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Sample records for salvage pathway studies

  1. The methionine salvage pathway in Bacillus subtilis

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    Danchin Antoine

    2002-04-01

    Full Text Available Abstract Background Polyamine synthesis produces methylthioadenosine, which has to be disposed of. The cell recycles it into methionine through methylthioribose (MTR. Very little was known about MTR recycling for methionine salvage in Bacillus subtilis. Results Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere as a major step in MTR recycling. Conclusions A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane.

  2. Bacterial variations on the methionine salvage pathway

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    Haas Dieter

    2004-03-01

    Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

  3. NAD+ salvage pathway in cancer metabolism and therapy.

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    Kennedy, Barry E; Sharif, Tanveer; Martell, Emma; Dai, Cathleen; Kim, Youra; Lee, Patrick W K; Gujar, Shashi A

    2016-12-01

    Nicotinamide adenine dinucleotide (NAD + ) is an essential coenzyme for various physiological processes including energy metabolism, DNA repair, cell growth, and cell death. Many of these pathways are typically dysregulated in cancer cells, making NAD + an intriguing target for cancer therapeutics. NAD + is mainly synthesized by the NAD + salvage pathway in cancer cells, and not surprisingly, the pharmacological targeting of the NAD + salvage pathway causes cancer cell cytotoxicity in vitro and in vivo. Several studies have described the precise consequences of NAD + depletion on cancer biology, and have demonstrated that NAD+ depletion results in depletion of energy levels through lowered rates of glycolysis, reduced citric acid cycle activity, and decreased oxidative phosphorylation. Additionally, depletion of NAD + causes sensitization of cancer cells to oxidative damage by disruption of the anti-oxidant defense system, decreased cell proliferation, and initiation of cell death through manipulation of cell signaling pathways (e.g., SIRT1 and p53). Recently, studies have explored the effect of well-known cancer therapeutics in combination with pharmacological depletion of NAD + levels, and found in many cases a synergistic effect on cancer cell cytotoxicity. In this context, we will discuss the effects of NAD + salvage pathway inhibition on cancer cell biology and provide insight on this pathway as a novel anti-cancer therapeutic target. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vernis, L.; Piskur, Jure; Diffley, J.F.X.

    2003-01-01

    The budding yeast Saccharomyces cerevisiae is unable to incorporate exogenous nucleosides into DNA. We have made a number of improvements to existing strategies to reconstitute an efficient thymidine salvage pathway in yeast. We have constructed strains that express both a nucleoside kinase as well...

  5. Vibrio Phage KVP40 Encodes a Functional NAD+ Salvage Pathway.

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    Lee, Jae Yun; Li, Zhiqun; Miller, Eric S

    2017-05-01

    The genome of T4-type Vibrio bacteriophage KVP40 has five genes predicted to encode proteins of pyridine nucleotide metabolism, of which two, nadV and natV , would suffice for an NAD + salvage pathway. NadV is an apparent nicotinamide phosphoribosyltransferase (NAmPRTase), and NatV is an apparent bifunctional nicotinamide mononucleotide adenylyltransferase (NMNATase) and nicotinamide-adenine dinucleotide pyrophosphatase (Nudix hydrolase). Genes encoding the predicted salvage pathway were cloned and expressed in Escherichia coli , the proteins were purified, and their enzymatic properties were examined. KVP40 NadV NAmPRTase is active in vitro , and a clone complements a Salmonella mutant defective in both the bacterial de novo and salvage pathways. Similar to other NAmPRTases, the KVP40 enzyme displayed ATPase activity indicative of energy coupling in the reaction mechanism. The NatV NMNATase activity was measured in a coupled reaction system demonstrating NAD + biosynthesis from nicotinamide, phosphoribosyl pyrophosphate, and ATP. The NatV Nudix hydrolase domain was also shown to be active, with preferred substrates of ADP-ribose, NAD + , and NADH. Expression analysis using reverse transcription-quantitative PCR (qRT-PCR) and enzyme assays of infected Vibrio parahaemolyticus cells demonstrated nadV and natV transcription during the early and delayed-early periods of infection when other KVP40 genes of nucleotide precursor metabolism are expressed. The distribution and phylogeny of NadV and NatV proteins among several large double-stranded DNA (dsDNA) myophages, and also those from some very large siphophages, suggest broad relevance of pyridine nucleotide scavenging in virus-infected cells. NAD + biosynthesis presents another important metabolic resource control point by large, rapidly replicating dsDNA bacteriophages. IMPORTANCE T4-type bacteriophages enhance DNA precursor synthesis through reductive reactions that use NADH/NADPH as the electron donor and NAD

  6. Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer.

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    Ju, Huai-Qiang; Zhuang, Zhuo-Nan; Li, Hao; Tian, Tian; Lu, Yun-Xin; Fan, Xiao-Qiang; Zhou, Hai-Jun; Mo, Hai-Yu; Sheng, Hui; Chiao, Paul J; Xu, Rui-Hua

    2016-08-28

    Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor for the redox reactions in the metabolic pathways of cancer cells that have elevated aerobic glycolysis (Warburg effect). Cancer cells are reported to rely on NAD recycling and inhibition of the NAD salvage pathway causes metabolic collapse and cell death. However, the underlying regulatory mechanisms and clinical implications for the NAD salvage pathway in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study showed that the expression of Nampt, the rate-limiting enzyme of the NAD salvage pathway, was significantly increased in PDAC cells and PDAC tissues. Additionally, inhibition of Nampt impaired tumor growth in vitro and tumorigenesis in vivo, which was accompanied by a decreased cellular NAD level and glycolytic activity. Mechanistically, the Nampt expression was independent of Kras and p16 status, but it was directly regulated by miR-206, which was inversely correlated with the expression of Nampt in PDAC tissues. Importantly, pharmacological inhibition of Nampt by its inhibitor, FK866, significantly enhanced the antitumor activity of gemcitabine in PDAC cells and in orthotopic xenograft mouse models. In conclusion, the present study revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis.

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    Wang, Guodong; Pichersky, Eran

    2007-03-01

    Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which is derived from NAD, have important roles as a redox carriers in metabolism. A combination of de novo and salvage pathways contribute to the biosynthesis of NAD in all organisms. The pathways and enzymes of the NAD salvage pathway in yeast and animals, which diverge at nicotinamide, have been extensively studied. Yeast cells convert nicotinamide to nicotinic acid, while mammals lack the enzyme nicotinamidase and instead convert nicotinamide to nicotinamide mononucleotide. Here we show that Arabidopsis thaliana gene At2g22570 encodes a nicotinamidase, which is expressed in all tissues, with the highest levels observed in roots and stems. The 244-residue protein, designated AtNIC1, converts nicotinamide to nicotinic acid and has a Km value of 118 +/- 17 microM and a Kcat value of 0.93 +/- 0.13 sec(-1). Plants homozygous for a null AtNIC1 allele, nic1-1, have lower levels of NAD and NADP under normal growth conditions, indicating that AtNIC1 participates in a yeast-type NAD salvage pathway. Mutant plants also exhibit hypersensitivity to treatments of abscisic acid and NaCl, which is correlated with their inability to increase the cellular levels of NAD(H) under these growth conditions, as occurs in wild-type plants. We also show that the growth of the roots of wild-type but not nic1-1 mutant plants is inhibited and distorted by nicotinamide.

  8. Increase in furfural tolerance by combinatorial overexpression of NAD salvage pathway enzymes in engineered isobutanol-producing E. coli.

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    Song, Hun-Suk; Jeon, Jong-Min; Kim, Hyun-Joong; Bhatia, Shashi Kant; Sathiyanarayanan, Ganesan; Kim, Junyoung; Won Hong, Ju; Gi Hong, Yoon; Young Choi, Kwon; Kim, Yun-Gon; Kim, Wooseong; Yang, Yung-Hun

    2017-12-01

    To reduce the furfural toxicity for biochemical production in E. coli, a new strategy was successfully applied by supplying NAD(P)H through the nicotine amide salvage pathway. To alleviate the toxicity, nicotinamide salvage pathway genes were overexpressed in recombinant, isobutanol-producing E. coli. Gene expression of pncB and nadE respectively showed increased tolerance to furfural among these pathways. The combined expression of pncB and nadE was the most effective in increasing the tolerance of the cells to toxic aldehydes. By comparing noxE- and fdh-harbouring strains, the form of NADH, rather than NAD + , was the major effector of furfural tolerance. Overall, this study is the application of the salvage pathway to isobutanol production in the presence of furfural, and this system seems to be applicable to alleviate furfural toxicity in the production of other biochemical. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The relative contribution of mannose salvage pathways to glycosylation in PMI-deficient mouse embryonic fibroblast cells.

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    Fujita, Naonobu; Tamura, Ayako; Higashidani, Aya; Tonozuka, Takashi; Freeze, Hudson H; Nishikawa, Atsushi

    2008-02-01

    Mannose for mammalian glycan biosynthesis can be imported directly from the medium, derived from glucose or salvaged from endogenous or external glycans. All pathways must generate mannose 6-phosphate, the activated form of mannose. Imported or salvaged mannose is directly phosphorylated by hexokinase, whereas fructose 6-phosphate from glucose is converted to mannose 6-phosphate by phosphomannose isomerase (PMI). Normally, PMI provides the majority of mannose for glycan synthesis. To assess the contribution of PMI-independent pathways, we used PMI-null fibroblasts to study N-glycosylation of DNase I, a highly sensitive indicator protein. In PMI-null cells, imported mannose and salvaged mannose make a significant contribution to N-glycosylation. When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated. Adding approximately 13 microm mannose to the medium completely restored normal glycosylation. Treatment with bafilomycin A(1), an inhibitor of lysosomal acidification, also markedly reduced N-glycosylation of DNase I, but in this case only 8 microm mannose was required to restore full glycosylation, indicating that a nonlysosomal source of mannose made a significant contribution. Glycosylation levels were greatly also reduced in glycoconjugate-free medium, when endosomal membrane trafficking was blocked by expression of a mutant SKD1. From these data, we conclude that PMI-null cells can salvage mannose from both endogenous and external glycoconjugates via lysosomal and nonlysosomal degradation pathways.

  10. Essential role of Bordetella NadC in a quinolinate salvage pathway for NAD biosynthesis.

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    Brickman, Timothy J; Suhadolc, Ryan J; McKelvey, Pamela J; Armstrong, Sandra K

    2017-02-01

    Nicotinamide adenine dinucleotide (NAD) is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are known to be auxotrophic for nicotinamide or nicotinic acid. This study confirmed that Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis have the recycling/salvage pathway genes pncA and pncB, for use of nicotinamide or nicotinic acid, respectively, for NAD synthesis. Although these Bordetellae lack the nadA and nadB genes needed for de novo NAD biosynthesis, remarkably, they have one de novo pathway gene, nadC, encoding quinolinate phosphoribosyltransferase. Genomic analyses of taxonomically related Bordetella and Achromobacter species also indicated the presence of an 'orphan' nadC and the absence of nadA and nadB. When supplied as the sole NAD precursor, quinolinate promoted B. bronchiseptica growth, and the ability to use it required nadC. Co-expression of Bordetella nadC with the nadB and nadA genes of Paraburkholderia phytofirmans allowed B. bronchiseptica to grow in the absence of supplied pyridines, indicative of de novo NAD synthesis and functional confirmation of Bordetella NadC activity. Expression of nadC in B. bronchiseptica was influenced by nicotinic acid and by a NadQ family transcriptional repressor, indicating that these organisms prioritize their use of pyridines for NAD biosynthesis. © 2016 John Wiley & Sons Ltd.

  11. De novo and salvage pathway precursor incorporation during DNA replication at the nuclear matrix

    International Nuclear Information System (INIS)

    Panzeter, P.L.

    1988-01-01

    Total nuclear DNA can be empirically subdivided into low salt-soluble (LS) DNA (75-80%), high salt-soluble (HS) DNA (18-23%), and nuclear matrix-associated (NM) DNA which remains tightly bound to the nuclear matrix (∼2%). The most-newly replicated DNA is that associated with the nuclear matrix in regenerating rat liver. Analyses of the DNA fractions after various pulse times revealed that the salvage and de novo pathway DNA precursors investigated were incorporated preferentially into NM-DNA at early pulse times, after which the radioactivity became progressively incorporated into HS- and LS-DNA, respectively. These results support two models of nuclear matrix-associated DNA replication, proposed previously, and a third model presented in this dissertation. In addition, the incorporation of de novo pathway precursors lagged significantly (> 10 minutes) behind the incorporation of precursors entering through the salvage pathway. Channeling of salvage pathway precursors to DNA replication sites would explain the more rapid uptake of salvage precursors into NM-DNA than de novo precursors. To investigate the possibility of this heretofore in vitro phenomenon, the incorporation of the salvage precursor, ( 3 H)deoxythymidine, and the de novo precursor, ( 14 C)orotic acid, into NM-DNA and dTTP was examined in regenerating rat liver. There was no significant difference between the incorporation pattern of ( 14 C)orotic acid into NM-DNA thymine and that of ( 14 C)orotic acid into soluble dTTP. Contrastingly, the salvage pathway precursor, ( 3 H)deoxythymidine, labeled NM-DNA before labeling the dTTP pool

  12. Nucleotide metabolism in Lactococcus lactis: Salvage pathways of exogenous pyrimidines

    DEFF Research Database (Denmark)

    Martinussen, Jan; Andersen, Paal Skytt; Hammer, Karin

    1994-01-01

    By measuring enzyme activities in crude extracts and studying the effect of toxic analogs (5-fluoropyrimidines) on cell growth, the metabolism of pyrimidines in Lactococcus lactis was analyzed. Pathways by which uracil, uridine, deoxyuridine, cytidine, and deoxycytidine are metabolized in L. lact...

  13. A Key Enzyme of the NAD+ Salvage Pathway in Thermus thermophilus: Characterization of Nicotinamidase and the Impact of Its Gene Deletion at High Temperatures.

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    Taniguchi, Hironori; Sungwallek, Sathidaphorn; Chotchuang, Phatcharin; Okano, Kenji; Honda, Kohsuke

    2017-09-01

    NAD (NAD + ) is a cofactor related to many cellular processes. This cofactor is known to be unstable, especially at high temperatures, where it chemically decomposes to nicotinamide and ADP-ribose. Bacteria, yeast, and higher organisms possess the salvage pathway for reconstructing NAD + from these decomposition products; however, the importance of the salvage pathway for survival is not well elucidated, except for in pathogens lacking the NAD + de novo synthesis pathway. Herein, we report the importance of the NAD + salvage pathway in the thermophilic bacterium Thermus thermophilus HB8 at high temperatures. We identified the gene encoding nicotinamidase (TTHA0328), which catalyzes the first reaction of the NAD + salvage pathway. This recombinant enzyme has a high catalytic activity against nicotinamide ( K m of 17 μM, k cat of 50 s -1 , k cat / K m of 3.0 × 10 3 s -1 · mM -1 ). Deletion of this gene abolished nicotinamide deamination activity in crude extracts of T. thermophilus and disrupted the NAD + salvage pathway in T. thermophilus Disruption of the salvage pathway led to the severe growth retardation at a higher temperature (80°C), owing to the drastic decrease in the intracellular concentrations of NAD + and NADH. IMPORTANCE NAD + and other nicotinamide cofactors are essential for cell metabolism. These molecules are unstable and decompose, even under the physiological conditions in most organisms. Thermophiles can survive at high temperatures where NAD + decomposition is, in general, more rapid. This study emphasizes that NAD + instability and its homeostasis can be one of the important factors for thermophile survival in extreme temperatures. Copyright © 2017 American Society for Microbiology.

  14. Two Distinct Aerobic Methionine Salvage Pathways Generate Volatile Methanethiol in Rhodopseudomonas palustris

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    Miller, Anthony R.; North, Justin A.; Wildenthal, John A.

    2018-01-01

    ABSTRACT 5′-Methyl-thioadenosine (MTA) is a dead-end, sulfur-containing metabolite and cellular inhibitor that arises from S-adenosyl-l-methionine-dependent reactions. Recent studies have indicated that there are diverse bacterial methionine salvage pathways (MSPs) for MTA detoxification and sulfur salvage. Here, via a combination of gene deletions and directed metabolite detection studies, we report that under aerobic conditions the facultatively anaerobic bacterium Rhodopseudomonas palustris employs both an MTA-isoprenoid shunt identical to that previously described in Rhodospirillum rubrum and a second novel MSP, both of which generate a methanethiol intermediate. The additional R. palustris aerobic MSP, a dihydroxyacetone phosphate (DHAP)-methanethiol shunt, initially converts MTA to 2-(methylthio)ethanol and DHAP. This is identical to the initial steps of the recently reported anaerobic ethylene-forming MSP, the DHAP-ethylene shunt. The aerobic DHAP-methanethiol shunt then further metabolizes 2-(methylthio)ethanol to methanethiol, which can be directly utilized by O-acetyl-l-homoserine sulfhydrylase to regenerate methionine. This is in contrast to the anaerobic DHAP-ethylene shunt, which metabolizes 2-(methylthio)ethanol to ethylene and an unknown organo-sulfur intermediate, revealing functional diversity in MSPs utilizing a 2-(methylthio)ethanol intermediate. When MTA was fed to aerobically growing cells, the rate of volatile methanethiol release was constant irrespective of the presence of sulfate, suggesting a general housekeeping function for these MSPs up through the methanethiol production step. Methanethiol and dimethyl sulfide (DMS), two of the most important compounds of the global sulfur cycle, appear to arise not only from marine ecosystems but from terrestrial ones as well. These results reveal a possible route by which methanethiol might be biologically produced in soil and freshwater environments. PMID:29636438

  15. Hyperthermophilic Archaeon Thermococcus kodakarensis Utilizes a Four-Step Pathway for NAD+ Salvage through Nicotinamide Deamination.

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    Hachisuka, Shin-Ichi; Sato, Takaaki; Atomi, Haruyuki

    2018-06-01

    Many organisms possess pathways that regenerate NAD + from its degradation products, and two pathways are known to salvage NAD + from nicotinamide (Nm). One is a four-step pathway that proceeds through deamination of Nm to nicotinic acid (Na) by Nm deamidase and phosphoribosylation to nicotinic acid mononucleotide (NaMN), followed by adenylylation and amidation. Another is a two-step pathway that does not involve deamination and directly proceeds with the phosphoribosylation of Nm to nicotinamide mononucleotide (NMN), followed by adenylylation. Judging from genome sequence data, the hyperthermophilic archaeon Thermococcus kodakarensis is supposed to utilize the four-step pathway, but the fact that the adenylyltransferase encoded by TK0067 recognizes both NMN and NaMN also raises the possibility of a two-step salvage mechanism. Here, we examined the substrate specificity of the recombinant TK1676 protein, annotated as nicotinic acid phosphoribosyltransferase. The TK1676 protein displayed significant activity toward Na and phosphoribosyl pyrophosphate (PRPP) and only trace activity with Nm and PRPP. We further performed genetic analyses on TK0218 (quinolinic acid phosphoribosyltransferase) and TK1650 (Nm deamidase), involved in de novo biosynthesis and four-step salvage of NAD + , respectively. The ΔTK0218 mutant cells displayed growth defects in a minimal synthetic medium, but growth was fully restored with the addition of Na or Nm. The ΔTK0218 ΔTK1650 mutant cells did not display growth in the minimal medium, and growth was restored with the addition of Na but not Nm. The enzymatic and genetic analyses strongly suggest that NAD + salvage in T. kodakarensis requires deamination of Nm and proceeds through the four-step pathway. IMPORTANCE Hyperthermophiles must constantly deal with increased degradation rates of their biomolecules due to their high growth temperatures. Here, we identified the pathway that regenerates NAD + from nicotinamide (Nm) in the

  16. Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenberg, Johannes [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Medical University of Vienna, Department of Pediatrics, Vienna (Austria); Radu, Caius G.; Tran, Andrew Q.; Phelps, Michael E.; Satyamurthy, Nagichettiar [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, Los Angeles, CA (United States); Benz, Matthias; Fueger, Barbara; Czernin, Johannes; Schiepers, Christiaan [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Witte, Owen N. [David Geffen School of Medicine, University of California, Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, CA (United States)

    2011-04-15

    Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo. PET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times. Renal excretion was common to all three probes. Bone marrow had higher uptake for L-{sup 18}F-FAC and L-{sup 18}F-FMAC than {sup 18}F-FAC. Prominent liver uptake was seen in L-{sup 18}F-FMAC and L-{sup 18}F-FAC, whereas splenic activity was highest for {sup 18}F-FAC. Muscle uptake was also highest for {sup 18}F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, respectively. The biodistribution of {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe

  17. Salvage radiation therapy following radical prostatectomy. A national Danish study

    DEFF Research Database (Denmark)

    Ervandian, Maria; Høyer, Morten; Petersen, Stine Elleberg

    2015-01-01

    BACKGROUND: The purpose of this observational cohort study was to evaluate the outcome and prognostic factors following salvage radiotherapy (SRT) in a consecutive national cohort. MATERIAL AND METHODS: Between 2006 and 2010, 259 patients received SRT in Denmark. Patient- and cancer-related chara...

  18. Methionine salvage pathway in relation to ethylene biosynthesis

    International Nuclear Information System (INIS)

    Miyazaki, J.H.

    1987-01-01

    The recycling of methionine during ethylene biosynthesis (the methionine cycle) was studied. During ethylene biosynthesis, the H 3 CS-group of S-adenosylmethionine (SAM) is released at 5'-methylthioadenosine (MTA), which is recycled to methionine via 5'-methylthioribose (MTS). In mungbean hypocotyls and cell-free extracts of avocado fruit, [ 14 C]MTR was converted to labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB) as intermediates. Radioactive tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract required an amino group donor. Among several potential donors tested, L-glutamine was the most efficient. Incubation of [ribose-U- 14 C]MTR with avocado extract resulted in the production of [ 14 C]formate, with little evolution of other 14 C-labeled one-carbon compounds, indicating that the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR

  19. Salvage and storage of infectious disease protein targets in the SSGCID high-throughput crystallization pathway using microfluidics

    International Nuclear Information System (INIS)

    Christensen, Jeff; Gerdts, Cory J.; Clifton, Mathew C.; Stewart, Lance

    2011-01-01

    SSGCID protein crystals were salvaged and stored using the MPCS Plug Maker and CrystalCards when high-throughput traditional sitting-drop vapor diffusion initially failed. The MPCS Plug Maker is a microcapillary-based protein-crystallization system for generating diffraction-ready crystals from nanovolumes of protein. Crystallization screening using the Plug Maker was used as a salvage pathway for proteins that failed to crystallize during the initial observation period using the traditional sitting-drop vapor-diffusion method. Furthermore, the CrystalCards used to store the crystallization experiments set up by the Plug Maker are shown be a viable container for long-term storage of protein crystals without a discernable loss of diffraction quality with time. Use of the Plug Maker with SSGCID proteins is demonstrated to be an effective crystal-salvage and storage method

  20. Clinical study of salvage surgery after concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    Shimane, Toshikazu; Nakamura, Taisuke; Shimotatara, Yuko

    2013-01-01

    As the use of concurrent chemoradiotherapy (CCRT) is becoming more widespread, with numerous facilities performing it to maintain function and form, the number of cases requiring salvage surgery is also increasing. We investigated the postoperative prognosis of patients who experienced complications during salvage surgery after CCRT. Subjects were 27 patients who underwent salvage surgery following CCRT at our department during the 7-year period between January 2005 and December 2011. We selected all cases of salvage surgery, comprising neck dissections, total laryngectomies, partial laryngectomies, esophageal resections, and reconstructive surgeries, for analysis. The results were favorable, with a complication rate during salvage surgery after CCRT of 14.8% and a survival rate of 77.8%. Although it is difficult to compare these complications and outcome findings with available reports on salvage surgery without CCRT, it is believed complications can arise in approximately half of the cases. Thus, surgeons should be cognizant of the potential for serious complications, which are sometimes unexpected. Different from our findings, the prognosis following salvage surgery is generally not thought to be favorable and therefore care should be taken to detect recurrence and provide treatment early in salvage surgery cases. (author)

  1. 1+1 = 3: a fusion of 2 enzymes in the methionine salvage pathway of Tetrahymena thermophila creates a trifunctional enzyme that catalyzes 3 steps in the pathway.

    Directory of Open Access Journals (Sweden)

    Hannah M W Salim

    2009-10-01

    Full Text Available The methionine salvage pathway is responsible for regenerating methionine from its derivative, methylthioadenosine. The complete set of enzymes of the methionine pathway has been previously described in bacteria. Despite its importance, the pathway has only been fully described in one eukaryotic organism, yeast. Here we use a computational approach to identify the enzymes of the methionine salvage pathway in another eukaryote, Tetrahymena thermophila. In this organism, the pathway has two fused genes, MTNAK and MTNBD. Each of these fusions involves two different genes whose products catalyze two different single steps of the pathway in other organisms. One of the fusion proteins, mtnBD, is formed by enzymes that catalyze non-consecutive steps in the pathway, mtnB and mtnD. Interestingly the gene that codes for the intervening enzyme in the pathway, mtnC, is missing from the genome of Tetrahymena. We used complementation tests in yeast to show that the fusion of mtnB and mtnD from Tetrahymena is able to do in one step what yeast does in three, since it can rescue yeast knockouts of mtnB, mtnC, or mtnD. Fusion genes have proved to be very useful in aiding phylogenetic reconstructions and in the functional characterization of genes. Our results highlight another characteristic of fusion proteins, namely that these proteins can serve as biochemical shortcuts, allowing organisms to completely bypass steps in biochemical pathways.

  2. Psychosocial reactions to upper extremity limb salvage: A cross-sectional study.

    Science.gov (United States)

    Sposato, Lindsay; Yancosek, Kathleen; Lospinoso, Josh; Cancio, Jill

    2017-08-09

    Descriptive cross-sectional survey study. Limb salvage spares an extremity at risk for amputation after a major traumatic injury. Psychosocial recovery for individuals with lower extremity limb salvage has been discussed in the literature. However, to date, psychosocial reactions for individuals with upper extremity (UE) limb salvage have not been examined. To determine which factors may influence psychosocial adaptation to UE limb salvage. Participants (n = 30; 28 males) were adults (mean, 30.13; range, 18-61) who sustained an UE limb salvage from a traumatic event. Adaptation was measured using a modified version of the Reactions to Impairment and Disability Inventory. A linear mixed-effects regression found that worse psychosocial adaptation was associated with having less than a college degree, being less than 6 months post-injury, being older than 23 years, and having more pain. Dominant hand injuries were found to influence poor adaptation on the denial Reactions to Impairment and Disability Inventory subscale only. The results of this study indicate that there is potential for nonadaptive reactions and psychological distress with certain variables in UE limb salvage. Therapists may use these results to anticipate which clients may be at risk for poor psychosocial outcomes. This study indicates the need for early consideration to factors that affect psychological prognosis for the UE limb salvage population. However, future research is indicated to better understand the unique psychosocial challenges and needs of these individuals. 4. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  3. Y-12 old salvage yard scrap metal characterization study

    International Nuclear Information System (INIS)

    Anderson, L.M.; Melton, S.G.; Shaw, S.S.

    1993-11-01

    The purpose of the Y-12 Old Salvage Yard scrap metal Characterization Study is to make conservative estimates of the quantities of total uranium and the wt % 235 U contained in scrap metal. The original project scope included estimates of thorium, but due to the insignificant quantities found in the yards, thorium was excluded from further analysis. Metal in three of the four Y-12 scrap metal yards were characterized. The scrap metal yard east of the PIDAS fence is managed by the Environmental Restoration Program and therefore was not included in this study. For all Y-12 Plant scrap metal shipments, Waste Transportation, Storage, and Disposal (WTSD) personnel must complete a Request for Authorization to Ship Nuclear Materials, UCN-16409, which requires the grams of total uranium, the wt % 235 U, and the grams of 235 U contained in the shipment. This information is necessary to ensure compliance with Department of Transportation regulations, as well as to ensure that the receiving facility is adhering to its operating license. This characterization study was designed to provide a technical basis for determining these necessary radioactive quantities

  4. Metabolic engineering of Escherichia coli to produce 2'-fucosyllactose via salvage pathway of guanosine 5'-diphosphate (GDP)-l-fucose.

    Science.gov (United States)

    Chin, Young-Wook; Seo, Nari; Kim, Jae-Han; Seo, Jin-Ho

    2016-11-01

    2'-Fucosyllactose (2-FL) is one of the key oligosaccharides in human milk. In the present study, the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway from fucose was employed in engineered Escherichia coli BL21star(DE3) for efficient production of 2-FL. Introduction of the fkp gene coding for fucokinase/GDP-l-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the fucT2 gene encoding α-1,2-fucosyltransferase from Helicobacter pylori allows the engineered E. coli to produce 2-FL from fucose, lactose and glycerol. To enhance the lactose flux to 2-FL production, the attenuated, and deleted mutants of β-galactosidase were employed. Moreover, the 2-FL yield and productivity were further improved by deletion of the fucI-fucK gene cluster coding for fucose isomerase (FucI) and fuculose kinase (FucK). Finally, fed-batch fermentation of engineered E. coli BL21star(DE3) deleting lacZ and fucI-fucK, and expressing fkp and fucT2 resulted in 23.1 g/L of extracellular concentration of 2-FL and 0.39 g/L/h productivity. Biotechnol. Bioeng. 2016;113: 2443-2452. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Characterization of an fungal l-fucokinase involved in Mortierella alpina GDP-l-fucose salvage pathway.

    Science.gov (United States)

    Wang, Hongchao; Zhang, Chen; Chen, Haiqin; Yang, Qin; Zhou, Xin; Gu, Zhennan; Zhang, Hao; Chen, Wei; Chen, Yong Q

    2016-08-01

    GDP-l-fucose functions as a biological donor for fucosyltransferases, which are required for the catalysis of l-fucose to various acceptor molecules including oligosaccharides, glycoproteins and glycolipids. Mortierella alpina is one of the highest lipid-producing fungi and can biosynthesis GDP-l-fucose in the de novo pathway. Analysis of the M. alpina genome suggests that there is a gene encoding l-fucokinase (FUK) for the conversion of fucose to l-fucose-1-phosphate in the GDP-l-fucose salvage pathway, which has never been found in fungi before. This gene was characterized to explore its role in GDP-l-fucose synthesis. The yield of GDP-l-fucose is relatively higher in lipid accumulation phase (0.096 mg per g cell) than that in cell multiplication phase (0.074 mg per g cell) of M. alpina Additionally, the transcript level of FUK is up regulated by nitrogen exhaustion when M. alpina starts to accumulate lipid, highlights the functional significance of FUK in the GDP-l-fucose biosynthesis in M. alpina Gene encoding FUK was expressed heterologously in Escherichia coli and the resulting protein was purified to homogeneity. The product of FUK reaction was analyzed by liquid chromatography and mass spectrometry. Kinetic parameters and other properties of FUK were investigated. Comparative analyses between the FUK protein and other homologous proteins were performed. To our knowledge, this study is the first to report a comprehensive characterization of FUK in a fungus. Mortierella alpina could be used as an alternative source for the production of GDP-l-fucose. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. The vascularised fibular graft for limb salvage after bone tumour surgery A MULTICENTRE STUDY

    NARCIS (Netherlands)

    Hilven, P. H.; Bayliss, L.; Cosker, T.; Dijkstra, P. D. S.; Jutte, P. C.; Lahoda, L. U.; Schaap, G. R.; Bramer, J. A. M.; van Drunen, G. K.; Strackee, S. D.; van Vooren, J.; Gibbons, M.; Giele, H.; van de Sande, M. A. J.

    2015-01-01

    Vascularised fibular grafts (VFGs) are a valuable surgical technique in limb salvage after resection of a tumour. The primary objective of this multicentre study was to assess the risk factors for failure and complications for using a VFG after resection of a tumour. The study involved 74

  7. Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1).

    Science.gov (United States)

    Harlan, Benjamin A; Pehar, Mariana; Sharma, Deep R; Beeson, Gyda; Beeson, Craig C; Vargas, Marcelo R

    2016-05-13

    Nicotinamide adenine dinucleotide (NAD(+)) participates in redox reactions and NAD(+)-dependent signaling pathways. Although the redox reactions are critical for efficient mitochondrial metabolism, they are not accompanied by any net consumption of the nucleotide. On the contrary, NAD(+)-dependent signaling processes lead to its degradation. Three distinct families of enzymes consume NAD(+) as substrate: poly(ADP-ribose) polymerases, ADP-ribosyl cyclases (CD38 and CD157), and sirtuins (SIRT1-7). Because all of the above enzymes generate nicotinamide as a byproduct, mammalian cells have evolved an NAD(+) salvage pathway capable of resynthesizing NAD(+) from nicotinamide. Overexpression of the rate-limiting enzyme in this pathway, nicotinamide phosphoribosyltransferase, increases total and mitochondrial NAD(+) levels in astrocytes. Moreover, targeting nicotinamide phosphoribosyltransferase to the mitochondria also enhances NAD(+) salvage pathway in astrocytes. Supplementation with the NAD(+) precursors nicotinamide mononucleotide and nicotinamide riboside also increases NAD(+) levels in astrocytes. Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Superoxide dismutase 1 (SOD1) mutations account for up to 20% of familial ALS and 1-2% of apparently sporadic ALS cases. Primary astrocytes isolated from mutant human superoxide dismutase 1-overexpressing mice as well as human post-mortem ALS spinal cord-derived astrocytes induce motor neuron death in co-culture. Increasing total and mitochondrial NAD(+) content in ALS astrocytes increases oxidative stress resistance and reverts their toxicity toward co-cultured motor neurons. Taken together, our results suggest that enhancing the NAD(+) salvage pathway in astrocytes could be a potential therapeutic target to prevent astrocyte-mediated motor neuron death in ALS. © 2016 by The American Society for Biochemistry and Molecular

  8. Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1)*

    Science.gov (United States)

    Harlan, Benjamin A.; Pehar, Mariana; Sharma, Deep R.; Beeson, Gyda; Beeson, Craig C.; Vargas, Marcelo R.

    2016-01-01

    Nicotinamide adenine dinucleotide (NAD+) participates in redox reactions and NAD+-dependent signaling pathways. Although the redox reactions are critical for efficient mitochondrial metabolism, they are not accompanied by any net consumption of the nucleotide. On the contrary, NAD+-dependent signaling processes lead to its degradation. Three distinct families of enzymes consume NAD+ as substrate: poly(ADP-ribose) polymerases, ADP-ribosyl cyclases (CD38 and CD157), and sirtuins (SIRT1–7). Because all of the above enzymes generate nicotinamide as a byproduct, mammalian cells have evolved an NAD+ salvage pathway capable of resynthesizing NAD+ from nicotinamide. Overexpression of the rate-limiting enzyme in this pathway, nicotinamide phosphoribosyltransferase, increases total and mitochondrial NAD+ levels in astrocytes. Moreover, targeting nicotinamide phosphoribosyltransferase to the mitochondria also enhances NAD+ salvage pathway in astrocytes. Supplementation with the NAD+ precursors nicotinamide mononucleotide and nicotinamide riboside also increases NAD+ levels in astrocytes. Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Superoxide dismutase 1 (SOD1) mutations account for up to 20% of familial ALS and 1–2% of apparently sporadic ALS cases. Primary astrocytes isolated from mutant human superoxide dismutase 1-overexpressing mice as well as human post-mortem ALS spinal cord-derived astrocytes induce motor neuron death in co-culture. Increasing total and mitochondrial NAD+ content in ALS astrocytes increases oxidative stress resistance and reverts their toxicity toward co-cultured motor neurons. Taken together, our results suggest that enhancing the NAD+ salvage pathway in astrocytes could be a potential therapeutic target to prevent astrocyte-mediated motor neuron death in ALS. PMID:27002158

  9. The outcome of rectal cancer after early salvage TME following TEM compared with primary TME: a case-matched study.

    Science.gov (United States)

    Levic, K; Bulut, O; Hesselfeldt, P; Bülow, S

    2013-08-01

    Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In case of unfavourable histology after TEM, or positive resection margins, salvage surgery can be performed. However, it is unclear if the results are equivalent to primary treatment with total mesorectal excision (TME). The aim of this retrospective study was to determine whether there is a difference in outcome between patients who underwent early salvage resection with TME after TEM, and those who underwent primary TME for rectal cancer. From 1997 to 2011, early salvage surgery with TME after TEM was performed in 25 patients in our institution. These patients were compared with 25 patients who underwent primary TME, matched according to gender, age (±2 years), cancer stage and operative procedure. Data were obtained from the patients' charts and reviewed retrospectively. No patients received preoperative chemotherapy. Perioperative data and oncological outcome were analysed. The Mann-Whitney U-test and Fisher's exact test were used to compare the results between the two groups. There was no significant difference between the two groups in median operating time (P = 0.39), median blood loss (P = 0.19) or intraoperative complications (P = 1.00). The 30-day mortality was 8 % (n = 2) among patients who underwent salvage TME after TEM, and no patients died in the primary TME group (P = 0.49). There was no significant difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8 %) with local recurrences among the patients with primary TME (P = 0.49). Distant metastasis occurred in one patient (4 %) after salvage TME and in 3 patients (12 %) with primary TME (P = 0.61). The median

  10. TEXTILE SALVAGE

    CERN Multimedia

    Relations with the Host States Service

    2002-01-01

    Readers are reminded that Geneva's agency for salvaging used clothing, other textiles and old shoes (Coordination d'oeuvres d'entraide pour la récupération de vêtements, textiles et chaussures usagés dans le canton de Genève) has a container in the car park outside CERN's Meyrin site. In 2001, 1000 tonnes of such items were collected in the Canton of Geneva (as compared with 840 tonnes in 2000), of which 4460 kg came from the container outside the Meyrin site. The operation's organisers (Caritas, Centre Social Protestant, the Geneva Section of the Swiss Red Cross, Terre des Hommes, the Geneva branch of Terre des Hommes Suisse and Emmaüs, Geneva) would like to thank all those who have donated clothing or otherwise supported their campaign. Relations with the Host States Service Tel. 72848 http://www.cern.ch/relations/

  11. Molecular cloning of a novel glucuronokinase/putative pyrophosphorylase from zebrafish acting in an UDP-glucuronic acid salvage pathway.

    Directory of Open Access Journals (Sweden)

    Roman Gangl

    Full Text Available In animals, the main precursor for glycosaminoglycan and furthermore proteoglycan biosynthesis, like hyaluronic acid, is UDP-glucuronic acid, which is synthesized via the nucleotide sugar oxidation pathway. Mutations in this pathway cause severe developmental defects (deficiency in the initiation of heart valve formation. In plants, UDP-glucuronic acid is synthesized via two independent pathways. Beside the nucleotide sugar oxidation pathway, a second minor route to UDP-glucuronic acid exist termed the myo-inositol oxygenation pathway. Within this myo-inositol is ring cleaved into glucuronic acid, which is subsequently converted to UDP-glucuronic acid by glucuronokinase and UDP-sugar pyrophosphorylase. Here we report on a similar, but bifunctional enzyme from zebrafish (Danio rerio which has glucuronokinase/putative pyrophosphorylase activity. The enzyme can convert glucuronic acid into UDP-glucuronic acid, required for completion of the alternative pathway to UDP-glucuronic acid via myo-inositol and thus establishes a so far unknown second route to UDP-glucuronic acid in animals. Glucuronokinase from zebrafish is a member of the GHMP-kinase superfamily having unique substrate specificity for glucuronic acid with a Km of 31 ± 8 µM and accepting ATP as the only phosphate donor (Km: 59 ± 9 µM. UDP-glucuronic acid pyrophosphorylase from zebrafish has homology to bacterial nucleotidyltransferases and requires UTP as nucleosid diphosphate donor. Genes for bifunctional glucuronokinase and putative UDP-glucuronic acid pyrophosphorylase are conserved among some groups of lower animals, including fishes, frogs, tunicates, and polychaeta, but are absent from mammals. The existence of a second pathway for UDP-glucuronic acid biosynthesis in zebrafish likely explains some previous contradictory finding in jekyll/ugdh zebrafish developmental mutants, which showed residual glycosaminoglycans and proteoglycans in knockout mutants of UDP

  12. A Longitudinal Study of Functional Outcomes in Patients with Limb Salvage Surgery for Soft Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Eunsun Oh

    2018-01-01

    Full Text Available Background. Many studies have reported on the surgical outcomes of soft tissue sarcoma. However, there was no longitudinal cohort study. Because time is the most valuable factor for functional recovery, adjusting time value was the key for finding the causal relationship between other risk factors and postoperative function. Therefore, existing cross-sectional studies can neither fully explain the causal relationship between the risk factors and the functional score nor predict functional recovery. The aim of this study was to determine important predictive factors that affect postoperative functional outcomes and longitudinal changes in functional outcomes in patients who had undergone limb-sparing surgery (LSS for soft tissue sarcoma (STS. Methods. Between January 2008 and December 2014, we retrospectively enrolled 150 patients who had undergone LSS for STS and had been assessed for postoperative functional outcomes with questionnaires. To evaluate functional outcomes, we used the Musculoskeletal Tumor Society (MSTS score and Toronto Extremity Salvage Score (TESS. Multivariate generalized estimating equation (GEE analysis was used to identify the predictive factors, including size, stage, and anatomic location of tumor, bone resection, flap reconstruction, age, and time after surgery. Each continuous variable such as age and time after surgery was explored for statistically significant cutoff points using the Wilcoxon rank sum test. Results. Functional scores significantly improved until the second year after surgery and plateaued for the rest of the 5-year period. Age p<0.0001, bone resection p=0.0004, and time after surgery p<0.0001 were identified as significant predictive factors. The functional score was significantly higher in patients younger than 47 years old. Conclusions. Functional outcomes can improve until the second year after surgery. Patients who were older than 47 and underwent bone resection may have poor final functional

  13. Timber salvage economics

    Science.gov (United States)

    Jeffrey P. Prestemon; Thomas P. Holmes

    2008-01-01

    Timber salvage is commonly done following natural disturbances, to recover some value from damaged forests. Decision making about salvage, however, is affected by ownership objectives, the nature of the damage agent, site factors, and the strength of the local timber market. For profit-maximizing landowners, salvage decisions must balance the cost of harvesting...

  14. Is Salvage of Recently Infected Breast Implant After Breast Augmentation or Reconstruction Possible? An Experimental Study.

    Science.gov (United States)

    Castus, P; Heymans, O; Melin, P; Renwart, L; Henrist, C; Hayton, E; Mordon, S; Leclère, F M

    2018-04-01

    could allow reinsertion of an infected implant when peri-prosthetic infection occurs early after breast augmentation or breast reconstruction and when a salvage procedure is indicated. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  15. Salvage robotic radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Samuel D Kaffenberger

    2014-01-01

    Full Text Available Failure of non-surgical primary treatment for localized prostate cancer is a common occurrence, with rates of disease recurrence ranging from 20% to 60%. In a large proportion of patients, disease recurrence is clinically localized and therefore potentially curable. Unfortunately, due to the complex and potentially morbid nature of salvage treatment, radical salvage surgery is uncommonly performed. In an attempt to decrease the morbidity of salvage therapy without sacrificing oncologic efficacy, a number of experienced centers have utilized robotic assistance to perform minimally invasive salvage radical prostatectomy. Herein, we critically evaluate the existing literature on salvage robotic radical prostatectomy with a focus on patient selection, perioperative complications and functional and early oncologic outcomes. These results are compared with contemporary and historical open salvage radical prostatectomy series and supplemented with insights we have gained from our experience with salvage robotic radical prostatectomy. The body of evidence by which conclusions regarding the efficacy and safety of robotic salvage radical prostatectomy can be drawn comprises fewer than 200 patients with limited follow-up. Preliminary results are promising and some outcomes have been favorable when compared with contemporary open salvage prostatectomy series. Advantages of the robotic platform in the performance of salvage radical prostatectomy include decreased blood loss, short length of stay and improved visualization. Greater experience is required to confirm the long-term oncologic efficacy and functional outcomes as well as the generalizability of results achieved at experienced centers.

  16. A Comparison of Four Year Health Outcomes following Combat Amputation and Limb Salvage

    Science.gov (United States)

    2017-01-25

    pathways that address the physical and psychological healthcare needs of such patients over time. Introduction Previous studies indicated that extremity...patients, there is a need to quan- tify and compare long-term health outcomes following amputation and limb salvage. A recent study followed the...and psychological complications. Wound complications. Wound complications selected for study were those that required prolonged surveillance

  17. Ecosystem Nitrogen Retention Following Severe Bark Beetle and Salvage Logging Disturbance in Lodgepole Pine Forests: a 15N Enrichment Study

    Science.gov (United States)

    Avera, B.; Rhoades, C.; Paul, E. A.; Cotrufo, M. F.

    2017-12-01

    In recent decades, bark beetle outbreaks have caused high levels of tree mortality in lodgepole pine (Pinus contorta) dominated forests across western North America. Previous work has found increased soil mineral nitrogen (N) with tree mortality in beetle infested stands, but surprisingly little change in stream N export. These findings suggest an important role of residual live vegetation and altered soil microbial response for retaining surplus N and mitigating N losses from disturbed lodgepole forests. Post outbreak salvage of merchantable timber reduces fuel levels and promotes tree regeneration; however, the implications of the combined bark beetle and harvesting disturbances on ecosystem N retention and productivity are uncertain. To advance understanding of post-disturbance N retention we compare unlogged beetle-infested forests and salvage logged stands with post-harvest woody residue retention or removal. We applied 15N-labeled (2 atom%) and natural abundance ammonium sulfate to eight year old lodgepole pine seedlings in three replicate plots of the three forest management treatments. This approach allows us to quantify the relative contributions of N retention in soil, microbial biomass, and plant tissue. Our study targets gaps in understanding of the processes that regulate N utilization and transfer between soil and vegetation that result in effective N retention in lodgepole pine ecosystems. These findings will also help guide forest harvest and woody residue management practices in order to maintain soil productivity.

  18. Salvage central lymphatic irradiation in follicular lymphomas following failure of chemotherapy: a feasibility study

    International Nuclear Information System (INIS)

    Ha, Chul S.; Tucker, Susan L.; Blanco, Angel I.; Cabanillas, Fernando; Cox, James D.

    1999-01-01

    Purpose: Management of follicular lymphoma after chemotherapy failure has been controversial and has ranged from watchful waiting to high-dose chemotherapy. High-dose chemotherapy with bone marrow reconstitution may produce clinical and molecular complete responses at the risk of serious morbidity and mortality. It has been previously reported that central lymphatic irradiation (CLI) can achieve long-term relapse-free survival in patients with Stage I, II, or III follicular lymphoma. Therefore, we investigated the feasibility of treating patients in whom front-line chemotherapy failed with salvage CLI instead of instituting more intensive chemotherapy. Methods and Materials: Salvage CLI with curative intent for patients with follicular lymphoma was started at The University of Texas M. D. Anderson Cancer Center in 1992. Eleven patients whose disease showed poor response to or relapsed after chemotherapy were managed with this approach. The median age of the patients was 61 years. Criteria for exclusion included bone marrow involvement or other evidence of Ann Arbor Stage IV disease at any time during the course of the disease. Overall survival and relapse-free survival were calculated from the first day of CLI. Results: Ten patients were alive at a median follow-up of 25 months (range 9-73 months). The treatment was well tolerated in general. Two patients could not complete CLI: one 75-year-old patient owing to prolonged platelet count depression and deterioration in general medical condition, and a 66-year-old patient because of exacerbation of preexisting pancytopenia and worsening of heart disease. Everyone who completed CLI remains in remission at the time of this report, except for one patient who had a relapse in the right lacrimal gland at 32 months. This patient was treated with local radiation therapy and is free of disease. Eventual recovery of the blood counts was observed for the patients who completed CLI. Conclusion: These results demonstrate for the

  19. Synthesizing and salvaging NAD: lessons learned from Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Huawen Lin

    2010-09-01

    Full Text Available The essential coenzyme nicotinamide adenine dinucleotide (NAD+ plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis, as in plants, or nicotinamide, as in mammals (salvage synthesis. The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO, quinolinate synthetase (QS, quinolate phosphoribosyltransferase (QPT, nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT, and NAD+ synthetase (NS. Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1 or plasmids with cloned genes (nic1-1 and nic15-1 into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1 has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity.

  20. Proposed salvage treatment strategy for biochemical failure after radical prostatectomy in patients with prostate cancer: a retrospective study

    International Nuclear Information System (INIS)

    Miyake, Makito; Tanaka, Nobumichi; Asakawa, Isao; Morizawa, Yosuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

    2014-01-01

    Treatment options for patients with recurrent disease after radical prostatectomy include salvage radiotherapy of the prostatic bed and/or androgen deprivation therapy. To establish an effective treatment strategy for recurrent disease after radical prostatectomy, we retrospectively analyzed the outcome of salvage radiation monotherapy in such cases. Data from 61 men who had undergone salvage radiation monotherapy for biochemical recurrent disease after radical prostatectomy were retrospectively reviewed. In all patients, salvage radiotherapy consisted of iraradiation to the prostatic bed (70 Gy) using three-dimensional conformal radiotherapy techniques. Treatment outcome was analyzed to identify predictive factors of salvage radiotherapy. The biochemical recurrence-free survival after salvage radiation monotherapy at 2 and 5 years was 55% and 38%, respectively. Cox proportional regression models revealed that the independent predictive factors for biochemical recurrence were Gleason Score ≥ 8, negative surgical margin, and PSA velocity ≥ 0.38 ng/mL/year. Negative surgical margin and PSA velocity ≥ 0.8 ng/mL/year were significantly associated with poor response in the serum PSA levels after salvage radiotherapy. Based on our findings, we propose a treatment strategy for biochemical recurrent disease after radical prostatectomy. Patients with Gleason score ≤ 7, positive surgical margin, and PSA velocity < 0.38 ng/mL/year are categorized the most favorable group, so that eradication by salvage radiation monotherapy could be expected. Other patients could be divided to two groups depending on surgical margin status and PSA velocity: 1) patients who might require combination of SRT and short-term androgen deprivation therapy and 2) patients who should be treated by androgen deprivation monotherapy

  1. Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

    International Nuclear Information System (INIS)

    Taguchi, Satoru; Shiraishi, Kenshiro; Fukuhara, Hiroshi; Nakagawa, Keiichi; Morikawa, Teppei; Naito, Akihiro; Kakutani, Shigenori; Takeshima, Yuta; Miyazaki, Hideyo; Nakagawa, Tohru; Fujimura, Tetsuya; Kume, Haruki; Homma, Yukio

    2016-01-01

    The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL

  2. Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction - a pilot study.

    Science.gov (United States)

    Chitose, Tadasuke; Sugiyama, Seigo; Sakamoto, Kenji; Shimomura, Hideki; Yamashita, Takuro; Hokamaki, Jun; Tsunoda, Ryusuke; Shiraishi, Shinya; Yamashita, Yasuyuki; Ogawa, Hisao

    2014-11-01

    Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI). Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with (123-)I-β-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI: AAR) and (201-)thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR-AAI) × 100/AAR (%)]. Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (-53.3% ± 48.8% versus -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01). Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with

  3. Salvage Stereotactic Reirradiation With or Without Cetuximab for Locally Recurrent Head-and-Neck Cancer: A Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Comet, Benedicte [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France); Kramar, Andrew [Department of Statistical Analysis, Centre Oscar Lambret and University Lille II, Lille (France); Faivre-Pierret, Mathieu [Department of Radiology, Centre Oscar Lambret and University Lille II, Lille (France); Dewas, Sylvain; Coche-Dequeant, Bernard [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France); Degardin, Marian; Lefebvre, Jean-Louis [Department of Head and Neck Surgery, Centre Oscar Lambret and University Lille II, Lille (France); Lacornerie, Thomas [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France); Lartigau, Eric F., E-mail: e-lartigau@o-lambret.fr [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France)

    2012-09-01

    Purpose: Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC. Methods and Materials: Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab. Results: Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients. Conclusion: These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.

  4. Salvage Stereotactic Reirradiation With or Without Cetuximab for Locally Recurrent Head-and-Neck Cancer: A Feasibility Study

    International Nuclear Information System (INIS)

    Comet, Bénédicte; Kramar, Andrew; Faivre-Pierret, Mathieu; Dewas, Sylvain; Coche-Dequeant, Bernard; Degardin, Marian; Lefebvre, Jean-Louis; Lacornerie, Thomas; Lartigau, Eric F.

    2012-01-01

    Purpose: Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC. Methods and Materials: Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab. Results: Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients. Conclusion: These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.

  5. Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

    Directory of Open Access Journals (Sweden)

    Viale Giuseppe

    2008-07-01

    Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

  6. Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.

    Science.gov (United States)

    Alsuliman, Tamim; Kitel, Caroline; Dulery, Rémy; Guillaume, Thierry; Larosa, Fabrice; Cornillon, Jérôme; Labussière-Wallet, Helene; Médiavilla, Clémence; Belaiche, Stéphanie; Delage, Jeremy; Alain, Sophie; Yakoub-Agha, Ibrahim

    2018-04-13

    Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.

  7. Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

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    Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Agrawal, Shree [Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Koontz, Bridget F. [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Efstathiou, Jason A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abramowitz, Matthew C.; Pollack, Alan [Department of Radiation Oncology, University of Miami, Miami, Florida (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Moghanaki, Drew [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia (United States); Den, Robert B. [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Stephans, Kevin L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lee, W. Robert [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Kattan, Michael W. [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States); and others

    2016-12-01

    Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

  8. Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

    International Nuclear Information System (INIS)

    Pisansky, Thomas M.; Agrawal, Shree; Hamstra, Daniel A.; Koontz, Bridget F.; Liauw, Stanley L.; Efstathiou, Jason A.; Michalski, Jeff M.; Feng, Felix Y.; Abramowitz, Matthew C.; Pollack, Alan; Anscher, Mitchell S.; Moghanaki, Drew; Den, Robert B.; Stephans, Kevin L.; Zietman, Anthony L.; Lee, W. Robert; Kattan, Michael W.

    2016-01-01

    Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

  9. Efficacy of Salvage Interferential Electrical Stimulation Therapy in Patients With Medication-Refractory Enuresis: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Hahn-Ey Lee

    2013-09-01

    Full Text Available Purpose In pediatric patients with enuresis, the protocol for salvage therapy in patients in whom first-line therapy was not successful has not yet been established. Interferential electrical stimulation (IF-ES therapy is advantageous because it is noninvasive and shows high compliance. We aimed to investigate the efficacy and safety of IF-ES therapy on pediatric enuresis in a pilot study. Methods We investigated 10 patients who underwent IF-ES therapy between August 2012 and March 2013 at our clinic. Patients with a history of previous treatment with desmopressin and anticholinergic agents for at least 3 months and those in whom alarm treatment previously failed or was refused by parents were eligible. Electrical current was given starting at approximately 20 mA and was increased until the patient complained of discomfort. Treatment was performed once a week, 20 minutes per treatment, 6 times per cycle. After each cycle, an interview was performed and voiding diaries were filled. The physician in charge evaluated improvement according to the International Children's Continence Society criteria. Results A final analysis was performed in 10 patients (5 male and 5 female patients in whom therapy for nocturnal enuresis had failed. Eight patients had nonmonosymptomatic enuresis and 2 had monosymptomatic enuresis. The mean age of the patients was 8.5±2.4 years, and the mean number of treatments was 10.6±3.6 times. A full response was observed in 1 patient (10%; a good response, in 1 patient (10%; a partial response, in 7 patients (70%; and no response, in 1 patient (10%. Conclusions Our study demonstrated that IF-ES therapy can be a promising treatment for the future, is safe, and can benefit from appropriate clinical trials in carefully selected groups. IF-ES therapy is expected to be a safe and effective treatment modality for children with enuresis.

  10. Local recurrence risk after previous salvage mastectomy.

    Science.gov (United States)

    Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

    2016-07-01

    Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Limb salvage surgery.

    Science.gov (United States)

    Kadam, Dinesh

    2013-05-01

    The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

  12. Limb salvage surgery

    Directory of Open Access Journals (Sweden)

    Dinesh Kadam

    2013-01-01

    Full Text Available The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

  13. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study.

    Science.gov (United States)

    Cuneo, Antonio; Follows, George; Rigolin, Gian Matteo; Piciocchi, Alfonso; Tedeschi, Alessandra; Trentin, Livio; Medina Perez, Angeles; Coscia, Marta; Laurenti, Luca; Musuraca, Gerardo; Farina, Lucia; Rivas Delgado, Alfredo; Orlandi, Ester Maria; Galieni, Piero; Mauro, Francesca Romana; Visco, Carlo; Amendola, Angela; Billio, Atto; Marasca, Roberto; Chiarenza, Annalisa; Meneghini, Vittorio; Ilariucci, Fiorella; Marchetti, Monia; Molica, Stefano; Re, Francesca; Gaidano, Gianluca; Gonzalez, Marcos; Forconi, Francesco; Ciolli, Stefania; Cortelezzi, Agostino; Montillo, Marco; Smolej, Lukas; Schuh, Anna; Eyre, Toby A; Kennedy, Ben; Bowles, Kris M; Vignetti, Marco; de la Serna, Javier; Moreno, Carol; Foà, Robin; Ghia, Paolo

    2018-04-19

    We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival was 74.5 months. Advanced Binet stage (i.e. III-IV or C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within named patient programs in the United Kingdom and in Italy was carried out with overall survival as objective endpoint. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, the overall survival did not differ between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in chronic lymphocytic leukemia in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of overall survival when used as first salvage treatment in patients without 17p deletion. ClinicalTrials.gov identifier: NCT02491398. Copyright © 2018, Ferrata Storti Foundation.

  14. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    Energy Technology Data Exchange (ETDEWEB)

    Swisher, Stephen G., E-mail: sswisher@mdanderson.org [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Winter, Kathryn A. [Headquarters, Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko U. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Wu, Tsung T. [Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Konski, Andre A. [Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Willett, Christopher G. [Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  15. Healthcare professionals' views of the use and administration of two salvage therapy drugs for acute ulcerative colitis: a nested qualitative study within the CONSTRUCT trial.

    Science.gov (United States)

    Clement, Clare; Rapport, Frances; Seagrove, Anne; Alrubaiy, Laith; Williams, John

    2017-02-22

    Insight into healthcare professionals' views and experiences of the use of ciclosporin and infliximab as salvage therapies for acute ulcerative colitis (UC) and how this may affect participation in a comparison trial is lacking. The study aimed to capture views and opinions of healthcare professionals about the two drugs within the CONSTRUCT trial. An interview-based qualitative study using Framework Analysis embedded within an open-label, pragmatic randomised trial. National Health Service Health Boards and Trusts, including large teaching and district hospitals in England, Scotland and Wales. Principal Investigators (PIs) for trial sites (who were all consultant gastroenterologists) and nurses responsible for administering and monitoring the salvage therapy drugs across trial sites. 15 PIs and 8 nurses recruited from a range of sites stratified by site recruitment rates were interviewed. Interviews revealed that professionals made judgements regarding the salvage therapies largely based on experience of giving the two drugs and perceptions of effectiveness and adverse side effects. A clear preference for infliximab among nurses was revealed, largely based on experiences of administration and drug handling, with some doctors strongly favouring infliximab based on experience of prescribing the drug as well as patient views and the existing evidence base. Most doctors were more equivocal, and all were prepared to suspend preferences and wait for evidence of effectiveness and safety from the CONSTRUCT trial. PIs also questioned guidelines around drug use and restrictions placed on personal autonomy in delivering best patient care. Findings highlight healthcare professionals' preference for the salvage treatment, infliximab in treating steroid-resistant UC, largely based on resource intensive nursing requirements of intravenous administration of ciclosporin. Not all doctors expressed this preference, being more equivocal, and all professionals were content to suspend

  16. Can Orthopedic Oncologists Predict Functional Outcome in Patients with Sarcoma after Limb Salvage Surgery in the Lower Limb? A Nationwide Study

    Directory of Open Access Journals (Sweden)

    Sjoerd Kolk

    2014-01-01

    Full Text Available Accurate predictions of functional outcome after limb salvage surgery (LSS in the lower limb are important for several reasons, including informing the patient preoperatively and, in some cases, deciding between amputation and LSS. This study aimed to elucidate the correlation between surgeon-predicted and patient-reported functional outcome of LSS in the Netherlands. Twenty-three patients (between six months and ten years after surgery and five independent orthopedic oncologists completed the Toronto Extremity Salvage Score (TESS and the RAND-36 physical functioning subscale (RAND-36 PFS. The orthopedic oncologists made their predictions based on case descriptions (including MRI scans that reflected the preoperative status. The correlation between patient-reported and surgeon-predicted functional outcome was “very poor” to “poor” on both scores (r2 values ranged from 0.014 to 0.354. Patient-reported functional outcome was generally underestimated, by 8.7% on the TESS and 8.3% on the RAND-36 PFS. The most difficult and least difficult tasks on the RAND-36 PFS were also the most difficult and least difficult to predict, respectively. Most questions had a “poor” intersurgeon agreement. It was difficult to accurately predict the patient-reported functional outcome of LSS. Surgeons’ ability to predict functional scores can be improved the most by focusing on accurately predicting more demanding tasks.

  17. Salvage versus amputation: Utility of mangled extremity severity score in severely injured lower limbs

    Directory of Open Access Journals (Sweden)

    Kumar M

    2007-01-01

    Full Text Available Background: The purpose of the present study was to evaluate the clinical utility of Mangled extremity severity score (MESS in severely injured lower limbs. Materials and Methods: Retrospectively 25 and prospectively 36 lower limbs in 58 patients with high-energy injuries were evaluated with the use of MESS, to assist in the decision-making process for the care of patients with such injuries. Difference between the mean MESS scores for amputated and salvaged limbs was analyzed. Results: In the retrospective study 4.65 (4.65 ± 1.32 was the mean score for the salvaged limbs and 8.80 (8.8 ± 1.4 for the amputated limbs. In the prospective study 4.53 (4.53 ± 2.44 was the mean score for the salvaged limbs and 8.83 (8.83 ± 2.34 for the amputated limbs. There was a significant difference in the mean scores for salvaged and amputated limbs. Retrospective 21 (84% and prospective 29 (80.5% limbs remained in the salvage pathway six months after the injury. Conclusion: MESS could predict amputation of severely injured lower limbs, having score of equal or more than 7 with 91% sensitivity and 98% specificity. There was a significant difference in the mean MESS scores in the prospective study (n=36, 4.53 (4.53 ± 2.44 in thirty salvaged limbs (83.33% and 8.83 (8.83 ± 2.34 in six amputated limbs (16.66% with a P -value 0.002 ( P -value < 0.01. Similarly there was a significant difference in the mean MESS score in the retrospective study (n=25, 4.65 (4.65 ± 1.32 in twenty salvaged limbs (80% and 8.80 (8.8 ± 1.4 in five amputated limbs (20% with a P -value 0.00005 ( P -value < 0.01. MESS is a simple and relatively easy and readily available scoring system which can help the surgeon to decide the fate of the lower extremity with a high-energy injury.

  18. Feasibility of salvage interstitial microwave thermal therapy for prostate carcinoma following failed brachytherapy: studies in a tissue equivalent phantom

    International Nuclear Information System (INIS)

    McCann, Claire; Kumaradas, J Carl; Gertner, Mark R; Davidson, Sean R H; Dolan, Alfred M; Sherar, Michael D

    2003-01-01

    Thermal therapy is an experimental treatment to destroy solid tumours by heating them to temperatures ranging from 55 deg C to 90 deg C, inducing thermal coagulation and necrosis of the tumour. We are investigating the feasibility of interstitial microwave thermal therapy as a salvage treatment for prostate cancer patients with local recurrence following failed brachytherapy. Due to the electrical and thermal conductivity of the brachytherapy seeds, we hypothesized that the seeds could scatter the microwave energy and cause unpredictable heating. To investigate this, a 915 MHz helical antenna was inserted into a muscle-equivalent phantom with and without brachytherapy seeds. Following a 10 W, 5 s input to the antenna, the temperature rise was used to calculate absorbed power, also referred to as specific absorption rate (SAR). Plane wave models based on Maxwell's equations were also used to characterize the electromagnetic scattering effect of the seeds. In addition, the phantom was heated with 8 W for 5 min to quantify the effect of the seeds on the temperature distribution during extended heating. SAR measurements indicated that the seeds had no significant effect on the shape and size of the SAR pattern of the antenna. However, the plane wave simulations indicated that the seeds could scatter the microwave energy resulting in hot spots at the seed edges. Lack of experimental evidence of these hot spots was probably due to the complex polarization of the microwaves emitted by the helical antenna. Extended heating experiments also demonstrated that the seeds had no significant effect on the temperature distributions and rates of temperature rise measured in the phantom. The results indicate that brachytherapy seeds are not a technical impediment to interstitial microwave thermal therapy as a salvage treatment following failed brachytherapy

  19. Exeresis and Brachytherapy as Salvage Treatment for Local Recurrence After Conservative Treatment for Breast Cancer: Results of a Ten-Year Pilot Study

    International Nuclear Information System (INIS)

    Guix, Benjamin; Lejarcegui, Jose Antonio; Tello, Jose Ignacio; Zanon, Gabriel; Henriquez, Ivan; Finestres, Fernando; Martinez, Antonio; Fernandez-Ibiza, Jaume; Quinzanos, Luis; Palombo, Pau; Encinas, Xavier; Guix, Ines

    2010-01-01

    Purpose: To analyze the long-term results of a pilot study assessing excision and brachytherapy as salvage treatment for local recurrence after conservative treatment of breast cancer. Methods and Materials: Between December 1990 and March 2001, 36 patients with breast-only recurrence less than 3 cm in diameter after conservative treatment for Stage I or II breast carcinoma were treated with local excision followed by high-dose rate brachytherapy implants (30 Gy in 12 fractions over a period of 5 days). No patient was lost to follow-up. Special attention was paid to local, regional, or distant recurrences; survival; cosmesis; and early and late side effects. Results: All patients completed treatment. During follow-up (range, 1-13 years), 8 patients presented metastases (2 regional and 6 distant) as their first site of failure, 1 had a differed local recurrence, and 1 died of the disease. Actuarial results at 10 years were as follows: local control, 89.4%; disease-free survival, 64.4%; and survival, 96.7%. Cosmetic results were satisfactory in 90.4%. No patient had Grade 3 or 4 early or late complications. Of the 11 patients followed up for at least 10 years, all but 1 still had their breast in place at the 10-year stage. Conclusions: High-dose rate brachytherapy is a safe, effective treatment for small-size, low-risk local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of high-dose rate brachytherapy (12 fractions over a period of 5 days twice daily) was well tolerated. The excellent results support the use of breast preservation as salvage treatment in selected patients with local recurrence after conservative treatment for breast cancer.

  20. A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma

    International Nuclear Information System (INIS)

    Hudes, Richard S.; Corn, Benjamin W.; Werner-Wasik, Maria; Andrews, David; Rosenstock, Jeffrey; Thoron, Louisa; Downes, Beverly; Curran, Walter J.

    1999-01-01

    Purpose: A phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy. Materials and Methods: From November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging. Results: No grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fisher's exact test, response of any kind correlated strongly to total dose (p = 0.0056). None

  1. The evolutionary portrait of metazoan NAD salvage.

    Directory of Open Access Journals (Sweden)

    João Carneiro

    Full Text Available Nicotinamide Adenine Dinucleotide (NAD levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs and Nicotinamidases (PNCs have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

  2. The evolutionary portrait of metazoan NAD salvage.

    Science.gov (United States)

    Carneiro, João; Duarte-Pereira, Sara; Azevedo, Luísa; Castro, L Filipe C; Aguiar, Paulo; Moreira, Irina S; Amorim, António; Silva, Raquel M

    2013-01-01

    Nicotinamide Adenine Dinucleotide (NAD) levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs) and Nicotinamidases (PNCs) have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

  3. Airway necrosis after salvage esophagectomy

    International Nuclear Information System (INIS)

    Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

    2010-01-01

    Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

  4. Prognostic and predictive factors in patients with advanced penile cancer receiving salvage (2nd or later line systemic treatment: a retrospective, multi-center study

    Directory of Open Access Journals (Sweden)

    Carlo Buonerba

    2016-12-01

    Full Text Available AbstractIntroduction & objectives: Metastatic penile squamous cell carcinoma (PSCC is associated with dismal outcomes with median overall survival (OS of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data versus predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment.Materials & methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS and response rate (RR. OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models. Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI]=16.6% to 39.7% and median OS and PFS were 20 (95% CI=20 to 21 and 12 (95% CI =12, 16 weeks, respectively. Visceral metastasis (VM and hemoglobin (Hb ≤10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI of 24 (20-40 weeks and 1-year (95% CI OS of 13.7% (4.4-42.7%, while the 37 patients with 1 or 2 risk factors had median OS (95% CI of 20 (16-20 weeks and 1-year (95% CI OS of 6.7% (1

  5. 25 CFR 700.99 - Salvage value.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Salvage value. 700.99 Section 700.99 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.99 Salvage value. Salvage value means the probable sale price of an...

  6. Antroduodenectomy with Gastroduodenal Anastomosis: Salvage Emergency Surgery for Complicated Peptic Ulcer Disease--Results of a Double Institution Study of 35 Patients.

    Science.gov (United States)

    Chereau, Nathalie; Chandeze, Marie-Maëlle; Tantardini, Camille; Trésallet, Christophe; Lefevre, Jérémie H; Parc, Yann; Menegaux, Fabrice

    2016-03-01

    Endoscopic and interventional techniques are currently the mainstay of management of bleeding duodenal ulcer. As well, for patients with perforated duodenal ulcer, laparoscopic simple closure is nowadays usually performed. Although indications for emergency antroduodenectomy have declined, this procedure is still necessary as a salvage option when conservative management has failed or is not practicable. Our study aimed to evaluate indications and results of antroduodenectomy with gastroduodenal anastomosis in current practice and to examine the factors that predict operative outcomes. All patients who underwent emergency antroduodenectomy with gastroduodenal anastomosis in two surgical care departments specialized in emergency digestive surgery were studied from 2000 to 2015. Thirty-five patients (27 males, 77 %) with a median age of 68 years (20-90) underwent emergency antroduodenectomy with gastroduodenal anastomosis. Indications were bleeding and perforated duodenal ulcer in 24 and 11 patients, respectively. The overall complication rate was 69 %, especially because of a high rate of medical complications (57 %). Only two patients (6 %) required reoperation for anastomotic leakage. The overall mortality rate was 40 % (n = 14). According to the univariate analysis, age >70, >3 comorbidities, ASA score >2, and postoperative medical complications were associated with an increased risk of in-hospital mortality. In the multivariate analysis, age and ASA score remained independent risk factors. No recurrence of complicated duodenal disease was observed. Antroduodenectomy with gastroduodenal anastomosis is a safe and effective long-term strategy, with a low and acceptable rate of surgical complications, for complicated duodenal ulcer not responding to conservative measures.

  7. The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

    Science.gov (United States)

    Rossi, Giuseppe; Marcheselli, Luigi; Dondi, Alessandra; Bottelli, Chiara; Tucci, Alessandra; Luminari, Stefano; Arcaini, Luca; Merli, Michele; Pulsoni, Alessandro; Boccomini, Carola; Puccini, Benedetta; Micheletti, Moira; Martinelli, Giovanni; Rossi, Andrea; Zilioli, Vittorio Ruggero; Bozzoli, Valentina; Balzarotti, Monica; Bolis, Silvia; Cabras, Maria Giuseppina; Federico, Massimo

    2015-01-01

    Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line. © 2014 Wiley Periodicals, Inc.

  8. Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: A retrospective study regarding toxicity, biochemical outcome and quality of life

    International Nuclear Information System (INIS)

    Peters, Max; Maenhout, Metha; Voort van Zyp, Jochem R.N. van der; Moerland, Marinus A.; Moman, Maaike R.; Steuten, Lotte M.G.; Deursen, Marijke J.H. van; Vulpen, Marco van

    2014-01-01

    Purpose: Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. Materials and methods: Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. Results: With a median follow-up of 36 months (range 10–45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. Conclusion: Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable

  9. Simplified analysis for liquid pathway studies

    International Nuclear Information System (INIS)

    Codell, R.B.

    1984-08-01

    The analysis of the potential contamination of surface water via groundwater contamination from severe nuclear accidents is routinely calculated during licensing reviews. This analysis is facilitated by the methods described in this report, which is codified into a BASIC language computer program, SCREENLP. This program performs simplified calculations for groundwater and surface water transport and calculates population doses to potential users for the contaminated water irrespective of possible mitigation methods. The results are then compared to similar analyses performed using data for the generic sites in NUREG-0440, Liquid Pathway Generic Study, to determine if the site being investigated would pose any unusual liquid pathway hazards

  10. What is the optimal salvage procedure for cut-out after surgical fixation of trochanteric fractures with the PFNA or TFN?: A multicentre study.

    Science.gov (United States)

    Brunner, Alexander; Büttler, Markus; Lehmann, Uwe; Frei, Hans Curd; Kratter, Renato; Di Lazzaro, Marco; Scola, Alexander; Sermon, An; Attal, Rene

    2016-02-01

    To evaluate the outcome after different types of revision operations for blade 'cut-out' and 'cut-through' after fixation of trochanteric fractures with proximal femoral nail antirotation (PFNA) or a trochanter fixation nail (TFN). Twenty hospitals participated in this multicentre study. A total of 4109 patients were retrospectively screened for cut-out or cut-through complications after nailing of trochanteric fractures using PFNA or TFN. Fifty-seven patients (28 with 'cut-through' and 29 with 'cut-out') were included in the study. In the 'cut-through' group, 16 patients underwent a blade exchange, six patients had a blade exchange with bone cement augmentation, and six received total hip arthroplasty (THA). In the 'cut-out' group, three patients had a blade exchange, one had a blade exchange with augmentation, three underwent re-nailing of the fracture with a new PFNA, one had a girdlestone procedure and 21 had THA procedures. In the 'cut-through' group, eight patients who had a blade exchanges (50%) and two patients with blade exchange and augmentation (33%) required further revision operations. THA was the definite treatment in all 6 cases. In the 'cut-out' group, two patients (66%) who had blade exchanges and two (66%) who underwent re-nailing required additional revision operations during the subsequent course. One patient (4%) who had total hip arthroplasty needed revision surgery for acetabular replacement. Overall, a total of 81 revision procedures were performed. Based on the data from this study, we recommend THA as the only valid salvage procedure for 'cut-out' and 'cut-through' of helical blades after fixation of trochanteric fractures with the PFNA and TFN. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Mitigating Hillslope Erosion After Post-fire Salvage Logging Operations

    Science.gov (United States)

    Robichaud, P. R.; Bone, E. D.; Brown, R. E.

    2017-12-01

    In the past decades, wildfires around the world have continued to increase in size, severity, and cost. Major concerns after wildfires are the increased runoff and erosion due to loss of the protective forest floor layer, loss of water storage, and creation of water repellent soil conditions. Salvage logging is often a post-fire forest management action to recoup the economic loss of the burned timber, yet concerns arise on the impacts of this activity on water quality. Recently, several studies have been conducted to determine the effect of salvage logging on hillslope erosion. Logging skid trails have been cited as being the cause of high erosion during and after salvage operations. We investigated the impacts of adding operational logging slash to skid trails to reduce hillslope erosion after salvage operations on the 2015 North Star Fire, Washington. We implemented well-designed rapid response approach to compare slash treatment effectiveness by monitoring sediment yield and runoff response from hillslopes with a concentrated flow (rill) experiment. Various runoff amounts are incrementally added to 4 m hillslope plots with and without slash treatments. Our initial results suggest that adding logging slash increased ground cover significantly which contributed to an order of magnitude decrease in hillslope erosion. Integrating erosion mitigation strategies into salvage logging operations should be commonplace when hillslope erosion is a concern.

  12. Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma

    Science.gov (United States)

    Larson, Erik W; Peterson, Halloran E; Lamoreaux, Wayne T; MacKay, Alexander R; Fairbanks, Robert K; Call, Jason A; Carlson, Jonathan D; Ling, Benjamin C; Demakas, John J; Cooke, Barton S; Lee, Christopher M

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed. PMID:24829861

  13. Bacterial reduction by cell salvage washing and leukocyte depletion filtration.

    Science.gov (United States)

    Waters, Jonathan H; Tuohy, Marion J; Hobson, Donna F; Procop, Gary

    2003-09-01

    Blood conservation techniques are being increasingly used because of the increased cost and lack of availability of allogeneic blood. Cell salvage offers great blood savings opportunities but is thought to be contraindicated in a number of areas (e.g., blood contaminated with bacteria). Several outcome studies have suggested the safety of this technique in trauma and colorectal surgery, but many practitioners are still hesitant to apply cell salvage in the face of frank bacterial contamination. This study was undertaken to assess the efficacy of bacterial removal when cell salvage was combined with leukocyte depletion filtration. Expired packed erythrocytes were obtained and inoculated with a fixed amount of a stock bacteria (Escherichia coli American Type Culture Collections [ATCC] 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, or Bacteroides fragilis ATCC 25285) in amounts ranging from 2,000 to 4,000 colony forming units/ml. The blood was processed via a cell salvage machine. The washed blood was then filtered using a leukocyte reduction filter. The results for blood taken during each step of processing were compared using a repeated-measures design. Fifteen units of blood were contaminated with each of the stock bacteria. From the prewash sample to the postfiltration sample, 99.0%, 99.6%, 100%, and 97.6% of E. coli, S. aureus, P. aeruginosa, and B. fragilis were removed, respectively. Significant but not complete removal of contaminating bacteria was seen. An increased level of patient safety may be added to cell salvage by including a leukocyte depletion filter when salvaging blood that might be grossly contaminated with bacteria.

  14. A case study in pathway knowledgebase verification

    Directory of Open Access Journals (Sweden)

    Shah Nigam H

    2006-04-01

    Full Text Available Abstract Background Biological databases and pathway knowledgebases are proliferating rapidly. We are developing software tools for computer-aided hypothesis design and evaluation, and we would like our tools to take advantage of the information stored in these repositories. But before we can reliably use a pathway knowledgebase as a data source, we need to proofread it to ensure that it can fully support computer-aided information integration and inference. Results We design a series of logical tests to detect potential problems we might encounter using a particular knowledgebase, the Reactome database, with a particular computer-aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language from the language implicit in the Reactome data format and specify a logic to evaluate models expressed using this language. We use the formalism of finite model theory in this work. We then use this logic to formulate tests for desirable properties (such as completeness, consistency, and well-formedness for pathways stored in Reactome. We apply these tests to the publicly available Reactome releases (releases 10 through 14 and compare the results, which highlight Reactome's steady improvement in terms of decreasing inconsistencies. We also investigate and discuss Reactome's potential for supporting computer-aided inference tools. Conclusion The case study described in this work demonstrates that it is possible to use our model theory based approach to identify problems one might encounter using a knowledgebase to support hypothesis evaluation tools. The methodology we use is general and is in no way restricted to the specific knowledgebase employed in this case study. Future application of this methodology will enable us to compare pathway resources with respect to the generic properties such resources will need to possess if they are to support automated reasoning.

  15. A case study in pathway knowledgebase verification.

    Science.gov (United States)

    Racunas, Stephen A; Shah, Nigam H; Fedoroff, Nina V

    2006-04-08

    Biological databases and pathway knowledge-bases are proliferating rapidly. We are developing software tools for computer-aided hypothesis design and evaluation, and we would like our tools to take advantage of the information stored in these repositories. But before we can reliably use a pathway knowledge-base as a data source, we need to proofread it to ensure that it can fully support computer-aided information integration and inference. We design a series of logical tests to detect potential problems we might encounter using a particular knowledge-base, the Reactome database, with a particular computer-aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language from the language implicit in the Reactome data format and specify a logic to evaluate models expressed using this language. We use the formalism of finite model theory in this work. We then use this logic to formulate tests for desirable properties (such as completeness, consistency, and well-formedness) for pathways stored in Reactome. We apply these tests to the publicly available Reactome releases (releases 10 through 14) and compare the results, which highlight Reactome's steady improvement in terms of decreasing inconsistencies. We also investigate and discuss Reactome's potential for supporting computer-aided inference tools. The case study described in this work demonstrates that it is possible to use our model theory based approach to identify problems one might encounter using a knowledge-base to support hypothesis evaluation tools. The methodology we use is general and is in no way restricted to the specific knowledge-base employed in this case study. Future application of this methodology will enable us to compare pathway resources with respect to the generic properties such resources will need to possess if they are to support automated reasoning.

  16. Use of antibiotic beads to salvage infected breast implants.

    Science.gov (United States)

    Sherif, Rami D; Ingargiola, Michael; Sanati-Mehrizy, Paymon; Torina, Philip J; Harmaty, Marco A

    2017-10-01

    When an implant becomes infected, implant salvage is often performed where the implant is removed, capsulectomy is performed, and a new implant is inserted. The patient is discharged with a PICC line and 6-8 weeks of intravenous (IV) antibiotics. This method has variable success and subjects the patient to long-term systemic antibiotics. In the 1960s, the use of antibiotic-impregnated beads for the treatment of chronic osteomyelitis was described. These beads deliver antibiotic directly to the site of the infection, thereby eliminating the complications of systemic IV antibiotics. This study aimed to present a case series illustrating the use of STIMULAN calcium sulfate beads loaded with vancomycin and tobramycin to increase the rate of salvage of the infected implant and forgo IV antibiotics. A retrospective analysis was performed of patients who were treated at Mount Sinai Hospital for implant infection with salvage and antibiotic beads. Twelve patients were identified, 10 of whom had breast cancer. Comorbidities included hypertension, smoking, and immunocompromised status. Infections were noted anywhere from 5 days to 8 years postoperatively. Salvage was successful in 9 out of the 12 infected implants using antibiotic bead therapy without home IV antibiotics. The use of antibiotic beads is promising for salvaging infected breast implants without IV antibiotics. Seventy-five percent of the implants were successfully salvaged. Of the three patients who had unsalvageable implants, one was infected with antibiotic-resistant Rhodococcus that was refractory to bead therapy and one was noncompliant with postoperative instructions. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Which is the best method of sterilization for recycled bone autograft in limb salvage surgery: a radiological, biomechanical and histopathological study in rabbit.

    Science.gov (United States)

    Yasin, Nor Faissal; Ajit Singh, Vivek; Saad, Marniza; Omar, Effat

    2015-04-15

    Limb salvage surgery is a treatment of choice for sarcomas of the extremities. One of the options in skeletal reconstruction after tumour resection is by using a recycled bone autograft. The present accepted methods of recycling bone autografts include autoclaving, pasteurization and irradiation. At the moment there is lack of studies that compare the effectiveness of various sterilization methods used for recycling bone autografts and their effects in terms of bone incorporation. This study was performed to determine the effects of different methods of sterilization on bone autografts in rabbit by radiological, biomechanical and histopathological evaluations. Fresh rabbit cortical bone is harvested from the tibial diaphysis and sterilized extracorporeally by pasteurization (n = 6), autoclaving (n = 6), irradiation (n = 6) and normal saline as control group (n = 6). The cortical bones were immediately reimplanted after the sterilization process. The subsequent process of graft incorporation was examined over a period of 12 weeks by serial radiographs, biomechanical and histopathological evaluations. Statistical analysis (ANOVA) was performed on these results. Significance level (α) and power (β) were set to 0.05 and 0.90, respectively. Radiographic analysis showed that irradiation group has higher score in bony union compared to other sterilization groups (p = 0.041). ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated no significant differences (p = 0.389) between treated and untreated specimens under mechanical loading. In macroscopic histopathological analysis, the irradiated group has the highest percentage of bony union (91.7 percent). However in microscopic analysis of union, the pasteurization group has significantly higher score (p = 0.041) in callus formation, osteocytes percentage and bone marrow cellularity at the end of the study indicating good union potential. This experimental study shown that both irradiation and

  18. Time consumption and productivity of skidding Silver fir (Abies alba Mill. round wood in reduced accessibility conditions: a case study in windthrow salvage logging form Romanian Carpathians

    Directory of Open Access Journals (Sweden)

    Stelian Alexandru Borz

    2013-11-01

    Full Text Available Natural calamities (especially windthrows may generate difficultwork conditions in timber harvesting operations. When associated with the reduced accessibility conditions, the work conditions become even harder. This study investigates the time consumptions on specific work elements in timber skidding, develops time prediction models for timber skidding work elements and assesses the production rates for timber skidding in reduced accessibility stands where windthrow salvage cuttings were applied.Following a time study done for two skidders (TAF 690 OP and TAF 657operating simultaneously in the same felling area, it has been found that, in average, in a delay free skidding cycle time, lateral winching accounted for a share of 26-33%, on-trail skidding accounted for a share of 64-71% and landing operations accounted for a share of 3%. Total delays accounted for 51% and 43% of the total work time in the case of TAF 690 OP skidder and TAF 657 skidder, respectively. Regression models for lateral winching(both skidders revealed that the winching distance and the number of logs were the relevant predictors for the time consumption estimation (p<0.01, whereas in the case of on-trail skidding only the skidding distance was relevant (p <0.01. For the overall skidding operation (excluding landingoperations winching and skidding distances were found as relevantpredictors (p <0.01 for 690 OP, whereas the number of logs became anadditional relevant predictor for 657. In conditions of an average winching distance of 19.90 m and an average on-trail skidding distance of 980.32 m, the time study yielded a net production rate of 7.70 m3 h-1 and a gross production rate of 3.75 m3 h-1 in the case of TAF 690 OP skidder. By comparison, in the case of TAF 657 skidder, for an average winching distance of 22.86 m and an average on-trail skidding distance of 871.00 m, the net and gross production rates were of 5.61 m3 h-1 and 3.20 m3 h-1 respectively.

  19. Time consumption and productivity of skidding Silver fir (Abies alba Mill. round wood in reduced accessibility conditions: a case study in windthrow salvage logging form Romanian Carpathians

    Directory of Open Access Journals (Sweden)

    Stelian Alexandru Borz

    2013-12-01

    Full Text Available Natural calamities (especially windthrows may generate difficult work conditions in timber harvesting operations. When associated with the reduced accessibility conditions, the work conditions become even harder. This study investigates the time consumptions on specific work elements in timber skidding, develops time prediction models for timber skidding work elements and assesses the production rates for timber skidding in reduced accessibility stands where windthrow salvage cuttings were applied. Following a time study done for two skidders (TAF 690 OP and TAF 657 operating simultaneously in the same felling area, it has been found that, in average, in a delay free skidding cycle time, lateral winching accounted for a share of 26-33%, on-trail skidding accounted for a share of 64-71% and landing operations accounted for a share of 3%.Total delays accounted for 51% and 43% of the total work time in the case of TAF 690 OP skidder and TAF 657skidder respectively. Regression models for lateral winching (both skidders revealed that the winching distance and the number of logs were the relevant predictors for the time consumption estimation (p<0.01, whereas in the case of on-trail skidding only the skidding distance was relevant (p<0.01. For the overall skidding operation (excluding landing operations winching and skidding distances were found as relevant predictors (p<0.01 in case of TAF 690 OP, whereas the number of logs became an additional relevant predictor in case of TAF 657.In conditions of an average winching distance of 19.90 m and an average on-trail skidding distance of 980.32 m, the time study yielded a net production rate of 7.70 m3h-1 and a gross production rate of 3.75 m3h-1 in the case of TAF 690 OP skidder. By comparison, in the case of TAF 657 skidder, for an average winching distance of 22.86 m and an average on-trail skidding distance of 871.00 m, the net and gross production rates were of 5.61 m3h-1 and 3.20 m3h-1 respectively.

  20. Outcome and renal function following salvage surgery for bilateral ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to determine the surgical outcomes and renal function following salvage surgery for bilateral Wilms tumor (BWT). Summary background data The challenge for the surgeon treating BWT lies in striking a fine balance between renal preservation and oncological clearance. Methods: This is ...

  1. Role of salvage esophagectomy after definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Tachimori, Yuji

    2009-01-01

    Chemoradiotherapy has become a popular definitive therapy among many patients and oncologists for potentially resectable esophageal carcinoma. Although the complete response rates are high and short-term survival is favorable after chemoradiotherapy, persistent or recurrent locoregional disease is quite frequent. Salvage surgery is the sole curative intent treatment option for this course. As experience with definitive chemoradiotherapy grows, the number of salvage surgeries may increase. Selected articles about salvage esophagectomy after definitive chemoradiotherapy for esophageal carcinoma are reviewed. The number of salvage surgeries was significantly lower than the number of expected candidates. To identify candidates for salvage surgery, patients undergoing definitive chemoradiotherapy should be followed up carefully. Salvage esophagectomy is difficult when dissecting fibrotic masses from irradiated tissues. Patients who underwent salvage esophagectomy had increased morbidity and mortality. Pulmonary complications such as pneumonia and acute respiratory distress syndrome were common. The anastomotic leak rate was significantly increased because of the effects of the radiation administered to the tissues used as conduits. The most significant factor associated with long-term survival appeared to be complete resection. However, precise evaluation of resectability before operation was difficult. Nevertheless, increased morbidity and mortality will be acceptable in exchange for potential long-term survival after salvage esophagectomy. Such treatment should be considered for carefully selected patients at specialized centers. (author)

  2. Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans.

    Science.gov (United States)

    Vrablik, Tracy L; Wang, Wenqing; Upadhyay, Awani; Hanna-Rose, Wendy

    2011-01-15

    Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) from nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD(+) after it is hydrolyzed. This pathway is emerging as a regulator of multiple biological processes. Here we probe the contribution of the NAM-NAD(+) salvage pathway to muscle development and function using Caenorhabditis elegans. C. elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the first step of this NAD(+) salvage pathway, cannot mate due to a spicule muscle defect. Multiple muscle types are impaired in the hermaphrodites, including body wall muscles, pharyngeal muscles and vulval muscles. An active NAD(+) salvage pathway is required for optimal function of each muscle cell type. However, we found surprising muscle-cell-type specificity in terms of both the timing and relative sensitivity to perturbation of NAD(+) production or NAM levels. Active NAD(+) biosynthesis during development is critical for function of the male spicule protractor muscles during adulthood, but these muscles can surprisingly do without salvage biosynthesis in adulthood under the conditions examined. The body wall muscles require ongoing NAD(+) salvage biosynthesis both during development and adulthood for maximum function. The vulval muscles do not function in the presence of elevated NAM concentrations, but NAM supplementation is only slightly deleterious to body wall muscles during development or upon acute application in adults. Thus, the pathway plays distinct roles in different tissues. As NAM-NAD(+) biosynthesis also impacts muscle differentiation in vertebrates, we propose that similar complexities may be found among vertebrate muscle cell types. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. In vitro metabolic engineering for the salvage synthesis of NAD(.).

    Science.gov (United States)

    Honda, Kohsuke; Hara, Naoya; Cheng, Maria; Nakamura, Anna; Mandai, Komako; Okano, Kenji; Ohtake, Hisao

    2016-05-01

    Excellent thermal and operational stabilities of thermophilic enzymes can greatly increase the applicability of biocatalysis in various industrial fields. However, thermophilic enzymes are generally incompatible with thermo-labile substrates, products, and cofactors, since they show the maximal activities at high temperatures. Despite their pivotal roles in a wide range of enzymatic redox reactions, NAD(P)(+) and NAD(P)H exhibit relatively low stabilities at high temperatures, tending to be a major obstacle in the long-term operation of biocatalytic chemical manufacturing with thermophilic enzymes. In this study, we constructed an in vitro artificial metabolic pathway for the salvage synthesis of NAD(+) from its degradation products by the combination of eight thermophilic enzymes. The enzymes were heterologously produced in recombinant Escherichia coli and the heat-treated crude extracts of the recombinant cells were directly used as enzyme solutions. When incubated with experimentally optimized concentrations of the enzymes at 60°C, the NAD(+) concentration could be kept almost constant for 15h. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  4. Windthrow and salvage logging in an old-growth hemlock-northern hardwoods forest

    Science.gov (United States)

    Lang, K.D.; Schulte, L.A.; Guntenspergen, G.R.

    2009-01-01

    Although the initial response to salvage (also known as, post-disturbance or sanitary) logging is known to vary among system components, little is known about longer term forest recovery. We examine forest overstory, understory, soil, and microtopographic response 25 years after a 1977 severe wind disturbance on the Flambeau River State Forest in Wisconsin, USA, a portion of which was salvage logged. Within this former old-growth hemlock-northern hardwoods forest, tree dominance has shifted from Eastern hemlock (Tsuga canadensis) to broad-leaf deciduous species (Ulmus americana, Acer saccharum, Tilia americana, Populus tremuloides, and Betula alleghaniensis) in both the salvaged and unsalvaged areas. While the biological legacies of pre-disturbance seedlings, saplings, and mature trees were initially more abundant in the unsalvaged area, regeneration through root suckers and stump sprouts was common in both areas. After 25 years, tree basal area, sapling density, shrub layer density, and seedling cover had converged between unsalvaged and salvaged areas. In contrast, understory herb communities differed between salvaged and unsalvaged forest, with salvaged forest containing significantly higher understory herb richness and cover, and greater dominance of species benefiting from disturbance, especially Solidago species. Soil bulk density, pH, organic carbon content, and organic nitrogen content were also significantly higher in the salvaged area. The structural legacy of tip-up microtopography remains more pronounced in the unsalvaged area, with significantly taller tip-up mounds and deeper pits. Mosses and some forest herbs, including Athyrium filix-femina and Hydrophyllum virginianum, showed strong positive responses to this tip-up microrelief, highlighting the importance of these structural legacies for understory biodiversity. In sum, although the pathways of recovery differed, this forest appeared to be as resilient to the compound disturbances of windthrow

  5. Psychosocial reactions to upper extremity limb salvage: A case series.

    Science.gov (United States)

    Sposato, Lindsay; Yancosek, Kathleen; Cancio, Jill

    2017-11-30

    Case series. A salvaged limb is one that has undergone a major traumatic injury, followed by repeated surgical attempts in order to avoid amputation. Psychological recovery for individuals with lower extremity limb salvage has been examined in a number of studies. However, psychosocial reactions for individuals with upper extremity (UE) limb salvage are understudied in the literature. The purpose of this study was to explore the process of psychosocial adaptation for 3 trauma cases after UE limb salvage. The Reactions to Impairment and Disability Inventory was used to assess psychosocial adaptation. Physical function outcomes (pain, range of motion, edema, sensation, and dexterity) are presented. The Disabilities of the Arm, Shoulder, and Hand measure was used to assess perceived disability. Medical and rehabilitation history are discussed for each case, in order to provide in-depth understanding of the impact of these injuries. Reactions to injury varied across the cases; however, outcomes suggest that psychosocial adaptation may be influenced by the experience of pain, the ability to participate in valued roles and activities, and having a supportive social network. For this population, therapists may consider emphasizing pain management, focusing on client-centered goals and interventions, and facilitating peer support. Providers should closely monitor patients for signs of poor adaptation, such as hand-hiding behaviors. This study is among the first to examine psychological outcomes for the UE limb salvage population. Future research would be beneficial to provide deeper understanding of the psychosocial challenges for these individuals. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  6. Targeting a Novel Plasmodium falciparum Purine Recycling Pathway with Specific Immucillins

    International Nuclear Information System (INIS)

    Ting, L; Shi, W; Lewandowicz, A; Singh, V; Mwakingwe, A; Birck, M R; Taylor Ringia, E A; Bench, G; Madrid, D C; Tyler, P C; Evans, G B; Furneaux, R H; Schramm, V L; Kim, K.

    2004-01-01

    Plasmodium falciparum is unable to synthesize purine bases and relies upon purine salvage and purine recycling to meet its purine needs. We report that purines formed as products of the polyamine pathway are recycled in a novel pathway in which 5'-methylthioinosine is generated by adenosine deaminase. The action of P. falciparum purine nucleoside phosphorylase is a convergent step of purine salvage, converting both 5'-methylthioinosine and inosine to hypoxanthine. We used accelerator mass spectrometry to verify that 5'-methylthioinosine is an active nucleic acid precursor in P. falciparum. Prior studies have shown that inhibitors of purine salvage enzymes kill malaria, but potent malaria-specific inhibitors of these enzymes have not previously been described. 5'-methylthio-Immucillin-H, a transition state analogue inhibitor that is selective for malarial over human purine nucleoside phosphorylase, kills P. falciparum in culture. Immucillins are currently in clinical trials for other indications and may have application as antimalarials

  7. A comparison of salvage surgery following CRT and following BRT for advanced hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Kamijo, Tomoyuki; Onitsuka, Tetsuro; Yokota, Tomoya

    2016-01-01

    There are still few comparison reports regarding the safety of salvage surgery for recurrence and persistence following platinum-based chemoradiotherapy (CRT) and cetuximab-based bioradiotherapy (BRT), which are frequently used as non-surgical therapies for advanced head and neck carcinomas. This study compared the safety of salvage surgery following CRT against that following BRT for advanced hypopharyngeal cancer. The study examined 34 cases who underwent salvage surgery following CRT and 7 cases who underwent salvage surgery following BRT from September 2002 to December 2015. The number of cases that were able to undergo salvage surgery was 34 among 67 recurrence and persistence cases following CRT and 7 of 8 cases following BRT. In terms of the surgical procedure, salvage neck dissection was conducted for 22 cases in the CRT group and 5 cases in the BRT group, with no significant differences observed between both including the surgical time and amount of bleeding, and with no major complications in either group. Total hypopharynx or total laryngectomy resection for salvage was conducted for 19 cases in the CRT group and 3 cases in the BRT group, upon which we observed anastomotic leakage in 3 cases in the CRT group and 1 case in the BRT group; however, there was no significant difference in the onset frequency. There was no clear difference regarding safety between salvage surgery following CRT and following BRT for locally advanced hypopharyngeal cancer. However, regarding the adaptation of salvage surgery, the possibility of limitations in the CRT group was suggested in comparison with the BRT group. (author)

  8. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    International Nuclear Information System (INIS)

    King, Christopher R.; Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-01-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity ≤1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level ≤1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = ∼0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates

  9. Ipsilateral breast tumor recurrence after breast conservation therapy: Outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation

    International Nuclear Information System (INIS)

    Alpert, Tracy E.; Kuerer, Henry M.; Arthur, Douglas W.; Lannin, Donald R.; Haffty, Bruce G.

    2005-01-01

    Purpose: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. Methods and Materials: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size <3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with ≤3 positive nodes. Results: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. Conclusions: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is

  10. Association of Preoperative Nutritional Status with Prognosis in Patients with Esophageal Cancer Undergoing Salvage Esophagectomy.

    Science.gov (United States)

    Sakai, Makoto; Sohda, Makoto; Miyazaki, Tatsuya; Yoshida, Tomonori; Kumakura, Yuji; Honjo, Hiroaki; Hara, Keigo; Ozawa, Daigo; Suzuki, Shigemasa; Tanaka, Naritaka; Yokobori, Takehiko; Kuwano, Hiroyuki

    2018-02-01

    To investigate whether malnutrition is associated with poor prognosis of patients who undergo salvage esophagectomy. We examined the association between the preoperative prognostic nutritional index (PNI) and prognosis of patients who undergo salvage esophagectomy. We conducted a single-center retrospective study and reviewed hospital patient records for tumor characteristics and patient outcomes. Univariate and multivariate survival analyses were carried out using the Cox proportional hazards regression model. Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who underwent salvage esophagectomy between 1998 and 2015 at our Institute were included in this study. Univariate analysis revealed that clinical response (p=0.045), preoperative PNI (pnutritional status is associated with the prognosis of patients undergoing salvage esophagectomy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Implant breast reconstruction after salvage mastectomy in previously irradiated patients.

    Science.gov (United States)

    Persichetti, Paolo; Cagli, Barbara; Simone, Pierfranco; Cogliandro, Annalisa; Fortunato, Lucio; Altomare, Vittorio; Trodella, Lucio

    2009-04-01

    The most common surgical approach in case of local tumor recurrence after quadrantectomy and radiotherapy is salvage mastectomy. Breast reconstruction is the subsequent phase of the treatment and the plastic surgeon has to operate on previously irradiated and manipulated tissues. The medical literature highlights that breast reconstruction with tissue expanders is not a pursuable option, considering previous radiotherapy a contraindication. The purpose of this retrospective study is to evaluate the influence of previous radiotherapy on 2-stage breast reconstruction (tissue expander/implant). Only patients with analogous timing of radiation therapy and the same demolitive and reconstructive procedures were recruited. The results of this study prove that, after salvage mastectomy in previously irradiated patients, implant reconstruction is still possible. Further comparative studies are, of course, advisable to draw any conclusion on the possibility to perform implant reconstruction in previously irradiated patients.

  12. Salvage image guided radiation therapy to the prostate after cryotherapy failure

    Directory of Open Access Journals (Sweden)

    Austin B. Hopper, BS

    2018-01-01

    Conclusions: High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

  13. Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure

    DEFF Research Database (Denmark)

    Wulff, N B; Andersen, E; Kristensen, C A

    2017-01-01

    with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.......OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142...... survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease...

  14. Liquid pathways generic studies; results, interpretation, and design implications

    International Nuclear Information System (INIS)

    Walker, D.H.; Nutant, J.A.

    1980-01-01

    Offshore Power Systems and the Nuclear Regulatory Commission have evaluated dose consequences resulting from a release of radioactivity to liquid pathways following a postulated core-melt accident. The objective of these studies was to compare the risks from postulated core-melt accidents for the Floating Nuclear Plant with those for a typical land-based nuclear plant. Offshore Power Systems concluded that the differences in liquid pathway risks between plant types are not significant when compared with the air pathways risks. Air pathways risk is similar to or significantly larger than liquid pathways risk depending on the accident scenario. The Nuclear Regulatory Commission judged the liquid pathways risks from the Floating Nuclear Plant to be significantly greater than the liquid pathway risks for the typical land-based plant. Although OPS disagrees with the NRC judgment, design changes dictated by the NRC are being implemented by OPS

  15. Thymidine kinases share a conserved function for nucleotide salvage and play an essential role in Arabidopsis thaliana growth and development.

    Science.gov (United States)

    Xu, Jing; Zhang, Lin; Yang, Dong-Lei; Li, Qun; He, Zuhua

    2015-12-01

    Thymidine kinases (TKs) are important components in the nucleotide salvage pathway. However, knowledge about plant TKs is quite limited. In this study, the molecular function of TKs in Arabidopsis thaliana was investigated. Two TKs were identified and named AtTK1 and AtTK2. Expression of both genes was ubiquitous, but AtTK1 was strongly expressed in high-proliferation tissues. AtTK1 was localized to the cytosol, whereas AtTK2 was localized to the mitochondria. Mutant analysis indicated that the two genes function coordinately to sustain normal plant development. Enzymatic assays showed that the two TK proteins shared similar catalytic specificity for pyrimidine nucleosides. They were able to complement an Escherichia coli strain lacking TK activity. 5'-Fluorodeoxyuridine (FdU) resistance and 5-ethynyl 2'-deoxyuridine (EdU) incorporation assays confirmed their activity in vivo. Furthermore, the tk mutant phenotype could be alleviated by nucleotide feeding, establishing that the biosynthesis of pyrimidine nucleotides was disrupted by the TK deficiency. Finally, both human and rice (Oryza sativa) TKs were able to rescue the tk mutants, demonstrating the functional conservation of TKs across organisms. Taken together, our findings clarify the specialized function of two TKs in A. thaliana and establish that the salvage pathway mediated by the kinases is essential for plant growth and development. © 2015 Institute of Plant Physiology and Ecology, SIBS, CAS New Phytologist © 2015 New Phytologist Trust.

  16. Clinical results for salvage surgery in head and neck carcinoma after chemoradiation or radiation

    International Nuclear Information System (INIS)

    Ishida, Katsuhiro; Makino, Yohjiroh; Nagaoka, Masato; Seino, Youichi; Hama, Takanori; Aoki, Kensuke; Uchida, Mitsuru; Kato, Takakuni

    2013-01-01

    The objective of this study was to examine the post-operative complications of surgical procedures in oral or pharyngeal carcinoma by analyzing and comparing between patients who underwent salvage surgery after chemoradiation and radiation. A retrospective review was performed of 18 patients who underwent salvage surgery and reconstruction after concurrent chemoradiotherapy (CCRT group), and another 41 patients who underwent salvage surgery and reconstruction after radiation therapy (RT group). No perioperative deaths or life threatening systemic complications occurred, and all flaps survived completely in both groups. Surgical site infection (SSI) occurred in five patients (12.2%) in the RT group and seven patients (38%) in the CCRT group. SSI other than donor site infection occurred in four patients (9%) in the RT group and four patients (22%) in the CCRT group. The rate of SSI excluding donor site infection did not differ significantly between patients who underwent salvage surgery after CCRT and RT. The rate of donor site infection was higher in the CCRT group than in the RT group (p=0.04). This study showed that salvage surgery after CCRT or RT can be performed safely, without significant morbidity or mortality. However, patients who received CCRT are at risk for major complications caused by minor troubles, and thus reconstruction after salvage surgery should be performed with sufficient care. (author)

  17. Peripheral Sympathectomy for Raynaud's Phenomenon: A Salvage Procedure

    Directory of Open Access Journals (Sweden)

    Wen-Her Wang

    2006-10-01

    Full Text Available We retrospectively reviewed the effectiveness of peripheral sympathectomy for severe Raynaud's phenomenon. In this study, a total of 14 digits from six patients with chronic digital ischemic change were included. All patients had pain, ulcer, or gangrenous change in the affected digits and were unresponsive to pharmacologic or other nonsurgical therapies. In all cases, angiography showed multifocal arterial lesions, so microvascular reconstruction was unfeasible. Peripheral sympathectomy was performed as a salvage procedure to prevent digit amputation. The results were analyzed according to reduction of pain, healing of ulcers, and prevention of amputation. In 12 of the 14 digits, the ulcers healed and amputation was avoided. In the other two digits, the ulcers improved and progressive gangrene was limited. As a salvage procedure for Raynaud's phenomenon recalcitrant to conservative treatment, peripheral sympathectomy improves perfusion to ischemic digits and enables amputation to be avoided.

  18. Radiotherapy salvage for Hodgkin's disease after chemotherapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Wirth, A; Corry, J; Liew, K H

    1995-07-01

    Purpose/Objective: The precise role of salvage radiotherapy (RT) following chemotherapy (CT) failure in patients with Hodgkin's disease (HD) remains undefined. The aims of this study are: (1) to assess the pattern of failure, failure-free and overall survival, in patients who receive salvage RT for HD after CT failure; and (2) to identify patient subsets most suitable for this treatment approach. Materials and Methods: A review of patients treated between 1978 and 1992 at the Peter MacCallum Cancer Institute identified 52 patients with relapsed/refractory HD following CT who received RT with curative intent. Eligibility for this study required either biopsy confirmation of relapse/residual disease, or else clear clinical or radiological disease progression. Patient characteristics at diagnosis: median age 26, with 32% > 40 years old; M/ F 31/21; stage I-4, II-16, III-25, IV-7. Initial CT was MOPP- 31 patients, ABVD-1, both-16. A median 6 cycles of CT was given per regimen. Prior to salvage RT, 26/52 patients had received both MOPP and ABVD, either as sequential regimens, or as alternating or hybrid protocols. The response to initial CT was: CR-30, PR/SD-18, PD-4. Duration of initial CR was < 12 months in 8/30 patients. Salvage treatment consisted of radiotherapy to all known areas of disease. Doses ranged from 3600-4000 cGy. Results: Twenty three patients (45%) achieved CR. With a median follow-up of 70 months (range 4.8-166), actuarial median failure free survival (FFS) and overall survival (OS) are 22 months and 83 months respectively. Actuarial 5 year FFS and OS are 26% and 57% respectively. Patients with CR duration > 12 months following initial CT, only one CT regimen prior to salvage RT, and anatomically limited relapse had a significantly longer FFS. These factors, and age < 40 were associated with significantly longer OS. Only 6% of patients failed solely in the irradiated volume as first site of relapse, with the total in-field relapse of 30%. Sixty

  19. Singular and interactive effects of blowdown, salvage logging, and wildfire in sub-boreal pine systems

    Science.gov (United States)

    D'Amato, A.W.; Fraver, S.; Palik, B.J.; Bradford, J.B.; Patty, L.

    2011-01-01

    The role of disturbance in structuring vegetation is widely recognized; however, we are only beginning to understand the effects of multiple interacting disturbances on ecosystem recovery and development. Of particular interest is the impact of post-disturbance management interventions, particularly in light of the global controversy surrounding the effects of salvage logging on forest ecosystem recovery. Studies of salvage logging impacts have focused on the effects of post-disturbance salvage logging within the context of a single natural disturbance event. There have been no formal evaluations of how these effects may differ when followed in short sequence by a second, high severity natural disturbance. To evaluate the impact of this management practice within the context of multiple disturbances, we examined the structural and woody plant community responses of sub-boreal Pinus banksiana systems to a rapid sequence of disturbances. Specifically, we compared responses to Blowdown (B), Fire (F), Blowdown-Fire, and Blowdown-Salvage-Fire (BSF) and compared these to undisturbed control (C) stands. Comparisons between BF and BSF indicated that the primary effect of salvage logging was a decrease in the abundance of structural legacies, such as downed woody debris and snags. Both of these compound disturbance sequences (BF and BSF), resulted in similar woody plant communities, largely dominated by Populus tremuloides; however, there was greater homogeneity in community composition in salvage logged areas. Areas experiencing solely fire (F stands) were dominated by P. banksiana regeneration, and blowdown areas (B stands) were largely characterized by regeneration from shade tolerant conifer species. Our results suggest that salvage logging impacts on woody plant communities are diminished when followed by a second high severity disturbance; however, impacts on structural legacies persist. Provisions for the retention of snags, downed logs, and surviving trees as part

  20. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    Science.gov (United States)

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  1. Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction

    International Nuclear Information System (INIS)

    Breault, Stéphane; Glauser, Frédéric; Babaker, Malik; Doenz, Francesco; Qanadli, Salah Dine

    2015-01-01

    PurposeImplanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques.Methods and MaterialsThrough a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new “mechanical adhesiolysis” maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication.ResultsEighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted.ConclusionThese IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement

  2. Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Breault, Stéphane, E-mail: stephane.breault@chuv.ch [Lausanne University Hospital, Diagnostic and Interventional Radiology Department (Switzerland); Glauser, Frédéric, E-mail: frederic.glauser@chuv.ch [Lausanne University Hospital, Angiology and Diagnostic and Interventional Radiology Departments (Switzerland); Babaker, Malik, E-mail: malik.babaker@chuv.ch; Doenz, Francesco, E-mail: francesco.doenz@chuv.ch; Qanadli, Salah Dine, E-mail: salah.qanadli@chuv.ch [Lausanne University Hospital, Diagnostic and Interventional Radiology Department (Switzerland)

    2015-06-15

    PurposeImplanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques.Methods and MaterialsThrough a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new “mechanical adhesiolysis” maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication.ResultsEighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted.ConclusionThese IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement.

  3. Salvage surgery for local failure of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Omura, Ken; Harada, Hiroyuki; Shimamoto, Hiroaki

    2003-01-01

    Local failure rates following treatment for squamous cell carcinoma of the oral cavity have been reported to be in the range of 25%-48%. This study investigated the pattern of failure for squamous cell carcinoma (SCC) of the oral cavity and evaluated salvage surgery for local recurrent disease. The tumor files of 549 patients undergoing treatment for SCC of the oral cavity between 1980 and 2000 at Chiba Cancer Center Hospital were reviewed. Of 549 patients, 289 were initially treated with radiation therapy for their primary tumor, and 260 with surgery, either with or without radiation therapy. One hundred and sixty-one patients developed failures, yielding a failure rate of 29.3%. The site of recurrent tumor was local in 72 (13.1%) patients, regional in 89 (16.2%) patients, and distant in 5 (0.9%) patients. Local failure developed in 49 (17.0%) patients with radiation therapy and in 23 (8.8%) patients with surgery. Out of these 72 patients with local failure, 41 (56.9%) patients had salvage surgery for their disease. Twenty-five (73.5%) of the 34 patients initially treated with radiation therapy were salvaged with surgery, and 4 (57.1%) of the 7 patients initially treated with surgery were cured with further surgery. For the treatment of patients with local failure, the disease should be diagnosed more carefully than untreated disease. The disease that has recurred after radiation therapy may be more likely to be salvaged by surgery, however, the disease that has developed after surgery may have a limited indication for re-surgery. (author)

  4. Designing a Care Pathway Model - A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway.

    Science.gov (United States)

    Oosterholt, Robin I; Simonse, Lianne Wl; Boess, Stella U; Vehmeijer, Stephan Bw

    2017-03-09

    Although the clinical attributes of total hip arthroplasty (THA) care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. The outpatient THA care pathway enables patients to be discharged on the day of surgery, shortening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation & discharge (4). The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. The design addressed existing problems and is an optimisation of the case hospital's pathway. The network of actors consists of the patient (1), radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1), orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and patient application (1,4). The critical value exchanges include patient preparation (mental and practical), patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

  5. Salvage Islet Auto Transplantation After Relaparatomy.

    Science.gov (United States)

    Balzano, Gianpaolo; Nano, Rita; Maffi, Paola; Mercalli, Alessia; Melzi, Raffaelli; Aleotti, Francesca; Gavazzi, Francesca; Berra, Cesare; De Cobelli, Francesco; Venturini, Massimo; Magistretti, Paola; Scavini, Marina; Capretti, Giovanni; Del Maschio, Alessandro; Secchi, Antonio; Zerbi, Alessandro; Falconi, Massimo; Piemonti, Lorenzo

    2017-10-01

    To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery. From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy. The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT (78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT. Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.

  6. Salvage esophagectomy post definitive chemoradiotherapy or radiotherapy

    International Nuclear Information System (INIS)

    Hosokawa, Masao; Suzuki, Yasuhiro; Nisida, Yasunori

    2008-01-01

    Outcome of salvage esophagectomy (SE), which was done due to rest development or recurrence after radical treatment of the esophageal cancer with radio- (RT) or chemoradio-therapy (CRT), was retrospectively studied and discussed. Subjects were 61 patients (M 54, F 7: average age, 63.5 y) with the cancer at Stage I- early IVB who had undergone radical CRT (35 cases) and RT (26) with >50 Gy, had no lymphatic and remote metastases at the diagnosis of the recurrence and then received SE and reconstruction surgery. Rough 5-year survival was found to be 29.2% in CRT group and 32.3% in RT. Operation-related death was 1 case (sepsis) and the rate of complication was slightly higher than the ordinary SE. Based on above outcome, discussion was made on following tasks and/or measures in authors' hospital: diagnostic means like the combination with positron emission tomography (PET), dose/regions of irradiation (dose to the heart and lung should be < TD 5/5=tolerance dose to be <5% incidence of adverse effect within 5 years) and of chemotherapy, decision of the irradiation area with consideration of SE afterward, careful surgery to reduce complication, and sufficient preoperative evaluation for radical surgery by images like PET/CT. Operation with consideration of these items conceivably makes SE safer. (R.T.)

  7. Potential for water salvage by removal of non-native woody vegetation from dryland river systems

    Science.gov (United States)

    Doody, T.M.; Nagler, P.L.; Glenn, E.P.; Moore, G.W.; Morino, K.; Hultine, K.R.; Benyon, R.G.

    2011-01-01

    Globally, expansion of non-native woody vegetation across floodplains has raised concern of increased evapotranspiration (ET) water loss with consequent reduced river flows and groundwater supplies. Water salvage programs, established to meet water supply demands by removing introduced species, show little documented evidence of program effectiveness. We use two case studies in the USA and Australia to illustrate factors that contribute to water salvage feasibility for a given ecological setting. In the USA, saltcedar (Tamarix spp.) has become widespread on western rivers, with water salvage programs attempted over a 50-year period. Some studies document riparian transpiration or ET reduction after saltcedar removal, but detectable increases in river base flow are not conclusively shown. Furthermore, measurements of riparian vegetation ET in natural settings show saltcedar ET overlaps the range measured for native riparian species, thereby constraining the possibility of water salvage by replacing saltcedar with native vegetation. In Australia, introduced willows (Salix spp.) have become widespread in riparian systems in the Murray-Darling Basin. Although large-scale removal projects have been undertaken, no attempts have been made to quantify increases in base flows. Recent studies of ET indicate that willows growing in permanently inundated stream beds have high transpiration rates, indicating water savings could be achieved from removal. In contrast, native Eucalyptus trees and willows growing on stream banks show similar ET rates with no net water salvage from replacing willows with native trees. We conclude that water salvage feasibility is highly dependent on the ecohydrological setting in which the non-native trees occur. We provide an overview of conditions favorable to water salvage. Copyright ?? 2011 John Wiley & Sons, Ltd.

  8. Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Partner Site Munich, Munich (Germany); Geinitz, Hans [Johannes Kepler University, Department of Radiation Oncology, Ordensklinikum Linz, Krankenhaus der Barmherzigen Schwestern and Medical Faculty, Linz (Austria); Duma, Marciana N. [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany)

    2017-08-15

    Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3{sup +} T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [German] Die Strahlentherapie (RT) ist eine bewaehrte Behandlung beim primaeren und rezidivierten Prostatakarzinoms. In dieser Studie wurde der Einfluss einer definitiven und Salvage RT auf die Zusammensetzung der Lymphozytensubpopulationen verglichen, um potenzielle Immuneffekte einer RT zu analysieren. In die Studie wurden 33 Prostatakarzinompatienten eingeschlossen

  9. Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy

    International Nuclear Information System (INIS)

    Kinoshita, Hidefumi; Shimizu, Yosuke; Mizowaki, Takashi

    2013-01-01

    Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥2 predictors, respectively. In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies. (author)

  10. Voriconazole salvage treatment of invasive candidiasis.

    NARCIS (Netherlands)

    Ostrosky-Zeichner, L.; Oude Lashof, A.M.L.; Kullberg, B.J.; Rex, J.H.

    2003-01-01

    Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received

  11. 19 CFR 4.97 - Salvage vessels.

    Science.gov (United States)

    2010-04-01

    ... United States and Great Britain ‘concerning reciprocal rights for United States and Canada in the... meaning of this statute. (e) A Mexican vessel may engage in a salvage operation on a Mexican vessel in any territorial waters of the United States in which Mexican vessels are permitted to conduct such operations by...

  12. Using Career Pathways to Guide Students through Programs of Study

    Science.gov (United States)

    Bragg, Debra D.; Krismer, Marianne

    2016-01-01

    This chapter describes career pathways that evolved through a Trade Adjustment Assistance Community College and Career Training consortium grant designed to help students complete programs of study and enter health care careers.

  13. Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

    International Nuclear Information System (INIS)

    Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael; Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele; Geinitz, Hans; Duma, Marciana N.

    2017-01-01

    Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3 + T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [de

  14. A randomized controlled trial of cell salvage in routine cardiac surgery.

    Science.gov (United States)

    Klein, Andrew A; Nashef, Samer A M; Sharples, Linda; Bottrill, Fiona; Dyer, Matthew; Armstrong, Johanna; Vuylsteke, Alain

    2008-11-01

    Previous trials have indicated that cell salvage may reduce allogeneic blood transfusion during cardiac surgery, but these studies have limitations, including inconsistent use of other blood transfusion-sparing strategies. We designed a randomized controlled trial to determine whether routine cell salvage for elective uncomplicated cardiac surgery reduces blood transfusion and is cost effective in the setting of a rigorous transfusion protocol and routine administration of antifibrinolytics. Two-hundred-thirteen patients presenting for first-time coronary artery bypass grafting and/or cardiac valve surgery were prospectively randomized to control or cell salvage groups. The latter group had blood aspirate during surgery and mediastinal drainage the first 6 h after surgery processed in a cell saver device and autotransfused. All patients received tranexamic acid and were subjected to an algorithm for red blood cell and hemostatic blood factor transfusion. There was no difference between the two groups in the proportion of patients exposed to allogeneic blood (32% in both groups, relative risk 1.0 P = 0.89). At current blood products and cell saver prices, the use of cell salvage increased the costs per patient by a minimum of $103. When patients who had mediastinal re-exploration for bleeding were excluded (as planned in the protocol), significantly fewer units of allogeneic red blood cells were transfused in the cell salvage compared with the control group (65 vs 100 U, relative risk 0.71 P = 0.04). In patients undergoing routine first-time cardiac surgery in an institution with a rigorous blood conservation program, the routine use of cell salvage does not further reduce the proportion of patients exposed to allogeneic blood transfusion. However, patients who do not have excessive bleeding after surgery receive significantly fewer units of blood with cell salvage. Although the use of cell savage may reduce the demand for blood products during cardiac surgery, this

  15. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

  16. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

    2014-01-01

    During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

  17. Influence of [18F] fluorodeoxyglucose positron emission tomography on salvage treatment decision making for locally persistent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zheng Xiaojang; Chen Longhua; Wang Quanshi; Wu Fubing

    2006-01-01

    Purpose: The purpose of this study was to evaluate the role of [ 18 F] fluorodeoxyglucose positron emission tomography (FDG-PET) in influencing salvage treatment decision making for locally persistent nasopharyngeal carcinoma (NPC). Methods and Materials: A total of 33 NPC patients with histologic persistence at nasopharynx 1 to 6 weeks after a full course of radiotherapy underwent both computed tomography (CT) and FDG-PET/CT simulation at the same treatment position. The salvage treatment decisions, with regard to the decision to offer salvage treatment and the definition of gross tumor volume (GTV), were made before knowledge of the FDG-PET findings. Subsequently the salvage treatment decisions were made again based on the FDG-PET findings and compared with the pre-FDG-PET decisions. Results: All 33 patients were referred for salvage treatment in the pre-FDG-PET decision. After knowledge of the FDG-PET results, the decision to offer salvage treatment was withdrawn in 4 of 33 patients (12.1%), as no abnormal uptake of FDG was found at nasopharynx. Spontaneous remission was observed in repeat biopsies and no local recurrence was found in these 4 cases. For the remaining 29 patients, GTV based on FDG-PET was smaller than GTV based on CT in 24 (82.8%) cases and was greater in 5 (17.2%) cases, respectively. The target volume had to be significantly modified in 9 of 29 patients (31%), as GTV based on FDG-PET images failed to be enclosed by the treated volume in the salvage treatment plan performed based on GTV based on CT simulation images. Conclusion: Use of FDG-PET was found to influence the salvage treatment decision making for locally persistent NPC by identifying patients who were not likely to benefit from additional treatment and by improving accuracy of GTV definition in salvage treatment planning

  18. Simulation and Analysis of Passive Rolling Compensation of High Sea Salvage System

    Directory of Open Access Journals (Sweden)

    Lin Liqun

    2017-01-01

    Full Text Available Method and device of a flexible interception and salvage system was introduced in this paper. In order to study the effect of wave motion on salvage operation, we proposed a passive wave compensation scheme that utilizes a combination of variable-pitch cylinders and accumulators, and established the mathematical vibration model of the rolling motion of the salvage compensation system. With the relationships between the stiffness coefficient and the accumulator parametric of passive compensated gas-liquid system, we determined the effective compensation stiffness range through Mathematica simulation analysis. The relationship between the roll displacement of the salvage arm and the initial volume Vo of the accumulator has been analysed. The results show that the accumulatorVo in a certain range has a great influence on the passive compensation. However, when the volume is greater than 20m3, the compensation effect is weakened, and tend to a certain value, irrespective of the passive system accumulator volume capacity, it does not achieve full compensation. The results have important guidance on the design and optimization of rolling passive compensation of the practical high sea salvage system.

  19. Gendered Pathways to Burnout: Results from the SALVEO Study.

    Science.gov (United States)

    Beauregard, Nancy; Marchand, Alain; Bilodeau, Jaunathan; Durand, Pierre; Demers, Andrée; Haines, Victor Y

    2018-02-19

    Burnout is a pervasive mental health problem in the workforce, with mounting evidence suggesting ties with occupational and safety outcomes such as work injuries, critical events and musculoskeletal disorders. While environmental [work and non-work, work-to-family conflict (WFC)] and individual (personality) pathways to burnout are well documented, little is known about how gender comes to influence such associative patterns. The aim of the study consisted in examining gendered pathways to burnout. Data were derived from the SALVEO study, a cross-sectional study of 2026 workers from 63 workplaces from the province of Québec (Canada). Data were analyzed using multilevel path analysis. Direct effects of gendered pathways were evidenced for work (e.g. decision latitude) and non-work (e.g. child-related strains) environmental pathways, as well as for individual pathways (i.e. internal locus of control). Indirect effects of gendered pathways were also evidenced, with women reporting higher levels of burnout compared to men due to lower levels of decision latitude and of self-esteem, as well as higher levels of WFC. Women also reported lower burnout levels through investing more time into domestic tasks, which could represent a recovery strategy to highly demanding work. WFC further mediated the associations between working hours and burnout, as well as the between irregular work schedules and burnout. These result suggest than men distinctively reported higher levels of burnout due to the specific nature of their work contract negatively impacting on WFC, and incidentally, on their mental health. Study results supported our hypotheses positing that gender distinctively shapes environmental and individual pathways to burnout. OHS prevention efforts striving for better mental health outcomes in the workforce could relevantly be informed by a gendered approach to burnout.

  20. Limb Salvage After Failed Initial Operative Management of Bimalleolar Ankle Fractures in Diabetic Neuropathy.

    Science.gov (United States)

    Vaudreuil, Nicholas J; Fourman, Mitchell S; Wukich, Dane K

    2017-03-01

    Ankle fractures in patients with diabetes mellitus (DM) can be difficult to manage, especially in the presence of peripheral neuropathy. In patients who fail initial operative management, attempts at limb salvage can be challenging, and no clear treatment algorithm exists. This study examined outcomes of different procedures performed for limb salvage in this population. This study retrospectively reviewed 17 patients with DM complicated by peripheral neuropathy who sustained a bimalleolar ankle fracture and failed initial operative management. Patients were treated with revision open reduction internal fixation (ORIF) (3/17), closed reduction external fixation (CREF) (8/17), or primary ankle joint fusion (3/17 tibiotalocalcaneal fusion with hindfoot nail [TTCN] and 3/17 with tibiotalar arthrodesis using plates and screws [TTA]). Median follow-up was 20 months. The overall rate of limb salvage was 82.3% (14/17). All patients who went on to amputation presented with infection and were treated initially with CREF (3/3). All patients who achieved successful limb salvage ended up with a clinically fused ankle joint (14/14); 9 underwent a primary or delayed formal fusion and 5 had a clinically fused ankle joint at study conclusion after undergoing revision ORIF or CREF with adjunctive procedures. This small study suggests that in this complicated group of patients it is difficult to achieve limb salvage with an end result of a functional ankle joint. CREF can be a viable option in cases where underlying infection or poor bone quality is present. Treatment with revision ORIF frequently requires supplementary external fixator or tibiotalar Steinman pin placement for additional stability. All patients who underwent revision ORIF ended up with clinically fused ankle joints at the end of the study period. Primary fusion procedures (TTA, TTCN) were associated with a high rate of limb salvage and a decreased number of operations. Level III, retrospective case series.

  1. Development of Composite Case Salvage Procedures

    Science.gov (United States)

    1982-04-01

    impacted by the high pressure water. Figure 25 shows damage to EPDM rubber from an MX case. Figure 26 shows the effect of the water on the V-45 ( NBR ... Rubber plus Polyester plus Degradation Elastomer Polyether Cleavage Recycling Reclamation Solvolysis Also: Salvage Rubber Reclamation Elastomers... rubber . 2. Analysis of the material extracted from the insu- lation showed that plasticizer (phthalates) was removed by the solvents. 3. After

  2. The Stringent Response Induced by Phosphate Limitation Promotes Purine Salvage in Agrobacterium fabrum.

    Science.gov (United States)

    Sivapragasam, Smitha; Deochand, Dinesh K; Meariman, Jacob K; Grove, Anne

    2017-10-31

    Agrobacterium fabrum induces tumor growth in susceptible plant species. The upregulation of virulence genes that occurs when the bacterium senses plant-derived compounds is enhanced by acidic pH and limiting inorganic phosphate. Nutrient starvation may also trigger the stringent response, and purine salvage is among the pathways expected to be favored under such conditions. We show here that phosphate limitation induces the stringent response, as evidenced by production of (p)ppGpp, and that the xdhCSML operon encoding the purine salvage enzyme xanthine dehydrogenase is upregulated ∼15-fold. The xdhCSML operon is under control of the TetR family transcription factor XdhR; direct binding of ppGpp to XdhR attenuates DNA binding, and the enhanced xdhCSML expression correlates with increased cellular levels of (p)ppGpp. Xanthine dehydrogenase may also divert purines away from salvage pathways to form urate, the ligand for the transcription factor PecS, which in the plant pathogen Dickeya dadantii is a key regulator of virulence gene expression. However, urate levels remain low under conditions that produce increased levels of xdhCSML expression, and neither acidic pH nor limiting phosphate results in induction of genes under control of PecS. Instead, expression of such genes is induced only by externally supplemented urate. Taken together, our data indicate that purine salvage is favored during the stringent response induced by phosphate starvation, suggesting that control of this pathway may constitute a novel approach to modulating virulence. Because bacterial purine catabolism appears to be unaffected, as evidenced by the absence of urate accumulation, we further propose that the PecS regulon is induced by only host-derived urate.

  3. Percutaneous anterior C1/2 transarticular screw fixation: salvage of failed percutaneous odontoid screw fixation for odontoid fracture

    OpenAIRE

    Wu, Ai-Min; Jin, Hai-Ming; Lin, Zhong-Ke; Chi, Yong-Long; Wang, Xiang-Yang

    2017-01-01

    Background The objective of this study is to investigate the outcomes and safety of using percutaneous anterior C1/2 transarticular screw fixation as a salvage technique for odontoid fracture if percutaneous odontoid screw fixation fails. Methods Fifteen in 108 odontoid fracture patients (planned to be treated by percutaneous anterior odontoid screw fixation) were failed to introduce satisfactory odontoid screw trajectory. To salvage this problem, we chose the percutaneous anterior C1/2 trans...

  4. Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, M M; Dallow, K C; Zietman, A L; Althausen, A F; Heney, N M; McGovern, F J; Shipley, W U

    1995-07-01

    Purpose: To assess the ability of adjuvant irradiation to prevent PSA failure in cases of pT3N0 disease, and of salvage irradiation to durably suppress a rising PSA following radical prostatectomy. Methods and Materials: 62 patients treated by post-operative radiation therapy (60-64Gy in 1.8Gy fractions to the tumor bed) between 1988 and 1993 were evaluated. All had complete pre- and post-radiation PSA data. Median follow up was 3.2 years from time of surgery and 2.2 years from irradiation. 20 patients had Gleason grade 3 disease (moderately differentiated) and 41 Gleason 4-5 (poorly differentiated). 46 had positive inked surgical margins, 18 involved seminal vesicles and 5 had palpable recurrent disease. None had known nodal or metastatic disease. 32 patients underwent adjuvant treatment (undetectable PSA at time of irradiation) and 30 salvage (detectable PSA at time of irradiation). Kaplan-Meier life table analysis was employed. The endpoint studied was freedom from biochemical failure. This was defined as a rise in the PSA of greater than 10% (intra laboratory error <8%) or a previously undetectable PSA becoming detectable. Results: The overall actuarial freedom from biochemical failure at 4 years from radiotherapy was 59%. A significant difference was seen between those receiving adjuvant and those receiving salvage irradiation (71% vs 51%, p=0.03). Amongst those in the salvage group neither the PSA prior to surgery, the PSA at the time of irradiation, the seminal vesicle status, nor the Gleason score (3 vs 4-5) correlated significantly with outcome. The time interval between surgery and irradiation was, however, significant. Those being treated within 6 months fared better than those treated later (60% vs 36%, p=0.04). Further, those treated early were more likely to achieve an undetectable nadir PSA level (94% vs 71%). Conclusion: The addition of adjuvant irradiation appears to improve the 4 year biochemical disease-free survival of patients with poor

  5. A study of the transition pathways of school level scholarship ...

    African Journals Online (AJOL)

    This study tracked the progress of alumni of an educational intervention two or three years post school, in order to investigate their pathways to their destinations of work and study. Forty percent of the alumni were successfully traced, and asked to fill in an online questionnaire. Of the 104 traced alumni, 80% reported good ...

  6. New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD+ salvage from nicotinamide

    Science.gov (United States)

    2014-01-01

    Background In an effort to reconstitute the NAD+ synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD+de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD+de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD+ metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD+ biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD+ salvage pathway from nicotinamide. Results Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Conclusions Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD+ salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD+ salvage pathway might be significant in some bacteria lacking NAD+de novo and NAD+ salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD+. However, this speculation needs to be experimentally tested. PMID:24506841

  7. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  8. Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

    International Nuclear Information System (INIS)

    Pasquier, David; Ballereau, Charles

    2008-01-01

    Purpose: Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. Methods and Materials: A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE. Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. Results: Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). Conclusion

  9. Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study

    International Nuclear Information System (INIS)

    Chen, Kuo-Hsing; Shao, Yu-Yun; Chen, Ho-Min; Lin, Yu-Lin; Lin, Zhong-Zhe; Lai, Mei-Shu; Cheng, Ann-Lii; Yeh, Kun-Huei

    2016-01-01

    Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004–2010) and National Health Insurance (2004–2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08–1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18–1.78, P = .0003). Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC

  10. Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Ali, Ashfaq

    2012-01-01

    and AtTK1b catalyze redundant reactions. The results obtained in the present study suggest a crucial role for the salvage of thymidine during early plant development. Sequence data from the present study have been deposited in the EMBL database/GenBank under accession numbers: AT3G07800.1 (AtTK1a), At5G...

  11. Regeneration response to tornado and salvage harvesting in a bottomland forest

    Science.gov (United States)

    John L. Nelson; John W. Groninger; Loretta L. Battaglia; Charles M. Ruffner

    2010-01-01

    A direct hit from an F4 tornado on May 2003, followed by a partial salvage logging operation at Mermet Lake State Conservation Area on the Ohio River bottoms of southern IL have provided a rare opportunity to assess the responses of a bottomland hardwood forest to severe wind and soil disturbances. The study area encompasses 700 acres and is representative of many...

  12. External and internal hemipelvectomy for sarcomas of the pelvic girdle : consequences of limb-salvage treatment

    NARCIS (Netherlands)

    Ham, SJ; Veth, RPH; van Horn, [No Value; Eisma, WH; Hoekstra, HJ; Schraffordt Koops, H.

    1997-01-01

    The outcome of different Limb-saving treatment modalities for pelvic girdle sarcoma is controversial. The oncological and functional results after 11 external and 10 internal hemipelvectomies and the consequences of limb-salvage treatment were studied in 21 consecutive patients with primary bone (19

  13. Impact of acute hyperglycemia on myocardial infarct size, area at risk and salvage in patients with ST elevation myocardial infarction and the association with exenatide treatment - results from a randomized study

    DEFF Research Database (Denmark)

    Lønborg, Jacob Thomsen; Vejlstrup, Niels Grove; Kelbæk, Henning Skov

    2014-01-01

    Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage....... In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction...... between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index...

  14. Malignant bone tumors and limb-salvage surgery in children

    International Nuclear Information System (INIS)

    Meyer, James S.; Mackenzie, William

    2004-01-01

    Limb-salvage surgery plays a major role in the management of children with malignant bone tumors. This article provides background on the clinical presentation and imaging evaluation of children with malignant bone tumors and describes various limb-salvage procedures used in the treatment of these children. (orig.)

  15. 18F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    International Nuclear Information System (INIS)

    D'Angelillo, Rolando M.; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A.; Trodella, Luca E.; Fiore, Michele; Gallucci, Michele; Maini, Carlo L.; Trodella, Lucio

    2014-01-01

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic 18 F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, 18 F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity

  16. Penalized differential pathway analysis of integrative oncogenomics studies.

    Science.gov (United States)

    van Wieringen, Wessel N; van de Wiel, Mark A

    2014-04-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

  17. Survival outcomes following salvage surgery for oropharyngeal squamous cell carcinoma: systematic review.

    Science.gov (United States)

    Kao, S S; Ooi, E H

    2018-04-01

    Recurrent oropharyngeal squamous cell carcinoma causes great morbidity and mortality. This systematic review analyses survival outcomes following salvage surgery for recurrent oropharyngeal squamous cell carcinoma. A comprehensive search of various electronic databases was conducted. Studies included patients with recurrent or residual oropharyngeal squamous cell carcinoma treated with salvage surgery. Primary outcomes were survival rates following salvage surgery. Secondary outcomes included time to recurrence, staging at time of recurrence, post-operative complications, and factors associated with mortality and recurrence. Methodological appraisal and data extraction were conducted as per Joanna Briggs Institute methodology. Eighteen articles were included. The two- and five-year survival rates of the patients were 52 per cent and 30 per cent respectively. Improvements in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were associated with improvements in two-year overall survival rates, with minimal change to five-year overall survival rates. Various factors were identified as being associated with long-term overall survival, thus assisting clinicians in patient counselling and selection for salvage surgery.

  18. Elucidation of salvage laryngectomy pathologic and clinical variables to guide further treatment intensification investigation.

    Science.gov (United States)

    Scharpf, Joseph; Ward, Matthew; Adelstein, David; Koyfman, Shlomo; Li, Mingsi

    2018-04-01

    There are limited treatment options beyond surgical salvage for patients who fail nonoperative treatment for laryngeal squamous cell carcinoma. In this study, we examine the failure patterns after surgical salvage and the potential pathologic and clinical prognostic variables that might guide further postoperative intensification investigation. Retrospective analysis at a tertiary academic referral center. From an institutional review board-approved institutional head and neck cancer registry, a consecutive series of 147 patients who underwent salvage laryngectomy for squamous cell cancer recurrence or persistence after radiotherapy with or without chemotherapy between May 1995 and May 2016 were identified. Variables potentially associated with oncologic outcome after surgical salvage were then collected and retrospectively evaluated. The projected 2-year locoregional failure rate was 21.8% (95% confidence interval [CI], 14.6%-29.0%]), and the overall survival 65% (95% CI, 57.5%-74.3%) for the entire cohort after salvage laryngectomy. On multivariable analysis, sarcomatoid/spindle cell pathology (hazard ratio [HR], 3.147; 95% CI, 1.181-8.386; P = 0.022), lymphovascular space invasion (LVSI) (positive vs. negative; HR, 2.31; 95% CI, 1.21-4.42; P = 0.011), and advanced initial American Joint Committee on Cancer 7th Edition grouped stage (stages III-IVB vs. stages I-II; HR, 1.64; 95% CI, 1.04-2.6; P = 0.035) were found to be independently associated with inferior disease-free survival. No other clinical or pathologic variables predicted failure. Salvage laryngectomy after nonoperative treatment failure results in successful locoregional control rates and survival in the majority of patients failing initial therapy. This should temper enthusiasm for routine treatment intensification with postoperative re-irradiation and/or other systemic treatments for the vast majority of patients. Sarcomatoid pathology, LVSI, and an advanced initial stage are associated with inferior

  19. Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation.

    Science.gov (United States)

    Lee, Sanghoon; Hyuck David Kwon, Choon; Man Kim, Jong; Joh, Jae-Won; Woon Paik, Seung; Kim, Bong-Wan; Wang, Hee-Jung; Lee, Kwang-Woong; Suh, Kyung-Suk; Lee, Suk-Koo

    2014-09-01

    Salvage liver transplantation (LT) is considered a feasible option for the treatment of recurrent hepatocellular carcinoma (HCC). We performed this multicenter study to assess the risk factors associated with the recurrence of HCC and patient survival after salvage LT. Between January 2000 and December 2011, 101 patients who had previously undergone liver resection (LR) for HCC underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at a median of 10.6 months after the initial LR, and patients underwent salvage LT. Recurrences were within the Milan criteria in 48 cases and were outside the Milan criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the 5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8 months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for poor recurrence-free survival after salvage LT. In conclusion, the timing and extent of HCC recurrence after primary LR both play significant roles in the outcome of salvage LT. © 2014 American Association for the Study of Liver Diseases.

  20. Post-fire salvage logging alters species composition and reduces cover, richness, and diversity in Mediterranean plant communities.

    Science.gov (United States)

    Leverkus, Alexandro B; Lorite, Juan; Navarro, Francisco B; Sánchez-Cañete, Enrique P; Castro, Jorge

    2014-01-15

    An intense debate exists on the effects of post-fire salvage logging on plant community regeneration, but scant data are available derived from experimental studies. We analyzed the effects of salvage logging on plant community regeneration in terms of species richness, diversity, cover, and composition by experimentally managing a burnt forest on a Mediterranean mountain (Sierra Nevada, S Spain). In each of three plots located at different elevations, three replicates of three treatments were implemented seven months after the fire, differing in the degree of intervention: "Non-Intervention" (all trees left standing), "Partial Cut plus Lopping" (felling 90% of the trees, cutting the main branches, and leaving all the biomass in situ), and "Salvage Logging" (felling and piling the logs, and masticating the woody debris). Plant composition in each treatment was monitored two years after the fire in linear point transects. Post-fire salvage logging was associated with reduced species richness, Shannon diversity, and total plant cover. Moreover, salvaged sites hosted different species assemblages and 25% lower cover of seeder species (but equal cover of resprouters) compared to the other treatments. Cover of trees and shrubs was also lowest in Salvage Logging, which could suggest a potential slow-down of forest regeneration. Most of these results were consistent among the three plots despite plots hosting different plant communities. Concluding, our study suggests that salvage logging may reduce species richness and diversity, as well as the recruitment of woody species, which could delay the natural regeneration of the ecosystem. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. A MULTICENTRE STUDY OF ASSESSING THE EFFECTIVENESS OF SALVAGING LYMPHADENECTOMY IN PATIENTS WITH PROSTATE CANCER WITH DISEASE PROGRESSION AFTER THE RADICAL TREATMENT

    Directory of Open Access Journals (Sweden)

    B. Y. Alekseev

    2016-01-01

    Full Text Available Prostate cancer (PC is one of the most urgent problems of modern oncourology because of the continuing high incidence of this pathology. The main methods of radical treatment of patients with localized and locally advanced prostate cancer are radical prostatectomy (RP and radiotherapy – remote (RRT or brachytherapy.  However, the frequency of biochemical markers of disease progression after curative treatment is high and reaches up to 27–53%. It is extremely important to find the tumor lesion that leads to the increase of the marker. The  palliative hormone therapy (PHT was the only accepted method in patients with occurrence of distant metastases in recent time. However, a significant number of patients relapse marker may be associated with the so-called oligo-metastatic disease progression, in which the number of detected metastatic lesions is minimal. As the results of the research, the use of surgical or radiological treatment in selected patients of this cohort can significantly increase the length of time prior to the appointment of HT, and in some cases completely abandon its holding.Purpose. To evaluate the results of the saving pelvic lymphadenectomy in patients with prostate cancer with disease progression after radical therapies.Patients and methods. The article summarizes the results of surgical treatment of patients who have undergone life-saving lymphadenectomy about oligo-nodal metastatic progression of prostate cancer after treatment in 3 centers – P. Hertsen MORI, the branch of NMRRC; N. Petrov Research Institute of Oncology and Russian scientific center of radiology and surgical technologies. In this multicenter study they evaluated the immediate and remote results of surgical treatment of 57 patients.Results. The results performed the high efficiency of the method of the saving pelvic lymphadenectomy in patients with prostate cancer with disease progression after radical treatment. So, response to therapy and reduction

  2. Pegylated liposomal doxorubicin (Lipo-Dox®) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study

    International Nuclear Information System (INIS)

    Rau, Kun-Ming; Lin, Yung-Chang; Chen, Yen-Yang; Chen, Jen-Shi; Lee, Kuan-Der; Wang, Cheng-Hsu; Chang, Hsien-Kun

    2015-01-01

    Anthracycline and taxane are classes of drugs that are frequently used in the adjuvant and palliative settings of metastatic breast cancer (MBC); however, treatment failure occurs in most cases. Limited data demonstrated favorable response in MBC after previous taxane-based treatment. The aim of this study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin (Lipo-Dox®) used as part of a combination salvage therapy for patients with MBC whose tumors progressed during or after taxane-based treatment. Patients with MBC who failed to respond to previous taxane-based treatments were recruited. Treatment with pegylated liposomal doxorubicin (40 mg/m 2 ), cyclophosphamide (500 mg/m 2 ), and 5-fluorouracil (500 mg/m 2 ) was administered every 3 weeks. Tumor response to treatment was determined by using the Response Evaluation Criteria in Solid Tumor criteria version 1.0, and left ventricular ejection fraction was measured before and after treatment using echocardiography. Each patient was followed for 30 days after the last dose of study medication or until resolution/stabilization of any drug-related adverse event. Forty-five patients were recruited. As of December 2012, the median follow-up duration was 29.8 months, the overall response rate was 41.9 %, the median progression-free survival was 8.2 months, and the median overall survival was 36.6 months for all treated patients. Grade 3/4 neutropenia, leucopenia, and neutropenic fever were observed in 14 %, 9 %, and 1 % of the cycles, respectively. Other non-hematologic adverse effects were mild to moderate and were manageable. No decrease in left ventricular ejection function was noted. This regimen of combined of pegylated liposomal doxorubicin, cyclophosphamide, and 5-fluorouracil exhibited a promising overall response rate, progression-free survival rate, and overall survival rate, with a safe cardiac toxicity profile and manageable adverse effects. This regimen could be considered as a

  3. Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. A comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Romagna, Alexander; Schwartz, Christoph; Tonn, Joerg-Christian; Kreth, Friedrich-Wilhelm [Ludwig-Maximilians-University, Department of Neurosurgery, Munich (Germany); Egensperger, Rupert [Ludwig-Maximilians-University, Center for Neuropathology and Prion Research, Munich (Germany); Watson, Juliana; Belka, Claus; Nachbichler, Silke Birgit [Ludwig-Maximilians-University, Department of Radiation-Oncology, Munich (Germany)

    2016-11-15

    Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy{sub 3} and 249.6 Gy{sub 3}). No toxicity-related risk factors were identified. SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment. (orig.) [German] Daten zu Risiko und Effizienz ablativer

  4. INDONESIAN SALVAGE LAW WITHIN THE FRAMEWORK OF CONTEMPORARY MARITIME LAW

    Directory of Open Access Journals (Sweden)

    Dhiana Puspitawati

    2015-12-01

    Full Text Available Located in a strategic position, that is between two great oceans and two land masses have made Indonesia a centre of international trade and shipping. In fact, 90% of international trades are carried out through the ocean. It is therefore crucial to assure that the activities in carrying goods across the ocean are incident free. However, if accident happens, assistance from professionals to preserve items of property is desirable. In such, salvage law emerged. This paper discusses comprehensively Indonesian salvage law within the framework of contemporary maritime law. While Indonesian maritime law is mostly based on its national law on the carriage of goods by the sea, in fact, the development of maritime law is highly affected by international practices which are largely based on international conventions and regulations. This research finds that while Indonesian salvage law can be found in Book II Chapter VII article 545-568k Wetboek Van Koophandel or known as Kitab Undang-undang Hukum Dagang (KUHD, which focused narrowly on the value of salved property as the primary measures of success, yet Indonesian salvage law has not been developed in accordance with current international salvage law, which adopted a broader and more balanced approached in both commercial and environmental aspects. Although it is believed that such approached is “culturally unrecognized” in Indonesia, this research argued that since Indonesian waters are part of international waters, all process by waters including salvage should confirm the relevant international practices and regulations. While Indonesia has taken out salvage law from KUHD and regulates it within Act Number 17/2008 on navigation, however, such act only provides one article for salvage stating that salvage will be regulates further by Ministry Regulation. Untill this paper was written no such government regulation produced yet by Indonesia. Since Indonesian waters is the centre of international

  5. Reaction pathways of the dissociation of methylal: A DFT study

    Energy Technology Data Exchange (ETDEWEB)

    Frey, H -M; Beaud, P; Gerber, T; Mischler, B; Radi, P P; Tzannis, A -P [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Schemata for modelling combustion processes do not yet include reaction rates for oxygenated fuels like methylal (DMM) which is considered as an additive or replacement for diesel due to its low sooting propensity. Density functional theory (DFT) studies of the possible reaction pathways for different dissociation steps of methylal are presented. Cleavage of a hydrogen bond to the methoxy group or the central carbon atom were simulated at the BLYP/6-311++G{sup **} level of theory. The results are compared to the experiment when dissociating and/or ionising DMM with femtosecond pulses. (author) 1 fig., 1 tab., 1 ref.

  6. Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model.

    Science.gov (United States)

    Spiess, Philippe E; Levy, David A; Mouraviev, Vladimir; Pisters, Louis L; Jones, J Stephen

    2013-08-01

    What's known on the subject? and what does the study add?: Previous studies have identified the most important prognostic factors of the likely outcomes of salvage prostate whole-gland ablation, including initial clinical stage, biopsy Gleason score, and PSA (total and doubling time). There is potential for further optimization of candidate selection for salvage cryoablation with curative intent and nadir PSA achieved after whole-gland cryotherapy may provide additional prognostic value. The study shows that the most important prognostic factors of biochemical progression-free survival for patients who have undergone whole-gland salvage prostate cryotherapy are nadir PSA achieved after therapy and pre-therapy biopsy Gleason score. Based on these two prognostic variables, we have identified risk stratification groups (low, intermediate and high) which help predict the expected outcomes of salvage whole-gland prostate cryotherapy in a given patient. This risk stratification constitutes a useful clinical tool in defining which patients maybe best suited for this local salvage treatment method. To assess the prognostic variables predicting the risk of biochemical progression-free survival (bPFS) after salvage prostate whole-gland cryotherapy using the Phoenix definition of bPFS. A total of 132 patients underwent prostate whole-gland salvage cryotherapy with curative intent. No patient underwent neoadjuvant/adjuvant hormonal ablative therapy, and all had extended post-salvage prostate-specific antigen (PSA) follow-up data. Cox univariate and multivariate logistic regression analyses of potential predictors of bPFS were conducted. Kaplan-Meier analyses of bPFS was also performed. At a mean (range) follow-up of 4.3 (0.9-12.7) years, the median (range) post-cryotherapy nadir PSA achieved was 0.17 (0-33.9) ng/mL. On multivariate analysis, predictors of bPFS were nadir PSA post-cryotherapy and pre-salvage biopsy Gleason score (P 2.5 ng/mL or biopsy Gleason score ≥ 7, with

  7. Neuro-ophthalmological conditions: Study of the clinical care pathway.

    Science.gov (United States)

    Layat, I; Challe, G; LeHoang, P; Bodaghi, B; Touitou, V

    2017-06-01

    Neuro-ophthalmologic conditions require specialized multidisciplinary management, both medical and surgical, for patients affected by visual loss due to nervous system disease. The primary goal of this study is to define the specificity of neuro-ophthalmology within the realm of visual health. The secondary goal is to review clinical care pathways by studying the organization of management, in terms of accessibility to care and personalization of the care pathway. A field study was carried out from February to June 2015, within the ophthalmology service of the Pitié-Salpêtrière University Medical Center in Paris. A 30-minute interview with the patient before or after his or her neuro-ophthalmology consultation was performed, to describe the clinical care pathway. The medical records of interviewed patients were also analyzed. Seventeen care pathways (10 women and 7 men) were reviewed. The mean age at appearance of visual involvement was 44.5 years (±8.4 years). If we exclude 3 patients over 66 years and retired, 35.71% were active, 35.71% were disabled, and 28.57% were on sick leave. Ten patients (58.82%) met the criteria for admission to long-term care. The first step had been carried out by local private practitioners. The first physician seen was the general medicine physician (59%), then the private ophthalmologist on an emergency basis (17%). On average, patients went through 8 steps during their care pathway (from 6 to 10 steps) and 14 medical departments were involved. The study showed collaboration with the other services of the University Hospital Department of Vision and Disabilities (notably with the Fondation Rothschild, the Quinze-Vingts National Ophthalmology Hospital, and the Fondation Sainte-Marie). In addition to rehabilitation services, health care professionals participating in the outpatient care of the patients included an orthoptist (11.7%), a psychologist (11.7%), and an optician specializing in low vision for visual aids. Finally

  8. Salvage cryotherapy for local recurrence after radiotherapy for prostate cancer.

    Science.gov (United States)

    Kvorning Ternov, Klara; Krag Jakobsen, Ane; Bratt, Ola; Ahlgren, Göran

    2015-04-01

    The aim of this study was to present the outcome of patients treated with salvage cryotherapy after radiotherapy for prostate cancer at one institution. Consecutive patients treated between 2007 and 2013 with transperineal cryotherapy for biopsy-verified local recurrence after radiotherapy were investigated. An external reviewer retrieved outcome data retrospectively from medical records. Complications were graded according to the Clavien classification. One patient with less than 1 year of follow-up was excluded from the analysis of side-effects. Thirty patients were included, 29 of whom had a follow-up of at least 1 year. The median follow-up was 2.7 years (range 1-6.5 years). Eleven of the 23 patients without hormonal treatment at the time of cryotherapy reached a prostate-specific antigen (PSA) nadir of less than 0.5 ng/ml. At the end of follow-up five of these 23 patients still had a PSA below 0.5 ng/ml and 10 were free from recurrence according to the Phoenix definition. Clinical recurrence (verified with imaging or biopsies) was detected in 13 patients, six of which were local. One patient died from prostate cancer. Eleven patients had urinary incontinence grade 1-2 and three had grade 3-4, seven had pelvic pain, three had severe but transitory tissue sloughing, three developed a urethral stricture or had prolonged urinary retention, and one developed a urinary fistula 4.5 years after cryotherapy. Salvage cryotherapy should be considered as an alternative to hormonal treatment and surgery for local recurrence after radiotherapy for prostate cancer. The results compare well to those reported from centres with longer experience.

  9. Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Joanne W. [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Guzzo, Thomas J.; Wein, Alan J. [Department of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Haas, Naomi B. [Department of Medical Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Both, Stefan [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Vapiwala, Neha, E-mail: vapiwala@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    2012-08-01

    Purpose: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Methods and Materials: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. Results: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores {<=}7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). Conclusions: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in

  10. Physical Activity Measurements: Lessons Learned from the Pathways Study

    Science.gov (United States)

    Going, Scott B.

    2015-01-01

    High obesity rates in American Indian children led to Pathways, a randomized school and community-based childhood prevention study. Seven tribes, five universities, the NIH/NHLBI, and four elementary schools partnered. Increasing physical activity (PA) was an important intervention target. PA assessment was based on study objectives, feasibility, and tribal acceptance. A time-segmented analysis was also desired. Two methods were developed during pilot testing, a new PA questionnaire and accelerometry. Together, the methods provided qualitative and quantitative information and showed 3 of 4 sites were able to increase average daily PA, although overall the control versus intervention difference was not significant. The main limitation was inability to distinguish PA among individuals. Accelerometer size and some community concerns led to a protocol based on a single day of wearing time. Newer model triaxial accelerometers which are much smaller and allow sampling of multiple days of activity are recommended for future studies. PMID:20689391

  11. Postoperative internal iliac artery embolisation as salvage therapy ...

    African Journals Online (AJOL)

    Postoperative internal iliac artery embolisation as salvage therapy for ... of blood products. Damage control surgery was performed, and bleeding was ultimately only ... abdomen was packed with adrenalin-soaked swabs. Coagulation.

  12. Aqueous photodegradation of antibiotic florfenicol: kinetics and degradation pathway studies.

    Science.gov (United States)

    Zhang, Ya; Li, Jianhua; Zhou, Lei; Wang, Guoqing; Feng, Yanhong; Wang, Zunyao; Yang, Xi

    2016-04-01

    The occurrence of antibacterial agents in natural environment was of scientific concern in recent years. As endocrine disrupting chemicals, they had potential risk on ecology system and human beings. In the present study, the photodegradation kinetics and pathways of florfenicol were investigated under solar and xenon lamp irradiation in aquatic systems. Direct photolysis half-lives of florfenicol were determined as 187.29 h under solar irradiation and 22.43 h under xenon lamp irradiation, respectively. Reactive oxygen species (ROS), such as hydroxyl radical (·OH) and singlet oxygen ((1)O2) were found to play an important role in indirect photolysis process. The presence of nitrate and dissolved organic matters (DOMs) could affect photolysis of florfenicol in solutions through light screening effect, quenching effect, and photoinduced oxidization process. Photoproducts of florfenicol in DOMs solutions were identified by solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) analysis techniques, and degradation pathways were proposed, including photoinduced hydrolysis, oxidation by (1)O2 and ·OH, dechlorination, and cleavage of the side chain.

  13. Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

    Science.gov (United States)

    Chae, Kum Ju; Shin, Jin Yong

    2016-01-01

    Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, pdiabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

  14. Designing a Care Pathway Model – A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway

    Directory of Open Access Journals (Sweden)

    Robin I. Oosterholt

    2017-03-01

    Full Text Available Introduction: Although the clinical attributes of total hip arthroplasty (THA care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. Theory: The outpatient THA care pathway enables patients to be discharged on the day of surgery, short- ening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. Methods: An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi- structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. Results: The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1 and mobilisation & discharge (4. The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. Conclusion: The design addressed existing problems and is an optimisation of the case hospital’s pathway. The network of actors consists of the patient (1, radiologist (1, anaesthetist (1, nurse specialist (1, pharmacist (1, orthopaedic surgeon (1,4, physiotherapist (1,4, nurse (4, doctor (4 and patient applica- tion (1,4. The critical value exchanges include patient preparation (mental and practical, patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

  15. Transsulfuration pathway thiols and methylated arginines: the Hunter Community Study.

    Directory of Open Access Journals (Sweden)

    Arduino A Mangoni

    Full Text Available Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH activity] and with symmetric dimethylarginine (SDMA. We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS, and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR = 64 (60-70 years].REGRESSION ANALYSIS SHOWED THAT: a age (P = 0.001, gender (P = 0.03, lower estimated glomerular filtration rate (eGFR, P = 0.08, body mass index (P = 0.008, treatment with beta-blockers (P = 0.03, homocysteine (P = 0.02, and glutamylcysteine (P = 0.003 were independently associated with higher ADMA concentrations; and b age (P = 0.001, absence of diabetes (P = 0.001, lower body mass index (P = 0.01, lower eGFR (P<0.001, cysteine (P = 0.007, and glutamylcysteine (P < 0.001 were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations.After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA and/or cationic amino acid transport requires further investigations.

  16. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    International Nuclear Information System (INIS)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

    2012-01-01

    either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied.

  17. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-09-01

    patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses {>=}70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied.

  18. Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy

    International Nuclear Information System (INIS)

    Cheung, Rex; Kamat, Ashish M.; Crevoisier, Renaud de; Allen, Pamela K.; Lee, Andrew K.; Tucker, Susan L.; Pisters, Louis; Babaian, Richard J.; Kuban, Deborah

    2005-01-01

    Background: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. Patients and Methods: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. Results: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA ≤0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. Conclusion: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal

  19. Limb salvage treatment vs. amputation in sarcoma

    Directory of Open Access Journals (Sweden)

    Motamedi M

    1993-05-01

    Full Text Available Many years ago the treatment of sarcoma was radiotherapy up to 2000-4000 rad. This treatment was very complicated, due to producing neoplasm after radiotherapy. By this method of treatment of osteosarcoma, the rate of survival became about 20% (two years. The second method of treatment was chemotherapy for a period of 2-5 weeks that amputation was performed afterwards. By chemotherapy, the rate of being alive reached up to 25-27% (five years. Right now, the best treatment for sarcoma is limb salvage. In our report, the chance of being alive in chondrosarcoma was about four years. This was nearly the same as that of the other institutes in the world especially in America, Europe, and Japan. The rate of recurrence was also more than that from different parts of the world. The survival rate in osteosarcomatic patients was about two years less for males the females, and it was more in tall people than short ones. The survival rate of the patients with giant cell tumor was more than osteosarcoma up to five years, and it has no recurrence or metastasis

  20. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

    International Nuclear Information System (INIS)

    Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E.

    2006-01-01

    Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery

  1. Salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy for prostate cancer. A single-center experience

    International Nuclear Information System (INIS)

    Yoshida, Takahiro; Nakayama, Masashi; Suzuki, Osamu

    2011-01-01

    The aim of this study was to investigate the efficacy and prognostic factors of salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy for prostate cancer at a single center in Japan. A retrospective review of the medical records of 51 patients who underwent salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy was carried out. Salvage radiotherapy was undergone for the single indication of at least two consecutive prostate-specific antigen elevations >0.1 ng/ml. Salvage radiotherapy was delivered to the prostatic bed at a total dose of 60 or 64 Gy. Late toxicity was scored according to the Common Terminology Criteria for Adverse Events 3.0. A total dose of 60 and 64 Gy were administered to 26 and 25 patients, respectively. The median prostate-specific antigen level at the initiation of radiotherapy was 0.29 ng/ml (range, 0.11-1.10 ng/ml). With a median follow-up of 57.3 months (range, 9.9-134.0 months), the prostate-specific antigen relapse-free rate at 5 years was 50.7%. Multivariate analysis using Cox's proportional hazards regression model revealed that the Gleason score at radical prostatectomy ≥8 significantly predicted prostate-specific antigen relapse after salvage radiotherapy (hazard ratio 4.531; 95% confidence interval 1.413-14.535; P=0.011). The prostate-specific antigen relapse-free rate at 5 years in the Gleason score at radical prostatectomy ≤7 and at radical prostatectomy ≥8 was 62.7 and 15.4%, respectively. Salvage radiotherapy was effective for prostate-specific antigen relapse after radical prostatectomy with tolerable toxicities in Japanese patients. A high Gleason score seemed to be a poor prognostic factor. (author)

  2. Comparative study on gene set and pathway topology-based enrichment methods.

    Science.gov (United States)

    Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

    2015-10-22

    Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

  3. Do indices of coronary conductance after reperfusion reflect the extent of salvaged myocardium?

    Science.gov (United States)

    Shibata, Takahiro; Watanabe, Hisashi; Tsurusaki, Tetsushi; Minai, Kousuke; Ogawa, Takayuki; Iwano, Keiji; Tamura, Tetsutarou; Yoshida, Satoshi; Mutou, Makoto; Imai, Kamon; Horie, Toshinobu; Mochizuki, Seibu

    2004-05-01

    Existing indices of coronary conductance (hyperemic flow-versus-pressure slope index, FPSI, and zero flow pressure, Pzf) have been developed as measures of microcoronary resistance. These indices, however, refer to cases of normal hearts, and there are no reports studying these indices following acute myocardial infarction. In this study, we investigated whether FPSI and Pzf truly measure the extent of myocardial salvage after successful reperfusion therapy. We also developed a new index of zero pressure flow, Fzp. Nineteen patients who underwent successful reperfusion therapy to the proximal portion of the left anterior descending artery (LAD) were studied. After successful reperfusion therapy, a Doppler wire was placed into the LAD. Aortic pressure was recorded in real time. Results from the aortic pressure and flow meter were combined to produce FPSI, Pzf, and Fzp. All cases underwent a resting thallium (Tl) and BMIPP scintigram within five days of successful reperfusion therapy. Infarcted myocardium was estimated using a severity score calculated from the Tl scintigraphy (TlSS), and the BMIPP (BMIPPSS) was estimated using a severity score. Patients with a TlSS/BMIPPSS ratio of less than 0.4 were assigned to the successful salvage group (group S), while the others were assigned to the failed salvage group (group F). FPSI of group F was 1.91 +/- 0.26 m/sec and of group S was 0.92 +/- 0.43 m/sec (P < 0.01). Pzf of group F was 51 +/- 3 mmHg and of group S was 51 +/- 5 mmHg (NS). Fzp of group F was -98 +/- 16 cm/sec and of group S was -46 +/- 4 cm/sec (P < 0.05). FPSI and the new index of Fzp were useful in estimating the extent of myocardial salvage. Our results suggest that the Pzf index could not differentiate between the two groups.

  4. Experimental test of postfire management in pine forests: impact of salvage logging versus partial cutting and nonintervention on bird-species assemblages.

    Science.gov (United States)

    Castro, Jorge; Moreno-Rueda, Gregorio; Hódar, José A

    2010-06-01

    There is an intense debate about the effects of postfire salvage logging versus nonintervention policies on regeneration of forest communities, but scant information from experimental studies is available. We manipulated a burned forest area on a Mediterranean mountain to experimentally analyze the effect of salvage logging on bird-species abundance, diversity, and assemblage composition. We used a randomized block design with three plots of approximately 25 ha each, established along an elevational gradient in a recently burned area in Sierra Nevada Natural and National Park (southeastern Spain). Three replicates of three treatments differing in postfire burned wood management were established per plot: salvage logging, nonintervention, and an intermediate degree of intervention (felling and lopping most of the trees but leaving all the biomass). Starting 1 year after the fire, we used point sampling to monitor bird abundance in each treatment for 2 consecutive years during the breeding and winter seasons (720 censuses total). Postfire burned-wood management altered species assemblages. Salvage logged areas had species typical of open- and early-successional habitats. Bird species that inhabit forests were still present in the unsalvaged treatments even though trees were burned, but were almost absent in salvage-logged areas. Indeed, the main dispersers of mid- and late-successional shrubs and trees, such as thrushes (Turdus spp.) and the European Jay (Garrulus glandarius) were almost restricted to unsalvaged treatments. Salvage logging might thus hamper the natural regeneration of the forest through its impact on assemblages of bird species. Moreover, salvage logging reduced species abundance by 50% and richness by 40%, approximately. The highest diversity at the landscape level (gamma diversity) resulted from a combination of all treatments. Salvage logging may be positive for bird conservation if combined in a mosaic with other, less-aggressive postfire

  5. Comparative study of ion conducting pathways in borate glasses

    International Nuclear Information System (INIS)

    Hall, Andreas; Swenson, Jan; Adams, Stefan

    2006-01-01

    The conduction pathways in metal-halide doped silver, lithium, and sodium diborate glasses have been examined by bond valence analysis of reverse Monte Carlo (RMC) produced structural models of the glasses. Although all glass compositions have basically the same short-range structure of the boron-oxygen network, it is evident that the intermediate-range structure is strongly dependent on the type of mobile ion. The topography of the pathways and the coordination of the pathway sites differ distinctly between the three glass systems. The mobile silver ions in the AgI-doped glass tend to be mainly iodine-coordinated and travel in homogeneously distributed pathways located in salt-rich channels of the borate network. In the NaCl-doped glass, there is an inhomogeneous spatial distribution of pathways that reflects the inhomogeneous introduction of salt ions into the glass. However, since the salt clusters are not connected, no long-range conduction pathways are formed without including also oxygen-rich regions. The pathways in the LiCl-doped glass are slightly more evenly distributed compared to the NaCl-doped glass (but not as ordered as in the AgI-doped glass), and the regions of mainly oxygen-coordinated pathway sites are of higher importance for the long-range migration. In order to more accurately investigate how these differences in the intermediate-range order of the glasses affect the ionic conductivity, we have compared the realistic structure models to more or less randomized structures. An important conclusion from this comparison is that we find no evidence that a pronounced intermediate-range order in the atomic structure or in the network of conduction pathways, as in the AgI-doped glass, is beneficial for the dc conductivity

  6. Trauma center variation in splenic artery embolization and spleen salvage: a multicenter analysis.

    Science.gov (United States)

    Banerjee, Aman; Duane, Therese M; Wilson, Sean P; Haney, Starre; O'Neill, Patrick J; Evans, Heather L; Como, John J; Claridge, Jeffrey A

    2013-07-01

    This study aimed to evaluate if variation in management of blunt splenic injury (BSI) among Level I trauma centers is associated with different outcomes related to the use of splenic artery embolization (SAE). All adult patients admitted for BSI from 2008 to 2010 at 4 Level I trauma centers were reviewed. Use of SAE was determined, and outcomes of spleen salvage and nonoperative management (NOM) failure were evaluated. A priori, a 10% SAE rate was used to group centers into high- or low-use groups. There were 1,275 BSI patients. There were intercenter differences in age, injury severity, and grade of spleen injury (Spleen Injury Scale [SIS]). Mortality was similar by center; however, BSI treatment varied significantly by center. Overall, SAE use was highest at center A compared with B, C, and D (19%, 11%, 1%, and 4%, respectively; p trauma centers. Centers with higher rates of SAE use have higher spleen salvage and less NOM failure. SAE was shown to be an independent predictor of spleen salvage. Therapeutic study, level IV.

  7. Travel distance and use of salvage palliative chemotherapy in patients with metastatic colorectal cancer.

    Science.gov (United States)

    Ahmed, Shahid; Iqbal, Mahjabeen; Le, Duc; Iqbal, Nayyer; Pahwa, Punam

    2018-04-01

    Salvage palliative chemotherapy in metastatic colorectal cancer has been associated with significant improvement in survival. However, not all patients receive all available therapies. Travel burden can affect patient access and use of future therapy. The present study aims to determine relationship between travel distance (TD) and salvage palliative chemotherapy in patients with metastatic colorectal cancer. A patient cohort diagnosed with metastatic colorectal cancer during 2006-2010 in the province of Saskatchewan, Canada was studied. Logistic regression analyses were performed to assess relationship between travel distance and subsequent line therapies. The median age of 264 eligible patients was 62 years [interquartile range (IQR): 53-72]. The patients who received salvage systemic therapy had a median distance to travel of 60.0 km (IQR: 4.7-144) compared with 88.1 km (IQR: 4.8-189) if they did not receive second- or third-line therapy (P=0.06). In multivariate analysis distance to the cancer center therapies. Our result revealed that travel distance to the cancer center greater than 100 km was associated less frequent use of second or subsequent line therapies in patients with metastatic colorectal cancer.

  8. Seminal vesicle involvement at salvage radical prostatectomy.

    Science.gov (United States)

    Meeks, Joshua J; Walker, Marc; Bernstein, Melanie; Eastham, James A

    2013-06-01

    To describe the incidence and clinical outcomes of seminal vesicle invasion (SVI) at salvage radical prostatectomy (SRP) and to describe the accuracy of SV biopsy. As SRP is used after biochemical recurrence (BCR) of prostate cancer after radiotherapy (RT) to gain local oncological control. The SVs receive lower doses of radiation from external-beam RT (EBRT) to avoid rectal exposure and are not targeted with brachytherapy (BT) with low-risk prostate cancer. SRP was performed on 206 men with BCR after RT at a tertiary care institution between 1998 and 2011. Post-RT biopsy and SRP specimens were reviewed by a genitourinary pathologist. SVI was detected in 65 (32%) of 206 patients. No difference was found between EBRT alone (65% vs 63%) and BT (29% vs 31%) with or without EBRT in patients with SVI. Men with SVI had higher rates of cT3 disease (20% vs 8%) and Gleason score ≥ 8 at SRP (52% vs 21%). BCR-free survival at 5 years was 18% and 56% in patients with and without SVI (hazard ratio 2.85, 95% confidence interval 1.87-4.36, P < 0.001), yet the rate of local recurrence was low (11%). Prostate cancer was identified in nine of 18 patients who underwent SV biopsy and was the only location of prostate cancer in two patients. SVI is a prognostic indicator for BCR after SRP, but local recurrence in patients with SVI after SRP remains low. We recommend SV biopsy to improve staging and cancer detection in men with BCR after radiotherapy. © 2013 BJU International.

  9. Immunohistochemical Studies of the Kynurenine Pathway in Morphea

    Directory of Open Access Journals (Sweden)

    Rowland Noakes

    2013-01-01

    Full Text Available Cutaneous sclerosis, resembling that seen in subcutaneous morphea, is a feature of eosinophilic fasciitis and eosinophilia-myalgia syndrome, two conditions in which the kynurenine pathway is known to be activated. To investigate the possibility of activation of the kynurenine pathway in morphea, skin biopsies were taken from involved and non-involved sites in a series of three patients with morphea. Immunohistochemical stains for quinolinic acid and indoleamine 2,3-dioxygenase (IDO were performed.

  10. Immunohistochemical Studies of the Kynurenine Pathway in Morphea

    OpenAIRE

    Noakes, Rowland; Mellick, Nick

    2013-01-01

    Cutaneous sclerosis, resembling that seen in subcutaneous morphea, is a feature of eosinophilic fasciitis and eosinophilia-myalgia syndrome, two conditions in which the kynurenine pathway is known to be activated. To investigate the possibility of activation of the kynurenine pathway in morphea, skin biopsies were taken from involved and non-involved sites in a series of three patients with morphea. Immunohistochemical stains for quinolinic acid and indoleamine 2,3-dioxygenase (IDO) were perf...

  11. Coupled Responses of Sewol, Twin Barges and Slings During Salvage

    Science.gov (United States)

    Yao, Zong; Wang, Wei-ping; Jiang, Yan; Chen, Shi-hai

    2018-04-01

    Korean Sewol is successfully lifted up with the strand jack system based on twin barges. During the salvage operation, two barges and Sewol encounter offshore environmental conditions of wave, current and wind. It is inevitable that the relative motions among the three bodies are coupled with the sling tensions, which may cause big dynamic loads for the lifting system. During the project engineering phase and the site operation, it is necessary to build up a simulation model that can precisely generate the coupled responses in order to define a suitable weather window and monitor risks for the salvage operation. A special method for calculating multibody coupled responses is introduced into Sewol salvage project. Each body's hydrodynamic force and moment in multibody configuration is calculated in the way that one body is treated as freely moving in space, while other bodies are set as fixed globally. The hydrodynamic force and moment are then applied into a numerical simulation model with some calibration coefficients being inserted. These coefficients are calibrated with the model test results. The simulation model built up this way can predict coupled responses with the similar accuracy as the model test and full scale measurement, and particularly generate multibody shielding effects. Site measured responses and the responses only resulted from from the simulation keep project management simultaneously to judge risks of each salvage stage, which are important for success of Sewol salvage.

  12. Natural recovery and leaf water potential after fire influenced by salvage logging and induced drought stress

    Directory of Open Access Journals (Sweden)

    D. Moya

    2013-01-01

    Full Text Available Salvage logging is one of the most common emergency actions in the short-term management after a fire. Several studies have been carried out and some obtained positive results which incite to carry it out but other, found negative effects on seedling establishment and regeneration. In addition, climatic changes will have large impacts on vegetation productivity and resilience since the regional models for south-eastern Spain predicts a rainfall decrease of about 20% and temperature increase of 4.5 ºC. Our aim was to determine how short-term forest management and induced drought affect the ecosystem recovery in Aleppo pine stands naturally recovered after a fire.In summer 2009, a mid-high severity fire burned 968 ha of Aleppo pine (Pinus halepensis Mill. forest in south-eastern Spain. Six months later, a salvage logging was carried out. The Aleppo pine recruitment was negligible. During summer 2010, twelve square plots (2m x 2m were set in the three scenarios: control, salvaged and drought induced. The surface cover and soil water availability for three dominant understory species were recorded in four field campaigns: Spring-2010, Fall-2010, Spring-2011 and Fall-2011.The season, management and the target species showed significant differences in growing and water stress. In general, Esparto grass showed lower water stress, mainly in Fall, a higher increase of total coverage. Both effects were showing their highest values in non-salvaged areas and no drought. Changes in leaf water potential and soil water content after the drought season influence the survival and development of individuals.Our results indicate that soil water content and ecosystem response can be modified by short-term silvicultural treatments. Therefore, management after fire could cause opposite effects to those initially foreseen, since they depend on fire severity, and type of ecosystem management response. So, their application must be evaluated and assessed before

  13. ent-Steroids: novel tools for studies of signaling pathways.

    Science.gov (United States)

    Covey, Douglas F

    2009-07-01

    Membrane receptors are often modulated by steroids and it is necessary to distinguish the effects of steroids at these receptors from effects occurring at nuclear receptors. Additionally, it may also be mechanistically important to distinguish between direct effects caused by binding of steroids to membrane receptors and indirect effects on membrane receptor function caused by steroid perturbation of the membrane containing the receptor. In this regard, ent-steroids, the mirror images of naturally occurring steroids, are novel tools for distinguishing between these various actions of steroids. The review provides a background for understanding the different actions that can be expected of steroids and ent-steroids in biological systems, references for the preparation of ent-steroids, a short discussion about relevant forms of stereoisomerism and the requirements that need to be fulfilled for the interaction between two molecules to be enantioselective. The review then summarizes results of biophysical, biochemical and pharmacological studies published since 1992 in which ent-steroids have been used to investigate the actions of steroids in membranes and/or receptor-mediated signaling pathways.

  14. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  15. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  16. Overlapping Bark Beetle Outbreaks, Salvage Logging and Wildfire Restructure a Lodgepole Pine Ecosystem

    Directory of Open Access Journals (Sweden)

    Charles C. Rhoades

    2018-02-01

    Full Text Available The 2010 Church’s Park Fire burned beetle-killed lodgepole pine stands in Colorado, including recently salvage-logged areas, creating a fortuitous opportunity to compare the effects of salvage logging, wildfire and the combination of logging followed by wildfire. Here, we examine tree regeneration, surface fuels, understory plants, inorganic soil nitrogen and water infiltration in uncut and logged stands, outside and inside the fire perimeter. Subalpine fir recruitment was abundant in uncut, unburned, beetle-killed stands, whereas lodgepole pine recruitment was abundant in cut stands. Logging roughly doubled woody fuel cover and halved forb and shrub cover. Wildfire consumed all conifer seedlings in uncut and cut stands and did not stimulate new conifer regeneration within four years of the fire. Aspen regeneration, in contrast, was relatively unaffected by logging or burning, alone or combined. Wildfire also drastically reduced cover of soil organic horizons, fine woody fuels, graminoids and shrubs relative to unburned, uncut areas; moreover, the compound effect of logging and wildfire was generally similar to wildfire alone. This case study documents scarce conifer regeneration but ample aspen regeneration after a wildfire that occurred in the later stage of a severe beetle outbreak. Salvage logging had mixed effects on tree regeneration, understory plant and surface cover and soil nitrogen, but neither exacerbated nor ameliorated wildfire effects on those resources.

  17. Extended Salvage Pelvic Lymph Node Dissection in Patients with Recurrent Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniar K. Osmonov

    2014-01-01

    Full Text Available Background. Treatment of patients with a biochemical recurrence (BCR of prostate cancer (PCa is generally difficult and without valid treatment options. Since 2004 we have been developing therapeutic possibilities for these patients. Methods. We retrospectively analyzed a cohort of 41 patients with a BCR of PCa and a mean followup of 40.3±20.8 months. Group 1 (n=10: salvage radical prostatectomy (sRP with SePLND (salvage extended pelvic lymph nodes dissection (initial treatment: combined brachytherapy. Group 2 (n=22: SePLND (initial treatment: radical prostatectomy (RP. Group 3 (n=9: SePLND (initial treatment: RP and adjuvant radiation therapy (RT. We observed PSA, PSA-velocity, localization of LNs and LNs+, BCR-free period, and BR (biochemical response. Results. Group 1: 60% with BCR-freedom (mean 27.2 months. Group 2: 63.6% with BCR-freedom (mean 17.5 months. Group 3: 33.3% with BCR-freedom (mean 17.6 months. In total, BCR-freedom was observed in 23 of 41 patients (56.1% after salvage surgery. 75.6% of all patients showed a BR. 765 LNs were removed and 14.8% of these were LN+. Conclusions. The BCR-free period and BR are comparable in all three groups. Sensibility to ADT can be reestablished and prolonged as a result of SePLND. Multicenter studies are needed for a reliable output.

  18. Free flap reconstruction for diabetic foot limb salvage.

    Science.gov (United States)

    Sato, Tomoya; Yana, Yuichiro; Ichioka, Shigeru

    2017-12-01

    Although free flap is gaining popularity for the reconstruction of diabetic foot ulcers, it is unclear whether free flap reconstruction increases the chances of postoperative independent ambulation. The aim of this study is to evaluate the relationship between free flap success and postoperative ambulation. This study reviewed 23 cases of free flap reconstruction for diabetic foot ulcers between January 2007 and March 2014. Free rectus abdominis, latissimus dorsi, and anterolateral thigh flaps were used in ten, eight, and five patients, respectively. A comparison was made between free flap success and postoperative independent ambulation using Fisher's exact test. Two patients developed congestive heart failure with fatal consequences within 14 days postoperatively, resulting in an in-hospital mortality rate of 8.7%. Five patients lost their flaps (21.7%). Of the 16 patients who had flap success, 12 achieved independent ambulation. Five patients with flap loss did not achieve independent ambulation, except one patient who underwent secondary flap reconstruction using a distally based sural flap. Fisher's exact test revealed that independent ambulation was associated with free flap success (p = 0.047). The present study indicates that free flap reconstruction may increase the possibility of independent ambulation for patients with extensive tissue defects due to diabetic ulcers. Intermediate limb salvage rates and independent ambulation rates were favourable in patients with successful reconstruction. The use of foot orthoses and a team approach with pedorthists were effective to prevent recurrence.

  19. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

    NARCIS (Netherlands)

    Nijhuis, Esther R.; van der Zee, Ate G. J.; In 't Hout, Bertha A.; Boomgaard, Jantine J.; de Hullu, Joanne A.; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Jijman, Hans W.; Willemse, Pax H. B.; Mourits, Marian J. E.

    2006-01-01

    Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective

  20. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery.

    NARCIS (Netherlands)

    Nijhuis, E.R.; Zee, A.G. van der; Hout, B.A. van; Boomgaard, J.J.; Hullu, J.A. de; Pras, E.; Hollema, H.; Aalders, J.G.; Nijman, H.W.; Willemse, P.H.B.; Mourits, M.J.E.

    2006-01-01

    PURPOSE: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. METHODS AND MATERIALS: In a retrospective

  1. Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

    Science.gov (United States)

    Batschinski, K; Dervisis, N G; Kitchell, B E

    2014-12-01

    A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

  2. Freeze-drying wet digital prints: An option for salvage?

    International Nuclear Information System (INIS)

    Juergens, M C; Schempp, N

    2010-01-01

    On the occasion of the collapse of the Historical Archive of the City of Cologne in March 2009 and the ensuing salvage effort, questions were raised about the use of freeze-drying for soaked digital prints, a technique that has not yet been evaluated for these materials. This study examines the effects of immersion, air-drying, drying in a blotter stack, freezing and freeze-drying on 35 samples of major digital printing processes. The samples were examined visually before, during and after testing; evaluation of the results was qualitative. Results show that some prints were already damaged by immersion alone (e.g. bleeding inks and soluble coatings) to the extent that the subsequent choice of drying method made no significant difference any more. For those samples that did survive immersion, air-drying proved to be crucial for water-sensitive prints, since any contact with the wet surface caused serious damage. Less water-sensitive prints showed no damage throughout the entire procedure, regardless of drying method. Some prints on coated media suffered from minor surface disruption up to total delamination of the surface coating due to the formation of ice crystals during shock-freezing. With few exceptions, freeze-drying did not cause additional damage to any of the prints that hadn't already been damaged by freezing. It became clear that an understanding of the process and materials is important for choosing an appropriate drying method.

  3. Radiolabeling as a tool to study uptake pathways in plants

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Reactive Transport; Fricke, T. [Vita34 BioPlanta, Leipzig (Germany)

    2017-06-01

    The identification of major uptake pathways in plants is an important factor when evaluation the fate of manufactured nanoparticles in the environment and the associated risks. Using different radiolabeling techniques we were able to show a predominantly particulate uptake for CeO{sub 2} nanoparticles (NPs) in contrast to a possible uptake in the form of ionic cerium.

  4. 78 FR 74128 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

    Science.gov (United States)

    2013-12-10

    ... Recovery Settlement; Cadie Auto Salvage Site, Belvidere, Boone County, Illinois AGENCY: Environmental... Auto Salvage Site in Belvidere, Boone County, Illinois with the following settling parties: UOP, LLC... Cadie Auto Salvage Site, Belvidere, Boone County, Illinois and EPA Docket No. and should be addressed to...

  5. 78 FR 77673 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

    Science.gov (United States)

    2013-12-24

    ... Recovery Settlement; Cadie Auto Salvage Site, Belvidere, Boone County, Illinois AGENCY: Environmental... Auto Salvage Site in Belvidere, Boone County, Illinois with the following settling party: Helen E... reference the Cadie Auto Salvage Site, Belvidere, Boone County, Illinois and EPA Docket No. and should be...

  6. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

    2014-02-15

    The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

  7. Suggestion for the prostatic fossa clinical target volume in adjuvant or salvage radiotherapy after a radical prostatectomy

    International Nuclear Information System (INIS)

    Park, Jun Su; Park, Won; Pyo, Hong Ryull; Park, Byung Kwan; Park, Sung Yoon; Choi, Han Yong; Lee, Hyun Moo; Jeon, Seong Soo; Seo, Seong Il; Jeong, Byong Chang; Jeon, Hwang Gyun

    2014-01-01

    Background and purpose: To assess the location of recurrent tumors and suggest the optimal target volume in adjuvant or salvage radiotherapy (RT) after a radical prostatectomy (RP). Material and methods: From January 2000 to December 2012, 113 patients had been diagnosed with suspected recurrent prostate cancer by MRI scan and received salvage RT in the Samsung Medical Center. This study assessed the location of the suspected tumor recurrences and used the inferior border of the pubic symphysis as a point of reference. Results: There were 118 suspect tumor recurrences. The most common site of recurrence was the anastomotic site (78.8%), followed by the bladder neck (15.3%) and retrovesical area (5.9%). In the cranial direction, 106 (87.3%) lesions were located within 30 mm of the reference point. In the caudal direction, 12 lesions (10.2%) were located below the reference point. In the transverse plane, 112 lesions (94.9%) were located within 10 mm of the midline. Conclusions: A MRI scan acquired before salvage RT is useful for the localization of recurrent tumors and the delineation of the target volume. We suggest the optimal target volume in adjuvant or salvage RT after RP, which includes 97% of suspected tumor recurrences

  8. Salvage surgery for hypopharyngeal carcinoma and cervical esophageal carcinoma with local recurrence or residual tumor after chemoradiotherapy

    International Nuclear Information System (INIS)

    Takemura, Hirokazu; Hayashi, Ryuichi; Yamazaki, Mitsuo

    2008-01-01

    In this study, we present the treatment results of salvage surgery in 34 patients with residual primary tumor or local relapse tumor in the hypopharynx and cervical esophagus after radiotherapy (15 patients) or chemoradiotherapy (19 patients) at the Division of Head and Neck Surgery, National Cancer Center Hospital East between 1997 and 2006. All patients underwent total pharyngolaryngoesophagectomy (TPLE) as salvage surgery. Among these patients, postoperative complication was observed in 11 patients (32.4%). Fisher's exact test revealed no significant difference in postoperative complication rate between the radiotherapy (RT) group and chemoradiotherapy (CRT) group. Tumors in the neck recurred in 10 patients (55.6%) after surgical resection. The tumor recurrence control rate for cervical lymph nodes was 84.7% for patients with clinically N0 disease after CRT who had not undergone neck dissection. The median survival time was 392 days. We consider that salvage surgery can he safely performed by considering the necessity and method of operation, and the outcome of patients receiving CRT would he improved by salvage surgery. (author)

  9. Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

    Science.gov (United States)

    Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

    2014-09-01

    Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

  10. Dismal salvage of testicular torsion: A call to action! | Maranya ...

    African Journals Online (AJOL)

    ... were not subjected to orchidopexy. There was no occurrence of torsion after orchidopexy. Conclusion: Testicular torsions were associated with low salvage rates. Increased public awareness coupled with clinician, parental, teacher, teenage and adult male education with respect to the consequences of acute scrotal pain ...

  11. Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

    International Nuclear Information System (INIS)

    Ovacik, Meric A.; Sen, Banalata; Euling, Susan Y.; Gaido, Kevin W.; Ierapetritou, Marianthi G.; Androulakis, Ioannis P.

    2013-01-01

    Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data

  12. Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

    Energy Technology Data Exchange (ETDEWEB)

    Ovacik, Meric A. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Sen, Banalata [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC 20460 (United States); Gaido, Kevin W. [U.S. Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Division of Human Food Safety, Rockville, MD 20855 (United States); Ierapetritou, Marianthi G. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Biomedical Engineering Department, Rutgers University, NJ 08854 (United States)

    2013-09-15

    Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.

  13. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    DEFF Research Database (Denmark)

    Sarwar, Nadeem; Sandhu, Manjinder S; Ricketts, Sally L

    2010-01-01

    Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality.......Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality....

  14. Serum PSA Evaluations during salvage radiotherapy for post-prostatectomy biochemical failures as prognosticators for treatment outcomes

    International Nuclear Information System (INIS)

    Do, Tri; Dave, Giatri; Parker, Robert; Kagan, A. Robert

    2001-01-01

    Introduction: Serum prostate specific antigen (PSA) levels have proved to be sensitive markers for the diagnosis of prostate cancer. In addition, PSA levels are useful for detecting and monitoring prostate cancer progression after radiotherapy. Serum PSA evaluations during radiotherapy, however, have not been well documented. In this study, we investigate the prognostic value of PSA evaluations during salvage radiotherapy for prostatectomy failures. Methods: Forty-one patients with biochemical failures after prostatectomy treated with salvage radiotherapy consented to have their serum PSA levels evaluated at 30 Gy and 45 Gy of irradiation. All 41 patients had negative metastatic workup and pathologically uninvolved pelvic lymph nodes at the time of referral for salvage radiotherapy. Radiation therapy was delivered with 10-25 MV photons, with doses of 59.4-66.6 Gy. No patients received hormonal ablation therapy before irradiation. Results: The mean follow-up for all patients was 30.9 months. At last follow-up, 28/41 patients (68.3%) were free from biochemical failure, with 20 of 41 patients (48.8%) expressing undetectable PSA levels. Serum PSA evaluations at 30 Gy did not significantly predict for either biochemical (p=0.0917) or clinical (p=0.106) disease-free outcome. However, serum PSA evaluations at 45 Gy significantly predicted for both biochemical (p=0.0043) and clinical (p=0.0244) disease-free outcomes, with PSA elevations at 45 Gy significantly associated with poor outcomes. On univariate analysis of prognosticators for biochemical failures, the following were significant: an elevation in serum PSA levels at 45 Gy, detectable serum PSA immediately after prostatectomy, Gleason score 7-10, and serum PSA level >1 ng/ml before salvage radiotherapy. Conclusion: Evaluation of serum PSA level at 45 Gy of salvage radiotherapy for biochemical relapses after prostatectomy may serve as a significant prognosticator for both biochemical and clinical disease-free outcomes

  15. Metabolic signature of sun exposed skin suggests catabolic pathway overweighs anabolic pathway.

    Directory of Open Access Journals (Sweden)

    Manpreet Randhawa

    Full Text Available Skin chronically exposed to sun results in phenotypic changes referred as photoaging. This aspect of aging has been studied extensively through genomic and proteomic tools. Metabolites, the end product are generated as a result of biochemical reactions are often studied as a culmination of complex interplay of gene and protein expression. In this study, we focused exclusively on the metabolome to study effects from sun-exposed and sun-protected skin sites from 25 human subjects. We generated a highly accurate metabolomic signature for the skin that is exposed to sun. Biochemical pathway analysis from this data set showed that sun-exposed skin resides under high oxidative stress and the chains of reactions to produce these metabolites are inclined toward catabolism rather than anabolism. These catabolic activities persuade the skin cells to generate metabolites through the salvage pathway instead of de novo synthesis pathways. Metabolomic profile suggests catabolic pathways and reactive oxygen species operate in a feed forward fashion to alter the biology of sun exposed skin.

  16. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

    Full Text Available Abstract Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.

  17. Oncologic outcome and patterns of recurrence after salvage radical prostatectomy.

    Science.gov (United States)

    Paparel, Philippe; Cronin, Angel M; Savage, Caroline; Scardino, Peter T; Eastham, James A

    2009-02-01

    Limited data on patterns of recurrence (local or metastatic) after salvage radical prostatectomy (SP) is available. To examine biochemical, local and metastatic patterns of recurrence in patients undergoing SP for radiation-recurrent prostate cancer. 146 patients with biopsy-proven local recurrence of prostate cancer after radiation therapy treated with SP were evaluated in a retrospective study at a single institution. All patients underwent SP by mainly two surgeons. Biochemical recurrence (BCR) after SP was defined as a serum prostate-specific antigen (PSA) level of >or=0.2 ng/ml or was defined by the initiation of androgen deprivation therapy. All predictors analyzed were determined after radiotherapy, before SP, and included PSA level, clinical stage, biopsy Gleason score, age at SP, and time interval from radiotherapy to SP. Of the 146 patients treated with SP, 65 developed BCR. The median follow-up period for recurrence-free patients was 3.8 yr; 43 patients (29%) were followed for >5 yr. Overall, the 5-yr recurrence-free probability was 54% (95% CI, 44-63%). Clinical local recurrence occurred in only one patient who also had bone metastases. Overall, there were 16 prostate cancer-specific deaths and 19 deaths from other causes. The 5-yr cumulative incidence of death from prostate cancer was 4% (95% CI, 2-11%). Pre-SP serum PSA level and biopsy Gleason score were significantly associated with death due to prostate cancer (p<0.0005 and p=0.002, respectively). This study is retrospective and included carefully selected patients treated over a long period by, mainly, two experienced surgeons. SP provides excellent local cancer control; only one patient in our series experienced a clinical local recurrence. Earlier identification of patients with persistent, viable local cancer despite radiation therapy will appropriately select patients for SP.

  18. Enriched pathways for major depressive disorder identified from a genome-wide association study.

    Science.gov (United States)

    Kao, Chung-Feng; Jia, Peilin; Zhao, Zhongming; Kuo, Po-Hsiu

    2012-11-01

    Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD. For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways. We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p⩽1×10-5), calcium signalling (p⩽6×10-5), arrhythmogenic right ventricular cardiomyopathy (p⩽1.6×10-4) and cell adhesion molecules (p⩽2.2×10-4). In conclusion, our comprehensive pathway analyses identified promising pathways for depression that are related to neurotransmitter and neuronal systems, immune system and inflammatory response, which may be involved in the pathophysiological mechanisms underlying depression. We demonstrated that pathway enrichment analysis is promising to facilitate our understanding of complex traits through a deeper interpretation of GWA data. Application of this comprehensive analytic strategy in upcoming GWA data for depression could validate the findings reported in this study.

  19. What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review.

    Science.gov (United States)

    Lawal, Adegboyega K; Rotter, Thomas; Kinsman, Leigh; Machotta, Andreas; Ronellenfitsch, Ulrich; Scott, Shannon D; Goodridge, Donna; Plishka, Christopher; Groot, Gary

    2016-02-23

    Clinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in healthcare. This may be attributable to both the differences in definition and a lack of conceptualization in the field of clinical pathways. This correspondence article describes a process of refinement of an operational definition for CPW research and proposes an operational definition for the future syntheses of CPWs literature. Following the approach proposed by Kinsman et al. (BMC Medicine 8(1):31, 2010) and Wieland et al. (Alternative Therapies in Health and Medicine 17(2):50, 2011), we used a four-stage process to generate a five criteria checklist for the definition of CPWs. We refined the operational definition, through consensus, merging two of the checklist's criteria, leading to a more inclusive criterion for accommodating CPW studies conducted in various healthcare settings. The following four criteria for CPW operational definition, derived from the refinement process described above, are (1) the intervention was a structured multidisciplinary plan of care; (2) the intervention was used to translate guidelines or evidence into local structures; (3) the intervention detailed the steps in a course of treatment or care in a plan, pathway, algorithm, guideline, protocol or other 'inventory of actions' (i.e. the intervention had time-frames or criteria-based progression); and (4) the intervention aimed to standardize care for a specific population. An intervention meeting all four criteria was considered to be a CPW. The development of operational definitions for complex interventions is a useful approach to appraise and synthesize evidence for policy development and quality improvement.

  20. Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD Concentration in Human Primary Astrocytes

    Directory of Open Access Journals (Sweden)

    Ross Grant

    2010-01-01

    Full Text Available Efficient synthesis of NAD + is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s by which cells of the central nervous system produce NAD + . The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP and de novo NAD + synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD + levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD + levels after 24 hrs. This decrease in NAD + was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide.

  1. Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD+ Concentration in Human Primary Astrocytes

    Science.gov (United States)

    Grant, Ross; Nguyen, Susan; Guillemin, Gilles

    2010-01-01

    Efficient synthesis of NAD+ is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s) by which cells of the central nervous system produce NAD+. The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP) and de novo NAD+ synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD+ levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD+ levels after 24 hrs. This decrease in NAD+ was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide. PMID:22084595

  2. 'Therapeutic landscapes' and the importance of nostalgia, solastalgia, salvage and abandonment for psychiatric hospital design.

    Science.gov (United States)

    Wood, Victoria J; Gesler, Wil; Curtis, Sarah E; Spencer, Ian H; Close, Helen J; Mason, James; Reilly, Joe G

    2015-05-01

    We examine emotional reactions to changes to medical spaces of care, linked with past experiences. In this paper we draw on findings from a qualitative study of the transfer of psychiatric inpatient care from an old to a newly built facility. We show how the meanings attributed to 'therapeutic landscapes' from one׳s past can evoke emotions and memories, manifesting in ideas about nostalgia, solastalgia, salvage and abandonment, which can impinge on one׳s present therapeutic experience. We reflect on how consideration of these ideas might contribute to better future design of psychiatric inpatient facilities and the wellbeing of those using them. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Failure pattern and salvage treatment after radical treatment of head and neck cancer

    DEFF Research Database (Denmark)

    Pagh, Anja; Grau, Cai; Overgaard, Jens

    2016-01-01

    Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal...... recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T...

  4. Deoxynucleoside Salvage in Fission Yeast Allows Rescue of Ribonucleotide Reductase Deficiency but Not Spd1-Mediated Inhibition of Replication

    Directory of Open Access Journals (Sweden)

    Oliver Fleck

    2017-04-01

    Full Text Available In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1 blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4Cdt2 E3 ubiquitin ligase mediates degradation of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have generated a conditional allele of CRL4Cdt2, by expressing the highly unstable substrate-recruiting protein Cdt2 from a repressible promoter. Unlike Spd1, Spd2 does not regulate deoxynucleotide triphosphate (dNTP pools; yet we find that Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly test whether this block of replication was solely due to insufficient dNTP levels, we established a deoxy-nucleotide salvage pathway in fission yeast by expressing the human nucleoside transporter human equilibrative nucleoside transporter 1 (hENT1 and the Drosophila deoxynucleoside kinase. We present evidence that this salvage pathway is functional, as 2 µM of deoxynucleosides in the culture medium is able to rescue the growth of two different temperature-sensitive alleles controlling ribonucleotide reductase. However, salvage completely failed to rescue S phase delay, checkpoint activation, and damage sensitivity, which was caused by CRL4Cdt2 inactivation, suggesting that Spd1—in addition to repressing dNTP synthesis—together with Spd2, can inhibit other replication functions. We propose that this inhibition works at the point of the replication clamp proliferating cell nuclear antigen, a co-factor for DNA replication.

  5. Modified endoscopic medial maxillectomy for zygomatic implant salvage.

    Science.gov (United States)

    Schwartz, Joseph S; Tajudeen, Bobby A; Adappa, Nithin D; Palmer, James N

    2016-01-01

    Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant.

  6. Salvage brachytherapy for local recurrences of prostate cancer treated previously with radiotherapy.

    Science.gov (United States)

    Gawkowska-Suwinska, Marzena; Fijałkowski, Marek; Białas, Brygida; Szlag, Marta; Kellas-Ślęczka, Sylwia; Nowicka, Elżbieta; Behrendt, Katarzyna; Plewicki, Grzegorz; Smolska-Ciszewska, Beata; Giglok, Monika; Zajusz, Aleksander; Owczarek, Grzegorz

    2009-12-01

    The aim of the study was to analyze early effects and toxicity of salvage high dose rate brachytherapy for local recurrences of adenocarcinoma of the prostate after external beam radiotherapy (EBRT). In MCS Memorial Institute of Oncology in Gliwice a research programme on salvage HDR brachytherapy for local recurrences of prostate cancer treated previously with EBRT has been ongoing since February 2008. The treatment consisted of 3 fractions of 10 Gy each given every 14 days. Maximal urethral doses were constrained to be ≤ 120% of the prescribed dose. Maximal bladder and rectum doses were constrained to be ≤ 70% of the prescribed dose. Fifteen eligible patients were treated and analyzed from February 2008. All patients completed the treatment without major complications. The most common early complications were: macroscopic haematuria, pain in lower part of the abdomen, and transient dysuria. During the first week after the procedure a transient increase in IPSS score was noticed. The Foley catheter was removed on day 2 to 5. No complications after spinal anaesthesia were observed. Acute toxicity according to EORTC/RTOG was low. For bladder EORTC/RTOG score ranged from 0 to 2. Only in two patients grade 1 toxicity for rectum was observed. The follow-up ranged from 3 to 9 months. In one patient grade 2 rectal toxicity was observed, and one had urethral stricture. Other patients did not have any other significant late toxicity of the treatment. Two patients developed bone metastases. Salvage brachytherapy for localized prostate cancer (3 × 10 Gy every 14 days) seems to be a safe and well tolerated procedure. A significant decline in prostate-specific antigen (PSA) level is seen in patients with hormone-responsive cancer. Long-term efficiency and toxicity of the procedure are yet to be established.

  7. Effectiveness and Morbidity Associated With Reirradiation in Conservative Salvage Management of Recurrent Soft-Tissue Sarcoma

    International Nuclear Information System (INIS)

    Indelicato, Daniel J.; Meadows, Kenyon; Gibbs, Charles P.; Morris, Christopher G.; Scarborough, Mark T.; Zlotecki, Robert A.

    2009-01-01

    Purpose: The management of isolated local recurrence of soft-tissue sarcoma is therapeutically complex, and functional conservative management is preferable to radical or amputative salvage surgery. This study reviews University of Florida experience using conservative resection and reirradiation to manage isolated local recurrences of soft-tissue sarcoma. Methods and Materials: Between 1976 and 2005, a total of 14 patients who underwent primary conservative resection and irradiation developed isolated local recurrence and were managed with salvage conservative resection and reirradiation. Of the patients treated, 3 had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3 had tumors of the trunk. At the time of recurrence, 64% of tumors were greater than 5 cm and 79% were high grade. In combination with gross total resection, 13 of 14 patients received external beam radiotherapy with or without brachytherapy, and 1 patient was treated with brachytherapy alone. Two patients received chemotherapy. Results: The median follow-up was 30 months, and no living patients were lost during follow-up. From retreatment, the 5-year actuarial overall survival, cause-specific survival, and local control rates were 40%, 40%, and 18% respectively. There was a 50% incidence of serious complication requiring either reoperation or leading to permanent functional impairment. Of the 14 patients, only 1 has remained disease free and without significant complications. No treatment factors, including achieving wide surgical margins or delivering higher radiation dosages, seemed to confer an advantage in local control. Conclusions: Salvage therapy for management of locally recurrent soft-tissue sarcoma is challenging, and the effects of reoperation and reirradiation can be severe

  8. Physiological and morphological responses of pine and willow saplings to post-fire salvage logging

    Science.gov (United States)

    Millions, E. L.; Letts, M. G.; Harvey, T.; Rood, S. B.

    2015-12-01

    With global warming, forest fires may be increasing in frequency, and post-fire salvage logging may become more common. The ecophysiological impacts of this practice on tree saplings remain poorly understood. In this study, we examined the physiological and morphological impacts of increased light intensity, due to post-fire salvage logging, on the conifer Pinus contorta (pine) and deciduous broadleaf Salix lucida (willow) tree and shrub species in the Crowsnest Pass region of southern Alberta. Photosynthetic gas-exchange and plant morphological measurements were taken throughout the summer of 2013 on approximately ten year-old saplings of both species. Neither species exhibited photoinhibition, but different strategies were observed to acclimate to increased light availability. Willow saplings were able to slightly elevate their light-saturated rate of net photosynthesis (Amax) when exposed to higher photosynthetic photon flux density (PPFD), thus increasing their growth rate. Willow also exhibited increased leaf inclination angles and leaf mass per unit area (LMA), to decrease light interception in the salvage-logged plot. By contrast, pine, which exhibited lower Amax and transpiration (E), but higher water-use efficiency (WUE = Amax/E) than willow, increased the rate at which electrons were moved through and away from the photosynthetic apparatus in order to avoid photoinhibition. Acclimation indices were higher in willow saplings, consistent with the hypothesis that species with short-lived foliage exhibit greater acclimation. LMA was higher in pine saplings growing in the logged plot, but whole-plant and branch-level morphological acclimation was limited and more consistent with a response to decreased competition in the logged plot, which had much lower stand density.

  9. Time interval between primary radiotherapy and salvage laryngectomy: a predictor of pharyngocutaneous fistula formation.

    Science.gov (United States)

    Scotton, William J; Nixon, I J; Pezier, T F; Cobb, R; Joshi, A; Urbano, T Guerrero; Oakley, R; Jeannon, J P; Simo, R S

    2014-08-01

    Salvage laryngectomy (SL) is associated with high levels of morbidity. Rates of pharyngocutaneous fistulae (PCF) are as high as 35 % in some series. Patients at highest risk of such complications may be candidates for altered surgical management in terms of additional tissue transfer, or delayed tracheoesophageal puncture. This study investigates the relationship between the time from primary radiotherapy (RT) to salvage surgery and the development of PCF. 26 consecutive patients who underwent SL between 2000 and 2010 were identified from our institutional database. Demographic, staging, treatment and complication data were collected. Subgroup analysis was performed using the Student's t test or Mann-Whitney U test for continuous variables and either Chi-squared test or Fisher's Exact test for categorical variables. 26 patients underwent SL between October 2003 and July 2010. Of these, 15 (58 %) developed a PCF. On analysis of the time between pre-operative RT and surgery, a significant difference was seen, with a mean time of 19.5 months in those who developed a PCF versus 47.0 months in those who did not (p = 0.02). Patient characteristics, treatment, and pathology results were comparable between the two groups. There was no significant difference in distribution of the other covariates between the PCF and non-PCF groups. We reported a high rate of PCF and identified an association between PCF and a short time from primary treatment to salvage surgery. Identifying factors associated with higher rates of post-operative morbidity allows surgeons to adapt surgical planning in an attempt to minimize rates of PCF.

  10. Implant salvage in breast reconstruction with severe peri-prosthetic infection.

    Science.gov (United States)

    Meybodi, Farid; Sedaghat, Negin; French, James; Keighley, Caitlin; Mitchell, David; Elder, Elisabeth

    2017-12-01

    Although treatment of mild peri-prosthetic infection in implant-based breast reconstruction results in high rates of resolution, successful management of severe peri-prosthetic infection remains a significant challenge. In this case series, a protocol utilizing a novel dressing - negative pressure wound therapy with instillation (NPWTi) - for the management of severe peri-prosthetic infection in breast reconstruction patients is described. This is an operative technique involving: (i) explantation of the breast prosthesis and application of the NPWTi dressing to the implant pocket; (ii) change of the NPWTi dressing; (iii) intraoperative fluid/tissue cultures; and (iv) reimplantation of the breast prosthesis when cultures yield no growth. This protocol was utilized in six cases of severe peri-prosthetic infection in five patients with immediate breast reconstruction for breast cancer or risk-reducing surgery. Cultures of fluid/tissue grew typical and/or unusual organisms. Only one case did not yield an organism. The hospital length of stay upon completion of the protocol ranged from 7-16 days (mean, 12 days). Successful implant salvage was achieved in five of six cases. The protocol was aborted in one case to allow for completion of adjuvant chemotherapy. Early findings from this case series suggest that in cases of severe peri-prosthetic infection this novel operative protocol may result in successful implant salvage for breast reconstruction patients. Further studies are needed to more fully elaborate the role of NPWTi to achieve implant salvage in challenging cases of peri-prosthetic infection. © 2015 Royal Australasian College of Surgeons.

  11. Review of Maxillofacial Hardware Complications and Indications for Salvage

    OpenAIRE

    Hernandez Rosa, Jonatan; Villanueva, Nathaniel L.; Sanati-Mehrizy, Paymon; Factor, Stephanie H.; Taub, Peter J.

    2015-01-01

    From 2002 to 2006, more than 117,000 facial fractures were recorded in the U.S. National Trauma Database. These fractures are commonly treated with open reduction and internal fixation. While in place, the hardware facilitates successful bony union. However, when postoperative complications occur, the plates may require removal before bony union. Indications for salvage versus removal of the maxillofacial hardware are not well defined. A literature review was performed to identify instances w...

  12. [Eyeball salvage treatment or enucleation for advanced retinoblastoma].

    Science.gov (United States)

    Qian, J; Xue, K

    2016-10-11

    The management of retinoblastoma (RB) has dramatically changed over the past two decades. The introduction of chemotherapy has transformed treatment algorithms completely. Chemotherapy is currently used as a first line approach for children with RB and can be delivered by intravenous, intra-arterial and intravitreal routes. However, there still remains some controversy on the treatment of advanced RB, especially in eyeball salvage. This article described domestic and international approaches to eyeball salvage treatment. We would like to further discuss our opinion on the management of advanced RB based on our clinical experience for attracting more clinical concern on this issue. Many factors should be considered when choosing the appropriate conservative therapy. The choice of eyeball salvage treatment not only depends upon the tumor staging and laterality but also upon compliance and economic factors. Doctors and parents should not blindly pursue eye saving. However, there are still cases where enucleation is definitely the treatment of choice. (Chin J Ophthalmol, 2016, 52: 728-732) .

  13. In situ saphenous vein bypass for limb salvage.

    Science.gov (United States)

    Sarcina, A; Carlesi, R; Bellosta, R; Agrifoglio, G

    1993-02-01

    A total of 130 infrapopliteal in situ saphenous vein bypasses were performed in 128 patients between January 1980 and June 1991. The indication for surgery was critical ischaemia with impending limb loss in 121 patients; seven suffered from severe claudication. The distal anastomosis was to the popliteal artery below the knee in 60 cases (46.2%) and in 70 (53.8%) to the tibioperoneal arteries. The results, in terms of secondary patency and limb salvage rates, of the first 68 procedures (1980-1985) and subsequent 62 (1986-June 1991) were compared. In the first period, a secondary patency rate of 42.6% and a limb salvage rate of 67.0% were obtained, compared with 71.3 and 80.8% respectively in the second. These differences are significant for patency (P < 0.005) and limb salvage (P < 0.01). These results show that the in situ technique can give acceptable results but a learning period with a high percentage of early failures is to be expected.

  14. Risk factors for local failure requiring salvage neurosurgery after radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Weltman, Eduardo; Hanriot, Rodrigo de Morais; Prisco, Flavio Eduardo; Nadalin, Wladimir; Brandt, Reynaldo Andre; Moreira, Frederico Rafael

    2004-01-01

    Objective: the aim of this study is to select the risk factors for local failure requiring salvage neurosurgery in patients with brain metastases treated with stereotactic radiosurgery in a single institution. Methods: the follow-up of 123 patients, with 255 brain metastases treated with radiosurgery at the Radiation Oncology Department of the Hospital Israelita Albert Einstein from July 1993 to August 2001, was retrospectively analyzed. The criteria for salvage neurosurgery were tumor volume enlargement, or tumor persistence leading to severe neurological symptoms, life threatening situation or critical steroid dependence. We considered the case as local failure when the histopathologic evaluation showed morphologically preserved cancer cells (tumor recurrence, persistence or progression). We applied the Fisher's exact test to evaluate the statistical correlation between local failure and primary tumor histology, volume of the brain metastases, prescribed radiosurgery dose, and whole brain radiotherapy. Results: fourteen of 123 patients (11%) underwent salvage neurosurgery. Histology showed preserved cancer cells with necrosis and/or bleeding in 11 cases (9% of the total accrual), and only necrosis with or without bleeding (without preserved cancer cells) in three cases. The primary tumor histology among the 11 patients considered with active neoplasia was malignant melanoma in five cases (21% of the patients with melanoma), breast adenocarcinoma in three (16% of the patients with breast cancer), and other histology in the remaining three. Breast cancer diagnosis, non-elective whole brain irradiation, volume of the brain metastases, and the prescribed radiosurgery dose did not correlate with the risk of local failure. Patients treated with elective whole brain radiotherapy showed fewer local failures, when compared to all patients receiving whole brain radiotherapy, and to the patients not receiving this treatment, with incidence of failure in 4%,7% and 14

  15. Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

    Science.gov (United States)

    Davies, L; Brown, T J; Haynes, S; Payne, K; Elliott, R A; McCollum, C

    2006-11-01

    To compare patient outcomes, resource use and costs to the NHS and NHS Blood Transfusion Authority (BTA) associated with cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion. Electronic databases covering the period 1996-2004 for systematic reviews and 1994-2004 for economic evidence. Existing systematic reviews were updated with data from selected randomised controlled trials (RCTs) that involved adults scheduled for elective non-urgent surgery. Any resource use or cost data were extracted for potential use in populating an economic model. Relative risks or weighted mean difference of each outcome for each intervention were assessed, taking into account the number of RCTs included in each outcome and intervention and the presence of any heterogeneity. This allowed indirect comparison of the relative effectiveness of each intervention when the intervention is compared with allogeneic blood transfusion. A decision analytic model synthesised clinical and economic data from several sources, to estimate the relative cost-effectiveness of cell salvage for people undergoing elective surgery with moderate to major expected blood loss. The perspective of the NHS and patients and a time horizon of 1 month were used. The economic model was developed from reviews of effectiveness and cost-effectiveness and clinical experts. Secondary analysis explored the robustness of the results to changes in the timing and costs of cell salvage equipment, surgical procedure, use of transfusion protocols and time horizon of analysis. Overall, 668 studies were identified electronically for the update of the two systematic reviews. This included five RCTs, of which two were cell salvage and three preoperative autologous donation (PAD). Five published systematic reviews were identified for antifibrinolytics, fibrin sealants and restrictive transfusion triggers, PAD plus erythropoietin, erythropoietin alone and acute normovolaemic haemodilution (ANH

  16. Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only

    International Nuclear Information System (INIS)

    Rischke, Hans Christian; Schultze-Seemann, Wolfgang; Kroenig, Malte; Schlager, Daniel; Jilg, Cordula Annette; Wieser, Gesche; Drendel, Vanessa; Stegmaier, Petra; Henne, Karl; Volegova-Neher, Natalia; Grosu, Anca-Ligia; Krauss, Tobias; Kirste, Simon

    2015-01-01

    Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only. ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse. (orig.) [de

  17. Transcriptomic analysis of genes in the nitrogen recycling pathway of meat-type chickens divergently selected for feed efficiency.

    Science.gov (United States)

    Aggrey, S E; Lee, J; Karnuah, A B; Rekaya, R

    2014-04-01

    The understanding of the dynamics of ammonia detoxification and excretion in uricotelic species is lagging behind ureotelic species. The relative expression of genes involved in nitrogen recycling and feed efficiency in chickens is unknown. The objective of this study was to investigate the transcriptomics differences in key genes in the nitrogen (N) metabolism and purine biosynthesis pathway in a chicken population divergently selected for low (LRFI) or high (HRFI) residual feed intake at days 35 and 42 using duodenum, liver, pectoralis major (P. major) and kidney. There was a significant positive correlation between RFI and fecal N. The purine salvage pathway was activated in the LRFI compared with HRFI at days 42. The birds in the LRFI population attained greater feed efficiency by having lower FI, increasing their protein retention and producing adequate glutamine to maintain growth compared with the HRFI line. To maintain growth, excess N is deaminated mostly to generate purine nucleotides. Generating purine nucleotides primarily from the purine biosynthesis pathway is energetically costly, and to preserve energy, they preferentially generate nucleotides from the purine salvage pathway. The LRFI birds need to generate sufficient nucleotides to maintain growth despite reduced FI that then results in reduced fecal N. © 2013 Stichting International Foundation for Animal Genetics.

  18. Salvage HIFU after radiotherapy and salvage radiotherapy after HIFU in locally recurrent prostate cancer: Retrospective analysis of morbidity

    International Nuclear Information System (INIS)

    Lee, J.-W.; Hannoun-Leviac, J.-M.; Chevallier, D.; Rouscoff, Y.; Durand, M.; Amiel, J.; Gal, J.; Natale, R.; Chand, M.-E.; Raffaelli, C.; Ambrosetti, D.

    2012-01-01

    To evaluate the toxicity of therapeutic sequences High Intensity Focused Ultrasound (HIFU)-salvage radiotherapy (HIFU-RT) or radiotherapy-salvage HIFU (RT-HIFU) in case of locally recurrent prostate cancer. Nineteen patients had a local recurrence of prostate cancer. Among them, 10 patients were treated by HIFU-RT and 9 patients by RT- HIFU (4 by external beam radiotherapy [EBR] and 5 by brachytherapy [BRACHY]). Urinary side effects were assessed using CTCAE v4. At the time of the initial management, the median age was 66.5 years (53 72), the median PSA was 10.8 ng/mL (3.4 50) and the median initial Gleason score was 6.3 (5 8). Median follow-up after salvage treatment was 46.3 months (2 108). Thirty percent of the patients in the HIFU-RT group and 33.3 % of the patients in the RT-HIFU group, all belonging to the sub-group BRACHY-HIFU, had urinary complication greater than or equal to grade 2. Among all the patients, only 1 had grade 1 gastrointestinal toxicity. BRACHY-HIFU sequence seems to be purveyor of many significant urinary side effects. A larger database is needed to confirm this conclusion. (authors)

  19. Exploring Student and Advisor Experiences in a College-University Pathway Program: A Study of the Bachelor of Commerce Pathway

    Science.gov (United States)

    Percival, Jennifer; DiGiuseppe, Maurice; Goodman, Bill; LeSage, Ann; Hinch, Ron; Samis, John; Sanchez, Otto; Rodrigues, Anna; Raby, Phil; Longo, Fabiola; De La Rocha, Arlene

    2015-01-01

    Currently, there is great interest across Ontario in the expansion of pathway programs between colleges and universities. Through strategic partnerships, two Ontario-based postsecondary institutions (a college and a university) have developed innovative and effective pathway programs that facilitate the transition of students between institutions…

  20. Pathway for inpatients with depressive episode in Flemish psychiatric hospitals: a qualitative study

    Directory of Open Access Journals (Sweden)

    Simoens Steven R

    2009-10-01

    Full Text Available Abstract Background Within the context of a biopsychosocial model of the treatment of depressive episodes, a multidisciplinary approach is needed. Clinical pathways have been developed and implemented in hospitals to support multidisciplinary teamwork. The aim of this study is to explore current practice for the treatment of depressive episodes in Flemish psychiatric hospitals. Current practice in different hospitals is studied to get an idea of the similarities (outlined as a pathway and the differences in the treatment of depressive episodes. Methods A convenience sample of 11 Flemish psychiatric hospitals participated in this qualitative study. Semi-structured interviews were conducted with different types of health care professionals (n = 43. The websites of the hospitals were searched for information on their approach to treating depressive episodes. Results A flow chart was made including the identified stages of the pathway: pre-admission, admission (observation and treatment, discharge and follow-up care. The characteristics of each stage are described. Although the stages are identified in all hospitals, differences between hospitals on various levels of the pathway exist. Hospitals emphasized the individual approach of each patient. The results point to a biopsychosocial approach to treating depressive episodes. Conclusion This study outlined current practice as a pathway for Flemish inpatients with depressive episodes. Within the context of surveillance of quality and quantity of care, this study may encourage hospitals to consider developing clinical pathways.

  1. Posterior transpedicular approach with circumferential debridement and anterior reconstruction as a salvage procedure for symptomatic failed vertebroplasty

    OpenAIRE

    Chiu, Yen-Chun; Yang, Shih-Chieh; Chen, Hung-Shu; Kao, Yu-Hsien; Tu, Yuan-Kun

    2015-01-01

    Background Complications and failure of vertebroplasty, such as cement dislodgement, cement leakage, or spinal infection, usually result in spinal instability and neural element compression. Combined anterior and posterior approaches are the most common salvage procedure for symptomatic failed vertebroplasty. The purpose of this study is to evaluate the feasibility and efficacy of a single posterior approach technique for the treatment of patients with symptomatic failed vertebroplasty. Metho...

  2. A study of the transition pathways of school level scholarship ...

    African Journals Online (AJOL)

    Hennie

    intervention. The benefits reported included a sound preparation for life and academic studies, and other benefits that the .... fied (on average) in this study as stress inducing. Adding further ...... Cambridge, MA: Harvard Education Press.

  3. 75 FR 54026 - Salvage and Marine Firefighting Requirements; Vessel Response Plans for Oil

    Science.gov (United States)

    2010-09-03

    ... information for resource providers for each vessel with appropriate equipment and resources located in each... appropriate salvage and marine firefighting resources were identified and available for responding to...

  4. Percutaneous Creation of Bare Intervascular Tunnels for Salvage of Thrombosed Hemodialysis Fistulas Without Recanalizable Outflow

    International Nuclear Information System (INIS)

    Chen, Matt Chiung-Yu; Wang, Yen-Chi; Weng, Mei-Jui

    2015-01-01

    PurposeThis study aimed to retrospectively assess the efficacy of a bare intervascular tunnel for salvage of a thrombosed hemodialysis fistula. We examined the clinical outcomes and provided follow-up images of the bare intervascular tunnel.Materials and MethodsEight thrombosed fistulas lacked available recanalizable outflow veins were included in this study. These fistulas were salvaged by re-directing access site flow to a new outflow vein through a percutaneously created intervascular tunnel without stent graft placement. The post-intervention primary and secondary access patency rates were calculated using the Kaplan–Meier method.ResultsThe procedural and clinical success rates were 100 %. Post-intervention primary and secondary access patency at 300 days were 18.7 ± 15.8 and 87.5 ± 11.7 %, respectively. The mean follow-up period was 218.7 days (range 10–368 days). One patient died of acute myocardial infarction 10 days after the procedure. No other major complications were observed. Minor complications, such as swelling, ecchymosis, and pain around the tunnel, occurred in all of the patients.ConclusionsPercutaneous creation of a bare intervascular tunnel is a treatment option for thrombosed hemodialysis fistulas without recanalizable outflow in selected patients

  5. The use of a prosthetic inlay resurfacing as a salvage procedure for a failed cartilage repair.

    Science.gov (United States)

    Dhollander, Aad Alfons Maria; Almqvist, Karl Fredrik; Moens, Kris; Vandekerckhove, Pieter-Jan; Verdonk, René; Verdonk, Peter; Victor, Jan

    2015-08-01

    This study was designed to describe the clinical and radiographical outcome of the HemiCAP(®) resurfacing system as a salvage treatment for a failed index cartilage procedure. Fourteen patients were treated consecutively and clinically prospectively followed for a mean period of 26.1 ± 12.8 months. All patients were previously treated for their cartilage lesion. Radiographical data were analysed based on the Kellgren and Lawrence system. The patients involved in this study demonstrated a gradual clinical improvement in time. However, radiographically significant osteoarthritic changes were observed during the follow-up period. The position of the HemiCAP(®) resurfacing system was adequate in all cases, and no signs of loosening were observed during the follow-up period. The HemiCAP(®) resurfacing system is feasible as a salvage treatment for a failed index cartilage procedure and resulted in a gradual clinical improvement. However, the favourable clinical outcome was not confirmed by the radiographical findings. IV.

  6. Building Data-Driven Pathways From Routinely Collected Hospital Data: A Case Study on Prostate Cancer

    Science.gov (United States)

    Clark, Jeremy; Cooper, Colin S; Mills, Robert; Rayward-Smith, Victor J; de la Iglesia, Beatriz

    2015-01-01

    Background Routinely collected data in hospitals is complex, typically heterogeneous, and scattered across multiple Hospital Information Systems (HIS). This big data, created as a byproduct of health care activities, has the potential to provide a better understanding of diseases, unearth hidden patterns, and improve services and cost. The extent and uses of such data rely on its quality, which is not consistently checked, nor fully understood. Nevertheless, using routine data for the construction of data-driven clinical pathways, describing processes and trends, is a key topic receiving increasing attention in the literature. Traditional algorithms do not cope well with unstructured processes or data, and do not produce clinically meaningful visualizations. Supporting systems that provide additional information, context, and quality assurance inspection are needed. Objective The objective of the study is to explore how routine hospital data can be used to develop data-driven pathways that describe the journeys that patients take through care, and their potential uses in biomedical research; it proposes a framework for the construction, quality assessment, and visualization of patient pathways for clinical studies and decision support using a case study on prostate cancer. Methods Data pertaining to prostate cancer patients were extracted from a large UK hospital from eight different HIS, validated, and complemented with information from the local cancer registry. Data-driven pathways were built for each of the 1904 patients and an expert knowledge base, containing rules on the prostate cancer biomarker, was used to assess the completeness and utility of the pathways for a specific clinical study. Software components were built to provide meaningful visualizations for the constructed pathways. Results The proposed framework and pathway formalism enable the summarization, visualization, and querying of complex patient-centric clinical information, as well as the

  7. Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

    NARCIS (Netherlands)

    Solin, Lawrence J.; Fourquet, Alain; Vicini, Frank A.; Taylor, Marie; Haffty, Bruce; Strom, Eric A.; Wai, Elaine; Pierce, Lori J.; Marks, Lawrence B.; Bartelink, Harry; Campana, Francois; McNeese, Marsha D.; Jhingran, Anuja; Olivotto, Ivo A.; Bijker, Nina; Hwang, Wei-Ting

    2005-01-01

    The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of

  8. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  9. Freshwater mussel salvage and relocation at the Pond Eddy Bridge, Delaware River, New York and Pennsylvania

    Science.gov (United States)

    Galbraith, Heather S.; Blakeslee, Carrie J.; Cole, Jeffrey C.

    2018-03-01

    In a study conducted by the U.S. Geological Survey, in cooperation with the Pennsylvania Department of Transportation, freshwater mussels were salvaged and relocated from the anticipated zone of impact for the Pond Eddy Bridge construction project in New York and Pennsylvania. Five 25-meter (m) by 25-m cells along the Pennsylvania bank of the Delaware River were sampled in three generally straight-line passes by four surveyors wearing snorkel gear for a total of 180 survey minutes per cell. All mussels encountered were collected and identified to species. A subset of individuals was marked with shellfish tags, weighed, and measured prior to relocation upstream from the zone of impact. A total of 3,434 mussels, including 3,393 Elliptio complanata (eastern elliptio mussels), 39 Anodonta implicata (alewife floaters), 1 Strophitus undulatus (creeper), and 1 Pyganodon cataracta (eastern floater), were salvaged and relocated. All non-eastern elliptio species were georeferenced using a high-resolution global positioning system unit; a subset of tagged eastern elliptio was placed in transects between georeferenced points. These mussels will be monitored to assess the effects of translocation on mortality and body condition at 1 month, 1 year, and 2 years.

  10. Effects of multiple interacting disturbances and salvage logging on forest carbon stocks

    Science.gov (United States)

    Bradford, J.B.; Fraver, S.; Milo, A.M.; D'Amato, A.W.; Palik, B.; Shinneman, D.J.

    2012-01-01

    Climate change is anticipated to increase the frequency of disturbances, potentially impacting carbon stocks in terrestrial ecosystems. However, little is known about the implications of either multiple disturbances or post-disturbance forest management activities on ecosystem carbon stocks. This study quantified how forest carbon stocks responded to stand-replacing blowdown and wildfire, both individually and in combination with and without post-disturbance salvage operations, in a sub-boreal jack pine ecosystem. Individually, blowdown or fire caused similar decreases in live carbon and total ecosystem carbon. However, whereas blowdown increased carbon in down woody material and forest floor, fire increased carbon in standing snags, a difference that may have consequences for long-term carbon cycling patterns. Fire after the blowdown caused substantial additional reduction in ecosystem carbon stocks, suggesting that potential increases in multiple disturbance events may represent a challenge for sustaining ecosystem carbon stocks. Salvage logging, as examined here, decreased carbon stored in snags and down woody material but had no significant effect on total ecosystem carbon stocks.

  11. The use of expanded microporous polytetrafluoroethylene for limb salvage: a preliminary report.

    Science.gov (United States)

    Campbell, C D; Brooks, D H; Webster, M W; Bahnson, H T

    1976-05-01

    Initial laboratory and clinical evaluations of a new prosthetic material, expanded microporous polytetrafluoroethylene (PTFE), for small vessel replacement is promising and encourages further clinical trial. Frequently the autogenous saphenous vein is not available for bypass procedures, and alternative arterial substitutes have not proved reliable for replacement of small vessels. In this study, 15 patients with impending loss of limb and no available saphenous vein underwent revascularization of the lower extremity with expanded microporous PTFE grafts. Thirteen of 15 patients now demonstrate viable extremities with a resulting over-all early patency and limb salvage rate of 87 percent for this series. Follow-up ranges from one to 8 months. Seven patients had diabetes mellitus and eight had atherosclerotic heart disease. Nine grafts crossed the knee joint. In all patients arterial runoff was poor. Six patients had previous femoropopliteal bypasses, five with autogenous veins and one with Dacron velour. Two patients had multiple previous operations that failed, first with autogenous vein and later with fabric grafts. The current limb salvage and patency rate of 87 percent in high-risk patients suggests that expanded PTFE may be the prosthesis of choice when an autogenous vein is not available and possibly an equally good substitute when the venous autograft is available.

  12. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  13. Impact of salvage therapy for biochemical recurrence on health-related quality of life following radical prostatectomy

    International Nuclear Information System (INIS)

    Namiki, Shunichi; Saito, Seiichi; Arai, Yoichi; Tochigi, Tatsuo; Ioritani, Naomasa; Terai, Akito

    2007-01-01

    The objective of this study was to determine the impact of salvage therapy for prostate-specific antigen (PSA) recurrence on the health-related quality of life (HRQOL) of patients after radical retropubic prostatectomy (RP). Between January 2000 and December 2003, a total of 249 patients who underwent RP were available for 2-year follow up. Of the respondents, 203 men did not show evidence of recurrence (group A), and 46 men received salvage hormonal therapy and/or radiotherapy after RP because of a rise in PSA (group B). The general and prostate-target HRQOL was assessed with the Medical Outcomes Study 36-Item Short Form and University of California, Los Angeles Prostate Cancer Index, respectively. Patients completed the HRQOL instruments by mail at baseline and at 24 months after RP. All of the patients completed both questionnaires. At baseline no significant differences were found between the two groups in any of the HRQOL domains. There were significant improvements in mental health and social function for the patients without biochemical recurrence postoperatively. Repeated measure analysis of variance (ANOVA) revealed significantly different patterns of alteration in several general HRQOL domains among the treatment groups. The urinary and bowel domains were equivalent between the two treatment groups at baseline and 24 months after RP. The patients treated with salvage hormonal therapy tended to show delayed recovery of sexual function. Using a self-administered questionnaire, biochemical recurrence following RP was found to impose a substantial burden in patients with localized prostate cancer. (author)

  14. Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

    Directory of Open Access Journals (Sweden)

    Adam R. Smith

    2016-06-01

    Full Text Available Alzheimer's disease is a complex neurodegenerative disorder. A large number of genome-wide association studies have been performed, which have been supplemented more recently by the first epigenome-wide association studies, leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Gatz et al., 2006, leading to the conclusion that a combination of genetic and epigenetic mechanisms is likely to be involved in disease etiology (Lunnon & Mill, 2013. This review focuses on identifying overlapping pathways between published genome-wide association studies and epigenome-wide association studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial, and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

  15. [Pain and its pathways. A study for therapeutic action].

    Science.gov (United States)

    Barbin, J Y; Robert, R; Fresche, F; Lajat, J; Menegalli-Boggelli, D

    1992-01-01

    Pain is as old as mankind. It has a threshold beyond which nobody can escape it. Pain is a biological and physiological phenomenon, an integrated part of our body and ego. Will all our efforts eventually make it disappear? Is its disappearance desirable? Pain is one of the major expressions of sensation. It is integrated by the central structures and expressed as a behavior of avoidance or attenuation of the effects produced by the cause of pain. The study of this behavior and of the transmission of the pain message corresponds to the study of how to fight against this message, which means that it should logically lead to the treatment of pain.

  16. Penalized differential pathway analysis of integrative oncogenomics studies

    NARCIS (Netherlands)

    van Wieringen, W.N.; van de Wiel, M.A.

    2014-01-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving

  17. Pathways to Children's Externalizing Behavior: A Three-Generation Study

    Science.gov (United States)

    Brook, Judith S.; Zhang, Chenshu; Balka, Elinor B.; Brook, David W.

    2012-01-01

    In this study, based on Family Interactional Theory (FIT), the authors tested a longitudinal model of the intergenerational effects of the grandmothers' parent-child relationships and the grandparents' smoking on the grandchildren's externalizing behavior via parents' psychological symptoms, tobacco use, and child rearing. Using Mplus, the authors…

  18. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

    Science.gov (United States)

    Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

    2017-01-01

    The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

  19. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

    Science.gov (United States)

    Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

    2017-01-01

    The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

  20. What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review

    OpenAIRE

    Lawal, Adegboyega K.; Rotter, Thomas; Kinsman, Leigh; Machotta, Andreas; Ronellenfitsch, Ulrich; Scott, Shannon D.; Goodridge, Donna; Plishka, Christopher; Groot, Gary

    2016-01-01

    textabstractClinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in healthcare. This may be attributable to both the differences in definition and a lack of conceptualization in the field of clinical pathways. This correspondence article describes a process of refin...

  1. Life-course pathways to psychological distress: A cohort study

    OpenAIRE

    Von Stumm, S.; Deary, I. J.; Hagger-Johnson, G.

    2013-01-01

    Abstract: Objectives: Early life factors, like intelligence and socioeconomic status (SES), are associated with health outcomes in adulthood. Fitting comprehensive life-course models, we tested (1) the effect of childhood intelligence and SES, education and adulthood SES on psychological distress at midlife, and (2) compared alternative measurement specifications (reflective and formative) of SES. Design: Prospective cohort study (the Aberdeen Children of the 1950s). Setting: Aberdeen, Scotla...

  2. Grande-Baie tugboat sinking and salvage operations

    International Nuclear Information System (INIS)

    Dussault, M.; Gauthier, F.

    2009-01-01

    This paper described the operations that took place during an oil spill that occurred in December 2007 when the Grande-Baie tugboat sank at the wharf in Port Alfred, in the Ha-Ha Bay on the Saguenay River, Quebec. Approximately 100 tonnes of diesel fuel was onboard the tug. Although the exact amount of diesel spilled during this event is not known, it is assumed that half of the ship's load in diesel was spilled into the ice-infested waters. Poor weather, the presence of pack ice and tides of 2.5 meters were present at the time. Two Canadian Coast Guard officers, one emergency officer from Environment Quebec and one from Environment Canada were called for response purposes, particularly to avoid spreading of the diesel fuel and to ensure that the oily water was recovered from inside the vessel during salvage operations. One of the key objectives was to prevent diesel spills by capping vessel vents, which proved to be very challenging. Oily water was pumped from inside the boat directly in the bay of the Saguenay River to facilitate salvage of the ship. This was the first time that this method was used in Canada, and was successful because of proper risk assessment. Many conditions were followed for the purpose of environmental protection, such as confinement, good observations by divers, agreed upon criteria to stop pumping, and adequate monitoring the the Regional Environmental Emergency Team (REET). The salvage operation lasted 19 days. The challenges associated with the migration and recovery of oil in icy waters were discussed along with the environmental issues associated with the spill, particularly with the imminent opening of the ice fishing season. 2 refs., 2 tabs.,5 figs.

  3. Care Pathways in Persistent Orofacial Pain: Qualitative Evidence from the DEEP Study.

    Science.gov (United States)

    Breckons, M; Bissett, S M; Exley, C; Araujo-Soares, V; Durham, J

    2017-01-01

    Persistent orofacial pain is relatively common and known to have an adverse effect on quality of life. Previous studies suggest that the current care pathway may be problematic, but it is not well understood which health services patients access and what their experience is. The aim of this study was to explore care pathways and their impact from the perspective of patients. Qualitative interviews were conducted with a maximum variation sample of patients recruited from primary (community based) and secondary (specialist hospital based) care in the United Kingdom. Questions focused on the stages in their pathway and the impact of the care that they had received. Interviews were digitally recorded and transcribed verbatim, and analysis followed principles of the constant comparative method. NVivo 10 was used to help organize and analyze data. Twenty-two patients were interviewed at baseline, and 18 took part in a second interview at 12 mo. Three main themes emerged from the data: the "fluidity of the care pathway," in which patients described moving among health care providers in attempts to have their pain diagnosed and managed, occurring alongside a "failure to progress," where despite multiple appointments, patients described frustration at delays in obtaining a diagnosis and effective treatment for their pain. Throughout their care pathways, patients described the "effects of unmanaged pain," where the longer the pain went unmanaged, the greater its potential to negatively affect their lives. Findings of this study suggest that the current care pathway is inefficient and fails to meet patient needs. Future work needs to focus on working with stakeholder groups to redesign patient-centered care pathways. Knowledge Transfer Statement: Data from qualitative interviews conducted with patients with persistent orofacial pain suggest significant problems with the existing care pathway, consisting of delays to diagnosis, treatment, and referral. Patients describing

  4. Male and Female Pathways to Psychopathology: Findings from a Preventive Intervention Study

    NARCIS (Netherlands)

    P. Vuijk (Patricia)

    2006-01-01

    textabstractThe objective of the present study was to extent the knowledge on the pathways to male and female psychopathology from childhood into early adolescence. In Chapter 1, the background of the Good Behavior Game (GBG) study was presented. The GBG study is a randomized controlled

  5. Life-course pathways to psychological distress: a cohort study.

    Science.gov (United States)

    von Stumm, Sophie; Deary, Ian J; Hagger-Johnson, Gareth

    2013-05-09

    Early life factors, like intelligence and socioeconomic status (SES), are associated with health outcomes in adulthood. Fitting comprehensive life-course models, we tested (1) the effect of childhood intelligence and SES, education and adulthood SES on psychological distress at midlife, and (2) compared alternative measurement specifications (reflective and formative) of SES. Prospective cohort study (the Aberdeen Children of the 1950s). Aberdeen, Scotland. 12 500 live-births (6282 boys) between 1950 and 1956, who were followed up in the years 2001-2003 at age 46-51 with a postal questionnaire achieving a response rate of 64% (7183). Psychological distress at age 46-51 (questionnaire). Childhood intelligence and SES and education had indirect effects on psychological distress at midlife, mediated by adult SES. Adult SES was the only variable to have a significant direct effect on psychological distress at midlife; the effect was stronger in men than in women. Alternative measurement specifications of SES (reflective and formative) resulted in greatly different model parameters and fits. Even though formative operationalisations of SES are theoretically appropriate, SES is better specified as reflective than as a formative latent variable in the context of life-course modelling.

  6. Interdot carrier's transfer via tunneling pathway studied from photoluminescence spectroscopy

    International Nuclear Information System (INIS)

    Rihani, J.; Sallet, V.; Yahyaoui, N.; Harmand, J.C.; Oueslati, M.; Chtourou, R.

    2009-01-01

    Self-assembled InAs quantum dots (QDs) on GaAs(0 0 1) substrate were grown by molecular beam epitaxy (MBE) at a growth temperature of 490 deg. C. Two different families of dots were observed in the atomic force microscopy (AFM) image and ambiguously identified in the photoluminescence (PL) spectra. Temperature-dependent PL study was carried out in the 8-270 K temperature range. The integrated-PL intensity behavior of the two QDs populations was fit with the help of a rate equations model. It is found that the evolutions of the integrated-PL intensity of the two QDs population were governed by two regimes. The first one occurs in the 8-210 K temperature range and reveals an unusual enhancement of the integrated-PL intensity of the larger QDs (LQDs) class. This was attributed to the carrier supplies from the smaller QDs (SQDs) class via the tunneling process. The second one occurs in the 210-270 K temperature range and shows a common quench of the PL signals of the two QDs families, reflecting the same thermal escape mechanism of carriers

  7. Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

    Directory of Open Access Journals (Sweden)

    Man-Hsin Hung

    2013-04-01

    Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

  8. Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy

    NARCIS (Netherlands)

    Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

    BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to

  9. SNP-based pathway enrichment analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Potkin Steven G

    2011-04-01

    Full Text Available Abstract Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs, have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1 for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2 ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one

  10. Forest structure following tornado damage and salvage logging in northern Maine, USA

    Science.gov (United States)

    Shawn Fraver; Kevin J. Dodds; Laura S. Kenefic; Rick Morrill; Robert S. Seymour; Eben Sypitkowski

    2017-01-01

    Understanding forest structural changes resulting from postdisturbance management practices such as salvage logging is critical for predicting forest recovery and developing appropriate management strategies. In 2013, a tornado and subsequent salvage operations in northern Maine, USA, created three conditions (i.e., treatments) with contrasting forest structure:...

  11. 12 CFR 714.6 - Are you required to retain salvage powers over the leased property?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Are you required to retain salvage powers over the leased property? 714.6 Section 714.6 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LEASING § 714.6 Are you required to retain salvage powers over the leased...

  12. 28 CFR 25.56 - Responsibilities of junk yards and salvage yards and auto recyclers.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Responsibilities of junk yards and salvage yards and auto recyclers. 25.56 Section 25.56 Judicial Administration DEPARTMENT OF JUSTICE... Responsibilities of junk yards and salvage yards and auto recyclers. (a) By no later than March 31, 2009, and...

  13. Cell salvage as part of a blood conservation strategy in anaesthesia.

    Science.gov (United States)

    Ashworth, A; Klein, A A

    2010-10-01

    The use of intraoperative cell salvage and autologous blood transfusion has become an important method of blood conservation. The main aim of autologous transfusion is to reduce the need for allogeneic blood transfusion and its associated complications. Allogeneic blood transfusion has been associated with increased risk of tumour recurrence, postoperative infection, acute lung injury, perioperative myocardial infarction, postoperative low-output cardiac failure, and increased mortality. We have reviewed the current evidence for cell salvage in modern surgical practice and examined the controversial issues, such as the use of cell salvage in obstetrics, and in patients with malignancy, or intra-abdominal or systemic sepsis. Cell salvage has been demonstrated to be safe and effective at reducing allogeneic blood transfusion requirements in adult elective surgery, with stronger evidence in cardiac and orthopaedic surgery. Prolonged use of cell salvage with large-volume autotransfusion may be associated with dilution of clotting factors and thrombocytopenia, and regular laboratory or near-patient monitoring is required, along with appropriate blood product use. Cell salvage should be considered in all cases where significant blood loss (>1000 ml) is expected or possible, where patients refuse allogeneic blood products or they are anaemic. The use of cell salvage in combination with a leucocyte depletion filter appears to be safe in obstetrics and cases of malignancy; however, further trials are required before definitive guidance may be provided. The only absolute contraindication to the use of cell salvage and autologous blood transfusion is patient refusal.

  14. Use of Intra-Arterial Chemotherapy and Embolization Before Limb Salvage Surgery for Osteosarcoma of the Lower Extremity

    International Nuclear Information System (INIS)

    Zhang Huojun; Yang Jijin; Lu Jianping; Lai Chaojen; Sheng Jin; Li Yuxiao; Hao Qiang; Zhang Shunmin; Gupta, Sanjay

    2009-01-01

    We report our experience with the use of intra-arterial chemotherapy and embolization before limb salvage surgery in patients with osteosarcoma of the lower extremity. We evaluated the effect of this procedure on the degree of tumor necrosis and on the amount of blood loss during surgery. We reviewed the medical records of all patients who received intra-arterial chemotherapy and embolization before undergoing limb salvage surgery for osteosarcoma of the lower extremity at our institution between January 2003 and April 2008. Patient demographic, tumor characteristics, treatment details, postembolization complications, and surgical and pathological findings were recorded for each patient. We evaluated the operative time, estimated blood loss (EBL), and volume of blood transfusion during surgery and in the postoperative period in all patients in the study group. The same parameters were recorded for 65 other patients with lower extremity osteosarcoma who underwent limb salvage operation at our institution without undergoing preoperative intervention. The study included 47 patients (25 males and 22 females). Angiography showed that the tumors were hypervascular. Intra-arterial chemotherapy and embolization were performed successfully, resulting in a substantial reduction or complete disappearance of tumor stain in all patients. No major complications were encountered. At the time of surgery, performed 3-7 days after embolization, a fibrous edematous band around the tumor was observed in 43 of the 47 patients, facilitating surgery. The goal of limb salvage was achieved successfully in all cases. Percentage tumor necrosis induced by treatment ranged from 70.2% to 94.2% (average, 82.9%). EBL during surgery, EBL from drains in the postoperative period, total EBL, and transfusion volumes were significantly lower in the 47 study patients compared to the 65 patients who underwent surgery without preoperative treatment with intra-arterial chemotherapy and embolization. The

  15. A Study of the Transition Pathways of School Level Scholarship Recipients into Work and Tertiary Education

    Science.gov (United States)

    Hobden, Sally; Hobden, Paul

    2015-01-01

    School-level educational interventions targeting learners from low socioeconomic backgrounds often have the long-term goal of enabling access to, and successful completion of tertiary studies. This study tracked the progress of alumni of an educational intervention two or three years post school, in order to investigate their pathways to their…

  16. Salvage surgery for radiation failure in oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Suzuki, Masahiro; Terada, Akihiro; Ogawa, Tetsuya; Suzuki, Hidenori; Hasegawa, Yasuhisa

    2007-01-01

    Few reports have covered salvage surgery after radiotherapy, especially with chemotherapy for oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. The feasibility of salvage surgery is unclear. We analyzed postoperative complications and prognosis after salvage surgery for local recurrence after definitive radiotherapy. Subjects were 37 patients with oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma treated from 1994 to 2003. Of these, 14 (37.8%) had postoperative complications. The complication rate was significantly high in the reconstructive operation group (p=0.031) and the chemotherapy group (p=0.049). The 5-year overall survival rate after salvage surgery was 70.7%. Although there was no significant improvement, the prognosis was good in early-stage groups with primary tumors. We found that salvage surgery after definitive radiotherapy was effective for recurrent oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. We stress the need to pay attention to postoperative complications in reconstructive operation and chemotherapy groups. (author)

  17. Improvement of limb salvage procedure using intraoperative radiotherapy for osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Toru; Iwasaki, Katsuo; Kamishiro,; Toshiyuki,; Hayashi, Yasuyuki [Nagasaki Univ. (Japan). School of Medicine

    1992-10-01

    Clinical outcome of limb salvage procedure combined with intraoperative irradiation was investigated in 6 patients with osteosarcoma in the distal part of femur (n=4) and proximal part of tibia (n=2). They ranged in age from 12 to 54 years, with a mean of 22.5. First, a lesion was separated from the surrounding soft tissue with curatively wide margin. Osteotomy was performed at the portion of diaphysis. After irradiation field was setted up by lifting the lesion, and was exposed to doses ranging from 60 Gy to 85 Gy of intraoperative irradiation, soft tissue and fragile tumor tissue, excluding joint capsule and ligament, were removed as soon as possible. Finally, bone was jointed by means of inner fixation or bone grafting. They had a median follow-up of one year and four months after surgery. Although superficial wound infection and delayed wound adhesion were encountered as postoperative complications in one and two patients, respectively, these were all healed. None of the patients had local recurrence. The ability of salvaged limb was excellent in one, good in 3, and fair in 2 patients. Because both of the two patients with sarcoma in the proximal part of tibia had excellent and good limb ability, this procedure was considered useful especially for sarcoma in the proximal part of tibia. (N.K.).

  18. Improvement of limb salvage procedure using intraoperative radiotherapy for osteosarcoma

    International Nuclear Information System (INIS)

    Hirano, Toru; Iwasaki, Katsuo; Kamishiro; Toshiyuki; Hayashi, Yasuyuki

    1992-01-01

    Clinical outcome of limb salvage procedure combined with intraoperative irradiation was investigated in 6 patients with osteosarcoma in the distal part of femur (n=4) and proximal part of tibia (n=2). They ranged in age from 12 to 54 years, with a mean of 22.5. First, a lesion was separated from the surrounding soft tissue with curatively wide margin. Osteotomy was performed at the portion of diaphysis. After irradiation field was setted up by lifting the lesion, and was exposed to doses ranging from 60 Gy to 85 Gy of intraoperative irradiation, soft tissue and fragile tumor tissue, excluding joint capsule and ligament, were removed as soon as possible. Finally, bone was jointed by means of inner fixation or bone grafting. They had a median follow-up of one year and four months after surgery. Although superficial wound infection and delayed wound adhesion were encountered as postoperative complications in one and two patients, respectively, these were all healed. None of the patients had local recurrence. The ability of salvaged limb was excellent in one, good in 3, and fair in 2 patients. Because both of the two patients with sarcoma in the proximal part of tibia had excellent and good limb ability, this procedure was considered useful especially for sarcoma in the proximal part of tibia. (N.K.)

  19. Accuracy of post-radiotherapy biopsy before salvage radical prostatectomy.

    Science.gov (United States)

    Meeks, Joshua J; Walker, Marc; Bernstein, Melanie; Kent, Matthew; Eastham, James A

    2013-08-01

    To determine whether post-radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer. SRP was performed between 1998 and 2011 on 198 patients. All patients underwent a PRB. PRB and SRP specimens were evaluated by a genitourinary pathologist. Patients had external-beam RT alone (EBRT; 71%) or brachytherapy with or without EBRT (29%). Of the men undergoing SRP, 26 (14%) were clinical stage ≥T3, with 13% of PRBs with Gleason score ≥8. Cancer was unilateral in 120 (61%) biopsies, with contralateral or bilateral prostate cancer at SRP in 49%. In the SRP specimen, cancer was multifocal in 57%. Cancer was upgraded at SRP in 58% of men, with 20% having an increase in primary Gleason grade. The accuracy of PRB varied by region from 62% to 76%, with undetected cancers ranging from 12% to 26% and most likely to occur at the mid-gland. Radiation-recurrent prostate cancers were often multifocal, and biopsy missed up to 20% of tumours. More than half of the cancers were upgraded at SRP, and many that were unilateral on PRB were bilateral at SRP. © 2013 BJU International.

  20. Salvaging a cultural identity through reintegration

    Directory of Open Access Journals (Sweden)

    Marta Gomez Ubierna

    2010-11-01

    Pietre Dure” in 2009 - lay in the recovery of the black and white polychromy, of the quintessentially Florentine marble inlay through various interventions involving the integration of the stone. Study of the techniques and materials used has provided a unique opportunity to map out the various stages of restoration that the piece underwent, identifying the materials used in each intervention, allowing choices to be made regarding the conservation methods. The aim of the current project was the integration of new, completely reversible and compatible elements into the polychromatic marble inlay, elements that were created on the basis of the results of an experiment  with synthetic materials and their various methods of application.

  1. Systemic Chemotherapy as Salvage Treatment for Locally Advanced Rectal Cancer Patients Who Fail to Respond to Standard Neoadjuvant Chemoradiotherapy.

    Science.gov (United States)

    Sclafani, Francesco; Brown, Gina; Cunningham, David; Rao, Sheela; Tekkis, Paris; Tait, Diana; Morano, Federica; Baratelli, Chiara; Kalaitzaki, Eleftheria; Rasheed, Shahnawaz; Watkins, David; Starling, Naureen; Wotherspoon, Andrew; Chau, Ian

    2017-06-01

    The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is

  2. Combination of Open Subtotal Calcanectomy and Stabilization With External Fixation as Limb Salvage Procedure in Hindfoot-Infected Diabetic Foot Ulcers.

    Science.gov (United States)

    Dalla Paola, Luca; Carone, Anna; Boscarino, Giulio; Scavone, Giuseppe; Vasilache, Lucian

    2016-12-01

    Diabetic hindfoot ulcers, complicated by osteomyelitis, are associated with a high risk of major amputation. Partial calcanectomy, preceded by an effective management of the infection and of the eventual peripheral artery disease, can be considered as valid therapeutic option. We have evaluated a therapeutic protocol for diabetic hindfoot ulcers complicated by osteomyelitis, which, besides an adequate surgical debridement, considers a reconstructive pathway assisted by the positioning of a circular external fixator. We made a prospective study of a cohort of diabetic patients affected by heel ulcer complicated by osteomyelitis. All patients underwent open partial calcanectomy associated with the positioning of a circular external frame specifically designed for hindfoot stabilization and offloading. A reconstructive procedure was implemented starting with the application of negative pressure wound therapy and coverage with dermal substitute and split thickness skin grafting. From November 2014 to November 2015, 18 consecutive patients were enrolled. Mean follow-up period was 212.3 ± 64.0 days. Healing was achieved in 18 (100%) patients. The mean healing time was 69.0 ± 64.0 days. No major amputation had to be performed during the follow-up. Open partial calcanectomy associated with external fixation and skin reconstruction was as efficient as limb salvage in patients with infected lesions of the hindfoot complicated by calcaneal osteomyelitis.

  3. Effects of salvage logging and pile-and-burn on fuel loading, potential fire behaviour, fuel consumption and emissions

    Science.gov (United States)

    Morris C. Johnson; Jessica E. Halofsky; David L. Peterson

    2013-01-01

    We used a combination of field measurements and simulation modelling to quantify the effects of salvage logging, and a combination of salvage logging and pile-and-burn fuel surface fuel treatment (treatment combination), on fuel loadings, fire behaviour, fuel consumption and pollutant emissions at three points in time: post-windstorm (before salvage logging), post-...

  4. What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review

    NARCIS (Netherlands)

    A.K. Lawal (Adegboyega K.); T. Rotter (Thomas); L. Kinsman (Leigh); A. Machotta (Andreas); U. Ronellenfitsch (Ulrich); S.D. Scott (Shannon D.); D. Goodridge (Donna); C. Plishka (Christopher); G. Groot (Gary)

    2016-01-01

    textabstractClinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in

  5. A study on the environmental aspects of hydrogen pathways in Korea

    International Nuclear Information System (INIS)

    Lee, Ji-Yong; Yu, Moo-Sang; Cha, Kyoung-Hoon; Lee, Soo-Yeon; Hur, Tak; Lim, Tae Won

    2009-01-01

    In this study, the environmental aspects of H 2 pathways are analyzed according to plausible H 2 production methods, production capacity, and distribution options in Korea, using life cycle assessment (LCA) methodology. The target H 2 pathways analyzed are H 2 via naphtha steam reforming (Naphtha SR), H 2 via natural gas steam reforming (NG SR), H 2 via liquefied petroleum gas steam reforming (LPG SR), H 2 via water electrolysis with wind power (WE[Wind]), and H 2 via water electrolysis with Korea electricity mix (WE[KEM]). The results are then compared with those of conventional fuels (gasoline, diesel, and LPG) to identify which H 2 pathway has less environmental impact than the conventional fuels. Global warming (GW) impact, fossil fuel consumption (FFC) and regulated air emissions are studied to examine the environmental aspects of each fuel pathway. Given that H 2 technologies and infrastructures have yet to be fully commercialized, the environmental aspects of each pathway are analyzed in both their present status and a future scenario in 2015. LCA results show that WE[Wind] is superior regarding global warming potential (GWP), FFC and regulated air emissions. When gasoline is replaced with H 2 from WE[Wind], 99.8% and 99.9% of GWP and FFC can be reduced, respectively. Among the H 2 pathways based on fossil fuels, Naphtha SR[C] has the lowest values of GWP since the CO 2 capture equipment is attached to it. On the other hand, Naphtha SR[S] which is the station-type H 2 pathway does not have the CO 2 capture equipment. Naphtha SR[C] can reduce CO 2 emissions by 23.60 tons compared to gasoline over the entire life cycle of a vehicle. At present, Naphtha SR[C] appears to be environmentally efficient as H 2 conversion and infrastructure technologies have already been commercialized and are suitably developed in Korea. In 2015, however, among the H 2 pathways based on fossil fuels LPG SR[S] is expected to be the best pathway in terms of FFC and regulated air

  6. Theoretical study of the decomposition pathways and products of C5- perfluorinated ketone (C5 PFK)

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yuwei; Wang, Xiaohua, E-mail: xhw@mail.xjtu.edu.cn, E-mail: mzrong@mail.xjtu.edu.cn; Li, Xi; Yang, Aijun; Wu, Yi; Rong, Mingzhe, E-mail: xhw@mail.xjtu.edu.cn, E-mail: mzrong@mail.xjtu.edu.cn [State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, No. 28 XianNing West Road, Xi’an, Shaanxi Province 710049 (China); Han, Guohui; Lu, Yanhui [Pinggao Group Co. Ltd., Pingdingshan, Henan Province 467001 (China)

    2016-08-15

    Due to the high global warming potential (GWP) and increasing environmental concerns, efforts on searching the alternative gases to SF{sub 6}, which is predominantly used as insulating and interrupting medium in high-voltage equipment, have become a hot topic in recent decades. Overcoming the drawbacks of the existing candidate gases, C5- perfluorinated ketone (C5 PFK) was reported as a promising gas with remarkable insulation capacity and the low GWP of approximately 1. Experimental measurements of the dielectric strength of this novel gas and its mixtures have been carried out, but the chemical decomposition pathways and products of C5 PFK during breakdown are still unknown, which are the essential factors in evaluating the electric strength of this gas in high-voltage equipment. Therefore, this paper is devoted to exploring all the possible decomposition pathways and species of C5 PFK by density functional theory (DFT). The structural optimizations, vibrational frequency calculations and energy calculations of the species involved in a considered pathway were carried out with DFT-(U)B3LYP/6-311G(d,p) method. Detailed potential energy surface was then investigated thoroughly by the same method. Lastly, six decomposition pathways of C5 PFK decomposition involving fission reactions and the reactions with a transition states were obtained. Important intermediate products were also determined. Among all the pathways studied, the favorable decomposition reactions of C5 PFK were found, involving C-C bond ruptures producing Ia and Ib in pathway I, followed by subsequent C-C bond ruptures and internal F atom transfers in the decomposition of Ia and Ib presented in pathways II + III and IV + V, respectively. Possible routes were pointed out in pathway III and lead to the decomposition of IIa, which is the main intermediate product found in pathway II of Ia decomposition. We also investigated the decomposition of Ib, which can undergo unimolecular reactions to give the

  7. Preliminary study on the bioaccumulation of saxitoxins in Perna viridis through the dissolved pathway

    International Nuclear Information System (INIS)

    Almeida, Carmelo Adrian B.

    2011-03-01

    Paralytic shellfish poisoning (PSP) is a common fear among shellfish consumers. Saxitoxins are the group of compounds that are responsible for PSP. These compounds are produced by Pyrodinium bahamense var compresssum (PbC) which accumulate in perna viridis as they feed on PbC. This study aims to determine the presence of an alternative pathway, called the dissolved pathway, through which saxitoxins accumulate in Perna viridis independent of PbC. Perna viridis were exposed to a certain concentration of saxitoxins for a period of 24 hours and saxitoxin levels were determined at certain times throughout the period. The High Performance Liquid Chromatography (HPLC) - Oshima method was used in the measurement of toxins levels. Results show that mussels accumulate saxitoxins even in the absence of PbC, which supported the hypothesis that an alternative dissolved pathway contributes to the accumulation of saxitoxins in Perna viridis. (author)

  8. Anatomical study of the final common pathway for vocalization in the cat

    Science.gov (United States)

    Holstege, Gert

    1989-01-01

    Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

  9. PAPA: a flexible tool for identifying pleiotropic pathways using genome-wide association study summaries.

    Science.gov (United States)

    Wen, Yan; Wang, Wenyu; Guo, Xiong; Zhang, Feng

    2016-03-15

    : Pleiotropy is common in the genetic architectures of complex diseases. To the best of our knowledge, no analysis tool has been developed for identifying pleiotropic pathways using multiple genome-wide association study (GWAS) summaries by now. Here, we present PAPA, a flexible tool for pleiotropic pathway analysis utilizing GWAS summary results. The performance of PAPA was validated using publicly available GWAS summaries of body mass index and waist-hip ratio of the GIANT datasets. PAPA identified a set of pleiotropic pathways, which have been demonstrated to be involved in the development of obesity. PAPA program, document and illustrative example are available at http://sourceforge.net/projects/papav1/files/ : fzhxjtu@mail.xjtu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Oncological outcome, complications, lower urinary tract symptoms, and health-related quality of life after low-dose-rate salvage brachytherapy for recurrent prostate cancer following primary radiotherapy: a report of 8 cases

    Directory of Open Access Journals (Sweden)

    Makito Miyake

    2017-07-01

    Full Text Available Purpose: We evaluated our experience with low-dose-rate salvage brachytherapy for local recurrence after primary prostate radiotherapy, and described the changes in lower urinary tract symptoms and health-related quality of life. Material and methods: Between 2011 and 2016, eight men with local recurrence after primary prostate radiotherapy underwent iodine-125 salvage brachytherapy with a prescribed dose of 110 or 145 Gy. Recurrence-free survival was evaluated with a post-treatment prostate-specific antigen profile. The toxicity and changes in lower urinary tract symptoms and health-related quality of life during the follow-up were evaluated on the Common Terminology Criteria for Adverse Events version 4.0, International Prostate Symptom Score, Short Form-8, and Expanded Prostate Cancer Index Composite, respectively. Results: The median follow-up was 12.2 months (range, 8.3-71.9 after salvage brachytherapy. Of all eight patients, two (25% experienced treatment failure, one of whom developed left seminal vesicle recurrence 36 months after salvage brachytherapy for the right seminal vesicle recurrence, while the other developed bone metastases after 6 months. The International Prostate Symptom Scores peaked at 3 months, and returned to baseline by 6 months. The scores of all domains of health-related quality of life remained unchanged during the 12-month follow-up after salvage brachytherapy. Early grade ≤ 2 genitourinary toxicity was observed in five patients (63%, and late grade 2 gastrointestinal toxicity in one patient (13% having persistent diarrhea. No patient required intermittent catheterization and no grade 3 or greater toxicity occurred during follow-up. Conclusions: The present study is our experiment of eight patients undergoing salvage brachytherapy, suggesting that this modality is noninvasive, safe, and an effective salvage local treatment in selected patients. To our knowledge, this is the first study to evaluate lower urinary

  11. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Bruggeman, Richard; Nolen, Willem A.; Penninx, Brenda W.

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  12. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  13. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; de Haan, Lieuwe; Linszen, Don H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  14. Implementation and Evaluation of a Clinical Pathway for Pancreaticoduodenectomy Procedures: a Prospective Cohort Study

    NARCIS (Netherlands)

    Kolk, M. van der; Boogaard, M.H.W.A. van den; Becking-Verhaar, F.; Custers, H.; Hoeven, H. van der; Pickkers, P.; Laarhoven, K. van

    2017-01-01

    INTRODUCTION: Medical and nursing protocols in perioperative care for pancreaticoduodenectomy are mainly mono-disciplinary, limiting their integration and transparency in a continuous health care system. The aims of this study were to evaluate adherence to a multidisciplinary clinical pathway for

  15. Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer.

    Science.gov (United States)

    Montorsi, Francesco; Gandaglia, Giorgio; Fossati, Nicola; Suardi, Nazareno; Pultrone, Cristian; De Groote, Ruben; Dovey, Zach; Umari, Paolo; Gallina, Andrea; Briganti, Alberto; Mottrie, Alexandre

    2017-09-01

    Salvage lymph node dissection has been described as a feasible treatment for the management of prostate cancer patients with nodal recurrence after primary treatment. To report perioperative, pathologic, and oncologic outcomes of robot-assisted salvage nodal dissection (RASND) in patients with nodal recurrence after radical prostatectomy (RP). We retrospectively evaluated 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan. Surgery was performed using DaVinci Si and Xi systems. A pelvic nodal dissection that included lymphatic stations overlying the external, internal, and common iliac vessels, the obturator fossa, and the presacral nodes was performed. In 13 (81.3%) patients a retroperitoneal lymph node dissection that included all nodal tissue located between the aortic bifurcation and the renal vessels was performed. Perioperative outcomes consisted of operative time, blood loss, length of hospital stay, and complications occurred within 30 d after surgery. Biochemical response (BR) was defined as a prostate-specific antigen level <0.2 ng/ml at 40 d after RASND. Median operative time, blood loss, and length of hospital stay were 210min, 250ml, and 3.5 d. The median number of nodes removed was 16.5. Positive lymph nodes were detected in 11 (68.8%) patients. Overall, four (25.0%) and five (31.2%) patients experienced intraoperative and postoperative complications, respectively. Overall, one (6.3%) and four (25.0%) patients had Clavien I and II complications within 30 d after RASND, respectively. Overall, five (33.3%) patients experienced BR after surgery. Our study is limited by the small cohort of patients evaluated and by the follow-up duration. RASND represents a feasible procedure in patients with nodal recurrence after RP and provides acceptable short-term oncologic outcomes, where one out of three patients experience BR immediately after surgery. Long-term data are needed to

  16. Salvage Treatment for Recurrent Intracranial Germinoma After Reduced-Volume Radiotherapy: A Single-Institution Experience and Review of the Literature

    International Nuclear Information System (INIS)

    Hu, Yu-Wen; Huang, Pin-I; Wong, Tai-Tong; Ho, Donald Ming-Tak; Chang, Kai-Ping; Guo, Wan-Yuo; Chang, Feng-Chi; Shiau, Cheng-Yin; Liang, Muh-Lii; Lee, Yi-Yen

    2012-01-01

    Purpose: Intracranial germinomas (IGs) are highly curable with radiotherapy (RT). However, recurrence still occurs, especially when limited-field RT is applied, and the optimal salvage therapy remains controversial. Methods and Materials: Between January 1989 and December 2010, 14 patients with clinically or pathologically diagnosed recurrent IGs after RT were reviewed at our institution. Of these, 11 received focal-field RT, and the other 3 received whole-brain irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the respective first course of RT. In addition, we identified from the literature 88 patients with recurrent IGs after reduced-volume RT, in whom the details of salvage therapy were recorded. Results: The median time to recurrence was 30.3 months (range, 3.8–134.9 months). One patient did not receive further treatment and was lost during follow-up. Of the patients, 7 underwent salvage with craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median follow-up time was 105.1 months (range, 24.2–180.9 months). Three patients died without evidence of disease progression: two from second malignancies and one from unknown cause. The others remained disease free. The 3-year survival rate after recurrence was 83.3%. A total of 102 patients from our study and the literature review were analyzed to determine the factors affecting prognosis and outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all patients and for those receiving salvage CSI, respectively. Univariate analysis showed that initial RT volume, initial RT dose, initial CT, and salvage RT type were significant prognostic predictors of survival. On multivariable analysis, salvage CSI was the most significant factor (p = 0.03). Conclusions: Protracted follow-up is recommended because late recurrence is not uncommon. CSI with or without CT is an effective

  17. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

    Science.gov (United States)

    Bøtker, Hans Erik; Kharbanda, Rajesh; Schmidt, Michael R; Bøttcher, Morten; Kaltoft, Anne K; Terkelsen, Christian J; Munk, Kim; Andersen, Niels H; Hansen, Troels M; Trautner, Sven; Lassen, Jens Flensted; Christiansen, Evald Høj; Krusell, Lars R; Kristensen, Steen D; Thuesen, Leif; Nielsen, Søren S; Rehling, Michael; Sørensen, Henrik Toft; Redington, Andrew N; Nielsen, Torsten T

    2010-02-27

    Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote

  18. A developing world experience with distal foot amputations for diabetic limb salvage

    Directory of Open Access Journals (Sweden)

    Omer Salahuddin

    2013-10-01

    Full Text Available Objectives: To evaluate the functional outcome, morbidity, and viability of foot salvage in diabetic patients. Materials and methods: This prospective case series was conducted from March 2007 to December 2012 at the department of surgery Pakistan Ordnance Factories Hospital, Wah Cantt, Pakistan. 123 males and 26 female patients were included in the study. All the patients were treated after getting admitted in the hospital and wounds were managed with daily dressings, nursing care and debridement of necrotic tissue with adequate antibiotic coverage. Results: In total, 149 patients (mean age: 56±7.52 years with 171 amputations were included in the study. The mean duration of diabetes mellitus (DM was 9±4.43 years. Ninety-seven percent of the patients were diagnosed with type 2 DM. Wound debridement was performed under general anesthesia in 48 (33.2% patients, whereas local anesthesia was used for the rest of the patients after having good glycemic control and improvement in general health. The most common pathogen isolated from the infected wounds was Staphylococcus aureus in approximately 46% cases. Regarding the types of amputation, partial toe amputation was performed in 21 (12.2% cases, second-toe amputation in 60 (35% cases, hallux amputation in 41 (24% cases, multiple toe amputations in 29 (17% cases, bilateral feet involvement was observed in 16 (9.3% cases, and transmetatarsal amputation was performed in 4 (2.3% cases. The wounds healed well except in 19 cases where amputation had to be revised to a more proximal level. Thirty-nine patients died during the study period: 3 died of wound-related complications and 36 died of systemic complications. Conclusion: With the ever-increasing epidemic of DM, the number of patients with diabetic foot ulcers has also significantly risen. Early surgical management with good glycemic control and foot care with close monitoring can decrease amputations and thus foot salvage can be successfully

  19. Procedures for the salvage and necropsy of the dugong (Dugong dugon)

    Science.gov (United States)

    Eros, Carole; Marsh, Helene; Bonde, Robert K.; O'Shea, Thomas A.; Beck, Cathy A.; Recchia, Cheri; Dobbs, Kirstin; Turner, Malcolm; Lemm, Stephanie; Pears, Rachel; Bowater, Rachel

    2007-01-01

    Data and specimens collected from dugong carcasses and live stranded individuals provide vital information for research and management agencies. The ability to assign a cause of death (natural and/or human induced) to a carcass assists managers to identify major threats to a population in certain areas and to evaluate and adapt management measures. Data collectedfrom dugong carcasses have contributed to research in areas such as life history, feeding biology, investigating the stock structure/genetics of dugongs, contaminants studies, heavy metal analyses, parasitology, and the effects of habitat change. Adapted from the 'Manual of Procedures for the Salvage and Necropsy of Carcasses of the West Indian Manatee (Trichechus manatus),' this manual provides a detailed guide for dugong (Dugong dugon) carcass handling and necropsy procedures. It is intended to be used as a resource and training guide for anyone involved in dugong incidents who may lack dugong expertise.

  20. [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography after limb salvage surgery: post-surgical appearance, attenuation correction and local complications

    Energy Technology Data Exchange (ETDEWEB)

    Gelfand, Michael J.; Sharp, Susan E. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Nuclear Medicine Division, Cincinnati, OH (United States)

    2015-08-15

    Metal endoprostheses and internal fixation devices cause significant artifacts on CT after limb salvage surgery; positron emission tomography (PET) images should be evaluated for artifacts. (1) To describe [F-18]2-fluoro-2-deoxyglucose (FDG) PET uptake patterns after limb salvage surgery. (2) To determine whether metal endoprostheses and fixation hardware cause significant artifacts on CT attenuation-corrected PET that interfere with diagnostic use of PET/CT after limb salvage surgery. We reviewed 92 studies from 18 patients ages 5-21 years. Diagnoses were osteogenic sarcoma in 14, Ewing sarcoma in 3, and malignant peripheral nerve sheath tumor originating in bone in 1. Nine patients had distal femur/knee endoprostheses, five had lower-extremity bone allografts secured by large metal plates and four had upper-extremity limb salvage procedures. Maximum standardized uptake value was calculated at lower-extremity soft-tissue-endoprosthesis interfaces. In 15 patients with PET/CT imaging, the first PET/CT scan after limb salvage surgery was reviewed for metal artifacts on CT images and for artifacts at locations on PET corresponding to the CT metal artifacts. Increased FDG uptake was consistently present at soft-tissue interfaces with endoprostheses, allografts and internal fixation devices, with little or no FDG uptake at cemented endoprosthesis-bone interfaces. Maximum standardized uptake value at margins of femur/knee endoprostheses ranged from 1.4 to 5.7. In four patients with distal femur/knee endoprostheses, minimal artifact was noted on attenuation-corrected PET images, but image interpretation was not affected. In the other 11 patients who had CT attenuation correction, we detected no artifacts caused by the attenuation correction. CT attenuation correction did not cause artifacts that affected interpretation of attenuation-corrected PET images. (orig.)

  1. [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography after limb salvage surgery: post-surgical appearance, attenuation correction and local complications

    International Nuclear Information System (INIS)

    Gelfand, Michael J.; Sharp, Susan E.

    2015-01-01

    Metal endoprostheses and internal fixation devices cause significant artifacts on CT after limb salvage surgery; positron emission tomography (PET) images should be evaluated for artifacts. (1) To describe [F-18]2-fluoro-2-deoxyglucose (FDG) PET uptake patterns after limb salvage surgery. (2) To determine whether metal endoprostheses and fixation hardware cause significant artifacts on CT attenuation-corrected PET that interfere with diagnostic use of PET/CT after limb salvage surgery. We reviewed 92 studies from 18 patients ages 5-21 years. Diagnoses were osteogenic sarcoma in 14, Ewing sarcoma in 3, and malignant peripheral nerve sheath tumor originating in bone in 1. Nine patients had distal femur/knee endoprostheses, five had lower-extremity bone allografts secured by large metal plates and four had upper-extremity limb salvage procedures. Maximum standardized uptake value was calculated at lower-extremity soft-tissue-endoprosthesis interfaces. In 15 patients with PET/CT imaging, the first PET/CT scan after limb salvage surgery was reviewed for metal artifacts on CT images and for artifacts at locations on PET corresponding to the CT metal artifacts. Increased FDG uptake was consistently present at soft-tissue interfaces with endoprostheses, allografts and internal fixation devices, with little or no FDG uptake at cemented endoprosthesis-bone interfaces. Maximum standardized uptake value at margins of femur/knee endoprostheses ranged from 1.4 to 5.7. In four patients with distal femur/knee endoprostheses, minimal artifact was noted on attenuation-corrected PET images, but image interpretation was not affected. In the other 11 patients who had CT attenuation correction, we detected no artifacts caused by the attenuation correction. CT attenuation correction did not cause artifacts that affected interpretation of attenuation-corrected PET images. (orig.)

  2. Deoxynucleoside salvage in fission yeast allows rescue of ribonucleotide reductase deficiency but not Spd1-mediated inhibition of replication

    DEFF Research Database (Denmark)

    Fleck, Oliver; Fahnøe, Ulrik; Løvschal, Katrine Vyff

    2017-01-01

    In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1) blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4(Cdt2) E3 ubiquitin...... ligase mediates degradation of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have generated a conditional allele of CRL4(Cdt2), by expressing the highly unstable substrate-recruiting protein Cdt2 from a repressible promoter. Unlike Spd1, Spd2 does not regulate deoxynucleotide...... triphosphate (dNTP) pools; yet we find that Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly test whether this block of replication was solely due to insufficient dNTP levels, we established a deoxy-nucleotide salvage pathway in fission yeast by expressing the human nucleoside...

  3. Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies.

    Science.gov (United States)

    Mocellin, Simone; Tropea, Saveria; Benna, Clara; Rossi, Carlo Riccardo

    2018-02-19

    Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10 -6 ; top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10 -6 ; top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10 -7 ; top gene RORA, gene P value = 2.0 × 10 -6 ), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer

  4. Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

    Science.gov (United States)

    Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

    2018-04-12

    To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

  5. Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L

    2010-06-01

    Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed.

  6. Multidisciplinary ''limb salvage'' treatment of soft tissue and skeletal sarcomas

    International Nuclear Information System (INIS)

    Weisenburger, T.H.; Eilber, F.R.; Grant, T.T.; Morton, D.L.; Mirra, J.J.; Steinberg, M.; Rickles, D.

    1984-01-01

    The goal of treating primary bone and soft tissue tumors, as with most other malignancies, is to control the disease locally and systematically while preserving as much function as possible. For soft tissue sarcomas the results following radical excision and post-operative radiation therapy with preservation of the limb have equaled the control rates of amputation. However, local recurrence rates of approximately 25-30% are reported for high-grade lesions of the proximal lower extremity. Amputations provides excellent local control for osteosarcoma but the functional results may be less than optimal. In an attempt to achieve limb salvage for these tumors, a multidisciplinary protocol was developed using intra-arterial doxorubicin, pre-operative radiation therapy and limb-sparing radical wide excision followed by post-operative chemotherapy for presumed micro-metastatic disease

  7. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

    International Nuclear Information System (INIS)

    Azuma, Koichi; Tsurutani, Junji; Sakai, Kazuko; Kaneda, Hiroyasu; Fujisaka, Yasuhito; Takeda, Masayuki; Watatani, Masahiro; Arao, Tokuzo; Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu; Nishio, Kazuto; Nakagawa, Kazuhiko

    2011-01-01

    Highlights: → A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. → Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. → Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC 50 of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  8. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, Koichi [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Tsurutani, Junji, E-mail: tsurutani_j@dotd.med.kindai.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Sakai, Kazuko; Kaneda, Hiroyasu [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Fujisaka, Yasuhito; Takeda, Masayuki [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Watatani, Masahiro [Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Arao, Tokuzo [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan)

    2011-04-01

    Highlights: {yields} A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. {yields} Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. {yields} Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC{sub 50} of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  9. Limb salvage and reconstruction following a zebra attack

    Directory of Open Access Journals (Sweden)

    Jacob T. Carlson

    2017-06-01

    Full Text Available Animal bites are fairly rare events but can cause devastating traumatic injuries to the victim. In addition to the soft tissue, vascular, and orthopedic trauma inflicted by these occurrences, bite injuries also have the potential to introduce an inoculum of microbes, which may progress to an infection if not treated properly and expeditiously.We present the case of a healthy male who sustained multiple bite wounds from a domestic zebra to his left upper extremity. This attack caused severe damage, including devascularization of the arm at the brachial artery, disruption of the distal biceps and brachialis, stripping of the forearm nerves, and shearing of the overlying soft tissue. The patient was taken emergently to the operating room for revascularization of the extremity utilizing a vein bypass graft. The soft tissue injuries were addressed with numerous irrigation and debridement procedures, during which coverage of the vein bypass graft was obtained using a variety of techniques, including skin flaps, musculocutaneous advancements, and the application of an acellular dermal matrix (AlloDerm and a collagen-glycosaminoglycan matrix (Integra.Wound cultures obtained intra-operatively during the irrigation and debridement procedures were notable for the growth of multiple microbes, including Rhodococcus spp., which have been documented to cause infection in immunocompromised patients. The patient in this case was treated with a prolonged course of antibiotics, and wound cultures negative for microbial growth were eventually obtained prior to final closure of his wound. The patient then underwent successful biceps reconstruction with a pedicled latissimus dorsi muscle transfer. This case documents the extraordinary multidisciplinary approach provided in the salvage, management, and eventual reconstruction of a mangled left upper extremity that had sustained devastating traumatic injuries resulting from a rather unusual source. Keywords: Zebra

  10. Study to elucidate formation pathways of selected roast-smelling odorants upon extrusion cooking.

    Science.gov (United States)

    Davidek, Tomas; Festring, Daniel; Dufossé, Thierry; Novotny, Ondrej; Blank, Imre

    2013-10-30

    The formation pathways of the N-containing roast-smelling compounds 2-acetyl-1-pyrroline, 2-acetyl-1(or 3),4,5,6-tetrahydropyridine, and their structural analogues 2-propionyl-1-pyrroline and 2-propionyl-1(or 3),4,5,6-tetrahydropyridine were studied upon extrusion cooking using the CAMOLA approach. The samples were produced under moderate extrusion conditions (135 °C, 20% moisture, 400 rpm) employing a rice-based model recipe enriched with flavor precursors ([U-(13)C6]-D-glucose, D-glucose, glycine, L-proline, and L-ornithine). The obtained data indicate that the formation of these compounds upon extrusion follows pathways similar to those reported for nonsheared model systems containing D-glucose and L-proline. 2-Acetyl-1-pyrroline is formed (i) by acylation of 1-pyrroline via C2 sugar fragments (major pathway) and (ii) via ring-opening of 1-pyrroline incorporating C3 sugar fragments (minor pathway), whereas 2-propionyl-1-pyrroline incorporates exclusively C3 sugar fragments. 2-Acetyl-1(or 3),4,5,6-tetrahydropyridine and the corresponding propionyl analogue incorporate C3 and C4 sugar fragments, respectively. In addition, it has been shown that the formation of 2-acetyl-1-pyrroline in low-moisture systems depends on the pH value of the reaction mixture.

  11. Limb salvage with microvascular free fibula following primary bone sarcoma resection

    Directory of Open Access Journals (Sweden)

    Sahasrabudhe Parag

    2016-01-01

    Full Text Available Background: Extremity sarcomas are challenging to manage. Total eradication of tumour has to be balanced with restoration of limb function to prevent mortality and morbidity. Disease-free survival with maximum limb function is the ultimate goal in these patients. Materials and Methods: We present a series of ten cases of extremity malignancies, where limb salvage was attempted with microvascular free fibula for limb reconstruction from the period of 2008 to 2015. Results: Of the ten cases in the study, there were two females and eight males. There were nine patients with lower limb malignancies and one patient with upper limb malignancy. There were four patients with Ewing's sarcoma of femur, five patients with osteosarcoma of femur and one patient with chondrosarcoma of the humerus. The follow-up period ranged from 1.2 to 6.2 years with mean follow-up of 3.1 years. There were two deaths during follow-up, both were due to distant metastasis. The assessment of the function was done on the basis of Musculoskeletal Tumour Society functional score. Maximum score was 30 and minimum score was 24, the average score being 26. Of the eight surviving patients, three patients had full weightbearing, four patients had partial weightbearing at end of 2 years and one patient of upper limb reconstruction had complete upper limb function. None of the patients had to undergo limb amputation. Conclusion: Limb salvage with vascularised fibula graft offers good functional outcome along with good disease-free survival rates.

  12. Salvaging of service exposed cast alloy 625 cracker tubes of ammonia based Heavy Water Plants

    International Nuclear Information System (INIS)

    Kumar, Niraj; Misra, B.; Mahajan, M.P.; Mittra, J.; Sundararaman, M.; Chakravartty, J.K.

    2006-01-01

    In ammonia based heavy water plants, cracking of ammonia vapour, enriched in deuterium is carried out inside a cracker tube, packed with catalyst. These cracker tubes are made of alloy 625 (either wrought or cast) having dimensions of about 12.5 metres long, 88 mm outer diameter and 7.9 mm wall thickness. Seventy such tubes are housed in a typical ammonia cracker unit. The anticipated design life of such tube is 1,00,000 hrs. when operated at 720 degC based on creep as main degradation mechanism. Presently, these tubes are being operated at 680 degC skin temperature. Alloy 625 tubes are costly and normally not manufactured in India and are being imported. The cast alloy 625 cracker tubes have outlived their design life of 100,000 hrs. Therefore it has been decided to salvage the cast cracker tubes and extend the life further as it had already been done for wrought tubes. Similar to the earlier attempt of resolutionising of wrought alloy 625 tubes, efforts are in progress to salvage these cast tubes. In this study, cast tubes samples were subjected to solution-annealing treatment at two different temperatures, 1100degC and 1160degC respectively for two hrs. Mechanical properties along with the microstructure of the samples, which were resolutionized at 1160degC were comparable with that of virgin material. The 12.5 metres long cast alloy 625 cracker tubes will also be shortly solution-annealed in a specially designed resistance heating furnace after completing some more tests. (author)

  13. Evaluations of the trans-sulfuration pathway in multiple liver toxicity studies

    International Nuclear Information System (INIS)

    Schnackenberg, Laura K.; Chen Minjun; Sun, Jinchun; Holland, Ricky D.; Dragan, Yvonne; Tong Weida; Welsh, William; Beger, Richard D.

    2009-01-01

    Drug-induced liver injury has been associated with the generation of reactive metabolites, which are primarily detoxified via glutathione conjugation. In this study, it was hypothesized that molecules involved in the synthesis of glutathione would be diminished to replenish the glutathione depleted through conjugation reactions. Since S-adenosylmethionine (SAMe) is the primary source of the sulfur atom in glutathione, UPLC/MS and NMR were used to evaluate metabolites involved with the transulfuration pathway in urine samples collected during studies of eight liver toxic compounds in Sprague-Dawley rats. Urinary levels of creatine were increased on day 1 or day 2 in 8 high dose liver toxicity studies. Taurine concentration in urine was increased in only 3 of 8 liver toxicity studies while SAMe was found to be reduced in 4 of 5 liver toxicity studies. To further validate the results from the metabonomic studies, microarray data from rat liver samples following treatment with acetaminophen was obtained from the Gene Expression Omnibus (GEO) database. Some genes involved in the trans-sulfuration pathway, including guanidinoacetate N-methyltransferase, glycine N-methyltransferase, betaine-homocysteine methyltransferase and cysteine dioxygenase were found to be significantly decreased while methionine adenosyl transferase II, alpha increased at 24 h post-dosing, which is consistent with the SAMe and creatine findings. The metabolic and transcriptomic results show that the trans-sulfuration pathway from SAMe to glutathione was disturbed due to the administration of heptatotoxicants

  14. A STUDY OF INTERMEDIATES INVOLVED IN THE FOLDING PATHWAY FOR RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR (M-CSF) - EVIDENCE FOR 2 DISTINCT FOLDING PATHWAYS

    NARCIS (Netherlands)

    WILKINS, JA; CONE, J; RANDHAWA, ZI; WOOD, D; WARREN, MK; WITKOWSKA, HE

    The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding

  15. Pros and Cons of Clinical Pathway Software Management: A Qualitative Study.

    Science.gov (United States)

    Aarnoutse, M F; Brinkkemper, S; de Mul, M; Askari, M

    2018-01-01

    In this study we aimed to assess the perceived effectiveness of clinical pathway management software for healthcare professionals. A case study on the clinical pathway management software program Check-It was performed in three departments at an academic medical center. Four months after the implementation of the software, interviews were held with healthcare professionals who work with the system. The interview questions were posed in a semi-structured interview format and the participant were asked about the perceived positive or negative effects of Check-It, and whether they thought the software is effective for them. The interviews were recorded and transcribed based on grounded theory, using different coding techniques. Our results showed fewer overlooked tasks, pre-filled orders and letters, better overview, and increased protocol insight as positive aspects of using the software. Being not flexible enough was experienced as a negative aspect.

  16. Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks

    OpenAIRE

    Zhao, Huiying; Nyholt, Dale R.; Yang, Yuanhao; Wang, Jihua; Yang, Yuedong

    2017-01-01

    Genome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous...

  17. Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45).

    Science.gov (United States)

    Wang, X; Ren, J; Zhang, J; Yan, Y; Jiang, N; Yu, J; Di, L; Song, G; Che, L; Jia, J; Zhou, X; Yang, H; Lyerly, H K

    2016-01-01

    The recent immunotherapy treatment on triple-negative breast cancer (TNBC) leads to the breakthrough assignation. In this study, we have tried the new combinations of specific chemo with DC-CIKs immunotherapy to treat those patients. Twenty-three metastatic anthracyclines and taxanes pretreated TNBC younger (mean 41.5 years) patients were initially mobilized with cyclophosphamide (3 g/m(2)) for the preparation of CD34(+) peripheral blood mononuclear cells as the resources for generating DC/CIKs and marrow function supports. All cases were subsequently experienced 2 cycles of chemotherapy with cyclophosphamide 3 g/m(2), thiotepa 150 mg/m(2), and carboplatin AUC = 6, Q4w. The patients then received 3 infusions of DC-CIKs at the chemo intervals and followed by maintenance therapy with oral cyclophosphamide 50 mg daily. The endpoints were progression-free survival and overall survival. The partial response rate was 13.0 %, stable and progressive disease rates were 56.5 and 30.4 %, respectively. The median PFS was 13.5 months (95 % confidence interval (CI) 10.1-16.9 months) and OS was 15.2 months (95 % CI 12.5-18.1 months). The most common serious adverse events were neutropenia (100.0 %) and anemia (69.7 %) but without treatment-related mortality. These data suggested that such combination therapy model be effective and safe for younger metastatic TNBC exposure to previous anthracyclines and taxanes based adjuvant chemotherapy.

  18. Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

    International Nuclear Information System (INIS)

    Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

    2014-01-01

    To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

  19. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  20. Pathways into mental health care for UK veterans: a qualitative study.

    Science.gov (United States)

    Mellotte, Harriet; Murphy, Dominic; Rafferty, Laura; Greenberg, Neil

    2017-01-01

    Background : It is well established that veterans suffering from mental health difficulties under use mental health services. Objective : This study aimed to understand more about the barriers that prevent veterans from seeking professional help and the enablers that assist veterans in seeking professional help. It also aimed to explore potential mechanisms to improve veterans' help-seeking and pathways to care. Method : The study employed a qualitative design whereby 17 veterans who had recently attended specialist veteran mental health services took part in semi-structured interviews. The resultant data were analysed using grounded theory. Results : Participants described two distinct stages to their help-seeking: initial help-seeking and pathways through treatment. Specific barriers and enablers to help-seeking were identified at each stage. Initial barriers included recognizing that there is a problem, self-stigma and anticipated public stigma. Initial enablers included being in crisis, social support, motivation and the media. Treatment pathway barriers included practical factors and negative beliefs about health services and professionals. Treatment pathway enablers included having a diagnosis, being seen in a veteran-specific service and establishing a good therapeutic relationship. Participants provided some suggestions for interventions to improve veterans' help-seeking in future; these focussed on enhancing both veterans and health professionals' knowledge regarding mental health difficulties. Conclusions : This study identified a number of barriers and enablers that may impact a veteran's journey in seeking help from professional services for mental health difficulties. Enablers such as reaching a crisis point, social support, the media, having a diagnosis of PTSD and veteran-specific mental health services appeared to be important in opposing stigma-related beliefs and in supporting veterans to engage in help-seeking behaviours.

  1. Saphenous vein grafts for perforator flap salvage in autologous breast reconstruction.

    Science.gov (United States)

    Flores, Jaime I; Rad, Ariel N; Shridharani, Sachin M; Stapleton, Sahael M; Rosson, Gedge D

    2009-01-01

    Although the use of saphenous vein grafts in free-flap salvage and extremity replantation is relatively common, their use in breast reconstruction is rare. These two case reports represent extreme alternatives for breast reconstruction flap salvage. In our normal daily practice, the overwhelming majority of elective breast reconstructions proceed smoothly. However, the occasional patient may require saphenous vein graft flap rescue for completion of the reconstruction. (c) 2008 Wiley-Liss, Inc.

  2. Salvage felling in the Slovak forests in the period 2004–2013

    Directory of Open Access Journals (Sweden)

    Kunca Andrej

    2015-09-01

    Full Text Available Salvage felling is one of the indicators of the forest health quality and stability. Most of the European Union countries monitor forest harmful agents, which account for salvage felling, in order to see trends or functionality between factors and to be able to predict their development. The systematic evidence of forest harmful agents and volume of salvage felling in Slovakia started at the Forest Research Institute in Zvolen in 1960. The paper focuses on the occurrence of the most relevant harmful agents and volume of salvage felling in the Slovak forests over the last decade. Within the 10 years period (2004–2013 salvage felling in Slovakia reached 42.31 mil. m3 of wood, which was 53.2% of the total felling. Wind and European spruce bark beetle Ips typographus damaged 78.4% of salvage wood, i.e. they were the most important pest agents. Norway spruce (Picea abies was the most frequently damaged tree species that represented the amount of 35.6 mil. m3 of wood (81.2% of total volume of salvage felling. As Norway spruce grows mostly in mountains, these regions of Central and Northern Slovakia were most affected. At the damaged localities new forests were prevailingly established with regard to suitable ecological conditions for trees, climate change scenarios and if possible, natural regeneration has been preferred. These approaches in forest stand regeneration together with silvicultural and control measures are assumed to gradually decrease the amount of salvage felling over long term perspective.

  3. Role of Pectoralis Major Myocutanuos Flap in Salvage Laryngeal Surgery for Prophylaxis of Pharyngocutaneuos Fistula and Reconstruction of Skin Defect

    International Nuclear Information System (INIS)

    Mebeed, A.; Hussein, H.A.; Saber, T.Kh.; Zohairy, M.A.; Lotayef, M.

    2009-01-01

    This study was carried out to minimize the incidence of pharyngocutaneous fistula (PCF) following salvage laryngeal surgery using vascularized pedicle pectoralis major myocutaneous flap (PMMC) for enhancing wound healing, rapid intake of oral feeding, reconstruction of desqauamated irradiated skin, achieving short hospital stay and protection against catastrophic blow out mortality. Patients and Methods: This case series study of sixteen patients carried out from May 2005 to July 2009, at the National Cancer Institute, Cairo University where we applied PMMC flap in salvage laryngeal surgery for those with high risk to develop complications: Patients of poor general conditions (anemia, hypoproteinaemia, diabetics) and/or poor local conditions for healing (irradiated neck, extensive local or nodal recurrence with skin desquamation, infiltration or tumor fungation which need extensive resection). Five cases had been treated with primary cobalt radiotherapy laryngeal field only and 4 cases laryngeal field with draining neck nodes, while photon therapy was given in 4 cases as laryngeal field only and 3 cases laryngeal field with draining neck nodes. All cases were squamous cell carcinoma (13 cases grade 2, 2 cases grade 3 and one case grade 1) proved before radiotherapy. Supraglottic recurrence was detected in 7 cases (43.75%) and glottis in 9 cases (56.25%). Following salvage surgery, 11 cases were staged T3 NO, Nl and N2, 3 cases were T2 NO or Nl and 2 cases were T4 N2 with skin infiltration. Tracheostomy was there in 4 cases. Results: The study included fifteen males (93.75%) and one female (6.25%), age was between 38-73 years (mean=55.5 years). Five cases were operated on as total laryngectomy with excision of skin flaps + PMMC flap, 4 cases as total laryngectomy with skin flap excision + functional block neck dissection + PMMC flap and 7 cases as total laryngectomy -f block neck dissection with skin, excision (modified radical in 4 cases and radical in 3 cases

  4. Resistance to chemotherapeutic antimetabolites: a function of salvage pathway involvement and cellular response to DNA damage.

    OpenAIRE

    Kinsella, A. R.; Smith, D.; Pickard, M.

    1997-01-01

    The inherent or acquired (induced) resistance of certain tumours to cytotoxic drug therapy is a major clinical problem. There are many categories of cytotoxic agent: the antimetabolites, e.g. methotrexate (MTX), N-phosphonacetyl-L-aspartate (PALA), 5-fluorouracil (5-FU), 6-mercaptopurine (6-TG), hydroxyurea (HU) and 1-beta-D-arabinofuranosylcytosine (AraC); the alkylating agents, e.g. the nitrogen mustards and nitrosoureas; the antibiotics, e.g. doxorubicin and mitomycin C; the plant alkaloid...

  5. Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial.

    Science.gov (United States)

    Jabbour, Mona; Curran, Janet; Scott, Shannon D; Guttman, Astrid; Rotter, Thomas; Ducharme, Francine M; Lougheed, M Diane; McNaughton-Filion, M Louise; Newton, Amanda; Shafir, Mark; Paprica, Alison; Klassen, Terry; Taljaard, Monica; Grimshaw, Jeremy; Johnson, David W

    2013-05-22

    The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for 'point of care' management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma--the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis--the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process

  6. Neuroimmune Pathways in Alcohol Consumption: Evidence from Behavioral and Genetic Studies in Rodents and Humans

    Science.gov (United States)

    Robinson, Gizelle; Most, Dana; Ferguson, Laura B.; Mayfield, Jody; Harris, R. Adron; Blednov, Yuri A.

    2014-01-01

    Immune or brain proinflammatory signaling has been linked to some of the behavioral effects of alcohol. Immune signaling appears to regulate voluntary ethanol intake in rodent models, and ethanol intake activates the immune system in multiple models. This bidirectional link raises the possibility that consumption increases immune signaling, which in turn further increases consumption in a feed-forward cycle. Data from animal and human studies provide overlapping support for the involvement of immune-related genes and proteins in alcohol action, and combining animal and human data is a promising approach to systematically evaluate and nominate relevant pathways. Based on rodent models, neuroimmune pathways may represent unexplored, nontraditional targets for medication development to reduce alcohol consumption and prevent relapse. Peroxisome proliferator-activated receptor agonists are one class of anti-inflammatory medications that demonstrate antiaddictive properties for alcohol and other drugs of abuse. Expression of immune-related genes is altered in animals and humans following chronic alcohol exposure, and the regulatory influences of specific mRNAs, microRNAs, and activated cell types are areas of intense study. Ultimately, the use of multiple datasets combined with behavioral validation will be needed to link specific neuroimmune pathways to addiction vulnerability. PMID:25175860

  7. Health-related quality of life after salvage high-intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer

    International Nuclear Information System (INIS)

    Berge, V.; Baco, E.; Dahl, A.A.; Karlsen, S.J.

    2011-01-01

    The objective of this study was to evaluate health-related quality of life (HRQOL) after salvage high-intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) questionnaire at baseline and at follow-up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow-up. Fifty-seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6-29 months). The mean score for urinary function decreased from 79.7±12.1 prior to HIFU to 67.4±17.8 after HIFU (P<0.001). The mean score for sexual function decreased from 32.1±24.1 prior to HIFU to 17.2±17.0 after HIFU (P<0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow-up of 17.5 months. (author)

  8. Intraoperative extracorporeal autogenous irradiated tendon grafts for functional limb salvage surgery of soft tissue sarcomas of the wrist and hand.

    Science.gov (United States)

    Omori, Shinsuke; Hamada, Kenichiro; Outani, Hidetatsu; Oshima, Kazuya; Joyama, Susumu; Tomita, Yasuhiko; Naka, Norifumi; Araki, Nobuhito; Yoshikawa, Hideki

    2015-05-12

    In patients with soft tissue sarcoma of the wrist and hand, limb salvage operation is extremely challenging for surgeons in attempting a complete tumor resection with negative surgical margins. In this study, we report four patients with soft tissue sarcoma of the wrist and hand treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts. The patients were all male, and the mean age at the time of surgery was 45 years. Histological diagnoses included clear cell sarcoma in two patients, synovial sarcoma in one, and angiosarcoma in one. All four patients had high grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage III disease and one with AJCC stage IV disease. The tumors were resected en bloc with involved tendons. The tendons were isolated from the resected tissues, irradiated ex vivo, and re-implanted into the host tendons. In one patient, the bone was resected additionally because of tumor invasion to the bone. Hand function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system. Of the four patients, three died of distant metastatic disease. The remaining patient lives and remains disease-free. The mean follow-up period was 33 months. One patient had local recurrence outside the irradiated graft at 20 months after surgery. The functional rating was 22. Lower scores were seen in patients with reconstruction of flexor tendons than extensor tendons. Limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts is an acceptable method in selected patients with soft tissue sarcoma of the wrist and hand.

  9. Original Article Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage Ill/TV neuroblastoma

    International Nuclear Information System (INIS)

    Abdel Rahman, M.; Zekri, W.Z.K.; Moussa, E.A.M.; El Debawy, E.; Mostafa, N.E.; Yones, A.; Ezzat, S.; Rayan, A.

    2011-01-01

    Neuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at h igh risk o f treatment failure. The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients. Patients and methods: Sixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%). Results: They were 40 males (60.6%) and 26 females (39.4%). Patients' age ranged between 3 months and 12.5 years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%)'died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%). Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy. By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR. Conclusion: Chemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation

  10. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    International Nuclear Information System (INIS)

    Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B.

    2017-01-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  11. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy.

    Science.gov (United States)

    Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P; Bekelman, Justin E; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B

    2017-02-01

    In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, Vivek [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mick, Rosemarie [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Subramanian, Pearl [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Haas, Naomi B., E-mail: naomi.haas@uphs.upenn.edu [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2017-02-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  13. An Evaluation of the Implementation of Maternal Obesity Pathways of Care: A Mixed Methods Study with Data Integration

    Science.gov (United States)

    Heslehurst, Nicola; Dinsdale, Sarah; Sedgewick, Gillian; Simpson, Helen; Sen, Seema; Summerbell, Carolyn Dawn; Rankin, Judith

    2015-01-01

    Objectives Maternal obesity has multiple associated risks and requires substantial intervention. This research evaluated the implementation of maternal obesity care pathways from multiple stakeholder perspectives. Study Design A simultaneous mixed methods model with data integration was used. Three component studies were given equal priority. 1: Semi-structured qualitative interviews explored obese pregnant women’s experiences of being on the pathways. 2: A quantitative and qualitative postal survey explored healthcare professionals’ experiences of delivering the pathways. 3: A case note audit quantitatively assessed pathway compliance. Data were integrated using following a thread and convergence coding matrix methods to search for agreement and disagreement between studies. Results Study 1: Four themes were identified: women’s overall (positive and negative) views of the pathways; knowledge and understanding of the pathways; views on clinical and weight management advice and support; and views on the information leaflet. Key results included positive views of receiving additional clinical care, negative experiences of risk communication, and weight management support was considered a priority. Study 2: Healthcare professionals felt the pathways were worthwhile, facilitated good practice, and increased confidence. Training was consistently identified as being required. Healthcare professionals predominantly focussed on women’s response to sensitive obesity communication. Study 3: There was good compliance with antenatal clinical interventions. However, there was poor compliance with public health and postnatal interventions. There were some strong areas of agreement between component studies which can inform future development of the pathways. However, disagreement between studies included a lack of shared priorities between healthcare professionals and women, different perspectives on communication issues, and different perspectives on women

  14. An evaluation of the implementation of maternal obesity pathways of care: a mixed methods study with data integration.

    Directory of Open Access Journals (Sweden)

    Nicola Heslehurst

    Full Text Available Maternal obesity has multiple associated risks and requires substantial intervention. This research evaluated the implementation of maternal obesity care pathways from multiple stakeholder perspectives.A simultaneous mixed methods model with data integration was used. Three component studies were given equal priority. 1: Semi-structured qualitative interviews explored obese pregnant women's experiences of being on the pathways. 2: A quantitative and qualitative postal survey explored healthcare professionals' experiences of delivering the pathways. 3: A case note audit quantitatively assessed pathway compliance. Data were integrated using following a thread and convergence coding matrix methods to search for agreement and disagreement between studies.Study 1: Four themes were identified: women's overall (positive and negative views of the pathways; knowledge and understanding of the pathways; views on clinical and weight management advice and support; and views on the information leaflet. Key results included positive views of receiving additional clinical care, negative experiences of risk communication, and weight management support was considered a priority. Study 2: Healthcare professionals felt the pathways were worthwhile, facilitated good practice, and increased confidence. Training was consistently identified as being required. Healthcare professionals predominantly focussed on women's response to sensitive obesity communication. Study 3: There was good compliance with antenatal clinical interventions. However, there was poor compliance with public health and postnatal interventions. There were some strong areas of agreement between component studies which can inform future development of the pathways. However, disagreement between studies included a lack of shared priorities between healthcare professionals and women, different perspectives on communication issues, and different perspectives on women's prioritisation of weight

  15. Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks.

    Science.gov (United States)

    Zhao, Huiying; Nyholt, Dale R; Yang, Yuanhao; Wang, Jihua; Yang, Yuedong

    2017-06-14

    Genome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous pathway-based methods have been developed. Here we propose a novel method, DGAT-path, to divide all SNPs assigned to genes in each pathway into LD blocks, and to sum the chi-square statistics of LD blocks for assessing the significance of the pathway by permutation tests. The method was proven robust with the type I error rate >1.6 times lower than other methods. Meanwhile, the method displays a higher power and is not biased by the pathway size. The applications to the GWAS summary statistics for schizophrenia and breast cancer indicate that the detected top pathways contain more genes close to associated SNPs than other methods. As a result, the method identified 17 and 12 significant pathways containing 20 and 21 novel associated genes, respectively for two diseases. The method is available online by http://sparks-lab.org/server/DGAT-path .

  16. Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

    KAUST Repository

    MacLean, Adam L.

    2015-12-16

    The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non-exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.

  17. Interaction pathways between soft lipid nanodiscs and plasma membranes: A molecular modeling study.

    Science.gov (United States)

    Li, Shixin; Luo, Zhen; Xu, Yan; Ren, Hao; Deng, Li; Zhang, Xianren; Huang, Fang; Yue, Tongtao

    2017-10-01

    Lipid nanodisc, a model membrane platform originally synthesized for study of membrane proteins, has recently been used as the carrier to deliver amphiphilic drugs into target tumor cells. However, the central question of how cells interact with such emerging nanomaterials remains unclear and deserves our research for both improving the delivery efficiency and reducing the side effect. In this work, a binary lipid nanodisc is designed as the minimum model to investigate its interactions with plasma membranes by using the dissipative particle dynamics method. Three typical interaction pathways, including the membrane attachment with lipid domain exchange of nanodiscs, the partial membrane wrapping with nanodisc vesiculation, and the receptor-mediated endocytosis, are discovered. For the first pathway, the boundary normal lipids acting as ligands diffuse along the nanodisc rim to gather at the membrane interface, repelling the central bola lipids to reach a stable membrane attachment. If bola lipids are positioned at the periphery and act as ligands, they diffuse to form a large aggregate being wrapped by the membrane, leaving the normal lipids exposed on the membrane exterior by assembling into a vesicle. Finally, by setting both central normal lipids and boundary bola lipids as ligands, the receptor-mediated endocytosis occurs via both deformation and self-rotation of the nanodiscs. All above pathways for soft lipid nanodiscs are quite different from those for rigid nanoparticles, which may provide useful guidelines for design of soft lipid nanodiscs in widespread biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Metabolic pathway analysis and kinetic studies for production of nattokinase in Bacillus subtilis.

    Science.gov (United States)

    Unrean, Pornkamol; Nguyen, Nhung H A

    2013-01-01

    We have constructed a reaction network model of Bacillus subtilis. The model was analyzed using a pathway analysis tool called elementary mode analysis (EMA). The analysis tool was used to study the network capabilities and the possible effects of altered culturing conditions on the production of a fibrinolytic enzyme, nattokinase (NK) by B. subtilis. Based on all existing metabolic pathways, the maximum theoretical yield for NK synthesis in B. subtilis under different substrates and oxygen availability was predicted and the optimal culturing condition for NK production was identified. To confirm model predictions, experiments were conducted by testing these culture conditions for their influence on NK activity. The optimal culturing conditions were then applied to batch fermentation, resulting in high NK activity. The EMA approach was also applied for engineering B. subtilis metabolism towards the most efficient pathway for NK synthesis by identifying target genes for deletion and overexpression that enable the cell to produce NK at the maximum theoretical yield. The consistency between experiments and model predictions proves the feasibility of EMA being used to rationally design culture conditions and genetic manipulations for the efficient production of desired products.

  19. A telephone questionnaire in order to assess functional outcome after post-traumatic limb salvage surgery: Development and preliminary validation.

    Science.gov (United States)

    Wulterkens, Leonie; Aurégan, Jean-Charles; Letellier, Thomas; Mebtouche, Nasser; Levante, Stéphane; Cottin, Philippe; Bégué, Thierry

    2015-12-01

    Post-traumatic limb salvage surgery is challenging and evaluation of the results remains arduous. No questionnaire specifically assessing functional outcome after post-traumatic limb salvage surgery of the lower extremity exists. Due to regionalization of specialized care, the patients' travel time to the hospital increases. To overcome a higher patients' travel burden, patients' follow up by telephone is an option. We aimed to develop a telephone questionnaire in order to assess functional outcome after post-traumatic limb salvage surgery of the lower extremity. From a review of scores of functional assessment of the lower limb surgery, we have developed a telephone questionnaire. A prospective study was performed to validate this telephone questionnaire. Twenty patients were included. The participants were called to complete the telephone questionnaire twice with an interval of a week. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was completed during the second telephone call. The internal consistency was analyzed by the Cronbach's alpha (α). With the outcome scores of both completions, the test-retest reliability was analyzed by the interclass correlation coefficient (ICC) 2,k with a 95% confidence interval (95% CI). The outcome scores of the second telephone questionnaire and the WOMAC questionnaire were used for the construct validity analysis by the Spearman's rank correlation coefficient (r(s)) with a 95% CI. The internal consistency analysis revealed a α=0.62 which improved to α=0.92 after removing one question from the telephone questionnaire. The final version of the telephone questionnaire comprises 32 questions, divided in 3 subscales: function, daily life and psychology. The total score varies between 0 and 86 points. The test-retest reliability was ICC 2,k=0.93 (95% CI: 0.82-0.97) and the construct validity was r(s)=0.92 (95% CI: 0.81-0.97). We present a specific telephone questionnaire in order to assess functional

  20. High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

    Science.gov (United States)

    Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

    2015-01-01

    Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

  1. The NAD+ metabolism of Leishmania, notably the enzyme nicotinamidase involved in NAD+ salvage, offers prospects for development of anti-parasite chemotherapy.

    Science.gov (United States)

    Michels, Paul A M; Avilán, Luisana

    2011-10-01

    NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox reactions it is key in the cellular energy metabolism and as a substrate it participates in many reactions leading to a variety of covalent modifications of enzymes with major roles in regulation of expression and metabolism. Cells may have the ability to produce this metabolite either via alternative de novo synthesis pathways and/or by different salvage pathways. In this issue of Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania species can only rely on the salvage of NAD+ building blocks. One of the enzymes involved, nicotinamidase, is absent from human cells. The enzyme is important for growth of Leishmania infantum and essential for establishing an infection. The crystal structure of the parasite protein has been solved and shows prospects for design of inhibitors to be used as leads for development of new drugs. Indeed, NAD+ metabolism is currently being considered as a promising drug target in various diseases and the vulnerability of Leishmania for interference of this metabolism has been proved in previous work by the same group, by showing that administration of NAD+ precursors has detrimental effect on the pathogenic, amastigote stage of this parasite. © 2011 Blackwell Publishing Ltd.

  2. Clinical results of salvage surgery in hypopharynx carcinoma after chemoradiotherapy

    International Nuclear Information System (INIS)

    Mitani, Hiroki; Gakibuchi, Masao; Asano, Takayuki; Sakurai, Hiroyuki; Kurita, Tomoyuki; Inoue, Youjiro

    2008-01-01

    The incidence of post-operative complications and treatment results of 60 cases of hypopharynx carcinoma receiving laryngo-pharyngo-esophagectomy followed by reconstruction with jejunum after chemoradiotherapy (CRT) from 1997 to 2006 in 6 hospitals was analyzed. The overall complication rate was 57%. There were 3 cases with carotid artery rupture (5%), 4 with jejunum necrosis (6%), 6 with major salivary fistula (10%), 8 with minor salivary fistula (13%), 8 with abscess alone (13%), 3 with trachea stoma necrosis (5%), and 3 with skin flap necrosis (5%). The death rate due to surgical complications was 3% (2/60). When the cases were divided into two groups, namely the cases with fistula and the cases without fistula, the number of days that permitted drinking was 18.1 in the latter and 81.8 in the former. The 5-year overall survival rate among all cases was 37%. We found that salvage surgery after CRT was effective for recurrent cases. These findings suggest that reconstruction with jejunum is a suitable type of operation with better surgical results. Care is required to reduce the incidence of post-operative complications. (author)

  3. The salvaging of the Mont Louis cargo ship

    International Nuclear Information System (INIS)

    Vastel, D.

    1985-01-01

    On Saturday the 25th of August 1984, at 2:20 P.M., the German car ferry Olau Britannia with 800 passengers aboard rammed the rear starboard side of the French cargo ship Mont Louis. The collision occurred in the English Channel at a point 18 kilometers north of Ostend. At 7:00 P.M. the Mont Louis sank to a depth of 15 meters at a distance of several miles by rail from Antwerp. Half the ship's hull lay uncovered at low tide. The cargo included 30 type 48-Y containers, each filled with 12 tons of UF 6 , and 22 empty type 30-B containers for return of the enriched uranium. The UF 6 was to be enriched to 4% in the Soviet Union for use as fuel in nuclear power plants. The table below details the nature of the UF 6 . After salvaging operation the containers have been inspected and no damage or leaks have been detected. The accident involved no risk of radioactive or chemical contamination of the sea water. The systematic misinformation campaign by Greenpeace and news media is briefly described. (orig./HP)

  4. Closure of difficult pharyngocutaneous fistula following salvage laryngectomy. Case report

    International Nuclear Information System (INIS)

    Suesada, Nobuko; Sakuraba, Minoru; Nagamatsu, Shogo; Miyamoto, Shimpei; Shinozaki, Takeshi; Hayashi, Ryuichi

    2013-01-01

    The patient was a 74-year-old man. A total laryngectomy was performed due to recurrence of laryngeal cancer after chemoradiotherapy (CRT). Postoperatively, a pharyngocutaneous fistula developed and patch-graft reconstruction using a pectoral major musculocutaneous flap was planned. However, due to expansion of the necrotic area, we needed to perform tubular reconstruction. Nevertheless, infection and pus discharge were observed and a second surgery was performed. Resection and reconstruction at the neck were considered impossible because advanced necrosis was seen at the cervical esophageal stump, and the operative procedure was changed to esophageal resection, gastric pull-up and free jejunum transfer. Although leakage was found at the jejunum-gastric anastomosis site by fluoroscopy on the 14th postoperative day, it disappeared through conservative therapy. In addition, oral ingestion was begun on the 28th postoperative day. At 6 months after the surgery, the patient was able to regularly intake food and no constriction of the tracheostoma was seen. In this case, unexpected expansion of the necrotic area was a significant problem. As for the causes, diminished blood flow to the esophagus due to total thyroidectomy and bilateral paratracheal lymph node dissection, and infection in the surrounding area, along with remarkable tissue damage with CRT were considered possible. In salvage surgery, attention will be necessary in evaluating necrotic range and selection of appropriate reconstructive procedure. (author)

  5. Success Stories of Undergraduate Retention: A Pathways Study of Graduate Students in Solar and Space Physics

    Science.gov (United States)

    Morrow, C. A.; Stoll, W.; Moldwin, M.; Gross, N. A.

    2012-12-01

    This presentation describes results from an NSF-funded study of the pathways students in solar and space physics have taken to arrive in graduate school. Our Pathways study has documented results from structured interviews conducted with graduate students attending two, week-long, NSF-sponsored scientific workshops during the summer of 2011. Our research team interviewed 48 solar and space physics students (29 males and 19 females currently in graduate programs at US institutions,) in small group settings regarding what attracted and retained them along their pathways leading to grad school. This presentation addresses what these students revealed about the attributes and influences that supported completion of their undergraduate experience and focused their aspirations toward graduate school. In advance of the interview process, we collected 125 on-line survey responses from students at the two workshops. This 20-item survey included questions about high school and undergraduate education, as well as about research and graduate experience. A subset of the 125 students who completed this on-line survey volunteered to be interviewed. Two types of interview data were collected from the 48 interviewees: 1) written answers to a pre-interview questionnaire; and 2) detailed notes taken by researchers during group interviews. On the pre-interview questionnaire, we posed the question: "How did you come to be a graduate student in your field?" Our findings to date are based on an analysis of responses to this question, cross correlated with the corresponding on-line survey data. Our analysis reveals the importance of early research experiences. About 80% of the students participating in the Pathways study cited formative undergraduate research experiences. Moreover, about 50% of participants reported undergraduate research experiences that were in the field of their current graduate studies. Graduate students interviewed frequently cited a childhood interest in science

  6. Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

    International Nuclear Information System (INIS)

    Bianco, Fernando J.; Scardino, Peter T.; Stephenson, Andrew J.; DiBlasio, Christopher J.; Fearn, Paul A.; Eastham, James A.

    2005-01-01

    Purpose: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. Methods and Materials: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of ≥0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). Results: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of 10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. Conclusions: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent

  7. Salvage surgery following radiation failure in squamous cell carcinoma of the supraglottic larynx

    International Nuclear Information System (INIS)

    Parsons, James T.; Mendenhall, William M.; Stringer, Scott P.; Cassisi, Nicholas J.; Million, Rodney R.

    1995-01-01

    Purpose: We analyzed the clinical course of patients who developed local (primary) recurrence following high-dose irradiation of squamous cell carcinoma of the supraglottic larynx. Methods and Materials: Between October 1964 and July 1991, 206 patients with previously untreated squamous cell carcinoma of the supraglottic larynx underwent radiotherapy with curative intent. Local failure occurred in 46 (22%) patients. Successful surgical salvage was defined as no evidence of recurrent cancer for at least 2 years after salvage surgery and continuously thereafter. Results: Sixteen patients did not undergo salvage surgery because of refusal (7 patients), severe medical illness (2 patients), concurrent distant metastasis (5 patients), or unresectable neck disease (2 patients). Twenty-six patients underwent total laryngectomy, and 4 patients had a voice-sparing procedure. Successful salvage was achieved in 50% of patients who underwent surgery. The rate of successful salvage did not correlate with preirradiation T-stage or time to failure after irradiation. Most of the failures after surgery were because of failure to control the primary cancer. The overall rate of postsurgical complications was 37%. No operative or perioperative deaths occurred. The 5-year survival rate for all 46 patients, calculated from the date of irradiation failure, was 20%, while the 5-year survival rate after salvage surgery for the 30 patients who underwent the procedure was 29%. Conclusion: There are few data in the literature regarding the clinical outcome in patients whose tumors are not controlled by initial radiotherapy. In the current and previous series, one-half to two-thirds of patients who developed primary failure underwent salvage surgery, which was successful in approximately half of the operated patients, leading to a 25-30% rate of long-term disease-free survival among the entire group of patients who developed failure

  8. Short-time effect of salvage harvesting on microbial soil properties in a Mediterranean area affected by a wildfire: preliminary results

    Science.gov (United States)

    Moltó, Jorge; Mataix-Solera, Jorge; Arcenegui, Victoria; Morugan, Alicia; Girona, Antonio; Garcia-orenes, Fuensanta

    2014-05-01

    In the Mediterranean region, wildfires are considered one of the main ecological factors, which, in addition to and in relation to changes in soil use, may cause soil loss and degradation, one of the most important environmental problems that humanity must face up to. As is well known, the soil-plant system is one of the key factors determining ecological recovery after the occurrence of a wildfire. Traditionally, a variety of forestry practices have been implemented on spanish sites after the incidence of a wildfire. Among them stands out the complete extraction of the burned wood, which consist in getting rid of the branches and other wooden debris using small controlled bonfires, splintering or mechanical extraction. This set of post-fire management practices is known as salvage logging or salvage harvesting. Despite the remarkable relevance and influence that this conjunction of techniques has on land management after a wildfire, very little experimental research focused on assessing the impact of salvage logging on the vegetal community has been done. Furthermore, even less research inquiring into the mode and grade of incidence that the salvage logging produces on soil properties has taken place. The aim of this research is to assess the effects that the salvage harvesting has on different soil microbial properties and other related properties. The study area is located in the Natural Park of the "Sierra de Mariola" in the province of Alicante, southeastern Spain. This location was affected by a wildfire whose extension reached more than 500 Ha in July 2012. Different post-fire treatments were proposed by the authorities, including salvage harvesting in some areas. Two different treatments were distinguished for the study, "control" (without any kind of burned wood removal) and "harvest" (where salvage logging was carried out), in each area three 4 m2 sampling plots were set up. These two treatments were established on the same slope with the same orography

  9. Longer-term Stream Nitrogen Dynamics after Wildfire and Salvage Harvesting: Implications for Management Concepts based on Trajectories of Post-disturbance Watershed Recovery.

    Science.gov (United States)

    Silins, U.; Emelko, M. B.; Bladon, K. D.; Stone, M.; Williams, C.; Martens, A. M.; Wagner, M. J.

    2015-12-01

    Biogeochemical processes reflecting interaction of vegetation and hydrology govern long-term export of nutrients such as nitrogen, phosphorus, and carbon over successional time scales. While management concepts of watershed "recovery" from disturbance back towards pre-disturbance conditions are often considered over much shorter timescales, few studies have directly explored watershed biogeochemical responses to disturbance long enough to directly document the longer-term trajectory of responses to severe land disturbance on nitrogen export. The objectives of this study were to document both the initial magnitude and patterns of longer-term recovery of stream nitrogen after the 2003 Lost Creek wildfire over nine years in front ranges of the Rocky Mountains in south-west Alberta, Canada. The study was conducted in seven instrumented catchments (4-14 km2), including burned, burned and salvage logged, and unburned (reference) conditions since 2004. Total nitrogen (TN) and nitrate (NO3-) concentrations and area-normalized yields were greater and more variable in burned and post-fire salvage logged catchments when compared with unburned catchments. Large initial increases in stream TN and NO3- production 1-3 years after both wildfire and post-fire salvage logging declined strongly to levels similar to, or below that of unburned watersheds 4-6 years after the fire, and continued to decline (although more slowly) 7-9 years after the wildfire. Post-fire salvage logging produced lower impacts on TN and NO3- in streams and these effects declined even more rapidly compared to the effects of wildfire alone. These changes closely corresponded to the early trajectory of establishment and rapid juvenile growth of post-fire regenerating forest vegetation in both catchment groups. While the concept of hydrologic recovery from disturbance is both a practical and meaningful concept for integrated landscape management for protection of forest water resources, the benchmark for

  10. Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia.

    Science.gov (United States)

    Wang, Jingbo; Yuan, Lei; Cheng, Haoyu; Fei, Xinhong; Yin, Yumin; Gu, Jiangying; Xue, Song; He, Junbao; Yang, Fan; Wang, Xiaocan; Yang, Yixin; Zhang, Weijie

    2018-01-09

    There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis. A total of 44 patients, of whom 28 had acute myeloid leukemia (AML), 13 had acute lymphocytic leukemia (ALL), and 3 had mixed phenotype leukemia (MPL), were enrolled in this study. With a median follow-up of 19 months, the estimated 2-year overall survival (OS) and progression free survival (PFS) were 34.3% (95% CI, 17.9-51.4%) and 33.6% (95% CI, 18.0-50.1%), respectively. The estimated 2-year incidence rates of relapse and non-relapse mortality (NRM) were 43.8% (95% CI 26.4-60.0%) and 19.6% (95% CI 9.1-32.9%), respectively. The estimated 100-day cumulative incidence of acute graft versus host disease (aGvHD) was 43.6% (95% CI 28.7-57.5%), and the 1-year cumulative incidence of chronic GvHD (cGvHD) was 45.5% (95% CI 30.5-59.3%). Compared with the previous studies, the multivariate analysis in this study additionally identified that female donors and cGvHD were associated with lower relapse and better PFS and OS. Male recipients, age younger than 10 years, a diagnosis of ALL, and the intermediate-adverse cytogenetic risk group were associated with increased relapse. On the contrary, extramedullary disease (EMD) and aGvHD were only linked to worse PFS. These data suggested that although only one-third of the patients would obtain PFS over 2 years, salvaged allo-HSCT is still the most reliable and best therapeutic strategy for refractory pediatric acute leukemia. If probable, choosing a female donor, better

  11. Association Study between Folate Pathway Gene Single Nucleotide Polymorphisms and Gastric Cancer in Koreans

    Directory of Open Access Journals (Sweden)

    Jae-Young Yoo

    2012-09-01

    Full Text Available Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR, methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR, and methyltetrahydrofolate-homocysteine methyltransferase (MTR. The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI, rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85 and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75. Especially, in the obese group (body mass index ≥ 25 kg/m2, the codominant (OR, 9.08; 95% CI, 1.01 to 94.59 and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59 showed dramatically increased risk (p < 0.05. In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.

  12. Model feasibility study of radioactive pathways from atmosphere to surface water

    International Nuclear Information System (INIS)

    Smith, R.E.; Summer, R.M.; Ferreira, V.A.

    1990-03-01

    A feasibility study of the atmosphere to surface-water radionuclide pathways was performed for small catchments, using a physically-based hydro-ecosystem model, Opus. Detailed time-intensity precipitation records from Arizona and Georgia were used as input to drive the model. Tests of model sensitivity to distribution coefficients, Kd, for Cs-137, Cs-134, and Sr-90 illustrated different vegetation-soil-erosion-runoff pathways, in response to agricultural management practices. Results reflected the fact that low Kd values allow a radionuclide to infiltrate into the soil profile and isolate it from subsequent runoff and erosion. Of the radionuclides and physical settings studied, only the Sr-90, with low Kd values, is sufficiently mobile and long-lived to be removed from the system via percolation below the root zone. Conversely, highly-adsorbed radionuclides were subject to removal by adsorption to sediment particles and subsequent runoff. Comparison of different effective half-lives of I-131 demonstrated the importance of the timing of an erosion-runoff storm event during or immediately after a fallout event. Seasonal timing of a fallout event and crop management also affect the fate of this short-lived radionuclide. Removal by solution to surface-water runoff was negligible for all nuclides studied. 34 refs., 14 figs., 2 tabs

  13. Tissue specific distribution of pyrimidine deoxynucleoside salvage enzymes shed light on the mechanism of mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L; Eriksson, S

    2010-06-01

    Deficiency in thymidine kinase 2 (TK2) activity due to genetic alterations caused tissue specific mitochondrial DNA (mtDNA) depletion syndrome with symptoms resembling these of AIDS patients treated with nucleoside analogues. Mechanisms behind this mitochondrial effects is still not well understood. With rat as a model we isolated mitochondrial and cytosolic fractions from major organs and studied enzymes involved in thymidine (dT) and deoxycytidine (dC) phosphorylation by using ionic exchange column chromatography. A cytosolic form of TK2 was identified in all tested tissues in addition to mitochondrial TK2. TK1 was detected in liver and spleen cytosolic extracts while dCK was found in liver, spleen and lung cytosolic extracts. Thus, the nature of dT and dC salvage enzymes in each tissue type was determined. In most tissues TK2 is the only salvage enzyme present except liver and spleen. These results may help to explain the mechanisms of mitochondrial toxicity of antiviral nucleoside analogues and mtDNA depletion caused by TK2 deficiency.

  14. Paclitaxel with Cisplatin as Salvage Treatment for Patients with Previously Treated Advanced Transitional Cell Carcinoma of the Urothelial Tract

    Directory of Open Access Journals (Sweden)

    Ji Eun Uhm

    2007-01-01

    Full Text Available BACKGROUND: This study was performed to evaluate the safety and efficacy of paclitaxel with cisplatin as salvage therapy in patients previously treated with gemcitabine and cisplatin (G/C for advanced transitional cell carcinoma (TCC of the urothelial tract. METHODS: Twenty-eight patients with metastatic or locally advanced TCC who had received prior G/C chemotherapy were enrolled. All patients received paclitaxel (175 mg/m2 and cisplatin (60 mg/m2 every 3 weeks for eight cycles or until disease progression. RESULTS: The median age was 61 years (range, 43–83 years, and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2. The overall response rate was 36% [95% confidence interval (95% CI = 18–54], with three complete responses and seven partial responses. The median time to progression was 6.2 months (95% CI = 3.9–8.5, and the median overall survival was 10.3 months (95% CI = 6.1–14.1. The most common Grade 3/4 nonhematologic and hematologic toxicities were emesis (10 of 28 patients; 36% and neutropenia (5 of 110 cycles; 5%. CONCLUSIONS: Salvage chemotherapy with paclitaxel and cisplatin displayed promising results with tolerable toxicity profiles in patients with metastatic or locally advanced TCC who had been pretreated with G/C.

  15. Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

    Science.gov (United States)

    Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

    2012-10-01

    The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

  16. Traumatic eye ball luxation: A stepwise approach to globe salvage

    Directory of Open Access Journals (Sweden)

    Himika Gupta

    2017-10-01

    Full Text Available Craniofacial trauma is often associated with orbital and ocular injuries. We report a case of a 21-year-old male with motor vehicular accident, orbital roof blow-in fracture, cerebrospinal fluid (CSF leak, and left sided globe luxation with corneal abrasion and complete conjunctival denuding. The patient was managed by a multispeciality team and the eyeball was protected by amniotic membrane graft (AMG biological dressing with novel use of inverted sterile metallic bowl as mechanical protection till the patient stabilized. During surgery, eyeball was reposited and ocular surface was reconstructed using amniotic membrane and symblepharon ring. Surgical correction and plating of the facial fractures and dural repair with autologus tensor fascia lata was done. Post surgery ocular surface was intact, ocular motility was well preserved and the globe was prephthisical. Traumatic eyeball luxation is a rare, but dramatic presentation which may occur in a blow in fracture when the intra orbital volume reduces and expels the eye ball out of the socket. This may be associated with extra ocular muscle rupture or optic nerve avulsion. The visual prognosis is nil in majority cases. However, the management is targeted towards globe preservation in view of psychological benefit and ease of cosmetic or prosthetic rehabilitation. Knowing the mechanism of luxation helps to plan the management. A stepwise approach for globe salvage is recommended. Team efforts to take care of various morbidities with special steps to safeguard the eye help to optimize outcomes. Keywords: Traumatic eyeball luxation, Blow in orbital fractures, Amniotic membrane graft for ocular surface, Globe reposition

  17. Internal carotid artery stenosis or occlusion: study of collateral circulation pathways on DSA and MRA

    International Nuclear Information System (INIS)

    Zhao Yunhui; Ma Zhubin; Xu Yikai

    2004-01-01

    Objectives: To evaluate the collateral pathways of internal carotid artery (ICA) stenosis or occlusion on digital subtraction angiography (DSA) and magnetic resonance angiography (MRA), and to compare these two methods in the study for collateral pathways. Methods: Seventy-four patients with ICA stenosis or occlusion were included as the study group. Sixty persons with normal findings on DSA or MRA each served as the control group. DSA, MRA, MRI, CT findings, and clinicall materials were analyzed in the two groups. Results: Stenosis or occlusion over ICA bifurcation was showed clearly in all patients on DSA or MRA. On DSA, the presence rate of ipsilateral posterior communicating artery (PCoA) in the study group (82.5%) was lower significantly than that of the control group (94.2%) (P=0.025). On MRA (3D-TOF), the rate in the study group (59.3%) was higher significantly than that of the controls (30.0%) (P=0.000). On DSA and MRA, the diameter of ipsilateral PCoA in the study group was larger than that of the control group (P=0.000). On DSA, the presence rate of OPhA in the study group was significantly different from that of the control group, and its diameter was larger than that of the control group (P=0.003). On MRA, its presence rate was lower than that of the control group. The presence rate of anterior communicating artery (ACoA) in the study group showed no statistical difference between DSA and MRA. In the study group, the presence rate of PCoA on DSA was significantly higher than that on MRA (P 0.05). The diameters of the three arteries showed no significant differences between DSA and MRA (P>0.05). Conclusion: DSA is highly valuable for the evaluation of collateral pathways of ICA stenosis or occlusion, and it is necessary for preoperative examination. MRA is a non-invasive angiographic method and can evaluate collateral circulation in both morphology and function, and can be the preferred method for the disease. (authors)

  18. Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

    Energy Technology Data Exchange (ETDEWEB)

    Menjot de Champfleur, Nicolas, E-mail: nicolasdechampfleur@orange.fr [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” Institut National de la Santé et de la Recherche Médicale Unité 1051, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier (France); Lima Maldonado, Igor [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” Institut National de la Santé et de la Recherche Médicale Unité 1051, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier (France); Divisão de Neurologia e Epidemiologia (CPPHO), Complexo Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador-Bahia (Brazil); Moritz-Gasser, Sylvie [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Department of Neurology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Machi, Paolo [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); and others

    2013-01-15

    Introduction: The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. Materials and methods: Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. Results: The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. Discussion: Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. Conclusion: The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF)

  19. Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

    International Nuclear Information System (INIS)

    Menjot de Champfleur, Nicolas; Lima Maldonado, Igor; Moritz-Gasser, Sylvie; Machi, Paolo

    2013-01-01

    Introduction: The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. Materials and methods: Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. Results: The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. Discussion: Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. Conclusion: The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF)

  20. Bipolar hip arthroplasty as salvage treatment for loosening of the acetabular cup with significant bone defects

    Directory of Open Access Journals (Sweden)

    Ghanem, Mohamed

    2016-04-01

    Full Text Available Introduction: Revision arthroplasty of the hip is becoming increasingly important in recent years. Early primary arthroplasty and longer life expectancy of the patients increases the number of revision surgery. Revision surgery of hip arthroplasty is major surgery for the patients, especially the elderly, with significant risks concerning the general condition of the patient. The aim of this work is to evaluate the outcome of bipolar hip arthroplasty as a salvage procedure for treatment of loosening of the acetabular cup with significant acetabular bone defects after total hip replacement (THR in multi-morbid patients.Patients and methods: During the period from January 1 2007 to December 31 2011 19 revision hip surgeries were performed in , in which the loosened acetabular cup was replaced by a bipolar head. The examined patient group consisted exclusively of female patients with an average of 75 years. The predominant diagnosis was “aseptic loosening” (84.2%. All patients in our study were multi-morbid. We decided to resort to bipolar hip arthroplasty due to the compromised general condition of patients and the major acetabular bone defects, which were confirmed intraoperatively. The postoperative follow-up ranged from 0.5 to 67 months (average 19.1 months. Results: Evaluation of the modified Harris Hip Score showed an overall improvement of the function of the hip joint after surgery of approximately 45%.Surgery was less time consuming and thus adequate for patients with significantly poor general health condition. We noticed different complications in a significant amount of patients (68.4%. The most common complication encountered was the proximal migration of the bipolar head.The rate of revision following the use of bipolar hip arthroplasty in revision surgery of the hip in our patients was high (21%. Despite the high number of complications reported in our study, we have noticed significant improvement of hip joint function as well

  1. Current therapeutic interventions in the glycation pathway: evidence from clinical studies.

    Science.gov (United States)

    Engelen, L; Stehouwer, C D A; Schalkwijk, C G

    2013-08-01

    The increased formation of advanced glycation endproducts (AGEs) constitutes a potential mechanism of hyperglycaemia-induced micro- and macrovascular disease in diabetes. In vitro and animal experiments have shown that various interventions can inhibit formation and/or actions of AGEs, in particular the specific AGE inhibitor aminoguanidine and the AGEs crosslink breaker alagebrium, and the B vitamins pyridoxamine and thiamine, and the latter's synthetic derivative, benfotiamine. The potential clinical value of these interventions, however, remains to be established. The present review provides, from the clinical point of view, an overview of current evidence on interventions in the glycation pathway relating to (i) the clinical benefits of specific AGE inhibitors and AGE breakers and (ii) the potential AGE-inhibiting effects of therapies developed for purposes unrelated to the glycation pathway. We found that safety and/or efficacy in clinical studies with the specific AGE inhibitor, aminoguanidine and the AGE breaker, alagebrium, appeared to be a concern. The clinical evidence on the potential AGE-inhibiting effects of B vitamins is still limited. Finally, current evidence for AGE inhibition by therapies developed for purposes unrelated to glycation is limited due to a large heterogeneity in study designs and/or measurement techniques, which have often been sub-optimal. We conclude that, clinical evidence on interventions to inhibit formation and/or action of AGEs is currently weak and unconvincing. © 2012 Blackwell Publishing Ltd.

  2. Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

    Science.gov (United States)

    Michel, L; Reygagne, P; Benech, P; Jean-Louis, F; Scalvino, S; Ly Ka So, S; Hamidou, Z; Bianovici, S; Pouch, J; Ducos, B; Bonnet, M; Bensussan, A; Patatian, A; Lati, E; Wdzieczak-Bakala, J; Choulot, J-C; Loing, E; Hocquaux, M

    2017-11-01

    Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. To identify biomarkers associated with AGA. Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/β-catenin and bone morphogenic protein/transforming growth factor-β signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches. © 2017 British Association of Dermatologists.

  3. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    International Nuclear Information System (INIS)

    Bolo, N.R.

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. 13 C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of [ 13 C-4] to [ 13 C-5]-glutamate, [ 13 C-3] to [ 13 C-2]-alanine or [ 13 C-3] to [ 13 C-2]-lactate produced when [ 13 C-2]-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the 13 C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in 13 C NMR human studies from the current literature

  4. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bolo, N.R.

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. {sup 13}C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of ({sup 13}C-4) to ({sup 13}C-5)-glutamate, ({sup 13}C-3) to ({sup 13}C-2)-alanine or ({sup 13}C-3) to ({sup 13}C-2)-lactate produced when ({sup 13}C-2)-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the {sup 13}C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in {sup 13}C NMR human studies from the current literature.

  5. A cell wall-bound adenosine nucleosidase is involved in the salvage of extracellular ATP in Solanum tuberosum.

    Science.gov (United States)

    Riewe, David; Grosman, Lukasz; Fernie, Alisdair R; Zauber, Henrik; Wucke, Cornelia; Geigenberger, Peter

    2008-10-01

    Extracellular ATP (eATP) has recently been demonstrated to play a crucial role in plant development and growth. To investigate the fate of eATP within the apoplast, we used intact potato (Solanum tuberosum) tuber slices as an experimental system enabling access to the apoplast without interference of cytosolic contamination. (i) Incubation of intact tuber slices with ATP led to the formation of ADP, AMP, adenosine, adenine and ribose, indicating operation of apyrase, 5'-nucleotidase and nucleosidase. (ii) Measurement of apyrase, 5'-nucleotidase and nucleosidase activities in fractionated tuber tissue confirmed the apoplastic localization for apyrase and phosphatase in potato and led to the identification of a novel cell wall-bound adenosine nucleosidase activity. (iii) When intact tuber slices were incubated with saturating concentrations of adenosine, the conversion of adenosine into adenine was much higher than adenosine import into the cell, suggesting a potential bypass of adenosine import. Consistent with this, import of radiolabeled adenine into tuber slices was inhibited when ATP, ADP or AMP were added to the slices. (iv) In wild-type plants, apyrase and adenosine nucleosidase activities were found to be co-regulated, indicating functional linkage of these enzymes in a shared pathway. (v) Moreover, adenosine nucleosidase activity was reduced in transgenic lines with strongly reduced apoplastic apyrase activity. When taken together, these results suggest that a complete ATP salvage pathway is present in the apoplast of plant cells.

  6. Efficacy and efficiency of a lean cataract pathway: a comparative study.

    Science.gov (United States)

    van Vliet, Ellen Joan; Sermeus, Walter; van Gaalen, Claudia M; Sol, Johannes C A; Vissers, Jan M H

    2010-12-01

    The demand for cataract surgery is rising, calling for pathways that have good access and are cost-effective. Lean thinking is a management strategy, aimed at improving quality while reducing costs. Lean production processes are designed to identify gaps between expected and actual performance. To analyse the efficacy and efficiency of a lean cataract pathway. Lean care delivered to a prospective cohort (616 cataract patients) was compared (1) with traditional care delivered to a historical cohort (591 cataract patients) and (2) with expected lean care in the prospective cohort. To evaluate efficacy, the authors analysed how many patients received care that adhered to the lean pathway's specifications. To evaluate efficiency, the authors analysed how often patients visited the hospital and how many additional patients could access the pathway. In the lean pathway, patient visits decreased by 23%, and access to the cataract pathway increased with 42%. A 40% decrease in patient visits and a 76% increase in access could have been realised if healthcare staff would have adhered to the lean pathway's specifications. Lean pathways can realise large improvements, and still have a significant gap between expected and actual care delivery. The challenge for healthcare teams is not to improve care delivery by using lean pathways as opposed to using traditional pathways, but to strive for optimal performance by consistently adhering to the specifications of the lean pathway.

  7. Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival?

    Science.gov (United States)

    Severino, N P; Chadi, S A; Rosen, L; Coiro, S; Choman, E; Berho, M; Wexner, S D

    2016-10-01

    This study aimed to investigate the results of salvage abdominoperineal excision (APR) in patients with persistent or recurrent squamous cell carcinoma of the anus (SCCA). Patients with anal neoplasia were identified from a prospective database. Patients with invasive SCCA with demonstrated failure of chemoradiation therapy (CRT) who underwent salvage APR for one of three disease categories (persistent,  24 months post-CRT) were included. The primary outcome was overall survival after salvage APR. Tumour size, metastatic lymph nodes (LN), circumferential resection margin positivity (CRM) and neurolymphovascular invasion (NLVI) were correlated with the outcome. Thirty-six patients with a median 3-year overall survival of 46% (median follow-up 24 months) underwent salvage APR due to persistent or recurrent SCCA (14 men, mean age 59 years). Eleven (31%) patients were diagnosed with persistent disease, 17 (47%) with early and 8 (22%) with late recurrence. Two-year overall survival of Stage 0/I/II and III/IV disease was 81.5% and 33.74%, respectively (P = 0.022). Overall disease stage was associated with disease categorization (P = 0.009): patients with persistent disease or early recurrence had a significantly higher disease stage than patients with late recurrence (OR = 20.9 and 17.2). Despite apparently improved survival in patients with late disease recurrence on live table analysis, no significant difference was identified in overall survival when stratified by disease category on log-rank test analysis. Persistent and recurrent disease does not show any significant difference in survival, but patients with late recurrence may have a better prognosis. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  8. Influence of mechanical cell salvage on red blood cell aggregation, deformability, and 2,3-diphosphoglycerate in patients undergoing cardiac surgery with cardiopulmonary bypass.

    Science.gov (United States)

    Gu, Y John; Vermeijden, Wytze J; de Vries, Adrianus J; Hagenaars, J Ans M; Graaff, Reindert; van Oeveren, Willem

    2008-11-01

    Mechanical cell salvage is increasingly used during cardiac surgery. Although this procedure is considered safe, it is unknown whether it affects the red blood cell (RBC) function, especially the RBC aggregation, deformability, and the contents of 2,3-diphosphoglycerate (2,3-DPG). This study examines the following: (1) whether the cell salvage procedure influences RBC function; and (2) whether retransfusion of the salvaged blood affects RBC function in patients. Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly allocated to a cell saver group (n = 20) or a control group (n = 20). In the cell saver group, the blood aspirated from the wound area and the residual blood from the heart-lung machine were processed with a continuous-flow cell saver before retransfusion. In the control group this blood was retransfused without processing. The RBC aggregation and deformability were measured with a laser-assisted optical rotational cell analyzer and 2,3,-DPG by conventional laboratory test. The cell saver procedure did not influence the RBC aggregation but significantly reduced the RBC deformability (p = 0.007) and the content of RBC 2,3-DPG (p = 0.032). However, in patients receiving the processed blood, their intraoperative and postoperative RBC aggregation, deformability, and 2,3-DPG content did not differ from those of the control patients. Both groups of patients had a postoperative drop of RBC function as a result of hemodilution. The mechanical cell salvage procedure reduces the RBC deformability and the cell 2,3-DPG content. Retransfusion of the processed blood by cell saver does not further compromise the RBC function in patients undergoing cardiac surgery with cardiopulmonary bypass.

  9. Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE Cohorts

    Directory of Open Access Journals (Sweden)

    Unjin Shim

    2014-12-01

    Full Text Available Metabolic syndrome (MetS is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs, important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs, explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2. A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6, and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05. Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF, the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

  10. Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation.

    Science.gov (United States)

    Zhou, Li; Todorovic, Viktor; Kakavas, Steve; Sielaff, Bernhard; Medina, Limary; Wang, Leyu; Sadhukhan, Ramkrishna; Stockmann, Henning; Richardson, Paul L; DiGiammarino, Enrico; Sun, Chaohong; Scott, Victoria

    2018-01-12

    IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36β, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays. Our results indicated that the agonists bind the IL-36R extracellular domain with micromolar affinity but do not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found that IL-1RAcP also does not bind IL-36R when no agonist is present. In the presence of IL-36α, however, IL-1RAcP bound IL-36R strongly. These results suggested that the main pathway to the IL-36R·IL-36α·IL-1RAcP ternary complex is through the IL-36R·IL-36α binary complex, which recruits IL-1RAcP. We could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we engineered a fragment crystallizable-linked construct to induce IL-36R·IL-1RAcP heterodimerization and predicted the binding affinity during a complete thermodynamic cycle to be 74 μm The SPR analysis also indicated that the IL-36R antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results reveal the landscape of IL-36 ligand and receptor interactions, improving our understanding of IL-36 pathway activation and inhibition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Enhanced Morbidity of Pectoralis Major Myocutaneous Flap Used for Salvage after Previously Failed Oncological Treatment and Unsuccessful Reconstructive Head and Neck Surgery

    Directory of Open Access Journals (Sweden)

    Christiana Maria Ribeiro Salles Vanni

    2012-01-01

    Full Text Available Introduction. The reconstruction of complex cervicofacial defects arising from surgical treatment for cancer is a real challenge for head and neck surgeons, especially in salvage reconstruction surgery and/or failed previous reconstruction. The pectoralis major myocutaneous flap (PMMF has been widely used in these specific situations due to its reliability and low rate of failure or complications. Objectives. Identify factors that determine complications and influence the final outcome of the reconstructions with PMMF in salvage cancer surgery or in salvage reconstruction. Methods. A cross-sectional study design was used to evaluate a sample including 17 surgical patients treated over a period of ten years that met the inclusion criteria. Results. Reconstruction was successful in 13 cases (76.5%, with two cases of partial flap loss and no case of total loss. Complications occurred in 13 cases (76.5% and were specifically related to the flap in nine instances (52.9%. An association was identified between the development of major complications and reconstruction of the hypopharynx (=0.013 as well as in patients submitted to surgery in association with radiation therapy as a previous cancer treatment (=0.002. The former condition is also associated with major reconstruction failure (=0.018. An even lower incidence of major complications was noted in patients under the age of 53 (=0.044. Conclusion. Older patients, with hypopharyngeal defects and submitted to previous surgery plus radiation therapy, presented a higher risk of complications and reconstruction failure with PMMF.

  12. Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

    International Nuclear Information System (INIS)

    Pearce, Andrew; Choo, Richard; Danjoux, Cyril; Morton, Gerard; Loblaw, D. Andrew; Szumacher, Ewa; Cheung, Patrick; Deboer, Gerrit; Chander, Sarat

    2006-01-01

    Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL

  13. An exploratory study on the gaps and pathways to the Korean fusion DEMO

    International Nuclear Information System (INIS)

    Kim, Hyuck Jong; Heo, Gyunyoung; Kim, Hyung Chan; Yeom, Jun Ho; Kim, Jong Kyung; Lee, Young-seok; Kwon, Myeun; Lee, Gyung-Su; Kim, Yong-soo; Kim, Eunbae; Lee, Chul-sik

    2012-01-01

    With the vision of being an early demonstrator of fusion energy, the strategic plans for the Fusion DEMO program of Korea (K-DEMO program) has been developed. A staged development of the K-DEMO plant was considered in the strategic plans as to verify technical feasibility in the first stage and economic feasibility in the second stage. The top-tier design requirements and assumptions of the first stage K-DEMO plant are defined and postulated. With these requirements and assumptions, the desired and current status of nuclear fusion technologies are compared to identify the gaps to be filled to design, fabricate, construct, and operate it. The pathways from KSTAR, ITER to K-DEMO plant have also been studied to identify R and D activities for K-DEMO program that are to go in parallel with KSTAR and ITER are extracted from the pathways. Cross-cutting with the fusion R and D activities of the other countries and utilizing the commonalities with the existing systems are discussed with the provision of open-innovation strategy that is one of the key strategies of K-DEMO program. The priority of the R and D activities of K-DEMO program is qualitatively determined in consideration of the gaps, cross-cutting, and risks associated with the R and D investments.

  14. The European quality of care pathways (EQCP study on the impact of care pathways on interprofessional teamwork in an acute hospital setting: study protocol: for a cluster randomised controlled trial and evaluation of implementation processes

    Directory of Open Access Journals (Sweden)

    Deneckere Svin

    2012-05-01

    Full Text Available Abstract Background Although care pathways are often said to promote teamwork, high-level evidence that supports this statement is lacking. Furthermore, knowledge on conditions and facilitators for successful pathway implementation is scarce. The objective of the European Quality of Care Pathway (EQCP study is therefore to study the impact of care pathways on interprofessional teamwork and to build up understanding on the implementation process. Methods/design An international post-test-only cluster Randomised Controlled Trial (cRCT, combined with process evaluations, will be performed in Belgium, Ireland, Italy, and Portugal. Teams caring for proximal femur fracture (PFF patients and patients hospitalized with an exacerbation of chronic obstructive pulmonary disease (COPD will be randomised into an intervention and control group. The intervention group will implement a care pathway for PFF or COPD containing three active components: a formative evaluation of the actual teams’ performance, a set of evidence-based key interventions, and a training in care pathway-development. The control group will provide usual care. A set of team input, process and output indicators will be used as effect measures. The main outcome indicator will be relational coordination. Next to these, process measures during and after pathway development will be used to evaluate the implementation processes. In total, 132 teams have agreed to participate, of which 68 were randomly assigned to the intervention group and 64 to the control group. Based on power analysis, a sample of 475 team members per arm is required. To analyze results, multilevel analysis will be performed. Discussion Results from our study will enhance understanding on the active components of care pathways. Through this, preferred implementation strategies can be defined. Trail registration NCT01435538

  15. Kinetic studies of the yeast His-Asp phosphorelay signaling pathway

    Science.gov (United States)

    Kaserer, Alla O.; Andi, Babak; Cook, Paul F.; West, Ann H.

    2010-01-01

    For both prokaryotic and eukaryotic His-Asp phosphorelay signaling pathways, the rates of protein phosphorylation and dephosphorylation determine the stimulus-to-response time frame. Thus, kinetic studies of phosphoryl group transfer between signaling partners are important for gaining a full understanding of how the system is regulated. In many cases, the phosphotransfer reactions are too fast for rates to be determined by manual experimentation. Rapid quench flow techniques thus provide a powerful method for studying rapid reactions that occur in the millisecond time frame. In this chapter, we describe experimental design and procedures for kinetic characterization of the yeast SLN1-YPD1-SSK1 osmoregulatory phosphorelay system using a rapid quench flow kinetic instrument. PMID:20946842

  16. Clinicians’ views and experiences of offering two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

    OpenAIRE

    Chhoa, C. Y.; Sawyer, A.; Ayers, S.; Pushpa-Rajah, A.; Duley, L.

    2017-01-01

    BACKGROUND: The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians’ views and experiences of offering two consent pathways for recruit...

  17. Clinicians? views and experiences of offering two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

    OpenAIRE

    Chhoa, Celine Y.; Sawyer, Alexandra; Ayers, Susan; Pushpa-Rajah, Angela; Duley, Lelia

    2017-01-01

    Background The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians? views and experiences of offering two consent pathways for recruitment...

  18. Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases.

    Science.gov (United States)

    Thibault, Isabelle; Campbell, Mikki; Tseng, Chia-Lin; Atenafu, Eshetu G; Letourneau, Daniel; Yu, Eugene; Cho, B C John; Lee, Young K; Fehlings, Michael G; Sahgal, Arjun

    2015-10-01

    We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (Pinitial SBRT is a feasible and efficacious salvage treatment option. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

    International Nuclear Information System (INIS)

    Wadasaki, Koichi; Kaneyasu, Yuko; Kenjo, Masahiro; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Ito, Katsuhide; Kiriu, Hiroshi; Ito, Atsushi

    2007-01-01

    The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate±seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate±seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe. (author)

  20. 49 CFR 599.402 - Requirements and limitations for salvage auctions that are consigned trade-in vehicles under the...

    Science.gov (United States)

    2010-10-01

    ... that are consigned trade-in vehicles under the CARS program. 599.402 Section 599.402 Transportation... SAVE ACT PROGRAM Disposal of Trade-in Vehicle § 599.402 Requirements and limitations for salvage auctions that are consigned trade-in vehicles under the CARS program. (a) The salvage auction must: (1...

  1. 33 CFR 155.4035 - Required pre-incident information and arrangements for the salvage and marine firefighting...

    Science.gov (United States)

    2010-07-01

    ... and arrangements for the salvage and marine firefighting resource providers listed in response plans... marine firefighting resource providers listed in response plans. (a) You must provide the information listed in §§ 155.1035(c) and 155.1040(c) to your salvage and marine firefighting resource providers. (b...

  2. 33 CFR 155.4045 - Required agreements or contracts with the salvage and marine firefighting resource providers.

    Science.gov (United States)

    2010-07-01

    ... with the salvage and marine firefighting resource providers. 155.4045 Section 155.4045 Navigation and... agreements or contracts with the salvage and marine firefighting resource providers. (a) You may only list resource providers in your plan that have been arranged by contract or other approved means. (b) You must...

  3. Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer

    NARCIS (Netherlands)

    N. Verstegen (Naomi); A.W.P.M. Maat (Alex); F.J. Lagerwaard (Frank); M.A. Paul (Marinus); M. Versteegh (Michel); J.J. Joosten (Joris); W. Lastdrager (Willem); E.F. Smit (Egbert); B.J. Slotman (Ben); J.J.M.E. Nuyttens (Joost); S. Senan (Suresh)

    2016-01-01

    markdownabstract__Introduction:__ The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence

  4. 26 CFR 1.167(f)-1 - Reduction of salvage value taken into account for certain personal property.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Reduction of salvage value taken into account for certain personal property. 1.167(f)-1 Section 1.167(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... for Individuals and Corporations § 1.167(f)-1 Reduction of salvage value taken into account for...

  5. A Genome Wide Association Study Links Glutamate Receptor Pathway to Sporadic Creutzfeldt-Jakob Disease Risk

    Science.gov (United States)

    Sanchez-Juan, Pascual; Bishop, Matthew T.; Kovacs, Gabor G.; Calero, Miguel; Aulchenko, Yurii S.; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J.; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G.; Collins, Steven J.; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S. G.; Will, Robert G.; van Duijn, Cornelia M.

    2015-01-01

    We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis. PMID:25918841

  6. Autologous Latissimus Dorsi Breast Reconstruction Flap Salvage: Microvascular Anastomosis with Serratus Branch

    Directory of Open Access Journals (Sweden)

    Victoria Kuta, BScH

    2017-07-01

    Full Text Available Summary:. Autologous breast reconstruction has become a standard option during the recovery of breast cancer survivors. Although pedicle damage is a rare complication of this procedure, extensive torsion or tension can lead to partial or total flap failure. We report a case of partial flap salvage after accidental transection of the pedicled blood supply within the intramuscular course of a latissimus dorsi musculocutaneous flap. This salvage technique involved microvascular anastomosis between the remaining vasculature of the latissimus dorsi pedicle and the serratus branch of the thoracodorsal artery and vein.

  7. Surgical and cryosurgical salvage of oral and oropharyngeal cancer recurring after radical radiotherapy

    International Nuclear Information System (INIS)

    Meyza, J.W.; Towpik, E.

    1991-01-01

    The results of salvage surgery or cryosurgery performed in 62 cases or oral or oropharyngeal cancer, recurring or persisting after radical radiotherapy, were analysed retrospectively. Salvage surgery was performed in 33 cases. The relatively high frequency of postoperative complications observed in years 1973-1984 has declined since 1985, concomitant with the introduction of myocutaneous flaps for reconstruction. Twenty-nine patients who were disqualified from major surgery, were treated by cryosurgery. Using both methods, 3-year overall survival was obtained in 24.1% of cases. (author)

  8. TA-60 Warehouse and Salvage SWPPP Rev 2 Jan 2017-Final

    Energy Technology Data Exchange (ETDEWEB)

    Burgin, Jillian Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-07

    The Stormwater Pollution Prevention Team (PPT) for the TA-60-0002 Salvage and Warehouse Area consists of operations and management personnel from the facility, Multi-Sector General Permitting (MSGP) stormwater personnel from Environmental Compliance Programs (EPC-CP) organization, and Deployed Environmental Professionals. The EPC-CP representative is responsible for Laboratory compliance under the National Pollutant Discharge Elimination System (NPDES) permit regulations. The team members are selected on the basis of their familiarity with the activities at the facility and the potential impacts of those activities on stormwater runoff. The Warehouse and Salvage Yard are a single shift operation; therefore, a member of the PPT is always present during operations.

  9. Process for gasification of heavy hydrocarbons or salvaged oil. [German patent

    Energy Technology Data Exchange (ETDEWEB)

    Koch, C

    1978-09-14

    The invention refers to the separation of solids which are carried over during evaporation of salvaged oil (oil recovered from used oil or fat). They are removed by exposing the oil vapour to an acceleration of 500 g to 20,000g in a hot gas cyclone. Subsequently the cleaned gas is converted to fission gas in a fission gas generator using an air-water gas mixture and is taken to the combustion equipment. By this process salvaged oil and heavy hydrocarbons can be used for burning in Diesel engines without previous refining.

  10. Stage IE Primary Bone Lymphoma:Limb Salvage for Local Recurrence

    Directory of Open Access Journals (Sweden)

    Khodamorad Jamshidi

    2015-01-01

    Full Text Available Background:   Primary bone lymphoma or non-Hodgkin lymphoma of bone is a rare disease. There are only a few case series of stage IE of this condition in medical literature. The aim of this study is to determine the rate of survival   for stage IE after combined modality treatment, the rate of local recurrence, and the results of limb salvage in cases   of local recurrence.     Methods:   We collected data from 61 patients with histologically confirmed PBL treated at the Musculoskeletal   Oncology Department of our hospital from 2000 to 2010. Retrospective evaluation included demographics, symptoms, tumor locations, outcomes of surgical treatment for local recurrence and survival rates. Results:   All patients received Combined Modality Therapy. Overall,five year survival was 89% and five year disease free survival rate was 78%. Local recurrence occurred in 6 patients during follow up period, which was treated surgically     by wide excision and reconstruction. The mean follow-up for the local recurrence group was 36(24-54 months and mortality rate in this group was 17%. Conclusions:   Combined Modality Therapy for stage IE primary bone lymphomaresults in good survival rate. In case   of local recurrence, wide excision and reconstruction improves the outcomes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Francis, Jasmine H., E-mail: francij1@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gobin, Y. Pierre; Marr, Brian P. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States); Brodie, Scott E. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mount Sinai School of Medicine, New York, New York (United States); Dunkel, Ira J.; Abramson, David H. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States)

    2013-11-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.

  12. Defining biochemical recurrence after radical prostatectomy and timing of early salvage radiotherapy. Informing the debate

    International Nuclear Information System (INIS)

    Budaeus, Lars; Schiffmann, Jonas; Graefen, Markus; Huland, Hartwig; Tennstedt, Pierre; Siegmann, Alessandra; Boehmer, Dirk; Budach, Volker; Bartkowiak, Detlef; Wiegel, Thomas

    2017-01-01

    The optimal prostate-specific antigen (PSA) level after radical prostatectomy (RP) for defining biochemical recurrence and initiating salvage radiation therapy (SRT) is still debatable. Whereas adjuvant or extremely early SRT irrespective of PSA progression might be overtreatment for some patients, SRT at PSA >0.2 ng/ml might be undertreatment for others. The current study addresses the optimal timing of radiation therapy after RP. Cohort 1 comprised 293 men with PSA 0.1-0.19 ng/ml after RP. Cohort 2 comprised 198 men with SRT. PSA progression and metastases were assessed in cohort 1. In cohort 2, we compared freedom from progression according to pre-SRT PSA (0.03-0.19 vs. 0.2-0.499 ng/ml). Multivariable Cox regression analyses predicted progression after SRT. In cohort 1, 281 (95.9%) men had further PSA progression ≥0.2 ng/ml and 27 (9.2%) men developed metastases within a median follow-up of 74.3 months. In cohort 2, we recorded improved freedom from progression according to lower pre-SRT PSA (0.03-0.19 vs. 0.2-0.499 ng/ml: 69 vs. 53%; log-rank p = 0.051). Patients with higher pre-SRT PSA ≥0.2 ng/ml were at a higher risk of progression after SRT (hazard ratio: 1.8; p [de

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

    International Nuclear Information System (INIS)

    Francis, Jasmine H.; Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil; Gobin, Y. Pierre; Marr, Brian P.; Brodie, Scott E.; Dunkel, Ira J.; Abramson, David H.

    2013-01-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG

  14. Pathway Linking Internet Health Information Seeking to Better Health: A Moderated Mediation Study.

    Science.gov (United States)

    Jiang, Shaohai; Street, Richard L

    2017-08-01

    The Internet increasingly has been recognized as an important medium with respect to population health. However, little is known about the mechanisms that underlie the potential impact of health-related Internet use on health outcomes. Based on the three-stage model of health promotion using interactive media, this study empirically tested a moderated mediation pathway model. Results showed that the effect of Internet health information seeking on three health outcomes (general, emotional, and physical) was completely mediated by respondents' access to social support resources. In addition, users' online health information seeking experience positively moderated this mediation path. The findings have significant theoretical and practical implications for the design of Internet-based health promotion resources to improve health outcomes.

  15. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine...... hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable......, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention...

  16. Unstable Modes and Order Parameters of Bistable Signaling Pathways at Saddle-Node Bifurcations: A Theoretical Study Based on Synergetics

    Directory of Open Access Journals (Sweden)

    Till D. Frank

    2016-01-01

    Full Text Available Mathematical modeling has become an indispensable part of systems biology which is a discipline that has become increasingly popular in recent years. In this context, our understanding of bistable signaling pathways in terms of mathematical modeling is of particular importance because such bistable components perform crucial functions in living cells. Bistable signaling pathways can act as switches or memory functions and can determine cell fate. In the present study, properties of mathematical models of bistable signaling pathways are examined from the perspective of synergetics, a theory of self-organization and pattern formation founded by Hermann Haken. At the heart of synergetics is the concept of so-called unstable modes or order parameters that determine the behavior of systems as a whole close to bifurcation points. How to determine these order parameters for bistable signaling pathways at saddle-node bifurcation points is shown. The procedure is outlined in general and an explicit example is worked out in detail.

  17. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review

    DEFF Research Database (Denmark)

    Benfield, T.; Atzori, C.; Miller, R.F.

    2008-01-01

    BACKGROUND: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). METHODS: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007...... and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs). RESULTS: Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82...... individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3...

  18. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bolo, Nicolas Robin [Univ. of California, Berkeley, CA (United States)

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. 13C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of [13C-4] to [13C-5]-glutamate, [13C-3] to [13C-2]-alanine or [13C-3] to [13C-2]-lactate produced when [13C-2]-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the 13C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in 13C NMR human studies from the current literature.

  19. ICSNPathway: identify candidate causal SNPs and pathways from genome-wide association study by one analytical framework.

    Science.gov (United States)

    Zhang, Kunlin; Chang, Suhua; Cui, Sijia; Guo, Liyuan; Zhang, Liuyan; Wang, Jing

    2011-07-01

    Genome-wide association study (GWAS) is widely utilized to identify genes involved in human complex disease or some other trait. One key challenge for GWAS data interpretation is to identify causal SNPs and provide profound evidence on how they affect the trait. Currently, researches are focusing on identification of candidate causal variants from the most significant SNPs of GWAS, while there is lack of support on biological mechanisms as represented by pathways. Although pathway-based analysis (PBA) has been designed to identify disease-related pathways by analyzing the full list of SNPs from GWAS, it does not emphasize on interpreting causal SNPs. To our knowledge, so far there is no web server available to solve the challenge for GWAS data interpretation within one analytical framework. ICSNPathway is developed to identify candidate causal SNPs and their corresponding candidate causal pathways from GWAS by integrating linkage disequilibrium (LD) analysis, functional SNP annotation and PBA. ICSNPathway provides a feasible solution to bridge the gap between GWAS and disease mechanism study by generating hypothesis of SNP → gene → pathway(s). The ICSNPathway server is freely available at http://icsnpathway.psych.ac.cn/.

  20. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  1. A two-hybrid assay to study protein interactions within the secretory pathway.

    Directory of Open Access Journals (Sweden)

    Danielle H Dube

    Full Text Available Interactions of transcriptional activators are difficult to study using transcription-based two-hybrid assays due to potent activation resulting in false positives. Here we report the development of the Golgi two-hybrid (G2H, a method that interrogates protein interactions within the Golgi, where transcriptional activators can be assayed with negligible background. The G2H relies on cell surface glycosylation to report extracellularly on protein-protein interactions occurring within the secretory pathway. In the G2H, protein pairs are fused to modular domains of the reporter glycosyltransferase, Och1p, and proper cell wall formation due to Och1p activity is observed only when a pair of proteins interacts. Cells containing interacting protein pairs are identified by selectable phenotypes associated with Och1p activity and proper cell wall formation: cells that have interacting proteins grow under selective conditions and display weak wheat germ agglutinin (WGA binding by flow cytometry, whereas cells that lack interacting proteins display stunted growth and strong WGA binding. Using this assay, we detected the interaction between transcription factor MyoD and its binding partner Id2. Interfering mutations along the MyoD:Id2 interaction interface ablated signal in the G2H assay. Furthermore, we used the G2H to detect interactions of the activation domain of Gal4p with a variety of binding partners. Finally, selective conditions were used to enrich for cells encoding interacting partners. The G2H detects protein-protein interactions that cannot be identified via traditional two-hybrid methods and should be broadly useful for probing previously inaccessible subsets of the interactome, including transcriptional activators and proteins that traffic through the secretory pathway.

  2. A study on apoptotic signaling pathway in HL-60 cells induced by radiation

    International Nuclear Information System (INIS)

    Kim, Hye Jung; Moon, Sung Keun; Lee, Jae Hoon; Moon, Sun Rock

    2001-01-01

    The mechanical insights of death at cancer cells by ionizing radiation are not yet clearly defined. Recent evidences have demonstrated that radiation therapy may induce cell death via activation of signaling pathway for apoptosis in target cells. This study is designed whether ionizing radiation may activate the signaling cascades of apoptosis including caspase family cysteine proteases, Bcl2/Bax, cytochrome c and Fas/Fas-L in target cells. HL-60 cells were irradiated in vitro with 6 MV X-ray at dose ranges from 2 Gy to 32 Gy. The cell viability was tested by MTT assay and the extent of apoptosis was determined using agarose gel electrophoresis. The activities of caspase proteases were measured by proteolytic cleavages of substrates. Western blot analysis was used to monitor PARP, caspase-3, Cytochrome-c, BcI-2, Bax, Fas and Fas-L. Ionizing radiation decreases the viability of HL -60 cells in a time and dose dependent manner. Ionizing radiation-induced death in HL- 60 cells is an apoptotic death which is revealed as characteristic ladder-pattern fragmentation at genomic DNA over 16 Gy at 4 hours. Ionizing radiation induces the activation of caspase-2, 3, 6, 8 and 9 of HL --60 cells in a time-dependent manner. The activation of caspase- 3 protease is also evidenced by the digestion of poly (ADP-ribose) polymerase and procaspase 3 with 16Gy ionizing irradiation. Anti-apoptotic Bcl2 expression is decreased but apoptotic Bax expression is increased with mitochondrial cytochrome c release in a time- dependent manner. In addition, expression of Fas and Fas-L is also increased in a time dependent manner. These data suggest that ionizing radiation-induced apoptosis is mediated by the activation of various signaling pathways including caspase family cysteine proteases, BcI 2 /Bax, Fas and Fas-L in a time and dose dependent manner

  3. Differential recovery of water quality parameters eight years after severe wildfire and salvage logging in Alberta's southern Rocky Mountains

    Science.gov (United States)

    Silins, U.; Bladon, K. D.; Stone, M.; Emelko, M. B.; Collins, A.; Boon, S.; Williams, C.; Wagner, M. J.; Martens, A. M.; Anderson, A.

    2012-12-01

    Broad regions of western North America rely on water supplies that originate from forested regions of the Rocky Mountain cordillera where landuse pressures, and stresses including changing natural disturbance regimes associated with shifting climates has been impacting critical source water supplies from this region. Increases in magnitude and severity of wildfires along with impacts on downstream water supplies has been observed along the length of the North American Rocky Mountain chain, however, the longevity of these impacts (including impacts to important water quality parameters) remain highly uncertain because processes regulating recovery from such disturbances can span a range of timescales from a few years to decades depending on both the hydro-climatic regime, and which water quality parameters are important. Studies document such long-term changes are few. The Southern Rockies Watershed Project (SRWP) was established to document the magnitude and recovery from the severe 2003 Lost Creek wildfire in the Crowsnest Pass region of southwest Alberta, Canada. Hydrology, water quality (physical & chemical) have been studies in 9 instrumented catchments (4-14 km2) encompassing burned, burned and salvage logged, prescribed burned, and unburned (reference) conditions since late winter 2004. While most important water quality parameters were strongly elevated in burned and burned-salvage logged catchments after the fire, strongly differential rates of recovery were observed for contaminant concentration, export, and yield across a range of water quality parameters (2004-2011). For example, while various nitrogen (N) species (total nitrogen, dissolved nitrogen, NO3-, NH4+) showed 2-7 fold increases in concentration the first 1-2 years after the wildfire, N recovered back to baseline concentrations 4-5 years after the wildfire. In contrast, eight full years after the wildfire (2011), no recovery of sediment or phosphorus (P) production (soluble reactive, total

  4. Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers.

    Science.gov (United States)

    Hamzić, Edin; Buitenhuis, Bart; Hérault, Frédéric; Hawken, Rachel; Abrahamsen, Mitchel S; Servin, Bertrand; Elsen, Jean-Michel; Pinard-van der Laan, Marie-Hélène; Bed'Hom, Bertrand

    2015-11-25

    Coccidiosis is the most common and costly disease in the poultry industry and is caused by protozoans of the Eimeria genus. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high costs for the development of efficient vaccines, respectively. Therefore, the current control programs must be expanded with complementary approaches such as the use of genetics to improve the host response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500 broilers using E. maxima for which we investigated variability among animals in response to the challenge. As a follow-up to this challenge study, we performed a genome-wide association study (GWAS) to identify genomic regions underlying variability of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis to increase our biological understanding of the underlying response to Eimeria maxima challenge. In total, we identified 22 single nucleotide polymorphisms (SNPs) with q value Eimeria maxima in broilers. Furthermore, the post-GWAS functional analysis indicates that biological pathways and networks involved in tissue proliferation and repair along with the primary innate immune response may play the most important role during the early stage of Eimeria maxima infection in broilers.

  5. NMR studies of stock process water and reaction pathways in hydrothermal carbonization of furfural residue

    Directory of Open Access Journals (Sweden)

    Fen Yue

    2018-04-01

    Full Text Available Hydrothermal carbonization (HTC is a valuable approach to convert furfural residue (FR into carbon material. The prepared biochars are usually characterized comprehensively, while the stock process water still remains to be studied in detail. Herein, a NMR study of the main components in stock process water generated at different HTC reaction conditions was reported. Various qualitative and quantitative NMR techniques (1H and 13C NMR, 1H–1H COSY and 1H13C HSQC etc. especially 1D selective gradient total correlation spectroscopy (TOCSY NMR were strategically applied in the analysis of HTC stock process water. Without separation and purification, it was demonstrated that the main detectable compounds are 5-hydroxymethylfurfural, formic acid, methanol, acetic acid, levulinic acid, glycerol, hydroxyacetone and acetaldehyde in this complicate mixture. Furthermore, the relationship between the concentration of major products and the reaction conditions (180–240 °C at 8 h, and 1–24 h at 240 °C was established. Finally, reasonable reaction pathways for hydrothermal conversion of FR were proposed based on this result and our previously obtained characteristics of biochars. The routine and challenging NMR methods utilized here would be an alternative other than HPLC or GC for biomass conversion research and can be extended to more studies. Keywords: NMR, Hydrothermal carbonization, Furfural residue, Stock process water

  6. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

    2017-01-01

    Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

  7. Salvage definitive chemo-radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: retrospective review

    International Nuclear Information System (INIS)

    Baxi, S. H.; Burmeister, B.; Harvey, J. A.; Smithers, M.; Thomas, J.

    2008-01-01

    Full text: To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo-radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo-radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo-radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo-radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival

  8. Immediate free jejunum transfer for salvage surgery of gastric tube necrosis.

    Science.gov (United States)

    Umezawa, Hiroki; Matsutani, Takeshi; Ogawa, Rei; Hyakusoku, Hiko

    2014-01-01

    Gastric tube necrosis after esophagus cancer surgery is a rare but critical situation. Salvage reconstruction of the esophagus remains a challenging procedure for head and neck surgeons. Historically, surgeons have employed a two-stage salvage surgery consisting of debridement followed by reconstruction. While this procedure generates good results, the time to restart oral alimentation is long. The present report describes the case of a 62-year-old male who developed gastric tube necrosis 3 days after undergoing surgery for thoracic-cervical esophageal cancer and immediate reconstruction with the retrosternal gastric pullup technique. He was treated with debridement and simultaneous free jejunum transfer 4 days after the primary surgery. He was able to restart oral alimentation 10 days after the salvage surgery. This rapid return to oral alimentation is a major advantage of the one-stage immediate esophagus salvage reconstruction. Another advantage is the ease of the reconstructive procedure: the absence of scarring and prolonged inflammation, which are disadvantages of the two-stage procedure, meant that recipient vessel selection and anastomosis were uncomplicated. The one-step procedure may be particularly useful in cases where the inflammation is discovered early.

  9. Preliminary evaluation of the Accident Response Mobile Manipulation System for accident site salvage operations

    International Nuclear Information System (INIS)

    Trujillo, J.M.; Morse, W.D.; Jones, D.P.

    1994-01-01

    This paper describes and evaluates operational experiences with the Accident Response Mobile Manipulation System (ARMMS) during simulated accident site salvage operations which might involve nuclear weapons. The ARMMS is based upon a teleoperated mobility platform with two Schilling Titan 7F Manipulators

  10. The outcome of rectal cancer after early salvage TME following TEM compared with primary TME

    DEFF Research Database (Denmark)

    Levic, K; Bulut, O; Hesselfeldt, P

    2012-01-01

    difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8...

  11. The outcome of rectal cancer after early salvage TME following TEM compared with primary TME

    DEFF Research Database (Denmark)

    Bulut, O; Levic, K; Hesselfeldt, P

    2014-01-01

    difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8...

  12. Vegetation response to large scale disturbance in a southern Appalachian forest: Hurricane Opal and salvage logging

    Science.gov (United States)

    Katherine J. Elliott; Stephanie L. Hitchcock; Lisa Krueger

    2002-01-01

    Disturbance such as catastrophic windthrow can play a major role in the structure and composition of southern Appalachian forests. We report effects of Hurricane Opal followed by salvage logging on vegetation dynamics (regeneration, composition, and diversity) the first three years after disturbance at the Coweeta Hydrologic Laboratory in western North Carolina. The...

  13. Modeling nest survival of cavity-nesting birds in relation to postfire salvage logging

    Science.gov (United States)

    Vicki Saab; Robin E. Russell; Jay Rotella; Jonathan G. Dudley

    2011-01-01

    Salvage logging practices in recently burned forests often have direct effects on species associated with dead trees, particularly cavity-nesting birds. As such, evaluation of postfire management practices on nest survival rates of cavity nesters is necessary for determining conservation strategies. We monitored 1,797 nests of 6 cavity-nesting bird species: Lewis'...

  14. An economic assessment of mountain pine beetle timber salvage in the west

    Science.gov (United States)

    Jeffrey P. Prestemon; Karen L. Abt; Kevin M. Potter; Frank H. Koch

    2013-01-01

    The mountain pine beetle has killed lodgepole pine and other species of pines in the western United States in an ongoing epidemic. The most heavily affected states are in the interior West: Colorado, Idaho, Montana, and Wyoming, with smaller losses elsewhere. Timber salvage is one response to the epidemic, which could generate revenues for affected landowners and...

  15. Late urinary morbidity and quality of life after radical prostatectomy and salvage radiotherapy for prostate cancer

    DEFF Research Database (Denmark)

    Ervandian, Maria; Hoyer, Morten; Petersen, Stine Elleberg

    2017-01-01

    OBJECTIVE: There is a paucity of knowledge of long-term urinary morbidity in patients treated for prostate cancer (PCa) with radical prostatectomy (RP) and salvage radiotherapy (SRT). Improved long-term survival calls for heightened awareness of late effects from radiotherapy after RP. The purpos...

  16. Response of HIV positive patients to the long-term salvage therapy by lopinavir/ritonavir

    Czech Academy of Sciences Publication Activity Database

    Prejdová, Jana; Machala, L.; Staňková, M.; Linka, M.; Brůčková, M.; Vandasová, J.; Konvalinka, Jan

    2005-01-01

    Roč. 33, č. 4 (2005), 319-323 ISSN 1386-6532 R&D Projects: GA MZd(CZ) NI6339 Grant - others:5th Framework(XE) QLK2-CT-2001-02360 Institutional research plan: CEZ:AV0Z4055905 Keywords : protease inhibitor * salvage therapy * resistance development Subject RIV: CE - Biochemistry Impact factor: 2.623, year: 2005

  17. 77 FR 19177 - Beaverhead-Deerlodge National Forest, Jefferson Ranger District, Montana, Boulder River Salvage...

    Science.gov (United States)

    2012-03-30

    ... statement. SUMMARY: The project proposes to salvage by clearcut harvest dead and lodgepole pine infested or... Need for Action The purpose and need for this project is to harvest merchantable wood products from..., before the value of the wood deteriorates; reduce stand density in lodgepole pine and Douglas-fir stands...

  18. Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

    International Nuclear Information System (INIS)

    Holtzman, Adam L.; Hoppe, Bradford S.; Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G.; Williams, Christopher R.; Li, Zuofeng; Mendenhall, Nancy P.

    2016-01-01

    Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

  19. Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, Adam L. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Williams, Christopher R. [Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida (United States); Li, Zuofeng; Mendenhall, Nancy P. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States)

    2016-05-01

    Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

  20. Molecular Pathways

    Science.gov (United States)

    Lok, Benjamin H.; Powell, Simon N.

    2012-01-01

    The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

  1. Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies.

    Science.gov (United States)

    Quell, Jan D; Römisch-Margl, Werner; Colombo, Marco; Krumsiek, Jan; Evans, Anne M; Mohney, Robert; Salomaa, Veikko; de Faire, Ulf; Groop, Leif C; Agakov, Felix; Looker, Helen C; McKeigue, Paul; Colhoun, Helen M; Kastenmüller, Gabi

    2017-12-15

    Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9

  2. Women's views and experiences of two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study.

    Science.gov (United States)

    Sawyer, Alexandra; Chhoa, Celine; Ayers, Susan; Pushpa-Rajah, Angela; Duley, Lelia

    2017-09-09

    The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. In addition to standard written consent, an oral assent pathway was developed for use when birth was imminent. The aim of this study was to explore women's views and experiences of two alternative consent pathways to participate in the Cord Pilot Trial. We conducted a qualitative study using semi-structured interviews. A total of 179 participants in the Cord Pilot Trial were sent a postal invitation to take part in interviews. Women who agreed were interviewed in person or by telephone to explore their experiences of two consent pathways for a preterm intrapartum trial. Data were analysed using inductive systematic thematic analysis. Twenty-three women who gave either written consent (n = 18) or oral assent followed by written consent (n = 5) to participate in the trial were interviewed. Five themes were identified: (1) understanding of the implications of randomisation, (2) importance of staff offering participation, (3) information about the trial and time to consider participation, (4) trial secondary in women's minds and (5) reasons for agreeing to take part in the trial. Experiences were similar for the two consent pathways. Women recruited by the oral assent pathway reported being given less information about the trial but felt it was sufficient to make a decision regarding participation. There were gaps in women's understanding of the trial and intervention, regardless of the consent pathway. Overall, women were positive about their experiences of being invited to participate in the trial. The oral assent pathway seems an acceptable option for women if the intervention is low-risk and time is limited. ISRCTN Registry, ISRCTN21456601 . Registered on 28 February 2013.

  3. Salvage Stereotactic Body Radiation Therapy (SBRT) for Local Failure After Primary Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Hearn, Jason W.D., E-mail: hearnj@ccf.org; Videtic, Gregory M.M.; Djemil, Toufik; Stephans, Kevin L.

    2014-10-01

    Purpose: Local failure after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is uncommon. We report the safety and efficacy of SBRT for salvage of local failure after previous SBRT with a biologically effective dose (BED) of ≥100 Gy{sub 10}. Methods and Materials: Using an institutional review board–approved lung SBRT registry, we identified all patients initially treated for early-stage NSCLC between August 2004 and January 2012 who received salvage SBRT for isolated local failure. Failure was defined radiographically and confirmed histologically unless contraindicated. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance, and received a BED of ≥100 Gy{sub 10} for each SBRT course. Tumor motion control involved a Bodyfix vacuum system for immobilization along with abdominal compression. Results: Of 436 patients treated from August 2004 through January 2012, we identified 22 patients with isolated local failure, 10 of whom received SBRT for salvage. The median length of follow-up was 13.8 months from salvage SBRT (range 5.3-43.5 months). Median tumor size was 3.4 cm (range 1.7-4.8 cm). Two of the 10 lesions were “central” by proximity to the mediastinum, but were outside the zone of the proximal bronchial tree. Since completing salvage, 3 patients are alive and without evidence of disease. A fourth patient died of medical comorbidities without recurrence 13.0 months after salvage SBRT. Two patients developed distant disease only. Four patients had local failure. Toxicity included grade 1-2 fatigue (3 patients) and grade 1-2 chest wall pain (5 patients). There was no grade 3-5 toxicity. Conclusions: Repeat SBRT with a BED of ≥100 Gy{sub 10} after local failure in patients with early-stage medically inoperable NSCLC was well tolerated in this series and may represent a viable salvage strategy in select patients with peripheral tumors ≤5 cm.

  4. Decomposition of clofibric acid in aqueous media by advance oxidation techniques: kinetics study and degradation pathway

    International Nuclear Information System (INIS)

    Syed, M.; Khan, A.M.; Khan, R.A.

    2016-01-01

    This study investigates the decomposition of clofibric acid (CLF) by different advanced oxidation processes (AOPs), such as UV (254 nm), VUV (185 nm), UV / TiO/sub 2/ and VUV / TiO/sub 2/. The removal efficiencies of applied AOPs were compared in the presence and absence of dissolved oxygen. The removal efficiency of the studied AOPs towards degradation of CLF were found in the order of VUV / TiO/sub 2/ + O/sub 2/ > VUV/TiO/sub 2/ + N/sub 2/ > VUV alone > UV / TiO/sub 2/ + O/sub 2/ > UV / TiO/sub 2/ +N/sub 2/ > UV alone. The decomposition kinetics of CLF was found to follow pseudo-first order rate law. VUV / TiO2 process was found to be most cheap and effective one for decomposition of CLF as compared to other applied AOPs in terms of electrical energy per order. Degradation products resulting from the degradation processes were also investigated using UPLC-MS /MS, accordingly degradation pathway was proposed. (author)

  5. OPS liquid pathway generic study. Topical report No. 22A60

    International Nuclear Information System (INIS)

    1977-06-01

    An evaluation of the consequences of radioactivity released from an offshore nuclear plant to liquid pathways as a result of postulated accidents more severe than the design basis Loss-of-Coolant Accident is presented

  6. Preparing for the Educational Black Hole? Teachers' Learning in Two Pathways into Middle School Social Studies Teaching

    Science.gov (United States)

    Conklin, Hilary G.

    2010-01-01

    The author presents findings from the first phase of a longitudinal, comparative case study that investigates what teachers learn about intellectually demanding social studies teaching at the middle school level from two distinctive teacher education pathways: a specialized middle school teacher education program and a secondary social studies…

  7. Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

    Directory of Open Access Journals (Sweden)

    Christopher J. D. Wallis MD

    2017-05-01

    Full Text Available Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence. Methods: We constructed a health state transition (Markov model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer–specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE (58.3 months as compared with adjuvant radiotherapy (53.7 months, a difference of 4.6 months (standard deviation 8.8. Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months. Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized

  8. Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Fernando G. Abarzua-Cabezas

    2015-02-01

    Full Text Available Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85% of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%. Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months. Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

  9. Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

    Directory of Open Access Journals (Sweden)

    Metha Maenhout

    2017-04-01

    Full Text Available Purpose : Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods : Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT. Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE version 4.0. Results : With a median follow-up of 12 months (range, 6-15, there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV was 4.8 cc (range, 1.9-6.6 cc. A median of 8 catheters (range, 6-9 were used, and the median dose to the treatment volume (GTV was a D95: 19.3 Gy (SD 15.5-19.4 Gy. Conclusions : Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

  10. The impact of post-fire salvage logging on microbial nitrogen cyclers in Mediterranean forest soil.

    Science.gov (United States)

    Pereg, Lily; Mataix-Solera, Jorge; McMillan, Mary; García-Orenes, Fuensanta

    2018-04-01

    Forest fires are a regular occurrence in the Mediterranean basin. High severity fires and post-fire management can affect biological, chemical and physical properties of soil, including the composition and abundance of soil microbial communities. Salvage logging is a post-fire management strategy, which involves the removal of burnt wood from land after a fire. The main objective of this work was to evaluate the impact of post-fire salvage logging and microaggregation on soil microbial communities, specifically on the abundance of nitrogen cyclers and, thus, the potential of the soil for microbial nitrogen cycling. The abundance of nitrogen cyclers was assessed by quantification of microbial nitrogen cycling genes in soil DNA, including nifH (involved in nitrogen fixation), nirS/K and nosZ (involved in denitrification), amoA-B and amoA-Arch (involved in bacterial and archaeal nitrification, respectively). It was demonstrated that salvage logging reduced bacterial load post-fire when compared to tree retention control and resulted in significant changes to the abundance of functional bacteria involved in nitrogen cycling. Microbial gene pools involved in various stages of the nitrogen cycle were larger in control soil than in soil subjected to post-fire salvage logging and were significantly correlated with organic matter, available phosphorous, nitrogen and aggregate stability. The microaggregate fraction of the soil, which has been associated with greater organic carbon, was shown to be a hotspot for nitrogen cyclers particularly under salvage logging. The impact of post-fire management strategies on soil microbial communities needs to be considered in relation to maintaining ecosystem productivity, resilience and potential impact on climate change. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Genes Involved in the Endoplasmic Reticulum N-Glycosylation Pathway of the Red Microalga Porphyridium sp.: A Bioinformatic Study

    Directory of Open Access Journals (Sweden)

    Oshrat Levy-Ontman

    2014-02-01

    Full Text Available N-glycosylation is one of the most important post-translational modifications that influence protein polymorphism, including protein structures and their functions. Although this important biological process has been extensively studied in mammals, only limited knowledge exists regarding glycosylation in algae. The current research is focused on the red microalga Porphyridium sp., which is a potentially valuable source for various applications, such as skin therapy, food, and pharmaceuticals. The enzymes involved in the biosynthesis and processing of N-glycans remain undefined in this species, and the mechanism(s of their genetic regulation is completely unknown. In this study, we describe our pioneering attempt to understand the endoplasmic reticulum N-Glycosylation pathway in Porphyridium sp., using a bioinformatic approach. Homology searches, based on sequence similarities with genes encoding proteins involved in the ER N-glycosylation pathway (including their conserved parts were conducted using the TBLASTN function on the algae DNA scaffold contigs database. This approach led to the identification of 24 encoded-genes implicated with the ER N-glycosylation pathway in Porphyridium sp. Homologs were found for almost all known N-glycosylation protein sequences in the ER pathway of Porphyridium sp.; thus, suggesting that the ER-pathway is conserved; as it is in other organisms (animals, plants, yeasts, etc..

  12. Energy pathway analysis - a hydrogen fuel cycle framework for system studies

    International Nuclear Information System (INIS)

    Badin, J.S.; Tagore, S.

    1997-01-01

    An analytical framework has been developed that can be used to estimate a range of life-cycle costs and impacts that result from the incremental production, storage, transport, and use of different fuels or energy carriers, such as hydrogen, electricity, natural gas, and gasoline. This information is used in a comparative analysis of energy pathways. The pathways provide the U.S. Department of Energy (DOE) with an indication of near-, mid-, and long-term technologies that have the greatest potential for advancement and can meet the cost goals. The methodology and conceptual issues are discussed. Also presented are results for selected pathways from the E3 (Energy, Economics, Emissions) Pathway Analysis Model. This model will be expanded to consider networks of pathways and to be compatible with a linear programming optimization processor. Scenarios and sets of constraints (energy demands, sources, emissions) will be defined so the effects on energy transformation activities included in the solution and on the total optimized system cost can be investigated. This evaluation will be used as a guide to eliminate technically feasible pathways if they are not cost effective or do not meet the threshold requirements for the market acceptance. (Author)

  13. Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Laaksonen, Jaakko; Taipale, Tuukka; Seppälä, Ilkka; Raitoharju, Emma; Mononen, Nina; Lyytikäinen, Leo-Pekka; Waldenberger, Melanie; Illig, Thomas; Hutri-Kähönen, Nina; Rönnemaa, Tapani; Juonala, Markus; Viikari, Jorma; Kähönen, Mika; Raitakari, Olli; Lehtimäki, Terho

    2017-10-01

    Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PR D ) and without dyslipidaemia (PR 0 ) and compared these to nonprediabetic controls without dyslipidaemia (C 0 ). The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49 years. Genome-wide expression data of peripheral blood and gene set enrichment analysis were used to investigate the differentially expressed genes and enriched pathways between different subtypes of prediabetes. Pathways for cholesterol synthesis, interleukin-12-mediated signalling events, and downstream signalling in naïve CD8+ T-cells were upregulated in the PR 0 group in comparison with controls (C 0 ). The upregulation of these pathways was independent of waist circumference, blood pressure, smoking status, and insulin. Adjustment for CRP left the CD8+ T-cell signalling and interleukin-12-mediated signalling event pathway upregulated. The cholesterol synthesis pathway was also upregulated when all prediabetic subjects (PR 0 and PR D ) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PR D group was compared with the C 0 group. Five genes in the PR 0 group and 1 in the PR D group were significantly differentially expressed in comparison with the C 0 group. Blood cell gene expression profiles differ significantly between prediabetic subjects with and without dyslipidaemia. Whether this classification may be used in detection of prediabetic individuals at a high risk of cardiovascular complications remains to be examined. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Salvage logging effect on soil properties in a fire-affected Mediterranean forest: a two years monitoring research

    Science.gov (United States)

    Mataix-Solera, Jorge; Moltó, Jorge; Arcenegui, Vicky; García-Orenes, Fuensanta; Chrenkovà, Katerina; Torres, Pilar; Jara-Navarro, Ana B.; Díaz, Gisela; Izquierdo, Ezequiel

    2015-04-01

    In the Mediterranean countries, forest fires are common and must be considered as an ecological factor, but changes in land use, especially in the last five decades have provoked a modification in their natural regime. Moreover, post-fire management can have an additional impact on the ecosystem; in some cases, even more severe than the fire. Salvage logging is a traditional management in most fire-affected areas. In some cases, the way of doing it, using heavy machinery, and the vulnerability of soils to erosion and degradation make this management potentially very agresive to soil, and therefore to the ecosystem. Very little research has been done to study how this treatment could affect soil health. In this research we show 2 years of monitoring of some soil properties in an area affected by a forest fire, where some months later this treatment was applied. The study area is located in 'Sierra de Mariola Natural Park' in Alcoi, Alicante (E Spain). A big forest fire (>500 has) occurred in July 2012. The forest is composed mainly of Pinus halepensis trees with an understory of typical Mediterranean shrubs species such as Quercus coccifera, Rosmarinus officinalis, Thymus vulgaris, Brachypodium retusum, etc. Soil is classified as a Typic Xerorthent (Soil Survey Staff, 2014) developed over marls. In February 2013, salvage logging (SL) treatment consisting in a complete extraction of the burned wood using heavy machinery was applied in a part of the affected forest. Plots for monitoring this effect were installed in this area and in a similar nearby area where no treatment was done, and then used as control (C) for comparison. Soil samplings were done immediately after treatment and every 6 months. Some soil properties were analysed, including soil organic matter (SOM) content, basal soil respiration (BSR), microbial biomass carbon (MBC), bulk density (BD), soil water repellency (SWR), aggregate stability (AS), field capacity, nitrogen, etc. After two years of

  15. Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes.

    Science.gov (United States)

    Cheah, C Y; Chihara, D; Romaguera, J E; Fowler, N H; Seymour, J F; Hagemeister, F B; Champlin, R E; Wang, M L

    2015-06-01

    Although ibrutinib is highly effective in patients with relapsed/refractory mantle cell lymphoma (MCL), a substantial proportion of patients have resistant disease. The subsequent outcomes of such patients are unknown. We carried out a retrospective review of all patients with MCL treated with ibrutinib at MD Anderson Cancer Center between January 2011 and January 2014 using pharmacy and clinical databases. Patients who had discontinued ibrutinib for any reason were included in the study. We identified 42 patients with MCL who discontinued therapy due to disease progression on treatment (n = 28), toxicity (n = 6), elective stem-cell transplant in remission (n = 4) or withdrawn consent (n = 4). The median age was 69 years, 35 (83%) were male; the median number of prior treatments was 2 (range 1-8) and the median time from initial diagnosis of MCL to commencing ibrutinib was 3.0 (range 0.5-15.5) years. Patients had received a median of 6.5 (range 1-43) cycles of ibrutinib. Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively. After a median follow-up of 10.7 (range 2.4-38.9) months from discontinuation of ibrutinib, the median overall survival (OS) among patients with disease progression was 8.4 months. By univariate analysis, elevated serum lactate dehydrogenase at progression was associated with inferior OS. The outcome of patients with MCL who experience disease progression following ibrutinib therapy is poor, with both low response rates to salvage therapy and short duration of responses. Further studies to better understand and overcome ibrutinib resistance are urgently needed. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients.

    Science.gov (United States)

    Domínguez-Hermosillo, Juan Carlos; Mata-Marin, José Antonio; Herrera-González, Norma Estela; Chávez-García, Marcelino; Huerta-García, Gloria; Nuñez-Rodríguez, Nohemí; García-Gámez, José Gerardo; Jiménez-Romero, Anai; Gaytán-Martínez, Jesús Enrique

    2016-09-30

    Although both tipranavir (TPV) and darunavir (DRV) represent important options for the management of patients with multi-protease inhibitor (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies comparing the effectiveness and safety of these two drugs in the Mexican population. The aim of this study was to compare the effectiveness of TPV versus DRV as a salvage therapy in HIV-1 treatment-experienced patients. This was a comparative, prospective, cohort study. Patients with HIV and triple-class drug resistance evaluated at the Hospital de Infectología "La Raza", National Medical Center, were included. All patients had the protease and retrotranscriptase genotype; resistance mutation interpretation was done using the Stanford database. A total of 35 HIV-1 triple-class drug-resistant patients were analyzed. All of them received tenofovir and raltegravir, 22 received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177-320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR, 252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load HIV-1 patients who were highly experienced in antiretroviral therapy.

  17. Understanding implementation processes of clinical pathways and clinical practice guidelines in pediatric contexts: a study protocol

    Directory of Open Access Journals (Sweden)

    Scott Shannon D

    2011-12-01

    Full Text Available Abstract Background Canada is among the most prosperous nations in the world, yet the health and wellness outcomes of Canadian children are surprisingly poor. There is some evidence to suggest that these poor health outcomes are partly due to clinical practice variation, which can stem from failure to apply the best available research evidence in clinical practice, otherwise known as knowledge translation (KT. Surprisingly, clinical practice variation, even for common acute paediatric conditions, is pervasive. Clinical practice variation results in unnecessary medical treatments, increased suffering, and increased healthcare costs. This study focuses on improving health outcomes for common paediatric acute health concerns by evaluating strategies that improve KT and reduce clinical practice variation. Design/Methods Using a multiple case study design, qualitative and quantitative data will be collected from four emergency departments in western Canada. Data sources will include: pre- and post-implementation focus group data from multidisciplinary healthcare professionals; individual interviews with the local champions, KT intervention providers, and unit/site leaders/managers; Alberta Context Tool (ACT survey data; and aggregated patient outcome data. Qualitative and quantitative data will be systematically triangulated, and matrices will be built to do cross-case comparison. Explanations will be built about the success or lack of success of the clinical practice guidelines (CPG and clinical pathways (CPs uptake based upon the cross-case comparisons. Significance This study will generate new knowledge about the potential causal mechanisms and factors which shape implementation. Future studies will track the impact of the CPG/CPs implementation on children's health outcome, and healthcare costs.

  18. Homelessness Pathways for Australian Single Mothers and Their Children: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Wayne Warburton

    2018-03-01

    Full Text Available There is increasing concern about family homelessness. Homeless mothers and their children are one of society’s most disadvantaged and at-risk populations. However, very little Australian research exploring mothers’ views on their homelessness experiences exists. Using semi-structured interviews with 14 mothers and four agency staff, this study explored homeless Australian mothers’ pathways into and out of homelessness, their specific needs and the services and supports that were (or would have been most helpful. In this sample of single mothers and their children, early experiences of homelessness and domestic violence contributed most commonly to homelessness episodes. Almost immediate engagement with welfare agencies seemed to be protective against re-experiencing homelessness, however Australian restrictions on length of program involvement and limited housing options for mothers exiting homelessness programs, may place such mothers and their children at high risk of re-entering homelessness. Younger mothers had greater needs and benefited most from personalised one-on-one support that addressed key parenting and life skills. The implications of these findings are considered in relation to service delivery to this vulnerable group and avenues for future research are noted.

  19. How does MBCT for depression work? studying cognitive and affective mediation pathways.

    Directory of Open Access Journals (Sweden)

    Tim Batink

    Full Text Available Mindfulness based cognitive therapy (MBCT is a non-pharmacological intervention to reduce current symptoms and to prevent recurrence of major depressive disorder. At present, it is not well understood which underlying mechanisms during MBCT are associated with its efficacy. The current study (n = 130 was designed to examine the roles of mindfulness skills, rumination, worry and affect, and the interplay between those factors, in the mechanisms of change in MBCT for residual depressive symptoms. An exploratory but systematic approach was chosen using Sobel-Goodman mediation analyses to identify mediators on the pathway from MBCT to reduction in depressive symptoms. We replicated earlier findings that therapeutic effects of MBCT are mediated by changes in mindfulness skills and worry. Second, results showed that changes in momentary positive and negative affect significantly mediated the efficacy of MBCT, and also mediated the effect of worry on depressive symptoms. Third, within the group of patients with a prior history of ≤ 2 episodes of MDD, predominantly changes in cognitive and to a lesser extent affective processes mediated the effect of MBCT. However, within the group of patients with a prior history of ≥ 3 episodes of MDD, only changes in affect were significant mediators for the effect of MBCT.[corrected] Nederlands Trial Register NTR1084.

  20. Isotope-labeling studies on the formation pathway of acrolein during heat processing of oils.

    Science.gov (United States)

    Ewert, Alice; Granvogl, Michael; Schieberle, Peter

    2014-08-20

    Acrolein (2-propenal) is classified as a foodborne toxicant and was shown to be present in significant amounts in heated edible oils. Up to now, its formation was mainly suggested to be from the glycerol part of triacylglycerides, although a clear influence of the unsaturation of the fatty acid moiety was also obvious in previous studies. To unequivocally clarify the role of the glycerol and the fatty acid parts in acrolein formation, two series of labeled triacylglycerides were synthesized: [(13)C(3)]-triacylglycerides of stearic, oleic, linoleic, and linolenic acid and [(13)C(54)]-triacylglycerides with labeled stearic, oleic, and linoleic acid, but with unlabeled glycerol. Heating of each of the seven intermediates singly in silicon oil and measurement of the formed amounts of labeled and unlabeled acrolein clearly proved the fatty acid backbone as the key precursor structure. Enzymatically synthesized pure linoleic acid and linolenic acid hydroperoxides were shown to be the key intermediates in acrolein formation, thus allowing the discussion of a radical-induced reaction pathway leading to the formation of the aldehyde. Surprisingly, although several oils contained high amounts of acrolein after heating, deep-fried foods themselves, such as donuts or French fries, were low in the aldehyde.

  1. Inflammatory and apoptotic signalling pathways and concussion severity: a genetic association study.

    Science.gov (United States)

    Mc Fie, Sarah; Abrahams, Shameemah; Patricios, Jon; Suter, Jason; Posthumus, Michael; September, Alison V

    2018-03-06

    The objective was to investigate the relationship between IL-1B rs16944, IL-6 rs1800795, and CASP8 rs3834129 genetic polymorphisms and concussion severity. Rugby players from high school, senior amateur, and professional teams completed a concussion severity questionnaire and donated a DNA sample. Participants (n = 163) were split into symptom severity groups around the median number and duration of symptoms. The frequency of participants with high symptom counts (more than five symptoms) increased across the IL-1B (C/C: 35%; C/T: 51%; T/T: 56%; P = 0.047) and the IL-6 (C/C: 31%; C/G: 44%; G/G: 58%; P = 0.027) genotypes. The C-C inferred interleukin allele construct frequency, created from combining the IL-1B and IL-6 genotype data, was lower in participants reporting a high symptom count (18%), compared to those with a low symptom count (fewer than six symptoms, 36%, P = 0.002). Similarly, the C-C inferred interleukin allele construct frequency was lower in those reporting prolonged symptom duration (more than one week, 16%), as opposed to short symptom duration (less than one week, 34%, P = 0.015). This study provides evidence of novel inflammatory pathway genetic associations with concussion severity, which supports the hypothesis implicating neuroinflammation in the development of concussion symptoms.

  2. Functional studies of signaling pathways in peri-implantation development of the mouse embryo by RNAi

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    Bell Graham

    2005-12-01

    Full Text Available Abstract Background Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages. Results We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages. Conclusion Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo.

  3. Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study.

    Science.gov (United States)

    Yacoub, Sophie; Lam, Phung Khanh; Huynh, Trieu Trung; Nguyen Ho, Hong Hanh; Dong Thi, Hoai Tam; Van, Nguyen Thu; Lien, Le Thi; Ha, Quyen Nguyen Than; Le, Duyen Huynh Thi; Mongkolspaya, Juthathip; Culshaw, Abigail; Yeo, Tsin Wen; Wertheim, Heiman; Simmons, Cameron; Screaton, Gavin; Wills, Bridget

    2017-10-16

    Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however, the association of endothelial nitric oxide (NO) pathways with disease severity is unknown. We performed a prospective observational study in 2 Vietnamese hospitals, assessing patients presenting early (dengue. The reactive hyperemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability, was evaluated using peripheral artery tonometry (EndoPAT), and plasma levels of l-arginine, arginase-1, and asymmetric dimethylarginine were measured at serial time-points. The main outcome of interest was plasma leakage severity. Three hundred fourteen patients were enrolled; median age of the participants was 21(interquartile range, 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness. Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs 2.00; P dengue illness and correlates with hypoargininemia and high arginase-1 levels. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  4. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Directory of Open Access Journals (Sweden)

    Norbert W Lutz

    Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

  5. Nitrogen uptake and regeneration pathways in the equatorial Pacific: a basin scale modeling study

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    R. Le Borgne

    2009-11-01

    Full Text Available It is well known that most primary production is fueled by regenerated nitrogen in the open ocean. Therefore, studying the nitrogen cycle by focusing on uptake and regeneration pathways would advance our understanding of nitrogen dynamics in the marine ecosystem. Here, we carry out a basin-scale modeling study, by assessing model simulations of nitrate and ammonium, and rates of nitrate uptake, ammonium uptake and regeneration in the equatorial Pacific. Model-data comparisons show that the model is able to reproduce many observed features of nitrate, ammonium, such as the deep ammonium maximum (DAM. The model also reproduces the observed de-coupling of ammonium uptake and regeneration, i.e., regeneration rate greater than uptake rate in the lower euphotic zone. The de-coupling largely explains the observed DAM in the equatorial Pacific Ocean. Our study indicates that zooplankton excretion and remineralization of organic nitrogen play a different role in nitrogen regeneration. Rates of zooplankton excretion vary from <0.01 mmol m−3 d−1 to 0.1 mmol m−3 d−1 in the upper euphotic zone while rates of remineralization fall within a narrow range (0.015–0.025 mmol m−3 d−1 . Zooplankton excretion contributes up to 70% of total ammonium regeneration in the euphotic zone, and is largely responsible for the spatial variability of nitrogen regeneration. However, remineralization provides a steady supply of ammonium in the upper ocean, and is a major source of inorganic nitrogen for the oligotrophic regions. Overall, ammonium generation and removal are approximately balanced over the top 150 m in the equatorial Pacific.

  6. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Science.gov (United States)

    Lutz, Norbert W; Fernandez, Carla; Pellissier, Jean-François; Cozzone, Patrick J; Béraud, Evelyne

    2013-01-01

    Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA) and spinal-cord homogenate (SC-H), whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group). Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE) or extra-cerebral (AA) inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and/or due to the

  7. Phase II Trial of Metronomic Chemotherapy as Salvage Therapy for Patients with Metastatic Breast Cancer

    International Nuclear Information System (INIS)

    SALEM, D.A.; GADO, N.M.; ABDELAZIZ, N.N.; ESSA, A.E.; ABDELHAFEEZ, Z.M.; KAMEL, T.H.

    2008-01-01

    Aim of Work: To evaluate the efficacy and tolerability of metronomic chemotherapy (which is the continuous administration of chemotherapy at relatively low minimally toxic doses on a frequent schedule of administration at close regular intervals with no prolonged drug-free breaks) in metastatic breast cancer patients as salvage therapy. Patients and Methods: In this phase II study we evaluated the clinical efficacy and tolerability of low dose, oral Methotrexate (MTX) and Cyclophosphamide (CTX) in patients with metastatic breast cancer. Between January 2004 and December 2005, 42 patients received MTX 2.5 mg bid on day 1 and 2 each week and CTX 50 mg/day administered continuously. Results: Forty two patients were evaluable. The overall clinical benefit was 31% complete response, partial response and stable disease (CR+PR+SD ³24 weeks), while the overall response rate was 16.7% (none of the patients attained CR). Toxicity was generally mild. The most common non hematological toxicity was elevation in transaminases level, it was reported in 40.4% of patients and was reversible, while mild grade 1 or 2 neutropenia was the most common hematological toxicity, (28.5% of patients). Median time to response was 3±0.18 while progression free survival (PFS) among patients with clinical benefit was 10 months (95% CI 6.65-13.44). Conclusions: This phase II study shows that, the combination of continuously low dose MTX and CTX is an active minimally toxic and significantly cost effective regimen for the treatment of metastatic breast cancer patients.

  8. The effects of metallic implants on electroporation therapies: feasibility of irreversible electroporation for brachytherapy salvage.

    Science.gov (United States)

    Neal, Robert E; Smith, Ryan L; Kavnoudias, Helen; Rosenfeldt, Franklin; Ou, Ruchong; Mclean, Catriona A; Davalos, Rafael V; Thomson, Kenneth R

    2013-12-01

    Electroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments. This study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expired radiotherapy seeds. Electrical current was measured and lesion dimensions were examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions. There was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all p > 0.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all p > 0.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins. This study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.

  9. Biceps tenodesis is a viable option for salvage of failed SLAP repair.

    Science.gov (United States)

    Werner, Brian C; Pehlivan, Hakan C; Hart, Joseph M; Lyons, Matthew L; Gilmore, C Jan; Garrett, Cara B; Carson, Eric W; Diduch, David R; Miller, Mark D; Brockmeier, Stephen F

    2014-08-01

    Outcomes of arthroscopic superior labral anterior-posterior (SLAP) repairs have been well reported with generally favorable outcomes. Unfortunately, a percentage of patients remain dissatisfied or suffer further injury after SLAP repair and may seek additional treatment. The purpose of this study was to evaluate the surgical outcomes of biceps tenodesis for failed SLAP repairs. A retrospective review of all patients undergoing biceps tenodesis was completed. Inclusion criteria were previous SLAP repair and subsequent revision biceps tenodesis. Exclusion criteria were additional shoulder procedures including rotator cuff repair, instability procedures, and preoperative frozen shoulder. Objective outcomes were postoperative assessments with Constant score, American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation, Simple Shoulder Test, and Veterans RAND 36-Item Health Survey. Physical examination was conducted to determine postoperative range of motion and strength compared with the nonoperative shoulder. A cohort of 24 patients was identified, and of these, 17 patients (71%) completed the study at 2 years' follow-up. The average postoperative Constant score was 84.4; American Shoulder and Elbow Surgeons score, 75.5; Single Assessment Numeric Evaluation score, 73.1%; Simple Shoulder Test score, 9.2; and Veterans RAND 36-Item Health Survey score, 76.1. Postoperative range of motion of the operative shoulder returned to near that of the asymptomatic nonoperative shoulder. Workers' compensation status led to inferior results. Options for patients with a failed prior SLAP repair are limited. As a salvage operation for failed SLAP repair, biceps tenodesis serves the majority of patients well, with favorable outcomes by validated measures and excellent shoulder range of motion and elbow strength at 2 years' follow-up. Workers' compensation status may predispose patients to poorer outcomes. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board

  10. Can salvage logging affect seed dispersal by birds into burned forests?

    Science.gov (United States)

    Rost, J.; Pons, P.; Bas, J. M.

    2009-09-01

    The recovery of vegetation in Mediterranean ecosystems after wildfire is mostly a result of direct regeneration, since the same species existing before the fire regenerate on-site by seeding or resprouting. However, the possibility of plant colonization by dispersal of seeds from unburned areas remains poorly studied. We addressed the role of the frugivorous, bird-dependent seed dispersal (seed rain) of fleshy-fruited plants in a burned and managed forest in the second winter after a fire, before on-site fruit production had begun. We also assessed the effect on seed rain of different microhabitats resulting from salvage logging (erosion barriers, standing snags, open areas), as well as the microhabitats of unlogged patches and an unburned control forest, taking account of the importance of perches as seed rain sites. We found considerable seed rain by birds in the burned area. Seeds, mostly from Olive trees Olea europaea and Evergreen pistaches Pistacia lentiscus, belonged to plants fruiting only in surrounding unburned areas. Seed rain was heterogeneous, and depended on microhabitat, with the highest seed density in the unburned control forest but closely followed by the wood piles of erosion barriers. In contrast, very low densities were found under perches of standing snags. Furthermore, frugivorous bird richness seemed to be higher in the erosion barriers than elsewhere. Our results highlight the importance of this specific post-fire management in bird-dependent seed rain and also may suggest a consequent heterogeneous distribution of fleshy-fruited plants in burned and managed areas. However, there needs to be more study of the establishment success of dispersed seeds before an accurate assessment can be made of the role of bird-mediated seed dispersal in post-fire regeneration.

  11. Transcatheter Arterial Chemoembolization (TACE) of Colorectal Cancer Liver Metastases by Irinotecan-Eluting Microspheres in a Salvage Patient Population

    Energy Technology Data Exchange (ETDEWEB)

    Huppert, Peter, E-mail: huppert@klinikum-darmstadt.de [Klinikum Darmstadt GmbH, Department of Diagnostic and Interventional Radiology (Germany); Wenzel, Thorsten [Klinikum Darmstadt GmbH, Department of Medical Oncology (Germany); Wietholtz, Hubertus [Klinikum Darmstadt GmbH, Department of Gastroenterology (Germany)

    2013-05-14

    PurposeThis prospective study evaluated the effectiveness and safety of TACE using irinotecan loaded superabsorbent polymer (SAP) microspheres for treatment of colorectal cancer liver metastases (CCLM) in a salvage setting of patients.MethodsA total of 71 TACE procedures were performed in 29 patients with liver only or liver-dominant CCLM. In all patients, systemic chemotherapy before TACE had failed. Two hundred milligrams of irinotecan were loaded into 50–100 mg of SAP microspheres (HepaSphere™ Microspheres) considering tumor size and vascularization. TACE was performed selectively with respect to tumor distribution. Response was evaluated following RECIST and EASL criteria, respectively. Median follow-up after last TACE was 8 (range 1–54) months. All patients had died at time of analysis.ResultsAll TACE procedures were performed successfully; 35–400 mg (mean 168.3 mg) of irinotecan loaded in 13–100 mg (mean 48.3 mg) SAP microspheres were injected during individual sessions. No major complications occurred. Three, 6, and 12 months after first TACE complete and partial response was present in 72, 32 %, 0 of patients by EASL criteria and stable disease was seen in 86, 48, and 8 % with no complete and no partial response by RECIST criteria. Median overall survival after first TACE was 8 months, and median time to progression was 5 months. Median overall survival was longer in patients with limited (<25 %) compared with extensive (>50 %) intrahepatic disease (21 vs. 5 months, p < 0.005).ConclusionsTACE using irinotecan loaded SAP microspheres is safe and effective in terms of tumor necrosis. Survival benefit in a salvage setting seems to be limited in patients with advanced intrahepatic tumor load.

  12. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

    International Nuclear Information System (INIS)

    Zhang, Jian; Gong, Youling; Peng, Feng; Li, Na; Liu, Yongmei; Xu, Yong; Zhou, Lin; Wang, Jin; Zhu, Jiang; Huang, Meijuan

    2012-01-01

    To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group). The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study. For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome

  13. A 20-year multicentre outcome analysis of salvage mechanical circulatory support for refractory cardiogenic shock after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Maziar Khorsandi

    2016-11-01

    Full Text Available Abstract Background Refractory post-cardiotomy cardiogenic shock (PCCS is a relatively rare phenomenon that can lead to rapid multi-organ dysfunction syndrome and is almost invariably fatal without advanced mechanical circulatory support (AMCS, namely extra-corporeal membrane oxygenation (ECMO or ventricular assist devices (VAD. In this multicentre observational study we retrospectively analyzed the outcomes of salvage venoarterial ECMO (VA ECMO and VAD for refractory PCCS in the 3 adult cardiothoracic surgery centres in Scotland over a 20-year period. Methods The data was obtained through the Edinburgh, Glasgow and Aberdeen cardiac surgery databases. Our inclusion criteria included any adult patient from April 1995 to April 2015 who had received salvage VA ECMO or VAD for PCCS refractory to intra-aortic balloon pump (IABP and maximal inotropic support following adult cardiac surgery. Results A total of 27 patients met the inclusion criteria. Age range was 34–83 years (median 51 years. There was a large male predominance (n = 23, 85 %. Overall 23 patients (85 % received VA ECMO of which 14 (61 % had central ECMO and 9 (39 % had peripheral ECMO. Four patients (15 % were treated with short-term VAD (BiVAD = 1, RVAD = 1 and LVAD = 2. The most common procedure-related complication was major haemorrhage (n = 10. Renal failure requiring renal replacement therapy (n = 7, fatal stroke (n = 5, septic shock (n = 2, and a pseudo-aneurysm at the femoral artery cannulation site (n = 1 were also observed. Overall survival to hospital discharge was 40.7 %. All survivors were NYHA class I-II at 12 months’ follow-up. Conclusion AMCS for refractory PCCS carries a survival benefit and achieves acceptable functional recovery despite a significant complication rate.

  14. Experimental Studies of the Molecular Pathways Regulated by Exercise and Resveratrol in Heart, Skeletal Muscle and the Vasculature

    Directory of Open Access Journals (Sweden)

    Vernon W. Dolinsky

    2014-09-01

    Full Text Available Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of exercise training and resveratrol on some of the organs and tissues that act in concert to transport oxygen throughout the body. In particular, we focus on animal studies that investigate the molecular signaling pathways induced by these interventions. We also compare and contrast the effects of exercise and resveratrol in diseased states.

  15. A cluster randomized controlled trial of a clinical pathway for hospital treatment of heart failure: study design and population

    Directory of Open Access Journals (Sweden)

    Gardini Andrea

    2007-11-01

    Full Text Available Abstract Background The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals. Methods/design Two-arm, cluster-randomized trial. 14 community hospitals were randomized either to arm 1 (clinical pathway: appropriate use of practice guidelines and supplies of drugs and ancillary services, new organization and procedures, patient education, etc. or to arm 2 (no intervention, usual care. 424 patients sample (212 in each group, 80% of power at the 5% significance level (two-sided. The primary outcome measure is in-hospital mortality. We will also analyze the impact of the clinical pathways comparing the length and the appropriateness of the stay, the rate of unscheduled readmissions, the customers' satisfaction and the costs treating the patients with the pathways and with the current practice along all the observation period. The quality of the care will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and by measuring key quality indicators at discharge. Discussion This paper examines the design of the evaluation of a complex

  16. Salvage radiotherapy for macroscopic local recurrences after radical prostatectomy. A national survey on patterns of practice

    Energy Technology Data Exchange (ETDEWEB)

    Dal Pra, Alan [Bern University Hospital, Inselspital Bern, Department of Radiation Oncology, Bern (Switzerland); Panje, Cedric; Glatzer, Markus; Putora, Paul Martin [Kantonsspital St. Gallen, Department of Radiation Oncology, St. Gallen (Switzerland); Zilli, Thomas [Hospitaux Universitaires de Geneve, Department of Radiation Oncology, Geneve (Switzerland); Arnold, Winfried [Luzerner Kantonsspital, Department of Radiation Oncology, Luzerner (Switzerland); Brouwer, Kathrin [Stadtspital Triemli, Department of Radiation Oncology, Zuerich (Switzerland); Garcia, Helena [Universitaetsspital Zuerich, Department of Radiation Oncology, Zuerich (Switzerland); Gomez, Silvia [Kantonsspital Aarau, Department of Radiation Oncology, Aarau (Switzerland); Herrera, Fernanda [Centre Hospitalier Universitaire Vaudois, Department of Radiation Oncology, Lausanne (Switzerland); Kaouthar, Khanfir [Hopital du Valais, Department of Radiation Oncology, Sion (Switzerland); Papachristofilou, Alexandros [Universitaetsspital Basel, Department of Radiation Oncology, Basel (Switzerland); Pesce, Gianfranco [EOC Bellinzona, Department of Radiation Oncology, Bellinzona (Switzerland); Reuter, Christiane [Kantonsspital Muensterlingen, Department of Radiation Oncology, Muensterlingen (Switzerland); Vees, Hansjoerg [Klinik Hirslanden, Department of Radiation Oncology, Zuerich (Switzerland); Zwahlen, Daniel Rudolf [Kantonsspital Graubuenden, Department of Radiation Oncology, Chur (Switzerland); Engeler, Daniel [Kantonsspital St. Gallen, Department of Urology, St. Gallen (Switzerland)

    2018-01-15

    Although salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy. A total of 14 Swiss radiation oncology centers were asked to complete a survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology. The majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66 Gy (range 65-72 Gy) with a boost to the macroscopic lesion used by 79% of the centers with a median total dose of 72 Gy (range 70-80 Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined. We observed a high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field. (orig.) [German] Obwohl die Evidenz fuer eine fruehzeitige Salvage-Radiotherapie (SRT) bei einem PSA-Rezidiv nach radikaler Prostatektomie spricht, werden viele Patienten erst bei einem

  17. Evaluation of magnocellular pathway abnormalities in schizophrenia: a frequency doubling technology study and clinical implications

    Directory of Open Access Journals (Sweden)

    Fabiana Benites Vaz de Lima

    2013-04-01

    Full Text Available BACKGROUND: Visual processing deficits have been reported for patients with schizophrenia. Previous studies demonstrated differences in early-stage processing of schizophrenics, although the nature, extent, and localization of the disturbance are unknown. The magnocellular and parvocellular visual pathways are associated with transient and sustained channels, but their respective contributions to schizophrenia-related visual deficits remains controversial. PURPOSE: The aim of this study was to evaluate magnocellular dysfunction in schizophrenia using frequency doubling technology. METHODS: Thirty-one patients with schizophrenia and 34 healthy volunteers were examined. Frequency doubling technology testing was performed in one session, consisting of a 15-minute screening strategy followed by the C-20 program for frequency doubling technology. RESULTS: Schizophrenic patients showed lower global mean sensitivity (30,97 ± 2,25 dB compared with controls (32,17 ± 3,08 dB, p<0.009. Although there was no difference in the delta sensitivity of hemispheres, there was a difference in sensitivity analysis of the fibers crossing the optic chiasm, with lower mean sensitivity in the patient group (28,80 dB versus controls (30,66 dB. The difference was higher in fibers that do not cross the optic chiasm, with lower mean sensitivity in patients (27,61 dB versus controls (30,26 dB, p<0.005. CONCLUSIONS: Our results suggest that there are differences between global sensitivity and fiber sensitivity measured by frequency doubling technology. The different sensitivity of fibers that do not cross the optic chiasm is consistent with most current etiological hypotheses for schizophrenia. The decreased sensitivity responses in the optic radiations may significantly contribute to research assessing early-stage visual processing deficits for patients with schizophrenia.

  18. Developmental Pathways to Depressive Symptoms in Adolescence: A Multi-Wave Prospective Study of Negative Emotionality, Stressors, and Anxiety

    Science.gov (United States)

    Barrocas, Andrea L.; Hankin, Benjamin L.

    2011-01-01

    This study examined two potential developmental pathways through which the temperament risk factor of negative emotionality (NE) leads to prospective increases in depressive symptoms through the mediating role of stressors and anxious symptoms in a sample of early to middle adolescents (N = 350, 6th-10th graders). The primary hypothesized model…

  19. Integrated QSAR study for inhibitors of Hedgehog Signal Pathway against multiple cell lines:a collaborative filtering method.

    Science.gov (United States)

    Gao, Jun; Che, Dongsheng; Zheng, Vincent W; Zhu, Ruixin; Liu, Qi

    2012-07-31

    The Hedgehog Signaling Pathway is one of signaling pathways that are very important to embryonic development. The participation of inhibitors in the Hedgehog Signal Pathway can control cell growth and death, and searching novel inhibitors to the functioning of the pathway are in a great demand. As the matter of fact, effective inhibitors could provide efficient therapies for a wide range of malignancies, and targeting such pathway in cells represents a promising new paradigm for cell growth and death control. Current research mainly focuses on the syntheses of the inhibitors of cyclopamine derivatives, which bind specifically to the Smo protein, and can be used for cancer therapy. While quantitatively structure-activity relationship (QSAR) studies have been performed for these compounds among different cell lines, none of them have achieved acceptable results in the prediction of activity values of new compounds. In this study, we proposed a novel collaborative QSAR model for inhibitors of the Hedgehog Signaling Pathway by integration the information from multiple cell lines. Such a model is expected to substantially improve the QSAR ability from single cell lines, and provide useful clues in developing clinically effective inhibitors and modifications of parent lead compounds for target on the Hedgehog Signaling Pathway. In this study, we have presented: (1) a collaborative QSAR model, which is used to integrate information among multiple cell lines to boost the QSAR results, rather than only a single cell line QSAR modeling. Our experiments have shown that the performance of our model is significantly better than single cell line QSAR methods; and (2) an efficient feature selection strategy under such collaborative environment, which can derive the commonly important features related to the entire given cell lines, while simultaneously showing their specific contributions to a specific cell-line. Based on feature selection results, we have proposed several

  20. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon; Lee, Jung Ae; Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2012-01-01

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  1. NAMPT-mediated salvage synthesis of NAD+ controls morphofunctional changes of macrophages.

    Directory of Open Access Journals (Sweden)

    Gerda Venter

    Full Text Available Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H (i.e. NAD+ and NADH and NADP(H (i.e. NADP+ and NADPH play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT, found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+'s cytosolic role in the regulation of morphofunctional characteristics of macrophages.

  2. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sun Hyun [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Hee Chul, E-mail: rophc@skku.edu [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Do Hoon; Lee, Jung Ae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  3. Characteristics and quality of intra-operative cell salvage in paediatric scoliosis surg