosity, however, decreased considerably. A uniform and narrow molecular weight distribution was observed by size exclusion chromatography. (13)C nuclear magnetic resonance spectroscopy and Raman microspectroscopy revealed that the cellulose structure consisted of cellulose I. Copyright 2010 Elsevier Ltd. All rights reserved.

  18. Improving survival of children with cancer worldwide: the St. Jude International Outreach Program approach.

    PubMed

    Ribeiro, Raul C

    2012-01-01

    The mission of the St. Jude International Outreach Program (IOP) is to improve the survival rate of children with cancer and other catastrophic diseases worldwide, through the sharing of knowledge, technology, and organizational skills. There are an estimated 160,000 newly diagnosed cases of childhood cancer worldwide each year, and cancer is emerging as a major cause of childhood death in the developing regions of Asia, South and Central America, northwest Africa, and the Middle East. Over the past 30 years improved therapy has dramatically increased survival rates for children with cancer, but still more than 70% of the world's children with cancer lack access to modern treatment. Although sick children from around the world have traveled to our hospital in Memphis, Tennessee, since its inception, treating children in their own countries is more efficient and less disruptive for them and their families. In the context of St. Jude's culture of sharing knowledge about the management of children with cancer, we now use modern technology to reach far more children than would ever be able to come to St. Jude Children's Research Hospital. St. Jude strives to address the needs of those children in countries that lack sufficient resources and to help them manage their own burden of cases effectively. By sharing knowledge and technology with the local governments, health care providers, and the private sector in these countries, St. Jude is improving diagnoses and treatments to increase the survival rates of children all across the globe. In addition to training medical teams locally, St. Jude Children's Research Hospital hosts many visiting fellows at our campus in Memphis. St. Jude helps partner medical institutions develop tailored evidence-based protocols for treating children with cancer and other catastrophic diseases. St. Jude physicians serve as mentors to physicians at our partner sites and consult on difficult cases. Nurses are trained on best practices in

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

    PubMed

    Rahman, Mahfuzar; Jhohura, Fatema Tuz; Mistry, Sabuj Kanti; Chowdhury, Tridib Roy; Ishaque, Tanveen; Shah, Rasheduzzaman; Afsana, Kaosar

    2015-01-01

    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.

  20. Why is continuum of care from home to health facilities essential to improve perinatal survival?

    PubMed

    Bahl, Rajiv; Qazi, Shamim; Darmstadt, Gary L; Martines, Jose

    2010-12-01

    The period around the time of delivery is extremely hazardous for infants in developing countries. After the first week the risk drops sharply, and survival improves markedly. To reduce perinatal mortality, a continuum of care between the home and the various facilities is essential during pregnancy, childbirth and the newborn period. This paper reviews strategies to promote the establishment of this continuum: providing health care within or close to home by frontline workers and increasing the use of services in health facilities through community mobilization and financing strategies. As perinatal care and care for seriously sick children face common challenges and lessons could be learned from successful strategies for management of other illnesses, this paper also reviews intervention models involving community health workers (CHWs) to improve case management of sick children at the household and community levels. Available evidence suggests that the community strategy with the greatest impact on neonatal mortality is home visits by CHWs combined with community mobilization. The same strategy appears to be effective in increasing health facility utilization. An equally effective strategy for increasing health facility utilization seems to be financing health care to remove financial access barriers, particularly using conditional cash transfers or vouchers. Although the availability of information on the effect of community interventions to improve newborn health has increased in the recent past, significant gaps remain. Information on the effectiveness of strategies in different settings, particularly in sub-Saharan Africa, cost-effectiveness and sustainability are particularly needed and should be gathered in future studies. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Cornel iridoid glycoside improves memory ability and promotes neuronal survival in fimbria-fornix transected rats.

    PubMed

    Zhao, Li-hong; Ding, Yue-xia; Zhang, Lan; Li, Lin

    2010-11-25

    Cornel iridoid glycoside (CIG) is a main component extracted from a traditional Chinese herb Cornus officinalis. Our previous study found that CIG improved neurological function in cerebral ischemic rats. The aim of this study was to investigate the therapeutic benefit of CIG in rats with fimbria-fornix transection (FFT) and explore the underlying molecular mechanisms. CIG (20, 60 and 180 mg/kg) or vehicle was intragastrically administered once daily to rats, starting immediately after the surgery and lasting for 4 weeks. Morris water maze and step-through tests showed that the memory deficits seen in FFT rats were significantly improved by CIG treatment. Immunohistochemical analysis showed that CIG treatment attenuated the loss of neurons in hippocampus. To elucidate the memory-improving mechanism of CIG, the neurotrophic factors, synaptic proteins and Bcl-2 family proteins in hippocampus were measured by Western blot analysis. FFT reduced hippocampal protein levels of nerve growth factor (NGF), tyrosine receptor kinase A (Trk A), brain-derived neurotrophic factor (BDNF), synaptophysin (SYP) and B-cell lymphoma-2 (Bcl-2), but not levels of tyrosine receptor kinase B (Trk B) and growth-associated protein 43 (GAP-43). FFT also elevated cytochorome C (Cyt c) and bcl-2-associated X protein (Bax). Administration of CIG to FFT rats significantly elevated the expression of NGF, TrkA, BDNF, SYP, GAP-43 and Bcl-2, and decreased the expression of Cyt c and Bax. These results indicated that CIG effectively counteracted cognitive impairments caused by fimbria-fornix lesions, and the mechanisms might be related to promoting neuronal survival and providing a beneficial environment for brain repair. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs.

    PubMed

    Liu, Rui; Hu, Xiao-Hang; Wang, Shu-Ming; Guo, Si-Jia; Li, Zong-Yu; Bai, Xiao-Dong; Zhou, Fang-Qiang; Hu, Sen

    2016-06-01

    To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. Forty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  3. Reducing sugar production of sweet sorghum bagasse kraft pulp

    NASA Astrophysics Data System (ADS)

    Solihat, Nissa Nurfajrin; Fajriutami, Triyani; Adi, Deddy Triyono Nugroho; Fatriasari, Widya; Hermiati, Euis

    2017-01-01

    Kraft pulping of sweet sorghum bagasse (SSB) has been used for effective delignification method for cellulose production. This study was conducted to evaluate the performance pulp kraft of SSB for reducing sugar production. The study intended to investigate the effect of active alkali and sulfidity loading variation of SSB pulp kraft on reducing sugar yield per biomass. The SSB pulp was prepared after pulping using three variations of active alkali (17, 19, and 22%) and sulfidity loading (20, 22, and 24%) at 170°C for 4 h with liquor to wood ratio of 10. A total of 9 pulps were obtained from these pretreatments. Delignification pretreatment has been succesfully removed lignin and hemicellulose more than 90% and 50%, respectively. Increasing active alkali and sulfidity loading has significantly increased lignin removal caused by disruption of the cell wall structure for releasing lignin into black liquor in the cellulose extraction. The enzymatic hydrolysis of pulp was carried out with cellulase loading of 40 FPU per g substrate in the shaking incubator at 50°C and 150 rpm for 78 h. For each 24 h, the reducing sugar yield (DNS assay) has been observed. Even though the lignin and hemicellulose loss occurred along with higher active alkali loading, this condition tends to decrease its yield. The reducing sugar concentration varied between 7-8 g/L. Increasing active alkali and sulfidity was significantly decreased the reducing sugar per biomass. Pulp delignified by 17% active alkali and 20% sulfidity has demonstrated the maximum reducing sugar yield per biomass of 45.57% resulted after 72 h enzymatic hydrolysis. These results indicated that kraft pulping was success to degrade more lignin and hemicellulose content to facilitate the enzyme for breaking down the cellulose into its sugar monomer. A high loss of lignin and hemicellulose are not single factor to improve digestibility of SSB. This sugar has potential for yeast fermented into bioethanol.

  4. A modified efficient method for dental pulp stem cell isolation

    PubMed Central

    Raoof, Maryam; Yaghoobi, Mohammad Mehdi; Derakhshani, Ali; Kamal-abadi, Ali Mohammadi; Ebrahimi, Behnam; Abbasnejad, Mehdi; Shokouhinejad, Noushin

    2014-01-01

    Background: Dental pulp stem cells can be used in regenerative endodontic therapy. The aim of this study was to introduce an efficient method for dental pulp stem cells isolation. Materials and Methods: In this in-vitro study, 60 extracted human third molars were split and pulp tissue was extracted. Dental pulp stem cells were isolated by the following three different methods: (1) digestion of pulp by collagenase/dispase enzyme and culture of the released cells; (2) outgrowth of the cells by culture of undigested pulp pieces; (3) digestion of pulp tissue pieces and fixing them. The cells were cultured in minimum essential medium alpha modification (αMEM) medium supplemented with 20% fetal bovine serum(FBS) in humid 37°C incubator with 5% CO 2. The markers of stem cells were studied by reverse transcriptase polymerase chain reaction (PCR). The student t-test was used for comparing the means of independent groups. P <0.05 was considered as significant. Results: The results indicated that by the first method a few cell colonies with homogenous morphology were detectable after 4 days, while in the outgrowth method more time was needed (10-12 days) to allow sufficient numbers of heterogeneous phenotype stem cells to migrate out of tissue. Interestingly, with the improved third method, we obtained stem cells successfully with about 60% efficiency after 2 days. The results of RT-PCR suggested the expression of Nanog, Oct-4, and Nucleostemin markers in the isolated cells from dental pulps. Conclusion: This study proposes a new method with high efficacy to obtain dental pulp stem cells in a short time. PMID:24932197

  5. High ratio plasma resuscitation does not improve survival in pediatric trauma patients.

    PubMed

    Cannon, Jeremy W; Johnson, Michael A; Caskey, Robert C; Borgman, Matthew A; Neff, Lucas P

    2017-08-01

    Damage control resuscitation including balanced resuscitation with high ratios of plasma (PLAS) and platelets (PLT) to packed red blood cells (PRBC) improves survival in adult patients. We sought to evaluate the effect of a high ratio PLAS to PRBC resuscitation strategy in massively transfused pediatric patients with combat injuries. The Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric trauma patients (<18 years). Burns, drowning, isolated head trauma, and older teens were excluded. Those who received massive transfusion (≥40 mL/kg total blood products in 24 hours) and early deaths who received any blood products were then evaluated. Primary outcomes were mortality at 24 hours and in-hospital. Secondary outcomes included blood product utilization over 24 hours, ventilator-free days, intensive care unit-free days, and hospital length of stay. The Department of Defense Trauma Registry yielded 4,980 combat-injured pediatric trauma patients, of whom 364 met inclusion criteria. Analysis of PLAS/PRBC ratios across the entire spectrum of possible ratios in these patients demonstrated no clear inflection point for mortality. Using a division between low (LO) and high (HI) ratios of PLAS/PRBC 1:2, there was no difference in all-cause mortality at 24 hours (LO, 9.2% vs. HI, 8.0%; p = 0.75) and hospital discharge (LO, 21.5% vs. HI, 17.1%; p = 0.39). HI ratio patients received less PRBC but more PLAS and PLT and more total blood products. Those in the HI ratio group also had longer hospital length of stay. Regression analysis demonstrated no associated mortality benefit with a HI ratio (hazards ratio, 2.04; 95% confidence interval, 0.48-8.73; p = 0.34). In combat-injured children undergoing a massive transfusion, a high ratio of PLAS/PRBC was not associated with improved survival. Further prospective studies should be performed to determine the optimal resuscitation strategy in critically injured pediatric patients. Therapeutic study, level

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

    PubMed

    Ballios, Brian G; Cooke, Michael J; Donaldson, Laura; Coles, Brenda L K; Morshead, Cindi M; van der Kooy, Derek; Shoichet, Molly S

    2015-06-09

    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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. A2B adenosine receptor blockade enhances macrophage-mediated bacterial phagocytosis and improves polymicrobial sepsis survival in mice.

    PubMed

    Belikoff, Bryan G; Hatfield, Stephen; Georgiev, Peter; Ohta, Akio; Lukashev, Dmitriy; Buras, Jon A; Remick, Daniel G; Sitkovsky, Michail

    2011-02-15

    Antimicrobial treatment strategies must improve to reduce the high mortality rates in septic patients. In noninfectious models of acute inflammation, activation of A2B adenosine receptors (A2BR) in extracellular adenosine-rich microenvironments causes immunosuppression. We examined A2BR in antibacterial responses in the cecal ligation and puncture (CLP) model of sepsis. Antagonism of A2BR significantly increased survival, enhanced bacterial phagocytosis, and decreased IL-6 and MIP-2 (a CXC chemokine) levels after CLP in outbred (ICR/CD-1) mice. During the CLP-induced septic response in A2BR knockout mice, hemodynamic parameters were improved compared with wild-type mice in addition to better survival and decreased plasma IL-6 levels. A2BR deficiency resulted in a dramatic 4-log reduction in peritoneal bacteria. The mechanism of these improvements was due to enhanced macrophage phagocytic activity without augmenting neutrophil phagocytosis of bacteria. Following ex vivo LPS stimulation, septic macrophages from A2BR knockout mice had increased IL-6 and TNF-α secretion compared with wild-type mice. A therapeutic intervention with A2BR blockade was studied by using a plasma biomarker to direct therapy to those mice predicted to die. Pharmacological blockade of A2BR even 32 h after the onset of sepsis increased survival by 65% in those mice predicted to die. Thus, even the late treatment with an A2BR antagonist significantly improved survival of mice (ICR/CD-1) that were otherwise determined to die according to plasma IL-6 levels. Our findings of enhanced bacterial clearance and host survival suggest that antagonism of A2BRs offers a therapeutic target to improve macrophage function in a late treatment protocol that improves sepsis survival.

  8. Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome.

    PubMed

    Skagen, Catherine; Einstein, Michael; Lucey, Michael R; Said, Adnan

    2009-08-01

    Few therapeutic modalities exist for the treatment of hepatorenal syndrome (HRS). The combination of octreotide, midodrine, and albumin has shown possible benefit in small preliminary studies in improving renal function and short-term survival. We examined the effect of octreotide, midodrine, and albumin on survival (censored for liver transplantation) and renal function in patients with HRS type 1 and type 2, compared with a historical cohort that did not receive this therapy (control group). Seventy-five patients with HRS received octreotide, midodrine, and albumin and 87 did not constitute the control group. HRS type 1 was present in 102 individuals and HRS type 2 in 60. Transplantation was performed in 45% of patients in the treatment group as compared with 26% of patients in the control group although a significant difference in transplantation rate was seen in only HRS type 2. In the treatment arm, transplant-free survival was higher compared with the control arm (median survival 101 d vs. 18 d, P<0.0001). Survival was significantly better in the treatment arm in both HRS type 1 (P=0.0003) and HRS type 2 (P=0.009). In multivariable analysis, treatment with octreotide, midodrine, and albumin (P=0.0001) and HRS type 2 (P=0.05) were independently associated with improved survival. Renal function was significantly improved at 1 month (glomerular filtration rate 48 mL/min) in the treatment group compared with the control group (34 mL/min), P=0.03. The therapeutic regimen of octreotide, midodrine, and albumin significantly improved short-term survival and renal function in both HRS type 1 and type 2. This may provide a significant benefit as a bridge to liver transplantation in HRS type 1 and may prevent progression of HRS type 2 to HRS type 1.

  9. Influence of dimethyl formamide pulping of bagasse on pulp properties.

    PubMed

    Rezayati-Charani, P; Mohammadi-Rovshandeh, J; Hashemi, S J; Kazemi-Najafi, S

    2006-12-01

    Organosolv pulping of bagasse was conducted following a central composite design using a two-level factorial plan involving three pulping variables (temperature: 190-210 degrees C, time: 120-180 min, organic solvent charge: 40-60% dimethyl formamide). Responses of pulp properties (yield and holocellulose, alpha-cellulose, kappa number, ash and ethanol-dichloromethane extractives contents) and the pH of the resulting wastewater to the process variables were analyzed using statistical software (MINITAB). Main factor analysis revealed that optimum pulp has the following characteristics: 82.7% (yield), 92.9 (kappa number), 95.84% (holocellulose), 83.53% (alpha-cellulose), 1.403% (ash), 2.562% (ethanol-dichloromethane extractives contents) and 6.39 (pH). These results showed that acceptable properties of pulps could be gained at 200-210 degrees C for 150 min and 40-60% DMF. Based on these results, this method could be used for pulping of bagasse equivalent NSSC concerning high yield at a fixed kappa number. In addition, bagasse could be pulped with ease to approximately 55% yield with a kappa number approximately 31. Numerical analyses showed that cooking temperature had the greatest influence on properties of obtained pulps within the DMF concentrations and cooking time as cooking variables.

  10. Rapid growth in the early marine period improves the marine survival of Chinook salmon (Oncorhynchus tshawytscha) in Puget Sound, Washington

    USGS Publications Warehouse

    Duffy, Elisabeth J.; Beauchamp, David A.

    2011-01-01

    We examined the effect of early marine entry timing and body size on the marine (smolt-to-adult) survival of Puget Sound Chinook salmon (Oncorhynchus tshawytscha). We used data from coded wire tag release groups of hatchery Chinook salmon to test whether hatchery release date, release size, and size in offshore waters in July and September influenced marine survival. Marine survival was most strongly related to the average body size in July, with larger sizes associated with higher survivals. This relationship was consistent over multiple years (1997–2002), suggesting that mortality after July is strongly size-dependent. Release size and date only slightly improved this relationship, whereas size in September showed little relationship to marine survival. Specifically, fish that experienced the highest marine survivals were released before 25 May and were larger than 17 g (or 120 mm fork length) by July. Our findings highlight the importance of local conditions in Puget Sound (Washington, USA) during the spring and summer, and suggest that declines in marine survival since the 1980s may have been caused by reductions in the quality of feeding and growing conditions during early marine life.

  11. Rapid growth in the early marine period improves the marine survival of Chinook salmon (Oncorhynchus tshawytscha) in Puget Sound, Washington

    USGS Publications Warehouse

    Duffy, E.J.; Beauchamp, D.A.

    2011-01-01

    We examined the effect of early marine entry timing and body size on the marine (smolt-to-adult) survival of Puget Sound Chinook salmon (Oncorhynchus tshawytscha). We used data from coded wire tag release groups of hatchery Chinook salmon to test whether hatchery release date, release size, and size in offshore waters in July and September influenced marine survival. Marine survival was most strongly related to the average body size in July, with larger sizes associated with higher survivals. This relationship was consistent over multiple years (1997-2002), suggesting that mortality after July is strongly size-dependent. Release size and date only slightly improved this relationship, whereas size in September showed little relationship to marine survival. Specifically, fish that experienced the highest marine survivals were released before 25 May and were larger than 17 g (or 120 mm fork length) by July. Our findings highlight the importance of local conditions in Puget Sound (Washington, USA) during the spring and summer, and suggest that declines in marine survival since the 1980s may have been caused by reductions in the quality of feeding and growing conditions during early marine life.

  12. Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

    PubMed Central

    Zhu, Ling-Yan; Li, Yu; Yu, Jiao; Wang, Jiao; Zeng, Xiang-Xia; Hu, Kai-Xiang; Liu, Jian-Ying

    2017-01-01

    Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80–0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45–0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients. PMID:28409158

  13. Survival improvement in patients with pancreatic cancer by decade: A period analysis of the SEER database, 1981–2010

    PubMed Central

    Sun, Huanhuan; Ma, Haiqing; Hong, Guobin; Sun, Hongliu; Wang, Jin

    2014-01-01

    Pancreatic cancer (PaCa) is an aggressive malignancy with a high mortality rate and a poor prognosis. To evaluate treatment outcomes of patients with pancreatic cancer over the past three decades, data from the Surveillance, Epidemiology, and End Results (SEER) registries were used to assess the survival of patients with PaCa. A total of 63,530 patients diagnosed with pancreatic cancer between 1981 and 2010 were identified from nine original SEER registries. The 1-year relative survival rates (RSRs) improved each decade, from 17.0% to 19.9% to 28.2% (p < 0.0001), with a larger increase during the third decade than during the second decade. However, the long-term survival rates have remained very low. The 5-year RSRs increased from 3.1% to 4.4% to 6.9% over these three decades—i.e., still only few patients with PaCa survive more than 5 years. Furthermore, our analysis demonstrated that the survival rates for all the patients with pancreatic cancer were lower in patients of lower socioeconomic status and black race. These results will help predict future trends in PaCa incidence and survival, contribute to better-designed clinical trials by eliminating disparities that may affect the results, and thereby improve the clinical management and outcomes of PaCa. PMID:25339498

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

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    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. PMID:27294163

  15. Lipophilic extractives from several nonwoody lignocellulosic crops (flax, hemp, sisal, abaca) and their fate during alkaline pulping and TCF/ECF bleaching.

    PubMed

    Marques, Gisela; del Río, José C; Gutiérrez, Ana

    2010-01-01

    The fate of lipophilic extractives from several nonwoody species (flax, hemp, sisal and abaca) used for the manufacturing of cellulose pulps, was studied during soda/anthraquinone (AQ) pulping and totally chorine free (TCF) and elemental chlorine free (ECF) bleaching. With this purpose, the lipophilic extracts from the raw materials and their unbleached and bleached industrial pulps, were analyzed by gas chromatography-mass spectrometry. Aldehydes, hydroxyfatty acids and esterified compounds such as ester waxes, sterol esters and alkylferulates strongly decreased after soda/AQ pulping while alkanes, alcohols, free sterols and sterol glycosides survived the cooking process. Among the lipophilic extractives that remained in the unbleached pulps, some amounts of free sterols were still present in the TCF pulps whereas they were practically absent in the ECF pulps. Sterol glycosides were also removed after both TCF and ECF bleaching. By contrast, saturated fatty acids, fatty alcohols and alkanes were still present in both bleached pulps.

  16. Trace elements improve survival of DTIC-treated mice with overt liver metastases of Lewis lung carcinoma.

    PubMed

    Rásó, Erzsébet; Paku, Sándor; Kopper, László; Tímár, József

    2003-01-01

    Trace elements have been previously shown to have specific antimetastatic effects in a mouse 3LLHH liver metastasis model. Here we have analyzed the effect on the survival of animals with liver metastases. Trace elements administered per os at 500-5000 mg/kg/day did not affect the survival of animals with liver metastases. However, when trace element treatment was combined with dacarbazine (DTIC) administration, the survival of animals was significantly improved (55%). This effect was specific for DTIC since trace elements did not influence the effect of 5-fluorouracil on survival in this liver metastasis model. These data and those found in the literature all suggest that trace elements can specifically modulate the antitumoral/antimetastatic effects of chemotherapeutic agents.

  17. Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma.

    PubMed

    Ishikawa, Toru

    2013-10-07

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death in the world. With advances in imaging diagnostics, accompanied by better understanding of high-risk patients, HCC is now frequently detected at an early stage; however, the prognosis remains poor. The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs. This may be because of the high incidence of intrahepatic distant recurrence and multicentric recurrence, especially with hepatitis C virus (HCV)-related hepatocellular carcinoma. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for the clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, transcatheter arterial chemoembolization, percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation) can improve survival in HCC patients diagnosed at an early stage and offer a potential long-term cure. However, treatment strategies for recurrent disease are not mentioned in the BCLC classification. The strategy for recurrence may differ according to the recurrence pattern, i.e., intrahepatic distant recurrence vs multicentric recurrence. In this article, we review recurrent HCC and the therapeutic strategies for reducing recurrent HCC, especially HCV-related HCC.

  18. Supercritical carbon dioxide interpolymer complexes improve survival of B. longum Bb-46 in simulated gastrointestinal fluids.

    PubMed

    Thantsha, Mapitsi S; Cloete, Thomas E; Moolman, Francis S; Labuschagne, Philip W

    2009-01-31

    Gastric acidity is the main factor affecting viability of probiotics in the gastrointestinal tract (GIT). This study investigated the survival in simulated gastrointestinal fluids of Bifidobacterium longum Bb-46 encapsulated in interpolymer complexes formed in supercritical carbon dioxide (scCO(2)). Bacteria were exposed sequentially to simulated gastric fluid (SGF, pH 2) for 2 h and simulated intestinal fluid (SIF, pH 6.8) for 6 or 24 h. Total encapsulated bacteria were determined by suspending 1 g of product in SIF for 6 h at 37 degrees C prior to plating out. Plates were incubated anaerobically at 37 degrees C for 72 h. The interpolymer complex displayed pH-responsive release properties, with little to no release in SGF and substantial release in SIF. There was a limited reduction in viable counts at the end of exposure period due to encapsulation. Protection efficiency of the interpolymer complex was improved by addition of glyceryl monostearate (GMS). Gelatine capsules delayed release of bacteria from the interpolymer complex thus minimizing time of exposure to the detrimental conditions. Use of poly(caprolactone) (PCL), ethylene oxide-propylene oxide triblock copolymer (PEO-PPO-PEO) decreased the protection efficiency of the matrix. Interpolymer complex encapsulation showed potential for protection of probiotics and therefore for application in food and pharmaceuticals.

  19. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer Normalization, Not Destruction

    PubMed Central

    Whatcott, Clifford J.; Hanl, Haiyong; Von Hoff, Daniel D.

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the “perfect storms” that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects. PMID:26222082

  20. Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis.

    PubMed

    Emrath, Elizabeth T; Fortenberry, James D; Travers, Curtis; McCracken, Courtney E; Hebbar, Kiran B

    2017-07-01

    To evaluate outcomes in patients receiving balanced fluids for resuscitation in pediatric severe sepsis. Observational cohort review of prospectively collected data from a large administrative database. PICUs from 43 children's hospitals. PICU patients diagnosed with severe sepsis. None. We reviewed data from the Pediatric Health Information System database from 2004 to 2012. Children with pediatric severe sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours of treatment were compared to those receiving unbalanced fluids. Thirty-six thousand nine hundred eight patients met entry criteria for analysis. Two thousand three hundred ninety-eight patients received exclusively balanced fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio, 0.76; 95% CI, 0.62-0.93), lower prevalence of acute kidney injury (16.0% vs 19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68-0.98), and fewer vasoactive infusion days (3.0 vs 3.3 d; p < 0.001) when compared with the unbalanced fluids group. In this retrospective analysis carried out by propensity matching, exclusive use of balanced fluids in pediatric severe sepsis patients for the first 72 hours of resuscitation was associated with improved survival, decreased prevalence of acute kidney injury, and shorter duration of vasoactive infusions when compared with exclusive use of unbalanced fluids.

  1. Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure.

    PubMed

    Hamaguchi, Sanae; Kinugawa, Shintaro; Tsuchihashi-Makaya, Miyuki; Goto, Kazutomo; Goto, Daisuke; Yokota, Takashi; Yamada, Satoshi; Yokoshiki, Hisashi; Takeshita, Akira; Tsutsui, Hiroyuki

    2010-12-01

    The RALES trial demonstrated that spironolactone improved the prognosis of patients with heart failure (HF). However, it is unknown whether the discharge use of spironolactone is associated with better long-term outcomes among hospitalized systolic HF patients in routine clinical practice. We examined the effects of spironolactone use at discharge on mortality and rehospitalization by comparing with outcomes in patients who did not receive spironolactone. The JCARE-CARD studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed with an average of 2.2 years of follow-up. A total of 946 patients had HF with reduced left ventricular ejection fraction (LVEF) (<40%), among whom spironolactone was prescribed at discharge in 435 patients (46%), but not in 511 patients (54%). The mean age was 66.3 years and 72.2% were male. Etiology was ischemic in 39.7% and mean LVEF was 27.1%. After adjustment for covariates, discharge use of spironolactone was associated with a significant reduction in all-cause death (adjusted hazard ratio 0.612, P=.020) and cardiac death (adjusted hazard ratio 0.524, P=.013). Among patients with HF hospitalized for systolic dysfunction, spironolactone use at the time of discharge was associated with long-term survival benefit. These findings provide further support for the idea that spironolactone may be useful in patients hospitalized with HF and reduced LVEF. Copyright © 2010 Mosby, Inc. All rights reserved.

  2. Statins improve survival by inhibiting spontaneous metastasis and tumor growth in a mouse melanoma model

    PubMed Central

    Tsubaki, Masanobu; Takeda, Tomoya; Kino, Toshiki; Obata, Naoya; Itoh, Tatsuki; Imano, Motohiro; Mashimo, Kenji; Fujiwara, Daichiro; Sakaguchi, Katsuhiko; Satou, Takao; Nishida, Shozo

    2015-01-01

    Metastatic melanoma is a life-threatening disease for which no effective treatment is currently available. In melanoma cells, Rho overexpression promotes invasion and metastasis. However, the effect of statins on spontaneous metastasis and tumor growth remains unclear. In the present study, we investigated the mechanism of statin-mediated tumor growth and metastasis inhibition in an in vivo model. We found that statins significantly inhibited spontaneous metastasis and tumor growth. Statins inhibited the mRNA expression and enzymatic activities of matrix metalloproteinases (MMPs) in vivo and also suppressed the mRNA and protein expression of very late antigens (VLAs). Moreover, statins inhibited the prenylation of Rho as well as the phosphorylation of LIM kinase, serum response factor (SRF), and c-Fos downstream of the Rho signaling pathway. In addition, statins enhanced p53, p21, and p27 expression and reduced phosphorylation of cyclin-dependent kinase and expression of cyclin D1 and E2. These results indicate that statins suppress Rho signaling pathways, thereby inhibiting tumor metastasis and growth. Furthermore, statins markedly improved the survival rate in a metastasis model, suggesting that statins have potential clinical applications for the treatment of metastatic cancers. PMID:26693069

  3. Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival

    PubMed Central

    Sinn, Marianne; Bahra, Marcus; Denecke, Timm; Travis, Sue; Pelzer, Uwe; Riess, Hanno

    2016-01-01

    Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of “borderline resectability”. Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future. PMID:26989460

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

    USGS Publications Warehouse

    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.

  5. Effect of shortening kraft pulping integrated with extended oxygen delignification on biorefinery process performance of eucalyptus.

    PubMed

    Li, Jing; Zhang, Chunyun; Hu, Huichao; Chai, Xin-Sheng

    2016-02-01

    The aim of this work was to study the impact of shortening kraft pulping (KP) process integrated with extended oxygen delignification (OD) on the biorefinery process performance of eucalyptus. Data showed that using kraft pulps with high kappa number could improve the delignification efficiency of OD, reduce hexenuronic acid formation in kraft pulps. Pulp viscosity for a target kappa number of ∼10 was comparable to that obtained from conventional KP and OD process. The energy and alkali consumption in the integrated biorefinery process could be optimized when using a KP pulp with kappa number of ∼27. The process could minimize the overall methanol formation, but greater amounts of carbonate and oxalate were formed. The information from this study will be helpful to the future implementation of short-time KP integrated with extended OD process in actual pulp mill applications for biorefinery, aiming at further improvement in the biorefinery effectiveness of hardwood. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Delayed low-dose supplemental oxygen improves survival following phosgene-induced acute lung injury.

    PubMed

    Grainge, C; Jugg, B J; Smith, A J; Brown, R F R; Jenner, J; Parkhouse, D A; Rice, P

    2010-06-01

    Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces life-threatening pulmonary edema within hours of exposure; no antidote exists. This study examines pathophysiological changes seen following treatment with elevated inspired oxygen concentrations (Fi(O2)), in a model of phosgene-induced acute lung injury. Anesthetized pigs were exposed to phosgene (Ct 2500 mg min m(-3)) and ventilated (intermittent positive pressure ventilation, tidal volume 10 ml kg(-1), positive end-expiratory pressure 3 cm H(2)O, frequency 20 breaths min(-1)). The Fi(O2) was varied: group 1, Fi(O2) 0.30 (228 mm Hg) throughout; group 2, Fi(O2) 0.80 (608 mm Hg) immediately post exposure, to end; group 3, Fi(O2) 0.30 from 30 min post exposure, increased to 0.80 at 6 h post exposure; group 4, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 (304 mm Hg) at 6 h post exposure. Group 5, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 at 12 h post exposure. The current results demonstrate that oxygen is beneficial, with improved survival, arterial oxygen saturation, shunt fraction, and reduced lung wet weight to body weight ratio in all treatment groups, and improved arterial oxygen partial pressure in groups 2 and 3, compared to phosgene controls (group 1) animals. The authors recommend that treatment of phosgene-induced acute lung injury with inspired oxygen is delayed until signs or symptoms of hypoxia are present or arterial blood oxygenation falls. The lowest concentration of oxygen that maintains normal arterial oxygen saturation and absence of clinical signs of hypoxia is recommended.

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

    PubMed Central

    2013-01-01

    Background To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT. Methods 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. Results 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. Conclusions Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS. PMID:23705661

  8. Medium Osmolarity and Pericellular Matrix Development Improves Chondrocyte Survival When Photoencapsulated in Poly(Ethylene Glycol) Hydrogels at Low Densities

    PubMed Central

    Villanueva, Idalis; Bishop, Nikki L.

    2009-01-01

    The ability to encapsulate cells over a range of cell densities is important toward mimicking cell densities of native tissues and rationally designing strategies where cell source and/or cell numbers are clinically limited. Our preliminary findings demonstrate that survival of freshly isolated adult bovine chondrocytes dramatically decreases when photoencapsulated in poly(ethylene glycol) hydrogels at low densities (4 million cells/mL). During enzymatic digestion of cartilage, chondrocytes undergo a harsh change in their microenvironment. We hypothesize that the absence of exogenous antioxidants, the hyposmotic environment, and the loss of a protective pericellular matrix (PCM) increase chondrocytes' susceptibility to free radical damage during photoencapsulation. Incorporation of antioxidants and serum into the encapsulation medium improved cell survival twofold compared to phosphate-buffered saline. Increasing medium osmolarity from 330 to 400 mOsm (physiological) improved cell survival by 40% and resulted in ∼2-fold increase in adenosine triphosphate (ATP) production 24 h postencapsulation. However, cell survival was only temporary. Allowing cells to reproduce some PCM before photoencapsulation in 400 mOsm medium resulted in superior cell survival during and postencapsulation for up to 15 days. In summary, the combination of antioxidants, physiological osmolarity, and the development of some PCM result in an improved robustness against free radical damage during photoencapsulation. PMID:19331581

  9. Medium osmolarity and pericellular matrix development improves chondrocyte survival when photoencapsulated in poly(ethylene glycol) hydrogels at low densities.

    PubMed

    Villanueva, Idalis; Bishop, Nikki L; Bryant, Stephanie J

    2009-10-01

    The ability to encapsulate cells over a range of cell densities is important toward mimicking cell densities of native tissues and rationally designing strategies where cell source and/or cell numbers are clinically limited. Our preliminary findings demonstrate that survival of freshly isolated adult bovine chondrocytes dramatically decreases when photoencapsulated in poly(ethylene glycol) hydrogels at low densities (4 million cells/mL). During enzymatic digestion of cartilage, chondrocytes undergo a harsh change in their microenvironment. We hypothesize that the absence of exogenous antioxidants, the hyposmotic environment, and the loss of a protective pericellular matrix (PCM) increase chondrocytes' susceptibility to free radical damage during photoencapsulation. Incorporation of antioxidants and serum into the encapsulation medium improved cell survival twofold compared to phosphate-buffered saline. Increasing medium osmolarity from 330 to 400 mOsm (physiological) improved cell survival by 40% and resulted in approximately 2-fold increase in adenosine triphosphate (ATP) production 24 h postencapsulation. However, cell survival was only temporary. Allowing cells to reproduce some PCM before photoencapsulation in 400 mOsm medium resulted in superior cell survival during and postencapsulation for up to 15 days. In summary, the combination of antioxidants, physiological osmolarity, and the development of some PCM result in an improved robustness against free radical damage during photoencapsulation.

  10. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

    PubMed Central

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-01-01

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes

  11. Betaxolol improves the survival rate and changes natriuretic peptide expression in rats with heart failure.

    PubMed

    Watanabe, Kenichi; Juan, Wen; Narasimman, Gurusamy; Ma, Meilei; Inoue, Mikio; Saito, Yuki; Wahed, Mir I I; Nakazawa, Mikio; Hasegawa, Go; Naito, Makoto; Tachikawa, Hitoshi; Tanabe, Naohito; Kodama, Makoto; Aizawa, Yoshifusa; Yamamoto, Tadashi; Yamaguchi, Kenichi; Takahashi, Toshihiro

    2003-01-01

    The cardioprotective effects of betaxolol were studied in a rat model with heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups; 0.1 mg/kg betaxolol per day (group 0.1), 1.0 mg/kg betaxolol per day (group 1), 10 mg/kg betaxolol per day (group 10), and vehicle (0.5% methylcellulose, group V) (all groups, n = 13). After oral administration for 1 month, the heart weight, the mRNA expression of atrial natriuretic peptide and brain natriuretic peptide in the left ventricle, the plasma atrial natriuretic peptide concentration, the mean blood pressure, the heart rate, the central venous pressure, the peak left ventricular pressure, the left ventricular end-diastolic pressure and its first derivative +/-dP/dt, and the area of myocardial fibrosis were measured. Betaxolol reduced the heart rate, the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA expression and the atrial natriuretic peptide concentration [group N (normal rats), 367 +/- 4 beats/min, 100%, 100% and 78 +/- 7 pg/ml, respectively; group V, 391 +/- 9 beats/min, 761 +/- 68% versus group N, 317 +/- 42% versus group N and 4374 +/- 312 pg/ml, respectively; group 0.1, 387 +/- 10 beats/min, 621 +/- 78%, 288 +/- 41% and 2875 +/- 331 pg/ml, respectively; group 1, 323 +/- 9 beats/min, 442 +/- 84%, 148 +/- 12% and 884 +/- 51 pg/ml, respectively; and group 10, 312 +/- 8 beats/min, 97 +/- 18%, 92 + 9% and 453 +/- 53 pg/ml, respectively], and increased survival (group V, 62%; group 0.1, 69%; groups N, 1 and 10, 100%). Betaxolol did not significantly alter the heart weight, the hemodynamic parameters or the area of fibrosis. These observations suggest that betaxolol may improve the survival rate by reducing sudden death and changing the atrial natriuretic peptide and brain natriuretic peptide mRNA expression in patients with heart failure.

  12. Pharmacologic cholinesterase inhibition improves survival in acetaminophen-induced acute liver failure in the mouse

    PubMed Central

    2014-01-01

    Background Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic pharmaceutical substances in the world and accounts for most cases of drug induced liver injury resulting in acute liver failure. Acute liver failure initiates a sterile inflammatory response with release of cytokines and innate immune cell infiltration in the liver. This study investigates, whether pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver damage in acute liver failure via the cholinergic anti-inflammatory pathway. Methods Acute liver failure was induced in BALB/c mice by a toxic dose of acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied therapeutically at set time points and the survival was investigated. Liver damage was assessed by serum parameters, histopathology and serum cytokine assays 12 h after initiation of acute liver failure. Results Serum parameters, histopathology and serum cytokine assays showed pronounced features of acute liver failure 12 h after application of acetaminophen (APAP). Neostigmine treatment led to significant reduction of serum liver enzymes (LDH (47,147 ± 12,726 IU/l vs. 15,822 ± 10,629 IU/l, p = 0.0014) and ALT (18,048 ± 4,287 IU/l vs. 7,585 ± 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP + neostigmine-treated mice), inflammatory cytokine levels (IL-1β (147 ± 19 vs. 110 ± 25, p = 0.0138) and TNF-α (184 ± 23 vs. 130 ± 33, p = 0.0086), APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and histopathological signs of damage. Animals treated with NAC in combination with the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and improved outcome. Conclusions Neostigmine is an acetylcholinesterase inhibitor that ameliorates the effects of APAP-induced acute liver failure in the mouse and therefore may provide new treatment options for affected patients. PMID:25139304

  13. Improved emergency myelopoiesis and survival in neonatal sepsis by caspase-1/11 ablation

    PubMed Central

    Gentile, Lori F; Cuenca, Angela L; Cuenca, Alex G; Nacionales, Dina C; Ungaro, Ricardo; Efron, Philip A; Moldawer, Lyle L; Larson, Shawn D

    2015-01-01

    Over one million newborns die annually from sepsis with the highest mortality in premature and low-birthweight infants. The inflammasome plays a central role in the regulation of innate immunity and inflammation, and is presumed to be involved in protective immunity, in large part through the caspase-1-dependent activation of interleukin-1β (IL-1β) and IL-18. Studies in endotoxic shock, however, suggest that endogenous caspase-1 activity and the inflammasome contribute to mortality primarily by promoting excessive systemic inflammatory responses. We examined whether caspase-1 and the inflammasome also regulate neonatal inflammation, host protective immunity and myelopoiesis during polymicrobial sepsis. Neonatal (5–7 days) C57BL/6 and caspase-1/11−/− mice underwent a low-lethality caecal slurry model of intra-abdominal sepsis (LD25–45). Ablation of caspase-1/11, but not apoptosis-associated speck-like protein containing a CARD domain or nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), improved neonatal survival following septic challenge compared with wild-type mice (P < 0·001), with decreased concentrations of inflammatory cytokines in the serum and peritoneum. Surprisingly, caspase-1/11−/− neonates also exhibited increased bone marrow and splenic haematopoietic stem cell expansion (P < 0·001), and increased concentrations of granulocyte and macrophage colony-stimulating factors in the peritoneum (P < 0·001) after sepsis. Ablation of caspase-1/11 signalling was also associated with increased recruitment of peritoneal macrophages and neutrophils (P < 0·001), increased phagocytosis by neutrophils (P = 0·003), and decreased bacterial colonization (P = 0·02) in the peritoneum. These findings suggest that endogenous caspase-1/11 activity, independent of the NLRP3 inflammasome, not only promotes the magnitude of the inflammatory response, but also suppresses protective immunity in the neonate, so contributing to

  14. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy.

    PubMed

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-10-15

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n = 8; 0.5, 0.3, 0.1 μg g(-1)) or D with vitamins C and E (DCE; n = 8; 200 and 100 mg kg(-1), respectively) on postnatal days 1-3 (P1-3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n = 8). A fourth group received vitamins alone (CCE; n = 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μM), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (cardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min(-1)) or afterload (cardiac output: -5.3 ± 2.0 vs.1.4 ± 1.2 ml min(-1)); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac

  15. Improved Estimates of Cancer-Specific Survival Rates From Population-Based Data

    PubMed Central

    Ries, Lynn A. G.; Mariotto, Angela B.; Reichman, Marsha E.; Ruhl, Jennifer; Cronin, Kathleen A.

    2010-01-01

    Background Accurate estimates of cancer survival are important for assessing optimal patient care and prognosis. Evaluation of these estimates via relative survival (a ratio of observed and expected survival rates) requires a population life table that is matched to the cancer population by age, sex, race and/or ethnicity, socioeconomic status, and ideally risk factors for the cancer under examination. Because life tables for all subgroups in a study may be unavailable, we investigated whether cause-specific survival could be used as an alternative for relative survival. Methods We used data from the Surveillance, Epidemiology, and End Results Program for 2 330 905 cancer patients from January 1, 1992, through December 31, 2004. We defined cancer-specific deaths according to the following variables: cause of death, only one tumor or the first of multiple tumors, site of the original cancer diagnosis, and comorbidities. Estimates of relative survival and cause-specific survival that were derived by use of an actuarial method were compared. Results Among breast cancer patients who were white, black, or of Asian or Pacific Islander descent and who were older than 65 years, estimates of 5-year relative survival (107.5%, 106.6%, and 103.0%, respectively) were higher than estimates of 5-year cause-specific survival (98.6%, 95% confidence interval [CI] = 98.4% to 98.8%; 97.4%, 95% CI = 96.2% to 98.2%; and 99.2%, 95% CI = 98.4%, 99.6%, respectively). Relative survival methods likely underestimated rates for cancers of the oral cavity and pharynx (eg, for white cancer patients aged ≥65 years, relative survival = 54.2%, 95% CI = 53.1% to 55.3%, and cause-specific survival = 60.1%, 95% CI = 59.1% to 60.9%) and the lung and bronchus (eg, for black cancer patients aged ≥65 years, relative survival = 10.5%, 95% CI = 9.9% to 11.2%, and cause-specific survival = 11.9%, 95% CI = 11.2 % to 12.6%), largely because of mismatches between the population with these diseases and

  16. Improved Survival Modeling in Cancer Research Using a Reduced Piecewise Exponential Approach

    PubMed Central

    Han, Gang; Schell, Michael J.; Kim, Jongphil

    2014-01-01

    Statistical models for survival data are typically nonparametric, e.g., the Kaplan-Meier curve. Parametric survival modeling, such as exponential modeling, however, can reveal additional insights and be more efficient than nonparametric alternatives. A major constraint of the existing exponential models is the lack of flexibility due to distribution assumptions. A flexible and parsimonious piecewise exponential model is presented to best use the exponential models for arbitrary survival data. This model identifies shifts in the failure rate over time based on an exact likelihood ratio test, a backward elimination procedure, and an optional presumed order restriction on the hazard rate. Such modeling provides a descriptive tool in understanding the patient survival in addition to the Kaplan-Meier curve. This approach is compared with alternative survival models in simulation examples and illustrated in clinical studies. PMID:23900779

  17. Adjuvant Radiation Improves Survival in Older Women Following Breast-Conserving Surgery for Estrogen Receptor-Negative Breast Cancer.

    PubMed

    Daugherty, Emily C; Daugherty, Michael R; Bogart, Jeffrey A; Shapiro, Anna

    2016-12-01

    Published prospective trials have questioned the role of post-lumpectomy radiotherapy in older women with early-stage, estrogen receptor-positive (ER(+)) breast cancer. As the population with ER(-) tumors may be at greater risk for relapse, particularly given that endocrine therapy is not effective, we hypothesize the addition of radiation would be of benefit in patients age ≥ 70. The Surveillance, Epidemiology, and End Results database was queried from 1998 to 2011 for patients age ≥ 70 years receiving breast-conserving surgery for T1, ER(-) invasive ductal carcinoma. Patients were separated into 2 cohorts: those treated with and without adjuvant radiotherapy. Chi-square analysis, unpaired t test and Kaplan-Meier log-rank were used to compare patient and tumor characteristics as well as overall and cancer-specific survival between the cohorts. Overall, 3685 patients received radiation and 1493 patients received lumpectomy alone. Patients treated with adjuvant radiation were younger (median age 76 vs. 78 years, P < .0001). Patients who received radiation had improved overall survival, with 5-year survival rates of 81.0% versus 61.7% without radiation (P < .0001). Cancer-specific survival was also improved with radiotherapy, with 5-year cancer-specific survival rates of 93.1% versus 85.0% (P < .0001). This analysis of the SEER database demonstrates that women ages 70 and older treated with lumpectomy and radiotherapy for ER(-), early-stage breast cancer have improved overall survival and breast cancer-specific survival compared with patients treated with lumpectomy alone. This information may help in the decision-making process for this patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Dissolving pulp industry : market trends

    Treesearch

    Irene. Durbak

    1993-01-01

    This report presents a worldwide overview of the dissolving pulp industry and highlights of this industry in Alaska. It describes trends in world markets and major end-use markets, with special emphasis on the manufacture and use of textile fibers in the United States. Figures and tables present data on production, consumption, and trade of dissolving pulp and the...

  19. [Dental pulp diseases. Ultramicroscopic studies].

    PubMed

    Conversini, A; Eramo, S; Manna, M G; Negri, P

    1998-12-01

    After the description of the anatomic and histologic aspects of the healthy dental pulp, stress is laid on pulpal pathologies and on the use of ultramicroscopic techniques to analyze the cytologic modifications in normal and pathologic dental pulp tissues. The results obtained are presented.

  20. Biobleaching of Eucalyptus globulus kraft pulps: comparison between pulps obtained from exploded and non-exploded chips.

    PubMed

    Martín-Sampedro, R; Eugenio, M E; Villar, J C

    2011-03-01

    The aim of this work was to evaluate the response to biobleaching of steam exploded kraft pulps and to compare the results with the controls. For this end, a laccase-mediator treatment using commercial laccase (Novozyme 51003) and a natural mediator (acetosyringone) were assayed, followed by alkaline extraction and hydrogen peroxide stages. Our approach resulted in exploded biobleached pulps with lower kappa number and improved optical properties compared to controls, even after subjecting pulps to accelerated ageing. Additionally, use of hydrogen peroxide was reduced. The LMS (laccase-mediator system) had a smaller impact on the properties of the bleached pulps and on hydrogen peroxide consumption than the steam explosion process did. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Resuscitation bundle compliance in severe sepsis and septic shock: improves survival, is better late than never.

    PubMed

    Coba, Victor; Whitmill, Melissa; Mooney, Roberta; Horst, H Mathilda; Brandt, Mary-Margaret; Digiovine, Bruno; Mlynarek, Mark; McLellan, Beth; Boleski, Gail; Yang, James; Conway, William; Jordan, Jack

    2011-01-01

    While clinicians' management of severe sepsis and septic shock has been positively influenced by a number of clinical research studies in the last decade, challenges remain regarding early hemodynamic optimization as envisioned in the Surviving Sepsis Campaign's (SSC) resuscitation bundle (RB). We examined the impact of a hospital-wide continuous quality improvement (CQI) initiative on patients presenting with severe sepsis and septic shock, and the impact of the sepsis RB on patient outcomes when completed beyond the 6-hour recommendation period. The study was an 18-month, prospective cohort study enrolling patients who met the definition of severe sepsis or septic shock. Compliance with the hemodynamic components of the sepsis RB was defined as achieving goal mean arterial pressure (MAP) ≥ 65 mm Hg, central venous pressure (CVP) ≥ 8 mm Hg, and central venous oxygen saturation (ScvO₂) ≥ 70%. Compliance was assessed at 6 hours and 18 hours after diagnosis of severe sepsis or septic shock. In all, 498 patients with severe sepsis and/or septic shock were evaluated to determine the upper limit of the range of hours that compliance with the RB would still improve outcomes. Using 18 hours as a marker, Compliers at 18 hrs and Non-Compliers at 18 hrs were compared. There were 202 patients who had the RB completed in less than or equal to 18 hours. There were 296 patients who did not complete the RB at 18 hours. The Compliers at 18 hrs had a significant 10.2% lower hospital mortality 37.1% (22% relative reduction) compared to the Non-Compliers at 18 hrs hospital mortality of 47.3% (P < .03). When the two groups were adjusted for differences in baseline illness severity, the Compliers at 18 hrs had a greater reduction in predicted mortality of 26.8% versus 9.4%, P < 0.01. Initiating the sepsis RB for patients with severe sepsis and/or septic shock decreased mortality. A CQI initiative that monitored the implementation in real-time allowed for improvement in

  2. Improved survival for patients with recurrent Wilms tumor: the experience at St. Jude Children's Research Hospital.

    PubMed

    Dome, Jeffrey S; Liu, Tiebin; Krasin, Matthew; Lott, Lennie; Shearer, Patricia; Daw, Najat C; Billups, Catherine A; Wilimas, Judith A

    2002-01-01

    Reported estimates of survival for patients with recurrent Wilms tumor are 24% to 43%. Because published survival data are more than a decade old and do not reflect advances in therapy, the authors reviewed their experience in treating recurrent Wilms tumor to determine whether the probability of survival has increased. The authors reviewed the cases of 54 patients with recurrent Wilms tumor who were treated on one of six consecutive clinical trials at St. Jude Children's Research Hospital between 1969 and 2000. Five-year overall survival estimates after relapse were 63.6 +/- 15.7% for patients treated during or after 1984 (n = 20) and 20.6 +/- 6.5% for patients treated before 1984 (n = 34) (P = 0.002). When the analysis was restricted to patients with high-risk clinical features, 5-year overall survival estimates were 47.6 +/- 15.7% for those treated in the modern era (n = 16) and 11.1 +/- 5.2% for those treated in the earlier era (n = 25) (P = 0.005). Only three patients received high-dose chemotherapy with autologous stem cell rescue; one survived. No patients with recurrent anaplastic histology disease survived. Significant progress has been achieved in the treatment of recurrent favorable-histology Wilms tumor using multimodality salvage regimens with conventional doses of chemotherapy. Novel therapeutic strategies will be necessary to cure patients with recurrent anaplastic Wilms tumor.

  3. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival.

    PubMed

    Baumann, Francine; Flores, Erin; Napolitano, Andrea; Kanodia, Shreya; Taioli, Emanuela; Pass, Harvey; Yang, Haining; Carbone, Michele

    2015-01-01

    BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients--11 alive--with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (24-67%), as compared with 6.7% (6.2-7.3%) in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P = 0.0716), survived for a longer time compared with patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall 7-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.

  4. Advanced Scaffolds for Dental Pulp and Periodontal Regeneration.

    PubMed

    Bottino, Marco C; Pankajakshan, Divya; Nör, Jacques E

    2017-10-01

    No current therapy promotes root canal disinfection and regeneration of the pulp-dentin complex in cases of pulp necrosis. Antibiotic pastes used to eradicate canal infection negatively affect stem cell survival. Three-dimensional easy-to-fit antibiotic-eluting nanofibers, combined with injectable scaffolds, enriched or not with stem cells and/or growth factors, may increase the likelihood of achieving predictable dental pulp regeneration. Periodontitis is an aggressive disease that impairs the integrity of tooth-supporting structures and may lead to tooth loss. The latest advances in membrane biomodification to endow needed functionalities and technologies to engineer patient-specific membranes/constructs to amplify periodontal regeneration are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Increased acylated plasma ghrelin, but improved lipid profiles 24-h after consumption of carob pulp preparation rich in dietary fibre and polyphenols.

    PubMed

    Gruendel, Sindy; Garcia, Ada L; Otto, Baerbel; Wagner, Karen; Bidlingmaier, Martin; Burget, Lukas; Weickert, Martin O; Dongowski, Gerhard; Speth, Maria; Katz, Norbert; Koebnick, Corinna

    2007-12-01

    We have recently shown that a polyphenol-rich insoluble dietary fibre preparation from carob pulp (Ceratonia siliqua L; carob fibre) decreased postprandial acylated ghrelin, TAG and NEFA during an acute liquid meal challenge test. However, delayed effects of carob fibre consumption are unknown. Therefore, a randomized controlled crossover study in nineteen healthy volunteers consuming foods with or without 50 g carob fibre was conducted. On the subsequent day (day 2), glucose, TAG, total and acylated ghrelin as well as insulin, NEFA and leptin were assessed at baseline and at timed interv