The human milk protein-lipid complex HAMLET sensitizes bacterial pathogens to traditional antimicrobial agents.

PubMed

Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

2012-01-01

The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a natural complex from human milk that kills Streptococcus pneumoniae (the pneumococcus) using a mechanism different from common antibiotics and is immune to resistance-development. In this study we show that sublethal concentrations of HAMLET potentiate the effect of common antibiotics (penicillins, macrolides, and aminoglycosides) against pneumococci. Using MIC assays and short-time killing assays we dramatically reduced the concentrations of antibiotics needed to kill pneumococci, especially for antibiotic-resistant strains that in the presence of HAMLET fell into the clinically sensitive range. Using a biofilm model in vitro and nasopharyngeal colonization in vivo, a combination of HAMLET and antibiotics completely eradicated both biofilms and colonization in mice of both antibiotic-sensitive and resistant strains, something each agent alone was unable to do. HAMLET-potentiation of antibiotics was partially due to increased accessibility of antibiotics to the bacteria, but relied more on calcium import and kinase activation, the same activation pathway HAMLET uses when killing pneumococci by itself. Finally, the sensitizing effect was not confined to species sensitive to HAMLET. The HAMLET-resistant respiratory species Acinetobacter baumanii and Moraxella catarrhalis were all sensitized to various classes of antibiotics in the presence of HAMLET, activating the same mechanism as in pneumococci. Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend

The Human Milk Protein-Lipid Complex HAMLET Sensitizes Bacterial Pathogens to Traditional Antimicrobial Agents

PubMed Central

Marks, Laura R.; Clementi, Emily A.; Hakansson, Anders P.

2012-01-01

The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a natural complex from human milk that kills Streptococcus pneumoniae (the pneumococcus) using a mechanism different from common antibiotics and is immune to resistance-development. In this study we show that sublethal concentrations of HAMLET potentiate the effect of common antibiotics (penicillins, macrolides, and aminoglycosides) against pneumococci. Using MIC assays and short-time killing assays we dramatically reduced the concentrations of antibiotics needed to kill pneumococci, especially for antibiotic-resistant strains that in the presence of HAMLET fell into the clinically sensitive range. Using a biofilm model in vitro and nasopharyngeal colonization in vivo, a combination of HAMLET and antibiotics completely eradicated both biofilms and colonization in mice of both antibiotic-sensitive and resistant strains, something each agent alone was unable to do. HAMLET-potentiation of antibiotics was partially due to increased accessibility of antibiotics to the bacteria, but relied more on calcium import and kinase activation, the same activation pathway HAMLET uses when killing pneumococci by itself. Finally, the sensitizing effect was not confined to species sensitive to HAMLET. The HAMLET-resistant respiratory species Acinetobacter baumanii and Moraxella catarrhalis were all sensitized to various classes of antibiotics in the presence of HAMLET, activating the same mechanism as in pneumococci. Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend

HAMLET interacts with histones and chromatin in tumor cell nuclei.

PubMed

Düringer, Caroline; Hamiche, Ali; Gustafsson, Lotta; Kimura, Hiroshi; Svanborg, Catharina

2003-10-24

HAMLET is a folding variant of human alpha-lactalbumin in an active complex with oleic acid. HAMLET selectively enters tumor cells, accumulates in their nuclei and induces apoptosis-like cell death. This study examined the interactions of HAMLET with nuclear constituents and identified histones as targets. HAMLET was found to bind histone H3 strongly and to lesser extent histones H4 and H2B. The specificity of these interactions was confirmed using BIAcore technology and chromatin assembly assays. In vivo in tumor cells, HAMLET co-localized with histones and perturbed the chromatin structure; HAMLET was found associated with chromatin in an insoluble nuclear fraction resistant to salt extraction. In vitro, HAMLET bound strongly to histones and impaired their deposition on DNA. We conclude that HAMLET interacts with histones and chromatin in tumor cell nuclei and propose that this interaction locks the cells into the death pathway by irreversibly disrupting chromatin organization.

HAMLET. LITERATURE CURRICULUM VI, TEACHER AND STUDENT VERSIONS.

ERIC Educational Resources Information Center

KITZHABER, ALBERT R.

THIS CULMINATING UNIT OF THE 12TH-GRADE OREGON LITERATURE CURRICULUM IS BASED UPON ONE WORK, "HAMLET." THE TEACHER VERSION INCLUDES DISCUSSIONS OF (1) THE RELEVANCE OF HAMLET'S CHARACTER TO MODERN TIMES, (2) THE PROBLEMS IN THE CHARACTERIZATIONS OF THE GHOST, CLAUDIUS, AND HAMLET, (3) THE PLAY'S THREE-PHASE STRUCTURE, (4) THE PLAY'S…

Reading Hamlet. The NCTE Chalkface Series.

ERIC Educational Resources Information Center

Mellor, Bronwyn

This book, for grades 9-12, contains a wealth of ideas and practical activities for studying Shakespeare's "Hamlet." The first section, "Revenge Tragedy," provides background materials to help prepare students to read "Hamlet," including a discussion of revenge tragedies, comparisons to other plays from the period,…

Stability of HAMLET--a kinetically trapped alpha-lactalbumin oleic acid complex.

PubMed

Fast, Jonas; Mossberg, Ann-Kristin; Svanborg, Catharina; Linse, Sara

2005-02-01

The stability toward thermal and urea denaturation was measured for HAMLET (human alpha-lactalbumin made lethal to tumor cells) and alpha-lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than alpha-lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15 degrees C lower for apo HAMLET than for apo alpha-lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than alpha-lactalbumin, although it is a complex of alpha-lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol.

Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

PubMed

Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

2007-09-15

We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.

Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells

PubMed Central

Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

2013-01-01

HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death. PMID:23519119

Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

PubMed

Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

2013-03-21

HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

Shaw on Hamlet

ERIC Educational Resources Information Center

Dukore, Bernard F.

1971-01-01

Shaw's preoccupation with Hamlet resonates in his creative writing. Article documents this statement not only by examining his novels and plays but by searching through prefaces, postscripts, reviews, letters, speeches, etc. that span Shaw's lifetime. (Author/RB)

Targeting of nucleotide-binding proteins by HAMLET--a conserved tumor cell death mechanism.

PubMed

Ho, J C S; Nadeem, A; Rydström, A; Puthia, M; Svanborg, C

2016-02-18

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills tumor cells broadly suggesting that conserved survival pathways are perturbed. We now identify nucleotide-binding proteins as HAMLET binding partners, accounting for about 35% of all HAMLET targets in a protein microarray comprising 8000 human proteins. Target kinases were present in all branches of the Kinome tree, including 26 tyrosine kinases, 10 tyrosine kinase-like kinases, 13 homologs of yeast sterile kinases, 4 casein kinase 1 kinases, 15 containing PKA, PKG, PKC family kinases, 15 calcium/calmodulin-dependent protein kinase kinases and 13 kinases from CDK, MAPK, GSK3, CLK families. HAMLET acted as a broad kinase inhibitor in vitro, as defined in a screen of 347 wild-type, 93 mutant, 19 atypical and 17 lipid kinases. Inhibition of phosphorylation was also detected in extracts from HAMLET-treated lung carcinoma cells. In addition, HAMLET recognized 24 Ras family proteins and bound to Ras, RasL11B and Rap1B on the cytoplasmic face of the plasma membrane. Direct cellular interactions between HAMLET and activated Ras family members including Braf were confirmed by co-immunoprecipitation. As a consequence, oncogenic Ras and Braf activity was inhibited and HAMLET and Braf inhibitors synergistically increased tumor cell death in response to HAMLET. Unlike most small molecule kinase inhibitors, HAMLET showed selectivity for tumor cells in vitro and in vivo. The results identify nucleotide-binding proteins as HAMLET targets and suggest that dysregulation of the ATPase/kinase/GTPase machinery contributes to cell death, following the initial, selective recognition of HAMLET by tumor cells. The findings thus provide a molecular basis for the conserved tumoricidal effect of HAMLET, through dysregulation of kinases and oncogenic GTPases, to which tumor cells are addicted.

Changes in proteasome structure and function caused by HAMLET in tumor cells.

PubMed

Gustafsson, Lotta; Aits, Sonja; Onnerfjord, Patrik; Trulsson, Maria; Storm, Petter; Svanborg, Catharina

2009-01-01

Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells.

HAMLET forms annular oligomers when deposited with phospholipid monolayers.

PubMed

Baumann, Anne; Gjerde, Anja Underhaug; Ying, Ming; Svanborg, Catharina; Holmsen, Holm; Glomm, Wilhelm R; Martinez, Aurora; Halskau, Oyvind

2012-04-20

Recently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75-100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutral pH-as observed by liposome content leakage and circular dichroism experiments-and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, the formation of which is promoted by, but not uniquely dependent on, the oleic acid molecules associated with HAMLET. Copyright © 2012 Elsevier Ltd. All rights reserved.

The inability to mourn and the inability to love in Shakespeare's Hamlet.

PubMed

Bergmann, Martin S

2009-04-01

The author discusses the special role played by Shakespeare's masterpiece Hamlet in the history of psychoanalysis. Freud and many of his followers have treated Hamlet as if he were a real person inhibited by the Oedipus complex. In this presentation, Hamlet is understood as the embodiment of a brilliant artistic endeavor aimed at both revealing and concealing the power of this complex. The author proposes that, if Hamlet is autobiographical, it expresses Shakespeare's inability to mourn and love until a childhood homosexual memory has emerged. Hidden in Hamlet is a cure through the recall of a childhood memory.

New geographic records of Hamlets, Hypoplectrus spp. (Serranidae), in the Caribbean Sea

USGS Publications Warehouse

Williams, Ernest H.; Bunkley-Williams, Lucy; Rogers, Caroline S.; Fenner, Robert

2006-01-01

The exact number of species of hamlets, Hypoplectrus spp., in the Caribbean is controversial and the geographic distributions of these species/forms are poorly documented. We report Curaçao, Netherlands Antilles, as a new locality for the Barred Hamlet, H. puella (Cuvier), and Shy Hamlet, H. guttavarius (Poey); and St. John and St. Thomas, U.S. Virgin Islands, for the Tan Hamlet, Hypoplectrus sp. The Black Hamlet, H. nigricans (Poey), has previously been reported from Curaçao, but we did not see it there.

Noble Gases in the Hamlet Meteorite (LL4)

NASA Astrophysics Data System (ADS)

Amari, S.; Sabe, Y.; Shiraishi, T.; Matsuda, J.

2014-09-01

We analyzed noble gases in a bulk sample and an HF-HCl residue of Hamlet (LL4). The Xe composition of the residue shows that no diamond is contained in the residue. The 20Ne/22Ne ratio of Hamlet Ne-Q has been determined to be 11.0 ± 0.5.

HAMLET interacts with lipid membranes and perturbs their structure and integrity.

PubMed

Mossberg, Ann-Kristin; Puchades, Maja; Halskau, Øyvind; Baumann, Anne; Lanekoff, Ingela; Chao, Yinxia; Martinez, Aurora; Svanborg, Catharina; Karlsson, Roger

2010-02-23

Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded alpha-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure. We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral pH and physiological conditions, as shown by fluorophore leakage experiments. These effects did not occur with either native HLA or a constitutively unfolded Cys-Ala HLA mutant (rHLA(all-Ala)). HAMLET also bound to plasma membrane vesicles formed from intact tumor cells, with accumulation in certain membrane areas, but the complex was not internalized by these vesicles or by the synthetic membrane vesicles. The results illustrate the difference in membrane affinity between the fatty acid bound and fatty acid free forms of partially unfolded HLA and suggest that HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. Furthermore, HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death.

HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

PubMed

Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

2009-03-01

HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

A novel method for preparation of HAMLET-like protein complexes.

PubMed

Permyakov, Sergei E; Knyazeva, Ekaterina L; Leonteva, Marina V; Fadeev, Roman S; Chekanov, Aleksei V; Zhadan, Andrei P; Håkansson, Anders P; Akatov, Vladimir S; Permyakov, Eugene A

2011-09-01

Some natural proteins induce tumor-selective apoptosis. α-Lactalbumin (α-LA), a milk calcium-binding protein, is converted into an antitumor form, called HAMLET/BAMLET, via partial unfolding and association with oleic acid (OA). Besides triggering multiple cell death mechanisms in tumor cells, HAMLET exhibits bactericidal activity against Streptococcus pneumoniae. The existing methods for preparation of active complexes of α-LA with OA employ neutral pH solutions, which greatly limit water solubility of OA. Therefore these methods suffer from low scalability and/or heterogeneity of the resulting α-LA - OA samples. In this study we present a novel method for preparation of α-LA - OA complexes using alkaline conditions that favor aqueous solubility of OA. The unbound OA is removed by precipitation under acidic conditions. The resulting sample, bLA-OA-45, bears 11 OA molecules and exhibits physico-chemical properties similar to those of BAMLET. Cytotoxic activities of bLA-OA-45 against human epidermoid larynx carcinoma and S. pneumoniae D39 cells are close to those of HAMLET. Treatment of S. pneumoniae with bLA-OA-45 or HAMLET induces depolarization and rupture of the membrane. The cells are markedly rescued from death upon pretreatment with an inhibitor of Ca(2+) transport. Hence, the activation mechanisms of S. pneumoniae death are analogous for these two complexes. The developed express method for preparation of active α-LA - OA complex is high-throughput and suited for development of other protein complexes with low-molecular-weight amphiphilic substances possessing valuable cytotoxic properties. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The Hamlet Project.

ERIC Educational Resources Information Center

Dynak, Dave

1998-01-01

Describes a three-week summer theater program for middle and high school students. Discusses the reconstructing of Shakespeare's play "Hamlet" by students in the class from prior viewings of movie versions of the play and from students' past experiences with the play. Includes the play script as rewritten by the students. (CR)

Temporal changes in hamlet communities (Hypoplectrus spp., Serranidae) over 17 years.

PubMed

Hench, K; Mcmillan, W O; Betancur-R, R; Puebla, O

2017-11-01

Transect surveys of hamlet communities (Hypoplectrus spp., Serranidae) covering 14 000 m 2 across 16 reefs off La Parguera, Puerto Rico, are presented and compared with a previous survey conducted in the year 2000. The hamlet community has noticeably changed over 17 years, with a > 30% increase in relative abundance of the yellowtail hamlet Hypoplectrus chlorurus on the inner reefs at the expense of the other hamlet species. The data also suggest that the density of H. chlorurus has declined and that its distribution has shifted towards shallower depths. Considering that H. chlorurus has been previously identified as one of the few fish showing a positive association with seawater turbidity on the inner reefs of La Parguera and that sedimentation of terrestrial origin has increased over recent decades on these reefs, it is proposed that turbidity may constitute an important but so far overlooked ecological driver of hamlet communities. © 2017 The Fisheries Society of the British Isles.

Can misfolded proteins be beneficial? The HAMLET case.

PubMed

Pettersson-Kastberg, Jenny; Aits, Sonja; Gustafsson, Lotta; Mossberg, Anki; Storm, Petter; Trulsson, Maria; Persson, Filip; Mok, K Hun; Svanborg, Catharina

2009-01-01

By changing the three-dimensional structure, a protein can attain new functions, distinct from those of the native protein. Amyloid-forming proteins are one example, in which conformational change may lead to fibril formation and, in many cases, neurodegenerative disease. We have proposed that partial unfolding provides a mechanism to generate new and useful functional variants from a given polypeptide chain. Here we present HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) as an example where partial unfolding and the incorporation of cofactor create a complex with new, beneficial properties. Native alpha-lactalbumin functions as a substrate specifier in lactose synthesis, but when partially unfolded the protein binds oleic acid and forms the tumoricidal HAMLET complex. When the properties of HAMLET were first described they were surprising, as protein folding intermediates and especially amyloid-forming protein intermediates had been regarded as toxic conformations, but since then structural studies have supported functional diversity arising from a change in fold. The properties of HAMLET suggest a mechanism of structure-function variation, which might help the limited number of human protein genes to generate sufficient structural diversity to meet the diverse functional demands of complex organisms.

"By Indirections Find Directions Out": The Soliloquies in Hamlet

ERIC Educational Resources Information Center

Champion, Larry S.

1976-01-01

Article analyzed the soliloquies in Hamlet and showed that Shakespeare used the device of the soliloquy not for clarification (as he did elsewhere) but for complication instead, so that the audience is made to see Hamlet's character as consisting of diverse ingredients, a personality fragmented rather than whole. (Editor/RK)

The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET.

PubMed

Ho, James; Sielaff, Hendrik; Nadeem, Aftab; Svanborg, Catharina; Grüber, Gerhard

2015-05-22

HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected. As shown by fluorescence correlation spectroscopy, HAMLET binds to the F1 domain of the F1F0 ATP synthase with a dissociation constant (KD) of 20.5μM. Increasing concentrations of the tumoricidal protein HAMLET added to the enzymatically active α3β3γ complex of the F-ATP synthase lowered its ATPase activity, demonstrating that HAMLET binding to the F-ATP synthase effects the catalysis of this molecular motor. Single-molecule analysis was applied to study HAMLET-α3β3γ complex interaction. Whereas the α3β3γ complex of the F-ATP synthase rotated in a counterclockwise direction with a mean rotational rate of 3.8±0.7s(-1), no rotation could be observed in the presence of bound HAMLET. Our findings suggest that direct effects of HAMLET on the F-ATP synthase may inhibit ATP-dependent cellular processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

PubMed

Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

2002-08-23

The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

Ruin and Revolution in ``Hamlet."

NASA Astrophysics Data System (ADS)

Usher, P. D.

1999-05-01

In the cosmic allegorical interpretation of Shakespeare's "Hamlet" (BAAS 28, 859 & 1305, 1996; Mercury 26:1, 20, 1997; RPS 18:3, 6, 1997; Giornale di Astronomia 24:3, 27, 1998), the usurper King Claudius, namesake of Ptolemy, personifies geocentricity. Textual support for this reading is found in 1.2 where Hamlet is associated with the Sun, as befits a rightful heir, while Claudius is associated with the Earth. In 3.3 Claudius fears Hamlet's antics. Rosencrantz states that the lives of many depend on the well-being of the King. He warns that if the King were to be imperiled, his subjects, those "ten thousand lesser things", would fall in a "boisterous ruin" along with "each small annexment" and "petty consequence." These 10,000 lesser lights are the naked eye stars (mv ~ 6.5) which would collapse with the demise of the pre-Diggesian firmament, along with ancient planets and their geometrical contrivances. In 5.1 Shakespeare puns on "De revolutionibus" when he refers to "fine revolution." The double meaning of "revolution" (alteration, orbital motion) was in use long before 1600. Since "revolution" is used in the context of digging, it may refer as much to the Diggesian as the Copernican Revolution. Shakespeare's prescience is revealed by his anticipation of change, as encapsulated geocentricity is transformed to stellar boundlessness, while his presence is suggested by fatherly concerns and ghost-like direction.

["I am but mad north-north-west"--Hamlet's portrayed delusion].

PubMed

Schulte Herbrüggen, H

1996-01-01

Whereas science refers to the real world existing independently and conditioned by cause and effect, the world of literature is fictitious, created by the artist in our imagination by means of language, an artefact conditioned by aesthetic laws, a world sui generis. Accordingly, Hamlet is no person, but a literary figure, doing, saying, thinking and feeling only what the poet dictated him word for word. The essential difference between the two worlds is often overlooked. That "blind spot" has a long-standing tradition in European intellectual history and goes back i.a. to the German "Hamlet experience" in the eighteenth, the "Hamlet fever" and the felt spiritual kinship (Seelenverwandtschaft) in the nineteenth century. Teleological literary criticism, centering around Hamlet's "character" and isolating his psychologically evaluated monologues (e.g. Bradley), refrained from Hamlet's fictionality and role-play and led to blurring beyond recognition the boundaries between real person and literary figure (e.g. Freud, Jones) and assisted in reducing a dramatic role to a medical case history. Speaking of Hamlet, one has to start from Shakespeare's text, our subject matter. A dramatic play being a plot turned into dialogue, the poet's vocabulary used (but indirectly also the vocabulary not used) is particularly informative. When referring to Hamlet's "antic disposition", Shakespeare uses a wide range of over 20 different terms, the most frequented being mad/madness (44 times). Evidence of primary importance are the five occasions after the apparition of his father's ghost, when Hamlet speaks of hist "madness" as an assumed role. In Act I "madness occurs first as a mere possibility when Hamlet informs his friends, he might "put an antic disposition on"; in Act II vis-a-vis Rosencrantz and Guildenstern ("I am but mad north-north-west") it is his deliberate action under certain conditions; in Act III it occurs thrice, first in his declaration of intent ("They are coming to

Irony in Tennyson's "Little Hamlet".

ERIC Educational Resources Information Center

Harrison, Antony H.

1981-01-01

Points out similarities between the events and characters of Tennyson's "Maud" and Shakespeare's "Hamlet." Identifies traits which "Maud" shares with Spasmodic poetry. Argues that Tennyson consciously employed these similarities to expose the deficiencies of the Spasmodic school. (DMM)

Leachate Testing of Hamlet City Lake, North Carolina, Sediment

DTIC Science & Technology

1992-11-01

release; distribution is unlimited. 13. ABSTRACT (Maximum 200 words) Sediment leaching studies of Hamlet City Lake, Hamlet, NC, were conducted in...laboratories at the U.S. Army Engineer Waterways Experiment Station. The pur- pose of these studies was to provide quantitative information on the...conditions similar to landfarming. The study involved three elements: batch leach tests, column leach tests, and simulations using the Hydrologic

HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

PubMed

Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

2003-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

A parapraxis in Hamlet. A note on the aesthetic genius of William Shakespeare.

PubMed

Mahon, E

1998-01-01

Shakespeare has placed a parapraxis in Hamlet's mouth in the soliloquy in Act I. Hamlet says, "But two months dead, nay not so much not two." The slip attributed to Hamlet is of course no slip at all when seen as an aesthetic contrivance of the bard's to suggest the tension between warring aspects of Hamlet's psychology. I argue that Shakespeare's artistic methodology, his aesthetic sleight of hand, so to speak, which layers this complex drama with meanings concealing other meanings, supports Freud's notion that an unconscious latent oedipal drama underlies the whole manifest content, imbuing it with subtle but substantial dramatic tension. The slip of the tongue is not only a window into the unconscious of Hamlet that sheds light on the hero's Oedipus complex and the complexities of his attempted resolutions, it is also an example of Shakespeare's aesthetic subtlety at its most refined.

Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

PubMed

Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

Low Resolution Solution Structure of HAMLET and the Importance of Its Alpha-Domains in Tumoricidal Activity

PubMed Central

Ho CS, James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells. PMID:23300861

Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis.

PubMed

Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

2004-05-01

A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.

Translational Implications of Tamil "Hamlets."

ERIC Educational Resources Information Center

Kanakaraj, S.

1994-01-01

Discusses the use of translation when teaching English as a Second Language in a Tamil context. Singles out the fencing episode in Shakespeare's "Hamlet" to illustrate the difficulties of translating cultural aspects. Concludes that successful translations of Shakespeare into Indian languages should involve collaboration between…

Structure and function of human α-lactalbumin made lethal to tumor cells (HAMLET)-type complexes.

PubMed

Mossberg, Ann-Kristin; Hun Mok, Kenneth; Morozova-Roche, Ludmilla A; Svanborg, Catharina

2010-11-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) and equine lysozyme with oleic acid (ELOA) are complexes consisting of protein and fatty acid that exhibit cytotoxic activities, drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s, a wealth of information has been accumulated, illuminating the structural, functional and therapeutic properties of protein complexes with oleic acid, which is summarized in this review. In vitro, both HAMLET and ELOA are produced by using ion-exchange columns preconditioned with oleic acid. However, the complex of human α-lactalbumin with oleic acid with the antitumor activity of HAMLET was found to be naturally present in the acidic fraction of human milk, where it was discovered by serendipity. Structural studies have shown that α-lactalbumin in HAMLET and lysozyme in ELOA are partially unfolded, 'molten-globule'-like, thereby rendering the complexes dynamic and in conformational exchange. HAMLET exists in the monomeric form, whereas ELOA mostly exists as oligomers and the fatty acid stoichiometry varies, with HAMLET holding an average of approximately five oleic acid molecules, whereas ELOA contains a considerably larger number (11- 48). Potent tumoricidal activity is found in both HAMLET and ELOA, and HAMLET has also shown strong potential as an antitumor drug in different in vivo animal models and clinical studies. The gain of new, beneficial function upon partial protein unfolding and fatty acid binding is a remarkable phenomenon, and may reflect a significant generic route of functional diversification of proteins via varying their conformational states and associated ligands. © 2010 The Authors Journal compilation © 2010 FEBS.

HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

PubMed

Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

2006-02-01

HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

Oleic acid is a key cytotoxic component of HAMLET-like complexes.

PubMed

Permyakov, Sergei E; Knyazeva, Ekaterina L; Khasanova, Leysan M; Fadeev, Roman S; Zhadan, Andrei P; Roche-Hakansson, Hazeline; Håkansson, Anders P; Akatov, Vladimir S; Permyakov, Eugene A

2012-01-01

HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, OA complexes with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death for these complexes were analogous to those for HAMLET, and the cytotoxicity of the complexes increased with OA content in the preparations. The half-maximal inhibitory concentration for HEp-2 cells linearly decreased with rise in OA content in the preparations, and OA concentration in the preparations causing HEp-2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic action of these complexes against HEp-2 cells is induced mostly by OA. Thermal stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA-45 complex cannot be ascribed to molten globule-like conformation of the protein component. Overall, the proteinaceous component of HAMLET-like complexes studied is not a prerequisite for their activity; the cytotoxicity of these complexes is mostly due to the action of OA.

Hamlet and psychoanalytic experience.

PubMed

Schwaber, Paul

2007-01-01

Hamlet draws us into its rendered world, enabling us to experience it with depth, awareness, and resonance, in a mode we recognize as aesthetic. By way of Shakespeare's play--primarily the first act--and a detailed case study, aesthetic and psychoanalytic experience are compared, to suggest that, for our own analytic discourse, we revalue Freud's unease that his case studies read like short stories.

Lipids as Tumoricidal Components of Human α-Lactalbumin Made Lethal to Tumor Cells (HAMLET)

PubMed Central

Ho, James C. S.; Storm, Petter; Rydström, Anna; Bowen, Ben; Alsin, Fredrik; Sullivan, Louise; Ambite, Inès; Mok, K. H.; Northen, Trent; Svanborg, Catharina

2013-01-01

Long-chain fatty acids are internalized by receptor-mediated mechanisms or receptor-independent diffusion across cytoplasmic membranes and are utilized as nutrients, building blocks, and signaling intermediates. Here we describe how the association of long-chain fatty acids to a partially unfolded, extracellular protein can alter the presentation to target cells and cellular effects. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin and oleic acid (OA). As OA lacks independent tumoricidal activity at concentrations equimolar to HAMLET, the contribution of the lipid has been debated. We show by natural abundance 13C NMR that the lipid in HAMLET is deprotonated and by chromatography that oleate rather than oleic acid is the relevant HAMLET constituent. Compared with HAMLET, oleate (175 μm) showed weak effects on ion fluxes and gene expression. Unlike HAMLET, which causes metabolic paralysis, fatty acid metabolites were less strongly altered. The functional overlap increased with higher oleate concentrations (500 μm). Cellular responses to OA were weak or absent, suggesting that deprotonation favors cellular interactions of fatty acids. Fatty acids may thus exert some of their essential effects on host cells when in the deprotonated state and when presented in the context of a partially unfolded protein. PMID:23629662

An Analysis of the Termination of Credit Business in Faulkner's "The Hamlet"

ERIC Educational Resources Information Center

Huang, Xiuguo

2015-01-01

Flem's economic reformation especially his replacement of credit business by cash business in Varner's Store in "The Hamlet" marked the social transition from a more traditional, closer and bonded community to a rather detached, rational and mechanical commercial society. The description in "The Hamlet" to a certain extent…

Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex.

PubMed

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L; James, Ho C S; Rydström, Anna; Ngassam, Viviane N; Klausen, Thomas Kjær; Pedersen, Stine Falsig; Lam, Matti; Parikh, Atul N; Svanborg, Catharina

2015-11-12

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ''receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.

Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components.

PubMed

Rath, Emma M; Duff, Anthony P; Håkansson, Anders P; Vacher, Catherine S; Liu, Guo Jun; Knott, Robert B; Church, William Bret

2015-01-01

The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Protein receptor-independent plasma membrane remodeling by HAMLET: A tumoricidal protein-lipid complex

DOE PAGES

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.; ...

2015-11-12

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ‘’protein-centric” view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. Wemore » identify a ‘’receptor independent” transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. In conclusion, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.« less

Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex

PubMed Central

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.; James, Ho C. S.; Rydström, Anna; Ngassam, Viviane N.; Klausen, Thomas Kjær; Pedersen, Stine Falsig; Lam, Matti; Parikh, Atul N.; Svanborg, Catharina

2015-01-01

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ‘’protein-centric” view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ‘’receptor independent” transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death. PMID:26561036

Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

PubMed

Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

2008-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

"Remember Me": Memory and Action in "Hamlet".

ERIC Educational Resources Information Center

Andrews, Michael Cameron

1981-01-01

Examines the relationship between Hamlet's commitments to the past and his failure to translate these commitments into action, as he permits himself to be deflected by preoccupation with the future consequences of his action. Cites supportive evidence from the text. (DMM)

A Sense of Worth: Seven Days with Hamlet.

ERIC Educational Resources Information Center

Harrison, Bernard T.

1984-01-01

Discusses the effectiveness of a week-long teacher inservice workshop on Shakespeare's "Hamlet" in the context of an analysis of participants' responses to a 10-question evaluation of the inservice. (AEA)

The Thing's the Play: Doing "Hamlet."

ERIC Educational Resources Information Center

Sowder, Wilbur H., Jr.

1993-01-01

Argues for the use of film in the teaching of William Shakespeare's "Hamlet" because the play was meant to be seen and heard and not just read. Outlines a method of teaching the play by which students select a scene and perform it. Gives an example of a successful student performance. (HB)

A New Reading of Shakespeare's Hamlet.

NASA Astrophysics Data System (ADS)

Usher, P. D.

1996-12-01

I argue that Hamlet is an allegory for the competition between the cosmological models of the contemporaries Thomas Digges (1546-1595) of England and Tycho Brahe (1546-1601) of Denmark. Through his acquaintance with the Digges' family, Shakespeare would have known of the essential elements of the revolutionary model of Nicholas Copernicus (1473-1543) as well as Digges' extension of it. Prior to 1601 when the writing of Hamlet was completed, Shakespeare knew also of Tycho and his relatives Rosencrantz and Guildenstern, and would have seen that Tycho's hybrid geocentric model was a substantial regression to the well-known geocentricism of Ptolemy (fl. 140 A.D.). It has been suggested that Polonius is named for a fictional character Pollinio, an Aristotelian pedant. I suggest that Claudius is named for Claudius Ptolemy for whom Polonius would have been a suitable attendant. I suggest further that the slaying of Rosencrantz and Guildenstern is the Bard's way of killing the Tychonic model. The slaying of Claudius signals the demise of Ptolemaic geocentricism, both ends being prolonged, the former dramatically, the latter as a matter of historical fact. But the climax of the play is not the slaughter of the chief protagonists; it is the triumphal arrival of Fortinbras from Poland and his timely salute to the ambassadors from England. By means of this apparent incongruity, Shakespeare celebrates the Copernican and Diggesian models and states poetically the nature of the new universal order. I present literary and historical evidence for the present reading which, if essentially correct, suggests that Hamlet evinces a scientific cosmology no less significant than its literary and philosophical counterparts. The last year of the sixteenth century saw the martyrdom of Bruno, but the first year of the next century saw the Bard affirm that there are more things in heaven than were dreamt of in contemporary philosophy.

Where to Be or Not to Be: The Question of Place in "Hamlet"

ERIC Educational Resources Information Center

Golden, John

2009-01-01

The author does not really like "Hamlet." He loves the play, the language, and the characters, but always finds it difficult to teach. Part of this is because he prefers to assign students scenes to perform as they read a Shakespeare text, but Hamlet does not divide nicely into manageable scenes, and he usually does not have enough teenage Ken…

Topographical memory analyzed in mice using the Hamlet test, a novel complex maze.

PubMed

Crouzier, Lucie; Gilabert, Damien; Rossel, Mireille; Trousse, Françoise; Maurice, Tangui

2018-03-01

The Hamlet test is an innovative device providing a complex environment for testing topographic memory in mice. Animals were trained in groups for weeks in a small village with a central agora, streets expanding from it towards five functionalized houses, where they can drink, eat, hide, run, interact with a stranger mouse. Memory was tested by depriving mice from water or food and analyzing their ability to locate the Drink/Eat house. Exploration and memory were analyzed in different strains, gender, and after different training periods and delays. After 2 weeks training, differences in exploration patterns were observed between strains, but not gender. Neuroanatomical structures activated by training, identified using FosB/ΔFosB immunolabelling, showed an involvement of the hippocampus-subiculum-parahippocampal gyrus axis and dopaminergic structures. Training increased hippocampal neurogenesis (cell proliferation and neuronal maturation) and modified the amnesic efficacy of muscarinic or nicotinic cholinergic antagonists. Moreover, topographical disorientation in Alzheimer's disease was addressed using intracerebroventricular injection of amyloid β 25-35 peptide in trained mice. When retested after 7 days, Aβ 25-35 -treated mice showed memory impairment. The Hamlet test specifically allows analysis of topographical memory in mice, based on complex environment. It offers an innovative tool for various ethological or pharmacological research needs. For instance, it allowed to examine topographical disorientation, a warning sign in Alzheimer's disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular mechanisms of the cytotoxicity of human α-lactalbumin made lethal to tumor cells (HAMLET) and other protein-oleic acid complexes.

PubMed

Nakamura, Takashi; Aizawa, Tomoyasu; Kariya, Ryusho; Okada, Seiji; Demura, Makoto; Kawano, Keiichi; Makabe, Koki; Kuwajima, Kunihiro

2013-05-17

Although HAMLET (human α-lactalbumin made lethal to tumor cells), a complex formed by human α-lactalbumin and oleic acid, has a unique apoptotic activity for the selective killing of tumor cells, the molecular mechanisms of expression of the HAMLET activity are not well understood. Therefore, we studied the molecular properties of HAMLET and its goat counterpart, GAMLET (goat α-lactalbumin made lethal to tumor cells), by pulse field gradient NMR and 920-MHz two-dimensional NMR techniques. We also examined the expression of HAMLET-like activities of complexes between oleic acid and other proteins that form a stable molten globule state. We observed that both HAMLET and GAMLET at pH 7.5 were heterogeneous, composed of the native protein, the monomeric molten globule-like state, and the oligomeric species. At pH 2.0 and 50 °C, HAMLET and GAMLET appeared in the monomeric state, and we identified the oleic acid-binding site in the complexes by two-dimensional NMR. Rather surprisingly, the binding site thus identified was markedly different between HAMLET and GAMLET. Furthermore, canine milk lysozyme, apo-myoglobin, and β2-microglobulin all formed the HAMLET-like complex with the anti-tumor activity, when the protein was treated with oleic acid under conditions in which their molten globule states were stable. From these results, we conclude that the protein portion of HAMLET, GAMLET, and the other HAMLET-like protein-oleic acid complexes is not the origin of their cytotoxicity to tumor cells and that the protein portion of these complexes plays a role in the delivery of cytotoxic oleic acid molecules into tumor cells across the cell membrane.

Molecular Mechanisms of the Cytotoxicity of Human α-Lactalbumin Made Lethal to Tumor Cells (HAMLET) and Other Protein-Oleic Acid Complexes*

PubMed Central

Nakamura, Takashi; Aizawa, Tomoyasu; Kariya, Ryusho; Okada, Seiji; Demura, Makoto; Kawano, Keiichi; Makabe, Koki; Kuwajima, Kunihiro

2013-01-01

Although HAMLET (human α-lactalbumin made lethal to tumor cells), a complex formed by human α-lactalbumin and oleic acid, has a unique apoptotic activity for the selective killing of tumor cells, the molecular mechanisms of expression of the HAMLET activity are not well understood. Therefore, we studied the molecular properties of HAMLET and its goat counterpart, GAMLET (goat α-lactalbumin made lethal to tumor cells), by pulse field gradient NMR and 920-MHz two-dimensional NMR techniques. We also examined the expression of HAMLET-like activities of complexes between oleic acid and other proteins that form a stable molten globule state. We observed that both HAMLET and GAMLET at pH 7.5 were heterogeneous, composed of the native protein, the monomeric molten globule-like state, and the oligomeric species. At pH 2.0 and 50 °C, HAMLET and GAMLET appeared in the monomeric state, and we identified the oleic acid-binding site in the complexes by two-dimensional NMR. Rather surprisingly, the binding site thus identified was markedly different between HAMLET and GAMLET. Furthermore, canine milk lysozyme, apo-myoglobin, and β2-microglobulin all formed the HAMLET-like complex with the anti-tumor activity, when the protein was treated with oleic acid under conditions in which their molten globule states were stable. From these results, we conclude that the protein portion of HAMLET, GAMLET, and the other HAMLET-like protein-oleic acid complexes is not the origin of their cytotoxicity to tumor cells and that the protein portion of these complexes plays a role in the delivery of cytotoxic oleic acid molecules into tumor cells across the cell membrane. PMID:23580643

Knowledge, Choice and Consequence: Reading and Teaching "Hamlet."

ERIC Educational Resources Information Center

Baumlin, James S.; Baumlin, Tita French

1990-01-01

Offers a Pyrrhonist reading of "Hamlet." Describes an experiment in teaching that attempts to reconstruct for literature students the prudential-ethical context of human rhetoric, placing "prudentia," or practical wisdom, at the center of their own imaginative involvement. (PRA)

Exploring Shakespeare through the Cinematic Image: Seeing "Hamlet."

ERIC Educational Resources Information Center

Felter, Douglas P.

1993-01-01

Describes an innovative approach to teaching William Shakespeare's "Hamlet" utilizing various film versions of the play. Outlines a method of showing several versions of the same scene from different film adaptations. Describes student reaction to the variations among the different films. (HB)

The Tragedy of Hamlet, Son of an Organic Chemist of Denmark

NASA Astrophysics Data System (ADS)

Brisbois, Ronald G.

2004-04-01

Once faced with structure reactivity relationships in the context of nucleophilic substitution at sp 3 carbon, introductory organic chemistry students must compare and contrast the various attributes and ramifications of S N 2 versus S N 1 reaction pathways. The dramatic (even melodramatic) way in which some students ask such comparative questions inspired a parody of Hamlet's famous to be or not to be soliloquy. Herein, Hamlet (the son of an organic chemist of Denmark) is the surrogate of any and every student as he uses a thoroughly Shakespearian approach to sorting out some of the key distinguishing features of S N 2 versus S N 1 reactions.

Hamlet in Freud's Thoughts: Reinterpretations in the Psychoanalytic Literature.

ERIC Educational Resources Information Center

Diaz de Chumaceiro, Cora L.

1998-01-01

Presents a selection of interpretations in the psychoanalytic literature of "Hamlet," by William Shakespeare, beginning with an extensive look at the role this literature played in Sigmund Freud's mind at the origins of psychoanalysis. Also examines later interpretations. (SR)

The Evaluation and Treatment of Delayed Ejaculation.

PubMed

Shin, Daniel H; Spitz, Aaron

2014-10-01

Delayed ejaculation is a small but important subsection of ejaculatory dysfunction, with prevalence estimated at 1-4%. It is most commonly defined by DSM-IV-TR criteria, as "a persistent delay in, or absence of, orgasm in a male following a normal sexual excitement phase during sexual activity that the clinician, taking into account the person's age, judges to be adequate in focus, intensity, and duration." The pathophysiology of delayed ejaculation is related to disruptions in ejaculatory apparatus, nervous transmission, hormonal or neurochemical ejaculatory control, or psychosocial factors. To update the clinician on the evaluation and treatment of delayed ejaculation. The keywords "delayed ejaculation" and "retarded ejaculation" were utilized to search Pubmed for relevant publications. 319 results were generated from the search, and those publications judged relevant to the pathophysiology, epidemiology, evaluation, and treatment of delayed ejaculation were included in the review. 110 articles were ultimately selected for inclusion in this review. The evaluation of this condition requires a focused history and physical, which includes a detailed sexual history, examination of the genitalia, and inquiry into the status of the partner. Laboratory tests are aimed at the detection of abnormalities in the blood count, glucose level, hormone levels, or kidney function. If a correctable etiology is discovered, treatment is directed towards the reversal of this condition. In some cases, the delayed ejaculation may be a lifelong problem. Also, in some cases the etiology of the delayed ejaculation may be irreversible, such as in the case of age-related sensation loss or diabetes-related neuropathy. In these instances treatment may require a combination of behavioral modification, sexual therapy, or perhaps pharmaceutical drugs. Participation of the partner in therapy may sometimes be necessary. Future investigations will continue to elucidate the complex biological and

IDEA: An Interdisciplinary Unit Comparing "Don Quixote" to "Hamlet."

ERIC Educational Resources Information Center

Harris, Mary J. G.

2001-01-01

Describes an idea for teaching language through content-based instruction in which a high school Spanish class studying a shortened abridged version of Cervantes'"Don Quixote" and an English class reading Shakespeare's "Hamlet," did a simple comparative analysis of the two texts. (Author/VWL)

Who is Mr. HAMLET? Interaction of human alpha-lactalbumin with monomeric oleic acid.

PubMed

Knyazeva, Ekaterina L; Grishchenko, Valery M; Fadeev, Roman S; Akatov, Vladimir S; Permyakov, Sergei E; Permyakov, Eugene A

2008-12-09

A specific state of the human milk Ca(2+) binding protein alpha-lactalbumin (hLA) complexed with oleic acid (OA) prepared using an OA-pretreated ion-exchange column (HAMLET) triggers several cell death pathways in various tumor cells. The possibility of preparing a hLA-OA complex with structural and cytotoxic properties similar to those of the HAMLET but under solution conditions has been explored. The complex was formed by titration of hLA by OA at pH 8.3 up to OA critical micelle concentration. We have shown that complex formation strongly depends on calcium, ionic strength, and temperature; the optimal conditions were established. The spectrofluorimetrically estimated number of OA molecules irreversibly bound per hLA molecule (after dialysis of the OA-loaded preparation against water followed by lyophilization) depends upon temperature: 2.9 at 17 degrees C (native apo-hLA; resulting complex referred to as LA-OA-17 state) and 9 at 45 degrees C (thermally unfolded apo-hLA; LA-OA-45). Intrinsic tryptophan fluorescence measurements revealed substantially decreased thermal stability of Ca(2+)-free forms of HAMLET, LA-OA-45, and OA-saturated protein. The irreversibly bound OA does not affect the Ca(2+) association constant of the protein. Phase plot analysis of fluorimetric and CD data indicates that the OA binding process involves several hLA intermediates. The effective pseudoequilibrium OA association constants for Ca(2+)-free hLA were estimated. The far-UV CD spectra of Ca(2+)-free hLA show that all OA-bound forms of the protein are characterized by elevated content of alpha-helical structure. The various hLA-OA complexes possess similar cytotoxic activities against human epidermoid larynx carcinoma cells. Overall, the LA-OA-45 complex possesses physicochemical, structural, and cytotoxic properties closely resembling those of HAMLET. The fact that the HAMLET-like complex can be formed in aqueous solution makes the process of its preparation more transparent and

Sensitization of Staphylococcus aureus to Methicillin and Other Antibiotics In Vitro and In Vivo in the Presence of HAMLET

PubMed Central

Marks, Laura R.; Clementi, Emily A.; Hakansson, Anders P.

2013-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus. PMID:23650551

Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

PubMed

Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

2013-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

Ecological wisdom of Hindu-Javanese community settlement in Cetho Hamlet, Lawu Mountains, Central Java, Indonesia

NASA Astrophysics Data System (ADS)

Ikhsan, Fauzan Ali; Setioko, Bambang; Suprapti, Atiek

2017-12-01

Dwelling culture of Java community has a long history. In Javanese community point of view, Javanese culture is not a homogeneous entity. There is a diversity characteristic of a regional nature of Javanese culture, which is caused by differences in the natural environment on the island of Java. Dwelling Culture settled in the mountains is a variant form of Javanese culture that has its own uniqueness. This study aimed to describe the local values of the rural settlement structure of in Lawu mountains with Hindu-Javanese culture background. This study used a qualitative approach with case study strategy. The locus of research is in the Cetho hamlet on the slopes of Mount Lawu Karanganyar, Central Java. The results showed that local values in the neighborhoods of Cetho hamlet is based on the Memayu Hayuning Bawana philosophy. These concepts are abstracted into various aspects of settlements in Cetho hamlet such as aspects of dwelling house setting, water management, and ritual activities related to environmental management. Memayu Hayuning Bawana philosophy becomes a cultural space coloring the ecological action of the population of Cetho hamlet. The comprehensive motivation of ecological action ultimately leads to one final goal, namely the desire to maintain a harmonic atmosphere with the surroundings.

Hamlet on the Macintosh: An Experimental Seminar That Worked.

ERIC Educational Resources Information Center

Strange, William C.

1987-01-01

Describes experimental college Shakespeare seminar that used Macintosh computers and software called ELIZA and ADVENTURE to develop character dialogs and adventure games based on Hamlet's characters and plots. Programming languages are examined, particularly their relationship to metaphor, and the use of computers in humanities is discussed. (LRW)

Curricular Deliberation about "Hamlet": An Exercise in the Practical.

ERIC Educational Resources Information Center

Siegel, Judith Susan

This study attempts to clarify and exploit Joseph Schwab's recent and current work on "practical" and "eclectic" curriculums in a simulated deliberation about a concrete curricular question, How might "Hamlet" be taught to one group of high school juniors? By exemplifying curricular deliberation, it aims to clarify…

A Country Discovered: Upper Juniors Explore Meanings in "Hamlet."

ERIC Educational Resources Information Center

Carter, Dennis

1989-01-01

Describes a project in England in which a class of 9- to 11-year olds enthusiastically and successfully explored the play "Hamlet" by writing about, discussing, performing, and visually interpreting the actual text. The teacher suggests that, with a little creativity, Shakespeare is very accessible to children. (SM)

Lipids as tumoricidal components of human α-lactalbumin made lethal to tumor cells (HAMLET): unique and shared effects on signaling and death.

PubMed

Ho, James C S; Storm, Petter; Rydström, Anna; Bowen, Ben; Alsin, Fredrik; Sullivan, Louise; Ambite, Inès; Mok, K H; Northen, Trent; Svanborg, Catharina

2013-06-14

Long-chain fatty acids are internalized by receptor-mediated mechanisms or receptor-independent diffusion across cytoplasmic membranes and are utilized as nutrients, building blocks, and signaling intermediates. Here we describe how the association of long-chain fatty acids to a partially unfolded, extracellular protein can alter the presentation to target cells and cellular effects. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin and oleic acid (OA). As OA lacks independent tumoricidal activity at concentrations equimolar to HAMLET, the contribution of the lipid has been debated. We show by natural abundance (13)C NMR that the lipid in HAMLET is deprotonated and by chromatography that oleate rather than oleic acid is the relevant HAMLET constituent. Compared with HAMLET, oleate (175 μm) showed weak effects on ion fluxes and gene expression. Unlike HAMLET, which causes metabolic paralysis, fatty acid metabolites were less strongly altered. The functional overlap increased with higher oleate concentrations (500 μm). Cellular responses to OA were weak or absent, suggesting that deprotonation favors cellular interactions of fatty acids. Fatty acids may thus exert some of their essential effects on host cells when in the deprotonated state and when presented in the context of a partially unfolded protein.

Harriot, Digges, and the Ghost in Hamlet.

NASA Astrophysics Data System (ADS)

Usher, P. D.

1998-12-01

The cosmic allegorical interpretation of Hamlet (BAAS 28, 1305, 1996; 29, 1262, 1997; Giornale di Astronomia 24:3, 27, 1998) may be regarded as a Galilean postulatum with testable consequences. It associates leading characters in the play with cosmologists from the time of Ptolemy (Claudius) to Tycho Brahe (Rosencrantz and Guildenstern) and Thomas Digges (Hamlet). Lines 3.3.8-23 describe how the concepts of geocentricism and the sphere of fixed stars shared by the Ptolemaic and Tychonic models are imperiled by the Infinite Universe of Digges. Hitherto baffling lines 5.2.100-125 list in short order at least 16 attributes of Thomas Harriot, including his short bibliography (``soul of great article'') which may explain why he receives mention only in passing. The Ghost is Thomas Digges' father Leonard, who is a ``mole'' in the ``cellarage.'' That Leonard may have gone underground following restoration of his lands is supported by the range of years (1559-1574) of his alleged death, and conspicuous absence of a gravesite. Circumstances of his disappearance have remained mysterious (N&Q 2:X, 162, 1860; 6:X, 368, 515, 1884; 8:V, 186, 1894.) I suggest that, having been saved from execution and restored to gentility, he continued to work, writing in the tradition of his confrere's father Thomas Wyatt, Sr. who pioneered the English sonnet. The first Dowden series of sonnets reflects his love for his only child. The history of the perspective glass explains lines in Sonnets 14 and 103 (``my blunt invention'') and in the I.M.S. encomium wherein he did ``rowle back the heavens'' with a ``cleere and equall surface'' that is ``reflecting ages past.'' A portrait of Tycho helps date Sonnet 16 to between 1581 and 1585. Sonnets 18 and 87 would date to 1583 and 1595. Allusions to old age are not surprising. I.M.'s words: ``Wee wondred (Shake-speare) that thou went'st so soone'' and ``An Actors Art, can dye, and liue to acte a second part'' are explained, as are sources for The

Hamlet's Suicide Soliloquy: A Case Study in Suicide Ideology.

ERIC Educational Resources Information Center

Jenkins, Andrew P.

This paper presents a secondary-level teaching technique that can be used in an integrated English and health education curriculum. The exercise provides students and teachers with a case study of a suicidal person for the purpose of teaching the warning signs of suicide, appropriate questioning, and referral skills. The case study uses Hamlet's…

Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.

PubMed

Hofmeijer, Jeannette; Kappelle, L Jaap; Algra, Ale; Amelink, G Johan; van Gijn, Jan; van der Worp, H Bart

2009-04-01

Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66). Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset

"Hamlet": Something Is Tragic in the State of Denmark.

ERIC Educational Resources Information Center

Fisher, Jessica

This unit seeks to teach Shakespeare's "Hamlet" in a way that the students will have a full understanding of the play. The unit's introduction is designed to get the students acquainted with Shakespeare's language, to motivate them to read the play, and to make them feel confident about approaching the play. Lessons in the unit are fun,…

"Hamlet" Meets "Chushingura": Traditions of the Revenge Tragedy. [Lesson Plan].

ERIC Educational Resources Information Center

2002

This lesson seeks to sensitize students to the similarities and difference between cultures by comparing the Shakespearean and the Bunraki/Kabuki dramas of Japan. In the lesson, the focus of this comparison is the complex nature of revenge explored in "The Tragedy of Hamlet, Prince of Denmark" and "Chusingura," or "The…

Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

PubMed

Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

2004-03-15

The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

"The Hound of the Baskervilles" and "Hamlet": Guide for Educators.

ERIC Educational Resources Information Center

KIDSNET, Washington, DC.

This study guide discusses the world premiere of two made-for-television movies of classics of English literature: "The Hound of the Baskervilles" and "Hamlet." The guide first provides a synopsis of the story of "The Hound of the Baskervilles" and gives a brief biography of the author, Sir Arthur Conan Doyle. It…

"The Lion King" and "Hamlet": A Homecoming for the Exiled Child.

ERIC Educational Resources Information Center

Gavin, Rosemarie

1996-01-01

Explains how the movie "The Lion King" may be used to elucidate Shakespeare's "Hamlet," a play about a prince who does not always seem heroic to modern audiences. Gives specific points of comparison between the two works concerning heroes, characters, conflicts, themes, ending scenes, and archetypal patterns. (TB)

Constructing Knowledge from an Ill-Structured Domain: Testing a Multimedia Hamlet.

ERIC Educational Resources Information Center

Barnes, William G. W.

How a multimedia program that employs concept maps and hypertext for teaching "Hamlet" facilitated comprehension in an undergraduate course is described. Results suggest factors that instructional designers should take into account to improve learning. Thirty-six upper-division college students were enrolled in a course on Shakespeare at…

p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents.

PubMed

Lafarga, Vanesa; Cuadrado, Ana; Nebreda, Angel R

2007-10-01

Cells organize appropriate responses to environmental cues by activating specific signaling networks. Two proteins that play key roles in coordinating stress responses are the kinase p38alpha (MAPK14) and the transcription factor p53 (TP53). Depending on the nature and the extent of the stress-induced damage, cells may respond by arresting the cell cycle or by undergoing cell death, and these responses are usually associated with the phosphorylation of particular substrates by p38alpha as well as the activation of specific target genes by p53. We recently characterized a new p38alpha substrate, named p18(Hamlet) (ZNHIT1), which mediates p53-dependent responses to different genotoxic stresses. Thus, cisplatin or UV light induce stabilization of the p18(Hamlet) protein, which then enhances the ability of p53 to bind to and activate the promoters of pro-apoptotic genes such as NOXA and PUMA leading to apoptosis induction. In a similar way, we report here that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).

Coagulation syndrome: Delayed perforation after colorectal endoscopic treatments

PubMed Central

Hirasawa, Kingo; Sato, Chiko; Makazu, Makomo; Kaneko, Hiroaki; Kobayashi, Ryosuke; Kokawa, Atsushi; Maeda, Shin

2015-01-01

Various procedure-related adverse events related to colonoscopic treatment have been reported. Previous studies on the complications of colonoscopic treatment have focused primarily on perforation or bleeding. Coagulation syndrome (CS), which is synonymous with transmural burn syndrome following endoscopic treatment, is another typical adverse event. CS is the result of electrocoagulation injury to the bowel wall that induces a transmural burn and localized peritonitis resulting in serosal inflammation. CS occurs after polypectomy, endoscopic mucosal resection (EMR), and even endoscopic submucosal dissection (ESD). The occurrence of CS after polypectomy or EMR varies according previous reports; most report an occurrence rate around 1%. However, artificial ulcers after ESD are largely theoretical, and CS following ESD was reported in about 9% of cases, which is higher than that for CS after polypectomy or EMR. Most cases of post-polypectomy syndrome (PPS) have an excellent prognosis, and they are managed conservatively with medical therapy. PPS rarely develops into delayed perforation. Delayed perforation is a severe adverse event that often requires emergency surgery. Since few studies have reported on CS and delayed perforation associated with CS, we focused on CS after colonoscopic treatments in this review. Clinicians should consider delayed perforation in CS patients. PMID:26380051

Delayed Ejaculation: Pathophysiology, Diagnosis, and Treatment

PubMed Central

2018-01-01

Delayed ejaculation (DE) is a poorly defined and uncommon form of male sexual dysfunction, characterized by a marked delay in ejaculation or an inability to achieve ejaculation. It is often quite concerning to patients and their partners, and sometimes frustrates couples' attempts to conceive. This article aims to review the pathophysiology of DE and anejaculation (AE), to explore our current understanding of the diagnosis, and to present the treatment options for this condition. Electronic databases were searched from 1966 to October 2017, including PubMed (MEDLINE) and Embase. We combined “delayed ejaculation,” “retarded ejaculation,” “inhibited ejaculation,” or “anejaculation” as Medical Subject Headings (MeSH) terms or keywords with “epidemiology,” “etiology,” “pathophysiology,” “clinical assessment,” “diagnosis,” or “treatment.” Relevant sexual medicine textbooks were searched as well. The literature suggests that the pathophysiology of DE/AE is multifactorial, including both organic and psychosocial factors. Despite the many publications on this condition, the exact pathogenesis is not yet known. There is currently no single gold standard for diagnosing DE/AE, as operationalized criteria do not exist. The history is the key to the diagnosis. Treatment should be cause-specific. There are many approaches to treatment planning, including various psychological interventions, pharmacotherapy, and specific treatments for infertile men. An approved form of drug therapy does not exist. A number of approaches can be employed for infertile men, including the collection of nocturnal emissions, prostatic massage, prostatic urethra catheterization, penile vibratory stimulation, probe electroejaculation, sperm retrieval by aspiration from either the vas deferens or the epididymis, and testicular sperm extraction. PMID:29299903

Municipalities' Priority Problems and Prospect of Establishing Ordinance to Measures for Marginal Hamlets

NASA Astrophysics Data System (ADS)

Nakanishi, Mayumi; Hoshino, Satoshi; Hashimoto, Shizuka; Kuki, Yasuaki

The problems of Marginal Hamlets are getting worse, in which more than half of the population is over 65 and community-based life is difficult. To contribute to effective policy making, we conducted a questionnaire survey to members of the National Liaison Council of ‘Suigen no Sato’ constituted to share information about problems and effective counter measures for marginal hamlets. Our study clarified that first, most of respondents had common problems such as lack of job-opportunities and animal damage on farm, and second, though most of respondents recognized the effectiveness of selecting target communities in policy implementations, it is difficult for municipal governments to establish such ordinance provided that councilors and those who were not living in areas of policy target wouldn't agree with it. Finally, we pointed out the roles of national and prefectural governments to help municipal governments effectively cope with such entangled situations.

Alpha-lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

PubMed

Svensson, Malin; Fast, Jonas; Mossberg, Ann-Kristin; Düringer, Caroline; Gustafsson, Lotta; Hallgren, Oskar; Brooks, Charles L; Berliner, Lawrence; Linse, Sara; Svanborg, Catharina

2003-12-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex of human alpha-lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from alpha-lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of alpha-lactalbumin is sufficient to induce cell death. We used the bovine alpha-lactalbumin Ca(2+) site mutant D87A, which is unable to bind Ca(2+), and thus remains partially unfolded regardless of solvent conditions. The D87A mutant protein was found to be inactive in the apoptosis assay, but could readily be converted to a HAMLET-like complex in the presence of oleic acid. BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) and D87A-BAMLET complexes were both able to kill tumor cells. This activity was independent of the Ca(2+)site, as HAMLET maintained a high affinity for Ca(2+) but D87A-BAMLET was active with no Ca(2+) bound. We conclude that partial unfolding of alpha-lactalbumin is necessary but not sufficient to trigger cell death, and that the activity of HAMLET is defined both by the protein and the lipid cofactor. Furthermore, a functional Ca(2+)-binding site is not required for conversion of alpha-lactalbumin to the active complex or to cause cell death. This suggests that the lipid cofactor stabilizes the altered fold without interfering with the Ca(2+)site.

Delay in Presentation, Diagnosis, and Treatment for Breast Cancer Patients in Jordan.

PubMed

Abu-Helalah, Ahmad Munir; Alshraideh, Hussam Ahmad; Al-Hanaqtah, Mo'tasem; Da'na, Moh'd; Al-Omari, Asim; Mubaidin, Rasmi

2016-01-01

Breast cancer is the most common cancer, and one of the leading causes of death for females in Jordan and many countries in the world. Studies have shown that delay in symptoms presentation, diagnosis or treatment would result in poor prognosis. There has been no published study from Jordan on delays in patient presentation, delays in diagnosis, or delays in treatment. Therefore, we conducted this study to assess these important quality indicators aiming to improve prognosis for breast cancer patients in Jordan. This project was a cross-sectional study on female breast cancer patients in Jordan. The total number of participants was 327. The proportion of patients with presentation delay, diagnosis delay, and treatment delay was 32.2%, 49.1%, or 32.4%, respectively. The main reported reasons for delay in presentation were ignorance of the nature of the problem (65.6%), limited/lack of knowledge that symptoms were suggestive of cancer diagnosis (16.7%), and misdiagnosis (16.7%). Predictors of delay and mean time for presentation, diagnosis, and treatment were identified. Our results reveal that breast cancer patients in Jordan are experiencing delays in presentation, diagnosis, and treatment. This could justify the advanced stages at diagnosis and poor outcomes for breast cancer patients in Jordan. We recommend revising the current early detection and down-staging programs in Jordan. © 2015 Wiley Periodicals, Inc.

"Hamlet" and the Elizabethan Revenge Ethic in Text and Film. [Lesson Plan].

ERIC Educational Resources Information Center

2002

This lesson seeks to sensitize students to the complex nature of revenge as it is portrayed in William Shakespeare's "The Tragedy of Hamlet, Prince of Denmark." In the lesson, students learn how Shakespeare's play interprets Elizabethan attitudes toward revenge, as reflected in the structure of the Elizabethan revenge tragedy, one of the…

The drug treatment of delayed ejaculation

PubMed Central

Elsaied, Moustafa A.; Mostafa, Taymour

2016-01-01

Delayed ejaculation (DE) is an uncommon and a challenging disorder to treat. It is often quite concerning to patients and it can affect psychosocial well-being. Here we reviewed how DE is treated pharmacologically .We also highlighted specific settings where drugs could be introduced to medical practice. Electronic databases were searched from 1966 to February 2016, including PubMed MEDLINE, EMBASE, EBCSO Academic Search Complete, Cochrane Systematic Reviews Database, and Google Scholar using key words; delayed ejaculation, retarded ejaculation, inhibited ejaculation, drugs, treatment, or pharmacology. To achieve the maximum sensitivity of the search strategy and to identify all studies, we combined “delayed ejaculation” as Medical Subject Headings (MeSH) terms or keywords with each of “testosterone” or “cabergoline” or “bupropion” or “amantadine” or “cyproheptadine” or “midodrine” or “imipramine” or “ephedrine” or “pseudoephedrine” or “yohimbine” or “buspirone” or “oxytocin” or “bethanechol” as MeSH terms or keywords. There are a number of drugs to treat patients with DE including: testosterone, cabergoline, bupropion, amantadine, cyproheptadine, midodrine, imipramine, ephedrine, pseudoephedrine, yohimbine, buspirone, oxytocin, and bethanechol. Although there are many pharmacological treatment options, the evidence is still limited to small trials, case series or case reports. Review of literature showed that evidence level 1 (Double blind randomized clinical trial) studies were performed with testosterone, oxytocin, buspirone or bethanechol treatment. It is concluded that successful drug treatment of DE is still in its infancy. The clinicians need to be aware of the pathogenesis of DE and the pharmacological basis underlying the use of different drugs to extend better care for these patients. Various drugs are available to address such problem, however their evidence of efficacy is still limited and their

The "Strange Alteration" of "Hamlet": Comic Books, Adaptation and Constructions of Adolescent Literacy

ERIC Educational Resources Information Center

Sabeti, Shari

2014-01-01

This article examines two comic book adaptations of Shakespeare's "Hamlet" produced for teenage readers and used in school classrooms. It seeks to understand the ways in which particular kinds of literacy are being implied and constructed through the textual practice of multimodal adaptation. It presents a close reading of sections of…

The Impact of Delays on Parents' Perceptions of Treatments for Problem Behavior

ERIC Educational Resources Information Center

Call, Nathan A.; Reavis, Andrea R.; McCracken, Courtney E.; Gillespie, Scott E.; Scheithauer, Mindy C.

2015-01-01

Parent engagement in behavioral interventions is critical for treatments to succeed. Parental decision-making regarding treatments can be impacted by systematic biases, such as the tendency to discount the value of delayed benefits, or "delay discounting". This study examined the impact of delay discounting on parents' perceptions of…

A study on delay in treatment of kala-azar patients in Bangladesh.

PubMed

Arif, Syed M; Basher, Ariful; Rahman, Mohammad R; Faiz, Mohammad A

2012-01-01

Visceral leishmaniasis (kala-azar) continues to be a major rural public health problem in Bangladesh. A cross-sectional study was carried out in two subdistricts of Mymensingh district from January 2006 to June 2007 to evaluate the delay kala-azar treatment. Suspected patients who attended to out patient department (OPD) were subjected to a dipstick test (RK39) for kala-azar. Sixty five from Bhaluka and 60 positive patients from Gafargaon subdistrict were enrolled. Most of the patients (80%) first visited nonqualified private practitioners, while only 15.2% consulted registered doctors. Fifty per cent were referred to the Upazilla health complex (UZHC) by the family members or relatives. About 49% and 43% patients required third and second health-care providers for kala-azar treatment, respectively. Patient delay ranged from 2 to 30 days; median 4 (IQR 3 to 7 days), the system delay ranged from 0 days to 225 days; median 54 (IQR 40-66 days). Residential status (p value <0.05) had impact on patient delay. Educational status and number of treatment providers had impact on system delay (p<0.05). System delay rather than patient delay is the important weakness of the kala-azar control programme in Bangladesh. Residence in rural areas, low educational background and treatment providers are associated with these delays. A proper educational programme may reduce the delay.

Hip-Hop Hamlet: Hybrid Interpretive Discourse in a Suburban High School English Class

ERIC Educational Resources Information Center

Anglin, Joanna L.; Smagorinsky, Peter

2014-01-01

This study investigates the collaborative composing processes of a group of five high school seniors who constructed interpretations of each of the five acts of Shakespeare's Hamlet through the medium of spoken word performances. The group composing processes were analyzed to identify how the students drew on conventions from the spoken word…

Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

PubMed

Hakansson, Anders P; Roche-Hakansson, Hazeline; Mossberg, Ann-Kristin; Svanborg, Catharina

2011-03-10

Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.

Does Hamlet Belong in Freshman Composition? The Debatable Role of Canonical Literature in Composition

ERIC Educational Resources Information Center

Fitzwilliam, Marie A.

2006-01-01

The question of whether "Hamlet" belongs in a freshman composition classroom is one that institutions are making easier to answer, though perhaps for political rather than pedagogical reasons. This article describes a project in which Marie Fitzwilliam and her colleagues were asked to engage in a dialogue with the administration on…

Applications of site-specific labeling to study HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

PubMed

Mercer, Natalia; Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Qasba, Pradman K

2011-01-01

Alpha-lactalbumin (α-LA) is a calcium-bound mammary gland-specific protein that is found in milk. This protein is a modulator of β1,4-galactosyltransferase enzyme, changing its acceptor specificity from N-acetyl-glucosamine to glucose, to produce lactose, milk's main carbohydrate. When calcium is removed from α-LA, it adopts a molten globule form, and this form, interestingly, when complexed with oleic acid (OA) acquires tumoricidal activity. Such a complex made from human α-LA (hLA) is known as HAMLET (Human A-lactalbumin Made Lethal to Tumor cells), and its tumoricidal activity has been well established. In the present work, we have used site-specific labeling, a technique previously developed in our laboratory, to label HAMLET with biotin, or a fluoroprobe for confocal microscopy studies. In addition to full length hLA, the α-domain of hLA (αD-hLA) alone is also included in the present study. We have engineered these proteins with a 17-amino acid C-terminal extension (hLA-ext and αD-hLA-ext). A single Thr residue in this extension is glycosylated with 2-acetonyl-galactose (C2-keto-galactose) using polypeptide-α-N-acetylgalactosaminyltransferase II (ppGalNAc-T2) and further conjugated with aminooxy-derivatives of fluoroprobe or biotin molecules. We found that the molten globule form of hLA and αD-hLA proteins, with or without C-terminal extension, and with and without the conjugated fluoroprobe or biotin molecule, readily form a complex with OA and exhibits tumoricidal activity similar to HAMLET made with full-length hLA protein. The confocal microscopy studies with fluoroprobe-labeled samples show that these proteins are internalized into the cells and found even in the nucleus only when they are complexed with OA. The HAMLET conjugated with a single biotin molecule will be a useful tool to identify the cellular components that are involved with it in the tumoricidal activity.

Apoptosis-Like Death in Bacteria Induced by HAMLET, a Human Milk Lipid-Protein Complex

PubMed Central

Hakansson, Anders P.; Roche-Hakansson, Hazeline; Mossberg, Ann-Kristin; Svanborg, Catharina

2011-01-01

Background Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. Methodology/Principal Findings We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Conclusions/Significance Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells. PMID:21423701

Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

PubMed

Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

2014-04-04

α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

PEMF as treatment for delayed healing of foot and ankle arthrodesis.

PubMed

Saltzman, Charles; Lightfoot, Andrew; Amendola, Annunziato

2004-11-01

Arthrodesis is the most common surgical treatment for foot and ankle arthritis. In adults, these procedures are associated with a 5% to 10% rate of nonunion. Pulsed electromagnetic field (PEMF) stimulation was approved by the Federal Drug Administration (FDA) for treatment of delayed unions after long-bone fractures and joint arthrodesis. The purpose of this study was to examine the results of PEMF treatment for delayed healing after foot and ankle arthrodesis. Three hundred and thirty-four foot and ankle arthrodeses were done. Nineteen resulted in delayed unions that were treated with a protocol of immobilization, limited weightbearing, and PEMF stimulation for a median of 7 (range 5 to 27) months. All patients were followed clinically and radiographically. The use of PEMF, immobilization, and limited weightbearing to treat delayed union after foot and ankle arthrodesis was successful in 5 of 19 (26%) patients. Of the other 14 patients with nonunions, nine had revision surgery with autogenous grafting, continued immobilization, and PEMF stimulation. Seven of these eventually healed at a median of 5.5 (range 2 to 26) months and two did not heal. One patient had a below-knee amputation, and four refused further treatment. The protocol of PEMF, immobilization, and limited weightbearing had a relatively low success rate in this group of patients. We no longer use this protocol alone to treat delayed union after foot and ankle arthrodesis.

Influence of age on delayed surgical treatment of proximal femoral fractures

PubMed Central

Gomes, Lisiane Pinto; do Nascimento, Leandra Delfim; Campos, Tulio Vinicius de Oliveira; Paiva, Edson Barreto; de Andrade, Marco Antonio Percope; Guimarães, Henrique Cerqueira

2015-01-01

ABSTRACT OBJECTIVE : To investigate the influence of patients' age on the delay between diagnosis and surgical treatment of proximal femoral fractures METHODS : This is a retrospective study, con-ducted at a tertiary university hospital, including all patients admitted with proximal femoral fractures between March 2013 and March 2014. The participants were categorized into four groups according to age levels. The groups were compared according to demographics, comorbidities, fracture type, trau-ma circumstances, and time between diagnosis and surgical procedure RESULTS : One hundred and sixty one patients were included, 37 adults and 124 elderly. Among adults, the mean delay between diagnosis and surgical procedure was 6.4±5.3 days; among elderly the delay was 9.5±7.6 days. There was a progressive increase in the delay from the young-adults group through the elderly individuals (Kruskal-Wallis: 13.7; p=0.003) CONCLUSION : In spite of being the patients most susceptible to complications due to surgical delay, the elderly individuals pre-sented the longest delays from admission to surgical treatment. Level of Evidence III, Retrospective Study. PMID:27057145

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

PubMed

Sánchez Fernández, I; Gaínza-Lein, M; Abend, N S; Anderson, A E; Arya, R; Brenton, J N; Carpenter, J L; Chapman, K E; Clark, J; Gaillard, W D; Glauser, T A; Goldstein, J L; Goodkin, H P; Helseth, A R; Jackson, M C; Kapur, K; Lai, Y-C; McDonough, T L; Mikati, M A; Nayak, A; Peariso, K; Riviello, J J; Tasker, R C; Tchapyjnikov, D; Topjian, A A; Wainwright, M S; Wilfong, A; Williams, K; Loddenkemper, T

2018-05-08

To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. We studied 219 patients (53% males) with a median (25th-75th percentiles [p 25 -p 75 ]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p 25 -p 75 ) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment. © 2018 American Academy of Neurology.

Speaking to the yet unknowing world: Hamlet, Horatio and the problem of imperfect witness.

PubMed

Phillips, Christine

2010-12-01

Every day doctors bear witness to others about the experiences, needs and feelings of their patients, drawing on what they have learnt from clinical consultations. This paper considers the medical task of bearing honourable and truthful witness through an examination of the role and actions of Horatio in Hamlet. Horatio is simultaneously located among the background machinery of the play, separate from the lives of the protagonists, and in the foreground, where his authoritative witness is repeatedly called upon by the play's characters. Horatio is invited to watch an unfolding disaster, his warnings are not heard, and at its conclusion he stands apart from the drama to give its account. The tensions between engagement and observation, and between partial and impartial accounting echo those faced by doctors in everyday clinical practice. The act of bearing witness, Shakespeare suggests, even for those who are tasked with being objective, is necessarily imperfect, and not dispassionate. Those people, including doctors, who are expected to construct authoritative accounts of the motives and actions of others may find in Hamlet a small lesson on the need to approach their summary narratives about others more humbly, aware of the narrowness and partiality of their perspective.

Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term function in neonatal rats surviving to adulthood.

PubMed

Liu, Xun; Dingley, John; Scull-Brown, Emma; Thoresen, Marianne

2015-06-01

We previously reported that combining immediate hypothermia with immediate or 2 h delayed inhalation of an inert gas, xenon, gave additive neuroprotection in rats after a hypoxic-ischemic insult, compared to hypothermia alone. Defining the therapeutic time window for this new combined intervention is crucial in clinical practice when immediate treatment is not always feasible. The aim of this study is to investigate whether combined hypothermia and xenon still provide neuroprotection in rats after a 5 h delay for both hypothermia and xenon. Seven-day-old Wistar rat pups underwent a unilateral hypoxic-ischemic insult. Pups received 5 h of treatment starting 5 h after the insult randomized between normothermia, hypothermia, or hypothermia with 50% xenon. Surviving pups were tested for fine motor function through weeks 8-10 before being euthanized at week 11. Their hemispheric and hippocampal areas were assessed. Both delayed hypothermia-xenon and hypothermia-only treated groups had significantly less brain tissue loss than those which underwent normothermia. The functional performance after 1 wk and adulthood was significantly better after hypothermia-xenon treatment as compared to the hypothermia-only or normothermia groups. Adding 50% xenon to 5 h delayed hypothermia significantly improved functional outcome as compared to delayed hypothermia alone despite similar reductions in brain area.

Local Stability of AIDS Epidemic Model Through Treatment and Vertical Transmission with Time Delay

NASA Astrophysics Data System (ADS)

Novi W, Cascarilla; Lestari, Dwi

2016-02-01

This study aims to explain stability of the spread of AIDS through treatment and vertical transmission model. Human with HIV need a time to positively suffer AIDS. The existence of a time, human with HIV until positively suffer AIDS can be delayed for a time so that the model acquired is the model with time delay. The model form is a nonlinear differential equation with time delay, SIPTA (susceptible-infected-pre AIDS-treatment-AIDS). Based on SIPTA model analysis results the disease free equilibrium point and the endemic equilibrium point. The disease free equilibrium point with and without time delay are local asymptotically stable if the basic reproduction number is less than one. The endemic equilibrium point will be local asymptotically stable if the time delay is less than the critical value of delay, unstable if the time delay is more than the critical value of delay, and bifurcation occurs if the time delay is equal to the critical value of delay.

The University and the Hamlets: Revitalizing Low-Income Communities through University Outreach and Community Visioning Exercises.

ERIC Educational Resources Information Center

Weinberg, Adam S.

1999-01-01

Explores an effort by Colgate University (New York) to enhance economic development in two low-income hamlets in New York through community-visioning programs. Describes the process of community visioning and shows how Colgate has been instrumental in its promotion. Argues that universities are better situated than governments or nonprofits to…

A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

PubMed

Clementi, Emily A; Marks, Laura R; Duffey, Michael E; Hakansson, Anders P

2012-08-03

To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.

A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

PubMed Central

Clementi, Emily A.; Marks, Laura R.; Duffey, Michael E.; Hakansson, Anders P.

2012-01-01

To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets. PMID:22700972

Survival outcome of early versus delayed bevacizumab treatment in patients with recurrent glioblastoma

PubMed Central

Hamza, Mohamed A.; Mandel, Jacob J.; Conrad, Charles A.; Gilbert, Mark R.; Yung, W. K. Alfred; Puduvalli, Vinay K.; DeGroot, John F.

2015-01-01

Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma. It is not known if there are differences in outcome between early versus delayed BEV treatment of recurrent glioblastoma. We examined the relationship between the time of starting BEV treatment and outcomes in patients with recurrent glioblastoma. In this retrospective chart review, we identified patients with recurrent glioblastoma diagnosed between 2005 and 2011 who were treated with BEV alone or BEV-containing regimens. Data was analyzed to determine overall survival (OS) from time of diagnosis and progression free survival (PFS) from time of starting BEV. A total of 298 patients were identified, 112 patients received early BEV, 133 patients received delayed BEV, and 53 patients were excluded because they either progressed within 3 months of radiation or received BEV at the time of diagnosis. There was no significant difference in PFS between patients that received early BEV and those that received delayed BEV (5.2 vs. 4.3 months, p = 0.2). Patients treated with delayed BEV had longer OS when compared to those treated with early BEV (25.9 vs. 20.8 months, p = 0.005). In patients with recurrent glioblastoma, there was no significant difference in PFS from the time of starting BEV between early and delayed BEV. Although patients treated with delayed BEV seemed to have longer OS, a conclusion regarding OS outcome requires further prospective trials. These results may indicate that delaying treatment with BEV is not detrimental for survival of patients with recurrent glioblastoma. PMID:24803001

Extracorporeal shock wave therapy in treatment of delayed bone-tendon healing.

PubMed

Wang, Lin; Qin, Ling; Lu, Hong-bin; Cheung, Wing-hoi; Yang, Hu; Wong, Wan-nar; Chan, Kai-ming; Leung, Kwok-sui

2008-02-01

Extracorporeal shock wave therapy is indicated for treatment of chronic injuries of soft tissues and delayed fracture healing and nonunion. No investigation has been conducted to study the effect of shock wave on delayed healing at the bone-tendon junction. Shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling of healing tissue in delayed healing of bone-tendon junction surgical repair. Controlled laboratory study. Twenty-eight mature rabbits were used for establishing a delayed healing model at the patella-patellar tendon complex after partial patellectomy and then divided into control and shock wave groups. In the shock wave group, a single shock wave treatment was given at week 6 postoperatively to the patella-patellar tendon healing complex. Seven samples were harvested at week 8 and 7 samples at week 12 for radiologic, densitometric, histologic, and mechanical evaluations. Radiographic measurements showed 293.4% and 185.8% more new bone formation at the patella-patellar tendon healing junction in the shock wave group at weeks 8 and 12, respectively. Significantly better bone mineral status was found in the week 12 shock wave group. Histologically, the shock wave group showed more advanced remodeling in terms of better alignment of collagen fibers and thicker and more mature regenerated fibrocartilage zone at both weeks 8 and 12. Mechanical testing showed 167.7% and 145.1% higher tensile load and strength in the shock wave group at week 8 and week 12, respectively, compared with controls. Extracorporeal shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling in the delayed bone-to-tendon healing junction in rabbits. These results provide a foundation for future clinical studies toward establishment of clinical indication for treatment of delayed bone-to-tendon junction healing.

Impact of delay to treatment upon survival in 1067 patients with breast-cancer.

PubMed

Rabinovich, M; Vallejo, C; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Lacava, J; Leone, B; Romero, A; Mickiewicz, E; Chacon, R; Estevez, R

1993-02-01

The medical records of 1067 patients with breast cancer were reviewed to evaluate the influence of delay between first symptom and first treatment upon survival. Three delay intervals were considered: <3 months; 3-6 months and >6 months. At a follow-up of 120 months, survival analyses identified a statistically significant difference (p=0.029) favoring patients with <3 months delay in the whole cohort, and in the group of women aged 50 or older (p=0.001). No differences were found when survival according to delay was considered within each clinical stage. A Cox multivariate analysis revealed that performance status, stage, age and menopausal status were significant predictors of survival for the whole group of patients. However, delay was an independent prognostic factor in patients with age greater-than-or-equal-to 50. In summary, 38/1067 patients (3.1%) could have been adversely affected by a >3 months delay between first symptom and first treatment. Better survival rate for patients with a short delay would obey to a greater number of patients in favorable stages and a higher proportion of women aged 50 or older in this group.

Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder

PubMed Central

Patel, Rashmi; Shetty, Hitesh; Jackson, Richard; Broadbent, Matthew; Stewart, Robert; Boydell, Jane; McGuire, Philip; Taylor, Matthew

2015-01-01

Background Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Method Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). Results The median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Conclusions Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify

Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

PubMed

Patel, Rashmi; Shetty, Hitesh; Jackson, Richard; Broadbent, Matthew; Stewart, Robert; Boydell, Jane; McGuire, Philip; Taylor, Matthew

2015-01-01

Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). The median diagnostic delay was 62 days (interquartile range: 17-243) and median treatment delay was 31 days (4-122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41) and substance misuse disorders (0.44, 0.31-0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner

Quantitative survival impact of composite treatment delays in head and neck cancer.

PubMed

Ho, Allen S; Kim, Sungjin; Tighiouart, Mourad; Mita, Alain; Scher, Kevin S; Epstein, Joel B; Laury, Anna; Prasad, Ravi; Ali, Nabilah; Patio, Chrysanta; St-Clair, Jon Mallen; Zumsteg, Zachary S

2018-05-09

Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis-to-treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC. Patients with HNC who underwent curative-intent surgery with radiation were identified in the National Cancer Database between 2004 and 2013. Multivariable models were constructed using restricted cubic splines to determine nonlinear relations with overall survival. Overall, 15,064 patients were evaluated. After adjustment for covariates, only prolonged postoperative interval (P < .001) and radiation interval (P < .001) independently predicted for worse outcomes, whereas the association of diagnosis-to-treatment interval with survival disappeared. By using multivariable restricted cubic spline functions, increasing postoperative interval did not affect mortality until 40 days after surgery, and each day of delay beyond this increased the risk of mortality until 70 days after surgery (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; P = .029). For radiation interval, mortality escalated continuously with each additional day of delay, plateauing at 55 days (hazard ratio, 1.25; 95% confidence interval, 1.11-1.41; P < .001). Delays beyond these change points were not associated with further survival decrements. Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

PubMed

Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

2015-01-01

To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs.

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

PubMed Central

Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

2015-01-01

Purpose To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. Materials and methods This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. Results We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Conclusion Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs. PMID:26124681

Choice between delayed food and immediate opioids in rats: treatment effects and individual differences.

PubMed

Panlilio, Leigh V; Secci, Maria E; Schindler, Charles W; Bradberry, Charles W

2017-11-01

Addiction involves maladaptive choice behavior in which immediate drug effects are valued more than delayed nondrug rewards. To model this behavior and extend our earlier work with the prescription opioid oxycodone, we allowed rats to choose between immediate intravenous delivery of the short-acting opioid remifentanil and delayed delivery of highly palatable food pellets. Treatment drugs were tested on a baseline where remifentanil was preferred over food. Treatment with a high dose of the opioid antagonist naltrexone decreased but did not reverse the preference for remifentanil. Treatment with the serotonin 5-HT 2C agonist lorcaserin decreased remifentanil and food self-administration nonselectively. Across conditions in which the alternative to delayed food was either a moderate dose of oxycodone, a moderate or high dose of remifentanil, a smaller more immediate delivery of food, or timeout with no primary reinforcement, choice was determined by both the length of the delay and the nature of the alternative option. Delayed food was discounted most steeply when the alternative was a high dose of remifentanil, which was preferred over food when food was delayed by 30 s or more. Within-subject comparisons showed no evidence for trait-like impulsivity or sensitivity to delay across these conditions. Choice was determined more by the current contingencies of reinforcement than by innate individual differences. This finding suggests that people might develop steep delay-discounting functions because of the contingencies in their environment, and it supports the use of contingency management to enhance the relative value of delayed nondrug reinforcers.

Why are there delays in seeking treatment for childhood diarrhoea in India?

PubMed

Malhotra, Nisha; Upadhyay, Ravi Prakash

2013-09-01

To examine the barriers and facilitating factors for seeking treatment for childhood diarrhoea and to determine the main causes for delay in seeking treatment. Data from Indian Demographic and Health survey 2005-06 (NFHS-III) were used. Mothers were asked whether their children (<5-years) had suffered from diarrhoea during the 2 weeks preceding the survey. Data were collected on the time of seeking treatment after start of the illness and days waited to seek treatment after the diarrhoea started. Multivariate logistic regression analysis was performed to find the determinants of seeking treatment at the health facility and the factors responsible for the 'delay' in seeking advice/treatment. Of a sample of 41 287 children, 3890 (9.4%) reportedly had diarrhoea. Sixty percentage of children with diarrhoea were taken to a health facility. Mother's education till higher secondary and above (OR 1.65; 95% CI, 1.08-2.54), richest (OR 1.76; 95% CI, 1.24-2.48) wealth index, and possession of a health card by the mother (OR 1.35; 95% CI, 1.12-1.62) increased the odds of seeking treatment. There was a strong gender bias; a male child had lower odds of experiencing a 'delay' in seeking treatment, compared with a female child (OR 0.71; 95% CI, 0.55-0.92). Access to a health facility still remains a major issue: treatment seeking was delayed when distance to a health facility was reported as a 'major problem' (OR 1.33; 95% CI, 1.01-1.76). Improved care seeking for childhood diarrhoea in India is still constrained by access to a health facility and requires expansion and strengthening of the public health system. The caregivers, especially the mothers need to be educated about the importance of seeking timely treatment and the benefits of oral rehydration solution. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

PubMed Central

Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

2015-01-01

Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

HAMLET -Matroshka IIA and IIB experiments aboard the ISS: comparison of organ doses

NASA Astrophysics Data System (ADS)

Kato, Zoltan; Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Hajek, Michael; Sihver, Lembit; Palfalvi, Jozsef K.; Hager, Luke; Burmeister, Soenke

The Matroshka experiments and the related FP7 HAMLET project aimed to study the dose burden of the cosmic rays in the organs of the crew working inside and outside the ISS. Two of the experiments will be discussed. They were performed in two different locations inside the ISS: during the Matroshka 2A (in 2006) the phantom was stored in the Russian Docking Module (Pirs), while during the Matroshka 2B (in 2007-08) it was inside the Russian Service Module (Zvezda). Both experiments were performed in the decreasing phase of the solar cycle. Solid state nuclear track detectors (SSNTD) were applied to investigate the dose contribution of the high LET radiation above ˜10 keV/µm. Two configurations of SSNTDs stacks were constructed: one for the exposure in the so called organ dose boxes (in the lung and kidney), another one for the skin dose measurements, embedded in the nomex poncho of the Phantom. In addition a reference package was placed outside the phantom. After exposure the detectors were transferred to the Earth for data evaluation. Short and long etching procedures were applied to distinguish the high and low LET particles, respectively. The particle tracks were evaluated by a semi automated image analyzer. Addi-tionally manual track parameter measurements were performed on very long tracks. As the result of measurements the LET spectra were deduced. Based on these spectra, the absorbed dose, the dose equivalent and the mean quality factor were calculated. The configuration of the stacks, the methods of the calibration and evaluation and finally the results will be presented and compared. The multiple etching and the combined evaluation method allowed to determine the fraction of the dose originated from HZE particles (Z>2 and range > major axis). Further on, data eval-uation was performed to separate the secondary particles (target fragments) from the primary particles. Although the number of high LET particles above a ˜80 keV/µm was found to be higher during

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

PubMed

Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

Barriers and Delays in Tuberculosis Diagnosis and Treatment Services: Does Gender Matter?

PubMed Central

Yang, Wei-Teng; Gounder, Celine R.; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N.; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita

2014-01-01

Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men. PMID:24876956

Barriers and delays in tuberculosis diagnosis and treatment services: does gender matter?

PubMed

Yang, Wei-Teng; Gounder, Celine R; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita

2014-01-01

Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men.

On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions.

PubMed

Waldinger, Marcel D; Schweitzer, Dave H; Olivier, Berend

2005-01-01

Recently, the idea has emerged that on-demand use of serotonin reuptake inhibitors (SSRIs), particularly short half-life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation. To provide evidence that SSRI-induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5-hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration. We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation. Intravaginal ejaculation latency time (IELT). Acute SSRI administration leads to only a mild or no increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5-HT receptors. Existing on-demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high-fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration. On-demand SSRI treatment has less ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half-life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on-demand treatment. On-demand SSRIs with short half-life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation-delaying drugs rather than drugs against premature ejaculation.

Calibration of solid state nuclear track detectors at high energy ion beams for cosmic radiation measurements: HAMLET results

NASA Astrophysics Data System (ADS)

Szabó, J.; Pálfalvi, J. K.

2012-12-01

The MATROSHKA experiments and the related HAMLET project funded by the European Commission aimed to study the dose burden of the crew working on the International Space Station (ISS). During these experiments a human phantom equipped with several thousands of radiation detectors was exposed to cosmic rays inside and outside the ISS. Besides the measurements realized in Earth orbit, the HAMLET project included also a ground-based program of calibration and intercomparison of the different detectors applied by the participating groups using high-energy ion beams. The Space Dosimetry Group of the Centre for Energy Research (formerly Atomic Energy Research Institute) participated in these experiments with passive solid state nuclear track detectors (SSNTDs). The paper presents the results of the calibration experiments performed in the years 2008-2011 at the Heavy Ion Medical Accelerator (HIMAC) of the National Institute of Radiological Sciences (NIRS), Chiba, Japan. The data obtained serve as update and improvement for the previous calibration curves which are necessary for the evaluation of the SSNTDs exposed in unknown space radiation fields.

Role of surgery in delayed local treatment for INSS 4 neuroblastoma.

PubMed

Uehara, Shuichiro; Yoneda, Akihiro; Oue, Takaharu; Nakahata, Kengo; Zenitani, Masahiro; Miyamura, Takako; Hashii, Yoshiko; Fukuzawa, Masahiro; Okuyama, Hiroomi

2017-09-01

The aim of the present study was to compare the efficacy, complications and outcomes of the following two surgical strategies for delayed local treatment for International Neuroblastoma Staging System (INSS) 4 neuroblastoma (NB): complete resection (CR; period A); and gross total resection/subtotal resection (GTR/STR) with local irradiation (period B). We retrospectively analyzed 17 patients with INSS 4 NB who received delayed local treatment (period A, n = 11; period B, n = 6). Eleven patients in period A received CR. Two patients underwent GTR and four patients underwent STR in period B. The amount of blood loss in period A was significantly greater than that in period B. Postoperative complications were observed in eight patients in period A (73%), but in only one patient in period B (17%; P < 0.01). Recurrence was observed in five patients in period A and in one patient in period B (45.4% vs 16.6%; P = n.s.). Distant metastasis at recurrence was observed in four patients in period A and in one patient in period B. Gross total resection/subtotal resection with local irradiation may be a safe and effective delayed local treatment for INSS 4 NB. © 2017 Japan Pediatric Society.

Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial.

PubMed

Deterding, Katja; Grüner, Norbert; Buggisch, Peter; Wiegand, Johannes; Galle, Peter R; Spengler, Ulrich; Hinrichsen, Holger; Berg, Thomas; Potthoff, Andrej; Malek, Nisar; Großhennig, Anika; Koch, Armin; Diepolder, Helmut; Lüth, Stefan; Feyerabend, Sandra; Jung, Maria Christina; Rogalska-Taranta, Magdalena; Schlaphoff, Verena; Cornberg, Markus; Manns, Michael P; Wedemeyer, Heiner

2013-06-01

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment. In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946. Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI -4·6 to 32·0; p=0·071). 18 (72%) of 25

HAMLET -Human Model MATROSHKA for Radiation Exposure Determination of Astronauts -Current status and results

NASA Astrophysics Data System (ADS)

Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Burmeister, Soenke; Labrenz, Johannes; Hager, Luke; Palfalvi, Jozsef K.; Hajek, Michael; Puchalska, Monika; Sihver, Lembit

The exploration of space as seen in specific projects from the European Space Agency (ESA) acts as groundwork for human long duration space missions. One of the main constraints for long duration human missions is radiation. The radiation load on astronauts and cosmonauts in space (as for the ISS) is a factor of 100 higher than the natural radiation on Earth and will further increase should humans travel to Mars. In preparation for long duration space missions it is important to evaluate the impact of space radiation in order to secure the safety of the astronauts and minimize their radiation risks. To determine the radiation risk on humans one has to measure the radiation doses to radiosensitive organs within the human body. One way to approach this is the ESA facility MATROSHKA (MTR), under the scientific and project lead of DLR. It is dedicated to determining the radiation load on astronauts within and outside the International Space Station (ISS), and was launched in January 2004. MTR is currently preparing for its fourth experimental phase inside the Japanese Experimental Module (JEM) in summer 2010. MTR, which mimics a human head and torso, is an anthropomorphic phantom containing over 6000 radiation detectors to determine the depth dose and organ dose distribution in the body. It is the largest international research initiative ever performed in the field of space dosimetry and combines the expertise of leading research institutions around the world, thereby generating a huge pool of data of potentially immense value for research. Aiming at optimal scientific exploitation, the FP7 project HAMLET aims to process and compile the data acquired individually by the participating laboratories of the MATROSHKA experiment. Based on experimental input from the MATROSHKA experiment phases as well as on radiation transport calculations, a three-dimensional model for the distribution of radiation dose in an astronaut's body will be built up. The scientific achievements

A favorable outcome despite a 39-hour treatment delay for arterial gas embolism: case report.

PubMed

Covington, Derek; Bielawski, Anthony; Sadler, Charlotte; Latham, Emi

2016-01-01

Cerebral arterial gas embolism (CAGE) occurs when gas enters the cerebral arterial vasculature. CAGE can occur during sitting craniotomies, cranial trauma or secondary to gas embolism from the heart. A far less common cause of CAGE is vascular entrainment of gas during endoscopic procedures. We present the case of a 49-year-old male who developed a CAGE following an esophagoduodenoscopy (EGD) biopsy. Due to a delay in diagnosis, the patient was not treated with hyperbaric oxygen (HBO₂) therapy until 39 hours after the inciting event. Despite presenting to our institution non-responsive and with decorticate posturing, the patient was eventually discharged to a rehabilitation facility, with only mild left upper extremity weakness. This delay in HBO₂ treatment represents the longest delay in treatment to our knowledge for a patient suffering from CAGE secondary to EGD. In addition to the clinical case report, we discuss the etiology of CAGE and the evidence supporting early HBO₂ treatment, as well as the data demonstrating efficacy even after considerable treatment delay. Copyright© Undersea and Hyperbaric Medical Society.

[Impact of care pathway on the delay for initiation of antituberculosis treatment in Conakry, Guinea].

PubMed

Camara, A; Bah-Sow, O Y; Baldé, N M; Camara, L M; Barry, I S; Bah, B; Diallo, M; Chaperon, J; Riou, F

2009-06-01

Complex care pathways can result in detrimental treatment delay particularly in tuberculosis patients. The purpose of this retrospective study was to assess the care pathways followed by tuberculosis patients prior to diagnosis and to assess impact on the delay for initiation of treatment in Conakry, Guinea. A total of 112 patients were interviewed at the time of first admission for pulmonary tuberculosis with positive bacilloscopy. Based on interview data, pathways were classified as conventional (use of health care facilities only) and mixed (use of health care facilities, self-medication, and traditional medicine). The correlation between patient characteristics and type of pathway was assessed by univariate and multivariate analysis and the two groups, i.e., conventional vs. mixed, were compared with regard to delay for initiation of treatment. The care pathway was classified as mixed in two out of three patients. Multivariate analysis showed that this type of pathway was only correlated with schooling (p=0.02). The mean delay for treatment was similar, i.e., 13.4 and 12.8 weeks for conventional and mixed pathways respectively (p<0.68). The percentage of pathways including three consultations at health care facilities was significantly higher in the conventional than mixed group (72% vs. 30%, p<0.001). The main reasons given for delayed use of health care facilities were poor knowledge of tuberculosis symptoms (26%) and high cost of care (12%). The findings of this study indicate that tuberculosis patients follow a variety of care pathways that can lead to delayed treatment. An information campaign is needed to increase awareness among the population and care providers.

Bright-light mask treatment of delayed sleep phase syndrome.

PubMed

Cole, Roger J; Smith, Julian S; Alcalá, Yvonne C; Elliott, Jeffrey A; Kripke, Daniel F

2002-02-01

We treated delayed sleep phase syndrome (DSPS) with an illuminated mask that provides light through closed eyelids during sleep. Volunteers received either bright white light (2,700 lux, n = 28) or dim red light placebo (0.1 lux, n = 26) for 26 days at home. Mask lights were turned on (< 0.01 lux) 4 h before arising, ramped up for 1 h, and remained on at full brightness until arising. Volunteers also attempted to systematically advance sleep time, avoid naps, and avoid evening bright light. The light mask was well tolerated and produced little sleep disturbance. The acrophase of urinary 6-sulphatoxymelatonin (6-SMT) excretion advanced significantly from baseline in the bright group (p < 0.0006) and not in the dim group, but final phases were not significantly earlier in the bright group (ANCOVA ns). Bright treatment did produce significantly earlier phases, however, among volunteers whose baseline 6-SMT acrophase was later than the median of 0602 h (bright shift: 0732-0554 h, p < 0.0009; dim shift: 0746-0717 h, ns; ANCOVA p = 0.03). In this subgroup, sleep onset advanced significantly only with bright but not dim treatment (sleep onset shift: bright 0306-0145 h, p < 0.0002; dim 0229-0211 h, ns; ANCOVA p < .05). Despite equal expectations at baseline, participants rated bright treatment as more effective than dim treatment (p < 0.04). We conclude that bright-light mask treatment advances circadian phase and provides clinical benefit in DSPS individuals whose initial circadian delay is relatively severe.

Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

PubMed

Bugg, George J; Siddiqui, Farah; Thornton, Jim G

2013-06-23

Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2013) and bibliographies of relevant papers. Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range

Delayed treatment of tuberculosis patients in rural areas of Yogyakarta province, Indonesia

PubMed Central

Mahendradhata, Yodi; Syahrizal, Bobby M; Utarini, Adi

2008-01-01

Background In year 2000, the entire population in Indonesia was 201 million and 57.6 percent of that was living in rural areas. This paper reports analyses that address to what extent the rural structure influence the way TB patients seek care prior to diagnosis by a DOTS facility. Methods We documented healthcare utilization pattern of smear positive TB patients prior to diagnosis and treatment by DOTS services (health centre, chest clinic, public and private hospital) in Yogyakarta province. We calculated the delay in treatment as the number of weeks between the onset of symptoms and the start of DOTS treatment. Statistical analysis was carried out with Epi Info version 3.3 (October 5, 2004). Results The only factor which was significantly associated with total delay was urban-rural setting (p = < 0.0001). The median total delay for TB patients in urban districts was 8 (1st Quartile = 4; 3rd Quartile = 12) weeks compared to 12 (1st Quartile = 7; 3rd Quartile = 23) weeks for patients in rural districts. Multivariate analysis suggested no confounding between individual factors and urban-rural setting remained as the main factor for total delay (p = < 0.0001). Primary health centre was the first choice provider for most (38.7%) of these TB patients. Urban-rural setting was also the only factor which was significantly associated with choice of first provider (p = 0.03). Conclusion Improving access to DOTS services in rural areas is an area of vital importance in aiming to make progress toward achieving TB control targets in Indonesia. PMID:19036164

Examining Delay Intervals in the Diagnosis and Treatment of Primary Open Angle Glaucoma in an Egyptian Population and Its Impact on Lifestyle

PubMed Central

Abu Hussein, Nahla B.; Habib, Ahmed E.; El Sayed, Yasmine M.

2016-01-01

Purpose. To examine causes as well as extent of delay in diagnosis and treatment of primary open angle glaucoma patients in a sample of Egyptians. Patients and Methods. 440 patients with primary open angle glaucoma were interviewed to evaluate delay in their diagnosis and treatment. The extent and cause of delay were investigated. The total delay interval, if any, was correlated with socioeconomic and other factors. Results. The median total delay was one year, with 50% of patients having a total delay of 1 year or less, of which 25% exhibited zero total delay. 25% of patients had a delay ranging from 1 to 3 years, and 25% had a total delay ranging from 3 to 27 years. Diagnostic delay accounted for 43.03% of cases. Longer delays were met in patients with certain socioeconomic factors. Patients with a positive family history of glaucoma displayed shorter delay periods. Conclusion. Significant delay in the diagnosis and treatment of glaucoma was found. Poor socioeconomic status seems to hinder timely diagnosis and treatment of POAG. Certain socioeconomic factors seem to correlate with the extent of delay. More effort is thus needed to subsidize the cost of investigations and treatment for glaucoma patients. PMID:28116140

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose

PubMed Central

Bailey, George P.; Najafi, Javad; Elamin, Muhammad E. M. O.; Waring, W. Stephen; Thomas, Simon H. L.; Archer, John R. H.; Wood, David M.

2016-01-01

Background The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. Method A 6‐month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. Results From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50–163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217–413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95–260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. Conclusion Long delays were identified during the three‐infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge. PMID:27412926

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Najafi, Javad; Elamin, Muhammad E M O; Waring, W Stephen; Thomas, Simon H L; Archer, John R H; Wood, David M; Dargan, Paul I

2016-11-01

The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. A 6-month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50-163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217-413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95-260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge. © 2016 The British Pharmacological Society.

The influence on survival of delay in the presentation and treatment of symptomatic breast cancer

PubMed Central

Richards, M A; Smith, P; Ramirez, A J; Fentiman, I S; Rubens, R D

1999-01-01

The aim of this study was to examine the possible influence on survival of delays prior to presentation and/or treatment among women with breast cancer. Duration of symptoms prior to hospital referral was recorded for 2964 women who presented with any stage of breast cancer to Guy's Hospital between 1975 and 1990. Median follow-up is 12.5 years. The impact of delay (defined as having symptoms for 12 or more weeks) on survival was measured from the date of diagnosis and from the date when the patient first noticed symptoms to control for lead-time bias. Thirty-two per cent (942/2964) of patients had symptoms for 12 or more weeks before their first hospital visit and 32% (302/942) of patients with delays of 12 or more weeks had locally advanced or metastatic disease, compared with only 10% (210/2022) of those with delays of less than 12 weeks (P< 0.0001). Survival measured both from the date of diagnosis (P< 0.001) and from the onset of the patient's symptoms (P= 0.003) was worse among women with longer delays. Ten years after the onset of symptoms, survival was 52% for women with delays less than 12 weeks and 47% for those with longer delays. At 20 years the survival rates were 34% and 24% respectively. Furthermore, patients with delays of 12–26 weeks had significantly worse survival rates than those with delays of less than 12 weeks. Multivariate analyses indicated that the adverse impact of delay in presentation on survival was attributable to an association between longer delays and more advanced stage. However, within individual stages, longer delay had no adverse impact on survival. Analyses based on ‘total delay’ (i.e. the interval between a patient first noticing symptoms and starting treatment) yielded very similar results in terms of survival to those based on delay to first hospital visit (delay in presentation). © 1999 Cancer Research Campaign PMID:10070881

High Dose and Delayed Treatment with Bile Acids Ineffective in RML Prion-Infected Mice.

PubMed

Norman, Grant; Campeau, Jody; Sim, Valerie L

2018-05-21

Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrP C ) into the infectious form (PrP Sc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein folding neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis, and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS). We previously reported that the bile acid, ursodeoxycholic acid (UDCA), given early in disease, prolonged incubation periods in male RML-infected mice. Here we expand on this result to include tauro-ursodeoxycholic acid (TUDCA) treatment trials and delayed UDCA treatment. We demonstrate that, despite a high dose of TUDCA given early in disease, there was no significant difference in incubation periods between treated and untreated cohorts, regardless of sex. In addition, delayed treatment with a high dose of UDCA resulted in a significant shortening of the average survival time for both male and female mice when compared to their sex-matched controls, with evidence of increased BiP, a marker of apoptosis, in treated female mice. Our findings suggest that treatment with high dose TUDCA provides no therapeutic benefit and that delayed treatment with high dose UDCA is ineffective and could potentially worsen outcomes. Copyright © 2018 American Society for Microbiology.

Factors affecting delay in seeking treatment among malaria patients along Thailand-Myanmar border in Tak Province, Thailand.

PubMed

Sonkong, Krit; Chaiklieng, Sunisa; Neave, Penny; Suggaravetsiri, Pornnapa

2015-01-07

Malaria is a major health problem in Thailand, especially in areas adjacent to the borders of Myanmar. Delay in seeking treatment is an important factor in the development of severe complications, death and the transmission of the disease. This study aimed to investigate factors affecting delays in seeking treatment of malaria patients. A cross-sectional analytic study was conducted in 456 malaria patients along the Thailand-Myanmar border. Patients were selected by stratified sampling from 11 malaria clinics and five public hospitals in Tak Province, Thailand. Data were collected by the use of a structured interview questionnaire and from patient's medical records. The majority of patients were categorized with an ethnicity of 'hill tribe' (65.8%), followed by Thai (34.2%). Seventy-nine per cent of patients delayed seeking treatment. A simple logistic regression identified significant factors affecting delays in seeking treatment: people of "hill tribe" ethnicity; plasmodium species; self-treatment; visiting sub-district health promotion hospital/malaria post before visiting a malaria clinic or public hospital; and low to medium social support. After being subjected to multivariate analysis, factors significantly associated with the delay were "hill tribe" ethnicity (ORadj = 2.32, 95% CI: 1.34-4.04); infection with P.vivax (ORadj=2.02, 95% CI: 1.19-3.41; self-treatment (ORadj = 1.73, 95% CI: 1.04-2.85); and receiving a low degree of social support (ORadj = 2.58, 95% CI: 1.24-5.35). Emphasis should be placed on need for early diagnosis and treatment in malaria patients as well as on ensuring the first facility for detection and treatment of malaria is a malaria clinic or public hospital, and the promotion of social support. These are especially important issues for the health of hill tribe people.

Delay in Diagnosis and Treatment of Breast Cancer among Women Attending a Reference Service in Brazil

PubMed

Romeiro Lopes, Tiara Cristina; Gravena, Angela Andréia França; Demitto, Marcela de Oliveira; Borghesan, Deise Helena Pelloso; Dell`Agnolo, Cátia Millene; Brischiliari, Sheila Cristina Rocha; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa

2017-11-26

Background: Cancer is a major public health problem. Early diagnosis and treatment are essential for reducing mortality. This study aimed to analyze factors associated with delay in breast cancer diagnosis and treatment among women attending a reference cancer service. Methods: This retrospective, cross-sectional study was performed with data collected from medical records and interviews conducted with women diagnosed with breast cancer and treated from October 2013 to October 2014 at a cancer reference hospital in Paraná, Southern Brazil. Results: A total of 82 participants were enrolled during the study period; their average age was 58.2 ± 11.5 years. The average time taken for final diagnosis of breast cancer was 102.5 ± 165.5 days. Treatment onset was delayed in the majority of cases, and the average time elapsing from diagnostic biopsy to onset of primary treatment was 72.3 ± 54.0 days. The odds of treatment delay were higher among the women with a low educational level. Conclusions: The results underline the need for proposals aimed at early detection, identification of risk factors and timely provision of treatment by health managers that focus on this group. Creative Commons Attribution License

Delayed access to treatments for rare diseases: who's to blame?

PubMed

Feltmate, Karen; Janiszewski, Peter M; Gingerich, Sheena; Cloutier, Michael

2015-04-01

The development and commercialization of drugs for rare diseases, termed 'orphan drugs', has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health-care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions--especially for rare disease therapies. © 2015 Asian Pacific Society of Respirology.

[Efficacy of the treatment for latent tuberculosis infection and delayed reactivation of tuberculosis].

PubMed

Toyota, Makoto

2013-09-01

To evaluate the efficacy of treatment for latent tuberculosis infection and delayed reactivation of tuberculosis. During a large tuberculosis outbreak, 129 individuals who were in close contact with tuberculosis patients and subsequently tested strongly positive by the tuberculin skin test were followed up for 10 years after identification of the source case. Of the 129 individuals, 105 received treatment for latent tuberculosis infection for 6 months as per recommendation, while the remaining 24 did not receive treatment, because most of them were above 30 years of age and were therefore discouraged from receiving treatment, as was done in the earlier times in Japan. Of the 105 individuals, 5 (4.8%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 53 months. Of the 24 individuals who did not receive treatment for latent tuberculosis infection, 6 (25.0%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 8.2 months. The risk of active tuberculosis was reduced by 81.0% with treatment for latent tuberculosis infection, compared with that without treatment. Delayed reactivation of tuberculosis was observed among patients treated with isoniazid for latent tuberculosis infection for 6 months.

Delayed treatment of decompression sickness with short, no-air-break tables: review of 140 cases.

PubMed

Cianci, Paul; Slade, John B

2006-10-01

Most cases of decompression sickness (DCS) in the U.S. are treated with hyperbaric oxygen using U.S. Navy Treatment Tables 5 and 6, although detailed analysis shows that those tables were based on limited data. We reviewed the development of these protocols and offer an alternative treatment table more suitable for monoplace chambers that has proven effective in the treatment of DCS in patients presenting to our facility. We reviewed the outcomes for 140 cases of DCS in civilian divers treated with the shorter tables at our facility from January 1983 through December 2002. Onset of symptoms averaged 9.3 h after surfacing. At presentation, 44% of the patients demonstrated mental aberration. The average delay from onset of symptoms to treatment was 93.5 h; median delay was 48 h. Complete recovery in the total group of 140 patients was 87%. When 30 patients with low probability of DCS were excluded, the recovery rate was 98%. All patients with cerebral symptoms recovered. Patients with the highest severity scores showed a high rate of complete recovery (97.5%). Short oxygen treatment tables as originally described by Hart are effective in the treatment of DCS, even with long delays to definitive recompression that often occur among civilian divers presenting to a major Divers Alert Network referral center.

Factors affecting professional delay in diagnosis and treatment of oral cancer in Iran.

PubMed

Esmaelbeigi, Farhad; Hadji, Maryam; Harirchi, Iraj; Omranipour, Ramesh; vand Rajabpour, Mojtaba; Zendehdel, Kazem

2014-04-01

Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country.  We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage. Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0-4.4). Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

PubMed

Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

2014-06-01

The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients.

PubMed

Kurtovic-Kozaric, Amina; Hasic, Azra; Radich, Jerald P; Bijedic, Vildan; Nefic, Hilada; Eminovic, Izet; Kurtovic, Sabira; Colakovic, Ferida; Kozaric, Mirza; Vranic, Semir; Bovan, Nada S

2016-02-01

Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib. © 2015 John Wiley & Sons Ltd.

Gender differences in reasons patients delay in seeking treatment for acute myocardial infarction symptoms.

PubMed

Moser, Debra K; McKinley, Sharon; Dracup, Kathleen; Chung, Misook L

2005-01-01

Patients (n = 194) with confirmed acute myocardial infarction (AMI) were interviewed to determine sociodemographic, clinical, social, behavioral, cognitive and emotional factors that contribute to delay in seeking treatment for their symptoms. Initial symptom experience was similar for men and women: both were most commonly at home when symptoms began; both were most commonly in the presence of their spouse or other family member; few patients (<10%) called the emergency medical system as their first reaction. Several factors contributed similarly to delay in men and women. Factors that exerted a differential effect on delay between men and women were age, history of AMI, type of AMI (Q-wave and non-Q-wave), concerns about not wanting to trouble others, and prior knowledge of thrombolytics. There was no difference in delay between men and women (median 3.08 versus 3.10 h), but there are important gender differences in the reasons patients delay and in their patterns of decision-making that may assist clinicians trying to tailor interventions.

No need to be HAMLET or BAMLET to interact with histones: binding of monomeric alpha-lactalbumin to histones and basic poly-amino acids.

PubMed

Permyakov, Serge E; Pershikova, Irina V; Khokhlova, Tatyana I; Uversky, Vladimir N; Permyakov, Eugene A

2004-05-18

The ability of a specific complex of human alpha-lactalbumin with oleic acid (HAMLET) to induce cell death with selectivity for tumor and undifferentiated cells was shown recently to be mediated by interaction of HAMLET with histone proteins irreversibly disrupting chromatin structure [Duringer, C., et al. (2003) J. Biol. Chem. 278, 42131-42135]. Here we show that monomeric alpha-lactalbumin (alpha-LA) in the absence of fatty acids is also able to bind efficiently to the primary target of HAMLET, histone HIII, regardless of Ca(2+) content. Thus, the modification of alpha-LA by oleic acid is not required for binding to histones. We suggest that interaction of negatively charged alpha-LA with the basic histone stabilizes apo-alpha-LA and destabilizes the Ca(2+)-bound protein due to compensation for excess negative charge of alpha-LA's Ca(2+)-binding loop by positively charged residues of the histone. Spectrofluorimetric curves of titration of alpha-LA by histone H3 were well approximated by a scheme of cooperative binding of four alpha-LA molecules per molecule of histone, with an equilibrium dissociation constant of 1.0 microM. Such a stoichiometry of binding implies that the binding process is not site-specific with respect to histone and likely is driven by just electrostatic interactions. Co-incubation of positively charged poly-amino acids (poly-Lys and poly-Arg) with alpha-LA resulted in effects which were similar to those caused by histone HIII, confirming the electrostatic nature of the alpha-LA-histone interaction. In all cases that were studied, the binding was accompanied by aggregation. The data indicate that alpha-lactalbumin can be used as a basis for the design of antitumor agents, acting through disorganization of chromatin structure due to interaction between alpha-LA and histone proteins.

Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

PubMed

Mistry, Nerges; Rangan, Sheela; Dholakia, Yatin; Lobo, Eunice; Shah, Shimoni; Patil, Akshaya

2016-01-01

Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB) in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai. A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values. The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days) and retreatment patients (25 days). Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation. Achieving positive behavioural changes in providers (especially non-allopaths) and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics would be

Delay Discounting and the use of Mindful Attention versus Distraction in the Treatment of Drug Addiction: A Conceptual Review

PubMed Central

Ashe, Melinda L.; Newman, Michelle G.; Wilson, Stephen J.

2015-01-01

In recent decades, researchers have integrated measurements of delay discounting, how the subjective valuation of a reward changes as a function of time, into their study of addiction. Research has begun to explore the idea that delay discounting may serve as both a marker for the effectiveness of existing treatments for addiction and a potential target for novel intervention strategies. As this work is in its infancy, many potentially significant connections between the construct of delay discounting and the treatment of addiction have yet to be explored. Here, we present a conceptual review highlighting novel points of intersection between delay discounting and two approaches to treating addiction that have become increasingly popular in recent years: those that focus on the development of mindfulness skills and those that emphasize the use of distraction techniques. Viewing these two techniques through the lens of delay discounting is particularly intriguing because of the very different way that they address the experience of drug cravings in the present moment (nonjudgmentally attending to versus shifting attention away from subjective cravings, respectively). We propose that these opposing strategies for dealing with cravings may interact with delay discounting in ways that have important implications for treatment effectiveness. PMID:25545725

Analysis of Decadal-Scale Shoreline Change along the Hamlet of Paulatuk (Canadian Arctic), using Landsat Satellite Imagery and GIS techniques from 1984 to 2014.

NASA Astrophysics Data System (ADS)

Sankar, R. D.; Murray, M. S.; Wells, P.

2016-12-01

Increased accuracy in estimating coastal change along localized segments of the Canadian Arctic coast is essential, in order to identify plausible adaptation initiatives to deal with the effects of climate change. This paper quantifies rates of shoreline movement along an 11 km segment of the Hamlet of Paulatuk (Northwest Territories, Canada), using an innovative modelling technique - Analyzing Moving Boundaries Using R (AMBUR). Approximately two dozen shorelines, obtained from high-resolution Landsat satellite imagery were analyzed. Shorelines were extracted using the band ratio method and compiled in ArcMapTM to determine decadal trends of coastal change. The unique geometry of Paulatuk facilitated an independent analysis of the western and eastern sections of the study area. Long-term (1984-2014) and short-term (1984-2003) erosion and accretion rates were calculated using the Linear Regression and End Point Rate methods respectively. Results reveal an elevated rate of erosion for the western section of the hamlet over the long-term (-1.1 m/yr), compared to the eastern portion (-0.92 m/yr). The study indicates a significant alongshore increase in the rates of erosion on both portions of the study area, over the short-term period 1984 to 2003. Mean annual erosion rates increased over the short-term along the western segment (-1.4 m/yr), while the eastern shoreline retreated at a rate of -1.3 m/yr over the same period. The analysis indicates that an amalgamation of factors may be responsible for the patterns of land loss experienced along Paulatuk. These include increased sea-surface temperature coupled with dwindling arctic ice and elevated storm hydrodynamics. The analysis further reveals that the coastline along the eastern portion of the hamlet, where the majority of the population reside, is vulnerable to a high rate of shoreline erosion.

Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea.

PubMed

Takasuna, K; Hagiwara, T; Watanabe, K; Onose, S; Yoshida, S; Kumazawa, E; Nagai, E; Kamataki, T

2006-10-01

An antitumor camptothecin derivative CPT-11 has proven a broad spectrum of solid tumor malignancy, but its severe diarrhea has often limited its more widespread use. We have demonstrated from a rat model that intestinal beta-glucuronidase may play a key role in the development of CPT-11-induced delayed diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a protective effect. In the present study, we assessed the efficacy of several potential treatments in our rat model to clarify which is the most promising treatment for CPT-11-induced delayed diarrhea. Oral dosing (twice daily from days -1 to 4) of streptomycin 20 mg/kg and penicillin 10 mg/kg (Str/Pen), neomycin 20 mg/kg and bacitracin 10 mg/kg (Neo/Bac), both of which inhibited almost completely the fecal beta-glucuronidase activity, or TJ-14 1,000 mg/kg improved the decrease in body weight and the delayed diarrhea symptoms induced by CPT-11 (60 mg/kg i.v. from days 1 to 4) to a similar extent. The efficacy was less but significant in activated charcoal (1,000 mg/kg p.o. twice daily from days -1 to 4). In a separate experiment using rats bearing breast cancer (Walker 256-TC), TJ-14, Neo/Bac, and charcoal at the same dose regimen improved CPT-11-induced intestinal toxicity without reducing CPT-11's antitumor activity. In contrast, oral dosing (twice a day) of cyclosporin A (50 mg/kg), a P-glycoprotein and cMOAT/MRP2 inhibitor or valproic acid (200 mg/kg), a UDP-glucuronosyltranferase inhibitor, exacerbated the intestinal toxicity without modifying CPT-11's antitumor activity. The result clearly demonstrated the ability of Neo/Bac, Str/Pen, and TJ-14, less but significant ability of activated charcoal, to ameliorate CPT-11-induced delayed-onset diarrhea, suggesting the treatments decreasing the exposure of the intestines to the luminal SN-38

Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C.

PubMed

Bascuñan-Castillo, Eric C; Erickson, Robert P; Howison, Christy M; Hunter, Robert J; Heidenreich, Randall H; Hicks, Chad; Trouard, Theodore P; Gillies, Robert J

2004-01-01

Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is the result of deficient intracellular cholesterol movement. We investigated the effects of tamoxifen and vitamin E (D-alpha tocopherol) treatment on patterns of weight loss and motor function in the mouse model of Niemann-Pick C disease (Npc1-/- mice). Tamoxifen has multiple metabolic effects, including reducing oxidative damage, while vitamin E primarily has this property. Npc1-/- mice were identified and treatment was initiated at an approximate age of 21 days. Tamoxifen suspended in peanut oil was administered via intraperitoneal injection (weekly, at a dose calculated to deliver 0.023 microg/g/day). Vitamin E (25 IU) was administered orally via gavage once a week. Weight loss and Rota-Rod performance were analyzed by using Kaplan-Meyer survival curves. Tamoxifen treatment by itself significantly delayed weight loss (an endpoint of neurodegeneration) in male and female mice compared to untreated controls. Motor function was evaluated by performance on a Rota-Rod. Tamoxifen maintained Rota-Rod performance for about an extra week. Vitamin E treatment significantly delayed weight loss in females only. Rota-Rod performance was maintained slightly longer in mice treated with vitamin E. Simultaneous use of both treatments did not delay weight loss longer than tamoxifen-only treatment but had a greater effect than either treatment alone on Rota-Rod performance and demonstrated a significant positive effect on the early "learning curve" portion of the Rota-Rod evaluations. We found significant but relatively small improvements in rate of disease progression by treating Npc1-/- mice with tamoxifen and/or vitamin E. Some sex differences in response and an early improvement in Rota-Rod performance suggest areas for further study.

Delayed treatment of ruptured brain AVMs: is it ok to wait?

PubMed

Beecher, Jeffrey S; Lyon, Kristopher; Ban, Vin Shen; Vance, Awais; McDougall, Cameron M; Whitworth, Louis A; White, Jonathan A; Samson, Duke; Batjer, H Hunt; Welch, Babu G

2018-04-01

OBJECTIVE Despite a hemorrhagic presentation, many patients with arteriovenous malformations (AVMs) do not require emergency resection. The timing of definitive management is not standardized in the cerebrovascular community. This study was designed to evaluate the safety of delaying AVM treatment in clinically stable patients with a new hemorrhagic presentation. The authors examined the rate of rehemorrhage or neurological decline in a cohort of patients with ruptured brain AVMs during a period of time posthemorrhage. METHODS Patients presenting to the authors' institution from January 2000 to December 2015 with ruptured brain AVMs treated at least 4 weeks posthemorrhage were included in this analysis. Exclusion criteria were ruptured AVMs that required emergency surgery involving resection of the AVM, prior treatment of AVM at another institution, or treatment of lesions within 4 weeks for other reasons (subacute surgery). The primary outcome measure was time from initial hemorrhage to treatment failure (defined as rehemorrhage or neurological decline as a direct result of the AVM). Patient-days were calculated from the day of initial rupture until the day AVM treatment was initiated or treatment failed. RESULTS Of 102 ruptured AVMs in 102 patients meeting inclusion criteria, 7 (6.9%) failed the treatment paradigm. Six patients (5.8%) had a new hemorrhage within a median of 248 days (interquartile range 33-1364 days). The total "at risk" period was 18,740 patient-days, yielding a rehemorrhage rate of 11.5% per patient-year, or 0.96% per patient-month. Twelve (11.8%) of 102 patients were found to have an associated aneurysm. In this group there was a single (8.3%) new hemorrhage during a total at-risk period of 263 patient-days until the aneurysm was secured, yielding a rehemorrhage risk of 11.4% per patient-month. CONCLUSIONS It is the authors' practice to rehabilitate patients after brain AVM rupture with a plan for elective treatment of the AVM. The present

Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

PubMed

Stoller, Glenn L; Kokame, Gregg T; Dreyer, Richard F; Shapiro, Howard; Tuomi, Lisa L

2016-05-12

Understanding the range of temporal responses to ranibizumab is critical for the assessment of individualized treatment regimens for neovascular age-related macular degeneration. To examine patterns of visual and anatomical response to ranibizumab treatment. This study is a retrospective subanalysis of HARBOR (a phase 3, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (PRN) in patients with subfoveal neovascular age-related macular degeneration). A total of 1097 patients with neovascular age-related macular degeneration were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (PRN) with monthly monitoring. Of the 1097 patients, 1057 were included in the analysis for early responders (best-corrected visual acuity [BCVA] obtained at baseline and month 3), and 988 patients were included in the analysis for delayed responders (BCVA obtained at baseline, month 3, and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015. Patients were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month 3) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month 3 but did so at month 12). Changes from baseline in BCVA and central foveal thickness (CFT). In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 0.5-mg PRN, 2.0-mg monthly, and 2.0-mg PRN treatment groups, 63 (24.0%) of 263, 65 (24.6%) of 264, 68 (25.7%) of 265, and 70 (26.4%) of 265 patients were early responders, respectively, and 40 (16.3%) of 246, 31 (12.6%) of 247, 35 (14.1%) of 248, and 29 (11.7%) of 247 patients were delayed responders, respectively. By month

Qualitative study of men's perceptions of why treatment delays occur in the UK for those with testicular cancer.

PubMed

Chapple, Alison; Ziebland, Sue; McPherson, Ann

2004-01-01

Many studies (but not all) have shown that for men with testicular cancer a longer treatment delay is associated with additional treatments, greater morbidity, and shorter survival. This paper explores patients' perspectives on why treatment delays occur. Qualitative study using narrative interviews Interviews in patient's homes throughout the United Kingdom (UK). Interviews with a maximum variation sample of 45 men with testicular cancer, recruited through general practitioners (GPs), urologists, support groups, and charities. Those who sought help relatively quickly responded to symptoms, had heard about testicular cancer in the media, had seen leaflets in GPs' surgeries, or knew others with this disease. Men delayed because they did not recognise signs and symptoms; feared appearing weak, a hypochondriac, or lacking in masculinity; recalled past illness or painful examinations; were embarrassed; feared the consequences of treatment; or lacked time to consult their doctors. Beliefs about symptoms and pessimistic associations with cancer also led to delay. Treatment delays also resulted from misdiagnosis or waiting lists. Whether or not men should be taught to examine themselves routinely to check for testicular cancer is much debated. This study suggests that it is important that men are aware of the normal shape and feel of their testicles, and may benefit from information about signs and symptoms of testicular cancer and the excellent cure rate. Information, provided in surgeries where men feel welcome, might encourage men to seek help promptly when a problem arises. Our study also suggests that GPs may need to accept a low threshold for ultrasound investigation of testicular symptoms and that the ultrasound service needs to be improved. These measures may further reduce mortality and morbidity.

Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India

PubMed Central

Mistry, Nerges; Rangan, Sheela; Dholakia, Yatin; Lobo, Eunice; Shah, Shimoni; Patil, Akshaya

2016-01-01

Background Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB) in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai. Methods A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values. Results The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days) and retreatment patients (25 days). Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation. Conclusion Achieving positive behavioural changes in providers (especially non-allopaths) and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of

Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study.

PubMed

Coimbra, Isabella; Maruza, Magda; Militão-Albuquerque, Maria de Fátima Pessoa; Moura, Líbia Vilela; Diniz, George Tadeu Nunes; Miranda-Filho, Demócrito de Barros; Lacerda, Heloísa Ramos; Rodrigues, Laura Cunha; Ximenes, Ricardo Arraes de Alencar

2012-09-07

The delay in initiating treatment for tuberculosis (TB) in HIV-infected individuals may lead to the development of a more severe form of the disease, with higher rates of morbidity, mortality and transmissibility. The aim of the present study was to estimate the time interval between the onset of symptoms and initiating treatment for TB in HIV-infected individuals, and to identify the factors associated to this delay. A nested case-control study was undertaken within a cohort of HIV-infected individuals, attended at two HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating treatment for TB was defined as the period of time, in days, which was greater than the median value between the onset of cough and initiating treatment for TB. The study analyzed biological, clinical, socioeconomic, and lifestyle factors as well as those related to HIV and TB infection, potentially associated to delay. The odds ratios were estimated with the respective confidence intervals and p-values. From a cohort of 2365 HIV-infected adults, 274 presented pulmonary TB and of these, 242 participated in the study. Patients were already attending 2 health services at the time they developed a cough (period range: 1 - 552 days), with a median value of 41 days. Factors associated to delay were: systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear-negative. The present study indirectly showed the difficulty of diagnosing TB in HIV-infected individuals and indicated the need for a better assessment of asthenia and chest pain as factors that may be present in co-infected patients. It is also necessary to discuss the role played by negative sputum smear results in diagnosing TB/HIV co-infection as well as the need to assess the best approach for drug users with TB/HIV.

Diagnosis and treatment delays among elderly breast cancer patients with pre-existing mental illness.

PubMed

Iglay, Kristy; Santorelli, Melissa L; Hirshfield, Kim M; Williams, Jill M; Rhoads, George G; Lin, Yong; Demissie, Kitaw

2017-11-01

This study aimed to compare diagnosis and treatment delays in elderly breast cancer patients with and without pre-existing mental illness. A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results-Medicare data including 16,636 women 68+ years, who were diagnosed with stage I-IIIa breast cancer in the United States from 2005 to 2007. Mental illness was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes recorded on inpatient and outpatient claims during the 3 years prior to breast cancer diagnosis. Patients were classified as having no mental illness, anxiety, depression, anxiety and depression, or severe mental illness (bipolar disorder, schizophrenia, and other psychotic disorder). Multivariable binomial regression was used to assess the association between mental illness and delays of ≥60 and ≥90 days after adjustment for confounders. Patients with comorbid anxiety and depression had an increased risk for diagnosis delay of ≥90 days from symptom recognition (RR 1.11; 95% CI 1.00, 1.23), and those with severe mental illness had an increased risk for initial treatment delay of ≥60 days from diagnosis (RR 1.36; 95% CI 1.06, 1.74). Patients with any mental illness experienced an increased risk for adjuvant chemotherapy delay of ≥90 days from last operation (RR 1.13; 95% CI 1.01, 1.26) and each category of mental illness, except depression, showed a non-significant trend for this association. Breast cancer patients with mental illness should be closely managed by a cross-functional care team, including a psychiatrist, a primary care physician, and an oncologist, to ensure adequate care is received within an appropriate timeframe.

Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala.

PubMed

Shah, Pooja Ajay; Coj, Merida; Rohloff, Peter

2017-10-09

A 23-year-old indigenous Guatemalan man presented in 2016 to our clinic in Sololá, Guatemala, with 10 months of recurrent neck swelling, fevers, night sweats and weight loss. Previously, he had sought care in three different medical settings, including a private physician-run clinic, a tertiary private cancer treatment centre and, finally, a rural government health post. With assistance from our institution's accompaniment staff, the patient was admitted to a public tertiary care hospital for work-up. Rifampin-susceptible tuberculosis was diagnosed, and appropriate treatment was begun. The case illustrates how low tuberculosis recognition among community health workers and health system segmentation creates obstacles to appropriate care, especially for patients with limited means. As a result, significant diagnostic and treatment delays can occur, increasing the public health burden of tuberculosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Extracorporeal shock wave treatment of non- or delayed union of proximal metatarsal fractures.

PubMed

Alvarez, Richard G; Cincere, Brandon; Channappa, Chandra; Langerman, Richard; Schulte, Robert; Jaakkola, Juha; Melancon, Keith; Shereff, Michael; Cross, G Lee

2011-08-01

Nonunion or delayed union of fractures in the proximal aspect of metatarsals 1 to 4 and Zone 2 of the fifth metatarsal were treated by high energy extracorporeal shock wave treatment (ESWT) to study the safety and efficacy of this method of treatment in a FDA study of the Ossatron device. In a prospective single-arm, multi-center study, 34 fractures were treated in 32 patients (two subjects had two independent fractures) with ESWT. All fractures were at least 10 (range, 10 to 833) weeks after injury, with a median of 23 weeks. ESWT application was conducted using a protocol totaling 2,000 shocks for a total energy application of approximately 0.22 to 0.51 mJ/mm2 per treatment. The mean ESWT application time for each of the treatments was 24.6 +/- 16.6 minutes, and anesthesia time averaged 27.1 +/- 10.4 minutes. All subjects were followed for 1 year after treatment at intervals of 12 weeks, 6, 9, and 12 months. The overall success rate at the 12-week visit was 71% with low complications, significant pain improvement as well as improvement on the SF-36. The success/fail criteria was evaluated again at the 6- and 12-month followup, showing treatment success rates of 89% (23/26) and 90% (18/20), respectively. The most common adverse event was swelling in the foot, reported by five subjects (15.6%). High-energy ESWT appears to be effective and safe in patients for treatment of nonunion or a delayed healing of a proximal metatarsal, and in fifth metatarsal fractures in Zone 2.

U.S. Progress Reports for the Vietnam War, 1967-68. A Study of the Hamlet Evaluation System and the Enemy Order of Battle

DTIC Science & Technology

1990-08-01

foreign policy. The physical and emotional toll of executive responsibility in State, the Pentagon, the White House, and other executive agencies is...enormousl that toll is...compounded by extended service...Complaints may be few, and physical health may remain unimpaired, though emotional health is far...Category V. The enemy are reported to be in physical control of the hamlet. 2 .cV.C supremacy, except for occasional allied forays) 40 specially

Listening to the Patient Voice in Narcolepsy: Diagnostic Delay, Disease Burden, and Treatment Efficacy

PubMed Central

Maski, Kiran; Steinhart, Erin; Williams, David; Scammell, Thomas; Flygare, Julie; McCleary, Kimberly; Gow, Monica

2017-01-01

Study Objectives: Describe common symptoms, comorbidities, functional limitations, and treatment responsiveness among patients with narcolepsy. Investigate the effect of pediatric onset of narcolepsy symptoms on time to diagnosis of narcolepsy and presence of comorbid depression. Methods: Cross-sectional survey of 1,699 people in the United States with self-reported diagnosis of narcolepsy. We utilized mixed-methods data analyses to report study findings. Results: Most participants reported receiving a diagnosis of narcolepsy more than 1 y after symptom onset. We found that the strongest predictor of this delayed diagnosis was pediatric onset of symptoms (odds ratio = 2.4, p < 0.0005). Depression was the most common comorbidity but we detected no association with pediatric onset of narcolepsy symptoms. Overall, participants reported that fatigue and cognitive difficulties were their most burdensome symptoms in addition to sleepiness and cataplexy. The majority of participants reported residual daytime fatigue and/or sleepiness despite treatment. Most participants reported they could not perform at work or school as well as they would like because of narcolepsy symptoms. Conclusions: This study provides unique insight into the narcolepsy disease experience. The study quantifies the problem of diagnostic delay for narcolepsy patients in the United States and highlights that symptoms are more likely to be missed if they develop before 18 y of age. These results suggest that narcolepsy awareness efforts should be aimed at parents, pediatric health care providers, school professionals, and children/adolescents themselves. Disease burden is high because of problems with fatigue, cognition, and persistence of residual symptoms despite treatment. Citation: Maski K, Steinhart E, Williams D, Scammell T, Flygare J, McCleary K, Gow M. Listening to the patient voice in narcolepsy: diagnostic delay, disease burden and treatment efficacy. J Clin Sleep Med. 2017;13(3):419–425

Effect of Delayed Reinforcement on Skill Acquisition during Discrete-Trial Instruction: Implications for Treatment-Integrity Errors in Academic Settings

ERIC Educational Resources Information Center

Carroll, Regina A.; Kodak, Tiffany; Adolf, Kari J.

2016-01-01

We used an adapted alternating treatments design to compare skill acquisition during discrete-trial instruction using immediate reinforcement, delayed reinforcement with immediate praise, and delayed reinforcement for 2 children with autism spectrum disorder. Participants acquired the skills taught with immediate reinforcement; however, delayed…

Immediate and delayed hyperbaric oxygen therapy as a neuroprotective treatment for traumatic brain injury in mice.

PubMed

Baratz-Goldstein, Renana; Toussia-Cohen, Shlomi; Elpaz, Aviya; Rubovitch, Vardit; Pick, Chaim G

2017-09-01

Traumatic brain injury is the most common cause of death or chronic disability among people under-35-years-old. There is no effective pharmacological treatment currently existing for TBI. Hyperbaric oxygen therapy (HBOT) is defined as the inhalation of pure oxygen in a hyperbaric chamber that is pressurized higher than 1atm. HBOT offers physiological and mechanical effects by inducing a state of increased pressure and hyperoxia. HBOT has been proposed as an effective treatment for moderate traumatic brain injury (mTBI), yet the exact therapeutic window and mechanism that underlies this effect is not completely understood. HBOT was administrated for 4 consecutive days, post a mouse closed head weight drop moderate TBI (mTBI) in 2 different time lines: immediate treatment - initiated 3h post-injury and delayed treatment - initiated 7days post-injury. Behavioral cognitive tests and biochemical changes were assessed. The results were similar for both the immediate and the delayed treatments. mTBI mice exhibited impairment in learning abilities, whereas mTBI mice treated with HBO displayed significant improvement compared with the mTBI group, performing similar to the sham groups. mTBI mice had a decline in myelin basic protein, an increase in neuronal loss (NeuN staining), and an increase in the number of reactive astrocytes (GFAP). The HBO treated mice in both groups did not exhibit these changes and remained similar to the sham group. The delayed HBOT has a potential to serve as a neuroprotective treatment for mTBI with a long therapeutic window. Further research is needed for fully understanding the cellular changes. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of delayed brincidofovir treatment against a lethal rabbitpox virus challenge in New Zealand White rabbits.

PubMed

Grossi, Irma M; Foster, Scott A; Gainey, Melicia R; Krile, Robert T; Dunn, John A; Brundage, Thomas; Khouri, Jody M

2017-07-01

In the event of a bioterror attack with variola virus (smallpox), exposure may only be identified following onset of fever. To determine if antiviral therapy with brincidofovir (BCV; CMX001) initiated at, or following, onset of fever could prevent severe illness and death, a lethal rabbitpox model was used. BCV is in advanced development as an antiviral for the treatment of smallpox under the US Food and Drug Administration's 'Animal Rule'. This pivotal study assessed the efficacy of immediate versus delayed treatment with BCV following onset of symptomatic disease in New Zealand White rabbits intradermally inoculated with a lethal rabbitpox virus (RPXV), strain Utrecht. Infected rabbits with confirmed fever were randomized to blinded treatment with placebo, BCV, or BCV delayed by 24, 48, or 72 h. The primary objective evaluated the survival benefit with BCV treatment. The assessment of reduction in the severity and progression of clinical events associated with RPXV were secondary objectives. Clinically and statistically significant reductions in mortality were observed when BCV was initiated up to 48 h following the onset of fever; survival rates were 100%, 93%, and 93% in the immediate treatment, 24-h, and 48-h delayed treatment groups, respectively, versus 48% in the placebo group (p < 0.05 for each vs. placebo). Significant improvements in clinical and virologic parameters were also observed. These findings provide a scientific rationale for therapeutic intervention with BCV in the event of a smallpox outbreak when vaccination is contraindicated or when diagnosis follows the appearance of clinical signs and symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Delay in initiation of treatment after diagnosis of pulmonary tuberculosis in primary health care setting: eight year cohort analysis from district Faridabad, Haryana, North India.

PubMed

Kant, Shashi; Singh, Arvind K; Parmeshwaran, Giridara G; Haldar, Partha; Malhotra, Sumit; Kaur, Ravneet

2017-01-01

Delay in initiation of tuberculosis (TB) treatment may have a tremendous impact on disease transmission, development of drug resistance, poor outcome and overall survival of TB patients. The delay can occur at various levels. Delay in initiation of treatment after diagnosis is mostly due to health system failure and has immense programmatic implications. It has not been studied extensively in the Indian setting. The authors did a cohort analysis of all TB patients initiated on treatment from two primary health centres (PHCs) at Ballabgarh Health and Demographic Surveillance System between January 2007 and December 2014. Diagnosis and treatment of TB in the study area was done as per the protocol envisaged in the national program. Information related to demography, details of diagnosis and treatment of TB and outcome of treatment were extracted from the TB register. Delay in initiation of treatment after diagnosis was considered if the gap between diagnosis and treatment was greater than 7 days. Bivariate and multivariate analyses were done to find the association of various factors with delay in initiation of treatment after diagnosis. Out of 885 patients, 662 patients started treatment for pulmonary TB. Mean time interval between diagnosis and initiation of treatment was 8.95 days. Only 57.7% of pulmonary TB patients were started on treatment within 7 days of diagnosis, and an additional 24.5% were started on treatment 8-14 days after diagnosis. Patients on retreatment regimens and those residing in villages without a PHC were more likely to have delayed initiation of treatment (odds ratio (OR)=1.82 (1.3-2.7, p=0.001) and OR=1.62 (1.1-2.5, p=0.01) respectively). Delay in initiation of treatment was also associated with unfavourable treatment outcome such as default, failure or death. There is a need to have healthcare changes related to TB care to enable initiation of treatment as early as possible. Pretreatment counselling especially for retreatment

Changes in tuberculosis notifications and treatment delay in Zambia when introducing a digital X-ray service

PubMed Central

Schaap, A.; Muyoyeta, M.; Mulenga, D.; Brown, J.; Ayles, H.

2012-01-01

Setting: In August 2009, a digital chest X-ray (CXR) machine was installed at a busy urban health centre in Lusaka, Zambia. Objective: To describe the changes in tuberculosis (TB) notifications and treatment delay ≥7 days in Zambia after introducing a digital X-ray service. Design: Operational retrospective research of TB notification, laboratory and CXR data for Q4 2008 (prior to digital CXR) compared to Q4 2009. Results: Notifications for sputum smear-negative TB increased by 8.1%, from 370/527 (70.2%) in Q4 2008 to 425/544 (78.1%) in Q4 2009, despite a 6.7% decrease in sputum smear positivity in Q4 2009. TB treatment delay decreased from 75/412 (18.2%) in Q4 2008 to 52/394 (13.2%) in Q4 2009 (P = 0.05). Conclusion: In Q4 2009, sputum smear-negative TB notifications increased and treatment delay decreased. However, accurate diagnosis of TB is challenging in this setting, and misdiagnosis and overtreatment may occur. Moreover, other factors in addition to the introduction of the digital X-ray service could have contributed to these findings. Nonetheless, we found that the digital X-ray service had many advantages and that it may aid in more efficient TB diagnosis. PMID:26392952

Delayed Orgasm and Anorgasmia

PubMed Central

Jenkins, Lawrence C.; Mulhall, John P.

2016-01-01

Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies; which include: medications, penile sensation loss, endocrinopathies, penile hyperstimulation and psychological etiologies, amongst others. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. PMID:26439762

Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

PubMed

Nemashkalova, Ekaterina L; Kazakov, Alexei S; Khasanova, Leysan M; Permyakov, Eugene A; Permyakov, Sergei E

2013-09-10

HAMLET is a complex of human α-lactalbumin (hLA) with oleic acid (OA) that kills various tumor cells and strains of Streptococcus pneumoniae. More potent protein-OA complexes were previously reported for bovine α-lactalbumin (bLA) and β-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore their structural features. The concentration dependencies of the tryptophan fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration at protein concentrations below the micromolar level. Chemical cross-linking experiments provide evidence that association with OA shifts the distribution of oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This effect is confirmed for bLA and bLG using the dynamic light scattering method, while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding increases the affinity of bLG for small unilamellar dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the vesicles irrespective of OA binding. The association of OA with bLG and pPA increases their α-helix and cross-β-sheet content and resistance to enzymatic proteolysis, which is indicative of OA-induced protein structuring. The lack of excess heat sorption during melting of bLG and pPA in complex with OA and the presence of a cooperative thermal transition at the level of their secondary structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary structure but exhibit a continuous thermal transition. Overall, despite marked differences, the HAMLET-like complexes that were studied exhibit a common feature: a tendency toward protein oligomerization. Because OA-induced oligomerization has been reported for other proteins, this phenomenon is inherent to many proteins.

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

PubMed

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

2015-12-01

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

Delayed orgasm and anorgasmia.

PubMed

Jenkins, Lawrence C; Mulhall, John P

2015-11-01

Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs.

PubMed

Tsavaris, Nicolas; Kosmas, Christos; Gouveris, Panagiotis; Vadiak, Maria; Dimitrakopoulos, Antonis; Karadima, Dimitra; Pagouni, Efterpi; Panagiotakopoulos, George; Tzima, Evanthia; Ispoglou, Sevasti; Sakelariou, Dimitris; Koufos, Christos

2004-02-01

Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia. One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B). The number of doses of G-CSF was similar in the two groups. There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001). Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A. Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B. Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

DTIC Science & Technology

1981-02-26

TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

Plasmodium falciparum malaria: Convergent evolutionary trajectories towards delayed clearance following artemisinin treatment.

PubMed

Wilairat, Prapon; Kümpornsin, Krittikorn; Chookajorn, Thanat

2016-05-01

Malaria is a major global health challenge with 300million new cases every year. The most effective regimen for treating Plasmodium falciparum malaria is based on artemisinin and its derivatives. The drugs are highly effective, resulting in rapid clearance of parasites even in severe P. falciparum malaria patients. During the last five years, artemisinin-resistant parasites have begun to emerge first in Cambodia and now in Thailand and Myanmar. At present, the level of artemisinin resistance is relatively low with clinical presentation of delayed artemisinin clearance (a longer time to reduce parasite load) and a small decrease in artemisinin sensitivity in cultured isolates. Nevertheless, multiple genetic loci associated with delayed parasite clearance have been reported, but they cannot account for a large portion of cases. Even the most well-studied kelch 13 propeller mutations cannot always predict the outcome of artemisinin treatment in vitro and in vivo. Here we propose that delayed clearance by artemisinin could be the result of convergent evolution, driven by multiple trajectories to overcome artemisinin-induced stress, but precluded to become full blown resistance by high fitness cost. Genetic association studies by several genome-wide approaches reveal linkage disequilibrium between multiple loci and delayed parasite clearance. Genetic manipulations at some of these loci already have resulted in loss in artemisinin sensitivity. The notion presented here is by itself consistent with existing evidence on artemisinin resistance and has the potential to be explored using available genomic data. Most important of all, molecular surveillance of artemisinin resistance based on multi-genic markers could be more informative than relying on any one particular molecular marker. Copyright © 2016 Elsevier Ltd. All rights reserved.

Delay in seeking treatment and adherence to tuberculosis medications in Russia: a survey of patients from two clinics.

PubMed

Woith, Wendy Mann; Larson, Janet L

2008-08-01

Tuberculosis is a global problem, especially in high burden countries such as Russia, that is fueled by delay in seeking treatment and nonadherence to prescribed medications. Stigma and illness representation (a person's mental image of a specific illness) have the potential to affect treatment seeking and adherence. To describe the illness representation of tuberculosis in Russians with active pulmonary tuberculosis, and to determine if stigma and illness representation are predictors of delay in seeking treatment and adherence to tuberculosis medications. Cross-sectional, descriptive survey. Two outpatient clinics in the Vladimir Region, Russia. A total of 105 adults, 18 years and older, being treated for active pulmonary tuberculosis, and on outpatient therapy for a minimum of four weeks participated in this study. Delay was measured with a question asking length of time between onset of symptoms and appointment with a physician. Stigma was measured using the Social Impact Scale. Illness representation was measured using the Revised Illness Perception Questionnaire. Participants' outpatient medication records were reviewed for medication adherence. Symptoms reported were not consistent with those described in the medical literature and other studies. Only four subjects suspected tuberculosis based on their symptoms; 60% believed they had other respiratory infections. Multiple regression showed that illness identity (an attribute of illness representation) (beta=0.23) was a significant predictor of delay, accounting for 29% of the variance (p=0.008); and financial insecurity (beta=-0.28) and internalized shame (beta=0.27) (measures of stigma) were both significant predictors of medication adherence, accounting for 23% of the variance (p=0.003). Illness identity was associated with delay. Internalized shame was associated with increased medication adherence while financial insecurity was associated with decreased adherence. Results point to the need for broad

A case report: delayed high fever and maculopapules during Sorafenib treatment of ectopic hepatocellular carcinoma.

PubMed

Cui, Tianxiang; Diao, Xinwei; Chen, Xiewan; Huang, Shaojiang; Sun, Jianguo

2016-07-27

Sorafenib is the standard first-line therapy for hepatocellular carcinoma (HCC) and probably ectopic hepatocellular carcinoma (EHCC) as well. No report involves a side effect of delayed high fever of sorafenib. This manuscript describes a case of EHCC in the thoracic and abdominal cavities, who showed a delayed high fever and maculopapules during sorafenib treatment. The patient is a 63-year-old Chinese male with advanced EHCC, taking sorafenib 400 mg twice daily. On the tenth day, red maculopapules appeared all over the body. On the same day, the patient began to suffer from continuous high fever. Due to these effects, the patient was asked to cease sorafenib treatment, and the high fever and maculopapules were alleviated quickly. However, the symptoms were present again upon re-challenge of sorafenib. Prednisone was then administered to control the symptoms, with the dosage gradually reduced from 30 to 5 mg/day in 1.5 months. No recurrence of fever or maculopapules has been found. Tumor response reached partial response (PR) and progression free survival (PFS) reached 392 days + by the date of Apr. 14th, 2016. EHCC could be treated like orthotopic HCC by oral administration of sorafenib, which shows good tumor response and survival benefit. Delayed high fever and maculopapules are potential, rare and severe side effects of sorafenib, and could be effectively controlled by glucocorticoid.

Perceived Discrimination and Reported Delay of Pharmacy Prescriptions and Medical Tests

PubMed Central

Van Houtven, Courtney Harold; Voils, Corrine I; Oddone, Eugene Z; Weinfurt, Kevin P; Friedman, Joëlle Y; Schulman, Kevin A; Bosworth, Hayden B

2005-01-01

BACKGROUND Access to health care varies according to a person's race and ethnicity. Delaying treatment is one measure of access with important health consequences. OBJECTIVE Determine whether perceptions of unfair treatment because of race or ethnicity are associated with reported treatment delays, controlling for economic constraints, self-reported health, depression, and demographics. DESIGN Cross-sectional, observational study. PARTICIPANTS A randomly selected community sample of 181 blacks, 148 Latinos, and 193 whites in Durham County, NC. MEASUREMENTS A phone survey conducted in 2002 to assess discrimination, trust in medical care, quality of care, and access to care. Treatment delays were measured by whether or not a person reported delaying or forgoing filling a prescription and delaying or forgoing having a medical test/treatment in the past 12 months. Perceived discrimination was measured as unfair treatment in health care and as racism in local health care institutions. RESULTS The odds of delaying filling prescriptions were significantly higher (odds ratio (OR)=2.02) for persons who perceived unfair treatment, whereas the odds of delaying tests or treatments were significantly higher (OR=2.42) for persons who thought racism was a problem in health care locally. People with self-reported depression and people who reported not working had greater odds of delaying both types of care. CONCLUSIONS A prospective cohort study with both personal and macro measures of discrimination, as well as more refined measures of treatment delays, would help us better understand the relationship between perceived discrimination and treatment delays. PMID:16050850

Treatment delays among women with breast cancer in a low socio-economic status region in Brazil.

PubMed

Alves Soares Ferreira, Naidhia; Melo Figueiredo de Carvalho, Sionara; Engrácia Valenti, Vitor; Pinheiro Bezerra, Italla Maria; Melo Teixeira Batista, Hermes; de Abreu, Luiz Carlos; Matos, Leandro Luongo; Adami, Fernando

2017-02-21

Considering the inequalities and the areas of low socioeconomic status in Brazil, access to health services is a challenge and the delay between diagnosis and treatment represents an important factor of worse prognosis in patients with breast cancer. Herein, we describe the clinical and epidemiological profiles of women with breast cancer and evaluate their access to health services, as well as treatment delays, at a reference centre of the Cariri region, Ceará, Brazil. This is a retrospective study that included 473 women treated with breast cancer between 2009 and 2011 at the Oncology Centre of the Cariri. The majority of these patients were aged between 40 and 69 years old (65.7%), without a completed high school degree (89.2%). They were married (62.9%) and were already diagnosed but had not yet been subjected to any previous treatment (77.8%). It was observed that 91.8% were referred from the public health service, and treatment was paid for by the public health service in 92.9% of the cases. The patients whose source of referral was the public system waited longer between diagnosis and the treatment initiation (p = 0.031; Mann-Whitney's test), with a median waiting time of 71.5 days versus 39 days for those receiving referrals from private services. In addition, those with public referrals prior to diagnosis also experienced a longer waiting time between the first medical visit and treatment initiation (77 days vs. 37 days; p = 0.036; Mann-Whitney's test), with the waiting time for the biopsy being an important factor in this delay. Late diagnosis was often the result of inefficiency of the prevention policies coupled with difficulty accessing the public health network. It was commonly observed that, even after diagnosis, the patients needed to wait too long before entering the Oncology Service because of long waiting queues in the public health system.

[Determinants of tuberculosis diagnosis delay in limited resources countries].

PubMed

Ndeikoundam Ngangro, N; Chauvin, P; Halley des Fontaines, V

2012-02-01

Delayed diagnoses of pulmonary tuberculosis contribute to the spread of the epidemic. This study aims to identify risk factors associated with patient delay (from symptoms onset to the first visit), health system delay (from the first visit to the tuberculosis treatment initiation) and total delay (sum of the patient and the health system delay) in low income and high tuberculosis burden countries. A systematic literature review has been performed using the keywords: "tuberculosis"; "delay", care seeking"; "health care seeking behavior"; "diagnosis" and "treatment". Only quantitative studies showing delays for pulmonary tuberculosis adult cases were included in this review. Low income, gender, rural life, unemployment, ageing and misunderstanding the microbial cause of tuberculosis are associated with delayed diagnoses. Systemic factors including low health care coverage, patient expenditures and entry into the health system by consulting a traditional healer or a non-skilled professional delay the beginning of tuberculosis treatment. Delays can be used as indicators to evaluate tuberculosis control programs. Active case finding in the households of contagious patients can help to diminish diagnostic delays in low-income countries with high endemicity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Maintained Physical Activity Induced Changes in Delay Discounting.

PubMed

Sofis, Michael J; Carrillo, Ale; Jarmolowicz, David P

2017-07-01

Those who discount the subjective value of delayed rewards less steeply are more likely to engage in physical activity. There is limited research, however, showing whether physical activity can change rates of delay discounting. In a two-experiment series, treatment and maintenance effects of a novel, effort-paced physical activity intervention on delay discounting were evaluated with multiple baseline designs. Using a lap-based method, participants were instructed to exercise at individualized high and low effort levels and to track their own perceived effort. The results suggest that treatment-induced changes in discounting were maintained at follow-up for 13 of 16 participants. In Experiment 2, there were statistically significant group-level improvements in physical activity and delay discounting when comparing baseline with both treatment and maintenance phases. Percentage change in delay discounting was significantly correlated with session attendance and relative pace (min/mile) improvement over the course of the 7-week treatment. Implications for future research are discussed.

Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

PubMed

Gunn, Katherine C; Cutfield, Wayne S; Hofman, Paul L; Jefferies, Craig A; Albert, Benjamin B; Gunn, Alistair J

2014-08-14

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from -1.9 (-3.6, -0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment.

Patient characteristics associated with self-presentation, treatment delay and survival following primary percutaneous coronary intervention.

PubMed

Austin, David; Yan, Andrew T; Spratt, James C; Kunadian, Vijay; Edwards, Richard J; Egred, Mohaned; Bagnall, Alan J

2014-09-01

Delayed arrival to a primary percutaneous coronary intervention (PPCI)-capable hospital following ST-elevation myocardial infarction (STEMI) is associated with poorer outcome. The influence of patient characteristics on delayed presentation during STEMI is unknown. This was a retrospective observational study. Patients presenting for PPCI from March 2008 to November 2011 in the north of England (Northumbria, Tyne and Wear) were included. The outcomes were self-presentation to a non-PPCI-capable hospital, symptom to first medical contact (STFMC) time, total ischaemic time and mortality during follow-up. STEMI patients included numbered 2297; 619 (26.9%) patients self-presented to a non-PPCI-capable hospital. STFMC of >30 min and total ischaemic time of >180 min was present in 1521 (70.7%) and 999 (44.9%) cases, respectively. Self-presentation was the strongest predictor of prolonged total ischaemic time (odds ratio, OR (95% confidence interval, CI): 5.05 (3.99-6.39)). Married patients (OR 1.38 (1.10-1.74)) and patients living closest to an Emergency Room self-presented more commonly (driving time (vs. ≤10 min) 11-20 min OR 0.66 (0.52-0.83), >20 minutes OR 0.46 (0.33-0.64). Unmarried females waited longest to call for help (OR vs. married males 1.89 (1.29-2.78) and experienced longer total ischaemic times (OR 1.51 (1.10-2.07)). Married patients had a borderline association with lower mortality (hazard ratio 0.75 (0.53-1.05), p=0.09). Unmarried female patients had the longest treatment delays. Married patients and those living closer to an Emergency Room self-present more frequently. Early and exclusive use of the ambulance service may reduce treatment delay and improve STEMI outcome. © The European Society of Cardiology 2014.

Acute and Delayed Systemic Treatment with Cannabinoid Receptor 2 Agonists to Prevent or Treat/Reverse Osteoporosis in a Mouse Model of SCI

DTIC Science & Technology

2017-08-01

AWARD NUMBER: W81XWH-16-1-0349 TITLE: Acute and Delayed Systemic Treatment with Cannabinoid Receptor 2 Agonists to Prevent or Treat/Reverse...REPORT TYPE Annual 3. DATES COVERED 1 Aug 2016 - 31 Jul 2017 4. TITLE AND SUBTITLE Acute and Delayed Systemic Treatment with Cannabinoid Receptor 2...for the cannabinoid-2 receptor, when systemically delivered, can prevent the onset of osteoporosis in mice when delivered during the acute phase of

Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes.

PubMed

Kushnirsky, Marina; Nguyen, Vinh; Katz, Joel S; Steinklein, Jared; Rosen, Lisa; Warshall, Craig; Schulder, Michael; Knisely, Jonathan P S

2016-02-01

Contrast-enhanced MRI is the preeminent diagnostic test for brain metastasis (BM). Detection of BMs for stereotactic radiosurgery (SRS) planning may improve with a time delay following administration of a high-relaxivity agent for 1.5-T and 3-T imaging systems. Metastasis detection with time-delayed MRI was evaluated in this study. Fifty-three volumetric MRI studies from 38 patients undergoing SRS for BMs were evaluated. All studies used 0.1-mmol/kg gadobenate dimeglumine (MultiHance; Bracco Diagnostics) immediately after injection, followed by 2 more axial T1-weighted sequences after 5-minute intervals (final image acquisition commenced 15 minutes after contrast injection). Two studies were motion limited and excluded. Two hundred eighty-seven BMs were identified. The studies were randomized and examined separately by 3 radiologists, who were blinded to the temporal sequence. Each radiologist recorded the number of BMs detected per scan. A Wilcoxon signed-rank test compared BM numbers between scans. One radiologist determined the scan on which BMs were best defined. All confirmed, visible tumors were contoured using iPlan RT treatment planning software on each of the 3 MRI data sets. A linear mixed model was used to analyze volume changes. The interclass correlations for Scans 1, 2, and 3 were 0.7392, 0.7951, and 0.7290, respectively, demonstrating excellent interrater reliability. At least 1 new lesion was detected in the second scan as compared with the first in 35.3% of subjects (95% CI 22.4%-49.9%). The increase in BM numbers between Scans 1 and 2 ranged from 1 to 10. At least 1 new lesion was detected in the third scan as compared with the second in 21.6% of subjects (95% CI 11.3%-35.3%). The increase in BM numbers between Scans 2 and 3 ranged from 1 to 9. Between Scans 1 and 3, additional tumors were seen on 43.1% of scans (increase ranged from 1 to 14). The median increase in tumor number for all comparisons was 1. There was a significant increase in number

Stressful life events predict delayed functional recovery following treatment for mania in bipolar disorder.

PubMed

Yan-Meier, Leslie; Eberhart, Nicole K; Hammen, Constance L; Gitlin, Michael; Sokolski, Kenneth; Altshuler, Lori

2011-04-30

Identifying predictors of functional recovery in bipolar disorder is critical to treatment efforts to help patients re-establish premorbid levels of role adjustment following an acute manic episode. The current study examined the role of stressful life events as potential obstacles to recovery of functioning in various roles. 65 patients with bipolar I disorder participated in a longitudinal study of functional recovery following clinical recovery from a manic episode. Stressful life events were assessed as predictors of concurrent vs. delayed recovery of role functioning in 4 domains (friends, family, home duties, work/school). Despite clinical recovery, a subset of patients experienced delayed functional recovery in various role domains. Moreover, delayed functional recovery was significantly associated with presence of one or more stressors in the prior 3 months, even after controlling for mood symptoms. Presence of a stressor predicted longer time to functional recovery in life domains, up to 112 days in work/school. Interventions that provide monitoring, support, and problem-solving may be needed to help prevent or mitigate the effects of stress on functional recovery. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Does post-exercise massage treatment reduce delayed onset muscle soreness? A systematic review

PubMed Central

Ernst, E.

1998-01-01

BACKGROUND: Delayed onset muscle soreness (DOMS) is a frequent problem after unaccustomed exercise. No universally accepted treatment exists. Massage therapy is often recommended for this condition but uncertainty exists about its effectiveness. AIM: To determine whether post-exercise massage alleviates the symptoms of DOMS after a bout of strenuous exercise. METHOD: Various computerised literature searches were carried out and located seven controlled trials. RESULTS: Most of the trials were burdened with serious methodological flaws, and their results are far from uniform. However, most suggest that post-exercise massage may alleviate symptoms of DOMS. CONCLUSIONS: Massage therapy may be a promising treatment for DOMS. Definitive studies are warranted. 


 PMID:9773168

TB questions, East Kwaio answers: community-based participatory research in a remote area of Solomon Islands.

PubMed

Massey, P D; Wakageni, J; Kekeubata, E; Maena'adi, J; Laete'esafi, J; Waneagea, J; Fangaria, G; Jimuru, C; Houaimane, M; Talana, J; MacLaren, D; Speare, R

2012-01-01

East Kwaio is a remote region on the island of Malaita, Solomon Islands. Atoifi Adventist Hospital (the Hospital) is the only hospital and tuberculosis (TB) services provider in the region. If people come to the Hospital with TB, they are usually admitted for the two-month intensive phase of treatment as there are no community-based TB services. Most people walk or travel by canoe to the Hospital as there are no roads. East Kwaio is known to have high rates of TB; however, it has a low case detection rate and low treatment completion. The aims of this study were to explore why people with TB, especially from the mountain areas, present to the Hospital so late in their illness or do not present at all. The study was part of a larger project to strengthen the research capacity of local health workers and community leaders, supported by visiting researchers from Australia. Semi-structured interviews with TB patients, a focus group of key informants and direct interaction with a community with a history of TB were used to explore reasons why people present to the Hospital late in their TB illness. Four interviews and a focus group of 12 key informants were conducted and a mountain hamlet with a history of TB was visited. The results represent the data from the interviews and the focus group. The time delay in presenting to the Hospital from when participants first became unwell ranged between two and three years. In the mountain hamlet, two additional people with probable TB were seen who had not presented to the Hospital during illnesses of five and nine months. Reasons for delays included: seeking care from traditional healers; the challenge of accessing health services due to distance, cost and cultural issues different from the Hospital's worldview; social isolation when in hospital; and being old so not having long to live. Delays in diagnosis of people with TB will increase the risk of transmission to family and through hamlets and villages. This study has led to

Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats.

PubMed

Baranova, Anna I; Whiting, Mark D; Hamm, Robert J

2006-08-01

Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. Three experiments were performed to determine (1) the optimal dose of aniracetam for treating cognitive impairment, (2) the effect of delaying drug treatment for a period of days following TBI, and (3) the effect of terminating drug treatment before cognitive assessment. In experiment 1, rats were administered moderate fluid percussion injury and treated with vehicle, 25, or 50 mg/kg aniracetam for 15 days. Both doses of aniracetam effectively reduced injury-induced deficits in the Morris water maze (MWM) as measured on postinjury days 11-15. In experiment 2, injured rats were treated with 50 mg/kg aniracetam or vehicle beginning on day 11 postinjury and continuing for 15 days. MWM performance, assessed on days 26-30, indicates that aniracetam-treated animals performed as well as sham-injured controls. In experiment 3, animals were injured and treated with aniracetam for 15 days. Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.

Constitutional Delay Influences the Auxological Response to Growth Hormone Treatment in Children with Short Stature and Growth Hormone Sufficiency

PubMed Central

Gunn, Katherine C.; Cutfield, Wayne S.; Hofman, Paul L.; Jefferies, Craig A.; Albert, Benjamin B.; Gunn, Alistair J.

2014-01-01

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from −1.9 (−3.6, −0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment. PMID:25317732

Gender and literacy: factors related to diagnostic delay and unsuccessful treatment of tuberculosis in the mountainous area of Yemen.

PubMed

Date, J; Okita, K

2005-06-01

People in the mountainous area of Yemen, having maintained their traditional lifestyle, generally believe that uneducated women are unsuccessful in using modern medical care. Whether this belief applies to tuberculosis (TB) diagnosis and treatment has not been researched in Yemen. To examine how gender and literacy influence TB diagnosis and treatment. Individual interviews and data collection were conducted for 74 smear-positive pulmonary TB patients visiting the National Tuberculosis Institute in Sana'a from December 2001 to March 2002. The treatment outcome for each patient was checked from September 2002 to March 2003. Illiterate patients had a longer diagnostic delay than literate patients (P = 0.006, univariate logistic regression analysis). They also maintained their traditional view of illness, not the illness 'TB'. More females than males completed treatment (P = 0.046, univariate logistic regression analysis). Supervision by male relatives contributed to completion of treatment among female patients. Lack of education does not hinder women from receiving TB diagnosis and treatment. The concept of traditional illness, however, causes a longer diagnostic delay among illiterate patients, and the role of male relatives positively influences treatment outcomes for female patients.

Symptom clusters and treatment time delay in Korean patients with ST-elevation myocardial infarction on admission.

PubMed

Kim, Hee-Sook; Eun, Sang Jun; Hwang, Jin Yong; Lee, Kun-Sei; Cho, Sung-Il

2018-05-01

Most patients with acute myocardial infarction (AMI) experience more than one symptom at onset. Although symptoms are an important early indicator, patients and physicians may have difficulty interpreting symptoms and detecting AMI at an early stage. This study aimed to identify symptom clusters among Korean patients with ST-elevation myocardial infarction (STEMI), to examine the relationship between symptom clusters and patient-related variables, and to investigate the influence of symptom clusters on treatment time delay (decision time [DT], onset-to-balloon time [OTB]). This was a prospective multicenter study with a descriptive design that used face-to-face interviews. A total of 342 patients with STEMI were included in this study. To identify symptom clusters, two-step cluster analysis was performed using SPSS software. Multinomial logistic regression to explore factors related to each cluster and multiple logistic regression to determine the effect of symptom clusters on treatment time delay were conducted. Three symptom clusters were identified: cluster 1 (classic MI; characterized by chest pain); cluster 2 (stress symptoms; sweating and chest pain); and cluster 3 (multiple symptoms; dizziness, sweating, chest pain, weakness, and dyspnea). Compared with patients in clusters 2 and 3, those in cluster 1 were more likely to have diabetes or prior MI. Patients in clusters 2 and 3, who predominantly showed other symptoms in addition to chest pain, had a significantly shorter DT and OTB than those in cluster 1. In conclusion, to decrease treatment time delay, it seems important that patients and clinicians recognize symptom clusters, rather than relying on chest pain alone. Further research is necessary to translate our findings into clinical practice and to improve patient education and public education campaigns.

Androgen therapy for delayed male puberty.

PubMed

Ambler, Geoffrey R

2009-06-01

Delayed puberty in men is a commonly presenting problem to paediatricians and an understanding of the available evidence on cause, treatments and outcomes is important to guide practice. Understanding of the regulation of the onset of puberty is gradually unfolding, although the genetic factors that dictate the timing of puberty in individuals and families remain poorly elucidated. Mutations and polymorphisms in candidate genes are being actively studied and it is likely that there is significant overlap between traditional diagnostic categories. Also, environmental endocrine disruptors may interact with the genetic regulation of puberty. Delayed puberty may not always be a benign condition, with increased risks of failing to achieve target height, adverse psychological and educational consequences, delayed sexual and psychosocial integration into society and effects on skeletal proportions and bone mass reported. Appropriate evaluation and follow-up is needed to guide clinical practice, particularly to distinguish constitutional delay in growth and puberty from that associated with other medical disease or permanent disorders. In milder cases of delayed puberty, treatment is often not required; however, considerable evidence exists for the efficacy and safety of short courses of low-dose testosterone therapy for appropriately selected individuals. This treatment is associated with high levels of patient satisfaction. There is not yet sufficient evidence for the routine use of other therapies (e.g. growth hormone, aromatase inhibitors) for constitutional delay in growth and puberty and better characterization of cause may lead to more targeted individual therapy.

Post onset, oral rapamycin treatment delays development of mitochondrial encephalopathy only at supramaximal doses.

PubMed

Felici, Roberta; Buonvicino, Daniela; Muzzi, Mirko; Cavone, Leonardo; Guasti, Daniele; Lapucci, Andrea; Pratesi, Sara; De Cesaris, Francesco; Luceri, Francesca; Chiarugi, Alberto

2017-05-01

Mitochondrial encephalopathies are fatal, infantile neurodegenerative disorders caused by a deficit of mitochondrial functioning, for which there is urgent need to identify efficacious pharmacological treatments. Recent evidence shows that rapamycin administered both intraperitoneally or in the diet delays disease onset and enhances survival in the Ndufs4 null mouse model of mitochondrial encephalopathy. To delineate the clinical translatability of rapamycin in treatment of mitochondrial encephalopathy, we evaluated the drug's effects on disease evolution and mitochondrial parameters adopting treatment paradigms with fixed daily, oral doses starting at symptom onset in Ndufs4 knockout mice. Molecular mechanisms responsible for the pharmacodynamic effects of rapamycin were also evaluated. We found that rapamycin did not affect disease development at clinically-relevant doses (0.5 mg kg -1 ). Conversely, an oral dose previously adopted for intraperitoneal administration (8 mg kg -1 ) delayed development of neurological symptoms and increased median survival by 25%. Neurological improvement and lifespan were not further increased when the dose raised to 20 mg kg -1 . Notably, rapamycin at 8 mg kg -1 did not affect the reduced expression of respiratory complex subunits, as well as mitochondrial number and mtDNA content. This treatment regimen however significantly ameliorated architecture of mitochondria cristae in motor cortex and cerebellum. However, reduction of mTOR activity by rapamycin was not consistently found within the brain of knockout mice. Overall, data show the ability of rapamycin to improve ultrastructure of dysfunctional mitochondria and corroborate its therapeutic potential in mitochondrial disorders. The non-clinical standard doses required, however, raise concerns about its rapid and safe clinical transferability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

PubMed Central

2010-01-01

Background Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. Methods A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Results Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. Conclusions This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for

Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study.

PubMed

Gross, Wibke; Linden, Ulrike; Ostermann, Thomas

2010-07-21

Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development

Delay-range-dependent chaos synchronization approach under varying time-lags and delayed nonlinear coupling.

PubMed

Zaheer, Muhammad Hamad; Rehan, Muhammad; Mustafa, Ghulam; Ashraf, Muhammad

2014-11-01

This paper proposes a novel state feedback delay-range-dependent control approach for chaos synchronization in coupled nonlinear time-delay systems. The coupling between two systems is esteemed to be nonlinear subject to time-lags. Time-varying nature of both the intrinsic and the coupling delays is incorporated to broad scope of the present study for a better-quality synchronization controller synthesis. Lyapunov-Krasovskii (LK) functional is employed to derive delay-range-dependent conditions that can be solved by means of the conventional linear matrix inequality (LMI)-tools. The resultant control approach for chaos synchronization of the master-slave time-delay systems considers non-zero lower bound of the intrinsic as well as the coupling time-delays. Further, the delay-dependent synchronization condition has been established as a special case of the proposed LK functional treatment. Furthermore, a delay-range-dependent condition, independent of the delay-rate, has been provided to address the situation when upper bound of the delay-derivative is unknown. A robust state feedback control methodology is formulated for synchronization of the time-delay chaotic networks against the L2 norm bounded perturbations by minimizing the L2 gain from the disturbance to the synchronization error. Numerical simulation results are provided for the time-delay chaotic networks to show effectiveness of the proposed delay-range-dependent chaos synchronization methodologies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Delay to Reconstruction of the Adolescent Anterior Cruciate Ligament: The Socioeconomic Impact on Treatment.

PubMed

Newman, Justin T; Carry, Patrick M; Terhune, Elizabeth B; Spruiell, Murray; Heare, Austin; Mayo, Meredith; Vidal, Armando F

2014-08-01

A delay in pediatric and adolescent anterior cruciate ligament (ACL) reconstruction is associated with an increase in the number of concomitant meniscal and chondral injuries. Factors that contribute to this delay have not been well described. Socioeconomic and demographic factors are related to ACL surgery timing. Cohort study; Level of evidence, 3. All subjects who underwent primary ACL reconstruction at a single tertiary pediatric hospital between 2005 and 2012 were retrospectively reviewed. Variables included concomitant knee injuries (cartilage or meniscus injuries requiring additional operative treatment) and chronologic, demographic, and socioeconomic factors. Multivariable Cox proportional-hazards analyses were used to identify factors related to ACL surgery timing. The mean age of the 272 subjects was 15.2 ± 2.12 years. Time to surgery was significantly different among subjects who required multiple additional surgical procedures at time of ACL reconstruction (median, 3.3 months) compared with subjects with 1 (median, 2.0 months) or no additional injuries (median, 1.6 months). Subjects underwent ACL reconstruction significantly sooner if they were older at the time of injury (hazard ratio [HR], 1.2 per 1 year; 95% CI, 1.1-1.2; P < .0001) or were covered by a commercial insurance plan (HR, 2.0; 95% CI, 1.6-2.6; P < .0001). Median time to ACL surgery was 1.5 months (95% CI, 1.3-1.7) for subjects with commercial insurance plans compared with 3.0 months (95% CI, 2.3-3.3) for subjects with noncommercial insurance coverage. The risk of delayed ACL surgery was significantly higher among pediatric and adolescent subjects who were less affluent, who were covered by a noncommercial insurance plan, and who were younger. This study also confirms previous studies that have reported an association between a delay in ACL surgery and the presence of additional knee injuries requiring operative treatment, accentuating the importance of timely care. Access to care is a

The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders.

PubMed

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

2017-09-26

The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis. THE EARLIER THE BETTER: The duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to

A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

PubMed

Huang, Fang; Takala-Harrison, Shannon; Jacob, Christopher G; Liu, Hui; Sun, Xiaodong; Yang, Henglin; Nyunt, Myaing M; Adams, Matthew; Zhou, Shuisen; Xia, Zhigui; Ringwald, Pascal; Bustos, Maria Dorina; Tang, Linhua; Plowe, Christopher V

2015-11-15

Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China. Therapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan Province of China near the border with Myanmar. K13 mutations were genotyped by capillary sequencing of DNA extracted from dried blood spots collected in these clinical trials and in routine surveillance. Associations between K13 mutations and delayed parasite clearance were tested using regression models. Parasite clearance half-lives were prolonged after artemisinin treatment, with 44% of infections having half-lives >5 hours (n = 109). Fourteen mutations in K13 were observed, with an overall prevalence of 47.7% (n = 329). A single mutation, F446I, predominated, with a prevalence of 36.5%. Infections with F446I were significantly associated with parasitemia on day 3 following artemisinin treatment and with longer clearance half-lives. Plasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Characeae Cells Plasma Membrane as a Model for Selection of Bioactive Compounds and Drugs: Interaction of HAMLET-Like Complexes with Ion Channels of Chara corallina Cells Plasmalemma.

PubMed

Kataev, Anatoly; Zherelova, Olga; Grishchenko, Valery

2016-12-01

Interaction of a HAMLET-like La-OA cytotoxic complex (human α-lactalbumin-oleic acid) and its constituents with the excitable plasmalemma of giant Chara corallina cells was investigated. The voltage-clamp technique was used to study Ca 2+ and Cl - transient currents in the plasmalemma of intact cells. The action of the complex and OA on the target cell membrane has a dose-dependent character. It was found that the La-OA complex has an inhibiting effect on Ca 2+ current across the plasmalemma, while α-lactalbumin alone does not affect the electrophysiological characteristics of the cellular membrane. However, oleic acid blocks Ca 2+ current across the plasmalemma. This is accompanied by the induction of a non-selective conductivity in the cellular membrane, a decrease in the resting potential and plasma membrane resistance of algal cells. We propose that the cytotoxicity of La-OA and other HAMLET-like complexes is determined by oleic acid acting as a blocker of potential-dependent Ca 2+ channels in the plasma membrane of target cells. The presented results show that the study model of green algae C. corallina cells plasmalemma is a convenient tool for the investigation of ion channels in many animal cells.

Cognitive performance in adolescents with Delayed Sleep-Wake Phase Disorder: Treatment effects and a comparison with good sleepers.

PubMed

Richardson, C; Micic, G; Cain, N; Bartel, K; Maddock, B; Gradisar, M

2018-06-01

The present study aimed to investigate whether Australian adolescents with Delayed Sleep-Wake Phase Disorder have impaired cognitive performance and whether chronobiological treatment for Delayed Sleep-Wake Phase Disorder improves adolescents' sleep, daytime functioning and cognitive performance. Adolescents with Delayed Sleep-Wake Phase Disorder (mean = 15.68 ± 2.1 y, 62% f) reported significantly later sleep timing (d = 1.03-1.45), less total sleep time (d = 0.82) and greater daytime sleepiness (d = 2.66), fatigue (d = 0.63) and impairment (d = 2.41), compared to good sleeping adolescents (mean = 15.9 ± 2.4 y, 75% f). However, there were no significant between-group differences (all p > 0.05) in performance on the Operation Span (ηp 2  = 0.043), Digit Span (forwards: ηp 2  = 0.002, backwards: ηp 2  = 0.003), Letter Number Sequencing (ηp 2  < 0.001) (working memory) and Digit-Symbol Substitution Tasks (ηp 2  = 0.010) (processing speed). Adolescents with Delayed Sleep-Wake Phase Disorder went on to receive 3 weeks of light therapy. At 3 months post-treatment, adolescents with Delayed Sleep-Wake Phase Disorder reported significantly advanced sleep timing (d = 0.56-0.65), greater total sleep time (d = 0.52) and improved daytime sleepiness (d = 1.33), fatigue (d = 0.84) and impairment (d = 0.78). Performance on the Operation Span (d = 0.46), Letter Number Sequencing (d = 0.45) and Digit-Symbol Substitution tasks (d = 0.57) also significantly improved. Copyright © 2018. Published by Elsevier Ltd.

Listening to the Patient Voice in Narcolepsy: Diagnostic Delay, Disease Burden, and Treatment Efficacy.

PubMed

Maski, Kiran; Steinhart, Erin; Williams, David; Scammell, Thomas; Flygare, Julie; McCleary, Kimberly; Gow, Monica

2017-03-15

Describe common symptoms, comorbidities, functional limitations, and treatment responsiveness among patients with narcolepsy. Investigate the effect of pediatric onset of narcolepsy symptoms on time to diagnosis of narcolepsy and presence of comorbid depression. Cross-sectional survey of 1,699 people in the United States with self-reported diagnosis of narcolepsy. We utilized mixed-methods data analyses to report study findings. Most participants reported receiving a diagnosis of narcolepsy more than 1 y after symptom onset. We found that the strongest predictor of this delayed diagnosis was pediatric onset of symptoms (odds ratio = 2.4, p < 0.0005). Depression was the most common comorbidity but we detected no association with pediatric onset of narcolepsy symptoms. Overall, participants reported that fatigue and cognitive difficulties were their most burdensome symptoms in addition to sleepiness and cataplexy. The majority of participants reported residual daytime fatigue and/or sleepiness despite treatment. Most participants reported they could not perform at work or school as well as they would like because of narcolepsy symptoms. This study provides unique insight into the narcolepsy disease experience. The study quantifies the problem of diagnostic delay for narcolepsy patients in the United States and highlights that symptoms are more likely to be missed if they develop before 18 y of age. These results suggest that narcolepsy awareness efforts should be aimed at parents, pediatric health care providers, school professionals, and children/adolescents themselves. Disease burden is high because of problems with fatigue, cognition, and persistence of residual symptoms despite treatment. © 2017 American Academy of Sleep Medicine

Effect of Aegle marmelos and Murraya koenigii in treatment of delayed pubertal buffaloes heifers

PubMed Central

Baitule, Mohan M.; Gawande, A. P.; Kumar, Umesh; Sahatpure, S. K.; Patil, Manoj S.; Baitule, Mansi M.

2016-01-01

Aim: This study aims to study the estrus induction, ovulation, and conception rate of delayed puberty in buffaloes heifers by feeding a herbal plants Aegle marmelos (bael/bili/bhel leaf) and Murraya koenigii (Curry leaf). Materials and Methods: Totally, 24 buffalo heifers with delayed puberty were selected for the present study and divided randomly in four equal groups (n=6). Before experiment, all animals were dewormed with albendazole at 10 mg/kg body weight to prevent them from the stress of parasitism. In the present experiment, four group taken and Group I (n=6) treated with A. marmelos, Group II (n=6) treated with M. koenigii, Group III (n=6) treated with mixture of A. marmelos and M. koenigii and fed for 9 days. Group IV (n=6) considered as control and fed with concentrate only. The blood samples were collected from all the animals on day 0 (before treatment), 4, 9 (during treatment), on the day of estrus and day 8 after the onset of estrus. The 10 ml blood was collected from the jugular vein of all the experimental animals for estimation of serum calcium, inorganic phosphorus, and progesterone (P4). The estrus response, ovulation, conception rate along with serum calcium, inorganic phosphorus, and progesterone level were determined by the standard protocol. Results: From Group III 4 heifers, from Group II 3 heifers, and from Group I and IV (Control) 2 heifers each, exhibited the estrus. The estrus response was recorded as 33.33%, 50.00%, 75.00%, and 33.33% in Group I, Group II, Group III, and Group IV, respectively. In treatment Group III, serum calcium found significantly more (p<0.05) on day 8 post-estrus as compared to other groups at a similar interval. Inorganic phosphorus and progesterone show no significant difference between groups. The ovulation and conception rates are comparatively better in Group III (75%) buffalo heifers than other groups. Conclusion: Herbal supplementation of A. marmelos and M. koenigii in combination, as well as M. koenigii

Classical conditioning for preserving the effects of short melatonin treatment in children with delayed sleep: a pilot study.

PubMed

van Maanen, Annette; Meijer, Anne Marie; Smits, Marcel G; Oort, Frans J

2017-01-01

Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism) received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism) who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light.

Delayed fungal endophthalmitis secondary to Curvularia.

PubMed

Xu, Kunyong; Almeida, David R P; Chin, Eric K; Mahajan, Vinit B

2016-10-01

To describe a case of fungal endophthalmitis secondary to Curvularia after cataract surgery. This case showed delayed and recalcitrant fungal endophthalmitis secondary to Curvularia despite treatment with pars plana vitrectomy, intravitreal antifungal therapy, and systemic antifungals. Curvularia -associated endophthalmitis should be considered in the differential diagnosis of delayed post-cataract endophthalmitis, especially in tropical or subtropical geographical areas. Awareness and early identification, timely removal of the nidi of sequestration, and prolonged antifungal treatments are important for the eradication of Curvularia -associated endophthalmitis.

Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs.

PubMed

Scheper, Verena; Paasche, Gerrit; Miller, Josef M; Warnecke, Athanasia; Berkingali, Nurdanat; Lenarz, Thomas; Stöver, Timo

2009-05-01

Electrical stimulation (ES) of spiral ganglion cells (SGC) via a cochlear implant is the standard treatment for profound sensor neural hearing loss. However, loss of hair cells as the morphological correlate of sensor neural hearing loss leads to deafferentation and death of SGC. Although immediate treatment with ES or glial cell line-derived neurotrophic factor (GDNF) can prevent degeneration of SGC, only few studies address the effectiveness of delayed treatment. We hypothesize that both interventions have a synergistic effect and that even delayed treatment would protect SGC. Therefore, an electrode connected to a pump was implanted into the left cochlea of guinea pigs 3 weeks after deafening. The contralateral untreated cochleae served as deafened intraindividual controls. Four groups were set up. Control animals received intracochlear infusion of artificial perilymph (AP/-). The experimental groups consisted of animals treated with AP in addition to continuous ES (AP/ES) or treated with GDNF alone (GDNF/-) or GDNF combined with continuous ES (GDNF/ES). Acoustically and electrically evoked auditory brain stem responses were recorded. All animals were killed 48 days after deafening; their cochleae were histologically evaluated. Survival of SGC increased significantly in the GDNF/- and AP/ES group compared with the AP/- group. A highly significant increase in SGC density was observed in the GDNF/ES group compared with the control group. Additionally, animals in the GDNF/ES group showed reduced EABR thresholds. Thus, delayed treatment with GDNF and ES can protect SGC from degeneration and may improve the benefits of cochlear implants.

Clinical research for delayed hemorrhage after endoscopic sphincterotomy

PubMed Central

Wang, Yundong; Han, Zhen; Niu, Xiaoping; Jia, Yuliang; Yuan, Heming; Zhang, Guozheng; He, Chiyi

2015-01-01

To analyze the effect of delayed hemorrhage after endoscopic sphincterotomy (EST) and compare the efficacy in improving complication between medicine treatment alone and medicine combined with endoscopic treatment. 1741 patients with EST admitted in Yijishan hospital of Wannan medical college from September 2009 to May 2014 were enrolled in this study. 32 cases suffered from delayed hemorrhage. The patients with delayed hemorrhage were evaluated through incision length of duodenal papilla, clinical manifestation, stool occult blood test and the difference of hemoglobin concentration between pre and post operation. 32 patients were divided into mild bleeding group, mild serious group and serious group through the speed and amount of bleeding. All cases in mild group accepted medicine treatment. Mild serious group were divided into medicine therapy group and medicine combined with endoscopic therapy group randomly. Serious group accepted vascular intervention therapy even traditional operation. The different treatments for delayed hemorrhage were judged by efficiency. The dates were analyzed by t-test or chi-square test. Nobody endured delayed hemorrhage who accepted small incision. Delayed hemorrhage was found in 7 patients out of 627 cases who accepted medium-large incision, 25 patients of 920 cases who accepted large incision. The patients who accepted lager EST were more dangerous than small EST (χ2=4.718, P=0.030) concerning delayed hemorrhage. 32 cases in 1741 patients suffered from delayed hemorrhage. 14 patients only have passed black stool after EST. Among 14 cases, 13 patients stop bleeding after medical therapy, and 1 case received endoscopic hemostasis. 15 cases with hematemesis or melena after EST, 7 patients who received combination therapy stop bleeding. 3 patients from 8 cases stop bleeding after single chemical treatment, 5 cases had to receive endoscopic hemostasis after ineffectual medical therapy. There are significant difference for concerning

Bangladeshi women's experiences of infant feeding in the London Borough of Tower Hamlets.

PubMed

Rayment, Juliet; McCourt, Christine; Vaughan, Lisa; Christie, Janice; Trenchard-Mabere, Esther

2016-07-01

This study examined the main factors that influence Bangladeshi women living in London's decisions to partially breastfeed their children, including the influence of older women within the community. Fifty-seven women of Bangladeshi origin living in the London Borough of Tower Hamlets took part in seven discussion groups between April and June 2013. Five groups were held with women of child-bearing age and two groups with older women in the community. A further eight younger women and three older women took part in one-on-one interviews. Interviews were also carried out with eight local health care workers, including public health specialists, peer support workers, breastfeeding coordinators and a health visitor. The influences on women's infant feeding choices can be understood through a 'socio-ecological model', including public health policy; diverse cultural influences from Bangladesh, London and the Bangladeshi community in London; and the impacts of migration and religious and family beliefs. The women's commitment to breastfeeding was mediated through the complexity of their everyday lives. The tension between what was 'best' and what was 'possible' leads them not only to partially breastfeed but also to sustain partial breastfeeding in a way not seen in other socio-cultural groups in the United Kingdom. © 2015 John Wiley & Sons Ltd.

[Prospective study of ketogenic diet in treatment of children with global developmental delay].

PubMed

Zhu, Deng-Na; Li, Ping; Wang, Jun; Yuan, Jun-Ying; Zhang, Guang-Yu; Liang, Jiang-Fang; Wang, Ming-Mei; Zhao, Yun-Xia; An, Shuang; Ma, Na; Ma, Dan-Dan

2017-10-01

To study the effect of ketogenic diet (KD) on neurobehavioral development, emotional and social behaviors, and life ability in children with global developmental delay (GDD). A prospective case-control study was performed for hospitalized children with GDD, who were randomly divided into KD treatment group (n=40) and conventional treatment group (n=37). The children in both groups were given comprehensive rehabilitation training, and those in the KD treatment group were given modified Atkins diet in addition to the comprehensive rehabilitation training. The children in both groups were assessed with the Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and Infants-Junior High School Students' Social Life Abilities Scale (S-M scale) before treatment and after 3, 6, and 9 months of treatment. The two groups were compared in terms of the improvements in neurobehavioral development, emotional and social behaviors, and social life ability. After 3, 6, and 9 months of treatment, the KD treatment group had significantly greater improvements in the scores of the adaptive, fine motor, and language quotients of the Gesell Developmental Scale compared with the conventional treatment group (P<0.05); the KD treatment group had significantly greater improvements in CITSEA/CBCL scores than the conventional treatment group (P<0.05). The KD treatment group had a greater improvement in the score of the S-M scale after 9 months of treatment (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1 experienced mild urinary stones. KD can improve the neurobehavioral development and behavioral and emotional behaviors in children with GDD, and it has few adverse effects.

Nipple-Sparing Mastectomy is Not Associated with a Delay of Adjuvant Treatment.

PubMed

Albright, Emily L; Schroeder, Mary C; Foster, Kendra; Sugg, Sonia L; Erdahl, Lillian M; Weigel, Ronald J; Lizarraga, Ingrid M

2018-07-01

High-volume single-institution studies support the oncologic safety of nipple sparing mastectomy (NSM). Concerns remain regarding the increased potential for complications, recurrence, and delays to subsequent adjuvant therapy. A national database was used to examine treatment and outcomes for NSM patients. Women undergoing unilateral NSM or skin sparing mastectomy (SSM) for stage 0-4 breast cancer from 2004 to 2013 were identified from the National Cancer Database. Demographic and oncologic characteristics, short-term outcomes and time to local and systemic treatment were compared. NSM was performed on 8173 patients: 8.7% were node positive, and for stage 1-4 disease, 10.6% were triple negative (TN) and 15.3% were HER2-positive. NSM patients were less likely than SSM patients to receive chemotherapy [CT] (37.4 vs. 43.4%) or radiation [PMRT] (15.6 vs. 16.9%), and were also more likely to present with clinically early-stage disease. NSM patients with high-risk features were more likely to receive CT in the neoadjuvant [NCT] than adjuvant setting [AC] (OR 3.76, 1.81, and 1.99 for clinical N2/3, TN, and HER2-positive disease, all p < 0.001). On multivariate analysis, NSM patients had a higher rate of pathologic complete response [pCR] (OR 1.41, p < 0.001). Readmission rate, positive margin rate and time to CT, PMRT or hormonal therapy were not increased for NSM compared to SSM patients. Over one third of NSM patients received chemotherapy and/or radiation. NSM patients with high-risk features were more likely to receive NAC and obtain a pCR. NSM patients did not experience worse outcomes or delayed adjuvant therapy compared to SSM.

Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

DTIC Science & Technology

2011-09-01

Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a

Effects of Annealing Treatment Prior to Cold Rolling on Delayed Fracture Properties in Ferrite-Austenite Duplex Lightweight Steels

NASA Astrophysics Data System (ADS)

Sohn, Seok Su; Song, Hyejin; Kim, Jung Gi; Kwak, Jai-Hyun; Kim, Hyoung Seop; Lee, Sunghak

2016-02-01

Tensile properties of recently developed automotive high-strength steels containing about 10 wt pct of Mn and Al are superior to other conventional steels, but the active commercialization has been postponed because they are often subjected to cracking during formation or to the delayed fracture after formation. Here, the delayed fracture behavior of a ferrite-austenite duplex lightweight steel whose microstructure was modified by a batch annealing treatment at 1023 K (750 °C) prior to cold rolling was examined by HCl immersion tests of cup specimens, and was compared with that of an unmodified steel. After the batch annealing, band structures were almost decomposed as strong textures of {100}<011> α-fibers and {111}<112> γ-fibers were considerably dissolved, while ferrite grains were refined. The steel cup specimen having this modified microstructure was not cracked when immersed in an HCl solution for 18 days, whereas the specimen having unmodified microstructure underwent the delayed fracture within 1 day. This time delayed fracture was more critically affected by difference in deformation characteristics such as martensitic transformation and deformation inhomogeneity induced from concentration of residual stress or plastic strain, rather than the difference in initial microstructures. The present work gives a promise for automotive applications requiring excellent mechanical and delayed fracture properties as well as reduced specific weight.

'Lost to follow up': rethinking delayed and interrupted HIV treatment among married Swazi women.

PubMed

Dlamini-Simelane, Thandeka T T; Moyer, Eileen

2017-03-01

Through various campaigns and strategies, more women are being tested for HIV in countries with a high prevalence of the virus. Despite the ready availability of treatment at government clinics in sub-Saharan African countries like Swaziland, women consistently report difficulty in maintaining access to treatment. Drawing on two individual case studies selected from a larger study of the so-called leaky cascade in Swaziland, we illustrate the protracted journeys married women undertake to initiate treatment. We demonstrate how women manoeuvre tactically after diagnosis, highlight factors that influence their decisions related to initiating treatment, and detail the actors involved in the decision-making process. Our research shows the persistence of structural factors that inhibit access, including economic constraints, gender inequality and patriarchal social norms. Patients referred as ‘lost to follow up’ are in many cases actively pursuing treatment within a context that includes the biomedical health system, but also extends well beyond it. We argue that the phrase ‘lost to follow up’ conceals the complex social navigation required by women to initiate and maintain access to treatment. Further, we suggest that many of the logistical challenges of monitoring and tracking people with HIV can be better addressed by taking into account the structural and social aspects of delayed treatment initiative.

Choice between delayed food and immediate oxycodone in rats.

PubMed

Secci, Maria E; Factor, Julie A; Schindler, Charles W; Panlilio, Leigh V

2016-12-01

The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.

Delayed pan-hypopituitarism as a complication following endovascular treatment of bilateral internal carotid artery aneurysms. A case report and review.

PubMed

Hall, Jonathan; Caputo, Carmela; Chung, Carlos; Holt, Michael; Wang, Yi Yuen

2015-04-01

Pan-hypopituitarism has been reported in patients who are subsequently found to have a cerebral aneurysm and there have been reports of pituitary dysfunction immediately following both surgical and endovascular treatment. The authors report a rare case of delayed pan-hypopituitarism following endovascular treatment of bilateral internal carotid artery aneurysms with coil embolisation and flow-diverting stents.

Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

PubMed

Yanagiha, Kumi; Ishii, Kazuhiro; Tamaoka, Akira

2017-02-01

Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data.

PubMed

Pratt, Arthur G; Lendrem, Dennis; Hargreaves, Ben; Aslam, Osman; Galloway, James B; Isaacs, John D

2016-10-01

To determine whether time to treatment following symptom onset differs between RA patients according to autoantibody status. A single-centre retrospective analysis of a UK early RA inception cohort was first undertaken to identify those components of the patient journey that differed by serological subtype. Data from a UK national audit of early inflammatory arthritis patients was accessed to replicate the key finding. A total of 173 RA patients were diagnosed over a 31-month period, of whom 80 (46%) were ACPA/RF double-seropositive (ACPA(+)/RF(+)), 53 (31%) ACPA(-)/RF(-), 17 (10%) ACPA(+)/RF(-) and 23 (13%) RF(+)/ACPA(-) Overall, ACPA(+)/RF(+) patients experienced significantly longer symptom duration before DMARD initiation. This was accounted for by delays in their presentation to primary care following symptom onset-a finding that was robustly confirmed in an independent dataset of 2192 UK early RA patients. In contrast, ACPA(-)/RF(-) patients were significantly more likely to experience delays in DMARD initiation after presenting to secondary care. Causes of treatment delays in early RA differ according to patients' autoantibody status. More insidious symptom onset and/or distinct health-seeking behaviours among ACPA(+)/RF(+) patients may contribute to late presentations in primary care, whereas ACPA(-)/RF(-) patients experience delayed diagnosis and treatment in secondary care. These observations inform the research agenda, potentially influencing the design of service delivery for early arthritis patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Factors affecting breast cancer treatment delay in Turkey: a study from Turkish Federation of Breast Diseases Societies

PubMed Central

Boylu, Sukru; Ok, Engin; Canturk, Nuh Zafer; Celik, Varol; Kapkac, Murat; Girgin, Sadullah; Tireli, Mustafa; Ihtiyar, Enver; Demircan, Orhan; Baskan, Mazhar Semih; Koyuncu, Ayhan; Tasdelen, Ismet; Dumanli, Esra; Ozdener, Fatih; Zaborek, Piotr

2015-01-01

Background: One of the most important factors in breast cancer (BC) mortality is treatment delay. The primary goal of this survey was to identify factors affecting the total delay time (TDT) in Turkish BC patients. Methods: A total of 1031 patients with BC were surveyed using a uniform questionnaire. The time between discovering the first symptom and signing up for the first medical visit (patient delay time; PDT) and the time between the first medical visit and the start of therapy (system delay time; SDT) were modelled separately with multilevel regression. Results: The mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks, respectively. In all, 42% of the patients had a TDT >12 weeks. Longer PDT was significantly correlated with disregarding symptoms and having age of between 30 and 39 years. Shorter PDT was characteristic of patients who: had stronger self-examination habits, received more support from family and friends and had at least secondary education. Predictors of longer SDT included disregard of symptoms, distrust in success of therapy and medical system and having PDT in excess of 4 weeks. Shorter SDT was linked to the age of >60 years. Patients who were diagnosed during a periodic check-up or opportunistic mammography displayed shorter SDT compared with those who had symptomatic BC and their first medical examination was by a surgeon. Conclusion: TDT in Turkey is long and remains a major problem. Delays can be reduced by increasing BC awareness, implementing organized population-based screening programmes and founding cancer centres. PMID:25096257

[Delays in diagnosing and treating tuberculosis in Croatia].

PubMed

Jurčev-Savičević, Anamarija; Popović-Grle, Sanja; Mulić, Rosanda; Smoljanović, Mladen; Miše, Kornelija

2012-09-01

The aim of this study was to determine factors causing delay in tuberculosis diagnosis and treatment in Croatia. It included 240 adults with pulmonary tuberculosis, who were interviewed for demographics, socioeconomic, lifestyle, and personal health data. Total delay was defined as a number of days from the onset of symptoms to the initiation of therapy. The median and the 75th percentile of the total delay were 68 and 120 days, respectively: 16.7 % of the patients initiated treatment within the first month, 23.8 % within the second month, 23.3 % within the third month, 12.9 % within the fourth month, and 23.3 % more than four months after the symptoms appeared. Long delay (exceeding median delay) was strongly associated with drug abuse (p=0.021). Extreme delay (75th percentile of delay) was significantly associated with the lowest level of education (p=0.021), below minimal income (p=0.039), minimal to average income (p=0.020), current smoking (p=0.050), and co-morbidity (p=0.048). In the multivariate model, long delay remained associated with drug abuse, while extreme delay was associated with the lowest level of education (p=0.033) and current (p=0.017) and ex-smoking (p=0.045).In a setting with decreasing TB incidence, the reported delay can be reduced by increasing health education, not only about tuberculosis per se, but about health in general and attitudes towards prevention and early care. It is also important to increase tuberculosis knowledge among healthcare workers as well as their diagnostic skills.

Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas; Griškevičius, Laimonas; Hallböök, Helene; Heyman, Mats; Klausen, Tobias Wirenfeldt; Jónsson, Ólafur Gísli; Palk, Katrin; Pruunsild, Kaie; Quist-Paulsen, Petter; Vaitkeviciene, Goda; Vettenranta, Kim; Asberg, Ann; Helt, Louise Rold; Frandsen, Thomas; Schmiegelow, Kjeld

2016-02-01

Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001). Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of delayed treatment of China-made Peramivir with repeated intravenous injections in a mouse influenza model: from clinical experience to basal experiment.

PubMed

Li, Zhengtu; Li, Runfeng; Li, Jing; Xie, Hui; Hao, Yanbing; Du, Qiuling; Chen, Tingting; Li, Yimin; Chen, Rongchang; Yang, Zifeng; Zhong, Nanshan

2016-07-08

China-made Peramivir, an anti-influenza neuraminidase inhibitor drug, is manufactured and widely used in China. Although effective if initiated within 48 h of the onset of symptoms, yet we observed that this drug shows an inconclusive efficacy if treatment is delayed in clinical. Thus we evaluated the efficacy of delayed treatment of China-made Peramivir in a mouse model. The mouse model of influenza infection was made and Peramivir was administered intravenously for 5 days following infection, and weight loss, lung index, viral shedding and survival rates were monitored. Peramivir (60 mg/kg · d, repeated intravenous injections, quaque die (QD) × 5 days) enhanced survival rate and suppressed weight loss when treatment was initiated 24, 36, 48, or even 60 h post-infection (p.i.) (p < 0.01), compared with the virus-untreated group, and efficacy was abolished at 72 h p.i.. However the efficacy of delayed treatment was dose dependent, with the highest dose (90 mg/kg · d) even showing efficacy at 72 h p.i.. Furthermore, Peramivir (60 mg/kg · d, repeated intravenous injections, QD × 5 days) also reduced the lung virus titer 24 and 36 h p.i. on day 5, and even at 48 and 60 h p.i. on day 7 after infection, and the lung index was also improved. What is interesting that the concentration of the drug was maintained in blood after infected. Delayed treatment with China-made Peramivir can reduce the severity of influenza disease, accelerate viral clearance and enhance the survival rate. This drug therefore shows good efficacy and is a promising candidate to control the influenza epidemic in China.

Sialoendoscopy combined with an internal stent and postoperative massage as a comprehensive treatment of delayed I131-induced parotitis.

PubMed

Meng, Q; Fang, W; Long, X; Deng, M; Li, J; Ke, J

2017-09-01

A common complication of radioiodine (I 131 ) treatment of thyroid cancer is parotitis. Here we describe our clinical experience in treating delayed I 131 -induced parotitis using sialoendoscopy together with an internal stent and postoperative massage. In this retrospective cohort study we reviewed 32 patients who were treated in that way under general anaesthesia between July 2010 and March 2015. Their age, sex, and the time to development of the parotitis were collected from the hospital's database. All patients were evaluated using a visual analogue scale (VAS), sialography, and computed tomography preoperatively. The analyses of VAS scores were made during postoperative follow-up visits. We used the paired Student's t test and one-way ANOVA to assess the significance of differences, and probabilities of < 0.05 were accepted as significant. The mean (SD) age of the 32 patients was 50 (11) years, and they developed symptoms of delayed parotitis after a mean (SD) of 12 (11) months. The mean time between treatment with I 131 and sialoendoscopy was 26 (10) months. Ductal stenosis was the most common sialoendoscopic feature, together with mucous plugs and fibrosis. Fifty of the 56 ducts were successfully dilated by sialoendoscopy, and VAS scores significantly decreased from a preoperative 7.3 (1.1) to a postoperative 3.3 (2.1) (p=0.000) during follow-up of 3 - 41 months. Sialoendoscopic interventions combined with an internal stent and postoperative massage may be optimal comprehensive treatment for delayed I 131 -induced parotitis. Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

An Altered Perception of Normal: Understanding Causes for Treatment Delay in Women with Symptomatic Uterine Fibroids.

PubMed

Ghant, Marissa S; Sengoba, Katherine S; Vogelzang, Robert; Lawson, Angela K; Marsh, Erica E

2016-08-01

Uterine fibroids are benign tumors that are the leading cause of hysterectomy in the United States. Despite their high prevalence and associated morbidity, there are little qualitative data characterizing what drives women's treatment-seeking behavior for their fibroids. Women with symptomatic or recently treated uterine fibroids completed in-depth interviews and demographic surveys. Interviews were transcribed verbatim and uploaded to NVivo version 10 for data management and thematic coding. Coders identified major themes and subthemes that emerged from the interviews. Sixty women (n = 60) completed the interviews. The kappa among coders was 0.94. The mean age of participants was 43.0 ± 6.8. 61.7% of participants self-identified as African American, 25.0% as Caucasian, 8.3% as Hispanic, and 5.0% as Asian. Many women reported obtaining a delayed diagnosis for their uterine fibroids despite experiencing severe symptoms. There were five subthemes that identified why women delayed seeking treatment, which included the perception that their symptoms were "normal," they had a low knowledge of fibroids, they did not perceive themselves to be at risk for fibroids, they engaged in avoidance-based coping strategies, and/or they dissociated themselves from their fibroids. Many women with symptomatic fibroids live with this condition chronically without seeking care. It appears that for some, limited knowledge regarding fibroids and normal menstruation may lead to a distorted view of what is normal with regard to uterine bleeding, resulting in limited treatment seeking behavior. Others know their symptoms are abnormal but simply avoid the problem. There is a need for patient-centered and community-based education to improve women's knowledge of fibroids and symptoms and to promote treatment options.

The treatment of posterior urethral disruption associated with pelvic fractures: comparative experience of early realignment versus delayed urethroplasty.

PubMed

Mouraviev, Vladimir B; Coburn, Michael; Santucci, Richard A

2005-03-01

Urological treatment of the patient with severe mechanical trauma and urethral disruption remains controversial. Debate continues regarding the advisability of early realignment vs delayed open urethroplasty. We analyzed our experience with 96 patients to determine the long-term results of the 2 approaches. We retrospectively reviewed the records of 191 men with posterior urethral disruption after severe blunt pelvic injury between 1984 and 2001, of whom 96 survived. Data on 57 patients who underwent early realignment were compared to those on 39 treated with delayed urethroplasty with an average 8.8-year followup (range 1 to 22). All patients were evaluated postoperatively for incontinence, impotence and urethral strictures. The majority of patients had severe concomitant organ injuries (78%) and severe pelvic fractures (76%). The overall mortality rate was 51%. Diagnosis of urethral rupture was based on clinical findings and retrograde urethrography. Strictures developed in 49% of the early realignment group and in 100% of the suprapubic tube group. Impotence (33.6%) and incontinence (17.7%) were less frequent in the early realignment group than in the delayed reconstruction group (42.1% and 24.9%, respectively). Patients with delayed reconstruction underwent an average of 3.1 procedures compared with an average of 1.6 in the early realignment group. Early realignment may provide better outcomes than delayed open urethroplasty after posterior urethral disruption. Increased complications are not seen and, although it can be inconvenient in the massively injured patient, it appears to be a worthwhile maneuver.

Factors affecting breast cancer treatment delay in Turkey: a study from Turkish Federation of Breast Diseases Societies.

PubMed

Ozmen, Vahit; Boylu, Sukru; Ok, Engin; Canturk, Nuh Zafer; Celik, Varol; Kapkac, Murat; Girgin, Sadullah; Tireli, Mustafa; Ihtiyar, Enver; Demircan, Orhan; Baskan, Mazhar Semih; Koyuncu, Ayhan; Tasdelen, Ismet; Dumanli, Esra; Ozdener, Fatih; Zaborek, Piotr

2015-02-01

One of the most important factors in breast cancer (BC) mortality is treatment delay. The primary goal of this survey was to identify factors affecting the total delay time (TDT) in Turkish BC patients. A total of 1031 patients with BC were surveyed using a uniform questionnaire. The time between discovering the first symptom and signing up for the first medical visit (patient delay time; PDT) and the time between the first medical visit and the start of therapy (system delay time; SDT) were modelled separately with multilevel regression. The mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks, respectively. In all, 42% of the patients had a TDT >12 weeks. Longer PDT was significantly correlated with disregarding symptoms and having age of between 30 and 39 years. Shorter PDT was characteristic of patients who: had stronger self-examination habits, received more support from family and friends and had at least secondary education. Predictors of longer SDT included disregard of symptoms, distrust in success of therapy and medical system and having PDT in excess of 4 weeks. Shorter SDT was linked to the age of >60 years. Patients who were diagnosed during a periodic check-up or opportunistic mammography displayed shorter SDT compared with those who had symptomatic BC and their first medical examination was by a surgeon. TDT in Turkey is long and remains a major problem. Delays can be reduced by increasing BC awareness, implementing organized population-based screening programmes and founding cancer centres. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association.

Delayed pressure urticaria: response to treatment with sulfasalazine in a case series of seventeen patients.

PubMed

Swerlick, Robert A; Puar, Neha

2015-01-01

We retrospectively identified 17 patients with delayed pressure urticaria (DPU), diagnosed by history and confirmed with provocative pressure testing. The average age in the cohort was 42.6 years with 10 women and seven men. The mean duration of disease before diagnosis was 19.7 months (range, 1-60 months). The diagnosis of DPU was not included in the differential diagnosis of referring physicians and was not a diagnostic consideration in any of seven biopsies obtained. None of the patients responded adequately to treatment with antihistamines, but all 17 responded transiently when treated with either oral or intramuscular steroids. Eleven patients experienced complete or near complete resolution of DPU with treatment with sulfasalazine (SZ). Four patients had a partial response while two were unable to continue therapy because of drug intolerance. SZ appears to be a low cost and effective treatment for DPU. © 2015 Wiley Periodicals, Inc.

[Usefulness of endovascular treatment for delayed massive epistaxis following endoscopic endonasal transsphenoidal surgery: a case report].

PubMed

Oka, Tetsuo; Sugiu, Kenji; Ishida, Joji; Hishikawa, Tomohito; Ono, Shigeki; Tokunaga, Koji; Date, Isao

2012-01-01

We report here a case of massive nasal bleeding from the sphenopalatine artery three weeks after endonasal transsphenoidal surgery. This 66-year-old male suffered from massive nasal bleeding with the status of hypovolemic shock. Under general anesthesia, an emergent angiography revealed an extravasation from the sphenopalatine artery. Trans-arterial embolization using coil and n-butyl-cyanoacrylate (NBCA) was performed following the diagnostic angiography. Complete occlusion of the injured artery was achieved. The patient showed good recovery from general anesthesia. Delayed nasal bleeding after endonasal transsphenoidal surgery is a rare but important complication. The sphenopalatine artery and its branch are located in the hidden inferior lateral corner of the sphenoid sinus and may be injured during enlargement of the sphenoid opening. When massive delayed nasal bleeding follows transsphenoidal surgery and damage of the internal carotid artery has been ruled out, endovascular treatment of the external carotid artery should be considered.

Behavior Problems in Toddlers with and without Developmental Delays: Comparison of Treatment Outcomes

ERIC Educational Resources Information Center

Holtz, Casey A.; Carrasco, Jennifer M.; Mattek, Ryan J.; Fox, Robert A.

2009-01-01

The purpose of this study is to examine the effectiveness of an in-home parent management program for toddlers with behavior problems and developmental delays by comparing outcomes for a group of toddlers with developmental delays (n = 27) and a group of toddlers without developmental delays (n = 27). The majority of children lived in single…

Tuberculosis diagnostic delay and therapy outcomes of non-national migrants in Tel Aviv, 1998-2008.

PubMed

Mor, Z; Kolb, H; Lidji, M; Migliori, Gb; Leventhal, A

2013-03-21

Non-national migrants have limited access to medical therapy. This study compares diagnostic delay and treatment outcomes of non-insured non-national migrants (NINNM) with insured Israeli citizens (IC) in the Tel Aviv tuberculosis (TB) clinic between 1998 and 2008. Patient delay was the time from symptoms onset to doctor's visit, while system delay was measured from doctor visit to anti-TB therapy administration. We randomly sampled 222 NINNM and 265 IC. NINNM were younger than IC, had lower male to female ratio and fewer smoked. They had less drug/alcohol abuse, more cavitations on chest radiography, longer patient and shorter system delay. Mean patient and system delays of all patients were 25 ± 14 and 79 ± 42 days, respectively. In multivariate analysis, being NINNM, asymptomatic or smoking predicted longer patient delay, while being asymptomatic or having additional co-morbidity predicted longer system delay. Treatment success in sputum smear-positive pulmonary TB NINNM was 81% and 95.7% in IC (p=0.01). Treatment success was not associated with patient or system delay. In multivariate analysis, work security and treatment adherence predicted treatment success. NINNM had longer patient delay and worse therapy outcome, while IC had longer system delay. Both delays should be reduced. NINNM should be informed that TB therapy is free and unlinked with deportation.

Various Treatment Techniques on Signs and Symptoms of Delayed Onset Muscle Soreness

PubMed Central

Gulick, Dawn T.; Kimura, Iris F.; Sitler, Michael; Paolone, Albert; Kelly, John D.

1996-01-01

Eccentric activities are an important component of physical conditioning and everyday activities. Delayed onset muscle soreness (DOMS) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise. An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living. The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS. In the selection of treatment methods, emphasis was directed toward treatments that could be rendered independently by an individual, therefore making the treatment valuable to an athletic trainer in team setting. DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer. All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced. Data were collected on 15 dependent variables: active and passive wrist flexion and extension, forearm girth, limb volume, visual analogue pain scale, muscle soreness index, isometric strength, concentric and eccentric wrist total work, concentric and eccentric angle of peak torque. Data were collected on six occasions: pre- and post-induced DOMS, 20 minutes after treatment, and 24, 48, and 72 hours after treatment. Subjects were randomly assigned to 1 of 7 groups (6 treatment and 1 control). Treatments included a nonsteroidal anti-inflammatory drug, high velocity concentric muscle contractions on an upper extremity ergometer, ice massage, 10-minute static stretching, topical Amica montana ointment, and sublingual A. montana pellets. A 7 × 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables. Significant main effects (p < .05) were found for all of the dependent variables on time only. There were no significant differences between

Delayed haemolysis secondary to treatment of severe malaria with intravenous artesunate: Report on the experience of a referral centre for tropical infections in Spain.

PubMed

Aldámiz-Echevarría Lois, Teresa; López-Polín, Ana; Norman, Francesca F; Monge-Maillo, Begoña; López-Vélez, Rogelio; Perez-Molina, Jose A

Post-artesunate delayed haemolysis is described as hemolytic anemia presenting days after malaria treatment in hyperparasitemic patients. Physiopathological mechanisms and clinical manifestations have not been thoroughly characterised. We conducted a retrospective study of hospitalised malaria patients who received artemisinin derivatives from January 1, 2010 to December 31, 2015. 21 patients were included in the study: 11 travellers, 8 travellers visiting friends and relatives and 2 immigrants. Median age was 35.5 years (IQR: 25.7-44.8) and 11 were men. Eight patients received oral and 13 received intravenous (IV) artemisinin-based drugs. Follow-up after the malaria episode was available for 15 patients (12 with IV treatment). Four patients presented with delayed haemolysis 9-14 days after artesunate treatment; all had been admitted with severe malaria, were treated IV and had hyperparasitaemia (17%-33%). Other than hyperparasitaemia, no other factors were associated with artesunate haemolysis. Patients' outcomes were favourable and the only additional therapeutic measure needed was a blood transfusion. Delayed haemolysis is a frequent complication in hyperparasitemic malaria treated with IV artesunate. Follow-up is mandatory for at least 2 weeks after treatment initiation. This condition is potentially severe but does not appear to be life threatening. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Mental health of children, adolescents and young adults--part 1: prevalence, illness persistence, adversities, service use, treatment delay and consequences].

PubMed

Lambert, M; Bock, T; Naber, D; Löwe, B; Schulte-Markwort, M; Schäfer, I; Gumz, A; Degkwitz, P; Schulte, B; König, H H; Konnopka, A; Bauer, M; Bechdolf, A; Correll, C; Juckel, G; Klosterkötter, J; Leopold, K; Pfennig, A; Karow, A

2013-11-01

Numerous birth-control studies, epidemiological studies, and observational studies have investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use by children, adolescents and young adults is low, even lower than for adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for a poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the interface of child and adolescent and adult psychiatry. Emerging studies show that these health-care structures are effective and efficient. Part 1 of the present review summarises the current state of mental health in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, and treatment delay with consequences. © Georg Thieme Verlag KG Stuttgart · New York.

Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor.

PubMed

Taverna, Livia; Tremolada, Marta; Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

2017-01-01

CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS's total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.

Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor

PubMed Central

Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

2017-01-01

CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07–5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children’s motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS’s total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children’s motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis’ tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia. PMID

Routine delayed voiding cystourethography after initial successful endoscopic treatment with Dextranomer/Hialuronic Acid Copolimer (Dx/HA) of vesicoureteral reflux (VUR). Is it necessary?

PubMed

García-Aparicio, L; Blázquez-Gómez, E; Vila Santandreu, A; Camacho Diaz, J A; Vila-Cots, J; Ramos Cebrian, M; de Haro, I; Martin, O; Tarrado, X

2016-12-01

Some guidelines recommend an early voiding cystourethrography (VCUG) after endoscopic treatment of vesicoureteral reflux (VUR), but there's no consensus if it's necessary a long-term follow-up in these patients. The aim of our study is analyze if it's necessary a delayed VCUG after initial successful treatment with Dx/HA. We have reviewed all medical charts of patients that underwent Dx/HA treatment from 2006 to 2010. We have selected patients with initial successful treatment and more than 3 years of radiological and clinical follow-up. We have analyzed late clinical and radiological outcomes. One hundred and sixty children with 228 refluxing ureters underwent Dx/HA endoscopic treatment with a mean follow-up of 52.13 months. Early VCUG was performed in 215 ureters with an initial successful rate of 84.1%. The group of study was 94/215 ureters with more than 3 years of follow-up with a delayed VCUG. VUR was still resolved in 79,8% of the ureters. Clinical success rate was 91.7%. The incidence of febrile urinary tract infection in those patients with cured VUR and those with a relapsed VUR was 8 and 15%, respectively; but there were no significant differences. We have not found any variable related with relapsed VUR except those ureters that initially received 2 injections (P<.05). If our objective in the treatment of VUR is to reduce the incidence of febrile urinary tract infection it is not necessary to perform a delayed VCUG even though the long-term radiological outcomes is worse than clinical outcome. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Patient and health system delay among patients with pulmonary tuberculosis in Beira city, Mozambique.

PubMed

Saifodine, Abuchahama; Gudo, Paula Samo; Sidat, Mohsin; Black, James

2013-06-07

TB control is based on the rapid identification of cases and their effective treatment. However, many studies have shown that there are important delays in diagnosis and treatment of patients with TB. The purpose of this study was to assess the prevalence of and identify risk factors associated with patient delay and health system delay among newly diagnosed patients with pulmonary TB. A cross sectional study was carried out in Beira city, Mozambique between September 2009 and February 2010. Patients in the first month of treatment were consecutively selected to this study if they had a diagnosis of pulmonary TB, had no history of previous TB treatment, and were 18 years or older and provided informed consent. Data was obtained through a questionnaire administered to the patients and from patients' files. Among the 622 patients included in the study the median age was 32 years (interquartile range, 26-40) and 272 (43.7%) were females. The median total delay, patient delay and health system delay was 150 days (interquartile range, 91-240), 61 days (28-113) and 62 days (37-120), respectively. The contribution of patient delay and health system delay to total delay was similar. Farming, visiting first a traditional healer, low TB knowledge and coexistence of a chronic disease were associated with increased patient delay. More than two visits to a health facility, farming and coexistence of a chronic disease were associated with increased health system delay. This study revealed a long total delay with a similar contribution of patient delay and health system delay. To reduce the total delay in this setting we need a combination of interventions to encourage patients to seek appropriate health care earlier and to expedite TB diagnosis within the health care system.

[Using delayed auditory feedback in the treatment of stuttering: evidence to consider].

PubMed

Van Borsel, John; Sierens, Sarah; Pereira, Mônica Medeiros de Britto

2007-01-01

There is some indication that the use of delayed auditory feedback (DAF) is a potentially helpful technique in the treatment of stuttering. Several devices for DAF are also commercially. However, not all individuals who stutter experience a positive effect on speech fluency when speaking under DAF. And those who do show a positive effect, may differ considerably as to the degree and the conditions in which the effect is seen. Therefore, the decision whether or not to attempt the use of DAF in an given client is usually not straightforward. Starting from a literature review, the present paper discusses and illustrates factors to take into account when considering the use of RAA in an individual client. Four types of factors are distinguished: factors inherent to the client such as gender, age, stuttering severity, dysfluency pattern, origin of stuttering, and biological subtype; factors outside the client including delay time, intensity, manner of delivery, speech mode, and speech situation; possible side-effects like a reduction in speech rate, an increase of speaking fundamental frequency and vocal intensity, lengthening of vowels, and a possible effect on speech naturalness; others namely cosmetics, finances, and the long-term effect. The review shows that most likely multiple factors play a role, but with the currently available data it is very hard to predict whether a given individual will or will not benefit from the use of DAF. Overall, the evidence for the influence of the different factors is still meager. Moreover, some studies present data of a quality that can hardly be considered "evidence".

Downhole delay assembly for blasting with series delay

DOEpatents

Ricketts, Thomas E.

1982-01-01

A downhole delay assembly is provided which can be placed into a blasthole for initiation of explosive in the blasthole. The downhole delay assembly includes at least two detonating time delay devices in series in order to effect a time delay of longer than about 200 milliseconds in a round of explosions. The downhole delay assembly provides a protective housing to prevent detonation of explosive in the blasthole in response to the detonation of the first detonating time delay device. There is further provided a connection between the first and second time delay devices. The connection is responsive to the detonation of the first detonating time delay device and initiates the second detonating time delay device. A plurality of such downhole delay assemblies are placed downhole in unfragmented formation and are initiated simultaneously for providing a round of explosive expansions. The explosive expansions can be used to form an in situ oil shale retort containing a fragmented permeable mass of formation particles.

The role of health system factors in delaying final diagnosis and treatment of breast cancer in Mexico City, Mexico.

PubMed

Bright, Kristin; Barghash, Maya; Donach, Martin; de la Barrera, Marcos Gutiérrez; Schneider, Robert J; Formenti, Silvia C

2011-04-01

In Mexico, breast cancer is the leading cancer-related death among women and most cases are diagnosed at advanced stages (50-60%). We hypothesized health system factors could be partly responsible for this delay and performed a prospective review of 166 new breast cases at a major public hospital in Mexico City. Our analysis confirmed the prevalence of locally advanced and metastatic disease (47% of patients). A subset analysis of 32 women with confirmed stage I-IIIC breast cancer found an average time interval of 1.8 months from symptom onset to first primary care consultation (PCC), with an additional 6.6 months from first PCC to confirmed diagnosis, and 0.6 months from diagnosis to treatment initiation. Patients underwent an average of 7.9 clinic visits before confirmed diagnosis. Findings suggest that protracted referral time from primary to specialty care accounts for the bulk of delay, with earlier stage patients experiencing longer delays. These findings reveal a critical need for further study and exploration of interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Testosterone treatment and arginine-induced growth hormone stimulation in male delayed puberty: effects on serum calcium, phosphate and vitamin D metabolites.

PubMed

Hyldstrup, L; Christiansen, C; Nielsen, M D; Transbøl, I

1984-06-01

Hormonal changes after arginine-induced growth hormone stimulation and subsequent testosterone treatment were examined in 5 patients classified as having male delayed puberty. All the patients responded well to growth hormone stimulation and a significant negative correlation was found between the delay in height age and the maximal growth hormone response, r = 0.80, P less than 0.05. The testosterone treatment did not alter this pattern. Changes in PTH, 25OHD, 24.25(OH)2D, and 1.25(OH)2D were examined at 24 h after the infusion. The results showed significant reductions in PTH (P less than 0.05) and 24.25 (OH)2D (P less than 0.05) and a possible increase in 1.25(OH)2D, whereas 25OHD remained unchanged. These results may support the conception of growth hormone as a common denominator of growth and bone metabolism.

Delays in definitive cervical cancer treatment: An analysis of disparities and overall survival impact.

PubMed

Ramey, Stephen J; Asher, David; Kwon, Deukwoo; Ahmed, Awad A; Wolfson, Aaron H; Yechieli, Raphael; Portelance, Lorraine

2018-04-01

Delays in time to treatment initiation (TTI) with definitive radiation therapy (RT) or chemotherapy and RT (CRT) for cervical cancer could lead to poorer outcomes. This study investigates disparities in TTI and the impact of TTI on overall survival (OS). Adult women with non-metastatic cervical squamous cell carcinoma diagnosed between 2004 and 2014, treated with definitive RT or CRT, and reported to the National Cancer Database were included. TTI was defined as days from diagnosis to start of RT or CRT. The impact of TTI on OS in patients treated with concurrent CRT which included brachytherapy was then assessed. Overall, 14,924 patients were included (84.7% CRT, 15.3% RT). TTI was significantly longer for Non-Hispanic Black (NHB) (RR, 1.14; 95% CI, 1.11 to 1.18) and Hispanic women (RR, 1.19; 95% CI, 1.15 to 1.24) compared to Non-Hispanic White (NHW) women. Expected TTI (eTTI) for NHW, NHB, and Hispanic women were 38.1, 45.2, and 49.4days. eTTI rose from 36.2days in 2004 to 44.3days by 2014. Intensity-modulated radiation therapy (IMRT) was associated with increased eTTI of 46.5days versus 40.0days for non-IMRT. Longer TTI was not associated with inferior OS in patients treated with concurrent CRT. Delays in starting RT/CRT for cervical cancer increased from 2004 to 2014. Delays disproportionately affect NHB and Hispanic women. However, increased TTI was not associated with increased mortality for women receiving CRT. Further study of TTI's impact on other endpoints is warranted to determine if TTI represents an important quality indicator. Copyright © 2017 Elsevier Inc. All rights reserved.

The delaying effect of stigma on mental health help-seeking in Sri Lanka.

PubMed

Fernando, Sunera M; Deane, Frank P; McLeod, Hamish J

2017-03-01

Mental health stigma has been associated with delays in seeking treatment. To describe perceived stigma experienced by patients and carers in Sri Lanka and to determine the effects of stigma on help-seeking delay. Survey of outpatients and family carers (n = 118 dyads) attending two psychiatric hospitals in Sri Lanka, using the Disclosure and Discrimination subscales of the Stigma Scale. Stigma was positively related to help-seeking delay for carers but not patients. Public stigma experienced by carers accounted for 23% of the variance in help-seeking delay. Reducing stigma may reduce help-seeking delays during the course of treatment. © 2016 John Wiley & Sons Australia, Ltd.

Disparities in breast cancer surgery delay: the lingering effect of race.

PubMed

Sheppard, Vanessa B; Oppong, Bridget A; Hampton, Regina; Snead, Felicia; Horton, Sara; Hirpa, Fikru; Brathwaite, Echo J; Makambi, Kepher; Onyewu, S; Boisvert, Marc; Willey, Shawna

2015-09-01

Delays to surgical breast cancer treatment of 90 days or more may be associated with greater stage migration. We investigated racial disparities in time to receiving first surgical treatment in breast cancer patients. Insured black (56 %) and white (44 %) women with primary breast cancer completed telephone interviews regarding psychosocial (e.g., self-efficacy) and health care factors (e.g., communication). Clinical data were extracted from medical charts. Time to surgery was measured as the days between diagnosis and definitive surgical treatment. We also examined delays of more than 90 days. Unadjusted hazard ratios (HRs) examined univariate relationships between delay outcomes and covariates. Cox proportional hazard models were used for multivariate analyses. Mean time to surgery was higher in blacks (mean 47 days) than whites (mean 33 days; p = .001). Black women were less likely to receive therapy before 90 days compared to white women after adjustment for covariates (HR .58; 95 % confidence interval .44, .78). Health care process factors were nonsignificant in multivariate models. Women with shorter delay reported Internet use (vs. not) and underwent breast-conserving surgery (vs. mastectomy) (p < .01). Prolonged delays to definitive breast cancer surgery persist among black women. Because the 90-day interval has been associated with poorer outcomes, interventions to address delay are needed.

Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out Procedure.

PubMed

Coppage, Sara; Meindl, James N

2017-09-01

Treatment plans focused on problem behavior often include punishment contingencies to decrease problem behavior. Immediate punishers are typically more effective than delayed punishers, but immediate delivery of a punisher is not always possible. Strategies need to be developed to increase the suppressive effects of delayed punishers. This study demonstrated the effectiveness of a treatment package involving replaying a video recording of problem behavior immediately before delivering a 15 min delayed time-out. This treatment package may prove to be an accessible and inexpensive strategy when using delayed punishers.

Contemporary Determinants of Delayed Benchmark Timelines in Acute Myocardial Infarction in Men and Women.

PubMed

Alnsasra, Hilmi; Zahger, Doron; Geva, Diklah; Matetzky, Shlomi; Beigel, Roy; Iakobishvili, Zaza; Alcalai, Ronny; Atar, Shaul; Shimony, Avi

2017-11-15

Treatment delays in patients with acute myocardial infarction (AMI) are related to increased morbidity and mortality. Hence, identifying determinants of delay may help reduce time to treatment. Importantly, limited data suggest that there may be sex-related disparities in benchmark timelines. Although guidelines advocate the use of the first medical contact (FMC) rather than hospital admission as the moment from which delays to treatment should be monitored, the latter is still often used for quality purposes. We aimed to identify factors associated with treatment delays, with an emphasis on sex-related disparities. We reviewed data on 3,658 patients with AMI from 2 contemporary, consecutive multicenter surveys. Measured delays were FMC-to-electrocardiogram >10 minutes in ST-elevation MI (STEMI) and non-STEMI, FMC-to-primary percutaneous coronary intervention >90 minutes in STEMI, and invasive angiography >72 hours after admission in non-STEMI patients. Timely electrocardiogram was performed in 48% of patients with STEMI and in 39.8% of non-STEMI patients without significant sex-related differences. Independent determinants of delay included atypical chest pain (CP) and presentation during daytime. In patients with STEMI, 37.5% had primary percutaneous coronary intervention in less than 90 minutes without significant sex-related disparities. Independent determinants of delay included atypical CP, night presentation, and diabetes. In non-STEMI patients, independent determinants of delayed invasive approach were female sex, age >75 years, atypical CP, and renal failure. In conclusion, significant treatment delays in patients with AMI are still frequent in contemporary practice, highlighting the need for improvement and guidelines implementation. Predictors of delay identified in our study may facilitate targeting of interventions to improve adherence to guidelines. Copyright © 2017 Elsevier Inc. All rights reserved.

No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

PubMed Central

Maiga, Amelia W.; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Dara, Antoine; Traore, Oumar Bila; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Kone, Aminatou; Thera, Mahamadou A.; Plowe, Christopher V.; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

2012-01-01

Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa. PMID:22764287

[Early versus delayed physiotherapy in the treatment of post-prostatectomy male urinary incontinence].

PubMed

Tarcía Kahihara, Carina; Ferreira, Ubirajora; Nardi Pedro, Renato; Matheus, Wagner Eduardo; Rodrigues Netto, Nelson

2006-10-01

To analyze the importance of the starting time for pelvic floor physiotherapy in patients with post radical prostatectomy urinary incontinence. Between May 2003 and February 2004 18 patients with the diagnosis of post radical prostatectomy urinary incontinence underwent physiotherapy of the pelvic floor. Each patient received 12 sessions using kinesotherapy and electric stimulation on a weekly basis. Patients were divided into two groups: Group 1 included eight patients that started therapy within the first six months after surgery; Group 2 included 10 patients starting therapy after the sixth post operative month. All patients were evaluated by the pad test and number of incontinence pads per day. Evaluating pad tests before and after treatment, six patients in group 1 had a reduction of the amount of urine leak in comparison to seven patients in group 2. The statistical analysis showed significant differences before and after treatment for both groups (group 1: p = 0.028; group 2: p = 0.018). The evaluation of the number of pads showed: Group 1: all eight patients using pods had a reduction in the number of pads. Group 2: 5 of the eight patients using pads had a reduction and the other three continued using the same number. Statistical analysis comparing the number of pads per day before and after treatment showed a significant difference in group 1 (p = 0.004). There was no statistically significant difference in the number of pads per day before and after physiotherapy in group 2, although half of the patients showed a diminishment in the number of pads required after treatment. Results demonstrate that early indication of physiotherapy for the treatment of post radical prostatectomy urinary incontinence is better than delayed treatment. New works may be developed in the future to confirm our results.

Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum.

PubMed

Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M

2015-06-01

The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (P<0.0005). Among characteristics of HG pregnancies, only early onset of symptoms (prior to 5 weeks gestation) was significantly linked to neurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

PubMed Central

Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

2013-01-01

Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance of the same capuchin monkeys, belonging to two study populations, between these tasks. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support to the hypothesis that these tasks provide equivalent measures of delay of gratification. PMID:23544770

Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Chinmaya; López, José Manuel; Azencott, Robert

Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemicalmore » Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.« less

Nonconvulsive status epilepticus and neurodevelopmental delay.

PubMed

Dirik, Eray; Yiş, Uluç; Hüdaoglu, Orkide; Kurul, Semra

2006-09-01

Nonconvulsive status epilepticus is characterized by continuous or near continuous epileptiform discharges on electroencephalography without overt motor or sensory phenomena. It is a symptomatic condition related to a disease such as epileptic encephalopathy or a metabolic disorder. Children with isolated nonconvulsive status epilepticus rarely present with global neurodevelopmental delay. This report describes an 18-month-old male who presented with global neurodevelopmental delay and decreased alertness in whom electrical status epilepticus during sleep, which is a form of nonconvulsive status epilepticus, was determined. Metabolic investigations and cranial magnetic resonance imaging were normal. He began to achieve developmental milestones after treatment with valproic acid. Although rare, pediatric neurologists and pediatricians must be aware of this condition in making the differential diagnosis of global neurodevelopmental delay and decreased alertness.

Is immediate adjunctive CBT more beneficial than delayed CBT in treating depression?: A Pilot Study.

PubMed

Rizvi, Sakina J; Zaretsky, Ari; Schaffer, Ayal; Levitt, Anthony

2015-03-01

Cognitive-behavioral therapy (CBT) is an efficacious first-line therapy for patients with major depressive disorder (MDD). Due to the limited accessibility of CBT, long wait lists result in delayed treatment, which may affect treatment outcomes. The goal of this pilot study was to obtain preliminary data from a randomized controlled trial to determine whether delayed CBT reduces the effectiveness of the therapy compared to immediate CBT in patients with MDD receiving pharmacotherapy. Patients were randomized to receive immediate CBT (n=18) or to begin CBT after 6 months (n=20) and received 14 weekly sessions, followed by two additional booster sessions. During the active treatment months, patients in the immediate group demonstrated reductions in scores on the Beck Depression Inventory II (BDI-II) that were similar to those in the delayed CBT group. However, when the analysis was performed using only data from patients in the delayed group who were still in a depressive episode, there was an overall greater decrease in BDI-II scores in the immediate group vs. the delayed group over the active treatment months, but not specifically at the 6-month endpoint. These findings suggest delays in depression treatment, similar to what occurs with real-world wait list times, may not have a significant impact on the effectiveness of CBT in patients who are already receiving treatment as usual. However, such delays may affect the effectiveness of CBT in those patients who remain depressed during the time delay. A larger trial is necessary to confirm these findings. (Journal of Psychiatric Practice 2015;21:107-113).

Diagnostic delay among pulmonary tuberculosis patients in Sarawak, Malaysia: a cross-sectional study.

PubMed

Chang, Ching Thon; Esterman, Adrain

2007-01-01

Delayed diagnosis of tuberculosis (TB) can lead to an increased period of infectivity in the community, a delay in treatment and a severe form of the disease. The objective of this study was to determine the length of delay, and factors linking the delay from the onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment in Sarawak, Malaysia. An institution based cross-sectional study was conducted in 10 TB clinics in randomly selected divisions in Sarawak from June 2003 to May 2004. Delay was analyzed from two perspectives: (1) period between the onset of TB symptoms to any first medical consultation (patients' delay); and (2) period between the first medical consultation to the diagnosis of TB (diagnosis delay). Patients were interviewed on diagnosis or within the admission period using a semi-structured questionnaire. A total of 316 new smear-positive PTB patients participated in the study. The median patient interval was 30 days. Gender was found to be significantly associated with patient delay. The median diagnosis interval was 22 days. Respondents' incomes, health-care professional first consulted and actions taken by the health-care providers during the first consultation were significantly associated with diagnosis delay. The medium treatment interval was 0 days. Both patients and health providers played a role in delaying TB diagnosis. Females appeared to have longer delay. Respondents living above the poverty line had diagnosis delay as they made more visits to GPs or different government clinics without proper investigations for TB. A mechanism is needed to increase all health-care providers' suspicion of TB so that proper investigations can be done during first consultation.

DELAYED TOOTH REPLANTATION AFTER ROOT SURFACE TREATMENT WITH SODIUM HYPOCHLORITE AND SODIUM FLUORIDE: HISTOMORPHOMETRIC ANALYSIS IN RATS

PubMed Central

Sottovia, André Dotto; Sonoda, Celso Koogi; Poi, Wilson Roberto; Panzarini, Sônia Regina; Lauris, José Roberto Pereira

2006-01-01

In cases of delayed tooth replantation, non-vital periodontal ligament remnants have been removed with sodium hypochlorite in an attempt to control root resorption. Nevertheless, reports of its irritating potential in contact with the alveolar connective tissue have been described. Therefore, this study evaluated the healing process on delayed replantation of rat teeth, after periodontal ligament removal by different treatment modalities. Twenty-four rats, assigned to 3 groups (n=8), had their upper right incisor extracted and left on the workbench for desiccation during 60 min. Afterwards, the teeth in group I were immersed in saline for 2 min. In group II, root surfaces were scrubbed with gauze soaked in saline for 2 min; and in group III, scrubbing was done with gauze soaked in 1% sodium hypochlorite solution. Thereafter, root surfaces were etched with 37% phosphoric acid and immersed in 2% acidulate-phosphate sodium fluoride solution, at pH 5.5. Root canals were filled with a calcium hydroxide-based paste and the teeth were replanted. The animals were sacrificed 60 days postoperatively and the pieces containing the replanted teeth were processed and paraffin-embedded. Semi-serial transversally sections were obtained from the middle third of the root and stained with hematoxylin and eosin for histomorphometric analysis. Data were analyzed statistically using Kruskal-Wallis and Dunn's tests. The results showed that root structure and cementum extension were more affected by resorption in group III (p<0.05). All groups were affected by root resorption but the treatment performed in group III was the least effective for its control. The treatment accomplished in groups I and II yielded similar results to each other. PMID:19089038

Delayed tooth replantation after root surface treatment with sodium hypochlorite and sodium fluoride: histomorphometric analysis in rats.

PubMed

Sottovia, André Dotto; Sonoda, Celso Koogi; Poi, Wilson Roberto; Panzarini, Sônia Regina; Lauris, José Roberto Pereira

2006-04-01

In cases of delayed tooth replantation, non-vital periodontal ligament remnants have been removed with sodium hypochlorite in an attempt to control root resorption. Nevertheless, reports of its irritating potential in contact with the alveolar connective tissue have been described. Therefore, this study evaluated the healing process on delayed replantation of rat teeth, after periodontal ligament removal by different treatment modalities. Twenty-four rats, assigned to 3 groups (n=8), had their upper right incisor extracted and left on the workbench for desiccation during 60 min. Afterwards, the teeth in group I were immersed in saline for 2 min. In group II, root surfaces were scrubbed with gauze soaked in saline for 2 min; and in group III, scrubbing was done with gauze soaked in 1% sodium hypochlorite solution. Thereafter, root surfaces were etched with 37% phosphoric acid and immersed in 2% acidulate-phosphate sodium fluoride solution, at pH 5.5. Root canals were filled with a calcium hydroxide-based paste and the teeth were replanted. The animals were sacrificed 60 days postoperatively and the pieces containing the replanted teeth were processed and paraffin- embedded. Semi-serial transversally sections were obtained from the middle third of the root and stained with hematoxylin and eosin for histomorphometric analysis. Data were analyzed statistically using Kruskal-Wallis and Dunn's tests. The results showed that root structure and cementum extension were more affected by resorption in group III (p<0.05). All groups were affected by root resorption but the treatment performed in group III was the least effective for its control. The treatment accomplished in groups I and II yielded similar results to each other.

Takotsubo cardiomyopathy with involvement of delayed-onset rhabdomyolysis and acute kidney injury after rosuvastatin treatment.

PubMed

Kamada, Tomohito; Hayashi, Mutsuharu; Yokoi, Hiroatsu; Fujiwara, Wakaya; Yoshikawa, Daiji; Mukaide, Daisuke; Sugishita, Yoshinori; Yoshinaga, Masataka; Ito, Takehiro; Ozaki, Yukio; Izawa, Hideo

2015-01-01

Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient's medical condition, in association with complaints of non-specific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient's cardiac function.

Programmable Differential Delay Circuit With Fine Delay Adjustment

DOEpatents

DeRyckere, John F.; Jenkins, Philip Nord; Cornett, Frank Nolan

2002-07-09

Circuitry that provides additional delay to early arriving signals such that all data signals arrive at a receiving latch with same path delay. The delay of a forwarded clock reference is also controlled such that the capturing clock edge will be optimally positioned near quadrature (depending on latch setup/hold requirements). The circuitry continuously adapts to data and clock path delay changes and digital filtering of phase measurements reduce errors brought on by jittering data edges. The circuitry utilizes only the minimum amount of delay necessary to achieve objective thereby limiting any unintended jitter. Particularly, this programmable differential delay circuit with fine delay adjustment is designed to allow the skew between ASICS to be minimized. This includes skew between data bits, between data bits and clocks as well as minimizing the overall skew in a channel between ASICS.

Predictors of delay in heart failure patients and consequences for outcomes.

PubMed

Sethares, Kristen A; Chin, Elizabeth; Jurgens, Corrine Y

2015-02-01

Persons with heart failure (HF) symptoms delay up to 7 days before seeking treatment. Delay can result in worse symptoms and potentially impact outcomes. The purpose of this review was to describe predictors and outcomes of delay in HF patients. Demographic factors, increased symptom number, social factors, greater HF knowledge, lower anxiety, and depression predicted increased delay. HF patients had difficulty recognizing and interpreting symptoms of HF. Results are conflicting related to symptom pattern, time of care seeking, and history of HF as predictors of delay. The only outcome predicted by delay was length of stay with those delaying longer reporting longer lengths of stay. Future research related to delay should include theoretical frameworks and larger, more ethnically diverse samples from multiple sites and link delay to outcomes. Valid and reliable instruments are needed to measure delay and related factors. HF education should include supportive others.

Ranitidine: forgotten drug of delayed gastric emptying.

PubMed

Veevers, Abbie E; Oxberry, Stephen G

2017-09-01

Delayed gastric emptying in the presence or absence of mechanical bowel obstruction can cause distressing symptoms in palliative care patients. We present two patients, both with vomiting due to delayed gastric emptying and gastric outlet obstruction secondary to pancreatic cancer, treated with subcutaneous ranitidine resulting in a symptomatic response. We hypothesise that ranitidine is a useful adjunct to standard treatment with prokinetic agents or octreotide in such patients and potentially those with proximal mechanical bowel obstruction from other malignancies with associated delayed gastric emptying. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Father's role in parent training for children with developmental delay.

PubMed

Bagner, Daniel M

2013-08-01

The current pilot study was a quasi-experimental examination of the impact of father involvement in parent training among 44 families with a young child who presented with elevated externalizing behavior problems and developmental delay. All families were offered to receive Parent-Child Interaction Therapy (PCIT), an evidence-based parent-training intervention, at a hospital-based outpatient clinic. Single-mother families were significantly more likely to drop out of treatment than two-parent families. Of the families that completed treatment, children from families in which a father participated in treatment had lower levels of parent-reported externalizing behavior problems than children from single-mother families and children from two-parent families in which the father did not participate in treatment. Additionally, children from father-involved families were significantly more compliant during a cleanup task than children from single-mother families following treatment. The current study is consistent with the limited research examining father involvement in parent training and extends the findings to children with developmental delay. These findings highlight the importance of involving fathers in parent training, particularly when working with children with developmental delay. © 2013 American Psychological Association

Delayed plumage maturation and delayed reproductive investment in birds.

PubMed

Hawkins, Gerard L; Hill, Geoffrey E; Mercadante, Austin

2012-05-01

Delayed plumage maturation is the delayed acquisition of a definitive colour and pattern of plumage until after the first potential breeding period in birds. Here we provide a comprehensive overview of the numerous studies of delayed plumage maturation and a revised theoretical framework for understanding the function of delayed plumage maturation in all birds. We first distinguish between hypotheses that delayed plumage maturation is attributable to a moult constraint with no adaptive function and hypotheses that propose that delayed plumage maturation is a component of an adaptive life-history strategy associated with delayed reproductive investment. We then recognize three potential benefits of delayed plumage maturation: crypsis, mimicry and status signaling. Evidence suggests that delayed plumage maturation is not a consequence of developmental constraints and instead represents a strategy to maximize reproductive success in circumstances where young adults cannot effectively compete with older adults for limited resources, particularly breeding opportunities. A multi-factorial explanation that takes into account lifespan and the degree of competition for limited breeding resources and that combines the benefits of an inconspicuous appearance with the benefits of honest signaling of reduced competitiveness provides a general explanation for the function of delayed plumage maturation in most bird species. Delayed plumage maturation should be viewed as a component of alternative reproductive strategies that can include delay in both plumage and sexual development. Such strategies are frequently facultative, with individuals breeding prior to the acquisition of definitive plumages when conditions are favourable. Presumably, the benefits of delayed plumage maturation ultimately enhance lifetime reproductive success, and studying delayed plumage maturation within the context of lifetime reproductive success should be a goal of future studies. © 2011 The Authors

Indeterminate QuantiFERON-TB Gold Increases Likelihood of Inflammatory Bowel Disease Treatment Delay and Hospitalization.

PubMed

Vajravelu, Ravy K; Osterman, Mark T; Aberra, Faten N; Roy, Jason A; Lichtenstein, Gary R; Mamtani, Ronac; Goldberg, David S; Lewis, James D; Scott, Frank I

2017-12-19

QuantiFERON-TB Gold (QFTG) is a blood test used to diagnose latent tuberculosis infection (LTBI) prior to TNF-α inhibitor (anti-TNF) initiation. We sought to determine factors associated with indeterminate QFTG results in inflammatory bowel disease (IBD) patients and whether indeterminate results are associated with IBD-related morbidity. This nested case-control study included IBD patients who underwent QFTG testing. Cases were patients with indeterminate QFTG and controls were those with negative QFTG. The association of demographic and clinical data with indeterminate QFTG result was assessed using logistic regression. We examined the clinical impact of indeterminate QFTG results on risk of hospitalization and delay in anti-TNF initiation using inverse probability-of-treatment weighting (IPTW) regression. We identified 411 patients with QFTG testing (320 negative, 80 indeterminate, and 11 positive results). No patient with an indeterminate result subsequently had LTBI. Systemic corticosteroid use (OR, 4.4; 95% CI, 2.0-9.6) and hospitalization at the time of QFTG (OR, 3.8; 95% CI, 1.9-7.7) were associated with indeterminate QFTG, while immunomodulator use was nearly statistically significant (OR, 3.1; 95% CI, 0.9-9.8) and anti-TNF use was not (OR, 0.9; 95% CI, 0.2-4.6). After IPTW adjustment, indeterminate QFTG was associated with a 23.1% (95% CI, 8.2%-37.9%) greater probability of delay in anti-TNF initiation beyond 30 days and an 11.9% (95% CI, 0.6%-23.1%) greater probability of hospitalization within 60 days. Systemic corticosteroid use and hospitalization were associated with an indeterminate QFTG result. Indeterminate QFTG results were associated with delayed anti-TNF initiation and subsequent hospitalization. © 2017 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Impact of geographic distance on appraisal delay for active TB treatment seeking in Uganda: a network analysis of the Kawempe Community Health Cohort Study.

PubMed

Fluegge, Kyle; Malone, LaShaunda L; Nsereko, Mary; Okware, Brenda; Wejse, Christian; Kisingo, Hussein; Mupere, Ezekiel; Boom, W Henry; Stein, Catherine M

2018-06-26

Appraisal delay is the time a patient takes to consider a symptom as not only noticeable, but a sign of illness. The study's objective was to determine the association between appraisal delay in seeking tuberculosis (TB) treatment and geographic distance measured by network travel (driving and pedestrian) time (in minutes) and distance (Euclidean and self-reported) (in kilometers) and to identify other risk factors from selected covariates and how they modify the core association between delay and distance. This was part of a longitudinal cohort study known as the Kawempe Community Health Study based in Kampala, Uganda. The study enrolled households from April 2002 to July 2012. Multivariable interval regression with multiplicative heteroscedasticity was used to assess the impact of time and distance on delay. The delay interval outcome was defined using a comprehensive set of 28 possible self-reported symptoms. The main independent variables were network travel time (in minutes) and Euclidean distance (in kilometers). Other covariates were organized according to the Andersen utilization conceptual framework. A total of 838 patients with both distance and delay data were included in the network analysis. Bivariate analyses did not reveal a significant association of any distance metric with the delay outcome. However, adjusting for patient characteristics and cavitary disease status, the multivariable model indicated that each minute of driving time to the clinic significantly (p = 0.02) and positively predicted 0.25 days' delay. At the median distance value of 47 min, this represented an additional delay of about 12 (95% CI: [3, 21]) days to the mean of 40 days (95% CI: [25, 56]). Increasing Euclidean distance significantly predicted (p = 0.02) reduced variance in the delay outcome, thereby increasing precision of the mean delay estimate. At the median Euclidean distance of 2.8 km, the variance in the delay was reduced by more than 25%. Of the four

Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

PubMed Central

Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine

2010-01-01

Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hypertrophied myocardium. Rats with either normal myocardium or cardiac hypertrophy induced by 8 weeks of abdominal aortic banding were fed one of four diets: control diet without DHA or EPA or diets enriched with either DHA, EPA, or DHA + EPA (1:1 ratio) at 2.5% of energy intake for 17 weeks. Aortic banding caused a 27% increase in left ventricular mass and 25% depletion in DHA in mitochondrial phosopholipids in rats fed the control diet. DHA supplementation raised DHA in phospholipids ∼2-fold in both normal and hypertrophied hearts and increased EPA. DHA + EPA supplementation also increased DHA, but to a lesser extent than DHA alone. EPA supplementation increased EPA, but did not affect DHA compared with the control diet. Ca2+-induced MPTP opening was delayed by DHA and DHA + EPA supplementation in both normal and hypertrophied hearts, but EPA had no effect on MPTP opening. These results show that supplementation with DHA alone effectively increases both DHA and EPA in cardiac mitochondrial phospholipids and delays MPTP and suggest that treatment with DHA + EPA offers no advantage over DHA alone. PMID:20624993

Factors influencing diagnosis delay of advanced breast cancer in Moroccan women.

PubMed

Maghous, A; Rais, F; Ahid, S; Benhmidou, N; Bellahamou, K; Loughlimi, H; Marnouche, E; Elmajjaoui, S; Elkacemi, H; Kebdani, T; Benjaafar, N

2016-06-07

Delay in the diagnosis of breast cancer in symptomatic women of 3 months or more is associated with advanced stage and low survival. We conducted this study to learn more about the extent and reasons behind diagnosis delay of advanced breast cancer in Moroccan women. A group of patients with advanced breast cancer were interviewed at the National Institute of Oncology in Rabat during the period from February to December 2014. Diagnosis delay was devised into patient delay and system delay. Patient delay was defined as time from first symptoms until first medical consultation. System delay was defined as time from first presentation to a health care provider until definite diagnosis or treatment. Prospective information and clinical data were collected on a form during an interview with each patient and from medical records. In all, 137 patients were interviewed. The mean age of women was 48.3 ± 10.4 years. The median of consultation time was 6[4,12] months and the median of diagnosis time was 1[1,3] months. Diagnosis delay was associated to a personal reason in 96 (70.1 %) patients and to a medical reason in 19 (13.9 %) patients. A number of factors predicted diagnosis delay: symptoms were not considered serious in 66 (55.9 %) patients; traditional therapy was applied in 15 (12.7 %) patients and fear of cancer diagnosis and/or treatment in 14 (11.9 %) patients. A use of traditional methods was significantly associated with rural residence and far away from basic health center (p = 0.000). Paradoxically, a family history of breast cancer was significantly higher in who report a fear of cancer diagnosis and/or treatment to diagnosis delay (p < 0.001). Also, a significantly higher risk of more than 6 months delay was found among rural women (P = 0.035) and women who live far away from specialized care center (P = 0.001). Diagnosis delay is very serious problem in Morocco. Diagnosis delay was associated with complex interactions between

Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

PubMed Central

Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

2014-01-01

Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

Stability of formation control using a consensus protocol under directed communications with two time delays and delay scheduling

NASA Astrophysics Data System (ADS)

Cepeda-Gomez, Rudy; Olgac, Nejat

2016-01-01

We consider a linear algorithm to achieve formation control in a group of agents which are driven by second-order dynamics and affected by two rationally independent delays. One of the delays is in the position and the other in the velocity information channels. These delays are taken as constant and uniform throughout the system. The communication topology is assumed to be directed and fixed. The formation is attained by adding a supplementary control term to the stabilising consensus protocol. In preparation for the formation control logic, we first study the stability of the consensus, using the recent cluster treatment of characteristic roots (CTCR) paradigm. This effort results in a unique depiction of the non-conservative stability boundaries in the domain of the delays. However, CTCR requires the knowledge of the potential stability switching loci exhaustively within this domain. The creation of these loci is done in a new surrogate coordinate system, called the 'spectral delay space (SDS)'. The relative stability is also investigated, which has to do with the speed of reaching consensus. This step leads to a paradoxical control design concept, called the 'delay scheduling', which highlights the fact that the group behaviour may be enhanced by increasing the delays. These steps lead to a control strategy to establish a desired group formation that guarantees spacing among the agents. Example case studies are presented to validate the underlying analytical derivations.

Thalidomide for Control Delayed Vomiting in Cancer Patients Receiving Chemotherapy.

PubMed

Han, Zhengxiang; Sun, Xuan; Jiang, Guan; Du, Xiuping

2016-11-01

To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Randomized, double-blind controlled study. The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the c2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (c2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

Comparison of Progressive Prompt Delay with and without Instructive Feedback

ERIC Educational Resources Information Center

Reichow, Brian; Wolery, Mark

2011-01-01

We examined the effectiveness and efficiency of 2 instructional arrangements using progressive prompt delay (PPD) with 3 young children with autism and 1 child with developmental delays. Specifically, we compared PPD with instructive feedback (IF) to PPD without IF in an adapted alternating treatment design. The results suggested that (a) children…

Management of the treatment delay in symptomatic carotid artery stenosis.

PubMed

Stiehm, Markus; Björses, Katarina; Kremer, Christine

2013-01-01

Saving time to intervention is crucial in patients with symptomatic carotid artery stenosis (SCAS). We introduced a fast-track protocol (FTP). Time frames from the onset of symptoms to intervention before and after the introduction of an FTP were analyzed. SCAS patients (403 patients/405 procedures) were evaluated according to whether surgery was performed before (group 1) or after (group 2) the introduction of the FTP. Time frames to surgery, causes of delay and frequency of recurrent events are reported. The median time delay decreased from 17 to 12 days (p<0.001), but time to ultrasound examination remained unchanged. Surgery was within 2 weeks in 41% in group 1 and in 57% in group 2 (p=0.001). Of 181 (30%) patients treated according to the FTP, 54 were operated within 7 days (median), and 80% had the intervention within 2 weeks. Time to surgery decreased significantly after the introduction of the FTP. © 2013 S. Karger AG, Basel.

Delayed Complications After Transsphenoidal Surgery for Pituitary Adenomas.

PubMed

Alzhrani, Gmaan; Sivakumar, Walavan; Park, Min S; Taussky, Philipp; Couldwell, William T

2018-01-01

Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively, and reports are sparse about their occurrence, management, and outcome. Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia, hypopituitarism, hydrocephalus, and sinonasal complications. Our findings from this review revealed an incidence of 0.6%-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases of postoperative vasospasm occurring 8 days postoperatively, a 3.6%-19.8% rate of delayed symptomatic hyponatremia at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4%-5.8% rate of hydrocephalus within 2.2 months postoperatively. Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning. Copyright © 2017 Elsevier Inc. All rights reserved.

Health system delay and its effect on clinical stage of breast cancer: Multicenter study.

PubMed

Unger-Saldaña, Karla; Miranda, Alfonso; Zarco-Espinosa, Gelasio; Mainero-Ratchelous, Fernando; Bargalló-Rocha, Enrique; Miguel Lázaro-León, Jesús

2015-07-01

The objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer. This was a cross-sectional study of 886 patients who were referred to 4 of the largest public cancer hospitals in Mexico City for the evaluation of a probable breast cancer. Data on time intervals, sociodemographic factors, and clinical stage at diagnosis were retrieved. A logistic regression model was used to estimate the average marginal effects of delay on the probability of being diagnosed with advanced breast cancer (stages III and IV). The median time between problem identification and the beginning of treatment was 7 months. The subinterval with the largest delay was that between the first medical consultation and diagnosis (median, 4 months). Only 15% of the patients who had cancer were diagnosed with stage 0 and I disease, and 48% were diagnosed with stage III and IV disease. Multivariate analyses confirmed independent correlations for the means of problem identification, patient delay, health system delay, and age with a higher probability that patients would begin cancer treatment in an advanced stage. In the sample studied, the majority of patients with breast cancer began treatment after a delay. Both patient delays and provider delays were associated with advanced disease. Research aimed at identifying specific access barriers to medical services is much needed to guide the design of tailored health policies that go beyond the promotion of breast care awareness and screening participation to include improvements in health services that facilitate access to timely diagnosis and treatment. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

PubMed

Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

2012-07-31

For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

Delayed emergency department presentation in critically ill patients.

PubMed

Rodriguez, R M; Passanante, M; Phelps, M A; Dresden, G; Kriza, K; Carrasco, M; Franklin, J

2001-12-01

To determine the frequency and causes of delayed emergency department presentation in critically ill patients who did not have acute myocardial infarction and to evaluate whether factors such as age, gender, prior medical advice, lack of insurance, or low educational level are associated with delayed presentation. Prospective, descriptive analysis. Emergency department and medical intensive care unit of an urban county hospital. All adult patients admitted from the emergency department to the medical intensive care unit for reasons other than unstable angina, acute myocardial infarction, or stroke over two 9-wk blocks. Within 72 hrs of intensive care unit admission, patients or their families were interviewed to determine time elapsed between the onset of symptoms and patient emergency department presentation and to elicit reasons for delays in seeking medical treatment. We interviewed 155 of 173 (90%) of eligible patients and found that 58% waited >24 hrs before presenting to the emergency department. The most commonly cited primary reason for delays were beliefs that symptoms were not serious enough for emergency care (31%) and that symptoms would resolve spontaneously (29%). Most (55%) sought medical treatment only at the urging of family members or other advocates. Although variables such as lack of insurance and low educational level were not associated with delayed presentation, male gender and having sought medical advice before presenting to the emergency department were significantly associated with delay (p =.036 for each). Because of poor understanding of the gravity and natural progression of their symptoms, most critically ill patients waited >24 hrs to present to our emergency department. Education on warning symptom recognition for serious illnesses may be warranted not only for patients themselves but also for family members and caregivers.

Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis.

PubMed

Camerota, A J; Creasey, A A; Patla, V; Larkin, V A; Fink, M P

1998-03-01

To determine whether treatment with recombinant human tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 microg/mL), porcine mucin (150 microg/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI. Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPI(LOW DOSE) (0.1 mg/kg, then 1 microg/kg/min), 3 of 12 (P = .14); TFPI(MID DOSE), (0.5 mg/kg, then 5 microg/kg/min), 7 of 12 (P = .002); TFPI(HIGH DOSE) (10 mg/kg, then 10 microg/kg/min), 4 of 13 (P = .04). Thus, delayed treatment with TFPI improves survival in septic rabbits.

Angiographic delay: a viable alternative to surgical delay.

PubMed

Aboutanos, Sharline Z; Spinos, Efstathios; Blanchet, Nadia P

2012-06-01

Selective embolization of the inferior epigastric arteries can serve as a method for transverse rectus abdominis musculocutaneous (TRAM) flap delay. The purpose of this study was to determine whether delay by selective arterial embolization is comparable to traditionally surgically delayed TRAM flaps as reported in the literature, in terms of skin and fat necrosis, and to examine whether certain risk factors play a role in TRAM flap fat necrosis despite angiographic delay. Retrospective chart review was performed for 88 consecutive patients who underwent unilateral TRAM flap breast reconstruction after selective embolization of bilateral inferior epigastric arteries. Between 1997 and 2009, 88 pedicled TRAM flaps were performed for breast reconstruction in women with a mean age of 49.7 years. No patients had flap skin necrosis or total flap loss. In all, 13.6% patients had TRAM flap fat necrosis. Two patients in the TRAM fat necrosis group (16.7%) had a positive history of smoking, which was a statistically significant risk factor for necrosis (P = 0.048). Outcomes of pedicled TRAM flaps delayed by selective arterial embolization are comparable to historical controls of those delayed by traditional surgical means (ligation of artery and vein) and better than nondelayed flaps. Smoking remains a significant risk factor for TRAM flap fat necrosis despite the benefit of delay.

Delay Banking for Managing Air Traffic

NASA Technical Reports Server (NTRS)

Green, Steve

2008-01-01

Delay banking has been invented to enhance air-traffic management in a way that would increase the degree of fairness in assigning arrival, departure, and en-route delays and trajectory deviations to aircraft impacted by congestion in the national airspace system. In delay banking, an aircraft operator (airline, military, general aviation, etc.) would be assigned a numerical credit when any of their flights are delayed because of an air-traffic flow restriction. The operator could subsequently bid against other operators competing for access to congested airspace to utilize part or all of its accumulated credit. Operators utilize credits to obtain higher priority for the same flight, or other flights operating at the same time, or later, in the same airspace, or elsewhere. Operators could also trade delay credits, according to market rules that would be determined by stakeholders in the national airspace system. Delay banking would be administered by an independent third party who would use delay banking automation to continually monitor flights, allocate delay credits, maintain accounts of delay credits for participating airlines, mediate bidding and the consumption of credits of winning bidders, analyze potential transfers of credits within and between operators, implement accepted transfers, and ensure fair treatment of all participating operators. A flow restriction can manifest itself in the form of a delay in assigned takeoff time, a reduction in assigned airspeed, a change in the position for the aircraft in a queue of all aircraft in a common stream of traffic (e.g., similar route), a change in the planned altitude profile for an aircraft, or change in the planned route for the aircraft. Flow restrictions are typically imposed to mitigate traffic congestion at an airport or in a region of airspace, particularly congestion due to inclement weather, or the unavailability of a runway or region of airspace. A delay credit would be allocated to an operator of a

Simulation analysis of the effect of initial delay on flight delay diffusion

NASA Astrophysics Data System (ADS)

Que, Zufu; Yao, Hongguang; Yue, Wei

2018-01-01

The initial delay of the flight is an important factor affecting the spread of flight delays, so clarifying their relationship conduces to control flight delays in the aeronautical network. Through establishing a model of the chain aviation network and making simulation analysis of the effects of initial delay on the delay longitudinal diffusion, it’s found that the number of delayed airports in the air network, the total delay time and the average delay time of the delayed airport are generally positively correlated with the initial delay. This indicates that the occurrence of the initial delay should be avoided or reduced as much as possible to improve the punctuality of the flight.

Stability and delay sensitivity of neutral fractional-delay systems.

PubMed

Xu, Qi; Shi, Min; Wang, Zaihua

2016-08-01

This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

[Delayed neurological syndrome after CO intoxication of elderly female].

PubMed

Vander Weyden, Liesbeth; Voigt, Roxana-Maria; Boonen, Steven; Fagard, Katleen; Dejaeger, Eddy

2015-10-01

This article discusses the case history of an 87-year old woman with loss of consciousness following accidental CO intoxication. A few weeks later, the patient's cognitive abilities progressively deteriorated. This is hence a case of Delayed Neurological Symptoms after CO intoxication. This condition occurs in 40% of patients with CO intoxication and manifests itself 3-240 days after apparent recovery. Symptoms can linger for a long time and are in some cases even permanent. Treatment of CO intoxication usually consists of administering normobaric oxygen and in certain cases hyperbaric oxygen. The role of treatment with hyberbaric oxygen in delayed neurological symptoms after CO intoxication remains controversial, however.

Profile of tuberculosis patients with delayed sputum smear conversion in the Pacific island of Vanuatu

PubMed Central

Viney, K.; Tarivonda, L.; Roseveare, C.; Tagaro, M.; Marais, B. J.

2014-01-01

Setting: National tuberculosis control programme, Vanuatu. Objective: To assess tuberculosis (TB) trends, characterise sputum smear-positive patients with non-conversion at 2 months and assess their treatment outcomes. Design: Evaluation of programme data over a 9-year period (2004–2012), comparing 2-month sputum non-converters (delayed converters) with sputum smear converters diagnosed in 2011 and 2012. Results: Annual TB case numbers were similar over the study period, with an average TB notification rate of 58 per 100 000 population. Of 417 sputum smear-positive cases, 74 (18%) were delayed converters. Delayed converters were more likely than converters (88% vs. 79%) to have had high pre-treatment sputum smear grades (OR 2.5, 95%CI 0.97–6.45). Among delayed converters, treatment adherence was high (99% good adherence), outcomes were generally good (90% treatment success, 85% cure, 4% treatment failure) and no drug resistance was detected. Deaths were unexpectedly common among converters (11/80, 14%), with significantly more deaths in Tafea than in Shefa Province (7/58 vs. 2/80, OR 5.35, 95%CI 1.07–26.79). Tafea Province also had the greatest number of delayed converters (30/74, 40.5%) and the highest TB incidence rate. Conclusion: Delayed sputum conversion was relatively uncommon, and was not associated with adverse outcomes or drug resistance. Regional differences require further investigation to better understand local factors that may compromise patient management. PMID:26477281

Independent predictors of delay in emergence from general anesthesia.

PubMed

Maeda, Shigeru; Tomoyasu, Yumiko; Higuchi, Hitoshi; Ishii-Maruhama, Minako; Egusa, Masahiko; Miyawaki, Takuya

2015-01-01

Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability.

Introduction to Focus Issue: Time-delay dynamics

NASA Astrophysics Data System (ADS)

Erneux, Thomas; Javaloyes, Julien; Wolfrum, Matthias; Yanchuk, Serhiy

2017-11-01

The field of dynamical systems with time delay is an active research area that connects practically all scientific disciplines including mathematics, physics, engineering, biology, neuroscience, physiology, economics, and many others. This Focus Issue brings together contributions from both experimental and theoretical groups and emphasizes a large variety of applications. In particular, lasers and optoelectronic oscillators subject to time-delayed feedbacks have been explored by several authors for their specific dynamical output, but also because they are ideal test-beds for experimental studies of delay induced phenomena. Topics include the control of cavity solitons, as light spots in spatially extended systems, new devices for chaos communication or random number generation, higher order locking phenomena between delay and laser oscillation period, and systematic bifurcation studies of mode-locked laser systems. Moreover, two original theoretical approaches are explored for the so-called Low Frequency Fluctuations, a particular chaotical regime in laser output which has attracted a lot of interest for more than 30 years. Current hot problems such as the synchronization properties of networks of delay-coupled units, novel stabilization techniques, and the large delay limit of a delay differential equation are also addressed in this special issue. In addition, analytical and numerical tools for bifurcation problems with or without noise and two reviews on concrete questions are proposed. The first review deals with the rich dynamics of simple delay climate models for El Nino Southern Oscillations, and the second review concentrates on neuromorphic photonic circuits where optical elements are used to emulate spiking neurons. Finally, two interesting biological problems are considered in this Focus Issue, namely, multi-strain epidemic models and the interaction of glucose and insulin for more effective treatment.

Loss-to-follow-up and delay to treatment initiation in Pakistan's national tuberculosis control programme.

PubMed

Ali, Syed Mustafa; Naureen, Farah; Noor, Arif; Fatima, Irum; Viney, Kerri; Ishaq, Muhammad; Anjum, Naveed; Rashid, Aamna; Haider, Ghulam Rasool; Khan, Muhammad Aamir; Aamir, Javariya

2018-03-09

Researchers and policy-makers have identified loss to follow-up as a major programmatic problem. Therefore, the objective of this study is to quantify TB related pre-treatment loss to follow up and treatment delay in private sector health care facilities in Pakistan. This was a retrospective, descriptive cohort study using routinely collected programmatic data from TB referral, diagnosis and treatment registers. Data from 48 private healthcare facilities were collected using an online questionnaire prepared in ODK Collect, for the period October 2015 to March 2016. Data were analysed using SPSS. We calculated the: (1) number and proportion of patients who were lost to follow-up during the diagnostic period, (2) number and proportion of patients with pre-treatment loss to follow-up, and (3) the number of days between diagnosis and initiation of treatment. One thousand five hundred ninety-six persons with presumptive TB were referred to the laboratory. Of these, 96% (n = 1538) submitted an on-the-spot sputum sample. Of the 1538 people, 1462 (95%) people subsequently visited the laboratory to submit the early morning (i.e. the second) sample. Hence, loss to follow-up during the diagnostic process was 8% overall (n = 134). Of the 1462 people who submitted both sputum samples, 243 (17%) were diagnosed with sputum smear-positive pulmonary TB and 231 were registered for anti-TB treatment, hence, loss in the pre-treatment phase was 4.9% (n = 12). 152 persons with TB (66%) initiated TB treatment either on the day of TB diagnosis or the next day. A further 79 persons with TB (34%) commenced TB treatment within a mean time of 7 days (range 2 to 64 days). Concentrated efforts should be made by the National TB Control Programme to retain TB patients and innovative methods such as text reminders and behavior change communication may need to be used and tested.

Neurodevelopmental delay associated with nonconvulsive status epilepticus in a toddler.

PubMed

Shinawi, M; Shahar, E

2001-03-01

Nonconvulsive status epilepticus is a prolonged and continuous state of increased unawareness without overt motor seizures linked with repetitive generalized epileptic discharges. In children, it may occur de novo but more commonly may complicate a preexisting epileptic disorder. We report on a 2-year-old female who presented with global developmental delay as the main manifestation of nonconvulsive status epilepticus. Following valproic acid treatment, her motor, cognitive, and speech delays had gradually subsided and nearly completely resolved, in concert with normalization of electroencephalography (EEG). Hence, given a possible, albeit rare, presentation of nonconvulsive status epilepticus with global developmental delay, we suggest that EEG should be recommended in any infant who manifests neurodevelopmental delay.

Have clinical studies demonstrated diabetes prevention or delay of diabetes through early treatment?

PubMed

Southwood, Robin L

2010-01-01

The incidence of type 2 diabetes continues to increase at alarming rates. Prediabetes is a state of abnormal glycemic values that are not abnormal enough to result in the diagnosis of type 2 diabetes. Significant interest in the prevention of diabetes has resulted in trials evaluating pharmacologic intervention and lifestyle intervention to prevent the development of diabetes. Controversy exists over the exact definition of diabetes prevention. Agents might possibly delay diagnosis of diabetes via pharmacologic lowering of blood glucose. Goals of diabetes prevention include decreased cardiovascular disease. Trials assessing diabetes prevention should assess 1) Impact of the study drug upon the incidence of diabetes, 2) Impact of the study drug upon diagnosis of diabetes after post-treatment washout phase, 3) Assessment of insulin sensitivity/@-cell function/insulin secretion and blood glucose, 4) Assessment of confounding factors, 5) Impact of the study drug on the occurrence of cardiovascular disease. The published studies were reviewed using these criteria. Six studies evaluating seven agents have been were reviewed. Six of the seven agents reduced diagnosis of diabetes during use, but only two demonstrated effect after washout phase. One of the two agents has been withdrawn from the market. The second agent had a short follow-up period making the results difficult to interpret. Assessment of insulin secretion at entry to trial was common, however ongoing reassessment was uncommon. All studies attempted to assess confounding factors, however stratification of drug benefit relative to amount of lifestyle modification benefit was not reported in trials. Cardiovascular benefit in the form of reduced hypertension was documented with three agents. Pharmacologic prevention of type 2 diabetes remains unproven, due in part to the difficulty distinguishing between prevention and delay. Reduction in cardiovascular benefit is unproven with most agents studied. Larger

THE TREATMENT OF INTERSEX AND THE PROBLEM OF DELAY: THE AUSTRALIAN SENATE INQUIRY INTO INTERSEX SURGERY AND CONFLICTING HUMAN RIGHTS FOR CHILDREN.

PubMed

O'Connor, Mike

2016-03-01

When a child is born with indeterminate genitalia (so-called intersex or disordered sex development), it becomes very difficult to balance the child's right to determine their own sexual future against the problems of living as a child with an indeterminate gender. Moreover, the initial assignment of gender may prove to be inappropriate and major psychological disturbances in the recipient can arise during adolescence and adult life. The problems of these children were explained to the Australian Senate Committee during its inquiry into intersex surgery in 2013. As a result, the Committee made a number of recommendations, including a proposal that all surgery be deferred until the child is able to consent to treatment. The author argues that the Committee's proposal to delay all modifications of indeterminate genitalia is impractical. The inclusion in the definition of intersex of common conditions (such as hypospadias in genetic male infants) means that necessary and uncontroversial surgery will be delayed until after puberty. This delay may be harmful and adverse to some children's best interests.

Treatment effect expressed as the novel Delay of Event measure is associated with high willingness to initiate preventive treatment - A randomized survey experiment comparing effect measures.

PubMed

Berglund, Erik; Westerling, Ragnar; Sundström, Johan; Lytsy, Per

2016-12-01

This study aimed to investigate patients' willingness to initiate a preventive treatment and compared two established effect measures to the newly developed Delay of Events (DoE) measure that expresses treatment effect as a gain in event-free time. In this cross-sectional, randomized survey experiment in the general Swedish population,1079 respondents (response rate 60.9%) were asked to consider a preventive cardiovascular treatment. Respondents were randomly allocated to one of three effect descriptions: DoE, relative risk reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate analyses were performed investigating willingness to initiate treatment, views on treatment benefit, motivation and importance to adhere and willingness to pay for treatment. Eighty-one percent were willing to take the medication when the effect was described as DoE, 83.0% when it was described as RRR and 62.8% when it was described as ARR. DoE and RRR was further associated with positive views on treatment benefit, motivation, importance to adhere and WTP. Presenting treatment effect as DoE or RRR was associated with a high willingness to initiate treatment. An approach based on the novel time-based measure DoE may be of value in clinical communication and shared decision making. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The pharmaceutical sector inquiry: 'Hamlet' in a nutshell.

PubMed

den Exter, André

2010-03-01

In July 2009, the European Commission (DG Competition) published a Communication on the pharmaceutical sector. This inquiry was launched because there were some indications that competition in the pharmaceutical market in the European Union might not be working well. The report examines the reasons for the observed delay. This article analyses the outcomes from a critical standpoint, arguing in favour of enhanced 'soft law' accountability mechanisms in the pharmaceutical sector, defending conditional patenting and the introduction of a Community patent.

The identification of risk factors associated with patient and healthcare system delays in the treatment of tuberculosis in Tabriz, Iran.

PubMed

Ebrahimi Kalan, Mohammad; Yekrang Sis, Hassan; Kelkar, Vinaya; Harrison, Scott H; Goins, Gregory D; Asghari Jafarabadi, Mohammad; Han, Jian

2018-01-24

the health care facilities. The knowledge generated from this study will be helpful for prioritizing and developing strategies for minimizing delays, initiating early treatment to TB patients, and improving TB-related training programs and healthcare systems in Tabriz, Iran.

[Diagnosis delay of pleural and pulmonary tuberculosis].

PubMed

Cherif, J; Mjid, M; Ladhar, A; Toujani, S; Mokadem, S; Louzir, B; Mehiri, N; Béji, M

2014-08-01

Tuberculosis (TB) is still being endemic in our country. Time until management determines both evolution and prognosis of this condition. The aim of this work is to evaluate the delay in diagnosis of TB in a respiratory unit from a university hospital series. The authors conducted a cross-sectional study including patients with pulmonary TBC and/or pleural. An evaluation of time management was conducted from the beginning of symptoms and various consultations with reference to the date of hospitalization and treatment set up. One hundred patients were included (pulmonary TB: 68 cases, pleural TB 23 cases, miliary pulmonary TB: 4 cases, pulmonary TB associated with other extrathoracic locations: 5 cases). The mean time of patient delay and total delay institution were respectively 43.6, 25.7 and 69.3 days. Variables responsible for long delays were: number of consultations more than 3 before hospitalization, empirical antibiotic therapy, of a regional hospital first consultation and the presence of extra-respiratory impairment. The patient delay was considered long. A reorganization of the TB control program, in particular by partial decentralization of care and health education is imperative in order to improve the quality of tuberculosis management in our country. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Delay discounting rates: a strong prognostic indicator of smoking relapse.

PubMed

Sheffer, Christine E; Christensen, Darren R; Landes, Reid; Carter, Larry P; Jackson, Lisa; Bickel, Warren K

2014-11-01

Recent evidence suggests that several dimensions of impulsivity and locus of control are likely to be significant prognostic indicators of relapse. One-hundred and thirty-one treatment seeking smokers were enrolled in six weeks of multi-component cognitive-behavioral therapy with eight weeks of nicotine replacement therapy. Cox proportional hazard regressions were used to model days to relapse with each of the following: delay discounting of $100, delay discounting of $1000, six subscales of the Barratt Impulsiveness Scale (BIS), Rotter's Locus of Control (RLOC), Fagerstrom's Test for Nicotine Dependence (FTND), and the Perceived Stress Scale (PSS). Hazard ratios for a one standard deviation increase were estimated with 95% confidence intervals for each explanatory variable. Likelihood ratios were used to examine the level of association with days to relapse for different combinations of the explanatory variables while accounting for nicotine dependence and stress level. These analyses found that the $100 delay discounting rate had the strongest association with days to relapse. Further, when discounting rates were combined with the FTND and PSS, the associations remained significant. When the other measures were combined with the FTND and PSS, their associations with relapse non-significant. These findings indicate that delay discounting is independently associated with relapse and adds to what is already accounted for by nicotine dependence and stress level. They also signify that delay discounting is a productive new target for enhancing treatment for tobacco dependence. Consequently, adding an intervention designed to decrease discounting rates to a comprehensive treatment for tobacco dependence has the potential to decrease relapse rates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relation between delay and survival in 596 patients with breast cancer.

PubMed

Machiavelli, M; Leone, B; Romero, A; Perez, J; Vallejo, C; Bianco, A; Rodriguez, R; Estevez, R; Chacon, R; Dansky, C

1989-01-01

To evaluate the influence of delay between first symptom and first treatment upon survival the medical records of 596 patients with breast cancer were reviewed. The following intervals were considered: less than 3 months; 3-6 months and greater than 6 months. Patients in the less than 3 months delay group had a better distribution by clinical stages and a 10-year survival rate higher than those in the longer delay groups (p = 0.034). However, within each stage no statistically significant difference in survival according to delay was observed. A Cox multivariate analysis revealed that performance status and stage of disease were independent predictors of survival, but not delay. Assuming the best prognosis for patients with clinical stages I and II and less than 3 months delay, the group with longer delay times had 15 deaths over what would have been predicted. This adverse effect was observed almost exclusively among patients over age 50 (14/15).

Effect of caffeine on radiation-induced mitotic delay: delayed expression of G/sub 2/ arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rowley, R.; Zorch, M.; Leeper, D.B.

1984-01-01

In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G/sub 2/ cells progressed to mitosis in register and without arrest in G/sub 2/. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G/sub 2/ arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delaymore » suggests a common basis for delay induction in S and G/sub 2/ phases.« less

Methyl bromide fumigation and delayed mortality: safe trade of live pests?

PubMed

Phillips, C B; Iline, I I; Novoselov, M; McNeill, M R; Richards, N K; van Koten, C; Stephenson, B P

Live organisms intercepted from treated commodities during phytosanitary inspections usually arouse suspicions of treatment failure, sub-standard treatment application, or post-treatment infestation. The additional possibility that some treatments could kill slowly, meaning commodities might be inspected before pests have succumbed, is seldom considered for treatments other than irradiation. We used a novel biochemical viability assay to measure delays between methyl bromide fumigation and mortality of dipteran eggs, and evaluated the correspondence between egg viability and egg morphological features. Our experimental conditions simulated shipping of rock melons from Australia to New Zealand by sea and air. No eggs survived fumigation, but they took 3-20 days to die, whereas phytosanitary inspections of rock melons occur within 2-7 days. Delays were not influenced by methyl bromide concentration, but were significantly lengthened by cooler storage temperatures. Methyl bromide's preservative effects delayed degradation of egg morphology, so the biochemical assay detected mortality long before morphological signs of egg death appeared. The results show that commodities subjected to effective methyl bromide treatments are at risk of being inspected before all pests have either died, or started to exhibit morphological signs of death. This could cause commodities to be unnecessarily rejected by quarantine authorities. Better methods than inspection for live pests are needed to assist authorities to gain assurance that treated commodities have been effectively disinfested. These could be developed by exploiting biochemical responses of pests and commodities to treatments.

Speech and language delay in two children: an unusual presentation of hyperthyroidism.

PubMed

Sohal, Aman P S; Dasarathi, Madhuri; Lodh, Rajib; Cheetham, Tim; Devlin, Anita M

2013-01-01

Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. Case reports of two children with hyperthyroidism presenting with speech and language delay. We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.

Combination of butylphthalide with umbilical mesenchymal stem cells for the treatment of delayed encephalopathy after carbon monoxide poisoning.

PubMed

Wang, Huanjun; Li, Yan; Wu, Qiang; Xu, Chenglong; Liu, Qingran

2016-12-01

Delayed encephalopathy after carbon monoxide (CO) poisoning (DEACMP) is still a clinical challenge. This study aimed to investigate the efficacy of combined therapy of mesenchymal stem cell (MSC) transplantation and butylphthalide in DEACMP patients.Forty-two DEACMP patients were treated with 1 of the 3 therapies: combined therapy of MSC transplantation and butylphthalide; MSC transplantation alone; or hyperbaric oxygen therapy. The MSCs were alternatively injected into the subarachnoid space and the carotid artery using a self-made high-pressure injector. The Mini-Mental State Examination and the Barthel index of activities of daily living were administered before the treatment, and at 1 month, 3 months, and 6 months after the treatment. Computed tomography and magnetic resonance imaging results before and after the treatment were compared.At 1 month, 3 months, and 6 months after the treatment, the Mini-Mental State Examination scores and the Barthl scores were significantly higher in patients with the combined therapy of MSC transplantation and butylphthalide than those in patients with MSC transplantation alone or hyperbaric oxygen therapy (all P < 0.0001). No significant adverse events occurred.The combination of MSC transplantation and butylphthalide is safe and effective in treating DEACMP.

Independent Predictors of Delay in Emergence From General Anesthesia

PubMed Central

Maeda, Shigeru; Tomoyasu, Yumiko; Higuchi, Hitoshi; Ishii-Maruhama, Minako; Egusa, Masahiko; Miyawaki, Takuya

2015-01-01

Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability. PMID:25849468

Dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide poisoning.

PubMed

Li, Q; Song, J J; Zhang, H Y; Fu, K; Lan, H B; Deng, Y

2015-01-01

We investigated dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide (CO) poisoning. Eighty healthy male rats were exposed to CO and randomly divided into four groups: hyperbaric oxygen treatment (H), treatment (D), combined hyperbaric and dexamethasone treatment (C), and a control (M) group in which the rats inhaled CO to coma in the hyperbaric oxygen chamber, then were removed without further treatment. Twelve rats were put into the hyperbaric oxygen chamber and treated with air for 60 min (N) group. An eight arm maze was used to evaluate cognitive and memory abilities of these mice. Serum myelin basic protein (MBP) levels were evaluated using ELISA, and magnetic resonance imaging was used to observe brain demyelination and morbidity associated with delayed encephalopathy. A sample of the hippocampus from each group was examined by light microscopy. Cognitive and memory functions decreased in the control group M. Three days after CO poisoning, the serum MBP level of each group increased significantly. On Day 10 after CO poisoning, the MBP levels in groups C and D decreased significantly, but returned to normal on Day 18. MBP levels in the M and H groups were elevated at all time points. Brain MRIs showed significant differences among C, D, H and control M groups. Hematoxylin & eosin staining of the hippocampus showed greater damage in the control M and H groups. Early dexamethasone treatment may be useful for preventing delayed encephalopathy after CO poisoning and may reduce serum MBP levels.

Topical Rifampin Powder for Orthopaedic Trauma Part I: Rifampin powder reduces recalcitrant infection in a delayed treatment musculoskeletal trauma model.

PubMed

Shiels, Stefanie M; Tennent, David J; Wenke, Joseph C

2018-05-21

Open fractures become infected despite meticulous debridement and care. Locally applied antibiotics, commonly embedded in polymethylmethacrylate, deliver high doses of drug directly to the fracture site. Direct application of antibiotic powder, which is being applied prophylactically in spine surgery, is a recent interest in the trauma sector, where bacterial biofilms are more prevalent. Traditional antibiotics, such as vancomycin, are poor performers against bacterial biofilms thus are ineffective in delayed treatment. Rifampin is an effective eradicator of Staphylococcal biofilms. Here, a rat model of musculoskeletal trauma was used to evaluate the utility of locally applied rifampin powder for reducing established orthopaedic Staphylococcal infections in a delayed treatment scenario that previously indicated the limited use of local vancomycin. By applying rifampin powder directly to the contaminated segmental defect, the number of bacteria, as well as clinical indications of infection, were significantly reduced compared to vancomycin and daptomycin. Considering the Infectious Disease Society of America's recommendation to use rifampin in combination with another antibiotic to reduce the onset of rifampin resistance, rifampin powder was also applied in combination with vancomycin or daptomycin with insignificant changes in eradication performance. No indications of rifampin resistance were identified. Statement of Clinical Significance: The use of locally applied rifampin is a promising therapy for mature and tolerant musculoskeletal infections. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

How do patients access the private sector in Chennai, India? An evaluation of delays in tuberculosis diagnosis.

PubMed

Bronner Murrison, L; Ananthakrishnan, R; Swaminathan, A; Auguesteen, S; Krishnan, N; Pai, M; Dowdy, D W

2016-04-01

The diagnosis and treatment of tuberculosis (TB) in India are characterized by heavy private-sector involvement. Delays in treatment remain poorly characterized among patients seeking care in the Indian private sector. To assess delays in TB diagnosis and treatment initiation among patients diagnosed in the private sector, and pathways to care in an urban setting. Cross-sectional survey of 289 consecutive patients diagnosed with TB in the private sector and referred for anti-tuberculosis treatment through a public-private mix program in Chennai from January 2014 to February 2015. Among 212 patients with pulmonary TB, 90% first contacted a formal private provider, and 78% were diagnosed by the first or second provider seen after a median of three visits per provider. Median total delay was 51 days (mean 68). Consulting an informal (rather than formally trained) provider first was associated with significant increases in total delay (absolute increase 22.8 days, 95%CI 6.2-39.5) and in the risk of prolonged delay >90 days (aRR 2.4, 95%CI 1.3-4.4). Even among patients seeking care in the formal (vs. informal) private sector in Chennai, diagnostic delays are substantial. Novel strategies are required to engage private providers, who often serve as the first point of contact.

Helping Young Children to Delay Gratification

ERIC Educational Resources Information Center

Lee, Pai-Lin; Lan, William; Wang, Chiao-Li; Chiu, Hsiu-Yueh

2008-01-01

The ability to delay gratification (DG) in young children is vital to their later development. Such ability should be taught as early as possible. One hundred kindergartners (Mean age = 6.11), randomly assigned to three groups; (a) labeling: received the treatment of being labeled as "patient" kids; (b) story-telling: were read a story about the…

Leveraging delay discounting for health: Can time delays influence food choice?

PubMed

Appelhans, Bradley M; French, Simone A; Olinger, Tamara; Bogucki, Michael; Janssen, Imke; Avery-Mamer, Elizabeth F; Powell, Lisa M

2018-07-01

Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916. Copyright © 2018 Elsevier Ltd. All rights reserved.

Observations on early and delayed colostomy closure.

PubMed

Tade, A O; Salami, B A; Ayoade, B A

2011-06-01

Traditional treatment of a variety of colorectal pathologies had included a diverting colostomy that was closed eight or more weeks later during a readmission. The aim of this retrospective study was to determine the outcomes of early colostomy closure and delayed colostomy closure in patients with temporary colostomies following traumatic and non-traumatic colorectal pathologies. In this study early colostomy closure was the closure of a colostomy within three weeks of its construction, while delayed colostomy closure referred to closure after 3 weeks. Complete records of the 37 adult patients who had temporary colostomy constructed and closed between Jan. 1997 December 2003 for various colorectal pathologies were studied. Fourteen patients had early colostomy closure while 23 had delayed closure. In the early colostomy closure group there were 10 men and 4 women. The mean age of the patients was 28yr with a range of 18-65yr. Colostomies were closed 9-18 days after initial colostomy construction. There was no mortality. Morbidity rate 28.6% (4 out of 14). There were two faecal fistulas (14.3%). Twenty-three patients had delayed colostomy closure 8 weeks to 18 months after initial colostomy construction. These were patients unfit for early surgery after initial colostomy construction because of carcinoma, significant weight loss, or sepsis. There was no mortality. Morbidity rate was 26.1%. There were 3 faecal fistulas (13.2%). Outcomes following early colostomy closure and delayed closure were comparable. Patients fit for surgery should have early closure whilst patients who may have compromised health should have delayed closure.

The Effects of Methylphenidate on Discounting of Delayed Rewards in ADHD

PubMed Central

Shiels, Keri; Hawk, Larry W.; Reynolds, Brady; Mazzullo, Rebecca; Rhodes, Jessica; Pelham, William E.; Waxmonsky, James G.; Gangloff, Brian P.

2010-01-01

Impulsivity is a central component of attention-deficit/hyperactivity disorder (ADHD). Delay discounting, or a preference for smaller, immediate rewards over larger, delayed rewards is considered an important aspect of impulsivity, and delay-related impulsivity has been emphasized in etiological models of ADHD. The current study examined whether stimulant medication, an effective treatment for ADHD, reduces discounting of delayed experiential and hypothetical rewards among 49 children (age 9–12 years) with ADHD. Following a practice day, participants completed a 3-day double-blind placebo-controlled acute medication assessment. Active doses were long-acting methylphenidate (Concerta), with the nearest equivalents of 0.3 and 0.6 mg/kg TID immediate-release methylphenidate. On each testing day, participants completed experiential (real-world money in real time) and hypothetical discounting tasks. Relative to placebo, methylphenidate reduced discounting of delayed experiential rewards, but not hypothetical rewards. Broadly consistent with etiological models that emphasize delay-related impulsivity among children with ADHD, these findings provide initial evidence that stimulant medication reduces delay discounting among those with the disorder. The present results also draw attention to task parameters that may influence the sensitivity of various delay discounting measures to medication effects. PMID:19803628

Representing delayed force feedback as a combination of current and delayed states.

PubMed

Avraham, Guy; Mawase, Firas; Karniel, Amir; Shmuelof, Lior; Donchin, Opher; Mussa-Ivaldi, Ferdinando A; Nisky, Ilana

2017-10-01

To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements. NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the

Delayed ejaculation

MedlinePlus

Ejaculatory incompetence; Sex - delayed ejaculation; Retarded ejaculation; Anejaculation; Infertility - delayed ejaculation ... include: Religious background that makes the person view sex as sinful Lack of attraction for a partner ...

[Comparison of effect between early and delayed in primary intramedullary nailing combined with locked plate fixation for the treatment of multi-segments tibial fractures of type].

PubMed

Gao, Wei-qiang; Hu, Jiang-hai; Gu, Zhu-chao; Zhang, Huai-xian; Min, Peng; Zhang, Lin-jun; Yu, Wen-wen; Wang, Guang-lin

2015-02-01

To compare the clinical results of early and delayed intramedullary nailing and locked plating for the treatment of multi-segments tibial fractures of type AO/ASIF-42C2. Between January 2010 and January 2013,45 patients with multi-segments closed tibial fractures of AO/ASIF-42C2 were treated by early primary intramedullary nailing and locked plating in 20 cases as early group and delayed in 25 cases as delayed group. In early group,20 cases included 13 males and 7 females with an average age of (37.9±14.3) years old ranging from 20 to 56 years;according to soft tissue injury Tscherne classification, 8 fractures were frade I,12 were grade II. In delayed group, 25 cases included 17 males and 8 females with an average age of (38.7±17.2) years old ranging from 24 to 55 years,4 fractures were grade I ,19 were grade II ,2 were grade III. The operative time, blood loss, hospital stay,fracture healing time and complications were recorded. At final follow-up, the Johner-Wruhs score were used to evaluate functional efficacy, and the posterior-anterior and lateral X-ray to evaluate fracture reduction and alignment. All the patients were followed up for (12.5±2.5) months in early group and (13.2±2.8) months in delayed group (P>0.05). No wounds infections were happened. At the last follow-up, the mean range of knee joint was 10°-0°-120°. According to Johner-Wruhs scoring,there were 15 cases in excellent,3 in good,fair in 2 in early group; 21 in excellent,2 in good,2 in fair. The average operative time,blood loss had no significant differences between two groups (P>0.05), but hospital stay in early group was significantly shorter than those in delayed group(P<0.05). Average fracture healing time of early group and delayed group were (5.3±2.6) months and (6.0±2.9) months, respectively (P>0.05). For multi-segments tibial fractures of type AO/ASIF-42C2 with preoperative minor soft tissue injuries lighter of Tscherne grade I or II, early primary intramedullary nailing and

Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

PubMed

Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

2018-04-01

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

Postharvest treatments with salicylic acid, acetylsalicylic acid or oxalic acid delayed ripening and enhanced bioactive compounds and antioxidant capacity in sweet cherry.

PubMed

Valero, Daniel; Díaz-Mula, Huertas M; Zapata, Pedro Javier; Castillo, Salvador; Guillén, Fabián; Martínez-Romero, Domingo; Serrano, María

2011-05-25

Sweet cherry cultivars ('Cristalina' and 'Prime Giant') harvested at commercial ripening stage were treated with salicylic acid (SA), acetylsalicylic acid (ASA) or oxalic acid (OA) at 1 mM and then stored for 20 days under cold temperature. Results showed that all treatments delayed the postharvest ripening process, manifested by lower acidity, color changes and firmness losses, and maintained quality attributes for longer periods than controls. In addition, total phenolics, anthocyanins and antioxidant activity increased in untreated fruit during the first 10 days of storage and then decreased, while in fruits of all treatments, these parameters increased continuously during storage without significant differences among treatments. Thus, postharvest treatments with natural compounds, such as SA, ASA or OA, could be innovative tools to extend the storability of sweet cherry with higher content of bioactive compounds and antioxidant activity as compared with control fruits.

Digital time delay

DOEpatents

Martin, A.D.

1986-05-09

Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay provides a first output signal at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits latch the high resolution data to form a first synchronizing data set. A selected time interval has been preset to internal counters and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses count down the counters to generate an internal pulse delayed by an internal which is functionally related to the preset time interval. A second LCD corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD to generate a second set of synchronizing data which is complementary with the first set of synchronizing data for presentation to logic circuits. The logic circuits further delay the internal output signal with the internal pulses. The final delayed output signal thereafter enables the output pulse generator to produce the desired output pulse at the preset time delay interval following input of the trigger pulse.

Above and below delayed endoscopic treatment of traumatic posterior urethral disruptions.

PubMed

Quint, H J; Stanisic, T H

1993-03-01

Between 1982 and 1990, 10 men with posterior urethral obliterations associated with pelvic fracture were managed with delayed above and below endoscopic reconstruction. After a mean of 43 months (range 7 to 108) of followup, all 10 men void with a peak flow rate of 12 ml. per second or greater and/or have a urethral caliber of 20F or greater. Concomitant prostatic hypertrophy somewhat compromises micturition in 4 older men. Nine patients are totally continent and 1 has mild stress incontinence. Five men who were potent after injury remain so after reconstruction. Of the 10 patients 6 required subsequent visual urethrotomy and/or scar resections, generally as outpatient or short stay procedures. In most instances voiding stabilized within 1 year, and interventions after this interval were unusual and generally trivial. We compare our experience with the results of others using a similar delayed endoscopic approach and conclude that this is a satisfactory method of managing traumatic posterior urethral obliterations, resulting in satisfactory voiding, continence and potency preservation.

Delayed onset muscle soreness : treatment strategies and performance factors.

PubMed

Cheung, Karoline; Hume, Patria; Maxwell, Linda

2003-01-01

Delayed onset muscle soreness (DOMS) is a familiar experience for the elite or novice athlete. Symptoms can range from muscle tenderness to severe debilitating pain. The mechanisms, treatment strategies, and impact on athletic performance remain uncertain, despite the high incidence of DOMS. DOMS is most prevalent at the beginning of the sporting season when athletes are returning to training following a period of reduced activity. DOMS is also common when athletes are first introduced to certain types of activities regardless of the time of year. Eccentric activities induce micro-injury at a greater frequency and severity than other types of muscle actions. The intensity and duration of exercise are also important factors in DOMS onset. Up to six hypothesised theories have been proposed for the mechanism of DOMS, namely: lactic acid, muscle spasm, connective tissue damage, muscle damage, inflammation and the enzyme efflux theories. However, an integration of two or more theories is likely to explain muscle soreness. DOMS can affect athletic performance by causing a reduction in joint range of motion, shock attenuation and peak torque. Alterations in muscle sequencing and recruitment patterns may also occur, causing unaccustomed stress to be placed on muscle ligaments and tendons. These compensatory mechanisms may increase the risk of further injury if a premature return to sport is attempted.A number of treatment strategies have been introduced to help alleviate the severity of DOMS and to restore the maximal function of the muscles as rapidly as possible. Nonsteroidal anti-inflammatory drugs have demonstrated dosage-dependent effects that may also be influenced by the time of administration. Similarly, massage has shown varying results that may be attributed to the time of massage application and the type of massage technique used. Cryotherapy, stretching, homeopathy, ultrasound and electrical current modalities have demonstrated no effect on the alleviation of

Patient and health service delay in pulmonary tuberculosis patients attending a referral hospital: a cross-sectional study.

PubMed

Kiwuwa, Mpungu S; Charles, Karamagi; Harriet, Mayanja Kizza

2005-11-24

Delays in diagnosis and initiation of effective treatment increase morbidity and mortality from tuberculosis as well as the risk of transmission in the community. The aim of this study was to determine the time taken for patients later confirmed as having TB to present with symptoms to the first health provider (patient delay) and the time taken between the first health care visit and initiation of tuberculosis treatment (health service delay). Factors relating to these 'delays' were analyzed. A cross-sectional survey, of 231 newly diagnosed smear-positive tuberculosis patients was conducted in Mulago National referral Hospital Kampala, from January to May 2002. Socio-demographic, lifestyle and health seeking factors were evaluated for their association with patient delay (> 2 weeks) and health service delay (> 4 weeks), using odds ratios with 95% confidence intervals (CI) including multivariate logistic regression. The median total delay to treatment initiation was 12 weeks. Patients often presented to drug shops or pharmacies (39.4%) and private clinics (36.8%) more commonly than government health units (14%) as initial contacts. Several independent predictors of 'patient delay' were identified: being hospitalized (odds ratio [0R] = 0.32; 95% CI: 0.12-0.80), daily alcohol consumption (OR = 3.7; CI: 1.57-9.76), subsistence farming (OR = 4.70; CI: 1.67-13.22), and perception of smoking as a cause of TB (OR = 5.54; CI: 2.26-13.58). Independent predictors of 'health service delay' were: > 2 health seeking encounters per month (OR = 2.74; CI: 1.10-6.83), and medical expenditure on TB related symptoms > 29 US dollars (OR = 3.88; CI: 1.19-12.62). Perceived TB stigma and education status was not associated with either form of delay. Delay in diagnosis of TB is prolonged at the referral centre with a significant proportion of Health service delay. More specific and effective health education of the general public on tuberculosis and seeking of appropriate medical

Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats

PubMed Central

Zhao, H; Watts, H R; Chong, M; Huang, H; Tralau-Stewart, C; Maxwell, P H; Maze, M; George, A J T; Ma, D

2013-01-01

Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival. PMID:23710625

Delayed Auditory Feedback in the Treatment of Stuttering: Clients as Consumers

ERIC Educational Resources Information Center

Van Borsel, John; Reunes, Gert; Van den Bergh, Nathalie

2003-01-01

Purpose: To investigate the effect of repeated exposure to delayed auditory feedback (DAF) during a 3-month period outside a clinical environment and with only minimal clinical guidance on speech fluency in people who stutter. Method: A pretest-post-test design was used with repeated exposure to DAF during 3 months as the independent variable.…

Delayed conifer mortality after fuel reduction treatments: Interactive effects of fuel, fire intensity, and bark beetles

USGS Publications Warehouse

Youngblood, A.; Grace, J.B.; Mciver, J.D.

2009-01-01

Many low-elevation dry forests of the western United States contain more small trees and fewer large trees, more down woody debris, and less diverse and vigorous understory plant communities compared to conditions under historical fire regimes. These altered structural conditions may contribute to increased probability of unnaturally severe wildfires, susceptibility to uncharacteristic insect outbreaks, and drought-related mortality. Broad-scale fuel reduction and restoration treatments are proposed to promote stand development on trajectories toward more sustainable structures. Little research to date, however, has quantified the effects of these treatments on the ecosystem, especially delayed and latent tree mortality resulting directly or indirectly from treatments. In this paper, we explore complex hypotheses relating to the cascade of effects that influence ponderosa pine (Pinus ponderosa) and Douglas-fir (Pseudotsuga menziesii) mortality using structural equation modeling (SEM). We used annual census and plot data through six growing seasons after thinning and four growing seasons after burning from a replicated, operational-scale, completely randomized experiment conducted in northeastern Oregon, USA, as part of the national Fire and Fire Surrogate study. Treatments included thin, burn, thin followed by burn (thin+burn), and control. Burn and thin+burn treatments increased the proportion of dead trees while the proportion of dead trees declined or remained constant in thin and control units, although the density of dead trees was essentially unchanged with treatment. Most of the new mortality (96%) occurred within two years of treatment and was attributed to bark beetles. Bark beetle-caused tree mortality, while low overall, was greatest in thin + burn treatments. SEM results indicate that the probability of mortality of large-diameter ponderosa pine from bark beetles and wood borers was directly related to surface fire severity and bole charring, which in

[Determinants of patient and health system delays for women with breast cancer in Morocco, 2013].

PubMed

Benbakhta, B; Tazi, M; Benjaafar, N; Khattabi, A; Maaroufi, A

2015-06-01

In Morocco, breast cancer is the first most common cancer in women. It is diagnosed in most cases at an advanced stage. Delay in diagnosis and access to treatment for breast cancer increases morbidity and mortality. The objective of this study was to determine the consultation delay (patient delay), diagnosis delay and access to treatment delay (health system delays) of women with breast cancer admitted at the National Institute of Oncology in Rabat. Factors associated with these delays were analyzed. We conducted a cross-sectional study from December 2012 to May 2013 at the National Institute of Oncology in Rabat. Two hundred eligible and consenting women were interviewed using a structured and pre-tested questionnaire. Stages I and II were identified as "early stages" and III and IV as "advanced stages". In our population, 54% were diagnosed at an early stage of breast cancer and 46% at an advanced stage. The median total delay was 120 days (interquartile interval [IIQ]=81-202 days). The patient delay (median=65 days, IIQ=31-121) was longer than the health system delay (median=50 days, IIQ=29-77). High risk for a long total delay (more than 4 months) was observed for women who were aged over 65 years (OR=1.30, 95% CI 1.10-4.20), illiterate (OR=4.50, 95% CI 2.10-6.20), rural residents (OR=3.40, 95% CI 1.23-8.13), in a lower socioeconomic category (OR=4.75, 95% CI 1.45-15.60), without knowledge about breast self-examination (OR=5.67, 95% CI 2.65-12.15) and seen more than 2 times before diagnosis (OR=7.70, 95% CI 2.88-20.50). A long total delay increased the risk of being diagnosed at an advanced stage (OR=5.62, 95% CI 3.03-10.45). Efforts should be directed to providing good information to the population at risk, better access to screening and continuing medical training to enable diagnosis and early treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Factors linked to delayed diagnosis of tuberculosis in Conakry (Guinea)].

PubMed

Camara, A; Diallo, A; Camara, L M; Fielding, K; Sow, O Y; Chaperon, J

2006-03-01

Untreated smear-positive pulmonary tuberculosis constitutes a reservoir of infection which is highly contagious. The present study was conducted in Conakry, Guinea, to determine the different options which are available when seeking treatment or care, and to ascertain the average delay in diagnosis of pulmonary tuberculosis and the main factors linked to the delay in diagnosis after the initial onset of symptoms. Through a cross-sectional study, 113 consecutive patients with smear-positive pulmonary tuberculosis were interviewed through the use of a questionnaire. The median total delay from the onset of symptoms of pulmonary tuberculosis until the diagnosis was 11 weeks. This delay period exceeded 4 weeks for 90 of the patients (80%). The average delay linked to the conventional health care system was double that of the one at the fault of the patient (6 weeks versus 3 weeks, respectively). 54% of the patients had initially resorted to non-conventional care. To shorten this mean delay period, it is necessary to both strengthen the professional abilities and skills which train for one to better to detect tuberculosis and to sensitize the population to the subject matter and information on the illness and its symptoms.

Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

PubMed

Warren, Travis K; Whitehouse, Chris A; Wells, Jay; Welch, Lisa; Charleston, Jay S; Heald, Alison; Nichols, Donald K; Mattix, Marc E; Palacios, Gustavo; Kugleman, Jeffrey R; Iversen, Patrick L; Bavari, Sina

2016-02-01

Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

Reasons for delay in decision making and reaching health facility among obstetric fistula and pelvic organ prolapse patients in Gondar University hospital, Northwest Ethiopia.

PubMed

Adefris, Mulat; Abebe, Solomon Mekonnen; Terefe, Kiros; Gelagay, Abebaw Addis; Adigo, Azmeraw; Amare, Selamawit; Lazaro, Dorothy; Berhe, Aster; Baye, Chernet

2017-08-22

Obstetric fistula and pelvic organ prolapse remain highly prevalent in sub-Saharan Africa, where women have poor access to modern health care. Women having these problems tend to stay at home for years before getting treatment. However, information regarding the reasons contributing to late presentation to treatment is scarce, especially at the study area. The objective of this study was to assess the reasons whywomen with obstetric fistula and pelvic organ prolapse at Gondar University Hospital delay treatment. A hospital based cross-sectional study was conducted among 384 women. Delay was evaluated by calculating symptom onset and time of arrival to get treatment at Gondar University Hospital. Regression analysis was conducted to elicit predictors of delay for treatment. Of the total 384 participants, 311 (80.9%) had pelvic organ prolapse and 73(19.1%) obstetric fistula. The proportion of women who delayed treatment of pelvic organ prolapse was 82.9% and that of obstetric fistula 60.9%. Fear of disclosing illness due to social stigma (AOR = 2; 1.03, 3.9) and lack of money (AOR = 1.97; 1.01, 3.86) were associated with the delay of treatment for pelvic organ prolapse,while increasing age (AOR =1.12; 1.01, 1.24) and divorce (AOR = 16.9; 1.75, 165.5) were were responsible for delaying treatment forobstetric fistula. A large numberof women with pelvic organ prolapse and obstetric fistula delayed treatment. Fear of disclosure due to social stigma and lack of moneywere the major factors that contributed to thedelay to seek treatment for pelvic organ prolapse,while increasing age and divorce were the predictors for delaying treatment for obstetric fistula.

Effects of Acute and Chronic Flunitrazepam on Delay Discounting in Pigeons

PubMed Central

Eppolito, Amy K; France, Charles P; Gerak, Lisa R

2011-01-01

Delay to delivery of a reinforcer can decrease responding for that reinforcer and increase responding for smaller reinforcers that are available concurrently and delivered without delay; acute administration of drugs can alter responding for large, delayed reinforcers, although the impact of chronic treatment on delay discounting is not well understood. In this experiment, the effects of repeated administration of the benzodiazepine flunitrazepam were studied in 6 pigeons responding on one key to receive food that was delivered immediately and on a second key to receive a larger amount of food that was delivered following delays which increased across a single session. Pigeons responded predominantly for the large reinforcer when there were no delays and when delays were short; however, as delays increased, responding for the large reinforcer decreased. Acutely, flunitrazepam (0.32, 1.0 and 3.2 mg/kg) dose-dependently increased responding for the large reinforcer, shifting the discounting curve rightward and upward. Repeated administration of flunitrazepam (0.32, 1.0 and 3.2 mg/kg, each for six sessions, separated by one session during which vehicle was administered) did not markedly alter its effects on responding for the large reinforcer, indicating that the development of tolerance to this effect of flunitrazepam is modest under these conditions. PMID:21541119

Hereditary angioedema with C1 inhibitor deficiency: delay in diagnosis in Europe

PubMed Central

2013-01-01

Background Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening disease characterized by recurrent edema attacks. Important advances in HAE treatment have been made, including the development of new therapies for treating or preventing attacks. Nevertheless, the disease is still frequently misdiagnosed and inappropriately treated, potentially exposing patients with laryngeal attacks to the risk of asphyxiation. Methods The Icatibant Outcome Survey (IOS) is an international, observational study that documents the clinical outcome of HAE patients eligible for treatment with icatibant. Patient ages at first symptoms and at diagnosis were recorded at enrolment, and the delay between first symptoms and diagnosis was calculated. Results The median [range] diagnostic delay in HAE type I and II patients across eight countries was 8.5 years [0–62.0]. The median delay in diagnosis was longer for HAE type II versus type I (21 versus 8 years, respectively), although this did not quite reach statistical significance. Conclusions Although it can be difficult to differentiate HAE symptoms from those of more common angioedema sub-types (e.g. idiopathic or acquired angioedema), our results show that HAE type I and II patients have an unacceptable delay in diagnosis, even those with a family history of the disease. Raising physician awareness of this disabling and potentially fatal disease may lead to a more accurate diagnosis and timely treatment. PMID:23937903

Delay in treatment of biliary disease during pregnancy increases morbidity and can be avoided with safe laparoscopic cholecystectomy.

PubMed

Muench, J; Albrink, M; Serafini, F; Rosemurgy, A; Carey, L; Murr, M M

2001-06-01

Recent reports indicate that laparoscopic cholecystectomy in pregnancy is safe. The aim of this study was to evaluate whether delays in definitive treatment of symptomatic cholelithiasis increase morbidity. We reviewed the records of 16 women who underwent laparoscopic cholecystectomy during pregnancy between 1992 and 1999. Mean age was 24 +/- 5 years (mean +/- standard error). Symptom onset was during the first trimester in nine patients, second trimester in six patients, and third trimester in one patient. Patients had abdominal pain (93%), nausea (93%), emesis (80%), and fever (66%) for a median of 45 days (range 1-195 days) before cholecystectomy. Nine of 11 women who underwent cholecystectomy more than 5 weeks after onset of symptoms experienced recurrent attacks necessitating 15 hospital admissions and four emergency room visits. Moreover four women who developed symptoms in the first and second trimesters but whose operations were delayed to the third trimester had 11 hospital admissions and four emergency room visits; three of those four (75%) women developed premature contractions necessitating tocolytics. Cholecystectomy was completed laparoscopically in 14 women. There was no hospital infant or maternal mortality or morbidity. We recommend prompt laparoscopic cholecystectomy in pregnant women with symptomatic biliary disease because it is safe and it reduces hospital admissions and frequency of premature labor.

Percutaneous drainage of Morel-Lavallée lesions when the diagnosis is delayed.

PubMed

Zhong, Biao; Zhang, Chi; Luo, Cong-feng

2014-10-01

Morel-Lavallée lesions are a closed internal degloving, and open débridement can damage the only remaining blood supply to the skin. We performed percutaneous draining and débridement to treat 8 patients in whom the diagnosis of Morel-Lavallée lesions was delayed more than 1 week. Here we discuss our treatment procedures and the outcomes in these 8 patients. We consider percutaneous drainage to be an effective treatment for patients with delayed diagnosis of Morel-Lavallée lesions.

Magnetic resonance imaging (MRI) evaluation of developmental delay in pediatric patients.

PubMed

Ali, Althaf S; Syed, Naziya P; Murthy, G S N; Nori, Madhavi; Abkari, Anand; Pooja, B K; Venkateswarlu, J

2015-01-01

Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child's ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with

Hot water bath treatments assisted by microwave energy to delay postharvest ripening and decay in strawberries (Fragaria × ananassa).

PubMed

Villa-Rojas, Rossana; López-Malo, Aurelio; Sosa-Morales, María Elena

2011-09-01

A lab-scale approach using microwave (MW)-assisted hot water treatments was developed and tested to assess the potential of this heating method to delay postharvest ripening and decay in strawberries. Strawberries (Fragaria × ananassa) immersed in water were exposed to microwaves at a frequency of 2450 MHz for 3 min at 514 W or 1 min 50 s at 763 W to reach an average temperature of 43.8 ± 0.6 °C at the fruit centre. Another batch was treated in hot water at 45 °C for 15 min, and a final batch was not treated (control). After 9 days of refrigerated storage (3 °C and 90% relative humidity), all heat-treated strawberries showed significant retention of quality parameters such as colour and firmness and significantly lower yeast and mould populations (P < 0.05). Strawberries subjected to MW-assisted hot water treatments showed significantly better retention of lightness compared with conventionally treated berries. A short (1 min 50 s) treatment at 763 W was the best choice to prevent strawberry decay. Copyright © 2011 Society of Chemical Industry.

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared with 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial

PubMed Central

Hanauer, Stephen B; Sandborn, William J; Dallaire, Christian; Archambault, André; Yacyshyn, Bruce; Yeh, Chyon; Smith-Hall, Nancy

2007-01-01

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day. PMID:18080055

Electrophysiologic changes following treatment with organophosphorus-induced delayed neuropathy-producing agents in the adult hen.

PubMed

Robertson, D G; Schwab, B W; Sills, R D; Richardson, R J; Anderson, R J

1987-03-15

Although clinical, pathological, and biochemical effects of organophosphorus-induced delayed neuropathy (OPIDN) have been intensively investigated in the adult hen, detailed electrophysiological studies are lacking. Adult white leghorn hens were treated with a single oral dose of either 30 mg/kg tri-2-cresyl phosphate (TOCP), 750 mg/kg TOCP, 4 mg/kg di-n-butyl-2,2-dichlorovinyl phosphate (DBCV), or 30 mg/kg di-n-butyl-2,2-dichlorovinyl phosphinate (DBCV-P). The 750 mg/kg TOCP and DBCV, but not the 30 mg/kg TOCP and DBCV-P, treatments resulted in clinical signs of OPIDN and mild to marked damage of the tibial nerve 21 days after dose. Twenty-four hr lymphocyte neurotoxic esterase (NTE) inhibition was used as an index of brain NTE inhibition for the various organophosphorus compound (OP) treatment. Twenty-four hr lymphocyte NTE inhibition for 30 mg/kg TOCP, 750 mg/kg TOCP, DBCV, and DBCV-P was 54.1, 87.1, 84.8, and 68.3%, respectively. Twenty-one days after dose, the TOCP-treated hens exhibited some abnormalities in conduction velocity and action potential duration in the tibial or sciatic nerves. No abnormalities were observed in action potential parameters of either the DBCV or DBCV-P treatments. Neurotoxic OP (TOCP and DBCV) treatment resulted in decreased refractoriness in the tibial nerve, increased refractoriness in the sciatic nerve, and elevated strength duration threshold for both nerves. These changes were not present in nerves from DBCV-P (a non-neurotoxic NTE inhibitor)-treated hens. These results suggest that refractory period and strength duration abnormalities in peripheral nerve correlate well with the production of OPIDN and are evident without coincident clinical signs or histopathology.

Delayed luminescence in a multiparameter approach to evaluation and reduction of radiobiological risks

NASA Astrophysics Data System (ADS)

Grasso, Rosaria; Cammarata, Francesco Paolo; Minafra, Luigi; Marchese, Valentina; Russo, Giorgio; Manti, Lorenzo; Musumeci, Francesco; Scordino, Agata

2017-07-01

In the framework of the research project ETHICS "Pre-clinical experimental and theoretical studies to improve treatment and protection by charged particles" funded by the National Nuclear Physics Institute, Italy, we studied the phenomenon called delayed luminescence emitted by non-tumorigenic breast epithelial MCF10A cell line after proton irradiation at different doses (0.5, 2, 6, 9 Gy). The aim is to found possible correlations between delayed luminescence and in vitro damaging induced by ion irradiation. The first results of this research show that the delayed luminescence kinetics is proton dose dependent. An interesting correlation between delayed luminescence and clonogenic potential was observed.

A comprehensive review of prehospital and in-hospital delay times in acute stroke care.

PubMed

Evenson, K R; Foraker, R E; Morris, D L; Rosamond, W D

2009-06-01

The purpose of this study was to systematically review and summarize prehospital and in-hospital stroke evaluation and treatment delay times. We identified 123 unique peer-reviewed studies published from 1981 to 2007 of prehospital and in-hospital delay time for evaluation and treatment of patients with stroke, transient ischemic attack, or stroke-like symptoms. Based on studies of 65 different population groups, the weighted Poisson regression indicated a 6.0% annual decline (P<0.001) in hours/year for prehospital delay, defined from symptom onset to emergency department arrival. For in-hospital delay, the weighted Poisson regression models indicated no meaningful changes in delay time from emergency department arrival to emergency department evaluation (3.1%, P=0.49 based on 12 population groups). There was a 10.2% annual decline in hours/year from emergency department arrival to neurology evaluation or notification (P=0.23 based on 16 population groups) and a 10.7% annual decline in hours/year for delay time from emergency department arrival to initiation of computed tomography (P=0.11 based on 23 population groups). Only one study reported on times from arrival to computed tomography scan interpretation, two studies on arrival to drug administration, and no studies on arrival to transfer to an in-patient setting, precluding generalizations. Prehospital delay continues to contribute the largest proportion of delay time. The next decade provides opportunities to establish more effective community-based interventions worldwide. It will be crucial to have effective stroke surveillance systems in place to better understand and improve both prehospital and in-hospital delays for acute stroke care.

Delayed surgical repair of penile fracture under local anesthesia.

PubMed

Nasser, Taha Abdel; Mostafa, Taymour

2008-10-01

Penile fracture is a traumatic rupture of the tunica albuginea because of blunt injury of an erect penis. To assess the efficacy of a simple delayed surgical repair of penile fracture after a conservative treatment under local anesthesia in patients presented after 24 hours. Twenty-four patients with penile fracture presented after 24 hours were subjected to history taking, clinical examination, urine analysis, and penile ultrasound. They underwent conservative treatment for 7-12 days, and then a surgical repair under local anesthesia was carried out. A follow-up for 6 months for sexual activity and any associated complaints in addition to local examination. All cases were presented with unilateral single tear, and the main cause of penile fracture was sexual intercourse. No intraoperative or postoperative complications were encountered. They regained their sexual activity 4-6 weeks after the repair. One case developed a mild penile deviation that did not interfere with sexual relation after the 6-month follow-up. Surgical repair of penile fracture after a conservative treatment is an effective method for patients with delayed presentation devoid of urethral involvement.

Delayed leucoencephalopathy after coil embolisation of unruptured cerebral aneurysm.

PubMed

Fukushima, Yoshihisa; Nakahara, Ichiro

2018-06-23

A 56-year-old right-handed woman was successfully treated by coil embolisation for a large unruptured paraclinoid aneurysm of the left internal carotid artery. Though she was discharged on day 3 after the intervention with uneventful clinical course, she was rehospitalised for continuous headache and right upper limb weakness 2 weeks after the treatment. Subsequent progression of cognitive dysfunction and right hemiparesis were observed. Repeated MRI revealed diffuse leucoencephalopathy within the ipsilateral brain hemisphere. Clinical course, serological examination, and radiological findings were consistent with localised hypocomplemental vasculitis caused by delayed hypersensitivity reaction. Immunosuppressive treatments using prednisolone successfully improved her symptoms. After a washout period for immunosuppressant, skin reaction test was performed and revealed polyglycolic-polylactic acid, coating material of the coil, positive for delayed allergic reaction. Given the increased frequency of endovascular treatment for unruptured aneurysms, even such a rare complication should be recognised and treated properly to avoid neurological sequelae. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Choice between delayed food and immediate oxycodone in rats

PubMed Central

Secci, Maria E.; Factor, Julie A.; Schindler, Charles W.; Panlilio, Leigh V.

2016-01-01

Rationale The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. Objectives To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. Results Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pretreatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pretreatment decreased drug intake and increased food intake. Oxycodone pretreatment decreased drug intake, but also produced extended periods with no food or drug responding. Conclusions These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction. PMID:27678551

Treatment of intra-oral injection phobia: a randomized delayed intervention controlled trial among Norwegian 10- to 16-year-olds.

PubMed

Berge, Karin G; Agdal, Maren Lillehaug; Vika, Margrethe; Skeie, Marit Slåttelid

2017-05-01

To evaluate the effect of five sessions of cognitive behavioural therapy (CBT) for 10- to 16-year-olds with intra-oral injection phobia. This was a randomized delayed intervention controlled trial in 67 patients, fulfilling the DSM-5 criteria for specific phobia. All patients received the same CBT performed by dentists specially trained in CBT. The patients were randomly assigned to either an immediate treatment group (ITG) (34 patients) or a waitlist-control group (WCG) (33 patients). The WCG was put on a waitlist for 5 weeks. After treatment, all patients were combined for post-treatment analyses. Assessments including the psychometric self-report scales Intra-oral injection fear scale (IOIF-s), Children's Fear Survey Schedule-Dental Subscale (CFSS-DS), Injection Phobia Scale for children (IS-c) and Mutilation Questionnaire for children (MQ-c) and a behavioural avoidance test (BAT) followed by a questionnaire on cognitions during the BAT, occurred pre-, post-treatment/waitlist and at a 1-year follow-up. CBT had a significant effect compared to no treatment (WCG). After treatment, the scores on the psychometric self-report scales were significantly reduced and higher levels in the BAT were achieved. The results were maintained at 1-year follow-up. Of the 67 patients, 70.1% received intra-oral injections during CBT treatment, whereas 69.4% of those completing the CBT, in need for further dental treatment, managed to receive the necessary intra-oral injections at their regular dentist. The 10- to 16-year-olds diagnosed with intra-oral injection phobia benefitted positively on CBT performed by specially trained dentists.

Xenon treatment protects against cold ischemia associated delayed graft function and prolongs graft survival in rats.

PubMed

Zhao, H; Watts, H R; Chong, M; Huang, H; Tralau-Stewart, C; Maxwell, P H; Maze, M; George, A J T; Ma, D

2013-08-01

Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia-hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Effect of longer health service provider delays on stage at diagnosis and mortality in symptomatic breast cancer.

PubMed

Murchie, P; Raja, E A; Lee, A J; Brewster, D H; Campbell, N C; Gray, N M; Ritchie, L D; Robertson, R; Samuel, L

2015-06-01

This study explored whether longer provider delays (between first presentation and treatment) were associated with later stage and poorer survival in women with symptomatic breast cancer. Data from 850 women with symptomatic breast cancer were linked with the Scottish Cancer Registry; Death Registry; and hospital discharge dataset. Logistic regression and Cox survival analyses with restricted cubic splines explored relationships between provider delays, stage and survival, with sequential adjustment for patient and tumour factors. Although confidence intervals were wide in both adjusted analyses, those with the shortest provider delays had more advanced breast cancer at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are associated with more advanced stage, but is not statistically significant. Those with symptomatic breast cancer and the shortest presentation to treatment time (within 4 weeks) had the poorest survival. Longer time to treatment was not significantly associated with worsening mortality. Poor prognosis patients with breast cancer are being triaged for rapid treatment with limited effect on outcome. Prolonged time to treatment does not appear to be strongly associated with poorer outcomes for patients with breast cancer, but the power of this study to assess the effect of very long delays (>25 weeks) was limited. Efforts to reduce waiting times are important from a quality of life perspective, but tumour biology may often be a more important determinant of stage at diagnosis and survival outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Breast cancer delay in Latinas: the role of cultural beliefs and acculturation.

PubMed

Tejeda, Silvia; Gallardo, Rani I; Ferrans, Carol Estwing; Rauscher, Garth H

2017-04-01

Cultural beliefs about breast cancer may act as a barrier to Latina women seeking preventive services or timely follow-up for breast symptoms regardless of access. This study examines the association between factors and breast cancer cultural beliefs and the extent to which cultural beliefs are associated with delays in breast cancer care. Participants who were Latina, ages 30-79, and had been diagnosed with a primary breast cancer were examined (n = 181). Interviews included a 15-item cultural beliefs scale spanning beliefs inconsistent with motivation to seek timely healthcare. Self-reported date of symptom discovery, date of first medical presentation, and date of first treatment were used to construct measures of prolonged patient, clinical, and total delay. Logistic regression with model-based standardization was used to estimate crude and confounder-adjusted prevalence differences for prolonged delay by number of cultural beliefs held. Women held a mean score of three cultural beliefs. The belief most commonly held was, "Faith in God can protect you from breast cancer" (48 %). Holding three or more cultural beliefs was associated with lower acculturation, lower socioeconomic status and less access to care (p < 0.01). After adjusting for age, education, income, acculturation, trust, and insurance, likelihood of prolonged total delay remained 21 percentage points higher in women who held a higher number cultural beliefs (p = 0.02). Cultural beliefs may predispose Latina women to prolong delays in seeking diagnosis and treatment for breast symptoms. Cultural beliefs represent a potential point of intervention to decrease delays among Latina breast cancer patients.

Breast cancer delay in Latinas: the role of cultural beliefs and acculturation

PubMed Central

Tejeda, Silvia; Gallardo, Rani I.; Ferrans, Carol Estwing

2016-01-01

Cultural beliefs about breast cancer may act as a barrier to Latina women seeking preventive services or timely follow-up for breast symptoms regardless of access. This study examines the association between factors and breast cancer cultural beliefs and the extent to which cultural beliefs are associated with delays in breast cancer care. Participants who were Latina, ages 30–79, and had been diagnosed with a primary breast cancer were examined (n = 181). Interviews included a 15-item cultural beliefs scale spanning beliefs inconsistent with motivation to seek timely healthcare. Self-reported date of symptom discovery, date of first medical presentation, and date of first treatment were used to construct measures of prolonged patient, clinical, and total delay. Logistic regression with model-based standardization was used to estimate crude and confounder-adjusted prevalence differences for prolonged delay by number of cultural beliefs held. Women held a mean score of three cultural beliefs. The belief most commonly held was, “Faith in God can protect you from breast cancer” (48 %). Holding three or more cultural beliefs was associated with lower acculturation, lower socioeconomic status and less access to care (p < 0.01). After adjusting for age, education, income, acculturation, trust, and insurance, likelihood of prolonged total delay remained 21 percentage points higher in women who held a higher number cultural beliefs (p = 0.02). Cultural beliefs may predispose Latina women to prolong delays in seeking diagnosis and treatment for breast symptoms. Cultural beliefs represent a potential point of intervention to decrease delays among Latina breast cancer patients. PMID:27572092

Delay of Gratification and Delay Discounting: A Unifying Feedback Model of Delay-Related Impulsive Behavior

ERIC Educational Resources Information Center

Reynolds, Brady; Schiffbauer, Ryan

2005-01-01

Delay of Gratification (DG) and Delay Discounting (DD) represent two indices of impulsive behavior often treated as though they represent equivalent or the same underlying processes. However, there are key differences between DG and DD procedures, and between certain research findings with each procedure, that suggest they are not equivalent. In…

Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals.

PubMed

Chen, Yanmei; Zhang, Chuanxi; Shen, Shuxin; Guo, Shengcun; Zhong, Lintao; Li, Xinzhong; Chen, Guojun; Chen, Gangbin; He, Xiang; Huang, Chixiong; He, Nvqin; Liao, Wangjun; Liao, Yulin; Bin, Jianping

2016-12-01

Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction (MI) does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. In the present study, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs and subsequently attenuate post-infarction cardiac remodelling. A myocardial ischaemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligation for 45 min followed by reperfusion. Western blotting revealed that engraftment signals peaked at 7 days post-I/R and were dramatically lower at 14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be triggered by UTMD treatment at a mechanical index of 1.0-1.9. The troponin I levels in the 1.9 mechanical index group were higher than in the other groups. Simultaneous haematoxylin and eosin staining and fluorescence revealed that the number of engrafted BMCs in the ischaemic zone was greater in the group treated with both UTMD and delayed BMC transplantation than in the control groups (P<0.05). Both UTMD and delayed BMC transplantation improved cardiac function and decreased cardiac fibrosis at 4 weeks after treatment, as compared with control groups (both P<0.05). Histopathology demonstrated that UTMD combined with delayed BMC transplantation increased capillary density, myocardial cell proliferation and c-kit + cell proliferation. These findings indicated that UTMD treatment could induce engraftment signals and enhance homing of delayed BMCs to ischaemic myocardium, attenuating post-infarction cardiac remodelling by promoting neovascularization, cardiomyogenesis and expansion of cardiac c-kit + cells. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Effects of N-methyl-D-aspartate receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure

PubMed Central

Yates, Justin R; Gunkel, Benjamin T; Rogers, Katherine K; Hughes, Mallory N; Prior, Nicholas A

2016-01-01

Rationale The N-methyl-D-aspartate (NMDA) receptor has been recently identified as an important mediator of impulsive choice, as assessed in delay discounting. Although discounting is independently influenced by sensitivity to reinforcer magnitude and delayed reinforcement, few studies have examined how NMDA receptor ligands differentially affect these parameters. Objectives The current study examined the effects of various NMDA receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure. Methods Following behavioral training, rats received treatments of the following NMDA receptor ligands: the uncompetitive antagonists ketamine (0, 1.0, 5.0, or 10.0 mg/kg; i.p.), MK-801 (0, 0.003, 0.01, or 0.03 mg/kg; s.c.), and memantine (0, 2.5, 5.0, or 10.0 mg/kg; i.p.), the competitive antagonist CGS 19755 (0, 5.0, 10.0, or 20.0 mg/kg; s.c.), the non-competitive NR2B subunit-selective antagonist ifenprodil (0, 1.0, 3.0, or 10.0 mg/kg; i.p), and the partial agonist D-cycloserine (0, 3.25, 15.0, or 30.0 mg/kg; s.c.). Results When an exponential model was used to describe discounting, CGS 19755 (5.0 mg/kg) increased impulsive choice without altering sensitivity to reinforcer magnitude. Conversely, ketamine (10.0 mg/kg), memantine (5.0 mg/kg), and ifenprodil (10.0 mg/kg) decreased sensitivity to reinforcer magnitude without altering impulsive choice. MK-801 and D-cycloserine did not alter delay-discounting performance, although two-way ANOVA analyses indicated D-cycloserine (15.0 mg/kg) decreased impulsive choice. Conclusions The behavioral changes observed in delay discounting following administration of NMDA receptor antagonists do not always reflect an alteration in impulsive choice. These results emphasize the utility in employing quantitative methods to assess drug effects in delay discounting. PMID:27837332

Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

PubMed

Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

2016-02-01

With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

Determinants of Patient Delay in Seeking Diagnosis and Treatment among Moroccan Women with Cervical Cancer

PubMed Central

Hanchi, Zaki; Bekkali, Rachid; Ahid, Samir; Mesfioui, Abdelhalem

2016-01-01

Introduction. This study sought to investigate potential determinants of patient delay among Moroccan women with cervical cancer. Methods. A cross-sectional study was conducted from June 2014 to June 2015 at the National Institute of Oncology in Rabat. Data were collected using questionnaire among patients with cervical cancer locally advanced or metastatic (stages IIA–IVB). Medical records were abstracted to complete clinical information. An interval longer than 90 days between discovery of initial symptoms and presentation to a provider was defined as a patient delay. Results. Four hundred and one patients with cervical cancer enrolled in this study. The mean age was 52.4 years (SD = 11.5). 53.6% were illiterate. Abnormal vaginal bleeding was identified for 65.8% of patients. 60.1% were diagnosed at stages IIA-IIB. 55.4% were found having patient delay. The regression analyses showed the association between literacy (p < 0.001), distance of the place of the first consultation (p = 0.031), abnormal vaginal bleeding as an earlier symptom (p < 0.001), stage at diagnosis (p < 0.03), knowledge of symptoms (p < 0.001), knowledge of causes (p = 0.008), and practice of gynecological exam during the last three years (p = 0.018) and the patient delay. Conclusion. Educational messages should aim at increasing awareness of cervical cancer, assisting women in symptom recognition, and encouraging earlier presentation. PMID:27882055

Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

PubMed

Solomon, P R; Groccia-Ellison, M E

1996-06-01

Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

Delayed Union of a Sacral Fracture: Percutaneous Navigated Autologous Cancellous Bone Grafting and Screw Fixation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huegli, R. W.; Messmer, P.; Jacob, A. L.

2003-09-15

Delayed or non-union of a sacral fracture is a serious clinical condition that may include chronic pain, sitting discomfort, gait disturbances, neurological problems, and inability to work. It is also a difficult reconstruction problem. Late correction of the deformity is technically more demanding than the primary treatment of acute pelvic injuries. Open reduction, internal fixation (ORIF), excision of scar tissue, and bone grafting often in a multi-step approach are considered to be the treatment of choice in delayed unions of the pelvic ring. This procedure implies the risk of neurological and vascular injuries, infection, repeated failure of union, incomplete correctionmore » of the deformity, and incomplete pain relief as the most important complications. We report a new approach for minimally invasive treatment of a delayed union of the sacrum without vertical displacement. A patient who suffered a Malgaigne fracture (Tile C1.3) was initially treated with closed reduction and percutaneous screw fixation (CRPF) of the posterior pelvic ring under CT navigation and plating of the anterior pelvic ring. Three months after surgery he presented with increasing hip pain caused by a delayed union of the sacral fracture. The lesion was successfully treated percutaneously in a single step procedure using CT navigation for drilling of the delayed union, autologous bone grafting, and screw fixation.« less

Delayed Single Stage Perineal Posterior Urethroplasty.

PubMed

Ali, Shahzad; Shahnawaz; Shahzad, Iqbal; Baloch, Muhammad Umar

2015-06-01

To determine the delayed single stage perineal posterior urethroplasty for treatment of posterior urethral stricture/distraction defect. Descriptive case series. Department of Urology, Jinnah Postgraduate Medical Centre, Karachi, from January 2009 to December 2011. Patients were selected for delayed single stage perineal posterior urethroplasty for treatment of posterior urethral stricture / distraction defect. All were initially suprapubically catheterized followed by definitive surgery after at least 3 months. Thirty male patients were analyzed with a mean follow-up of 10 months, 2 patients were excluded as they developed failure in first 3 months postoperatively. Mean patient's age was 26.25 ± 7.9 years. On follow-up, 7 patients (23.3%) experienced recurrent stricture during first 10 months. Five (16.6%) patients were treated successfully with single direct visual internal urethrotomy. Two patients (6.6%) had more than one direct visual internal urethrotomy and considered failed. Re-do perineal urethroplasty was eventually performed. The overall success rate was 93.3% with permissive criteria allowing single direct visual internal urethrotomy and 76.6% with strict criteria allowing no more procedures postoperatively. Posterior anastomotic urethroplasty offers excellent long-term results to patients with posterior urethral trauma and distraction defect even after multiple prior procedures.

Modeling and Control of a Delayed Hepatitis B Virus Model with Incubation Period and Combination Treatment.

PubMed

Sun, Deshun; Liu, Fei

2018-06-01

In this paper, a hepatitis B virus (HBV) model with an incubation period and delayed state and control variables is firstly proposed. Furthermore, the combination treatment is adopted to have a longer-lasting effect than mono-therapy. The equilibrium points and basic reproduction number are calculated, and then the local stability is analyzed on this model. We then present optimal control strategies based on the Pontryagin's minimum principle with an objective function not only to reduce the levels of exposed cells, infected cells and free viruses nearly to zero at the end of therapy, but also to minimize the drug side-effect and the cost of treatment. What's more, we develop a numerical simulation algorithm for solving our HBV model based on the combination of forward and backward difference approximations. The state dynamics of uninfected cells, exposed cells, infected cells, free viruses, CTL and ALT are simulated with or without optimal control, which show that HBV is reduced nearly to zero based on the time-varying optimal control strategies whereas the disease would break out without control. At last, by the simulations, we prove that strategy A is the best among the three kinds of strategies we adopt and further comparisons have been done between model (1) and model (2).

'Patient's delay'--analysis of the preclinical phase of occupational dermatoses.

PubMed

Rusca, C; Hinnen, U; Elsner, P

1997-01-01

In order to cure diseases effectively it is important that they are detected in their early stages so that medical precautions can be taken. With job-related disorders it is conceivable that anxiety concerning the workplace, as well as other factors of a demanding nature, may lead to a further delay of diagnosis and treatment. The study was carried out for the purpose of gathering information about the patients' reactions in the preclinical phase of job-related eczema. 79 patients suffering from a job-related skin disease were questioned. The patients were divided up into groups according to their respective delay and the results evaluated in line with the method of logistic regression. The average delay was 8.6 months. Fear of losing their job was mentioned by most participants as the reason for the postponement of seeking medical care. People with a long delay were mainly men, senior and Swiss citizens, those with a higher education and those with a longer professional training. Patient delay in occupational dermatology highly depends on the support of employers and on the counseling of workers on job-related skin disease and their insurance protection.

Delaying the start of iron until 28 days after antimalarial treatment is associated with lower incidence of subsequent illness in children with malaria and iron deficiency.

PubMed

Jaramillo, Ericka G; Mupere, Ezekiel; Opoka, Robert O; Hodges, James S; Lund, Troy C; Georgieff, Michael K; John, Chandy C; Cusick, Sarah E

2017-01-01

We evaluated the incidence of all-cause and malaria-specific clinic visits during follow-up of a recent trial of iron therapy. In the main trial, Ugandan children 6-59 months with smear-confirmed malaria and iron deficiency [zinc protoporphyrin (ZPP > = 80 μmol/mol heme)] were treated for malaria and randomized to start a 27-day course of oral iron concurrently with (immediate group) or 28 days after (delayed group) antimalarial treatment. All children were followed for the same 56-day period starting at the time of antimalarial treatment (Day 0) and underwent passive and active surveillance for malaria and other morbidity for the entire follow-up period. All ill children were examined and treated by the study physician. In this secondary analysis of morbidity data from the main trial, we report that although the incidence of malaria-specific visits did not differ between the groups, children in the immediate group had a higher incidence rate ratio of all-cause sick-child visits to the clinic during the follow-up period (Incidence Rate Ratio (IRR) immediate/delayed = 1.76; 95%CI: 1.05-3.03, p = 0.033). Although these findings need to be tested in a larger trial powered for malaria-specific morbidity, these preliminary results suggest that delaying iron by 28 days in children with coexisting malaria and iron deficiency is associated with a reduced risk of subsequent all-cause illness.

Delayed histochemical alterations within the neurovascular unit due to transient focal cerebral ischemia and experimental treatment with neurotrophic factors.

PubMed

Michalski, Dominik; Pitsch, Roman; Pillai, Deepu R; Mages, Bianca; Aleithe, Susanne; Grosche, Jens; Martens, Henrik; Schlachetzki, Felix; Härtig, Wolfgang

2017-01-01

Current stroke therapy is focused on recanalizing strategies, but neuroprotective co-treatments are still lacking. Modern concepts of the ischemia-affected neurovascular unit (NVU) and surrounding penumbra emphasize the complexity during the transition from initial damaging to regenerative processes. While early treatment with neurotrophic factors was shown to result in lesion size reduction and blood-brain barrier (BBB) stabilization, cellular consequences from these treatments are poorly understood. This study explored delayed cellular responses not only to ischemic stroke, but also to an early treatment with neurotrophic factors. Rats underwent 60 minutes of focal cerebral ischemia. Fluorescence labeling was applied to sections from brains perfused 7 days after ischemia. Analyses focused on NVU constituents including the vasculature, astrocytes and microglia in the ischemic striatum, the border zone and the contralateral hemisphere. In addition to histochemical signs of BBB breakdown, a strong up-regulation of collagen IV and microglia activation occurred within the ischemic core with simultaneous degradation of astrocytes and their endfeet. Activated astroglia were mainly depicted at the border zone in terms of a glial scar formation. Early treatment with pigment epithelium-derived factor (PEDF) resulted in an attenuation of the usually up-regulated collagen IV-immunoreactivity. However, glial activation was not influenced by treatment with PEDF or the epidermal growth factor (EGF). In conclusion, these data on ischemia-induced cellular reactions within the NVU might help to develop treatments addressing the transition from injury towards regeneration. Thereby, the integrity of the vasculature in close relation to neighboring structures like astrocytes appears as a promising target.

Signal functions in delayed reinforcement

PubMed Central

Lattal, Kennon A.

1984-01-01

Three experiments were conducted with pigeons to examine the role of the signal in delay-of-reinforcement procedures. In the first, a blackout accompanying a period of nonreinforcement increased key-peck response rates maintained by immediate reinforcement. The effects of dissociating the blackout from the delay interval were examined in the second experiment. In three conditions, blackouts and unsignaled delays were negatively correlated or occurred randomly with respect to one another. A signaled delay and an unsignaled delay that omitted the blackouts were studied in two other conditions. All delay-of-reinforcement conditions generally produced response rates lower than those produced by immediate reinforcement. Signaled delays maintained higher response rates than did any of the various unsignaled-delay conditions, with or without dissociated blackouts. The effects of these latter conditions did not differ systematically from one another. The final experiment showed that response rates varied as a function of the frequency with which a blackout accompanied delay intervals. By eliminating a number of methodological difficulties present in previous delay-of-reinforcement experiments, these results suggest the importance of the signal in maintaining responding during delay-of-reinforcement procedures and, conversely, the importance of the delay interval in decreasing responding. PMID:16812387

Stochastic parameter estimation in nonlinear time-delayed vibratory systems with distributed delay

NASA Astrophysics Data System (ADS)

Torkamani, Shahab; Butcher, Eric A.

2013-07-01

The stochastic estimation of parameters and states in linear and nonlinear time-delayed vibratory systems with distributed delay is explored. The approach consists of first employing a continuous time approximation to approximate the delayed integro-differential system with a large set of ordinary differential equations having stochastic excitations. Then the problem of state and parameter estimation in the resulting stochastic ordinary differential system is represented as an optimal filtering problem using a state augmentation technique. By adapting the extended Kalman-Bucy filter to the augmented filtering problem, the unknown parameters of the time-delayed system are estimated from noise-corrupted, possibly incomplete measurements of the states. Similarly, the upper bound of the distributed delay can also be estimated by the proposed technique. As an illustrative example to a practical problem in vibrations, the parameter, delay upper bound, and state estimation from noise-corrupted measurements in a distributed force model widely used for modeling machine tool vibrations in the turning operation is investigated.

Effect of delayed reinforcement on skill acquisition during discrete-trial instruction: Implications for treatmen-integrity errors in academic settings.

PubMed

Carroll, Regina A; Kodak, Tiffany; Adolf, Kari J

2016-03-01

We used an adapted alternating treatments design to compare skill acquisition during discrete-trial instruction using immediate reinforcement, delayed reinforcement with immediate praise, and delayed reinforcement for 2 children with autism spectrum disorder. Participants acquired the skills taught with immediate reinforcement; however, delayed reinforcement decreased the efficiency and effectiveness of discrete-trial instruction. We discuss the importance of evaluating the influence of treatment-integrity errors on skill acquisition during discrete-trial instruction. © 2015 Society for the Experimental Analysis of Behavior.

Measurement of time delay for a prospectively gated CT simulator.

PubMed

Goharian, M; Khan, R F H

2010-04-01

For the management of mobile tumors, respiratory gating is the ideal option, both during imaging and during therapy. The major advantage of respiratory gating during imaging is that it is possible to create a single artifact-free CT data-set during a selected phase of the patient's breathing cycle. The purpose of the present work is to present a simple technique to measure the time delay during acquisition of a prospectively gated CT. The time delay of a Philips Brilliance BigBore (Philips Medical Systems, Madison, WI) scanner attached to a Varian Real-Time Position Management (RPM) system (Varian Medical Systems, Palo Alto, CA) was measured. Two methods were used to measure the CT time delay: using a motion phantom and using a recorded data file from the RPM system. In the first technique, a rotating wheel phantom was altered by placing two plastic balls on its axis and rim, respectively. For a desired gate, the relative positions of the balls were measured from the acquired CT data and converted into corresponding phases. Phase difference was calculated between the measured phases and the desired phases. Using period of motion, the phase difference was converted into time delay. The Varian RPM system provides an external breathing signal; it also records transistor-transistor logic (TTL) 'X-Ray ON' status signal from the CT scanner in a text file. The TTL 'X-Ray ON' indicates the start of CT image acquisition. Thus, knowledge of the start time of CT acquisition, combined with the real-time phase and amplitude data from the external respiratory signal, provides time-stamping of all images in an axial CT scan. The TTL signal with time-stamp was used to calculate when (during the breathing cycle) a slice was recorded. Using the two approaches, the time delay between the prospective gating signal and CT simulator has been determined to be 367 +/- 40 ms. The delay requires corrections both at image acquisition and while setting gates for the treatment delivery

Magnetic Resonance Imaging (MRI) Evaluation of Developmental Delay in Pediatric Patients

PubMed Central

Syed, Naziya P.; Murthy, G.S.N.; Nori, Madhavi; Abkari, Anand; Pooja, B.K.; Venkateswarlu, J.

2015-01-01

Introduction: Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child’s ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. Aims and Objectives: To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. Materials and Methods: It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Results: Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was

Determinants of delay in malaria care-seeking behaviour for children 15 years and under in Bata district, Equatorial Guinea.

PubMed

Romay-Barja, Maria; Cano, Jorge; Ncogo, Policarpo; Nseng, Gloria; Santana-Morales, Maria A; Valladares, Basilio; Riloha, Matilde; Benito, Agustin

2016-03-31

Malaria remains a major cause of morbidity and mortality in children under 5 years of age in Equatorial Guinea. Early appropriate treatment can reduce progression of the illness to severe stages, thus reducing of mortality, morbidity and onward transmission. The factors that contribute to malaria treatment delay have not been studied previously in Equatorial Guinea. The objective of this study was to assess the determinants of delay in seeking malaria treatment for children in the Bata district, in mainland Equatorial Guinea. A cross-sectional study was conducted in Bata district, in 2013, which involved 428 houses in 18 rural villages and 26 urban neighbourhoods. Household caregivers were identified in each house and asked about their knowledge of malaria and about the management of the last reported malaria episode in a child 15 years and younger under their care. Bivariate and multivariate statistical analyses were conducted to determine the relevance of socio-economic, geographical and behavioural factors on delays in care-seeking behaviour. Nearly half of the children sought treatment at least 24 h after the onset of the symptoms. The median delay in seeking care was 2.8 days. Children from households with the highest socio-economic status were less likely to be delayed in seeking care than those from households with the lowest socio-economic status (OR 0.37, 95% CI 0.19-0.72). Children that first received treatment at home, mainly paracetamol, were more than twice more likely to be delayed for seeking care, than children who did not first receive treatment at home (OR 2.36, 95% CI 1.45-3.83). Children living in a distance >3 km from the nearest health facility were almost two times more likely to be delayed in seeking care than those living closer to a facility but with non significant association once adjusted for other variables (OR 1.75, 95% CI 0.88-3.47). To decrease malaria morbidity and mortality in Bata district, efforts should be addressed to reduce

Advanced Transport Delay Compensation Algorithms: Results of Delay Measurement and Piloted Performance Tests

NASA Technical Reports Server (NTRS)

Guo, Liwen; Cardullo, Frank M.; Kelly, Lon C.

2007-01-01

This report summarizes the results of delay measurement and piloted performance tests that were conducted to assess the effectiveness of the adaptive compensator and the state space compensator for alleviating the phase distortion of transport delay in the visual system in the VMS at the NASA Langley Research Center. Piloted simulation tests were conducted to assess the effectiveness of two novel compensators in comparison to the McFarland predictor and the baseline system with no compensation. Thirteen pilots with heterogeneous flight experience executed straight-in and offset approaches, at various delay configurations, on a flight simulator where different predictors were applied to compensate for transport delay. The glideslope and touchdown errors, power spectral density of the pilot control inputs, NASA Task Load Index, and Cooper-Harper rating of the handling qualities were employed for the analyses. The overall analyses show that the adaptive predictor results in slightly poorer compensation for short added delay (up to 48 ms) and better compensation for long added delay (up to 192 ms) than the McFarland compensator. The analyses also show that the state space predictor is fairly superior for short delay and significantly superior for long delay than the McFarland compensator.

The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy.

PubMed

Madjunkova, Svetlana; Maltepe, Caroline; Koren, Gideon

2014-06-01

Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis(®), and has been on the Canadian market since 1979, currently under the brand name Diclectin(®). The efficacy of Diclegis(®)/Diclectin(®) has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis(®)/Diclectin(®) for the treatment of NVP to justify its use as first-line treatment for NVP.

Maximising platelet availability by delaying cold storage.

PubMed

Wood, B; Johnson, L; Hyland, R A; Marks, D C

2018-04-06

Cold-stored platelets may be an alternative to conventional room temperature (RT) storage. However, cold-stored platelets are cleared more rapidly from circulation, reducing their suitability for prophylactic transfusion. To minimise wastage, it may be beneficial to store platelets conventionally until near expiry (4 days) for prophylactic use, transferring them to refrigerated storage to facilitate an extended shelf life, reserving the platelets for the treatment of acute bleeding. Two ABO-matched buffy-coat-derived platelets (30% plasma/70% SSP+) were pooled and split to produce matched pairs (n = 8 pairs). One unit was stored at 2-6°C without agitation (day 1 postcollection; cold); the second unit was stored at 20-24°C with constant agitation until day 4 then stored at 2-6°C thereafter (delayed-cold). All units were tested for in vitro quality periodically over 21 days. During storage, cold and delayed-cold platelets maintained a similar platelet count. While pH and HSR were significantly higher in delayed-cold platelets, other metabolic markers, including lactate production and glucose consumption, did not differ significantly. Furthermore, surface expression of phosphatidylserine and CD62P, release of soluble CD62P and microparticles were not significantly different, suggesting similar activation profiles. Aggregation responses of delayed-cold platelets followed the same trend as cold platelets once transferred to cold storage, gradually declining over the storage period. The metabolic and activation profile of delayed-cold platelets was similar to cold-stored platelets. These data suggest that transferring platelets to refrigerated storage when near expiry may be a viable option for maximising platelet inventories. © 2018 International Society of Blood Transfusion.

Delay-dependent coupling for a multi-agent LTI consensus system with inter-agent delays

NASA Astrophysics Data System (ADS)

Qiao, Wei; Sipahi, Rifat

2014-01-01

Delay-dependent coupling (DDC) is considered in this paper in a broadly studied linear time-invariant multi-agent consensus system in which agents communicate with each other under homogeneous delays, while attempting to reach consensus. The coupling among the agents is designed here as an explicit parameter of this delay, allowing couplings to autonomously adapt based on the delay value, and in order to guarantee stability and a certain degree of robustness in the network despite the destabilizing effect of delay. Design procedures, analysis of convergence speed of consensus, comprehensive numerical studies for the case of time-varying delay, and limitations are presented.

Lithium, but not Valproate, Reduces Impulsive Choice in the Delay-Discounting Task in Mice

PubMed Central

Halcomb, Meredith E; Gould, Todd D; Grahame, Nicholas J

2013-01-01

Both lithium and valproate are well-established treatments for bipolar disorder. Studies have also found that lithium is effective at reducing suicidal behaviors in patients with mood disorders. Impulsivity is a validated endophenotype of both bipolar disorder and suicidal behavior. We assessed effects of treatment with lithium or valproate on cognitive impulsivity in selectively bred mice previously shown to manifest relatively high levels of cognitive impulsivity. Mice were trained in the delay-discounting paradigm, a measure of cognitive impulsivity reflecting a behavioral bias towards immediacy, and then treated with lithium, valproate, or control chow. After 3 weeks of drug treatment, mice were tested at various delays to a large, delayed reward. Drug treatment continued during this time. Lithium reduced impulsivity, whereas valproate had no effect on choice behavior. Both drugs increased the number of choice trials and reinforcer intake, but effects on choice behavior did not depend on these motivational changes. To our knowledge, this is the first study demonstrating lithium's effects to reduce cognitive impulsivity. Future studies may focus on the ability of putative pharmacotherapies for patients at risk for bipolar disorder or suicide to modify the impulsive choice dimension of this diseases. PMID:23584261

Differentiation of Speech Delay and Global Developmental Delay in Children Using DTI Tractography-Based Connectome.

PubMed

Jeong, J-W; Sundaram, S; Behen, M E; Chugani, H T

2016-06-01

Pure speech delay is a common developmental disorder which, according to some estimates, affects 5%-8% of the population. Speech delay may not only be an isolated condition but also can be part of a broader condition such as global developmental delay. The present study investigated whether diffusion tensor imaging tractography-based connectome can differentiate global developmental delay from speech delay in young children. Twelve children with pure speech delay (39.1 ± 20.9 months of age, 9 boys), 14 children with global developmental delay (39.3 ± 18.2 months of age, 12 boys), and 10 children with typical development (38.5 ± 20.5 months of age, 7 boys) underwent 3T DTI. For each subject, whole-brain connectome analysis was performed by using 116 cortical ROIs. The following network metrics were measured at individual regions: strength (number of the shortest paths), efficiency (measures of global and local integration), cluster coefficient (a measure of local aggregation), and betweeness (a measure of centrality). Compared with typical development, global and local efficiency were significantly reduced in both global developmental delay and speech delay (P < .0001). The nodal strength of the cognitive network is reduced in global developmental delay, whereas the nodal strength of the language network is reduced in speech delay. This finding resulted in a high accuracy of >83% ± 4% to discriminate global developmental delay from speech delay. The network abnormalities identified in the present study may underlie the neurocognitive and behavioral consequences commonly identified in children with global developmental delay and speech delay. Further validation studies in larger samples are required. © 2016 by American Journal of Neuroradiology.

Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.

PubMed

Castagna, Maria Grazia; Maino, Fabio; Cipri, Claudia; Belardini, Valentina; Theodoropoulou, Alexandra; Cevenini, Gabriele; Pacini, Furio

2011-09-01

After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

Delayed treatment with hypothermia protects against the no-reflow phenomenon despite failure to reduce infarct size.

PubMed

Hale, Sharon L; Herring, Michael J; Kloner, Robert A

2013-01-04

Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no-reflow. Our aim was to test the effects of hypothermia on no-reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size. Rabbits received 30 minutes coronary artery occlusion/3 hours CAR. In protocol 1, hearts were treated for 1 hour with topical hypothermia (myocardial temperature ≈32°C) initiated at 5 minutes before or 5 minutes after CAR, and the results were compared with a normothermic group. In protocol 2, hypothermia was delayed until 30 minutes after CAR and control hearts remained normothermic. In protocol 1, risk zones were similar and infarct size was not significantly reduced by hypothermia initiated close to CAR. However, the no-reflow defect was significantly reduced by 43% (5 minutes before CAR) and 38% (5 minutes after CAR) in hypothermic compared with normothermic hearts (P=0.004, ANOVA, P=ns between the 2 treated groups). In protocol 2, risk zones and infarct sizes were similar, but delayed hypothermia significantly reduced no-reflow in hypothermic hearts by 30% (55±6% of the necrotic region in hypothermia group versus 79±6% with normothermia, P=0.008). These studies suggest that treatment with hypothermia reduces no-reflow even when initiated too late to reduce infarct size and that the microvasculature is especially receptive to the protective properties of hypothermia and confirm that microvascular damage is in large part a form of true reperfusion injury.

Predictors of healthcare seeking delays among children with chronic musculoskeletal disorders in Nepal.

PubMed

LeBrun, Drake G; Talwar, Divya; Pham, Tuyetnhi A; Banskota, Bibek; Spiegel, David A

2017-12-01

Healthcare seeking behaviors among children with musculoskeletal disorders are poorly understood. We sought to analyze healthcare seeking delays among children with chronic musculoskeletal conditions in Nepal and identify predictors of clinically significant delays. A cross-sectional study was conducted at a large pediatric musculoskeletal rehabilitation center in Nepal. Baseline sociodemographic data and healthcare seeking behaviors were assessed via interviews with 75 randomly selected caregivers. Delays of at least 3 months between disease recognition and presentation to a health worker were considered clinically significant. Predictors of significant delay were assessed via multivariable logistic regression. Clubfoot was the most common condition seen in the study sample (N = 33; 37%). Mean and median presentation delays were 33 months and 14 months, respectively. Sixty-seven percent of children were delayed at least 3 months and 40% were delayed at least 2 years. Caregiver occupation in agriculture or unskilled labor was associated with an increased risk of delayed presentation (adjusted OR = 4.05; 95% CI: 1.36-12.09). Children with chronic musculoskeletal disorders in Nepal face significant delays in accessing healthcare. This poses a major clinical problem as the delayed diagnosis and treatment of childhood musculoskeletal disorders can complicate management options and decrease long-term quality of life. Copyright © 2017 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

PubMed Central

2012-01-01

Background There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. Methods/design We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will

Neonatal morbidities and developmental delay in moderately preterm-born children.

PubMed

Kerstjens, Jorien M; Bocca-Tjeertes, Inger F; de Winter, Andrea F; Reijneveld, Sijmen A; Bos, Arend F

2012-08-01

Children born moderately preterm (32-35(6/7) weeks' gestation) are at increased risk of both neonatal morbidities and developmental delays in early childhood. It is unknown whether neonatal morbidities contribute to the increased risk of developmental delay. The objective of this study was to determine the effect of neonatal morbidities after moderately preterm birth on development at preschool age. In a community-based, stratified cohort, parents of 832 moderately preterm children born in 2002 or 2003 completed the Ages and Stage Questionnaire when their child was 43 to 49 months old. Data on Apgar scores, asphyxia, tertiary NICU admission, hospital transfer, circulatory insufficiency, hypoglycemia, septicemia, mechanical ventilation, continuous positive airway pressure, apneas, caffeine treatment, and hyperbilirubinemia were obtained from medical records. We assessed associations of neonatal characteristics with developmental delay, adjusted for gender, small-for-gestational-age status, gestational age, and maternal education. Hypoglycemia and asphyxia were associated with developmental delay; odds ratios (ORs) were 2.42 (95% confidence interval [CI]: 1.23-4.77) and 3.18 (95% CI: 1.01-10.0), respectively. Tertiary NICU admission and hyperbilirubinemia had positive but statistically borderline nonsignificant associations with developmental delay: ORs were 1.74 (95% CI: 0.96-3.15) and 1.52 (95% CI: 0.94-2.46), respectively. No other neonatal morbidities were associated with developmental delay. In multivariate analyses, only hypoglycemia was associated with developmental delay (OR: 2.19; 95% CI: 1.08-4.46). In moderately preterm-born children, only hypoglycemia increased the risk of developmental delay at preschool age. A concerted effort to prevent hypoglycemia might enhance developmental outcome in this group.

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

PubMed

Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

2015-10-22

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Responsiveness of emergency obstetric care systems in low- and middle-income countries: a critical review of the "third delay".

PubMed

Cavallaro, Francesca L; Marchant, Tanya J

2013-05-01

We reviewed the evidence on the duration, causes and effects of delays in providing emergency obstetric care to women attending health facilities (the third delay) in low- and middle-income countries. We performed a critical literature review using terms related to obstetric care, birth outcome, delays and developing countries. A manual search of reference lists of key articles was also performed. 69 studies met the inclusion criteria. Most studies reported long delays in providing care, and the mean waiting time for women admitted with complications was as much as 24 h before treatment. The three most cited barriers to providing timely care were shortage of treatment materials, surgery facilities and qualified staff. Existing evidence is insufficient to estimate the effect of delays on birth outcomes. Delays in providing emergency obstetric care seem common in resource-constrained settings but further research is necessary to determine the effect of the third delay on birth outcomes. © 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

Delayed Catheter-Related Intracranial Hemorrhage After a Ventriculoperitoneal or Ventriculoatrial Shunt in Hydrocephalus.

PubMed

Qian, Zhouqi; Gao, Liang; Wang, Ke; Pandey, Sajan

2017-11-01

Delayed catheter-related intracranial hemorrhage is not rare after a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt for the treatment of hydrocephalus. Immediate postoperative catheter-related intracranial hemorrhage is possibly due to the procedure itself; however, delayed intracranial hemorrhage may have other underlying mechanisms. This study aimed to investigate the clinical characteristics and reveal the risk factors of delayed catheter-related intracranial hemorrhage after a VP or VA shunt. We did a retrospective study to review patients with hydrocephalus and underwent VP or VA shunt in our department from September 2011 to December 2015. We reviewed the clinical characteristics of the patients with delayed catheter-related intracranial hemorrhage, and its risk factors were analyzed with SPSS 16.0. Of the 218 patients enrolled in the study (145 male, 73 female), 17 (7.8%) patients experienced delayed catheter-related intracranial hemorrhage, including 11 of 151 (7.3%) patients with a VP shunt and 6 of 67 (9.0%) patients with a VA shunt. Additionally, 4 of the 16 patients with postoperative low-molecular-weight heparin (LMWH) therapy and 13 of the 202 patients without LMWH experienced bleeding, showing a significant difference (25% vs. 6.4%, P = 0.026). The relative risk was 4.8 (95% confidence interval: 1.4-17.1). Delayed catheter-related intracranial hemorrhage is not rare after a VP or VA shunt. However, most patients can be cured after appropriate treatment. Postoperative anticoagulation therapy with enoxaparin may be associated with an increased risk of bleeding. Copyright © 2017. Published by Elsevier Inc.

The use of low-intensity pulsed ultrasound in treating delayed union of fifth metatarsal fractures.

PubMed

Teoh, Kar Hao; Whitham, Robert; Wong, Jenny F; Hariharan, Kartik

2018-01-31

There are no studies looking at the success rate of low-intensity pulsed ultrasound (LIPUS) in fifth metatarsal fracture delayed unions to our knowledge. The aim of this study is to investigate the use of LIPUS treatment for delayed union of fifth metatarsal fractures. A retrospective review of patients who were treated with LIPUS following a delayed union of fifth metatarsal fracture was conducted over a three-year period. There were thirty patients (9 males, 21 females) in this cohort. The average age was 39.3 years. Type 2 fractures made up 43% of our cohort. Twenty-seven (90%) patients went on to progress to union clinically and radiologically following LIPUS treatment. Smoking (p=0.014) was predictive of non-union. Assuming that there were 10 delayed unions a year and 6 went on to non-union as previously suggested by a systematic review, the cost savings of using LIPUS (90% success rate; 10 LIPUS machine and surgery for 1 non-union) vs operative intervention (surgery for 6 non-union) equates to a cost saving of £7765 a year. There is a role for the use of LIPUS in delayed union of fifth metatarsal fractures and can serve as an adjunct prior to consideration of surgery. The findings of this study also suggest the use of LIPUS to be a cost effective treatment modality compared to surgical management. Level 4. Copyright © 2018 Elsevier Ltd. All rights reserved.

Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia.

PubMed

Burrell, Christian; Avalon, Nicole E; Siegel, Jason; Pizzi, Michael; Dutta, Tumpa; Charlesworth, M Cristine; Freeman, William D

2016-11-01

Precision medicine provides individualized treatment of diseases through leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage carries tremendous morbidity and mortality with cerebral vasospasm and delayed cerebral ischemia proving devastating and unpredictable. Lack of treatment measures for these conditions could be improved through precision medicine. Areas covered: Discussed are the pathophysiology of CV and DCI, treatment guidelines, and evidence for precision medicine used for prediction and prevention of poor outcomes following aSAH. A PubMed search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were evaluated. The studies presented cover biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert commentary: The biomarkers reviewed here correlate with CV, DCI, and neurologic outcomes after aSAH. Though practical use in clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine.

The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

PubMed

Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

2015-01-01

Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

Effects of Immediate and Delayed Loading on the Outcomes of All-on-4 Treatment: A Prospective Study

PubMed Central

Najafi, Hossein; Siadat, Hakimeh; Rokn, Amirreza

2016-01-01

Objectives: The purpose of this study was to compare the outcomes of immediate and delayed rehabilitation of edentulous jaws by means of two straight and two tilted implants after one year of function. Materials and Methods: Thirty consecutive patients (16 males, 14 females) were enrolled in this study. Two anterior straight and two posterior tilted implants were placed in each patient. According to the implant insertion torque and the need for bone grafting, implants were loaded immediately (at 72 hours) or delayed (after four months) using a fixed metal resin prosthesis. Results: One axial implant failed in the delayed group after one year of loading, resulting in cumulative implant survival rate of 99.3%. The mean marginal bone loss was 0.84mm. No significant difference was found between axial and tilted implants in the two groups (P>0.05) Conclusions: Based on the results, immediate or delayed fabrication of final prosthesis on two tilted and two axial implants did not result in significant differences in survival rates or marginal bone loss. PMID:28243303

Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development.

PubMed

Schambra, Uta B; Goldsmith, Jeff; Nunley, Kevin; Liu, Yali; Harirforoosh, Sam; Schambra, Heidi M

2015-01-01

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about

Prospective Memory Deficits in Ecstasy Users: Effects of Longer Ongoing Task Delay Interval

PubMed Central

WEINBORN, MICHAEL; WOODS, STEVEN PAUL; NULSEN, CLAIRE; PARK, KATHERINE

2011-01-01

Ecstasy use has been associated with neurotoxicity and neurocognitive impairment in a variety of domains, including prospective memory (ProM), which involves the delayed execution of a previously encoded intention in response to a specific cue. The present study adopted the multiprocess theory of ProM to evaluate the hypothesis that ecstasy users would evidence differentially impaired ProM on longer versus shorter ongoing task delays. Ecstasy (n = 31) users, high-risk alcohol users (n = 21) and healthy nonusers (n = 31) completed the short (2-min) and long (15-min) delay ProM scales of the Memory for Intentions Screening Test. Results showed a significant group by ProM delay interaction, such that ecstasy users performed comparably to the comparison groups on short-delay trials, but were impaired on long-delay ProM, particularly for time-based cues. Among the ecstasy users, long-delay ProM was positively associated with risky decision-making, but not with retrospective memory or other aspects of executive functions. These findings suggest that ecstasy users may be particularly susceptible to deficits in strategic target monitoring and maintenance of cue-intention pairings over longer ProM delays. Findings are discussed in the context of their potential everyday functioning (e.g., academic, vocational) and treatment implications for ecstasy users. PMID:22047194

Modulation of ovarian steroidogenesis by adiponectin during delayed embryonic development of Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-09-01

The aim of present study was to evaluate role of adiponectin in ovarian steroidogenesis during delayed embryonic development of Cynopterus sphinx. This study showed significantly low circulating adiponectin level and a decline in expression of adiponectin receptor 1 (AdipoR1) in the ovary during the period of delayed embryonic development as compared with the normal development. The adiponectin treatment in vivo during the period of delayed development caused significantly increased in circulating progesterone and estradiol levels together with increased expression of AdipoR1 in the ovary. The in vitro study confirmed the stimulatory effect of adiponectin on progesterone synthesis. Both in vivo and in vitro studies showed that the effects of adiponectin on ovarian steroidogenesis were mediated through increased expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein and 3β-hydroxyl steroid dehydrogenase enzyme. The adiponectin treatment may also promote progesterone synthesis by modulating ovarian angiogenesis, cell survival and rate of apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull.

PubMed

Chambless, Lola B; Angel, Federica B; Abel, Ty W; Xia, Fen; Weaver, Kyle D

2010-10-25

Cerebral radiation necrosis is a relatively common complication of radiation therapy for intracranial malignancies which can also rarely be encountered after radiation of extracranial lesions of the head and neck. We present the first reported case of cerebral radiation necrosis in a patient who underwent radiation therapy for a plasmacytoma of the skull. A 68-year-old male with multiple myeloma presented with an enhancing right frontal mass, 8 years after receiving radiation therapy for a plasmacytoma of the left frontal skull. The patient underwent a diagnostic and therapeutic craniotomy for a presumed neoplastic lesion. The pathologic diagnosis made in this case was delayed radiation necrosis. The patient was followed for over a year during which this process continued to evolve before the ultimate resolution of his clinical symptoms and radiographic abnormality. This case highlights the importance of considering radiation necrosis in the differential diagnosis of any patient with an intracranial mass and a history of radiation for an extracranial head and neck malignancy, regardless of timing and laterality. This case also provides unique insights into the ongoing debate regarding the role of the aberrant immune response in the pathogenesis of delayed cerebral radiation necrosis.

Complementary and alternative medicine (CAM) use and delays in presentation and diagnosis of breast cancer patients in public hospitals in Malaysia

PubMed Central

Emran, Nor Aina; Abdul Hadi, Imisairi; Wai, Yan Yang; Arulanantham, Sarojah; Hooi, Chea Chan

2017-01-01

Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients’ journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1

Complementary and alternative medicine (CAM) use and delays in presentation and diagnosis of breast cancer patients in public hospitals in Malaysia.

PubMed

Mohd Mujar, Noor Mastura; Dahlui, Maznah; Emran, Nor Aina; Abdul Hadi, Imisairi; Wai, Yan Yang; Arulanantham, Sarojah; Hooi, Chea Chan; Mohd Taib, Nur Aishah

2017-01-01

Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients' journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1

Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-12-01

The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma.

PubMed

Withers, Sita S; Kass, Philip H; Rodriguez, Carlos O; Skorupski, Katherine A; O'Brien, Danielle; Guerrero, Teri A; Sein, Kristen D; Rebhun, Robert B

2014-05-12

Fasting reduces gastrointestinal cellular proliferation rates through G 1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed. Copyright © 2014 Elsevier Inc. All rights reserved.

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults.

PubMed

Abramoff, Benjamin A; Lange, Hannah L H; Matson, Steven C; Cottrill, Casey B; Bridge, Jeffrey A; Abdel-Rasoul, Mahmoud; Bonny, Andrea E

2015-01-01

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence.

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults

PubMed Central

Abramoff, Benjamin A.; Lange, Hannah L. H.; Matson, Steven C.; Cottrill, Casey B.; Bridge, Jeffrey A.; Abdel-Rasoul, Mahmoud; Bonny, Andrea E.

2015-01-01

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence. PMID:26664819

DELAYED HYPERSENSITIVITY

PubMed Central

Uhr, Jonathan W.; Salvin, S. B.; Pappenheimer, A. M.

1957-01-01

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed. PMID:13385403

The delay period as an opportunity to think about future intentions: Effects of delay length and delay task difficulty on young adult's prospective memory performance.

PubMed

Mahy, Caitlin E V; Schnitzspahn, Katharina; Hering, Alexandra; Pagobo, Jacqueline; Kliegel, Matthias

2018-05-01

The current study examined the impact of length and difficulty of the delay task on young adult's event-based prospective memory (PM). Participants engaged in either a short (2.5 min) or a long (15 min) delay that was filled with either a simple item categorization task or a difficult cognitive task. They also completed a questionnaire on whether they thought about the PM intention during the delay period and how often they thought about it. Results revealed that participants' PM was better after a difficult delay task compared to an easy delay task. Participants thought about the PM intention more often during the difficult delay task than during the easy delay task. PM performance was positively related to participants' reports of how many times they thought about their intentions. The important role of delay task difficulty in allowing or preventing individuals from refreshing their future intentions is discussed.

PRECISION TIME-DELAY CIRCUIT

DOEpatents

Creveling, R.

1959-03-17

A tine-delay circuit which produces a delay time in d. The circuit a capacitor, an te back resistance, connected serially with the anode of the diode going to ground. At the start of the time delay a negative stepfunction is applied to the series circuit and initiates a half-cycle transient oscillatory voltage terminated by a transient oscillatory voltage of substantially higher frequency. The output of the delay circuit is taken at the junction of the inductor and diode where a sudden voltage rise appears after the initiation of the higher frequency transient oscillations.

Interpretation of symptoms as a cause of delays in patients with acute myocardial infarction, Istanbul, Turkey.

PubMed

Koc, Sema; Durna, Zehra; Akin, Semiha

2017-06-14

This cross-sectional study aimed to assess interpretation of symptoms as a cause of delays in patients with acute myocardial infarction (AMI). It was conducted at a university hospital in Istanbul, Turkey. The sample included 93 patients: 73 male, mean age 57.89 (12.13) years. Prehospital delay time ranged from 15 minutes to 10 days, with a median of 2 hours (interquartile range: 9.50). Patients waited for pain to go away (48.4%) and tried to calm down (39.8%). Most patients attributed AMI-related symptoms to a reason other than heart disease. In a multivariate logistic regression analysis, the type of AMI was classified based on electrocardiography findings (odds ratio 5.18, 95% confidence interval: 1.69-15.91, P=0.004) and was independently associated with a long prehospital delay time, indicating that patients with ST segment elevation MI would seek early medical care. Misinterpretation of symptoms and misconceptions about emergency treatment during AMI cause delays in admission and may affect treatment.

ADHD and Delay Aversion: The Influence of Non-Temporal Stimulation on Choice for Delayed Rewards

ERIC Educational Resources Information Center

Antrop, Inge; Stock, Pieter; Verte, Sylvie; Wiersema, Jan Roelt; Baeyens, Dieter; Roeyers, Herbert

2006-01-01

Background: Delay aversion, the motivation to escape or avoid delay, results in preference for small immediate over large delayed rewards. Delay aversion has been proposed as one distinctive psychological process that may underlie the behavioural symptoms and cognitive deficits of attention deficit/hyperactivity disorder (ADHD). Furthermore, the…

Effects of amphetamine on delay discounting in rats depend upon the manner in which delay is varied

PubMed Central

Maguire, David R; Henson, Cedric; France, Charles P

2014-01-01

Whether stimulant drugs like amphetamine increase or decrease choice of larger delayed reinforcers over smaller immediately available reinforcers under delay discounting procedures can depend on several factors, including the order in which delay is presented. This study examined whether the order of delay presentation impacts drug effects on discounting in rats (n=8) trained and tested under an ascending order, a descending order, as well as under a fixed delay condition. Responses on one lever delivered 1 food pellet immediately and responses on the other lever delivered 3 food pellets immediately or after a delay (4–32 s). In Experiment 1, the delay to the larger reinforcer varied within session and the order of delay presentation (ascending or descending) varied across conditions. In Experiment 2, the same delay value was presented in all blocks of the session (i.e., delay was fixed), and delay varied across phases. Under the ascending order of delay, amphetamine (0.32–1.78 mg/kg) increased choice of the larger reinforcer in some rats and decreased choice in others. In the same rats responding under the descending and fixed delay conditions, amphetamine markedly decreased choice of the larger reinforcer even in the component associated with no delay. In some subjects, the effects of amphetamine differed depending on the manner in which delay was presented, indicating that drug-induced changes in performance were due, in part, to mechanisms other than altered sensitivity to reinforcer delay. These results also suggest that a history of responding under both orders of delay presentation can modulate drug effects. PMID:24780379

What an otolaryngologist should know about evaluation of a child referred for delay in speech development.

PubMed

Tonn, Christopher R; Grundfast, Kenneth M

2014-03-01

Otolaryngologists are asked to evaluate children who a parent, physician, or someone else believes is slow in developing speech. Therefore, an otolaryngologist should be familiar with milestones for normal speech development, the causes of delay in speech development, and the best ways to help assure that children develop the ability to speak in a normal way. To provide information for otolaryngologists that is helpful in the evaluation and management of children perceived to be delayed in developing speech. Data were obtained via literature searches, online databases, textbooks, and the most recent national guidelines on topics including speech delay and language delay and the underlying disorders that can cause delay in developing speech. Emphasis was placed on epidemiology, pathophysiology, most common presentation, and treatment strategies. Most of the sources referenced were published within the past 5 years. Our article is a summary of major causes of speech delay based on reliable sources as listed herein. Speech delay can be the manifestation of a spectrum of disorders affecting the language comprehension and/or speech production pathways, ranging from disorders involving global developmental limitations to motor dysfunction to hearing loss. Determining the cause of a child's delay in speech production is a time-sensitive issue because a child loses valuable opportunities in intellectual development if his or her communication defect is not addressed and ameliorated with treatment. Knowing several key items about each disorder can help otolaryngologists direct families to the correct health care provider to maximize the child's learning potential and intellectual growth curve.

Stochastic resonance in a tumor-immune system subject to bounded noises and time delay

NASA Astrophysics Data System (ADS)

Guo, Wei; Mei, Dong-Cheng

2014-12-01

Immunotherapy is one of the most recent approaches in cancer therapy. A mathematical model of tumor-immune interaction, subject to a periodic immunotherapy treatment (imitated by a periodic signal), correlative and bounded stochastic fluctuations and time delays, is investigated by numerical simulations for its signal power amplification (SPA). Within the tailored parameter regime, the synchronous response of tumor growth to the immunotherapy, stochastic resonance (SR), versus both the noises and delays is obtained. The details are as follows (i) the peak values of SPA versus the noise intensity (A) in the proliferation term of tumor cells decrease as the frequency of periodic signal increases, i.e. an increase of the frequency restrains the SR; (ii) an increase of the amplitude of periodic signal restrains the SR versus A, but boosts up the SR versus the noise intensity B in the immune term; (iii) there is an optimum cross-correlated degree between the two bounded noises, at which the system exhibits the strongest SR versus the delay time τα(the reaction time of tumor cell population to their surrounding environment constraints); (iv) upon increasing the delay time τα, double SR versus the delay time τβ (the time taken by both the tumor antigen identification and tumor-stimulated proliferation of effectors) emerges. These results may be helpful for an immunotherapy treatment for the sufferer.

Optimal therapies of a virus replication model with pharmacological delays based on reverse transcriptase inhibitors and protease inhibitors

NASA Astrophysics Data System (ADS)

Pei, Yongzhen; Li, Changguo; Liang, Xiyin

2017-11-01

A short delay in the pharmacological effect on account of the time required for drug absorption, distribution, and penetration into target cells after application of any anti-viral drug, is defined by the pharmacological delay (Herz et al 1996 Proc. Natl Acad. Sci. USA 93 7247-51). In this paper, a virus replication model with Beddington-DeAngelis incidence rate and the pharmacological and intracellular delays is presented to describe the treatment to cure the virus infection. The optimal controls represent the efficiency of reverse transcriptase inhibitors and protease inhibitors in suppressing viral production and prohibiting new infections. Due to the fact that both the control and state variables contain delays, we derive a necessary conditions for our optimal problem. Based on these results, numerical simulations are implemented not only to show the optimal therapeutic schedules for different infection and release rates, but also to compare the effective of three treatment programs. Furthermore, comparison of therapeutic effects under different maximum tolerable dosages is shown. Our research indicates that (1) the proper and specific treatment program should be determined according to the infection rates of different virus particles; (2) the optimal combined drug treatment is the most efficient; (3) the appropriate proportion of medicament must be formulated during the therapy due to the non-monotonic relationship between maximum tolerable dosages and therapeutic effects; (4) the therapeutic effect is advantageous when the pharmacological delay is considered.